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Urinary sodium excretion and risk of heart failure in men and women in the EPIC-Norfolk study
Abstract
Interventional trials provide evidence for a beneficial effect of reduced dietary sodium intake on blood pressure. The association of sodium intake with heart failure which is a long-term complication of hypertension has not been examined.
Hazard ratios [HRs, 95% confidence interval (CI)] of heart failure comparing quintiles of estimated 24 h urinary sodium excretion (USE) were calculated in apparently healthy men (9017) and women (10 840) aged 39-79 participating in the EPIC study in Norfolk. During a mean follow-up of 12.9 years, 1210 incident cases of heart failure occurred. Compared with the reference category (128 mmol/day ≤USE ≤148 mmol/day), the top quintile (USE ≥191 mmol/day) was associated with a significantly increased hazard of heart failure (1.32, 1.07-1.62) in multivariable analysis adjusting for age, sex, body mass index, diabetes, cholesterol, social class, educational level, smoking, physical activity, and alcohol consumption, with a marked attenuation (1.21, 0.98-1.49) when further adjusting for blood pressure. The bottom quintile (USE ≤127 mmol/day) was also associated with an increased hazard of heart failure (1.29, 1.04-1.60) in multivariable analysis without relevant attenuation by blood pressure adjustment (1.26, 1.02-1.56), but with substantial attenuation when adjusting for interim ischaemic heart disease and baseline C-reactive protein levels and exclusion of events during the first 2 years (1.18, 0.96-1.47).
We demonstrate a U-shaped association between USE and heart failure risk in an apparently healthy middle-aged population. The risk associated with the high range of USE was attenuated after adjustment for blood pressure, whereas the risk associated with the low range of USE was attenuated after adjustment for pre-existing disease processes.
... Data for the current study included baseline, 24 h collection of urine which spanned 1984-1989, and incident MACE outcomes which were obtained through record linkage to national hospital discharge (Finnish Institute for Health and Welfare, Data License THL/93/5.05.00/2013) and death certificate databases (Statistics Finland, Data License TK-53-1770- 16) 1984-2017. This is available from the corresponding author upon request. ...
... Our data indicates U Na is may be of prognostic value regarding all-cause mortality but less so for MACE. This association appeared to be U-shaped in nature, which has been previously seen U Na and MACE events [15] as well as for incident heart failure [16]. An explanation for a lack of association between U Na and MACE outcomes in this study could be due to type 1 error owing to a lack of statistical power due to the limited number of events in the KIHD cohort. ...
... It is thought to be associated with HF due to reduced ejection fraction resulting in compensatory upregulation of the renin angiotensin system [18]. Furthermore, poor response to diuretic therapy in patients with HF is associated with a worse prognosis [16]. On the other hand, high U Na is a reflection of dietary sodium intake, which correlates with a greater risk of developing HF [19]. ...
Background
Lower urinary sodium concentrations (U Na ) may be a biomarker for poor prognosis in chronic heart failure (HF). However, no data exist to determine its prognostic association over the long-term. We investigated whether U Na predicted major adverse coronary events (MACE) and all-cause mortality over 28–33 years.
Methods
One hundred and eighty men with chronic HF from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) were included. Baseline data was collected between 1984 and 1989. MACE and all-cause outcomes were obtained using hospital linkage data (1984–2017) with a follow-up of 28–33 years. Cox proportional hazards models were generated using 24-h U Na tertiles at baseline (1 ≤ 173 mmol/day; 2 = 173-229 mmol/day; 3 = 230-491 mmol/day) as a predictor of time-to-MACE outcomes, adjusted for relevant covariates.
Results
Overall, 63% and 83% of participants (n = 114 and n = 150) had a MACE event (median 10 years) and all-cause mortality event (median 19 years), respectively. On multivariable Cox Model, relative to the lowest U Na tertile, no significant difference was noted in MACE outcome for individuals in tertiles 2 and 3 with events rates of 28% (HR:0.72; 95% CI: 0.46–1.12) and 21% (HR 0.79; 95% CI: 0.5–1.25) respectively.. Relative to the lowest U Na tertile, those in tertile 2 and 3 were 39% (HR: 0.61; 95% CIs: 0.41, 0.91) and 10% (HR: 0.90; 95% CIs: 0.62, 1.33) less likely to experience to experience all-cause mortality. The multivariable Cox model had acceptable prediction precision (Harrell's C concordance measure 0.72).
Conclusion
U Na was a significant predictor of all-cause mortality but not MACE outcomes over 28–33 years with 173–229 mmol/day appearing to be the optimal level. U Na may represent an emerging long-term prognostic biomarker that warrants further investigation.
... Méthodologie non recommandée par le consortium TRUE, du fait de l'importance des erreurs systématiques d'estimation de l'excrétion sodée pour des niveaux faibles et élevés [33]. [40]. ...
... Furthermore, a study that evaluated the hemodynamic effects of sodium bicarbonate and sodium chloride in normotensive patients of black ethnicity (age showed that both sodium salts were associated with a significant elevation of blood pressure in salt-sensitive, but not salt resistant patients, in the interval between the low sodium diet and sodium load phase. The hypertensive effect observed with sodium bicarbonate was half that of sodium chloride [40]. We postulate that a high sodium intake through drugs (non-chloride salts), in subjects consuming important amount of sodium chloride through food, can be associated with an elevation of BP, especially in subjects with SSBP traits. ...
... Enfin, l'absence d'ajustement sur des facteurs de confusion a pu également contribuer, dans certaines études, à biaiser les estimations du risque cardiovasculaire pour les faibles niveaux d'apport sodé. C'est le cas notamment de l'étude publiée par Pfister et al., ayant montré une relation en « U » entre le niveau d'apport sodé et le risque d'insuffisance cardiaque incidente chez des sujets apparement sains à l'inclusion.Après ajustement sur les antécédents cardiovasculaires et le niveau d'inflammation, le sur-risque pour les faibles niveaux d'excrétion sodée n'était plus significatif[40]. ...
... Furthermore, these guidelines were developed without evidence that it would be possible to reduce sodium to such low levels on a prolonged basis in entire populations or that such as strategy will lower cardiovascular events or death. Current evidence from cohort studies suggests a J-shaped relationship between sodium intake and cardiovascular events, as would be expected for an essential nutrient [6,8], and suggests that the lowest risk of death or cardiovascular disease occurs in populations consuming an average sodium intake (3 to 5 g/day) [9][10][11][12][13]. To date, no study (observational or randomized trial) has demonstrated a significantly lower risk of cardiovascular events with low sodium intake (below 2.3 g/day) compared with average intake [14]. ...
... The higher risk for cardiovascular events or death with low sodium intake, compared to average intake, has been seen in studies conducted by several different investigators from over 50 countries [11,12,34,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] (e.g., PURE [11,53,54], ONTARGET/TRANSCEND [11,51], EPIDREAM [11], EPIC-Norfolk [12], NHANES-I, II and III [55][56][57], FLEMENGHO/EPOGH [50], SURDIAGENE [52], PREVEND [46], and CRIC [58] studies), and has been found in those with and without vascular disease, those with and without diabetes, and those with and without hypertension, and has been observed despite extensive statistical adjustments for confounders and extensive efforts to avoid "reverse causation". These findings have also been seen in studies using different methods of sodium estimation, including repeated 24-h urine, single 24-h urine, an overnight urine, and dietary assessment. ...
... The higher risk for cardiovascular events or death with low sodium intake, compared to average intake, has been seen in studies conducted by several different investigators from over 50 countries [11,12,34,[46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] (e.g., PURE [11,53,54], ONTARGET/TRANSCEND [11,51], EPIDREAM [11], EPIC-Norfolk [12], NHANES-I, II and III [55][56][57], FLEMENGHO/EPOGH [50], SURDIAGENE [52], PREVEND [46], and CRIC [58] studies), and has been found in those with and without vascular disease, those with and without diabetes, and those with and without hypertension, and has been observed despite extensive statistical adjustments for confounders and extensive efforts to avoid "reverse causation". These findings have also been seen in studies using different methods of sodium estimation, including repeated 24-h urine, single 24-h urine, an overnight urine, and dietary assessment. ...
Several health organizations recommend low sodium intake (below 2.3 g/day, 5.8 g/day of salt) for entire populations, on the premise that lowering of sodium intake, irrespective of its level of intake, will lower blood pressure and, in turn, will result in a lower incidence of cardiovascular disease. These guidelines were developed without effective interventions to achieve long term sodium intakes at low levels in free-living individuals and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with average levels of intake). In this review, we examine whether advice to consume low amounts of sodium is supported by robust evidence. We contend that current evidence indicates that most people around the world consume a moderate range of dietary sodium (3 to 5 g/day), that this level of intake is associated with the lowest risk of cardiovascular disease and mortality, and that the risk of adverse health outcomes increases when sodium intakes exceeds 5 g/day or is below 3 g/day. While the current evidence has limitations, it is reasonable, based upon prospective cohort studies, to suggest a mean target of below 5 g/day in populations, while awaiting the results of large randomized controlled trials of sodium reduction on cardiovascular disease and death.
... Nevertheless, a metanalysis of prospective cohort studies has reported nonsignificant associations between Na intake and incident fatal and non-fatal cardiovascular disease, coronary heart disease and all-cause mortality [18]. Additionally, in the last decade, a significant number of studies [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] showed that not only high but also low levels of dietary Na intake are associated with increased cardiovascular risk. These studies [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] suggested the presence of a J-shaped or inverse linear association between daily Na intake and cardiovascular mortality [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52], verifying early findings of the Alderman et al. study [53]. ...
... Additionally, in the last decade, a significant number of studies [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] showed that not only high but also low levels of dietary Na intake are associated with increased cardiovascular risk. These studies [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] suggested the presence of a J-shaped or inverse linear association between daily Na intake and cardiovascular mortality [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52], verifying early findings of the Alderman et al. study [53]. The major studies that implicated low levels of dietary Na intake in cardiovascular morbidity/mortality raising are presented in Fig. 1. ...
... Additionally, in the last decade, a significant number of studies [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] showed that not only high but also low levels of dietary Na intake are associated with increased cardiovascular risk. These studies [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52] suggested the presence of a J-shaped or inverse linear association between daily Na intake and cardiovascular mortality [5,[39][40][41][42][43][44][45][46][47][48][49][50][51][52], verifying early findings of the Alderman et al. study [53]. The major studies that implicated low levels of dietary Na intake in cardiovascular morbidity/mortality raising are presented in Fig. 1. ...
The last decade, a growing number of evidence support J-shape or inverse - instead of positive linear -- associations between dietary sodium intake and cardiovascular morbidity/mortality. A careful evaluation of these studies leads to the following observations: less accurate methods for dietary sodium assessment are usually used; most studies included high-risk participants, enhancing the possibility of a 'reverse causality' phenomenon. However, these limitations do not explain all the findings. Few carefully designed randomized clinical trials comparing different levels of sodium intake that address the issue of the optimal and safe range exist; therefore, current guidelines recommend a higher cut-off instead of a safe range of intake. Given the demonstrated harmful effects of very low sodium diets leading to subclinical vascular damage in animal studies, the 'J-shape hypothesis' cannot yet be either neglected or verified. There is a great need of well-designed general population-based prospective randomized clinical trials to address the issue.
... Moreover, potential side effects of SR (activation of the reninaldosterone system and the sympathetic nervous system, and increases in blood concentrations of lipids) (3) may increase, rather than decrease, mortality in a population. Side effects have been claimed to be transient (4), but a study of primitive populations on permanent low salt intake has indicated that side effects are persistent (7), as also indicated by recent metaanalyses (8,9) and population studies (10,11), which have shown an increased mortality risk associated with low sodium intake. In contrast, population modeling studies have projected that SR would result in millions of lives being saved worldwide (12,13). ...
... A recent long-term follow-up study of 3126 overweight individuals with prehypertension who were randomly assigned to a low-sodium diet or a usual-sodium diet for ≤3 y failed to demonstrate a difference in all-cause mortality during a 20-y period (low sodium: 8% vs. usual sodium: 9%; P = 0.19) (31,32). Similarly, despite a significant association between sodium intake and BP (27,28), population studies show low sodium intake to be associated with increased mortality (8)(9)(10)(11). The latest meta-analysis of 133,118 individuals from across 4 large population studies concluded that, "Compared with moderate sodium intake, high sodium intake is associated with an increased risk of cardiovascular events and death in hypertensive populations (no association in normotensive population), while the association of low sodium intake with increased risk of cardiovascular events and death is observed in those with or without hypertension" (8). Thus, these findings indicate that the identified potential adverse effects (3,18,29) may in fact be harmful and that SR should probably not be a target for the general population but only for hypertensives with a high sodium intake (33). ...
... Based on these longer-term levels of salt reductions, our results suggest that a reduction of SBP of −0.1 to −0.6 mm Hg is likely to be obtainable with no effect on DBP. Taking into consideration that SR has side effects (3,18,29), and that a low sodium intake has been associated with increased mortality in several population studies (8)(9)(10)(11), it is questionable whether this modest systolic dose-response relation justifies SR in the general population. ...
Background:
The projected reduced mortality effect of reduced sodium intake in model-based studies conflicts with the observed increased mortality associated with low sodium intake in population studies. This may reflect an overestimation of the dose-response relation between sodium reduction (SR) and blood pressure (BP) used in mortality modeling studies.
Objectives:
The present meta-regression analysis sought to estimate the dose-response relations between SR and BP in study groups with mean BP above or below the 75th percentile of the general population.
Methods:
Based on a literature search from 1 January 1946 to 11 April 2018, we identified 133 randomized controlled trials allocating healthy or hypertensive individuals to SR or usual sodium intake. Multivariable regression analyses of the mean SR versus the mean blood pressure effect adjusted for effect modifiers were performed.
Results:
In study groups with mean BP above the 75th percentile [131/78 mm Hg systolic BP (SBP)/diastolic BP (DBP)], there was strong evidence of a linear dose-response relation between SR and BP. For SBP, the dose-response relation was -7.7 mm Hg/100 mmol SR (95% CI: -10.4, -5.0), and for DBP it was -3.0 mm Hg/100 mmol SR (95% CI: -4.6, -1.4). In study groups with mean BP ≤ 131/78 mm Hg, the relation between SR and BP was weak. For SBP it was -1.46 mm Hg/100 mmol SR (95% CI: -2.7, -0.20) and for DBP it was: -0.07 mm Hg/100 mmol SR (95% CI: -1.5, 1.4).
Conclusions:
Only study groups with a BP in the highest 25th percentile of the population showed a clinically significant drop in BP with SR. The policy of lowering dietary sodium intake in the general population may need to be reframed to target patients with hypertension. This study was registered at PROSPERO 2015 as CRD42015017773.
... The INTERSALT study proved a di-rect connection between daily salt intake and blood pressure. This was later confirmed by the epidemiological studies INTERMAP (International Population Study on Macronutrients and BP) [6] and EPIC (European Prospective Investigation on Cancer and Nutrition) [7]. Namely, the data of the INTERMAP study confirm the correlation of sodium and sodium/potassium in the diet with blood pressure, despite the intake of other macronutrients. ...
... This conclusion about the sodiumblood pressure relationship adds to the abundance of data from other studies that imply that sodium intake influences the increase in blood pressure with age, which contributes to the high prevalence rate of prehypertension/hypertension and the high incidence rate of cardiovascular events [6]. The conclusion of the EPIC study, related to 24 h excretion of sodium, is that the risk of heart attack in an apparently healthy population is associated with high concentrations of sodium in diuresis, but with a decrease in natriuresis, blood pressure drops and thus the risk of heart attack [7]. ...
People consumed salt exclusively through food millions of years ago, which amounted to less than 0.5 g/day. Recent researches indicate that the average daily consumption of salt is more than 10 g/day. The general conclusion of studies investigating the relationship between dietary salt intake and blood pressure led to recommendations on reducing salt intake and limiting total intake to 5 g of salt per day by the World Health Organization and the European Safety Agency of Food. Increased salt intake causes suppression of the Renin-Angiotensin-Aldosterone system by reducing sodium renal excretion. Also, an increase in salt intake leads to an increase in the concentration of sodium in the blood, which causes high secretion of vasopressin and causes high blood pressure. Namely, bread is a basic food and is high in salt, but the salt parameter is not mandatory in accordance with the regulations. Today, almost every EU country has different strategies that include recommending salt reduction through food reformulation to reduce the salt content of food, including bread and bakery products. Achieving and maintaining the reduction of the population's salt intake will soon give a great benefit in terms of the prevention of cardiovascular events as the first cause of death globally, then great savings for the health system and an individual.
... Excessive sodium intake is a major public health concern globally. 1,2 Numerous studies have found high sodium intake to be associated with increased risks of cardiovascular disease (CVD) and all-cause mortality among patients with hypertension, [3][4][5][6][7] but findings among individuals without hypertension have been equivocal. [3][4][5][6][7][8][9][10][11][12] Although several randomized controlled trials have evaluated the effect of reduction in sodium intake, [13][14][15] no trial has been conducted to assess the effect of extra sodium intake on the risks of CVD and mortality owing to ethical considerations. ...
... 1,2 Numerous studies have found high sodium intake to be associated with increased risks of cardiovascular disease (CVD) and all-cause mortality among patients with hypertension, [3][4][5][6][7] but findings among individuals without hypertension have been equivocal. [3][4][5][6][7][8][9][10][11][12] Although several randomized controlled trials have evaluated the effect of reduction in sodium intake, [13][14][15] no trial has been conducted to assess the effect of extra sodium intake on the risks of CVD and mortality owing to ethical considerations. ...
Aims
Previous studies have found high sodium intake to be associated with increased risks of cardiovascular disease (CVD) and all-cause mortality among individuals with hypertension; findings on the effect of intake among individuals without hypertension have been equivocal. We aimed to compare the risks of incident CVD and all-cause mortality among initiators of sodium-containing acetaminophen with the risk of initiators of non-sodium-containing formulations of the same drug according to the history of hypertension.
Methods and results
Using The Health Improvement Network, we conducted two cohort studies among individuals with and without hypertension. We examined the relation of sodium-containing acetaminophen to the risk of each outcome during 1-year follow-up using marginal structural models with an inverse probability weighting to adjust for time-varying confounders. The outcomes were incident CVD (myocardial infarction, stroke, and heart failure) and all-cause mortality. Among individuals with hypertension (mean age: 73.4 years), 122 CVDs occurred among 4532 initiators of sodium-containing acetaminophen (1-year risk: 5.6%) and 3051 among 146 866 non-sodium-containing acetaminophen initiators (1-year risk: 4.6%). The average weighted hazard ratio (HR) was 1.59 [95% confidence interval (CI) 1.32–1.92]. Among individuals without hypertension (mean age: 71.0 years), 105 CVDs occurred among 5351 initiators of sodium-containing acetaminophen (1-year risk: 4.4%) and 2079 among 141 948 non-sodium-containing acetaminophen initiators (1-year risk: 3.7%), with an average weighted HR of 1.45 (95% CI 1.18–1.79). Results of specific CVD outcomes and all-cause mortality were similar.
Conclusion
The initiation of sodium-containing acetaminophen was associated with increased risks of CVD and all-cause mortality among individuals with or without hypertension. Our findings suggest that individuals should avoid unnecessary excessive sodium intake through sodium-containing acetaminophen use.
Key question
Previous studies have found high sodium intake to be associated with increased risks of cardiovascular disease and all-cause mortality among individuals with hypertension; findings on the effect of intake among individuals without hypertension have been equivocal.
Key finding
Sodium-containing acetaminophen was associated with a statistically significant higher risk of incident cardiovascular disease and all-cause mortality than the non-sodium-containing acetaminophen initiation among individuals with and without hypertension.
Take-home message
Both individuals with and without hypertension should avoid unnecessary excessive sodium intake through sodium-containing acetaminophen use.
... Predictive equations have been developed to estimate 24-h urinary sodium excretion from spot urine samples ( Kawasaki et al., 1993;Tanaka et al., 2002;Brown et al., 2013). Their validity has been assessed in a number of studies ( Kawasaki et al., 1993;Tanaka et al., 2002;Brown et al., 2013;Cogswell et al., 2013;Ji et al., 2014;Mente et al., 2014;Pfister et al., 2014;Polonia et al., 2017;Zhou et al., 2017) (Appendix B). Associations between these estimates and 24-h urinary excretions have primarily been assessed through correlation coefficients, which ranged between +0.33 (one timed morning urine collection in a sample of 297 white women in the UK and application of the Tanaka formula ( Ji et al., 2014)) and + 0.53 (one morning urine collection in a sample of 159 men and women in Japan and application of the Kawasaki formula ( Kawasaki et al., 1993)). ...
... Afssa (2001) suggested that healthy adults should not consume more than 12 g/day and not less than 5 g/day of sodium chloride (corresponding to 4.8 and 2.0 g/day of sodium). In 2016, Anses considered recent literature on the relationship between sodium intake and blood pressure ( Mente et al., 2014) and cardiovascular risk (IOM, 2013;Adler et al., 2014;O'Donnell et al., 2014;Pfister et al., 2014) and noted a lack of consensus; the experts concluded that current data were insufficient to set a UL, a PRI or an AI for sodium (Anses, 2016b). In its update of the food-based dietary guidelines for the French population, Anses selected the median consumption of sodium as the maximum value not to be exceeded, which amounts to reducing intake in the half of the population with higher intake levels, in agreement with public health policies. ...
Abstract Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) derived dietary reference values (DRVs) for sodium. Evidence from balance studies on sodium and on the relationship between sodium intake and health outcomes, in particular cardiovascular disease (CVD)‐related endpoints and bone health, was reviewed. The data were not sufficient to enable an average requirement (AR) or population reference intake (PRI) to be derived. However, by integrating the available evidence and associated uncertainties, the Panel considers that a sodium intake of 2.0 g/day represents a level of sodium for which there is sufficient confidence in a reduced risk of CVD in the general adult population. In addition, a sodium intake of 2.0 g/day is likely to allow most of the general adult population to maintain sodium balance. Therefore, the Panel considers that 2.0 g sodium/day is a safe and adequate intake for the general EU population of adults. The same value applies to pregnant and lactating women. Sodium intakes that are considered safe and adequate for children are extrapolated from the value for adults, adjusting for their respective energy requirement and including a growth factor, and are as follows: 1.1 g/day for children aged 1–3 years, 1.3 g/day for children aged 4–6 years, 1.7 g/day for children aged 7–10 years and 2.0 g/day for children aged 11–17 years, respectively. For infants aged 7–11 months, an Adequate Intake (AI) of 0.2 g/day is proposed based on upwards extrapolation of the estimated sodium intake in exclusively breast‐fed infants aged 0–6 months.
... Although dietary sodium restriction reduces BP and prevents hypertension, previous studies show that a LS diet increases CVD risk factors including sympathetic activation and stimulation of the renin-angiotensin-aldosterone system (RAAS), peripheral insulin resistance [3,5], and enhanced plasma lipid concentrations [6,7]. Therefore, a J-or U-shaped association between sodium intake and cardiovascular mortality has been suggested [8,9]. Clinical and preclinical studies also report that dietary sodium chloride restriction elevates plasma lipids and induces arterial-wall lipid infiltration [3,6,7,[10][11][12][13][14]. ...
Dietary sodium restriction increases plasma triglycerides (TG) and total cholesterol (TC) concentrations as well as causing insulin resistance and stimulation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system. Stimulation of the angiotensin II type-1 receptor (AT1) is associated with insulin resistance, inflammation, and the inhibition of adipogenesis. The current study investigated whether aerobic exercise training (AET) mitigates or inhibits the adverse effects of dietary sodium restriction on adiposity, inflammation, and insulin sensitivity in periepididymal adipose tissue. LDL receptor knockout mice were fed either a normal-sodium (NS; 1.27% NaCl) or a low-sodium (LS; 0.15% NaCl) diet and were either subjected to AET for 90 days or kept sedentary. Body mass, blood pressure (BP), hematocrit, plasma TC, TG, glucose and 24-hour urinary sodium (UNa) concentrations, insulin sensitivity, lipoprotein profile, histopathological analyses, and gene and protein expression were determined. The results were evaluated using two-way ANOVA. Differences were not observed in BP, hematocrit, diet consumption, and TC. The LS diet was found to enhance body mass, insulin resistance, plasma glucose, TG, LDL-C, and VLDL-TG and reduce UNa, HDL-C, and HDL-TG, showing a pro-atherogenic lipid profile. In periepididymal adipose tissue, the LS diet increased tissue mass, TG, TC, AT1 receptor, pro-inflammatory macro-phages contents, and the area of adipocytes; contrarily, the LS diet decreased anti-inflammatory macrophages, protein contents and the transcription of genes related to insulin sensitivity. The AET prevented insulin resistance, but did not protect against dyslipidemia, adipose tissue pro-inflammatory profile, increased tissue mass, AT1 receptor expression, TG, and TC induced by the LS diet.
... Some studies found the relationship between sodium intake and all-cause mortality was linearhigh sodium intake was associated with high mortality in a doseresponse fashion, [4][5][6][7][8][9][10][11][12] while others revealed a U-shaped or J-shaped relationshipboth low and high sodium intake were associated with higher mortality. [13][14][15][16][17][18][19][20][21][22][23][24] Consequently, the optimal level of sodium intake for overall health has become highly controversial. 12,24 The purpose of this study is to examine the potential methodological gaps resulting in the contradictory findings on the relationship between sodium intake and health outcomes. ...
Background and aims
The findings on the relationship between sodium intake and health outcomes such as cardiovascular disease and all-cause mortality have been controversial. Some studies found the relationship between sodium intake and all-cause mortality was linear while others found a U-shaped or J-shaped relationship. This study aimed to identify the methodological issues contributing to the conflicting findings.
Methods and results
The present study investigated methodological gaps in assessing the relationship between sodium intake and health outcomes (hypertension, cardiovascular disease, and all-cause mortality). The contradictory findings appear to stem from flawed methods used in the published studies: (1) Both spot and 24-h urinary sodium collection methods underestimate the adverse effects of low sodium intake and overestimate the harmful effects of high sodium intake, (2) the linear relationship between sodium intake and all-cause mortality appears to be a result of random chance due to small sample sizes, and (3) the divergent temporal trends of sodium consumption and hypertension prevalence indicate sodium intake was not the primary cause of the worldwide hypertension epidemic.
Conclusion
Considering, (1) sodium is an essential nutrient, (2) the adverse effects of low and high sodium intake appear to be under- and over-estimated, respectively, (3) large studies have found a U-shaped or J-shaped relationship between sodium intake and all-cause mortality, and (4) sodium consumption is unlikely to be the major driver behind the worldwide hypertension epidemic and has little effect on the blood pressure of most normotensive individuals, the recommendation for population-wide low sodium intake merits further evaluation.
... spot urine in 9 studies[25][26][27][28][29][30][31][32][33];(3) dietary methods in 7 studies[34][35][36][37][38][39][40]; and (4) overnight urine in 1 study[41].The results from this pooled analysis (38 effect sizes) indicated that BMI was significantly greater among adults in the highest intake group of sodium compared to those in the lowest intake group of sodium (BMI mean difference = 1.52 kg/m 2 ; 95% confidence interval [CI], 1.24-1.80; P < 0.001; I 2 = 97%), presenting considerable heterogeneity. ...
Background/objectives:
The scientific evidence of a sodium-obesity association is limited by sodium intake assessments. Our specific aim is to synthesize the association between dietary sodium intake and obesity across the sodium intake assessments as evidenced by systematic reviews in adults.
Subjects/methods:
A systematic search identified systematic reviews comparing the association of dietary sodium intakes with obesity-related outcomes such as body mass index (BMI), body weight, waist circumference, and risk of (abdominal) obesity. We searched PubMed on October 24, 2022. To assess the Risk of Bias in Systematic Reviews (ROBIS), we employed the ROBIS tool.
Results:
This review included 3 systematic reviews, consisting of 39 unique observational studies (35 cross-sectional studies and 4 longitudinal studies) and 15 randomized controlled trials (RCTs). We found consistently positive associations between dietary sodium intake and obesity-related outcomes in cross-sectional studies. Studies that used 24-h urine collection indicated a greater BMI for those with higher sodium intake (mean difference = 2.27 kg/m2; 95% confidence interval [CI], 1.59-2.51; P < 0.001; I2 = 77%) compared to studies that used spot urine (mean difference = 1.34 kg/m2; 95% CI, 1.13-1.55; P < 0.001; I2 = 95%) and dietary methods (mean difference = 0.85 kg/m2; 95% CI, 0.1-1.51; P < 0.05; I2 = 95%).
Conclusions:
Quantitative synthesis of the systematic reviews has shown that cross-sectional associations between dietary sodium intake and obesity outcomes were substantially different across the sodium intake assessments. We need more high-quality prospective cohort studies and RCTs using 24-h urine collection to examine the causal effects of sodium intake on obesity.
... To present the risk of all-cause mortality, equal quartiles of sodium intake were made. As the range of the third quartile (3.6-4.7 g/24 h; mean 3.9 g/24 h) best reflects the intake of >2.3 g/day and <5 g/day, which has been shown to be most beneficial with regard to (CV) mortality [14][15][16][17][18], it was used as the reference group. ...
Background:
Several studies have found a U-shaped association between sodium intake and mortality. The increased mortality risk of low sodium intake has raised debates and hampers widespread acceptance of public health campaigns and dietary guidelines on reducing sodium intake. Whether the excess risk can be attributed to low sodium intake alone or concomitant inadequate intake of other relevant nutrients is unknown.
Objective:
We investigated whether concomitant low protein intake could explain the lower part of the U-shaped association of sodium intake with all-cause mortality.
Methods:
We included 1603 individuals aged between 60 and 75 years old from the gender- and socioeconomic status-balanced prospective Lifelines-MINUTHE cohort study. Using multivariable Cox regression analyses, we investigated the association of sodium intake (24 h urinary sodium excretion) with all-cause mortality, including the interaction with protein intake calculated from the Maroni formula.
Results:
Mean intakes of sodium and protein were 3.9 ± 1.6 g/day and 1.1 ± 0.3 g/kg/day, respectively. After a median follow-up of 8.9 years, 125 individuals (7.8%) had died. The proportion of participants with insufficient protein intake (<0.8 g/kg/day) was inversely related to sodium intake (i.e., 23.3% in Q1 versus 2.8% in Q4, p < 0.001). We found an increased risk for mortality in both the highest quartile (Q4, >4.7 g/day; hazard ratio (HR) 1.74 (95% confidence interval (CI) 1.03-2.95)) and the lowest two quartiles of sodium intake (Q1, 0.7-2.8 g/day; 2.05 (1.16-3.62); p = 0.01 and Q2, 2.8-3.6 g/day; 1.85 (1.08-3.20); p = 0.03), compared with the third quartile of sodium intake (Q3, 3.6-4.7 g/day). This U-shaped association was significantly modified by protein intake (Pinteraction = 0.006), with the increased mortality risk of low sodium intake being reversed to the lowest mortality risk with concomitant high protein intake. In contrast, the increased mortality risk of low sodium intake was magnified by concomitant low protein intake.
Conclusions:
We found that a higher protein intake counteracts the increased mortality risk observed in subjects with a low sodium intake. In contrast, a joint low intake of sodium and protein is associated with an increased mortality risk, allegedly due to poor nutritional status. These findings support the guidelines that advocate a lower sodium intake, while highlighting the importance of recognizing overall nutritional status among older adults.
... g/day) was associated with an increased risk of cardiovascular diseases or death in a large cohort study (35). Similar findings were noted regarding the associations of urinary sodium excretion and dietary sodium restriction with adverse heart failure outcomes (36)(37)(38). Our findings were in line with these reports, and were further supported by a recent randomized controlled trial (39) in which a low sodium diet (<1,500 mg/day vs. usual care) was not associated with a risk reduction in clinical outcomes in patients with chronic heart failure. ...
Background and aims
We investigated the association of adherence to the Dietary Approaches to Stop Hypertension (DASH) diet with all-cause mortality in patients with a history of heart failure.
Methods
We analyzed data from the National Health and Nutrition Examination Survey (NHANES). Dietary information was obtained from a 24-h dietary recall interview. Adherence to the DASH diet was assessed using the DASH score. The primary outcome was all-cause mortality which was confirmed by the end of 2011. Weighted Cox proportional hazards regression models were used to determine the hazard ratios and 95% CI for the association of the DASH score and all-cause mortality with multivariate adjustment.
Results
The median DASH score was 2 among the 832 study participants. There were 319 participants who died after a median follow-up duration of 4.7 years. A higher DASH score (>2 vs. ≤ 2) was not associated with a decrease in the risk of all-cause mortality (adjusted HR 1.003, 95% CI 0.760–1.323, p = 0.983). With respect to the components of the DASH score, a lower sodium intake was not associated with a decreased risk of mortality (adjusted HR 1.045, 95% CI 0.738–1.478, p = 0.803).
Conclusion
A higher DASH score (>2 vs. ≤ 2) was not associated with all-cause mortality in patients with heart failure.
... These mechanisms are more evident in profound clinical stages of HF. Another reason is that low sodium intake has undesirable effects on insulin resistance and serum lipids, factors that predispose patients to cardiovascular diseases [9][10][11]. A meta-analysis of 23 cohort studies and 2 clinical trials demonstrated that dietary sodium restriction did not improve the quality of life over the long term, did not reduce the readmission rate within the short term (≤30 days), and increased the readmission rate over the long term. ...
The main challenges in heart failure (HF) treatment are to manage patients with refractory acute decompensated HF and to stabilize the clinical status of a patient with chronic heart failure. Beyond the use of medications targeted in the inhibition of the neurohormonal system, the balance of salt and fluid plays an important role in the maintenance of clinical compensation in respect of renal function. In the case of heart failure, a debate of opinion exists on salt restriction. Restricted dietary sodium might lead to worse outcomes in heart failure patients due to the activation of the neurohormonal system and malnutrition. On the contrary, positive sodium balance is the primary driver of water retention and, ultimately, volume overload in acute HF. Some recent studies reported associations of decreased salt consumption with higher readmission rates and increased mortality. Thus, the usefulness of salt restriction in heart failure management remains debated. The use of individualized nutritional support, compared with standard hospital food, was effective in reducing these risks, particularly in the group of patients at high nutritional risk.
... Notwithstanding the compelling evidence, some studies have reported contradictory results on the association between sodium consumption and health outcomes [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. The studies report that, rather than there being a linear rise in CVD as sodium intake rises, CVD declines as sodium levels declines from high levels, with the benefit then leveling off and CVD increasing for lower sodium levels (describing a J-shaped curve). ...
Purpose of Review
The scientific consensus on which global health organizations base public health policies is that high sodium intake increases blood pressure (BP) in a linear fashion contributing to cardiovascular disease (CVD). A moderate reduction in sodium intake to 2000 mg per day helps ensure that BP remains at a healthy level to reduce the burden of CVD.
Recent Findings
Yet, since as long ago as 1988, and more recently in eight articles published in the European Heart Journal in 2020 and 2021, some researchers have propagated a myth that reducing sodium does not consistently reduce CVD but rather that lower sodium might increase the risk of CVD. These claims are not well-founded and support some food and beverage industry’s vested interests in the use of excessive amounts of salt to preserve food, enhance taste, and increase thirst. Nevertheless, some researchers, often with funding from the food industry, continue to publish such claims without addressing the numerous objections. This article analyzes the eight articles as a case study, summarizes misleading claims, their objections, and it offers possible reasons for such claims.
Summary
Our study calls upon journal editors to ensure that unfounded claims about sodium intake be rigorously challenged by independent reviewers before publication; to avoid editorial writers who have been co-authors with the subject paper’s authors; to require statements of conflict of interest; and to ensure that their pages are used only by those who seek to advance knowledge by engaging in the scientific method and its collegial pursuit. The public interest in the prevention and treatment of disease requires no less.
... The PURE study group and other investigators examined the association between the amount of dietary sodium intake and risk of major morbidity and mortality in the PURE population itself and in studies of other high-risk populations. [48][49][50][51][52][53][54] In the PURE study, the population attributable fraction (PAF) for high sodium consumption (>6 gm per day) for CVD (3.2%) and death (3.9%), were relatively small in the overall cohort. This was consistent with other studies that observed a modest association when examining the direct association of urinary sodium excretion (as an indirect measure of sodium intake). ...
By the beginning of the 21st century, cardiovascular disease (CVD) had become the leading cause of premature mortality and morbidity worldwide, with 80% originating from less developed lower income countries in line with societal and economic developments. Extensive research on causes and risk factors have been carried out since the mid-20th century and have established individual factors such as smoking, hypertension, diabetes and dyslipidemia as CVD risk factors, followed by others. Two recent major case-control studies have summarized the role of common major CVD risk factors in determining the risk of myocardial infarction (INTERHEART Study) and stroke (INTERSTROKE Study). They showed that 9 and 10 common risk factors accounted for over 90% of the risk of myocardial infarction and stroke, respectively, and established the focus in prevention of these common CVD. The efficacy of lowering blood pressure, blood glucose and lipid lowering therapies has been shown to reduce subsequent morbidity and mortality.
Leading international health organizations have published guidelines which are updated regularly to set the standards for providing guidance for implementation and management of risk factors. Interventions can also be costly and long-term adherence, essential to be effective in reducing risks, tends to decrease drastically with time.
Dietary recommendations have been incorporated into national and professional guidelines for CVD prevention since the 1960’s. Based on new research, some existing dietary recommendation may be outdated and should be reviewed, and revised, if necessary.
A perspective of CVD prevention and treatment in developing countries is highlighted.
... Given that the large within-individual variability in consumption may be overestimated, the strengths of the associations of sodium and potassium intake with BP may be underestimated 46 . Second, given the observational nature of the study, although we adjusted for major confounders of the association between sodium and potassium excretion and BP, adjustment for these factors may attenuate or amplify the association, and residual confounding is a potential limitation [47][48][49] . Third, causality in outcomes and exposure cannot be inferred from the cross-sectional survey data in this study. ...
The direction and magnitude of the association between sodium and potassium excretion and blood pressure (BP) may differ depending on the characteristics of the study participant or the intake assessment method. Our objective was to assess the relationship between BP, hypertension and 24-h urinary sodium and potassium excretion among Chinese adults. A total of 1424 provincially representative Chinese residents aged 18 to 69 years participated in a cross-sectional survey in 2017 that included demographic data, physical measurements and 24-h urine collection. In this study, the average 24-h urinary sodium and potassium excretion and sodium-to-potassium ratio were 3811.4 mg/day, 1449.3 mg/day, and 4.9, respectively. After multivariable adjustment, each 1000 mg difference in 24-h urinary sodium excretion was significantly associated with systolic BP (0.64 mm Hg; 95% confidence interval [CI] 0.05–1.24) and diastolic BP (0.45 mm Hg; 95% CI 0.08–0.81), and each 1000 mg difference in 24-h urinary potassium excretion was inversely associated with systolic BP (− 3.07 mm Hg; 95% CI − 4.57 to − 1.57) and diastolic BP (− 0.94 mm Hg; 95% CI − 1.87 to − 0.02). The sodium-to-potassium ratio was significantly associated with systolic BP (0.78 mm Hg; 95% CI 0.42–1.13) and diastolic BP (0.31 mm Hg; 95% CI 0.10–0.53) per 1-unit increase. These associations were mainly driven by the hypertensive group. Those with a sodium intake above about 4900 mg/24 h or with a potassium intake below about 1000 mg/24 h had a higher risk of hypertension. At higher but not lower levels of 24-h urinary sodium excretion, potassium can better blunt the sodium-BP relationship. The adjusted odds ratios (ORs) of hypertension in the highest quartile compared with the lowest quartile of excretion were 0.54 (95% CI 0.35–0.84) for potassium and 1.71 (95% CI 1.16–2.51) for the sodium-to-potassium ratio, while the corresponding OR for sodium was not significant (OR, 1.28; 95% CI 0.83–1.98). Our results showed that the sodium intake was significantly associated with BP among hypertensive patients and the inverse association between potassium intake and BP was stronger and involved a larger fraction of the population, especially those with a potassium intake below 1000 mg/24 h should probably increase their potassium intake.
... However, consensus has not been reached regarding the association between Na intake, blood pressure, and heart disease (5)(6)(7)(8) . The findings of previous studies have not been consistent with regard to the association between high and low Na intake and mortality related to heart disease (7)(8)(9)(10)(11)(12)(13) . Although the definitions of "high" and "low" for Na intake are unclear (8) , the average daily consumption of Na is between 3.0 -6.0 g/d globally (14)(15)(16) , and many countries and regions have instituted salt reduction programs. ...
Intakes of excess sodium [Na] and insufficient potassium [K] are two major contributors of heart diseases and stroke development. However, no precise study has existed on Na and K intakes among Indonesian adults. This study aimed to estimate the Na and K intakes using two consecutive 24-h urine collections. Participants were community-dwelling adults aged between 20 and 96 years, randomly selected from a pool of resident registration numbers. Of the 506 participants, 479 (240 men and 239 women) completed urine collections. The mean Na excretion was 102.8 and 100.6 mmol/d, while the mean K excretion was 25.0 and 23.4 mmol/d for men and women, respectively. Na and K excretions were higher in participants with a higher body mass index (BMI). A higher K excretion was associated only with younger age. More than 80% of the participants consumed more than 5 g/d of salt (the upper limit recommended by the Indonesian government). Whereas none of them consumed more than 3,510 mg/d of K (the lower limit). The high Na and low K intakes, especially high Na among participants with high BMI, should be considered when the intervention programs are future planned in this country.
... Additionally, the follow up duration was only 31.4 months [47]. The other study determined CVD by using self-reported intake of drugs and assessed sodium intake by spot urine collection with a loss follow-up rate higher than 20% [56]. ...
Dietary sodium intake has received considerable attention as a potential risk factor of cardiovascular disease. However, evidence on the dose-response association between dietary sodium intake and cardiovascular disease risk is unclear. Embase and PubMed were searched from their inception to 17 August 2020 and studies that examined the association between sodium intake and cardiovascular disease in adolescents were not included in this review. We conducted a meta-analysis to estimate the effect of high sodium intake using a random effects model. The Newcastle-Ottawa Scale assessment was performed. A random-effects dose-response model was used to estimate the linear and nonlinear dose-response relationships. Subgroup analyses and meta-regression were conducted to explain the observed heterogeneity. We identified 36 reports, which included a total of 616,905 participants, and 20 of these reports were also used for a dose-response meta-analysis. Compared with individuals with low sodium intake, individuals with high sodium intake had a higher adjusted risk of cardiovascular disease (Rate ratio: 1.19, 95% confidence intervals = 1.08–1.30). Our findings suggest that there is a significant linear relationship between dietary sodium intake and cardiovascular disease risk. The risk of cardiovascular disease increased up to 6% for every 1 g increase in dietary sodium intake. A low-sodium diet should be encouraged and education regarding reduced sodium intake should be provided.
... 10 Consumption of sodium more than 3.5 gm/day is also associated with cardiovascular events. [11][12][13] WHO recommends a reduction in salt intake to less than 5 gm/day (sodium 2 gm/day) to reduce blood pressure and risk of coronary heart disease and stroke. 14 Measured data on mean population salt intake are available mainly for high and middle income countries with the increased processing in food industry and a greater availability of processed foods both in urban and rural areas of low and middle income countries, sources of sodium are shifting towards these foods. ...
Background: Healthy dietary practice is an important lifestyle modification and one of the key adjuncts to pharmacotherapy in management of hypertension. A modest reduction in salt intake of 5 gm/day lowered blood pressure by 7/4 mmHg diastolic in hypertensive patients. Despite knowledge about the ill consequences, many people continue to consume high levels of salt in their diet. To motivate people to reduce salt in their diet, a solid understanding of barriers encountered by those under salt reduction recommendation is necessary. Hence, this study was conducted with the aim of identifying the barriers to dietary salt reduction among hypertensive patients.Methods: A community based cross sectional study was conducted on a sample of 356 hypertensive patients in field practice areas (urban and rural) in Department of Community Medicine, JNMC, AMU, Aligarh. A pretested semi-structured questionnaire was used for the study. Compliance to dietary salt intake was assessed by calculating average salt intake per person per day. The tenets of health belief model were used to examine the key determinants of human behavior. Analysis was done by using correlation, proportions, chi-square and multiple linear regression.Results: 31.4% of the participants took salt <5 gm per day. A significant association was noticed with area, religion, social class, family size, perceived benefits and perceived susceptibility. A significant positive correlation was seen with total adherence score and family size.Conclusions: A lot of barriers hinder the compliance to dietary salt reduction. Health Education stressing the role of salt reduction in control of blood pressure is recommended.
... To our knowledge, the association of excess sodium intake and incident HF has not been studied before using the 24-h urinary sodium excretion data. Using spot urine samples and lifestyle questionnaires, the EPIC-Norfolk study showed a statistically significant increased risk of HF (hazard ratio 1.32 in the highest quintile compared with the second lowest quintile) in a study sample of 25,639 persons from the UK [27]. There was a marked attenuation of this association (hazard ratio, 1.21; 95% confidence interval, 0.98-1.49) ...
Aims: The objective was to evaluate whether sodium intake, assessed with the gold standard 24-h urinary collections, was related to long-term incidence of death, cardiovascular disease (CVD) and diabetes mellitus (DM).
Methods: A cohort of 4630 individuals aged 25–64 years collected 24-h urine samples in 1979–2002 and were followed up to 14 years for the incidence of any CVD, coronary heart disease (CHD), stroke, heart failure (HF) and DM event, and death. Cox proportional hazards models were used to estimate the association between the baseline salt intake and incident events and adjusted for baseline age, body mass index, serum cholesterol, prevalent DM, and stratified by sex and cohort baseline year.
Results: During the follow-up, we observed 423 deaths, 424 CVD events (288 CHD events, 142 strokes, 139 HF events) and 161 DM events. Compared with the highest quartile of salt intake, persons in the lowest quartile had a lower incidence of CVD (hazard ratio [HR] 0.70; 95% confidence interval [CI], 0.51–0.95, p = .02), CHD (HR 0.63 [95% CI 0.42–0.94], p = .02) and DM (HR 0.52 [95% CI 0.31–0.87], p = .01). The results were non-significant for mortality, HF, and stroke.
Conclusion: High sodium intake is associated with an increased incidence of CVD and DM.
... Within studies, many factors may influence the outcome such as sex, age, energy intake, smoking, blood pressure, social status, and comorbidities. Adjustment for these factors may attenuate 35 or amplify 11 36 37 the association between sodium intake and outcome. Despite such within study adjustments, there may still be unexplained differences across studies (residual confounding). ...
... Optimal dietary sodium targets are a matter of ongoing debate. Observational studies demonstrate that sodium intakes below 2645 mg (115 mmol/24 h) and above 4945 mg (215 mmol/24 h) are associated with higher mortality 49,51 . The results of a meta-analysis supports these findings by comparing three sodium groups; high (>5000 mg/24 h or 217 mmol/24 h), moderate (2700-5000 mg/24 h or 117-217 mmol/24 h) and low (<2700 mg/24 h or 117 mmol/24 h), with the risk of a cardiovascular event 20 . ...
Despite public health bodies advocating for lowering dietary sodium and increasing potassium intake to improve cardiovascular outcomes, people with diabetes are not meeting these targets. We hypothesize that (i) both at an individual level and within the cohort, there will be a low adherence to the guidelines and (ii) sodium and potassium intake will remain stable over time.
We conducted this prospective study in a cohort of 904 participants with diabetes who provided 24-h urine collections from 2009 to 2015. Dietary sodium and potassium intake were estimated from 24-h urinary sodium (uNa) and potassium (uK) measurements. Additional data were collected for: 24-h urinary volume (uVol), creatinine (uCr),; serum creatinine, urea, estimated glomerular filtration rate (eGFR), glycated haemoglobin (HbA1c), fasting glucose, lipids); clinical characteristics (age, blood pressure (BP), body mass index (BMI) and duration of diabetes). Adherence to recommended dietary sodium (uNa < 2300 mg/24 h (100mmol/24 h)) and potassium (uK > 4680 mg/24 h(120 mmol/24)) intake were the main outcome measures.
Participants (n = 904) completed 3689 urine collections (average four collections/participant). The mean ± SD (mmol/24 h) for uNa was 181 ± 73 and uK was 76 ± 25. After correcting uNa for uCr, 7% and 5% of participants met dietary sodium and potassium guidelines respectively. Males were less likely to meet sodium guidelines (OR 0.40, p < 0.001) but were more likely to meet potassium guidelines (OR 6.13, p < 0.001). Longer duration of diabetes was associated with higher adherence to sodium and potassium guidelines (OR 1.04, p < 0.001 and OR 0.96, p = 0.006 respectively). Increasing age was significantly associated with adherence to potassium guidelines (OR 0.97, p = 0.007).
People with diabetes do not follow current dietary sodium and potassium guidelines and are less likely to change their dietary intake of sodium and potassium over time.
... Previous studies reported not only that high sodium intake was strongly related to the development of HTN and increased risk of cardiovascular diseases (CVDs) but also that dietary intervention could decrease arterial blood pressure (BP) and reduce left ventricular mass in hypertensive individuals [5][6][7][8][9]. These findings suggest that an excess sodium diet is one of the most important modifiable risk factors for HTN and other CVDs. ...
Background
A high salt diet is associated with the development of hypertension, one of the most important cardiovascular risk factors. A reduction in sodium intake seems to have an effect on increasing serum triglycerides (TGs). Elevated TGs are independently linked to cardiovascular risk. However, there is limited evidence of a possible interactive effect of sodium intake and serum TGs on high blood pressure (BP).
Methods
We conducted a nationwide, population-based interaction analysis using the Kawasaki method for estimating 24-h urinary sodium excretion (e24hUNaEKawasaki) as a candidate indicator of dietary sodium intake. All native Koreans aged 20 years or older without significant medical illness were eligible for inclusion.
Results
A total of 16936 participants were divided into quintiles according to their e24hUNaEKawasaki results. Participants in the highest quintile were more obese and hypertensive and had higher white blood cell count, lower hemoglobin, greater glycemic exposure, and poor lipid profiles compared to the same parameters of individuals in other quintiles. Linear regression revealed that e24UNaEKawasaki was related to systolic BP, diastolic BP, and TGs. Multiple logistic regression, adjusted for dietary sodium intake and various conventional risk factors for chronic vascular diseases, showed that both e24UNaEKawasaki and TGs were significant predictors of hypertension. Our interaction analysis demonstrated that increased sodium intake was associated with higher risk of hypertension in participants with elevated TGs than in those without (adjusted RERI = 0.022, 95% CI = 0.017–0.027; adjusted AP = 0.017, 95% CI = 0.006–0.028; adjusted SI = 1.010, 95% CI = 1.007–1.014).
Conclusion
Our findings suggest that the interaction between a high salt diet and elevated TGs may exert synergistic biological effects on the risk of hypertension.
... 12 Recently, 'e-24hr-U sodium ' has known to be associated with cardiovascular disease, obesity, metabolic syndrome, and cancer and mortality. 36 This study has limitation of retrospective cohort study. However, we applied to the same methodology of history taking, urinary sample collection and endoscopic resection to all enrolled patients. ...
Background : Although previous studies have suggested a high salt intake as a risk factor for precancerous and cancerous lesions of stomach, the evidence is not sufficient to draw a conclusion yet. We aimed to evaluate the association between ‘estimated 24-hour urinary sodium excretion’ and prevalence of synchronous gastric epithelial neoplasm.
Methods: Among 2017 patients with gastric epithelial neoplasms, who had test results for estimated 24-hour urinary sodium excretion, 1310 were enrolled.
Results: There were 545 (41.6%) patients with high-grade dysplasia and early gastric cancer. The mean age was 64.5 years; 853 (65.1%) were men and 244 (18.6%) were smokers. The rate of Helicobacter pylori infection was 71.0% (797/1123). The incidence of synchronous gastric epithelial neoplasm was 10.6% (139/1310). Significant interactions were seen between estimated 24-hour urine sodium’ and sex ( P -interaction =0.003), with the association largely limited to women; ‘estimated 24-hour urine sodium’ (aOR, 1.26; 95% CI, 1.05 to 1.51, P = 0.012) was an independent risk factor for synchronous gastric neoplasm in women.
Conclusions: High ‘estimated 24-hour urinary sodium excretion’ was associated with synchronous gastric epithelial neoplasm in women.
... 55 Some studies have found a positive association between dietary sodium intake and these clinical outcomes, whereas others have found inverse, J-shaped or U-shaped associations. [56][57][58][59][60][61][62][63][64][65] These conflicting findings can likely be partly explained by methodological limitations, such as systematic and random error in sodium measurements, reverse causality, insufficient statistical power, residual confounding, and inadequate followup duration. 55,64,66 In summary, dietary sodium reduction should be recommended to lower population BP levels and risk of hypertension. ...
Hypertension is the leading cause of cardiovascular disease and premature death worldwide. Owing to the widespread use of antihypertensive medications, global mean blood pressure (BP) has remained constant or has decreased slightly over the past four decades. By contrast, the prevalence of hypertension has increased, especially in low- and middle-income countries (LMICs). Estimates suggest that 31.1% of adults (1.39 billion) worldwide had hypertension in 2010. The prevalence of hypertension among adults was higher in LMICs (31.5%, 1.04 billion people) than in high-income countries (28.5%, 349 million people). Variations in the levels of risk factors for hypertension, such as high sodium intake, low potassium intake, obesity, alcohol consumption, physical inactivity and unhealthy diet, may explain some of the regional heterogeneity in hypertension prevalence. Despite the increasing prevalence, the proportions of hypertension awareness, treatment and BP control are low, particularly in LMICs, and few comprehensive assessments of the economic impact of hypertension exist. Future studies are warranted to test implementation strategies for hypertension prevention and control, especially in low-income populations, and to accurately assess the prevalence and financial burden of hypertension worldwide.
... 4 5 8 9 Current public health policy on targets for sodium intake is based primarily on small, and mostly short term, clinical trials evaluating the relation of changes in sodium and potassium intake with blood pressure. 4 8 Although clinical trials have reported a decrease in blood pressure with a reduction in sodium intake, 8 many prospective cohort studies have reported a J-shaped association of sodium intake and cardiovascular disease or mortality, [10][11][12][13][14][15][16] with an increased risk emerging at sodium intakes <2.7 g/ day and >5 g/day. 10 The increased cardiovascular risk associated with high sodium intake seems to be especially in those with hypertension, 17 whereas the increased risk associated with low sodium intake might be mediated through activation of physiological systems to conserve sodium (eg, reninangiotensin-aldosterone system). ...
OBJECTIVE To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults. DESIGN International prospective cohort study. SETTING 18 high, middle, and low income countries, sampled from urban and rural communities. PARTICIPANTS 103 570 people who provided morning fasting urine samples. MAIN OUTCOME MEASURES Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day). RESULTS Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007). CONCLUSIONS These findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.
... 19,20,21 Studi lain menghubungkan asupan natrium lebih dari 3,5 g/hari dengan kejadian penyakit kardiovaskular. 22 Menurunkan konsumsi garam (NaCl) atau asupan natrium menjadi sangat penting untuk penduduk Indonesia, dengan mengurangi konsumsi makanan jadi atau makanan yang cenderung mengandung natrium tinggi, seperti mi instan; yang cenderung untuk mengonsumsi makanan ini, terutama pada usia remaja. ...
Indonesia is facing a very complex health problems. Non-communicable diseases is increasing, while infectious diseases still quite dominant. Among other contributing factors is the imbalance of daily required nutrients intake. Overweight is closely associated with daily intake level of consumed foods, especially the calorie contributors such as sugar and fat, besides, excessive salt intake drives people to eat more. This article is intended to determine the intake of sugar, salt and fat of Indonesian population that is exceeding the WHO recommendations. The analysis used the data of Individual Food Consumption Survey or SKMI 2014 that collected data and asked all food consumed in the last 24 hours from 45,802 households and 145,360 household members in all provinces in Indonesia. Descriptive analysis of all 17 food groups was undertaken to calculate the intake level of sugar, salt, and fat of each individual, and also calculated the proportion based on the characteristics of age group, sex, place of residence, socio-economic, and by province as well. The analysis showed that 77 million people or 29.7 percent of Indonesia's population consumed sugar, salt, and fat exceeding WHO recommendations: sugar (> 50 g/day), salt (> 5 g/day), and fat (> 67 g/day). This should be anticipated due to the increasing trend of people with non-communicable diseases, such as obesity, hypertension, diabetes mellitus, and stroke which have already apparent from 2007 to 2013. It was suggested to reduce the intake of sugar, salt, and fat need of the population through advocacy, counseling, socialization at schools, food and beverage industries, restaurants, factories, and other relevant institutions.
Keywords: intake sugar-salt-fat, non-communicable diseases, Indonesian population
... 23 Could this be explained by the apparent U-shaped association between heart failure risk and urine sodium excretion in healthy men and women with the lowest incidence of heart failure in the group of 3000-3400 mg/d? 45 That association was confirmed in a meta-analysis of 23 cohort studies and 2 clinical trials. 46 However, reverse causation in the observational studies might have been a confounding factor. ...
Restricting dietary sodium is a common recommendation given by clinicians to patients with heart failure and is one supported by current guidelines. However, the quality of evidence for this recommendation is suboptimal, and there is no consensus on the optimal level of sodium intake. Though excessive sodium intake is associated with left ventricular hypertrophy and hypertension, recent data have suggested that very low sodium intake is paradoxically associated with worse outcomes for patients with heart failure. This is possibly explained by the association between low sodium intake and activation of the sympathetic and renin-angiotensin-aldosterone systems. Nevertheless, sodium restriction is routinely recommended and remains a cornerstone of heart failure and blood pressure therapy. In this editorial review we discuss the pros and cons of sodium restriction for patients with heart failure from the current literature.
... More recently, some studies (Graudal, Jürgens, Baslund, & Alderman, 2014;O'donnell et al., 2014;Pfister et al., 2014) reported a U-or J-shaped curve describing the relationship between sodium intake and HBP-this finding is debated because of the adjustment for the presence of other variables, such as preexisting cardiac or inflammatory disorders. Despite the fact that 95% of the world's population has an average salt consumption of between 6 and 12 g, well below the threshold level tolerated per day (up to 55 g/day), the upper limit recommended by many institutions does not exceed 5.8 g/day (Graudal & Jürgens, 2018). ...
Currently, there is major consumer concern about dietary salt intake worldwide. However, even with the development of contemporary preservation practices, sodium chloride is still essential in processed meat products. Despite a long history of use, salt is now seriously controversial in food due to health concerns that are mostly related to high blood pressure and cardiovascular risks. Changes in meat processing methods have reduced those potential risks, but different perceptions continue to shape how consumers and society view dietary salt. The current consumer demand for additive‐free food, such as the clean‐label movement, has renewed consumer willingness for naturalness in food products.
... Lower levels of Na (<3 g/d) have also been identified to be associated with higher risk of death and cardiovascular events [26]. Several prospective cohort studies have indicated a U-shaped relationship between salt consumption and cardiovascular disease or mortality, with increased risk at both high-and low-intake extremes [27][28][29][30]. In comparison with a moderate consumption of salt, observational data demonstrate that very high intakes (>6 g Na/day, representing only 10% of the population studied) are associated with an excessive risk of cardiovascular events and death, but only in the case of those with hypertension. ...
Rapid urbanization in low- and middle-income countries (LMICs) is transforming dietary patterns from reliance on traditional staples to increased consumption of energy-dense foods high in saturated fats, trans fats, sugars, and salt. A systematic literature review was conducted to determine major food sources of salt in LMICs that could be targeted in strategies to lower population salt intake. Articles were sourced using Medline, Web of Science, Scopus, and grey literature. Inclusion criteria were: reported dietary intake of Na/salt using dietary assessment methods and food composition tables and/or laboratory analysis of salt content of specific foods in populations in countries defined as low or middle income (LMIC) according to World Bank criteria. Of the 3207 records retrieved, 15 studies conducted in 12 LMICs from diverse geographical regions met the eligibility criteria. The major sources of dietary salt were breads, meat and meat products, bakery products, instant noodles, salted preserved foods, milk and dairy products, and condiments. Identification of foods that contribute to salt intake in LMICs allows for development of multi-faceted approaches to salt reduction that include consumer education, accompanied by product reformulation.
... Over the last years, some prospective cohort studies have shown a J-or U-shaped relationship between sodium intake and cardiovascular diseases (O'Donnell et al. 2014;Pfister et al. 2014;Mente et al. 2016), as well as between higher risk of kidney failure (Ekinci et al. 2011;Stolarz-Skrzypek et al. 2011;Thomas et al. 2011;O'Donnell et al. 2014;Mills et al. 2016). However, Cogswell et al. (2016) argue that the studies showing a J-or U-shaped relationship used conveniently but potentially biased methods to estimate individual intake. ...
The relationship between salt intake and cardiovascular diseases is a contemporary scientific controversy, which has been attributed to the limits of the measures of salt intake used in the studies. Thus, this article sought to systematically review the literature on the methods used to estimate salt intake in different study designs. Of the 124 articles, 60.5% used only biochemical measures, 26.6% only self-report measures and 12.9% reported the combined use of both methods. The 24-hour urinary sodium excretion was the predominant biochemical method (79.1%) and the Food Frequency Questionnaire was the predominant self-report measure (36.4%). Interventional studies used mostly 24-hour urinary sodium excretion; while longitudinal studies used self-report measures. The question guiding the study and its design, as well as constraints related to costs, sample size and feasibility seems to influence the choice of the type of measurement.
... Although 1 observational study in healthy individuals linked a higher U na output to a higher incidence of new onset HF, this association was not statistically significant after adjusting for blood pressure (20). Our HF patients, under optimal neurohormonal blockade, did not exhibit hypertension. ...
Objectives:
This study sought to determine the relationship between urinary sodium (Una) concentration and the pathophysiologic interaction with the development of acute heart failure (AHF) hospitalization.
Background:
No data are available on the longitudinal dynamics of Una concentration in patients with chronic heart failure (HF), including its temporal relationship with AHF hospitalization.
Methods:
Stable, chronic HF patients with either reduced or preserved ejection fraction were prospectively included to undergo prospective collection of morning spot Una samples for 30 consecutive weeks. Linear mixed modeling was used to assess the longitudinal changes in Una concentration. Patients were followed for the development of the clinical endpoint of AHF.
Results:
A total of 80 chronic HF patients (71 ± 11 years of age; an N-terminal pro-B-type natriuretic peptide [NT-proBNP] concentration of 771 [interquartile range: 221 to 1,906] ng/l; left ventricular ejection fraction [LVEF] 33 ± 7%) prospectively submitted weekly pre-diuretic first void morning Una samples for 30 weeks. A total of 1,970 Una samples were collected, with mean Una concentration of 81.6 ± 41 mmol/l. Sodium excretion remained stable over time on a population level (time effect p = 0.663). However, interindividual differences revealed the presence of high (88 mmol/l Una [n = 39]) and low (73 mmol/l Una [n = 41]) sodium excreters. Only younger age was an independent predictor of high sodium excretion (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83 to 1.00; p = 0.045 per year). During 587 ± 54 days of follow-up, 21 patients were admitted for AHF. Patients who developed AHF had significantly lower Una concentrations (F[1.80] = 24.063; p < 0.001). The discriminating capacity of Una concentration to detect AHF persisted after inclusion of NT-proBNP and estimated glomerular filtration rate (eGFR) measurements as random effects (p = 0.041). Furthermore, Una concentration dropped (Una = 46 ± 16 mmol/l vs. 70 ± 32 mmol/l, respectively; p = 0.003) in the week preceding the hospitalization and returned to the individual's baseline (Una = 71 ± 22 mmol/l; p = 0.002) following recompensation, while such early longitudinal changes in weight and dyspnea scores were not apparent in the week preceding decompensation.
Conclusions:
Overall, Una concentration remained relatively stable over time, but large interindividual differences existed in stable, chronic HF patients. Patients who developed AHF exhibited a chronically lower Una concentration and exhibited a further drop in Una concentration during the week preceding hospitalization. Ambulatory Una sample collection is feasible and may offer additional prognostic and therapeutic information.
... 4 5 8 9 Current public health policy on targets for sodium intake is based primarily on small, and mostly short term, clinical trials evaluating the relation of changes in sodium and potassium intake with blood pressure. 4 8 Although clinical trials have reported a decrease in blood pressure with a reduction in sodium intake, 8 many prospective cohort studies have reported a J-shaped association of sodium intake and cardiovascular disease or mortality, [10][11][12][13][14][15][16] with an increased risk emerging at sodium intakes <2.7 g/ day and >5 g/day. 10 The increased cardiovascular risk associated with high sodium intake seems to be especially in those with hypertension, 17 whereas the increased risk associated with low sodium intake might be mediated through activation of physiological systems to conserve sodium (eg, reninangiotensin-aldosterone system). ...
Objective
To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.
Design
International prospective cohort study.
Setting
18 high, middle, and low income countries, sampled from urban and rural communities.
Participants
103 570 people who provided morning fasting urine samples.
Main outcome measures
Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category variable for joint sodium and potassium was generated: sodium excretion (low (<3 g/day), moderate (3-5 g/day), and high (>5 g/day) sodium intakes) by potassium excretion (greater/equal or less than median 2.1 g/day).
Results
Mean estimated sodium and potassium urinary excretion were 4.93 g/day and 2.12 g/day, respectively. After a median follow-up of 8.2 years, 7884 (6.1%) participants had died or experienced a major cardiovascular event. Increasing urinary sodium excretion was positively associated with increasing potassium excretion (unadjusted r=0.34), and only 0.002% had a concomitant urinary excretion of <2.0 g/day of sodium and >3.5 g/day of potassium. A J-shaped association was observed of sodium excretion and inverse association of potassium excretion with death and cardiovascular events. For joint sodium and potassium excretion categories, the lowest risk of death and cardiovascular events occurred in the group with moderate sodium excretion (3-5 g/day) and higher potassium excretion (21.9% of cohort). Compared with this reference group, the combinations of low potassium with low sodium excretion (hazard ratio 1.23, 1.11 to 1.37; 7.4% of cohort) and low potassium with high sodium excretion (1.21, 1.11 to 1.32; 13.8% of cohort) were associated with the highest risk, followed by low sodium excretion (1.19, 1.02 to 1.38; 3.3% of cohort) and high sodium excretion (1.10, 1.02 to 1.18; 29.6% of cohort) among those with potassium excretion greater than the median. Higher potassium excretion attenuated the increased cardiovascular risk associated with high sodium excretion (P for interaction=0.007).
Conclusions
These findings suggest that the simultaneous target of low sodium intake (<2 g/day) with high potassium intake (>3.5 g/day) is extremely uncommon. Combined moderate sodium intake (3-5 g/day) with high potassium intake is associated with the lowest risk of mortality and cardiovascular events.
... Rather, the data should provide impetus for similar trials of salt substitution in countries where mean sodium intake is lower than 5 g/day. 2 Meta-analyses of individual participant data in cohort studies have revealed a J-shaped association between sodium intake and cardiovascular disease, 28,29 mirroring findings from physiological studies reporting adverse cardiovascular biomarker effects at extremes of sodium intake. 3,8,9,30,31 J-shaped or inverse associations have been seen in several studies assessing sodium intake by 24 h urine collection, 32-35 morning fasting urine, 11,[36][37][38] or diet, [39][40][41] and in different types of populations (elderly people, patients with vascular disease or diabetes, and the general population). 11,32-41 Furthermore, no study has shown significantly reduced rates of clinical events with sodium intake less than 3 g/day versus 3-5 g/day. ...
Background:
WHO recommends that populations consume less than 2 g/day sodium as a preventive measure against cardiovascular disease, but this target has not been achieved in any country. This recommendation is primarily based on individual-level data from short-term trials of blood pressure (BP) without data relating low sodium intake to reduced cardiovascular events from randomised trials or observational studies. We investigated the associations between community-level mean sodium and potassium intake, cardiovascular disease, and mortality.
Methods:
The Prospective Urban Rural Epidemiology study is ongoing in 21 countries. Here we report an analysis done in 18 countries with data on clinical outcomes. Eligible participants were adults aged 35-70 years without cardiovascular disease, sampled from the general population. We used morning fasting urine to estimate 24 h sodium and potassium excretion as a surrogate for intake. We assessed community-level associations between sodium and potassium intake and BP in 369 communities (all >50 participants) and cardiovascular disease and mortality in 255 communities (all >100 participants), and used individual-level data to adjust for known confounders.
Findings:
95 767 participants in 369 communities were assessed for BP and 82 544 in 255 communities for cardiovascular outcomes with follow-up for a median of 8·1 years. 82 (80%) of 103 communities in China had a mean sodium intake greater than 5 g/day, whereas in other countries 224 (84%) of 266 communities had a mean intake of 3-5 g/day. Overall, mean systolic BP increased by 2·86 mm Hg per 1 g increase in mean sodium intake, but positive associations were only seen among the communities in the highest tertile of sodium intake (p<0·0001 for heterogeneity). The association between mean sodium intake and major cardiovascular events showed significant deviations from linearity (p=0·043) due to a significant inverse association in the lowest tertile of sodium intake (lowest tertile <4·43 g/day, mean intake 4·04 g/day, range 3·42-4·43; change -1·00 events per 1000 years, 95% CI -2·00 to -0·01, p=0·0497), no association in the middle tertile (middle tertile 4·43-5·08 g/day, mean intake 4·70 g/day, 4·44-5.05; change 0·24 events per 1000 years, -2·12 to 2·61, p=0·8391), and a positive but non-significant association in the highest tertile (highest tertile >5·08 g/day, mean intake 5·75 g/day, >5·08-7·49; change 0·37 events per 1000 years, -0·03 to 0·78, p=0·0712). A strong association was seen with stroke in China (mean sodium intake 5·58 g/day, 0·42 events per 1000 years, 95% CI 0·16 to 0·67, p=0·0020) compared with in other countries (4·49 g/day, -0·26 events, -0·46 to -0·06, p=0·0124; p<0·0001 for heterogeneity). All major cardiovascular outcomes decreased with increasing potassium intake in all countries.
Interpretation:
Sodium intake was associated with cardiovascular disease and strokes only in communities where mean intake was greater than 5 g/day. A strategy of sodium reduction in these communities and countries but not in others might be appropriate.
Funding:
Population Health Research Institute, Canadian Institutes of Health Research, Canadian Institutes of Health Canada Strategy for Patient-Oriented Research, Ontario Ministry of Health and Long-Term Care, Heart and Stroke Foundation of Ontario, and European Research Council.
... 97 Surprisingly, that recommendation was made without caveat despite clear evidence from the Institute of Medicine and experimental trials that the clinical significance of sodium reduction in healthy populations is trivial [98][99][100] and despite studies on health outcomes showing that sodium restriction to the 2,300 mg/day range in healthy populations increases the risk of death and cardiovascular disease. [101][102][103][104] Evidence shows that the relationship of sodium to health follows the same J-shaped or Ushaped pattern as most nutrients. 105 This finding agrees with both the ancient wisdom of Paracelsus, who stated that it is "the dose that makes a thing a poison," 106(p511) and the basic physiologic fact that human fluid regulation can accommodate a wide range of sodium intakes without affecting blood pressure. ...
Objectives
To test the hypothesis that the association of formula-estimated sodium intake from spot urine with cardiovascular disease is independent of spot urinary sodium concentration.
Methods
We included 435 336 participants in the UK Biobank whose sodium intake was estimated from spot urine using INTERSALT, Kawasaki, and Tanaka formulas. Hazard ratios for cardiovascular disease (CVD) events and deaths were estimated using Cox proportional-hazard model adjusted for multiple covariates. Penalized Cox regression was used to assess nonlinear relations. Hazard ratios were recalculated after replacement of the sodium concentration term with sex-specific mean values (women: 67.5 mmol/l; men: 89.8 mmol/l) to assess how other components of the formulas influenced these associations.
Results
Forty-four thousand two hundred and sixty-eight CVD events and 3251 CVD deaths occurred during a median follow-up of 12 years. The mean estimated sodium intake was 143 (SD = 35), 178 (52), and 147 (33) mmol/day based on INTERSALT, Kawasaki, and Tanaka formulas, respectively. For CVD incidence, linear inverse associations were observed for INTERSALT and Tanaka estimates [hazard ratios (95% CIs) for every 50 mmol reduction in estimated sodium intake: 0.9 (0.83–0.97) and 0.93 (0.89– 0.97); P -linear = 0.0047 and 0.0021], and a U-shaped association for the Kawasaki estimates ( P -nonlinear = 0.0026). When the sodium concentration term was fixed, inverse associations were seen for all formulas [0.86 (0.77–0.95), 0.96 (0.93–0.99) and 0.94 (0.89–0.99) for INTERSALT, Kawasaki, and Tanaka; P linear = 0.0054, 0.0166 and 0.0188]. For CVD mortality, no association was observed, but a nonlinear association was identified for the INTERSALT equation ( P -nonlinear = 0.0287) after fixing the sodium concentration.
Conclusion
These formula-estimated sodium intakes were associated with CVD incidence and mortality independently of spot urinary sodium concentration. We recommend these formulas not be used in studies associating sodium intake with CVD outcomes to avoid generating misleading evidence.
Importance
Numerous prospective cohort studies have reported a J-shaped association of urinary sodium excretion with cardiovascular events and mortality.
Objective
To study the association between sodium intake and incident atrial fibrillation (AF).
Design, Setting, and Participants
This cohort study included participants in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and Telmisartan Randomised Assessment Study in ACE Intolerant Subjects With Cardiovascular Disease (TRANSCEND) multicenter, randomized clinical trials comparing the effect of ramipril 10 mg daily with telmisartan 80 mg daily, or their combination (ONTARGET) or 80 mg telmisartan daily with placebo (TRANSCEND) for the outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure. ONTARGET and TRANSCEND included 31 546 participants with vascular disease or high-risk diabetes, and this study excluded participants without a urine sample for sodium measurement, missing data for key covariates, a history of AF, or AF detected in the first year after enrollment. Analyses were performed in July 2023 to May 2024.
Exposure
Estimated sodium intake from a morning fasting urine sample (Kawasaki formula).
Main Outcomes and Measures
The main outcome was incident AF. The association between estimated sodium intake and incident AF was modeled using multivariable adjusted Cox regression and cubic splines.
Results
A total of 27 391 participants (mean [SD] age, 66.3 [7.2] years; 19 310 [70.5%] male) were included. Mean (SD) estimated sodium intake was 4.8 (1.6) g/d. During a mean (SD) follow-up of 4.6 (1.0) years, 1562 participants (5.7%) had incident AF. After multivariable adjustment, a J-shaped association between sodium intake and AF risk was observed ( P for nonlinearity = .03). Sodium intake of 8 g/d or greater (3% of participants) was associated with incident AF (hazard ratio, 1.32; 95% CI, 1.01-1.74) compared with sodium intake of 4 to 5.99 g/d. Cubic splines showed that sodium intake greater than 6 g/d (19% of participants) was associated with a 10% increased AF risk per additional 1-g/d sodium intake (hazard ratio, 1.10; 95% CI, 1.03-1.18), but with no further lowering of AF risk at lower levels of sodium intake.
Conclusions and Relevance
In this cohort study of sodium intake and AF risk, there was a J-shaped association between sodium intakes and AF risk in patients with cardiovascular disease or diabetes. Lowering sodium intake for AF prevention is best targeted at individuals who consume high sodium diets.
Background
The impact of sodium intake on cardiovascular disease (CVD) health and mortality has been studied for decades, including the well-established association with blood pressure. However, non-linear patterns, dose–response associations, and sex differences in the relationship between sodium and potassium intakes and overall and cause-specific mortality remain to be elucidated and a comprehensive examination is lacking. Our study objective was to determine whether intake of sodium and potassium and the sodium–potassium ratio are associated with overall and cause-specific mortality in men and women.
Methods
We conducted a prospective analysis of 237,036 men and 179,068 women in the National Institutes of Health-AARP Diet and Health Study. Multivariable-adjusted Cox proportional hazard regression models were utilized to calculate hazard ratios. A systematic review and meta-analysis of cohort studies was also conducted.
Results
During 6,009,748 person-years of follow-up, there were 77,614 deaths, 49,297 among men and 28,317 among women. Adjusting for other risk factors, we found a significant positive association between higher sodium intake (≥ 2,000 mg/d) and increased overall and CVD mortality (overall mortality, fifth versus lowest quintile, men and women HRs = 1.06 and 1.10, Pnonlinearity < 0.0001; CVD mortality, fifth versus lowest quintile, HRs = 1.07 and 1.21, Pnonlinearity = 0.0002 and 0.01). Higher potassium intake and a lower sodium–potassium ratio were associated with a reduced mortality, with women showing stronger associations (overall mortality, fifth versus lowest quintile, HRs for potassium = 0.96 and 0.82, and HRs for the sodium–potassium ratio = 1.09 and 1.23, for men and women, respectively; Pnonlinearity < 0.05 and both P for interaction ≤ 0.0006). The overall mortality associations with intake of sodium, potassium and the sodium–potassium ratio were generally similar across population risk factor subgroups with the exception that the inverse potassium-mortality association was stronger in men with lower body mass index or fruit consumption (Pinteraction < 0.0004). The updated meta-analysis of cohort studies based on 42 risk estimates, 2,085,904 participants, and 80,085 CVD events yielded very similar results (highest versus lowest sodium categories, pooled relative risk for CVD events = 1.13, 95% CI: 1.06–1.20; Pnonlinearity < 0.001).
Conclusions
Our study demonstrates significant positive associations between daily sodium intake (within the range of sodium intake between 2,000 and 7,500 mg/d), the sodium–potassium ratio, and risk of CVD and overall mortality, with women having stronger sodium–potassium ratio-mortality associations than men, and with the meta-analysis providing compelling support for the CVD associations. These data may suggest decreasing sodium intake and increasing potassium intake as means to improve health and longevity, and our data pointing to a sex difference in the potassium-mortality and sodium–potassium ratio-mortality relationships provide additional evidence relevant to current dietary guidelines for the general adult population.
Systematic review registration
PROSPERO Identifier: CRD42022331618.
Background
We recently found that the frequency of adding salt to foods could reflect a person’s long-term salt taste preference and sodium intake, and was significantly related to life expectancy.
Objective
We analyzed whether the frequency of adding salt to foods was associated with incident cardiovascular disease (CVD) risk.
Methods
This study included 176,570 adults in UK Biobank who were initially free of CVD. Cox proportional hazards models were used to estimate the association between the frequency of adding salt to foods and incident CVD events.
Results
During a median of 11.8 years of follow-up, 9,963 total CVD events, 6,993 ischemic heart disease (IHD) cases, 2,007 stroke cases, and 2,269 heart failure cases were documented. Lower frequency of adding salt to foods was significantly associated with lower risk of total CVD events after adjustment for covariates and the DASH (Dietary Approaches to Stop Hypertension) diet (a modified DASH score was used without considering sodium intake). Compared with the group of always adding salt to foods, the adjusted HRs were 0.81 (95% CI: 0.73-0.90), 0.79 (95% CI: 0.71-0.87), and 0.77 (95% CI: 0.70-0.84) across the groups of usually, sometimes, and never/rarely, respectively (P trend < 0.001). Among the subtypes of CVD, adding salt showed the strongest association with heart failure (P trend <0.001), followed by IHD (P trend < 0.001), but was not associated with stroke. We found that participants who combined a DASH-style diet with the lowest frequency of adding salt had the lowest CVD risk.
Conclusions
Our findings indicate that lower frequency of adding salt to foods is associated with lower risk of CVD, particularly heart failure and IHD.
Objective
Copper plays a crucial role in redox reactions. The aims of this research are to examine the effects of copper consumption on general obesity and abdominal obesity risk.
Methods
Overall, data of 13,282 participants were obtained from the China Health and Nutrition Survey (1997–2011). A combination of individual 24-h recall and household survey was used to assess dietary intake. Time-dependent mixed effect Cox regression model treating family as a random effect were used to assess the associations between quintiles of copper intake, general obesity and abdominal obesity risk. Obesity was defined by BMI ≥ 28 kg/m2, and abdominal obesity was defined as waist circumference ≥85 cm in men and ≥80 cm in women.
Results
During follow-up, 1,073 and 4,583 incident cases of general obesity and abdominal obesity occurred respectively. There were U-shaped associations of dietary copper intakes with general obesity and abdominal obesity (P for nonlinearity <0.001). In the general obesity track, compared with quintile 3 (reference category), participants in the top quintile and bottom quintile showed higher general obesity risk (HR, 2.00; 95%CI: 1.63, 2.45 for the top quintile, HR, 1.34; 95%CI: 1.08, 1.68 for the bottom quintile). In the abdominal obesity track, compared with quintile 3, the top quintile and bottom quintile were also associated with a significantly increased risk of abdominal obesity (HR, 1.68; 95%CI: 1.52, 1.87 for the top quintile, HR, 1.36; 95%CI: 1.22, 1.52 for the bottom quintile).
Conclusions
We demonstrated U-shaped associations between dietary copper, general and abdominal obesity risk in Chinese and emphasized the importance of maintaining appropriate copper intake level for the prevention of obesity.
Excess salt intake is viewed as a major contributor to hypertension and cardiovascular disease, and dietary salt restriction is broadly recommended by public health guidelines. However, individuals can have widely varying physiological responses to salt intake, and a tailored approach to evaluation and intervention may be needed. The traditional sodium related concepts are challenging to assess clinically for two reasons: (1) spot and 24-hour urine sodium are frequently used to evaluate salt intake, but are more suitable for population study, and (2) some adverse effects of salt may be blood pressure-independent. In recent years, previously unknown mechanisms of sodium absorption and storage have been discovered. This review will outline the limitations of current methods to assess sodium balance and discuss new potential evaluation methods and treatment targets.
Background
Sodium, potassium, and the balance between these 2 nutrients are associated with hypertension and cardiovascular disease, and prevalence of these conditions increases with age. However, limited information is available on these intakes among older adults.
Objective
Our aim was to explore the socioeconomic and health factors associated with usual sodium and potassium intakes and the sodium to potassium (Na:K) ratio of older adults.
Design
This was a cross-sectional, secondary analysis of the 2011-2012, 2013-2014, and 2015-2016 National Health and Nutrition Examination Survey.
Participants/setting
This study included the data of 5,104 adults 50 years and older, with at least one reliable 24-hour dietary recall and an estimated glomerular filtration rate ≥60 mL/min/1.73 m².
Main outcome measures
Sodium and potassium intake, as absolute intake, density (per 1,000 kcal) and ratio of Na:K intake.
Statistical analyses
We used t tests and χ² tests to examine significant differences in intakes on a given day by characteristics. Linear and logistic regression models were used to assess associations of socioeconomic and health characteristics with usual sodium and potassium intakes, determined using the National Cancer Institute method.
Results
Only 26.2% of participants consumed <2,300 mg sodium (16.2% of men and 35.2% of women) and 36.0% of men and 38.1% of women consumed at least 3,400 mg and 2,600 mg of potassium, respectively. Fewer than one-third of participants consumed a Na:K ratio of <1.0. Women, those with lower blood pressure, and those with a lower body mass index were more likely to have a ratio <1.0.
Conclusions
Participants consumed too much sodium and not enough potassium, based on current recommendations. A higher Na:K ratio was significantly associated with established risk factors for cardiovascular disease. The study findings suggest that more research on cardiovascular health should include both sodium and potassium, as well as balance between these nutrients.
Background:
The low accuracy of equations predicting 24-h urinary sodium excretion using a single spot urine sample contributed to the misclassification of individual sodium intake levels. The application of single spot urine sample is limited by a lack of representativity of urinary sodium excretion, possibly due to the circadian rhythm in urinary excretion. This study aimed to explore the circadian rhythm, characteristics, and parameters in a healthy young adult Chinese population as a theoretical foundation for developing new approaches.
Methods:
Eighty-five participants (mean age 32.4 years) completed the 24-h urine collection by successively collecting each of the single-voided specimens within 24 h. The concentrations of the urinary sodium, potassium, and creatinine for each voided specimen were measured. Cosinor analysis was applied to explore the circadian rhythm of the urinary sodium, potassium, and creatinine excretion. The excretion per hour was computed for analyzing the change over time with repeated-measures analysis of variance and a cubic spline model.
Results:
The metabolism of urinary sodium, potassium, and creatinine showed different patterns of circadian rhythm, although the urinary sodium excretion showed non-significant parameters in the cosinor model. A significant circadian rhythm of urinary creatinine excretion was observed, while the circadian rhythm of sodium was less significant than that of potassium. The circadian rhythm of urinary sodium and creatinine excretion showed synchronization to some extent, which had a nocturnal peak and fell to the lowest around noon to afternoon. In contrast, the peak of potassium was observed in the morning and dropped to the lowest point in the evening. The hourly urinary excretion followed a similar circadian rhythm.
Conclusion:
It is necessary to consider the circadian rhythm of urinary sodium, potassium, and creatinine excretion in adults while exploring the estimation model for 24-h urinary sodium excretion using spot urine.
Background:
Recent cohort studies show that salt intake below 6 g is associated with increased mortality. These findings have not changed public recommendations to lower salt intake below 6 g, which are based on assumed blood pressure (BP) effects and no side-effects.
Objectives:
To assess the effects of sodium reduction on BP, and on potential side-effects (hormones and lipids) SEARCH METHODS: The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to April 2018 and a top-up search in March 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. The top-up search articles are recorded under "awaiting assessment."
Selection criteria:
Studies randomizing persons to low-sodium and high-sodium diets were included if they evaluated at least one of the outcome parameters (BP, renin, aldosterone, noradrenalin, adrenalin, cholesterol, high-density lipoprotein, low-density lipoprotein and triglyceride,.
Data collection and analysis:
Two review authors independently collected data, which were analysed with Review Manager 5.3. Certainty of evidence was assessed using GRADE.
Main results:
Since the first review in 2003 the number of included references has increased from 96 to 195 (174 were in white participants). As a previous study found different BP outcomes in black and white study populations, we stratified the BP outcomes by race. The effect of sodium reduction (from 203 to 65 mmol/day) on BP in white participants was as follows: Normal blood pressure: SBP: mean difference (MD) -1.14 mmHg (95% confidence interval (CI): -1.65 to -0.63), 5982 participants, 95 trials; DBP: MD + 0.01 mmHg (95% CI: -0.37 to 0.39), 6276 participants, 96 trials. Hypertension: SBP: MD -5.71 mmHg (95% CI: -6.67 to -4.74), 3998 participants,88 trials; DBP: MD -2.87 mmHg (95% CI: -3.41 to -2.32), 4032 participants, 89 trials (all high-quality evidence). The largest bias contrast across studies was recorded for the detection bias element. A comparison of detection bias low-risk studies versus high/unclear risk studies showed no differences. The effect of sodium reduction (from 195 to 66 mmol/day) on BP in black participants was as follows: Normal blood pressure: SBP: mean difference (MD) -4.02 mmHg (95% CI:-7.37 to -0.68); DBP: MD -2.01 mmHg (95% CI:-4.37, 0.35), 253 participants, 7 trials. Hypertension: SBP: MD -6.64 mmHg (95% CI:-9.00, -4.27); DBP: MD -2.91 mmHg (95% CI:-4.52, -1.30), 398 participants, 8 trials (low-quality evidence). The effect of sodium reduction (from 217 to 103 mmol/day) on BP in Asian participants was as follows: Normal blood pressure: SBP: mean difference (MD) -1.50 mmHg (95% CI: -3.09, 0.10); DBP: MD -1.06 mmHg (95% CI:-2.53 to 0.41), 950 participants, 5 trials. Hypertension: SBP: MD -7.75 mmHg (95% CI:-11.44, -4.07); DBP: MD -2.68 mmHg (95% CI: -4.21 to -1.15), 254 participants, 8 trials (moderate-low-quality evidence). During sodium reduction renin increased 1.56 ng/mL/hour (95%CI:1.39, 1.73) in 2904 participants (82 trials); aldosterone increased 104 pg/mL (95%CI:88.4,119.7) in 2506 participants (66 trials); noradrenalin increased 62.3 pg/mL: (95%CI: 41.9, 82.8) in 878 participants (35 trials); adrenalin increased 7.55 pg/mL (95%CI: 0.85, 14.26) in 331 participants (15 trials); cholesterol increased 5.19 mg/dL (95%CI:2.1, 8.3) in 917 participants (27 trials); triglyceride increased 7.10 mg/dL (95%CI: 3.1,11.1) in 712 participants (20 trials); LDL tended to increase 2.46 mg/dl (95%CI: -1, 5.9) in 696 participants (18 trials); HDL was unchanged -0.3 mg/dl (95%CI: -1.66,1.05) in 738 participants (20 trials) (All high-quality evidence except the evidence for adrenalin).
Authors' conclusions:
In white participants, sodium reduction in accordance with the public recommendations resulted in mean arterial pressure (MAP) decrease of about 0.4 mmHg in participants with normal blood pressure and a MAP decrease of about 4 mmHg in participants with hypertension. Weak evidence indicated that these effects may be a little greater in black and Asian participants. The effects of sodium reduction on potential side effects (hormones and lipids) were more consistent than the effect on BP, especially in people with normal BP.
Objective:
To investigate the associations of sodium excretion with blood pressure, mortality and cardiovascular diseases in Chinese population.
Methods:
We studied 39 366 individuals aged 35-70 years from 115 urban and rural communities in 12 centers across mainland China. Trained research staff conducted face-to-face interview to record baseline information of all participants based on questionnaires, and collected their morning fasting urine samples to estimate 24-h sodium excretion (24hUNaE). Multivariable frailty Cox regression accounting for clustering by centre was performed to examine the association between estimated 24hUNaE and the primary composite outcome of death and major cardiovascular events in a Chinese population.
Results:
Mean 24hUNaE was 5.68 (SD 1.69) g/day. After a median follow-up of 8.8 years, the composite outcome occurred in 3080 (7.8%) participants, of which 1426 (3.5%) died and 2192 (5.4%) suffered from cardiovascular events. 24hUNaE was positively associated with increased SBP and DBP. Using the 24hUNaE level of 4-4.99 g/day as the reference group, a 24hUNaE of either lower (<3 g/day) or higher (≥7 g/day) was associated with an increased risk of the composite outcome with a hazard ratio of 1.22 (95% confidence interval: 1.01-1.49) and 1.15 (95% confidence interval: 1.01-1.30), respectively. A similar trend was observed between 24hUNaE level and risk of death or major cardiovascular events.
Conclusion:
These findings support a positive association between estimated urinary sodium excretion and blood pressure, and a possible J-shaped pattern of association between sodium excretion and clinical outcomes, with the lowest risk in participants with sodium excretion between 3 and 5 g/day.
Several blood pressure guidelines recommend low sodium intake (<2.3 g/day, 100 mmol, 5.8 g/day of salt) for the entire population, on the premise that reductions in sodium intake, irrespective of the levels, will lower blood pressure, and, in turn, reduce cardiovascular disease occurrence. These guidelines have been developed without effective interventions to achieve sustained low sodium intake in free-living individuals, without a feasible method to estimate sodium intake reliably in individuals, and without high-quality evidence that low sodium intake reduces cardiovascular events (compared with moderate intake). In this review, we examine whether the recommendation for low sodium intake, reached by current guideline panels, is supported by robust evidence. Our review provides a counterpoint to the current recommendation for low sodium intake and suggests that a specific low sodium intake target (e.g. <2.3 g/day) for individuals may be unfeasible, of uncertain effect on other dietary factors and of unproven effectiveness in reducing cardiovascular disease. We contend that current evidence, despite methodological limitations, suggests that most of the world's population consume a moderate range of dietary sodium (2.3-4.6g/day; 1-2 teaspoons of salt) that is not associated with increased cardiovascular risk, and that the risk of cardiovascular disease increases when sodium intakes exceed 5 g/day. While current evidence has limitations, and there are differences of opinion in interpretation of existing evidence, it is reasonable, based upon observational studies, to suggest a population-level mean target of <5 g/day in populations with mean sodium intake of >5 g/day, while awaiting the results of large randomized controlled trials of sodium reduction on incidence of cardiovascular events and mortality.
We report on an analysis to explore the association between estimated 24-hour urinary sodium excretion (surrogate for sodium intake) and incident cardiovascular disease (CVD) and mortality. Data were obtained from 398 628 UK Biobank prospective cohort study participants (40–69 years) recruited between 2006 and 2010, with no history of CVD, renal disease, diabetes mellitus or cancer, and cardiovascular events and mortality recorded during follow-up. Hazard ratios between 24-hour sodium excretion were estimated from spot urinary sodium concentrations across incident CVD and its components and all-cause and cause-specific mortality. In restricted cubic splines analyses, there was little evidence for an association between estimated 24-hour sodium excretion and CVD, coronary heart disease, or stroke; hazard ratios for CVD (95% CIs) for the 15th and 85th percentiles (2.5 and 4.2 g/day, respectively) compared with the 50th percentile of estimated sodium excretion (3.2 g/day) were 1.05 (1.01–1.10) and 0.96 (0.92–1.00), respectively. An inverse association was observed with heart failure, but that was no longer apparent in sensitivity analysis. A J-shaped association was observed between estimated sodium excretion and mortality. Our findings do not support a J-shaped association of estimated sodium excretion with CVD, although such an association was apparent for all-cause and cause-specific mortality across a wide range of diseases. Reasons for these differences are unclear; methodological limitations, including the use of estimating equations based on spot urinary data, need to be considered in interpreting our findings.
Background and objectives:
Low sodium and high potassium intake is reported to be a risk of hypertension. However, it is uncertain whether these associations can be generalized to those without hypertension. This study is to evaluate the associations of systolic and diastolic blood pressure (SBP and DBP, respectively) with estimated urinary sodium excretion (eUNaE), estimated urinary potassium excretion (eUKE) and their ratio (Na/K ratio) among hypertensive, normotensive, and hypotensive Chinese individuals.
Methods and study design:
A large institution-based cross-sectional study was conducted at the Third Xiangya Hospital, Changsha between August 2017 and November 2018. Spot urine samples were collected to test urinary sodium, potassium, and creatinine excretions for each participant. The Kawasaki formula was used to estimate 24-hour urinary sodium and potassium excretions.
Results:
A total of 26,363 eligible subjects were used to analyze the associations of blood pressure with eUNaE, eUKE, and their ratio. 27.3% (n=7,201) of participants were diagnosed with hypertension, 5.4% (n=1,427) were diagnosed with hypotension, and the remaining of 17,735 participants were normotensive. A significant increase in SBP and DBP was related to the Na/K ratio increase in hypertensive and normotensive subgroups (all ptrend<0.01), but the association was not significant for DBP among hypotensive individuals (ptrend=0.58). Stronger associations of SBP with the Na/K ratio were observed in older people (pinteraction<0.01) and females (pinteraction<0.0001), but the same trend was not observed for DBP (pinteraction=0.10 and 0.88, respectively).
Conclusions:
High potassium and low sodium intake were further confirmed to reduce blood pressure in hypotensive, normotensive, and hypertensive individuals.
Effective population-based interventions are required to reduce the global burden of cardiovascular disease (CVD). Reducing salt intake has emerged as a leading target, with many guidelines recommending sodium intakes of 2.3 g/day or lower. These guideline thresholds are based largely on clinical trials reporting a reduction in blood pressure with low, compared with moderate, intake. However, no large-scale randomized trials have been conducted to determine the effect of low sodium intake on CV events. Prospective cohort studies evaluating the association between sodium intake and CV outcomes have been inconsistent and a number of recent studies have reported an association between low sodium intake (in the range recommended by current guidelines) and an increased risk of CV death. In the largest of these studies, a J-shaped association between sodium intake and CV death and heart failure was found. Despite a large body of research in this area, there are divergent interpretations of these data, with some advocating a re-evaluation of the current guideline recommendations. In this article, we explore potential reasons for the differing interpretations of existing evidence on the association between sodium intake and CVD. Similar to other areas in prevention, the controversy is likely to remain unresolved until large-scale definitive randomized controlled trials are conducted to determine the effect of low sodium intake (compared to moderate intake) on CVD incidence.
Summary points
Summary pointsHeart failure is a malignant condition with high rates of morbidity and mortality even in so called mild casesLeft ventricular dysfunction is the main cause of heart failure, and echocardiography can quickly distinguish less common but reversible causesThe most effective medical treatments for heart failure are diuretics, usually a loop diuretic, and angiotensin converting enzyme inhibitorsIf patients remain symptomatic or cannot tolerate angiotensin converting enzyme inhibitors, other treatments such as hydralazine and isosorbide dinitrate or digoxin may be used, and as a last resort cardiac transplantation may be consideredConcomitant problems that may need treatment are atrial fibrillation, angina, and ventricular arrhythmia
Doctors diagnose heart failure when patients whom they suspect of having heart disease develop fatigue, dyspnoea, or oedema. By these standards, this is a terminal condition because in severe cases its annual mortality may exceed 60 %1 Even in so called mild cases detected in community screening programmes such as the Framingham study the five year mortality approached 50 %.2 These survival rates are worse than for many of the common forms of cancer, emphasising that heart failure is indeed a malignant condition. Heart failure also imposes a heavy burden of symptoms. In studies of the major chronic illnesses such as diabetes, arthritis, and hypertension, heart failure had the greatest negative impact on quality of life, and not just slightly so.3,4 The high morbidity is also reflected in the number of hospital admissions for heart failure, about 120 000 cases each year in the United Kingdom.5,6 These represent 5% of all adult medical and geriatric admissions and are about the same as the number of admissions for acute myocardial infarction.7Heart failure is a serious public health problem, with a prevalence in the United Kingdom, Scandinavia, and the …
Background/objectives:
In this study, we hypothesized that dietary salt intake may be related with inflammation and albuminuria independently from blood pressure (BP) in non-diabetic hypertensive patients.
Subjects/methods:
A total of 224 patients with primary hypertension were included in the study. Serum C-reactive protein (CRP) levels, 24-h urine sodium and albumin excretion were measured in all patients. The subjects were divided into tertiles according to the level of 24-h urinary sodium excretion: low-salt-intake group (n = 76, mean urine sodium: 111.7 ± 29.1 mmol/24 h), medium-salt-intake group (n = 77, mean urine sodium: 166.1 ± 16.3 mmol/24 h) and high-salt-intake group (n = 71, mean urine sodium: 263.6 ± 68.3 mmol/24 h).
Results:
Systolic and diastolic BP measurements of patients were similar in the three salt-intake groups. CRP and urinary albumin levels were significantly higher in high-salt-intake group compared with medium- and low-salt-intake groups (P = 0.0003 and P = 0.001, respectively). CRP was positively correlated with 24-h urinary sodium excretion (r = 0.28, P = 0.0008) and albuminuria, whereas albuminuria was positively correlated with 24-h urinary sodium excretion (r = 0.21, P = 0.0002). Multiple regression analysis revealed that urinary sodium excretion was an independent predictor of both CRP and albuminuria.
Conclusions:
These findings suggest that high salt intake is associated with enhanced inflammation and target organ damage reflected by increased albuminuria in treated hypertensive patients independent of any BP effect.
ESC Committee for Practice Guidelines (CPG): Jeroen J. Bax (CPG Chairperson) (The Netherlands), Helmut Baumgartner (Germany), Claudio Ceconi (Italy), Veronica Dean (France), Christi Deaton (UK), Robert Fagard (Belgium), Christian Funck-Brentano (France), David Hasdai (Israel), Arno Hoes (The Netherlands), Paulus Kirchhof (Germany/UK), Juhani Knuuti (Finland), Philippe Kolh (Belgium), Theresa McDonagh (UK), Cyril Moulin (France), Bogdan A. Popescu (Romania), Z. eljko Reiner (Croatia), Udo Sechtem (Germany), Per Anton Sirnes (Norway), Michal Tendera (Poland), Adam Torbicki (Poland), Alec Vahanian (France), Stephan Windecker (Switzerland). Document Reviewers: Theresa McDonagh (CPG Co-Review Coordinator) (UK), Udo Sechtem (CPG Co-Review Coordinator) (Germany), Luis Almenar Bonet (Spain), Panayiotis Avraamides (Cyprus), Hisham A. Ben Lamin (Libya), Michele Brignole (Italy), Antonio Coca (Spain), Peter Cowburn (UK), Henry Dargie (UK), Perry Elliott (UK), Frank Arnold Flachskampf (Sweden), Guido Francesco Guida (Italy), Suzanna Hardman (UK), Bernard Iung (France), Bela Merkely (Hungary), Christian Mueller (Switzerland), John N. Nanas (Greece), Olav Wendelboe Nielsen (Denmark), Stein Orn (Norway), John T. Parissis (Greece), Piotr Ponikowski (Poland). The disclosure forms of the authors and reviewers are available on the ESC website www.escardio.org/guidelines
The precise relationship between sodium and potassium intake and cardiovascular (CV) risk remains uncertain, especially in patients with CV disease.
To determine the association between estimated urinary sodium and potassium excretion (surrogates for intake) and CV events in patients with established CV disease or diabetes mellitus.
Observational analyses of 2 cohorts (N = 28,880) included in the ONTARGET and TRANSCEND trials (November 2001-March 2008 from initial recruitment to final follow-up). We estimated 24-hour urinary sodium and potassium excretion from a morning fasting urine sample (Kawasaki formula). We used restricted cubic spline plots to describe the association between sodium and potassium excretion and CV events and mortality, and to identify reference categories for sodium and potassium excretion. We used Cox proportional hazards multivariable models to determine the association of urinary sodium and potassium with CV events and mortality.
CV death, myocardial infarction (MI), stroke, and hospitalization for congestive heart failure (CHF).
At baseline, the mean (SD) estimated 24-hour excretion for sodium was 4.77 g (1.61); and for potassium was 2.19 g (0.57). After a median follow-up of 56 months, the composite outcome occurred in 4729 (16.4%) participants, including 2057 CV deaths, 1412 with MI, 1282 with stroke, and 1213 with hospitalization for CHF. Compared with the reference group with estimated baseline sodium excretion of 4 to 5.99 g per day (n = 14,156; 6.3% participants with CV death, 4.6% with MI, 4.2% with stroke, and 3.8% admitted to hospital with CHF), higher baseline sodium excretion was associated with an increased risk of CV death (9.7% for 7-8 g/day; hazard ratio [HR], 1.53; 95% CI, 1.26-1.86; and 11.2% for >8 g/day; HR, 1.66; 95% CI, 1.31-2.10), MI (6.8%; HR, 1.48; 95% CI, 1.11-1.98 for >8 g/day), stroke (6.6%; HR, 1.48; 95% CI, 1.09-2.01 for >8 g/day), and hospitalization for CHF (6.5%; HR, 1.51; 1.12-2.05 for >8 g/day). Lower sodium excretion was associated with an increased risk of CV death (8.6%; HR, 1.19; 95% CI, 1.02-1.39 for 2-2.99 g/day; 10.6%; HR, 1.37; 95% CI, 1.09-1.73 for <2 g/day), and hospitalization for CHF (5.2%; HR, 1.23; 95% CI, 1.01-1.49 for 2-2.99 g/day) on multivariable analysis. Compared with an estimated potassium excretion of less than 1.5 g per day (n = 2194; 6.2% with stroke), higher potassium excretion was associated with a reduced risk of stroke (4.7% [HR, 0.77; 95% CI, 0.63-0.94] for 1.5-1.99 g/day; 4.3% [HR, 0.73; 95% CI, 0.59-0.90] for 2-2.49 g/day; 3.9% [HR, 0.71; 95% CI, 0.56-0.91] for 2.5-3 g/day; and 3.5% [HR, 0.68; 95% CI, 0.49-0.92] for >3 g/day) on multivariable analysis.
The association between estimated sodium excretion and CV events was J-shaped. Compared with baseline sodium excretion of 4 to 5.99 g per day, sodium excretion of greater than 7 g per day was associated with an increased risk of all CV events, and a sodium excretion of less than 3 g per day was associated with increased risk of CV mortality and hospitalization for CHF. Higher estimated potassium excretion was associated with a reduced risk of stroke.
Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.
We analysed the association between levels of the N-terminal fragment of pro-BNP (NT-pro-BNP) in blood and risk of incident T2D in a prospective case-cohort study and genotyped the variant rs198389 within the BNP locus in three T2D case-control studies. We combined our results with existing data in a meta-analysis of 11 case-control studies. Using a Mendelian randomization approach, we compared the observed association between rs198389 and T2D to that expected from the NT-pro-BNP level to T2D association and the NT-pro-BNP difference per C allele of rs198389. In participants of our case-cohort study who were free of T2D and cardiovascular disease at baseline, we observed a 21% (95% CI 3%-36%) decreased risk of incident T2D per one standard deviation (SD) higher log-transformed NT-pro-BNP levels in analysis adjusted for age, sex, body mass index, systolic blood pressure, smoking, family history of T2D, history of hypertension, and levels of triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The association between rs198389 and T2D observed in case-control studies (odds ratio = 0.94 per C allele, 95% CI 0.91-0.97) was similar to that expected (0.96, 0.93-0.98) based on the pooled estimate for the log-NT-pro-BNP level to T2D association derived from a meta-analysis of our study and published data (hazard ratio = 0.82 per SD, 0.74-0.90) and the difference in NT-pro-BNP levels (0.22 SD, 0.15-0.29) per C allele of rs198389. No significant associations were observed between the rs198389 genotype and potential confounders.
Our results provide evidence for a potential causal role of the BNP system in the aetiology of T2D. Further studies are needed to investigate the mechanisms underlying this association and possibilities for preventive interventions. Please see later in the article for the Editors' Summary.
Extrapolations from observational studies and short-term intervention trials suggest that population-wide moderation of salt intake might reduce cardiovascular events.
To assess whether 24-hour urinary sodium excretion predicts blood pressure (BP) and health outcomes.
Prospective population study, involving 3681 participants without cardiovascular disease (CVD) who are members of families that were randomly enrolled in the Flemish Study on Genes, Environment, and Health Outcomes (1985-2004) or in the European Project on Genes in Hypertension (1999-2001). Of 3681 participants without CVD, 2096 were normotensive at baseline and 1499 had BP and sodium excretion measured at baseline and last follow-up (2005-2008).
Incidence of mortality and morbidity and association between changes in BP and sodium excretion. Multivariable-adjusted hazard ratios (HRs) express the risk in tertiles of sodium excretion relative to average risk in the whole study population.
Among 3681 participants followed up for a median 7.9 years, CVD deaths decreased across increasing tertiles of 24-hour sodium excretion, from 50 deaths in the low (mean, 107 mmol), 24 in the medium (mean, 168 mmol), and 10 in the high excretion group (mean, 260 mmol; P < .001), resulting in respective death rates of 4.1% (95% confidence interval [CI], 3.5%-4.7%), 1.9% (95% CI, 1.5%-2.3%), and 0.8% (95% CI, 0.5%-1.1%). In multivariable-adjusted analyses, this inverse association retained significance (P = .02): the HR in the low tertile was 1.56 (95% CI, 1.02-2.36; P = .04). Baseline sodium excretion predicted neither total mortality (P = .10) nor fatal combined with nonfatal CVD events (P = .55). Among 2096 participants followed up for 6.5 years, the risk of hypertension did not increase across increasing tertiles (P = .93). Incident hypertension was 187 (27.0%; HR, 1.00; 95% CI, 0.87-1.16) in the low, 190 (26.6%; HR, 1.02; 95% CI, 0.89-1.16) in the medium, and 175 (25.4%; HR, 0.98; 95% CI, 0.86-1.12) in the high sodium excretion group. In 1499 participants followed up for 6.1 years, systolic blood pressure increased by 0.37 mm Hg per year (P < .001), whereas sodium excretion did not change (-0.45 mmol per year, P = .15). However, in multivariable-adjusted analyses, a 100-mmol increase in sodium excretion was associated with 1.71 mm Hg increase in systolic blood pressure (P.<001) but no change in diastolic BP.
In this population-based cohort, systolic blood pressure, but not diastolic pressure, changes over time aligned with change in sodium excretion, but this association did not translate into a higher risk of hypertension or CVD complications. Lower sodium excretion was associated with higher CVD mortality.
Many guidelines recommend reduced consumption of salt in patients with type 1 diabetes, but it is unclear whether dietary sodium intake is associated with mortality and end-stage renal disease (ESRD).
In a nationwide multicenter study (the FinnDiane Study) between 1998 and 2002, 2,807 enrolled adults with type 1 diabetes without ESRD were prospectively followed. Baseline urinary sodium excretion was estimated on a 24-h urine collection. The predictors of all-cause mortality and ESRD were determined by Cox regression and competing risk modeling, respectively.
The median follow-up for survival analyses was 10 years, during which 217 deaths were recorded (7.7%). Urinary sodium excretion was nonlinearly associated with all-cause mortality, such that individuals with the highest daily urinary sodium excretion, as well as the lowest excretion, had reduced survival. This association was independent age, sex, duration of diabetes, the presence and severity of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] and log albumin excretion rate), the presence of established cardiovascular disease, and systolic blood pressure. During follow-up, 126 patients developed ESRD (4.5%). Urinary sodium excretion was inversely associated with the cumulative incidence of ESRD, such that individuals with the lowest sodium excretion had the highest cumulative incidence of ESRD.
In patients with type 1 diabetes, sodium was independently associated with all-cause mortality and ESRD. Although we have not demonstrated causality, these findings support the calls for caution before applying salt restriction universally. Clinical trials must be performed in diabetic patients to formally test the utility/risk of sodium restriction in this setting.
Many guidelines recommend that patients with type 2 diabetes should aim to reduce their intake of salt. However, the precise relationship between dietary salt intake and mortality in patients with type 2 diabetes has not been previously explored.
Six hundred and thirty-eight patients attending a single diabetes clinic were followed in a prospective cohort study. Baseline sodium excretion was estimated from 24-h urinary collections (24hU(Na)). The predictors of all-cause and cardiovascular mortality were determined by Cox regression and competing risk modeling, respectively.
The mean baseline 24hU(Na) was 184 ± 73 mmol/24 h, which remained consistent throughout the follow-up (intraindividual coefficient of variation [CV] 23 ± 11%). Over a median of 9.9 years, there were 175 deaths, 75 (43%) of which were secondary to cardiovascular events. All-cause mortality was inversely associated with 24hU(Na), after adjusting for other baseline risk factors (P < 0.001). For every 100 mmol rise in 24hU(Na), all-cause mortality was 28% lower (95% CI 6-45%, P = 0.02). After adjusting for the competing risk of noncardiovascular death and other predictors, 24hU(Na) was also significantly associated with cardiovascular mortality (sub-hazard ratio 0.65 [95% CI 0.44-0.95]; P = 0.03).
In patients with type 2 diabetes, lower 24-h urinary sodium excretion was paradoxically associated with increased all-cause and cardiovascular mortality. Interventional studies are necessary to determine if dietary salt has a causative role in determining adverse outcomes in patients with type 2 diabetes and the appropriateness of guidelines advocating salt restriction in this setting.
Multiple imputation is commonly used to impute missing data, and is typically more efficient than complete cases analysis in regression analysis when covariates have missing values. Imputation may be performed using a regression model for the incomplete covariates on other covariates and, importantly, on the outcome. With a survival outcome, it is a common practice to use the event indicator D and the log of the observed event or censoring time T in the imputation model, but the rationale is not clear.
We assume that the survival outcome follows a proportional hazards model given covariates X and Z. We show that a suitable model for imputing binary or Normal X is a logistic or linear regression on the event indicator D, the cumulative baseline hazard H0(T), and the other covariates Z. This result is exact in the case of a single binary covariate; in other cases, it is approximately valid for small covariate effects and/or small cumulative incidence. If we do not know H0(T), we approximate it by the Nelson–Aalen estimator of H(T) or estimate it by Cox regression.
We compare the methods using simulation studies. We find that using log T biases covariate-outcome associations towards the null, while the new methods have lower bias. Overall, we recommend including the event indicator and the Nelson–Aalen estimator of H(T) in the imputation model. Copyright © 2009 John Wiley & Sons, Ltd.
Heart failure is a malignant condition with high rates of morbidity and mortality even in so called mild cases. Left ventricular dysfunction is the main cause of heart failure, and echocardiography can quickly distinguish less common but reversible causes. The most effective medical treatments for heart failure and diuretics, usually a loop diuretic, and angiotensin converting enzyme inhibitors. If patients remain symptomatic or cannot tolerate angiotensin converting enzyme inhibitors, other treatments such as hydralazine and isosorbide dinitrate or digoxin may be used, and as a last resort cardiac transplantation may be considered. Concomitant problems that may need treatment are atrial fibrillation, angina, and ventricular arrhythmia.
- To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects.
- Inception cohort study.
- General community.
- Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970. EXPOSURE MEASURES:- Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations.
- The development of CHF.
- A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years.
- Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.
To determine the incidence and aetiology of heart failure in the general population.
New cases of heart failure were identified from a population of 151 000 served by 82 general practitioners in Hillingdon, West London through surveillance of acute hospital admissions and through a rapid access clinic to which general practitioners referred all new cases of suspected heart failure. On the basis of clinical assessment, electrocardiography, chest radiography and transthoracic echocardiography, a panel of three cardiologists decided that 220 patients met the case definition of new heart failure over a 20 month period (crude incidence rate of 1.3 cases per 1000 population per year for those aged 25 years or over). The incidence rate increased from 0.02 cases per 1000 population per year in those aged 25-34 years to 11.6 in those aged 85 years and over. The incidence was higher in males than females (age-adjusted incidence ratio 1.75 [95% confidence interval 1.34-2.29, P<0.0001]). The median age at presentation was 76 years. The primary aetiologies were coronary heart disease (36%), unknown (34%), hypertension (14%), valve disease (7%), atrial fibrillation alone (5%), and other (5%).
Within the general population, new cases of heart failure largely occur in the elderly, and the incidence is higher in men than women. The single most common aetiology is coronary heart disease, but in a third of cases the aetiology cannot be determined on the basis of non-invasive investigation alone. To be relevant to clinical practice, future clinical trials in heart failure should not exclude the elderly.
In order to estimate the salt and potassium intake in a population and to compare their annual trends, we developed a simple method to estimate population mean levels of 24-h urinary sodium (24HUNaV) and potassium (24HUKV) excretion from spot urine specimens collected at any time. Using 591 Japanese data items from the INTERSALT study as a gold standard, we developed formulas to estimate 24-h urinary creatinine (24HUCrV), 24HUNaV and 24HUKV using both spot and 24-h urine collection samples. To examine the accuracy of the formulas, we applied these equations to 513 external manual workers. The obtained formulas were as follows: (1) PRCr (mg/day) = -2.04 x age + 14.89 x weight (kg) + 16.14 x height (cm) -2244.45; (2) estimated 24HUNaV (mEq/day) = 21.98 x XNa (0.392); (3) estimated 24HUKV (mEq/day) = 7.59 x XK(0.431); where PRCr = predicted value of 24HUCr, SUNa = Na concentration in the spot voiding urine, SUK = K concentration in the spot voiding urine, SUCr = creatinine concentration in the spot voiding urine, XNa (or XK) = SUNa (or SUK)/SUCr x PRCr. In the external group, there was a significant but small difference between the estimated and measured values in sodium (24.0 mmol/day) and potassium (3.8 mmol/day) excretion. In every quintile divided by the estimated 24HUNaV or 24HUKV, the measured values were parallel to the estimated values. In conclusion, although this method is not suitable for estimating individual Na and K excretion, these formulas are considered useful for estimating population mean levels of 24-h Na and K excretion, and are available for comparing different populations, as well as indicating annual trends of a particular population.
Cross-sectional epidemiologic studies suggest that a higher intake of dietary sodium is associated with an increased risk of left ventricular hypertrophy. We studied the relationship between dietary sodium intake and incidence of congestive heart failure (CHF) in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study participants.
The study sample consisted of 5233 nonoverweight and 5129 overweight men and women without a history of CHF at their baseline examination. Dietary sodium and other nutrient intake estimates were obtained by a 24-hour dietary recall method at the baseline examination, conducted from 1971 to 1975. The incidence of CHF was assessed using medical records and death certificates obtained in 1982 to 1984, 1986, 1987, and 1992.
During an average of 19 years of follow-up, we documented 413 cases of CHF in nonoverweight and 679 cases of CHF in overweight participants. After adjustment for known CHF risk factors, the relative risk of CHF among overweight participants was 1.43 (95% confidence interval, 1.07-1.91) for those whose sodium intake was greater than 113.6 mmol/d compared with those whose intake was less than 50.2 mmol/d. The relative risks of CHF for a 100-mmol/d higher intake of sodium or per 1743 kcal (average energy intake in the study population) were 1.26 (95% confidence interval, 1.03-1.53) and 1.21 (95% confidence interval, 1.04-1.40), respectively.
A higher intake of dietary sodium is a strong independent risk factor for CHF in overweight persons. A reduction in sodium intake may play an important role in the prevention of CHF in overweight individuals and populations.
To assess the validity and repeatability of a simple index designed to rank participants according to their energy expenditure estimated by self-report, by comparison with objectively measured energy expenditure assessed by heart-rate monitoring with individual calibration.
Energy expenditure was assessed over one year by four separate episodes of 4-day heart-rate monitoring, a method previously validated against whole-body calorimetry and doubly labelled water. Cardio-respiratory fitness was assessed by four repeated measures of sub-maximum oxygen uptake. At the end of the 12-month period, participants completed a physical activity questionnaire that assessed past-year activity. A simple four-level physical activity index was derived by combining occupational physical activity together with time participating in cycling and other physical exercise (such as keep fit, aerobics, swimming and jogging).
One hundred and seventy-three randomly selected men and women aged 40 to 65 years.
The repeatability of the physical activity index was high (weighted kappa=0.6, ). There were positive associations between the physical activity index from the questionnaire and the objective measures of the ratio of daytime energy expenditure to resting metabolic rate and cardio-respiratory fitness As an indirect test of validity, there was a positive association between the physical activity index and the ratio of energy intake, assessed by 7-day food diaries, to predicted basal metabolic rate.
The summary index of physical activity derived from the questions used in the European Prospective Investigation into Cancer and Nutrition (EPIC) study suggest it is useful for ranking participants in terms of their physical activity in large epidemiological studies. The index is simple and easy to comprehend, which may make it suitable for situations that require a concise, global index of activity.
The epidemic of heart failure has yet to be fully investigated, and data on incidence, survival, and sex-specific temporal trends in community-based populations are limited.
To test the hypothesis that the incidence of heart failure has declined and survival after heart failure diagnosis has improved over time but that secular trends have diverged by sex.
Population-based cohort study using the resources of the Rochester Epidemiology Project conducted in Olmsted County, Minnesota. Patients were 4537 Olmsted County residents (57% women; mean [SD] age, 74 [14] years) with a diagnosis of heart failure between 1979 and 2000. Framingham criteria and clinical criteria were used to validate the diagnosis
Incidence of heart failure and survival after heart failure diagnosis.
The incidence of heart failure was higher among men (378/100 000 persons; 95% confidence interval [CI], 361-395 for men; 289/100 000 persons; 95% CI, 277-300 for women) and did not change over time among men or women. After a mean follow-up of 4.2 years (range, 0-23.8 years), 3347 deaths occurred, including 1930 among women and 1417 among men. Survival after heart failure diagnosis was worse among men than women (relative risk, 1.33; 95% CI, 1.24-1.43) but overall improved over time (5-year age-adjusted survival, 43% in 1979-1984 vs 52% in 1996-2000, P<.001). However, men and younger persons experienced larger survival gains, contrasting with less or no improvement for women and elderly persons.
In this community-based cohort, the incidence of heart failure has not declined during 2 decades, but survival after onset of heart failure has increased overall, with less improvement among women and elderly persons.
In this large cross-sectional study, we investigated the relationship between phytoestrogen exposure and circulating sex hormones and sex hormone-binding globulin (SHBG) levels in 1988 healthy postmenopausal women and their interactions with polymorphisms in genes involved in estrogen signaling. Plasma estradiol, testosterone, androstenedione, estrone, and SHBG were measured. Urinary levels of five isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and two lignans (enterodiol and enterolactone) were measured and used as biomarkers for dietary intakes. Eighteen polymorphisms in ESR1, ESR2, and NR1I2 genes were genotyped. Results showed that lignans were positively associated with plasma SHBG levels (eta(p)(2) = 1.2%; P < 0.001) and negatively associated with plasma testosterone (eta(p)(2) = 0.2%; P = 0.042). Equol was negatively associated with plasma estradiol levels (eta(p)(2) = 0.3%; P = 0.028), whereas O-desmethylangolensin was positively associated with plasma estradiol level (eta(p)(2) = 0.3%; P = 0.010). There were significant phytoestrogen interactions with polymorphisms in ESR1 and NR1I2 genes in affecting estrone levels. We conclude that phytoestrogens modulate sex hormone and SHBG levels in postmenopausal women and interact with gene variants involved in estrogen signaling. Such phytoestrogen-gene interactions may explain the conflicting literature on the hormonal effects of phytoestrogens.
The aim of the present study was to evaluate the effects of a normal-sodium (120 mmol sodium) diet compared with a low-sodium diet (80 mmol sodium) on readmissions for CHF (congestive heart failure) during 180 days of follow-up in compensated patients with CHF. A total of 232 compensated CHF patients (88 female and 144 male; New York Heart Association class II-IV; 55-83 years of age, ejection fraction <35% and serum creatinine <2 mg/dl) were randomized into two groups: group 1 contained 118 patients (45 females and 73 males) receiving a normal-sodium diet plus oral furosemide [250-500 mg, b.i.d. (twice a day)]; and group 2 contained 114 patients (43 females and 71 males) receiving a low-sodium diet plus oral furosemide (250-500 mg, b.i.d.). The treatment was given at 30 days after discharge and for 180 days, in association with a fluid intake of 1000 ml per day. Signs of CHF, body weight, blood pressure, heart rate, laboratory parameters, ECG, echocardiogram, levels of BNP (brain natriuretic peptide) and aldosterone levels, and PRA (plasma renin activity) were examined at baseline (30 days after discharge) and after 180 days. The normal-sodium group had a significant reduction (P<0.05) in readmissions. BNP values were lower in the normal-sodium group compared with the low sodium group (685+/-255 compared with 425+/-125 pg/ml respectively; P<0.0001). Significant (P<0.0001) increases in aldosterone and PRA were observed in the low-sodium group during follow-up, whereas the normal-sodium group had a small significant reduction (P=0.039) in aldosterone levels and no significant difference in PRA. After 180 days of follow-up, aldosterone levels and PRA were significantly (P<0.0001) higher in the low-sodium group. The normal-sodium group had a lower incidence of rehospitalization during follow-up and a significant decrease in plasma BNP and aldosterone levels, and PRA. The results of the present study show that a normal-sodium diet improves outcome, and sodium depletion has detrimental renal and neurohormonal effects with worse clinical outcome in compensated CHF patients. Further studies are required to determine if this is due to a high dose of diuretic or the low-sodium diet.
Restriction of dietary salt is widely recommended in the management of hypertension, but assessment of individual salt intake has drawn little attention. The understanding of salt intake is important as a guide for optimizing salt-restriction strategies. However, precise evaluation of salt intake is difficult. More reliable methods are more difficult to perform, whereas easier methods are less reliable. Thus, the method to assess salt intake should be determined as the situation demands. The Working Group for Dietary Salt Reduction of the Japanese Society of Hypertension recommends the assessment of individual salt intake using one of the following methods in the management of hypertension. 1) The measurement of the sodium (Na) excretion from 24-h urine sampling or nutritionist's analysis of the dietary contents, which are reliable but difficult to perform, are suitable for facilities specializing in the treatment of hypertension. 2) Estimation of the Na excretion from the Na/creatinine (Cr) ratio in spot urine is less reliable but practical and is suitable for general medical facilities. 3) Estimation using an electronic salt sensor equipped with a calculation formula is also less reliable but is simple enough that patients can use it themselves. The patients are considered to be compliant with the salt-restriction regimen if salt intake measured by whichever method is less than 6 g (100 mmol)/day.
The increase in heart failure (HF) rates throughout the developed and developing regions of the world poses enormous challenges for caregivers, researchers, and policymakers. Therefore, prevention of this global scourge deserves high priority. Identifying and preventing the well-recognized illnesses that lead to HF, including hypertension and coronary heart disease, should be paramount among the approaches to prevent HF. Aggressive implementation of evidence-based management of risk factors for coronary heart disease should be at the core of HF prevention strategies. Questions currently in need of attention include how to identify and treat patients with asymptomatic left ventricular systolic dysfunction (Stage B HF) and how to prevent its development. The relationship of chronic kidney disease to HF and control of chronic kidney disease in prevention of HF need further investigation. Currently, we have limited understanding of the pathophysiological basis of HF in patients with preserved left ventricular systolic function and management techniques to prevent it. New developments in the field of biomarker identification have opened possibilities for the early detection of individuals at risk for developing HF (Stage A HF). Patient groups meriting special interest include the elderly, women, and ethnic/racial minorities.
Future research ought to focus on obtaining a much better knowledge of genetics and HF, especially both genetic risk factors for development of HF and genetic markers as tools to guide prevention. Lastly, a national awareness campaign should be created and implemented to increase public awareness of HF and the importance of its prevention. Heightened public awareness will provide a platform for advocacy to create national research programs and healthcare policies dedicated to the prevention of HF.
Files that implement full Mahalanobis and propensity score matching, common support graphing, and covariate imbalance testing. This routine supersedes the previous 'psmatch' routine of B. Sianesi.
Aims
To determine the incidence and aetiology of heart failure in the general population.
Methods and Results
New cases of heart failure were identified from a population of 151000 served by 82 general practitioners in Hillingdon, West London through surveillance of acute hospital admissions and through a rapid access clinic to which general practitioners referred all new cases of suspected heart failure. On the basis of clinical assessment, electrocardiography, chest radiography and transthoracic echocardiography, a panel of three cardi-ologists decided that 220 patients met the case definition of new heart failure over a 20 month period (crude incidence rate of 1·3 cases per 1000 population per year for those aged 25 years or over). The incidence rate increased from 0·02 cases per 1000 population per year in those aged 25–34 years to 11·6 in those aged 85 years and over. The incidence was higher in males than females (age-adjusted incidence ratio 1·75 [95% confidence interval 1·34–2·29, P <0·0001]). The median age at presentation was 76 years. The primary aetiologies were coronary heart disease (36%), unknown (34%), hypertension (14%), valve disease (7%), atrial fibrillation alone (5%), and other (5%).
Conclusions
Within the general population, new cases of heart failure largely occur in the elderly, and the incidence is higher in men than women. The single most common aetiology is coronary heart disease, but in a third of cases the aetiology cannot be determined on the basis of non-invasive investigation alone. To be relevant to clinical practice, future clinical trials in heart failure should not exclude the elderly.
Objective.
—To study the relative and population-attributable risks of hypertension for the development of congestive heart failure (CHF), to assess the time course of progression from hypertension to CHF, and to identify risk factors that contribute to the development of overt heart failure in hypertensive subjects.Design.
—Inception cohort study.Setting.
—General community.Participants.
—Original Framingham Heart Study and Framingham Offspring Study participants aged 40 to 89 years and free of CHF. To reflect more contemporary experience, the starting point of this study was January 1, 1970.Exposure Measures.
—Hypertension (blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or current use of medications for treatment of high blood pressure) and other potential CHF risk factors were assessed at periodic clinic examinations.Outcome Measure.
—The development of CHF.Results.
—A total of 5143 eligible subjects contributed 72422 person-years of observation. During up to 20.1 years of follow-up (mean, 14.1 years), there were 392 new cases of heart failure; in 91% (357/392), hypertension antedated the development of heart failure. Adjusting for age and heart failure risk factors in proportional hazards regression models, the hazard for developing heart failure in hypertensive compared with normotensive subjects was about 2-fold in men and 3-fold in women. Multivariable analyses revealed that hypertension had a high population-attributable risk for CHF, accounting for 39% of cases in men and 59% in women. Among hypertensive subjects, myocardial infarction, diabetes, left ventricular hypertrophy, and valvular heart disease were predictive of increased risk for CHF in both sexes. Survival following the onset of hypertensive CHF was bleak; only 24% of men and 31% of women survived 5 years.Conclusions.
—Hypertension was the most common risk factor for CHF, and it contributed a large proportion of heart failure cases in this population-based sample. Preventive strategies directed toward earlier and more aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of CHF and its associated mortality.(JAMA. 1996;275:1557-1562)
Aims: Hospital discharge registries are frequently used for identification of individuals with heart failure in large cohort studies. However, validity of discharge codes is heterogeneous across earlier studies and current data on European populations are sparse. We examined the validity of the ICD-10 discharge code I50 for heart failure in participants of the population-based EPIC-Norfolk study.
Methods and results: Hospital records of a random subset of participants with a hospital discharge code I50 between 1997-2009 identified through a national hospital record linkage system were scrutinized for diagnostic criteria of heart failure according to recommendations of the European Society of Cardiology. Of 396 cases with records available for review 77.8% were classified as definite, 10.4% as probable, 7.6% as possible and 4.3% as no heart failure, i.e. 95.8% of cases had definitive, probable or possible diagnosis of heart failure. Of the 17 participants with no heart failure, 10 had evidence of LV-dysfunction or structural heart disease. The validity of I50 was similar in subgroups by age, gender, BMI and time period of hospitalization.
Conclusion: Obtaining ICD-10 discharge code I50 through hospital record linkage provides a feasible and accurate method of identifying heart failure in contemporary cohort studies in the UK.
For more than four decades, starting in the late 1960s, a sometimes furious battle has raged among scientists over the extent to which elevated salt consumption has adverse implications for population health and contributes to deaths from stroke and cardiovascular disease. Various studies and trials have produced conflicting results. Despite this scientific controversy over the quality of the evidence implicating dietary salt in disease, public health leaders at local, national, and international levels have pressed the case for salt reduction at the population level. This article explores the development of this controversy. It concludes that the concealment of scientific uncertainty in this case has been a mistake that has served neither the ends of science nor good policy. The article poses questions that arise from this debate and frames the challenges of formulating evidence-based public health practice and policy, particularly when the evidence is contested.
Recent reports of selected observational studies and a meta-analysis have stirred controversy and have become the impetus for calls to abandon recommendations for reduced sodium intake by the US general population. A detailed review of these studies documents substantial methodological concerns that limit the usefulness of these studies in setting, much less reversing, dietary recommendations. Indeed, the evidence base supporting recommendations for reduced sodium intake in the general population remains robust and persuasive. The American Heart Association is committed to improving the health of all Americans through implementation of national goals for health promotion and disease prevention, including its recommendation to reduce dietary sodium intake to <1500 mg/d.
This study evaluates how often the self-report of a low sodium (Na) intake is reflected by a low 24-h urinary sodium excretion and examines the influence of incomplete urinary collections on this comparison.
In a study in which 24-h urine collections were obtained for measurement of Na and creatinine excretion, 120 participants were asked whether their Na intake was low, medium, or high. A 24-h urine collection was considered complete if creatinine excretion was ≥20 mg/kg in men or ≥15 mg/kg in women, and incomplete if below those amounts. The kappa statistic was computed to assess the level of agreement between 24-h Na excretion, dichotomized at 100 meq and self-report responses.
Agreement between self-reported and actual Na excretion was poor. The kappa statistic was 0.18 for the total sample, 0.04 for complete collectors, and 0.51 for incomplete collectors, respectively. Overall, 24-h Na excretion exceeded 100 meq among 75% of those reporting an average or high Na intake, but it also exceeded 100 meq among 57% of those reporting a low sodium intake. Further, among those reporting a low sodium intake, Na excretion exceeded 100 meq in 80% of those who submitted a complete collection, but in only 29% of those who submitted an incomplete collection.
These findings suggest that many individuals who report a low salt diet actually excrete ≥100 meq/day. Na intake is also frequently underestimated because many 24-h urine collections are incomplete.
The question of whether reduced sodium intake is effective as a health prophylaxis initiative is unsolved. The purpose was to estimate the effects of low-sodium vs. high-sodium intake on blood pressure (BP), renin, aldosterone, catecholamines, and lipids.
Studies randomizing persons to low-sodium and high-sodium diets evaluating at least one of the above outcome parameters were included. Data were analyzed with Review Manager 5.1.
A total of 167 studies were included. The effect of sodium reduction in: (i) Normotensives: Caucasians: systolic BP (SBP) -1.27 mm Hg (95% confidence interval (CI): -1.88, -0.66; P = 0.0001), diastolic BP (DBP) -0.05 mm Hg (95% CI: -0.51, 0.42; P = 0.85). Blacks: SBP -4.02 mm Hg (95% CI: -7.37, -0.68; P = 0.002), DBP -2.01 mm Hg (95% CI: -4.37, 0.35; P = 0.09). Asians: SBP -1.27 mm Hg (95% CI: -3.07, 0.54; P = 0.17), DBP -1.68 mm Hg (95% CI: -3.29, -0.06; P = 0.04). (ii) Hypertensives: Caucasians: SBP -5.48 mm Hg (95% CI: -6.53, -4.43; P < 0.00001), DBP -2.75 mm Hg (95% CI: -3.34, -2.17; P < 0.00001). Blacks: SBP -6.44 mm Hg (95% CI: -8.85, -4.03; P = 0.00001), DBP -2.40 mm Hg (95% CI: -4.68, -0.12; P = 0.04). Asians: SBP -10.21 mm Hg (95% CI: -16.98, -3.44; P = 0.003), DBP -2.60 mm Hg (95% CI: -4.03, -1.16; P = 0.0004). Sodium reduction resulted in significant increases in renin (P < 0.00001), aldosterone (P < 0.00001), noradrenaline (P < 0.00001), adrenaline (P < 0.0002), cholesterol (P < 0.001), and triglyceride (P < 0.0008).
Sodium reduction resulted in a significant decrease in BP of 1% (normotensives), 3.5% (hypertensives), and a significant increase in plasma renin, plasma aldosterone, plasma adrenaline, and plasma noradrenaline, a 2.5% increase in cholesterol, and a 7% increase in triglyceride.
Fruit and vegetable intake has been associated with lower risk for cardiovascular risk factors and disease, but data on heart failure are sparse and inconsistent. The association of plasma vitamin C, a biomarker reflecting fruit and vegetable intake, with heart failure has not been studied.
We examined the prospective association of plasma vitamin C concentrations with incident fatal and nonfatal heart failure events in apparently healthy 9,187 men and 11,112 women aged 39 to 79 years participating in the "European Prospective Investigation into Cancer and Nutrition" study in Norfolk.
The risk of heart failure decreased with increasing plasma vitamin C; the hazard ratios comparing each quartile with the lowest were 0.76 (95% CI 0.65-0.88), 0.70 (95% CI 0.60-0.81), and 0.62 (95% CI 0.53-0.74) in age- and sex-adjusted analyses (P for trend <.0001). Every 20 μmol/L increase in plasma vitamin C concentration (1 SD) was associated with a 9% relative reduction in risk of heart failure after adjustment for age, sex, smoking, alcohol consumption, physical activity, occupational social class, educational level, systolic blood pressure, diabetes, cholesterol concentration, and body mass index, with similar result if adjusting for interim coronary heart disease.
Plasma vitamin C, a biomarker reflecting fruit and vegetable intake, was inversely associated with the risk of heart failure in this healthy population. This observation should be regarded as hypothesis generating for further prospective trials aimed at examining the effect of a diet rich in fruit and vegetables for prevention of heart failure.
Cardiovascular disease includes heart attacks, strokes, and the need for heart surgery and is a major cause of premature death and disability. This review set out to assess whether intensive support and encouragement to cut down on salt in foods reduced the risk of death or cardiovascular disease. This advice did reduce the amount of salt eaten which led to a small reduction in blood pressure by six months. There was not enough information to detect the expected effects on deaths and cardiovascular disease predicted by the blood pressure reductions found. There was limited evidence that dietary advice to reduce salt may increase deaths in people with heart failure. Our review does not mean that asking people to reduce salt should be stopped. People should continue to strive to do this. However, additional measures - reducing the amount of hidden salt in processed foods, for example – will make it much easier for people to stick to a lower salt diet. Further evidence of measures to cut dietary salt is needed from experimental or observational studies of population based interventions to reduce salt in hypertensives or healthy individuals assessing mortality and cardiovascular events.
Multiple imputation by chained equations is a flexible and practical approach to handling missing data. We describe the principles of the method and show how to impute categorical and quantitative variables, including skewed variables. We give guidance on how to specify the imputation model and how many imputations are needed. We describe the practical analysis of multiply imputed data, including model building and model checking. We stress the limitations of the method and discuss the possible pitfalls. We illustrate the ideas using a data set in mental health, giving Stata code fragments.
To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease.
Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction.
Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis.
In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected].
The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.
To estimate the quantitative relation between blood pressure and sodium intake.
Data were analysed from published reports of blood pressure and sodium intake for 24 different communities (47 000 people) throughout the world.
Difference in blood pressure for a 100 mmol/24 h difference in sodium intake. Allowance was made for differences in blood pressure between economically developed and undeveloped communities to minimise overestimation of the association through confounding with other determinants of blood pressure.
Blood pressure was higher on average in the developed communities, but the association with sodium intake was similar in both types of community. A difference in sodium intake of 100 mmol/24 h was associated with an average difference in systolic blood pressure that ranged from 5 mm Hg at age 15-19 years to 10 mm Hg at age 60-69. The differences in diastolic blood pressure were about half as great. The standard deviation of blood pressure increased with sodium intake implying that the association of blood pressure with sodium intake in individuals was related to the initial blood pressure--the higher the blood pressure the greater the expected reduction in blood pressure for the same reduction in sodium intake. For example, at age 60-69 the estimated systolic blood pressure reduction in response to a 100 mmol/24 h reduction in sodium intake was on average 10 mm Hg but varied from 6 mm Hg for those on the fifth blood pressure centile to 15 mm Hg for those on the 95th centile.
The association of blood pressure with sodium intake is substantially larger than is generally appreciated and increases with age and initial blood pressure.
Long-term therapy with antihypertensive agents that reduce sympathetic nervous system activity has been demonstrated by echocardiographic measurements to reverse left ventricular hypertrophy. This investigation evaluated the effects of salt depletion obtained by both chlorthalidone (25 mg/day) and severe restriction of salt intake (about 1016 mg Na+/day) on left ventricular mass (LVM) in as short a time as 12 weeks. Before the study, the patients had been off medication and on a balanced diet without salt restriction for at least 2 weeks; they were then randomly allocated to either the diuretic or low-salt regimen for 6 weeks and finally to alternative treatment according to a crossover model. Blood pressure, body weight, myocardial mass, and noninvasive measurements of left ventricular function (LVF) were determined at baseline and at the end of both periods of treatment. Results were evaluated by two-way analysis of variance in randomized blocks. Systolic and diastolic blood pressure and LVM were significantly and similarly reduced by diuretic therapy or salt restriction. A significant correlation was demonstrated between noninvasive measurements of LVM, expressed as cross-sectional area, and systolic blood pressure. No impairment of LVF could be detected over the treatment period.
Experimental and clinical data suggest salt intake to be an important factor in the pathogenesis of essential hypertension. However, the relationship between dietary sodium and blood pressure has been found to be relatively weak, perhaps because casual blood pressure levels fluctuate considerably. We hypothesized that a closer correlation could be expected between salt intake and the degree of hypertensive target organ disease. We reviewed the literature for studies dealing with 24-hour urinary sodium excretion (as a measure of salt intake) and hypertensive target organ disease as assessed by left ventricular structure and function, microproteinuria, cerebrovascular disease, and arterial compliance. Salt intake as assessed by 24-hour urinary sodium excretion was found to be a close independent determinant of left ventricular mass in 9 different studies worldwide. A reduction in dietary sodium has been shown to reduce left ventricular hypertrophy. There is clinical and experimental evidence, particularly in salt-sensitive patients, that salt intake directly affects hypertensive renal disease, cerebrovascular disease, and compliance of the large arteries. The close and partially independent correlation between salt intake and hypertensive target organ disease suggests dietary sodium to be a direct perpetrator of cardiovascular disease.
Arch Intern Med. 1997;157:2449-2452
Thus the lesions of atherosclerosis represent a protective, inflammatory-fibroproliferative response against the different agents that can cause the disease. If the injury continues over a long period of time, it may become excessive, and in its excess it becomes the disease itself. It has been shown that this excessive, inflammatory, fibroproliferative response can be reversed given sufficient opportunity for the injurious factors to be modified. Approaches to modifying specific cellular interactions, growth- regulatory molecules, or intracellular signaling molecules may afford opportunities to modify these processes and lead to lesion prevention or regression.
The effect of dietary composition on blood pressure is a subject of public health importance. We studied the effect of different levels of dietary sodium, in conjunction with the Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in vegetables, fruits, and low-fat dairy products, in persons with and in those without hypertension.
A total of 412 participants were randomly assigned to eat either a control diet typical of intake in the United States or the DASH diet. Within the assigned diet, participants ate foods with high, intermediate, and low levels of sodium for 30 consecutive days each, in random order.
Reducing the sodium intake from the high to the intermediate level reduced the systolic blood pressure by 2.1 mm Hg (P<0.001) during the control diet and by 1.3 mm Hg (P=0.03) during the DASH diet. Reducing the sodium intake from the intermediate to the low level caused additional reductions of 4.6 mm Hg during the control diet (P<0.001) and 1.7 mm Hg during the DASH diet (P<0.01). The effects of sodium were observed in participants with and in those without hypertension, blacks and those of other races, and women and men. The DASH diet was associated with a significantly lower systolic blood pressure at each sodium level; and the difference was greater with high sodium levels than with low ones. As compared with the control diet with a high sodium level, the DASH diet with a low sodium level led to a mean systolic blood pressure that was 7.1 mm Hg lower in participants without hypertension, and 11.5 mm Hg lower in participants with hypertension.
The reduction of sodium intake to levels below the current recommendation of 100 mmol per day and the DASH diet both lower blood pressure substantially, with greater effects in combination than singly. Long-term health benefits will depend on the ability of people to make long-lasting dietary changes and the increased availability of lower-sodium foods.
To estimate the incidence rate of heart failure in the general population and to assess risk factors associated with the occurrence of newly diagnosed heart failure.
From the source population that was derived from the UK General Practice Research Database, we identified patients aged 40--84 years newly diagnosed with heart failure in 1996, and estimated incidence rates. We sent questionnaires to a random sample of heart failure patients (N=1200) and performed a nested case-control analysis to assess risk factors for heart failure.
The overall incidence rate for heart failure was 4.4 per 1000 person-years in men and 3.9 per 1000 person-years in women. The incidence increased steeply with age in both sexes. The relative risk of heart failure was 2.1 (95% C.I.: 1.7--2.6) among men compared with women less than 65 years old and 1.3 (95% C.I.: 1.2--1.4) above the age of 65. Slightly more than half of the cases were categorized in NYHA III--IV at the time of the first diagnosis. Within one month of initial diagnosis 62% of the men and 50% of the women were referred to specialists and/or hospitalized for heart failure. Smoking, hypertension, diabetes, obesity were independently associated with heart failure as well as history of distant dyspnoea. Coronary heart disease was the most common cause of heart failure with a greater relative prevalence in men than women.
Incident heart failure cases mainly comprised elderly men and women frequently burdened with several diseases in general practice. Women had a lower incidence of heart failure than men. However, traditional risk factors such as smoking, hypertension, obesity, diabetes and dyspnoea appeared to confer the same relative increase in heart failure risk among women and men.
Inflammation plays a pivotal role in both the development of atherosclerosis and the acute activation of the vascular wall with consequent local thrombosis and vasoconstriction (with or without plaque fissure). In many patients with unstable angina and acute myocardial infarction, systemic signs of inflammation are detectable. The use of systemic inflammatory markers, such as C-reactive protein as marker of disease activity and short- and long-term prognosis, seems to be of clinical value. Therefore, acute inflammatory reaction, detectable systematically, appears to be an independent determinant of prognosis in some patients with acute ischemic syndromes, but is not detectable in all. Understanding the causes of inflammation and the additional elusive components that result in the progression to aggressive acute coronary syndromes, is the future goal of cardiology.
Abundant evidence indicates that a high sodium intake is causally related to high blood pressure, but debate over recommendations to reduce dietary sodium in the general population continues. A key issue is whether differences in usual sodium intake within the range feasible in free-living populations have clinical or public health relevance.
We examined the relation between blood pressure and urinary sodium as a marker of dietary intake.
This was a study of 23104 community-living adults aged 45-79 y.
Mean systolic and diastolic blood pressure increased as the ratio of urinary sodium to creatinine increased (as estimated from a casual urine sample), with differences of 7.2 mm Hg for systolic blood pressure and 3.0 mm Hg for diastolic blood pressure (P < 0.0001) between the top and bottom quintiles. This trend was independent of age, body mass index, urinary potassium:creatinine, and smoking and was consistent by sex and history of hypertension. The prevalence of those with systolic blood pressure >/= 160 mm Hg halved from 12% in the top quintile to 6% in the bottom quintile; the odds ratio for having systolic blood pressure >/= 160 mm Hg was 2.48 (95% CI: 1.90, 3.22) for men and 2.67 (95% CI: 2.08, 3.43) for women in the top compared with the bottom quintile of urinary sodium. Estimated mean sodium intakes in the lowest and highest quintiles were approximately 80 and 220 mmol/d, respectively.
Within the usual range found in a free-living population, differences in urinary sodium, an indicator of dietary sodium intake, are associated with blood pressure differences of clinical and public health relevance. Our findings reinforce recommendations to lower average sodium intakes in the general population.
Blood pressure (BP) follows a circadian rhythm, with 10% to 15% lower values during nighttime than during daytime. The absence of a nocturnal BP decrease (dipping) is associated with target organ damage, but the determinants of dipping are poorly understood. We assessed whether the nighttime BP and the dipping are associated with the circadian pattern of sodium excretion. Ambulatory BP and daytime and nighttime urinary electrolyte excretion were measured simultaneously in 325 individuals of African descent from 73 families. When divided into sex-specific tertiles of day:night ratios of urinary sodium excretion rate, subjects in tertile 1 (with the lowest ratio) were 6.5 years older and had a 9.8-mm Hg higher nighttime systolic BP (SBP) and a 23% lower SBP dipping (expressed in percentage of day value) compared with subjects in tertile 3 (P for trend <0.01). After adjustment for age, the SBP difference across tertiles decreased to 5.4 mm Hg (P=0.002), and the SBP dipping difference decreased to 17% (P=0.05). A similar trend across tertiles was found with diastolic BP. In multivariate analyses, daytime urinary sodium and potassium concentrations were independently associated with nighttime SBP and SBP dipping (P<0.05 for each). These data, based on a large number of subjects, suggest that the capacity to excrete sodium during daytime is a significant determinant of nocturnal BP and dipping. This observation may help us to understand the pathophysiology and clinical consequences of nighttime BP and to develop therapeutic strategies to normalize the dipping profile in hypertensive patients.
Multiple imputation using chained equations: issues and guidance for practice
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EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer
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ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC
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- Lip GY
- Maggioni AP
- Parkhomenko A
- Pieske BM
- Popescu BA
- Ronnevik PK
- Rutten FH
- Schwitter J
- Seferovic P
- Stepinska J
- Trindade PT
- Voors AA
- Zannad F
- Zeiher A
- Bax JJ
- Baumgartner H
- Ceconi C
- Dean V
- Deaton C
- Fagard R
- Funck-Brentano C
- Hasdai D
- Hoes A
- Kirchhof P
- Knuuti J
- Kolh P
- McDonagh T
- Moulin C
- Reiner Z
- Sechtem U
- Sirnes PA
- Tendera M
- Torbicki A
- Vahanian A
- Windecker S
- Bonet LA
- Avraamides P
- Ben Lamin HA
- Brignole M
- Coca A
- Cowburn P
- Dargie H
- Elliott P
- Flachskampf FA
- Guida GF
- Hardman S
- Iung B
- Merkely B
- Mueller C
- Nanas JN
- Nielsen OW
- Orn S
- Parissis JT
- Ponikowski P