Journal of Human Hypertension

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Low expression levels of miR-126 and miR-223 are found in the serum of patients with CA
A Volcano graph of differentially expressed miRNAs in the serum of 6 normal people and 6 patients with CA. B Heatmap of the top 30 differentially expressed miRNAs from the microarray analysis results. C RT-qPCR for detecting the levels of the top 10 differentially expressed miRNAs in the serum of 25 normal people and 52 patients with CA. D ROC curve for the predictive power of the top 10 differentially expressed miRNAs in patients with CA. Three independent repeated experiments were performed. The unpaired t test was utilized to analyze the data between two groups in panel C. *P < 0.05; **P < 0.01.
Both miR-223 and miR-126 have good predictive efficiency in unstable plaques in patients with CA
A Expression levels of miR-223 and miR-126 in the serum of patients with CA in the PS and PU groups. B ROC analysis for the predictive power of miR-223 and miR-126 on plaque stability in patients with CA. Each dot represents a subject, and three independent repeated experiments were performed. The unpaired t test was utilized to analyze the data between two groups in panel A. *P < 0.05; **P < 0.01.
MiR-126 and miR-223 are negatively associated with plaque instability factors in patients with CA
A ELISA was used to measure the serum levels of IL-6, MMP1, MMP9, and MCP1 in patients with CA. B–F Pearson’s correlation analysis for the relationships of miR-223 and miR-126 expression with the IL-6, MMP1, MMP9, and MCP1 levels, as well as plaque thickness in patients with CA. Each dot represents a subject, and three independent repeated experiments were performed. The unpaired t-test was utilized to analyze the data in panel A. **P < 0.01.
COX2 is a direct target gene of miR-126 and miR-233
A StarBase and TargetScan predicted the downstream target gene COX2 of miR-126 and miR-223. B, C Luciferase activity assay detected the target relationships of miR-223 and miR-126 with COX2. D RT-qPCR detected COX2 mRNA expression in the serum of normal controls and patients with CA. E Expression levels of COX2 mRNA in the serum of patients in the PS and PU groups. F Pearson’s correlation analysis for the relationships of miR-223 and miR-126 expression with COX2 expression. Each dot represents a subject, and three independent repeated experiments were performed. The unpaired t-test was utilized to analyze the data between two groups in panels D, E. **P < 0.01.
The COX2 expression level is positively correlated with plaque instability factors in patients with CA
A–E Pearson’s correlation analysis for the relationships of the expression of COX2 with the serum levels of IL-6, MMP1, MMP9, and MCP1 as well as plaque thickness in patients with CA. Each dot represents a subject, and three independent repeated experiments were performed.
  • Luya ZhuLuya Zhu
  • Yu WangYu Wang
  • Fengjie QiaoFengjie Qiao
Studies have demonstrated the essential functions of microRNAs (miRNAs) in cardiovascular disease. Herein, we explored the roles of miR-126 and miR-223 in the prediction of plaque stability in carotid atherosclerosis (CA).Patients with CA (N = 52) and healthy volunteers (N = 25) were recruited as the study subjects and controls. First, a miRNA microarray was performed to analyze the differentially expressed miRNAs in the serum of normal controls and patients with CA. Next, the correlations of miR-223 and miR-126 expression with plaque stability-related factors were analyzed. Then, the predictive efficacy of miR-223 and miR-126 on plaque stability was analyzed by the ROC curve, and the targeting relationships of miR-223 and miR-126 with COX2 were verified. Finally, the relationship between COX2 expression and CA plaque stability was analyzed. miR-223 and miR-126 were decreased in the serum of CA patients and had good diagnostic efficacy for CA. miR-223 and miR-126 in the serum of CA patients with unstable plaques were lower than that in patients with stable plaques. miR-223 and miR-126 were negatively correlated with plaque instability-related indicators, while COX2, a direct target of miR-223 and miR-126, was positively related to plaque instability-related indicators. Lowly expressed miR-223 and miR-126 in the serum of CA patients can be used as indicators for plaque stability.
RCT and AVS success rate
The left panel demonstrates the number of successful (black) and unsuccessful (white) procedures with RCT and without RCT. The right panel demonstrates the success rates according to year, with RCT being introduced in 2018. The time without RCT is represented by white, with RCT black and combination of RCT and no RCT hashed.
Effect of RCT on time in theatre and number of samples collected
The left panel represents the time spent in theatre in minutes. White with black circles demonstrates the procedures without RCT whilst black those with white circles RCT. The bar represents the mean time ± the SEM. Individual procedure times are represented by circles. The right panel depicts the number of samples taken during each AVS. White with black circles demonstrates the procedures without RCT whilst black with white circles those with RCT. The bar represents the mean time ± the SEM. The number of samples taken in each procedure are represented by circles. P values have been derived using an unpaired two sided t-test.
RCT and referral for adrenalectomy
Figure 3 represents the number of patients referred for adrenalectomy or chosen for medical management with and without RCT.
Effect of baseline success rate on cost effectiveness of intraprocedural cortisol testing
This a graphical representation of the cost in Australian Dollars of using RCT to prevent a single failed AVS. This analysis takes into account and the cost of the strips—the average number we of samples analysed (eight samples) if using RCT. It assumes an increase to a 100% success rate. It assumes a cost of $40 per strip.
Primary aldosteronism is the most common cause of secondary hypertension. Identifying individuals who have unilateral secretion from aldosterone secreting adenomas allows adrenalectomy. Surgical treatment when feasible may be superior to medical management with improved cardiovascular outcomes and reduced medication dependence. Adrenal vein sampling (AVS) is required to biochemically lateralise aldosterone secretion prior to adrenalectomy. However, diagnostic success of AVS is variable and can be poor even at tertiary centres; failure is largely due to unsuccessful adrenal vein cannulation. Intra-procedural rapid semiquantitative cortisol testing (RCT) identifies correct catheter placement in real time. We compared diagnostic success rates of AVS before and after the introduction of intraprocedural cortisol testing at the Royal Adelaide Hospital—a medium throughput tertiary centre (average 6.2 procedures a year over the last 8 years). We observed an increase in success rate from 63% to 94%. Intraprocedural cortisol testing also led to a net financial saving of ~$100 AUD per procedure. RCT is likely to be cost effective if pre-RCT success rate is less than 78%. Procedure time and number of samples collected, however, were increased with RCT. This suggests that intraprocedural cortisol testing will improve success in low to medium throughput centres and may make AVS feasible in less specialised centres.
Comparison of SII, hs-CRP, NLR, and PLR of the study groups
The levels of SII, NLR, and PLR were higher in patients with LVH compared to non-LVH (p < 0.001).
The receiver-operating characteristics (ROC) curve analyses of SII, hs-CRP, NLR, and PLR for the identification of left ventricular hypertrophy
AUC of SII was larger than NLR, PLR, and hs-CRP.
The relationship between SII and different left ventricle geometry patterns
SII was higher in groups with eccentric LVH and concentric LVH compared to the groups with normal left ventricular geometry and concentric remodeling.
The development of left ventricular hypertrophy (LVH) induced by hypertension is considered a poor prognosis for patients. Similarly, high values of the systemic immune-inflammation index (SII) are correlated with high mortality and morbidity in cardiovascular events. Within this context, our study aimed to detect the association of SII with LVH caused by hypertension. The study included 150 patients diagnosed with hypertension in total and evaluated them as two separate groups with regard to left ventricular mass index (LVMI), including 56 patients (37.3%) with LVH and 94 patients (62.6%) with non-LVH. SII was calculated as platelet × neutrophil/lymphocyte counts. The SII values regarding the group with LVH were detected remarkably higher than those of the non-LVH group (p < 0.001). Additionally, the SII levels of patients with eccentric and concentric hypertrophy were detected higher than those of the normal ventricular geometry and concentric remodeling groups. About curve analysis of the receiver-operating characteristic (ROC), SII values above 869.5 predicted LVH with a sensitivity of 82.1% and specificity of 86.2% (AUC: 0.861; 95% CI: 0.792–0.930; p < 0.001). LVH can be predicted independently through the use of SII in patients diagnosed with hypertension, which may be a simple and easily calculable marker for judging LVH. Moreover, SII can serve as an accurate determinant for the prediction of LVH, in comparison to NLR and PLR.
Study population flowchart.
Nelson–Aalen cumulative hazard estimates for the primary outcome
Considering 4-day HBPM average (A) and discarding first day measurements (B).
Nelson–Aalen cumulative hazard estimates for the primary outcome considering measurement periods separately
Morning (A), afternoon (B), and evening (C).
The prognostic value of home blood pressure monitoring (HBPM) has been investigated in several studies in the general population, demonstrating its independent association with cardiovascular events. However, in the case of treated hypertensive subjects, evidence is controversial. Our purpose was to evaluate the prognostic value of HBPM in this population. Medicated hypertensive patients who performed a 4-day HBPM (Omron® HEM-705CP-II) between 2008 and 2015 were followed up for a median of 5.9 years, registering the occurrence of a composite primary outcome of fatal and non-fatal cardiovascular events. Cox regression models were used to analyze the prognostic value of HBPM, considering 4-day measurements, discarding the first day, and analyzing morning, afternoon and evening periods separately. We included 1582 patients in the analysis (33.4% men, median age 70.8 years, on an average of 2.1 antihypertensive drugs). During follow-up, 273 events occurred. HBPM was significantly associated with cardiovascular events in all five scenarios in the unadjusted models. When adjusting for office BP and other cardiovascular risk factors, the association remained marginally significant for the 4-day period, discarding first-day measurements HBPM (HR 1.04 [95% CI 1–1.1] and 1.04 [95% CI 1–1.1], respectively) and statistically significant for all separate periods of measurement: HR 1.32 (95% CI 1.01–1.72); 1.33 (95% CI 1.02–1.72); and 1.30 (95% CI 1.01–1.67), for morning, afternoon and evening, respectively. When analyzing separately fatal and non-fatal events, statistical significance was held for the former only. In conclusion, HBPM is an independent predictor of cardiovascular events in hypertensives under treatment.
Conceptual framework of the Mumbai hypertension project
The framework describes the underlying challenges in hypertension management in the private sector, the service delivery model, the implementation framework, and the expected outcomes.
Intervention models in lean and intensive wards in the Mumbai hypertension control project
This figure illustrates the interventions offered in the lean and intensive models.
Kaplan–Meier curve describing the time to blood pressure control in intensive and lean wards in the Mumbai Hypertension Project
This figure shows the time to BP control patients whose BP was uncontrolled at the time of registration and who came for follow-up.
In India, the private sector provides 70% of the total outpatient medical care. This study describes the Mumbai Hypertension Project, which aimed to deliver a standard hypertension management package in private sector clinics situated in urban slums. The project was conducted in two wards (one “lean” and one “intensive”) with 82 private providers in each. All hypertensive patients received free drug vouchers, baseline serum creatinine, adherence support, self-management counseling and follow-up calls. In the intensive-ward, project supported hub agents facilitated uptake of services. A total of 13,184 hypertensive patients were registered from January 2019 to February 2020. Baseline blood pressure (BP) control rates were higher in the intensive-ward (30%) compared with the lean-ward (13%). During the 14-month project period, 6752 (51%) patients followed-up, with participants in the intensive-ward more likely to follow-up (aOR: 2.31; p < 0.001). By project end, the 3–6-month cohort control rate changed little from baseline—29% for intensive ward and 14% for lean ward. Among those who followed up, proportion with controlled BP increased 13 percentage points in the intensive ward and 16 percentage points in the lean ward; median time to BP control was 97 days in the intensive-ward and 153 days in lean-ward (p < 0.001). Despite multiple quality-improvement interventions in Mumbai private sector clinics, loss to follow-up remained high, and BP control rates only improved in patients who followed up; but did not improve overall. Only with new systems to organize and incentivize patient follow-up will the Indian private sector contribute to achieving national hypertension control goals.
Representative example of the individualized physiologic flow waveform (light grey curve) estimated from the blood pressure waveform (white curve) morphology and compared with measured flow (dark grey curve)
Ft identifies the foot of the pressure waveform, P1 the first systolic inflection point, Li the late systolic inflection, and Es the end of systole. The amplitude of the BP and flow curves are arbitrarily scaled for presentation.
Examples of wave seperation performed using measured and estimated flow waveforms
Representative examples of Pf (dark grey curve) and Pb (light grey curve) derived from the pressure waveform (white curve) using measured flow (A), individualized physiologic flow (B), averaged flow (C), triangular flow (D), and excess flow (E). Pf forward pressure, Pb backward pressure.
Bland-Altman plots showing agreement between Pf and Pb derived via measured flow with Pf and Pb derived via estimated flow
Agreement of Pf and Pb derived using individualized physiologic flow (panels A and E), averaged flow (panels B and F), triangular flow (panels C and G), and excess flow (panels D and H) compared with Pf and Pb derived using measured flow. Values above zero represent an overestimation and values below zero represent an underestimation of Pf and Pb derived via estimated flow methods compared with measured flow. Pf forward pressure, Pb backward pressure, UB upper bound, MD mean difference, LB lower bound.
Early-life exposure to high blood pressure (BP) is associated with cardiovascular target organ damage but not all BP-related risk is attributable to systolic and diastolic BP alone. In adolescence, aortic wave separation (WS) parameters are associated with increased left ventricular mass index (LVMI) but this approach is limited by the requirement for aortic flow measurements. Several methods for estimating the aortic flow waveform from pressure waveforms have emerged, but their accuracy and associations with LVMI have never been tested in adolescents, which was the aim of our study. Carotid pressure waveforms were acquired by tonometry from 58 adolescents (age 16 ± 1.5 years, 59% female). Measured (aortic) flow and LVMI were acquired via 2D echocardiography. Three pressure-only approximations of aortic flow were synthesized, including triangular, excess, and individualized-physiologic flow. A 4th aortic flow (average flow) was approximated from the average of all 58 measured flow waveforms. Forward (Pf) and backward (Pb) pressure and reflection magnitude (Rm) were derived from WS analysis. The individualized-physiologic flow produced the best approximations of Pf (mean difference ± SD, −0.15 ± 2.38 mmHg), Pb (0.14 ± 0.25 mmHg), and Rm (0.01 ± 0.02 mmHg). Pf derived using measured, individualized-physiologic, and average flow, was similarly associated with LVMI adjusting for age, brachial systolic BP, cardiac output, and BMI (P ≤ 0.03 all). Pb derived using all flow waveforms was associated with LVMI and all associations yielded similar effect estimates. Of the estimated flow waveforms, individualized-physiologic flow yielded the best approximation of WS parameters and may provide important physiological and clinical insight among adolescents.
The incidence of atrial fibrillation (AF) and risk of cardiovascular events are reportedly higher in patients with primary aldosteronism (PA) than essential hypertension. However, associated factors of comorbid AF and cardiovascular events in PA patients after PA treatment remain unclear. This nationwide registration study included PA patients ≥20 years old. Incident cardiovascular events were observed with a mean follow-up of approximately 3 years. A total of 3654 patients with PA were included at the time of analysis. Prevalence of AF was 2.4%. PA patients with AF were older, more frequently male and had longer duration of hypertension than those without AF. No significant difference in basal plasma and adrenal venous aldosterone concentration, renin activity, potassium concentration, confirmatory tests of PA, laterality or surgery rate were seen between groups. Logistic regression analysis showed age, male sex, cardiothoracic ratio, past history of coronary artery disease and heart failure were independent factors associated with AF. PA patients with AF showed a higher frequency of cardiovascular events than those without AF (P < 0.001). Multivariate Cox analyses demonstrated AF in addition to older age, duration of hypertension, body mass index and chronic kidney disease as independent prognostic factors for cardiovascular events after PA treatment. Incidence of cardiovascular events were significantly lower in PA patients with AF than AF patients from the Fushimi registry during follow-up after adjusting age, sex and systolic blood pressure. Early diagnosis of PA may prevent AF and other cardiovascular events in PA patients by shortening the duration of hypertension and appropriate PA treatment.
Chronic kidney disease (CKD) is a complex condition with a prevalence of 10–15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. The proportion of deaths due to heart failure and sudden cardiac death increase with progression of chronic kidney disease with relatively fewer deaths from atheromatous, vasculo-occlusive processes. This phenomenon can largely be explained by the increased prevalence of CKD-associated cardiomyopathy with worsening kidney function. The key features of CKD-associated cardiomyopathy are increased left ventricular mass and left ventricular hypertrophy, diastolic and systolic left ventricular dysfunction, and profound cardiac fibrosis on histology. While these features have predominantly been described in patients with advanced kidney disease on dialysis treatment, patients with only mild to moderate renal impairment already exhibit structural and functional changes consistent with CKD-associated cardiomyopathy. In this review we discuss the key drivers of CKD-associated cardiomyopathy and the key role of hypertension in its pathogenesis. We also evaluate existing, as well as developing therapies in the treatment of CKD-associated cardiomyopathy.
Hypertension-mediated organ damage (HMOD) at cardiac level include a variety of abnormal phenotypes of recognized adverse prognostic value. Although the risk of cardiac HMOD is related with the severity of BP elevation, the interaction of numerous non-hemodynamic factors plays a relevant role in this unfavorable dynamic process. In particular, sex-related differences in cardiovascular (CV) risk factors and HMOD have been increasingly described. The objective of the present review is to provide comprehensive, updated information on sex-related differences in cardiac HMOD, focusing on the most important manifestations of subclinical hypertensive heart disease such as left ventricular hypertrophy (LVH), LV systolic and diastolic dysfunction, left atrial and aortic dilatation. Current evidence, based on cross-sectional and longitudinal observational studies as well as real-world registries and randomized controlled trials, suggests that women are more at risk of developing (and maintaining) LVH, concentric remodeling and subclinical LV dysfunction, namely the morpho-functional features of heart failure with preserved ejection fraction. It should be pointed out, however, that further studies are needed to fill the gap in defining gender-based optimal therapeutic strategies in order to protect women’s hearts.
Pharmacists need to consider the accuracy of automated blood pressure (BP) devices. However, Picone et al. reported that pharmacists had low awareness regarding the accuracy of automated BP devices. We agreed their suggestion that education of pharmacists and advocacy for policies are required to ensure that pharmacists sell only validated BP devices as they are primary providers of BP devices.
Study design of the DASH-sodium trial and urine samples available for TNF-α measurement
Urinary TNF-α was measured in 24 h urine samples obtained at the final screening visit of the trial (baseline) when all subjects were consuming a “typical American diet”. All subjects were then given a control diet at the higher sodium level (150 mmol/kg) for the 2-week run-in period after which they were randomized to either the control or DASH diet. Within diet, sodium levels (low: 50 mmol Na+/day, medium: 100 mmol Na+/day, high:150 mmol Na+/day) were given in randomized order for 30 days each. Urinary TNF-α was measured in 24 h urine samples at the end of each 30-day sodium intervention. The number of urine samples available for each of the conditions are shown in bold.
Unadjusted baseline levels of urinary TNF-α by race and sex
Urine concentrations of TNF-α in DASH-Sodium subjects by race (A) and sex (B) showing medians (central lines) and IQR ranges. Bars extend to 1.5 x IQR with dots identifying data points outside of 1.5 x IQR. P-values reflect significance levels using the Wilcoxon Rank Sum Test.
Adjusted baseline differences in urinary TNF-α levels according to sex and race
Predicted average of values of TNF-α (pg/mg creatinine) and 95% CI at the mean values of age, waist circumference, 24-hour urine volume, and urinary excretion of sodium and potassium were significantly different, p < 0.05, between categories of race within sex (*) and then sex within race (**) using multivariable linear regression followed by Bonferroni adjusted subgroup analysis (A and B).
Adjusted levels of urinary TNF-α among subjects randomized to the control diet (Low to High Sodium) and DASH diet low to high sodium)
Estimated average values of urinary TNF-α in DASH-Sodium subjects randomized to the DASH diet after 4 weeks of low-sodium (50 mmol/day) and Control diet after 4 weeks of high sodium (150 mmol/day) after adjustment for age, osmolality, 24 h urine volume and urinary sodium, potassium and phosphorous. P < 0.05 value indicates a significant difference between TNF-α levels between low to high sodium within those randomized to the control diet.
Previous work in mouse models shows that urinary TNF-α levels become elevated when dietary salt (NaCl) intake increases. To examine if this relationship exists in humans, we conducted a secondary analysis of the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial to determine levels of urinary TNF-α in 367 subjects categorized by race, sex, and blood pressure. The DASH-Sodium trial is a multicenter feeding trial in which subjects were randomly assigned to either the DASH or control diet, and high, medium, and low sodium in random order. Multivariable linear regression was used to model baseline TNF-α and a mixed model was used to model TNF-α as a function of dietary intervention. At baseline, with all subjects on a “typical American diet”, urinary TNF-α levels were lowest in Black, p = 0.002 and male subjects, p < 0.001. After randomization to either the DASH or control diet, with increasing levels of sodium, urinary TNF-α levels increased only in subjects on the control diet, p < 0.05. As in the baseline analysis, TNF-α levels were highest in White females, then White males, Black females and lowest in Black males. The results indicate that urinary TNF-α levels in DASH-Sodium subjects are regulated by NaCl intake, modulated by the DASH diet, and influenced by both race and sex. The inherent differences between subgroups support studies in mice showing that increases in renal TNF-α minimize the extent salt-dependent activation of NKCC2.
Unadjusted Kaplan Meier curve for time till IHD event by groups (All)
Incidence of Ischemic Heart Disease (IHD) - comparison between resistant hypertension (RH) and controlled hypertension on multi-drug regimen (CH-MDR).
Unadjusted Kaplan Meier curve for time till CVA/TIA event by groups (All)
Incidence of stroke (CVA/TIA) - comparison between resistant hypertension (RH) and controlled hypertension on multi-drug regimen (CH-MDR).
Mean cumulative hospitalizations during follow-up period.
Mean cumulative ER visits during follow-up period.
The long-term risk associated with resistant hypertension compared to other phenotypes of hypertension is still unclear. We aimed to assess cardiovascular and renal outcomes over 10 years of follow-up of patients with uncontrolled resistant hypertension (uRH) compared to a similarly treated (≥ 3 medication classes including a diuretic) and adherent group whose blood pressure is under control. This retrospective cohort study utilized the computerized database of Maccabi Healthcare Services, a state-mandated health provider covering 25% of the Israeli population. Clinical outcomes were assessed using Cox regression multivariable analyses. A total of 1487 patients (50% males, mean age at baseline = 68.3 ± 10.4 years) were included in the uRH cohort and 1343 patients (50% males, 66.2 ± 10.6 years) in the controlled hypertension reference group (Controlled hypertension on multi drug regimen- CH-MDR). After adjusting for age, sex, BMI and patients’ comorbidities, uRH was associated with a Hazard Ratio of 1.35 (95% CI: 1.08–1.69) for incidence of ischemic heart disease, 1.51 (1.06–2.16) for secondary cardiovascular events, and 1.36 (1.00–1.86) for risk of stroke or transient ischemic attack compared to the reference group. Patients with uRH were found to have more hospitalization days (mean, 4.2 vs. 3 days per year, p < 0.001), and more emergency room visits (83.3% vs. 77%, p < 0.001). Overall, uRH was associated with a 19% (95% CI 11% to 29%) increase in direct healthcare expenditures during the first year of follow-up. uRH is associated with a substantial increased risk of both cardiovascular and cerebrovascular events, when compared to similarly treated hypertensive patients whose blood pressure is under control.
NCC mRNA measured in different conditions
A UEV obtained using the precipitation reagent, visualized by transmission electron microscopy at 28000 X magnification. White arrowheads and numbers indicate UEV and their diameters in nm. The scale bar represents 200 nm. B Scatterplot of the relative abundance of NCC mRNA in the UE of hypertensive (PA and EH) patients and normotensive subjects, expressed in -dCt values. C Scatterplot of the relative abundance of UE NCC mRNA in PA patients according to their diagnostic subtype. The median and range are indicated. D Scatterplot of the relative abundance of UE NCC mRNA before and after IV-SLT. Fold-changes were calculated as 2-ddCt on mean dCt value measured in normotensive subjects. Y Axis was log2 transformed to improve readability. E Relative abundance of the normalizer, B2M, in PA and EH patients who underwent IV-SLT, values are expressed in 2-Ct ad Y Axis was log2 transformed; F Corresponding creatinine concentrations of samples showed in panel E, **p < 0.01. UEV urinary extracellular vesicles, NCC Na chloride cotransporter, UE urinary exosomes, PA primary aldosteronism, EH essential hypertension, iv-SLT intravenous salt loading test.
NCC mRNA level in MRA treatment
A Scatterplot of UE NCC mRNA values before and after MRA treatment. Fold-change values have been calculated using the mean NCC value in normotensive subjects as normalizer. B Scatterplot of plasma renin and NCC mRNA levels of patients after MRA treatment (Spearman’s R = −0.81; p = 0.04). NCC mRNA variation is expressed in fold-change, using dCt POST MRA – dCt PRE MRA treatment for each subject. Data were transformed as log2(FC) for graphical representation.
NCC mRNA level after adrenalectomy
A Scatterplot of UE NCC mRNA values of four APA patients before and after adrenalectomy. Fold-change values have been calculated using the mean NCC value in normotensive subjects as normalizer. B Trends of NCC mRNA expression level 3 months and 12 months after surgery represented as log2 transformed fold-change using the basal condition for each subject as normalizer. UE urinary exosomes, NCC Na chloride cotransporter, APA aldosterone-producing adenoma.
Urinary extracellular vesicles (UEV) mainly derive from cells of the urogenital tract and their cargo (proteins, nucleic acids, lipids, etc.) reflects their cells of origin. Na chloride cotransporter (NCC) is expressed at the kidney level in the distal convoluted tubule, is involved in salt reabsorption, and is the target of the diuretic thiazides. NCC protein has been recognized and quantified in UEV in previous studies; however, UEV NCC mRNA has never been studied. This study aimed to identify and analyze NCC mRNA levels in primary aldosteronism (PA). The rationale for this investigation stems from previous observations regarding NCC (protein) as a possible biomarker for the diagnosis of PA. To evaluate modulations in the expression of NCC, we analyzed NCC mRNA levels in UEV in PA and essential hypertensive (EH) patients under different conditions, that is, before and after saline infusion, anti-aldosterone pharmacological treatment, and adrenal surgery. NCC mRNA was measured by RT-qPCR in all the samples and was regulated by volume expansion. Its response to mineralocorticoid receptor antagonist was correlated with renin, and it was increased in PA patients after adrenalectomy. NCC mRNA is evaluable in UEV and it can provide insights into the pathophysiology of distal convolute tubule in different clinical conditions including PA.
The key concerns relating to blood pressure (BP) management among Australian adults (n = 465).
Preferences for accessing information regarding the management of blood pressure among Australian adults (n = 465)
A currently used sources to obtain information about blood pressure and B preferences for information delivery. The number of responses were n = 39 for social media for the delivery of information regarding the management of blood pressure.
Characteristics of participants from the Australian general public that completed the survey about knowledge of high blood pressure (n = 465).
Blood pressure(BP) management interventions have been shown to be more effective when accompanied by appropriate patient education. As high BP remains poorly controlled, there may be gaps in patient knowledge and education. Therefore, this study aimed to identify specific content and delivery preferences for information to support BP management among Australian adults from the general public. Given that BP management is predominantly undertaken by general practitioners(GPs), information preferences to support BP management were also ascertained from a small sample of Australian GPs. An online survey of adults was conducted to identify areas of concern for BP management to inform content preferences and preferred format for information delivery. A separate online survey was also delivered to GPs to determine preferred information sources to support BP management. Participants were recruited via social media. General public participants ( n = 465) were mostly female (68%), >60 years (57%) and 49% were taking BP-lowering medications. The management of BP without medications, and role of lifestyle in BP management were of concern among 30% and 26% of adults respectively. Most adults (73%) preferred to access BP management information from their GP. 57% of GPs (total n = 23) preferred information for supporting BP management to be delivered via one-page summaries. This study identified that Australian adults would prefer more information about the management of BP without medications and via lifestyle delivered by their GP. This could be achieved by providing GPs with one-page summaries on relevant topics to support patient education and ultimately improve BP management.
Availability of antihypertensive drugs in the IHCI project sites, March 2020. This chart describes the availability of three types of antihypertensive drugs in patient days (≥90 days is optimal) in five Indian states.
Blood pressure control in various types of facilities in JanMarch, 2020 among a cohort of patients under care in 26 districts in India.
Community level blood pressure control in IHCI project districts, India. Estimated community-level BP control in 26 districts among patients under care in Jan-March, 2020 compared to JanMarch, 2019, India. (Estimated hypertensives N = 45,41,994, Number with BP control = 2,18,340 in Jan-March 2020, Number with BP control = 64,704 in Jan-March, 2019).
Patients under the care and proportion of controlled blood pressure (BP), uncontrolled BP, and missed visits among patients on treatment in public sector facilities in 26 districts in
Hypertension is the leading single preventable risk factor for cardiovascular disease. The India Hypertension Control Initiative (IHCI) project was designed to improve hypertension control in public sector clinics. The project was launched in 2018–2019 in 26 districts across five states: Punjab (5), Madhya Pradesh (3), Kerala (4), Maharashtra (4), and Telangana (10), with five core strategies: standard treatment protocol, reliable supply of free antihypertensive drugs, team-based care, patient-centered care, and an information system to track individual patient treatment and blood pressure control. All states implemented simple treatment protocols with three drugs: a long-acting dihydropyridine calcium channel blocker (amlodipine), angiotensin receptor blocker (telmisartan), and thiazide or a thiazide-like diuretic (hydrochlorothiazide or chlorthalidone). Medication supplies were adequate to support at least one month of treatment. Overall, 570,365 hypertensives were enrolled in 2018–2019; 11% did not have follow-up visits in the most recent 12 months. Clinic-level blood pressure control averaged 43% (range 22–79%) by Jan-March, 2020. The proportion of the estimated people with hypertension who had it controlled and documented in public clinics increased three-fold, albeit from very low levels (1.4–5.0%). The IHCI demonstrated the feasibility of implementing protocol-based hypertension treatment and control supported by a reliable drug supply and accurate information systems at scale in Indian primary health care facilities. Lessons from the IHCI’s initial phase will inform plans to improve screening in health care facilities, increase retention in care, and ensure a sustained supply of drugs as part of a nationwide hypertension control program.
Prevalence of primary, secondary and white coat hypetension by age
Data arranged by age tertile and pertains to those aged <18 years of age diagnosed with hypertension.
Distribution of hypertension phenotype by ethnicity compared to background population
Data includes patient stated ethnicity and pertains to those aged <18 years of age diagnosed with hypertension.
We aimed to describe hypertensive phenotype and demographic characteristics in children and adolescents referred to our paediatric hypertension service. We compared age, ethnicity and BMI in primary hypertension (PH) compared to those with secondary hypertension (SH) and white coat hypertension (WCH). Demographic and anthropometric data were collected for children and adolescents up to age 18 referred to our service for evaluation of suspected hypertension over a 6 year period. Office blood pressure (BP) and out of office BP were performed. Patients were categorised as normotensive (normal office and out of office BP), WCH (abnormal office BP, normal out of office BP), PH (both office and out of office BP abnormal, no underlying cause identified) and SH (both office and out of office BP abnormal, with a secondary cause identified). 548 children and adolescents with mean ± SD age of 10.1 ± 5.8 years and 58.2% girls. Fifty seven percent (n = 314) were hypertensive; of these, 47 (15%), 84 (27%) and 183 (58%) had WCH, PH and SH, respectively. SH presented throughout childhood, whereas PH and WCH peaked in adolescence. Non-White ethnicity was more prevalent within those diagnosed with PH than both the background population and those diagnosed with SH. Higher BMI z-scores were observed in those with PH compared to SH. Hypertensive children <6 years are most likely to have SH and have negligible rates of WCH and PH. PH accounted for 27% of hypertension diagnoses in children and adolescents, with the highest prevalence in adolescence, those of non-White Ethnicity and with excess weight.
CONSORT flow chart of study enrollment
Enrollment and allocation information is summarised for invited patients.
Change in clinic BP and skin pigmentation after 2 weeks phototherapy
Clinic BP measurement of change in systolic (a) and diastolic (b) BP and skin pigmentation after 2 weeks daily whole body active or sham irradiation with 5 J/cm² UVA. Differences between sham and mean irradiation are significant (p = 0.034 for systolic and 0.029 for diastolic BP). a, b Measurements recorded over all seasons. c Systolic BP changes recorded in the lighter half of the year from Vernal to Autumnal Equinox. d Systolic BP changes recorded in the darker half of the year from Autumnal to Vernal Equinox. Error bars show sem.
Latitude and season determine exposure to ultraviolet radiation and correlate with population blood pressure. Evidence for Vitamin D causing this relationship is inconsistent, and temperature changes are only partly responsible for BP variation. In healthy individuals, a single irradiation with 20 J/cm2 UVA mobilises NO from cutaneous stores to the circulation, causes arterial vasodilatation, and elicits a transient fall in BP. We, therefore, tested whether low-dose daily UVA phototherapy might be an effective treatment for mild hypertension. 13 patients with untreated high-normal or stage 1 hypertension (BP 130-159/85-99 mm Hg), confirmed by 24-h ambulatory blood pressure (ABP), were recruited. Using home phototherapy lamps they were either exposed to 5 J/cm2 full body UVA (320–410 nm) radiation each day for 14 days, or sham-irradiated with lamps filtered to exclude wavelengths <500 nm. After a washout period of 3 ± 1 week, the alternate irradiation was delivered. 24-h ABP was measured on day 0 before either irradiation sequence and on day 14. Clinic BP was recorded on day 0, and within 90 min of irradiation on day 14. There was no effect on 24-h ABP following UVA irradiation. Clinic BP shortly after irradiation fell with UVA (−8.0 ± 2.9/−3.8 ± 1.1 mm Hg p = 0.034/0.029) but not sham irradiation (1.1 ± 3.0/0.9 ± 1.5 mm Hg). Once daily low-dose UVA does not control mildly elevated BP although it produces a transient fall shortly after irradiation. More frequent exposure to UVA might be effective. Alternatively, UVB, which photo-releases more NO from skin, could be tried.
Engagement with MyBP program
The figure displays participants in the active intervention group rank-ordered according to program engagement. The engagement was defined as the proportion of prompts to which each participant responded by submitting a BP reading over the duration of their participation. Program instructions and recurring feedback encouraged participants to submit at least 4 of 8 requested BP readings each week (50%).
Engagement time trend
The height of stacked bars indicates the proportion of participants who submitted at least four readings. The number of subjects represents the MyBP group participants that activated the program (39) and who were not taking a 2-week break and had not yet completed the study.
Scatter plots of change in systolic BP as a function of baseline systolic BP
The intervention effect on change in BP is moderated by baseline BP in linear regression [interaction effect (95% confidence interval): −0.59 (−1.00, −0.19)], such that MyBP was associated with a decline in systolic BP only in participants with relatively high systolic BP at baseline.
Home blood pressure monitoring (HBPM) can improve hypertension management. Digital tools to facilitate routinized HBPM and patient self-care are underutilized and lack evidence of effectiveness. MyBP provides video-based education and automated text messaging to support continuous BP self-monitoring with recurring feedback. In this pragmatic trial, we sought to generate preliminary evidence of feasibility and efficacy in community-dwelling adults ≥55 y/o with hypertension recruited from primary care offices. Enrollees were provided a standard automatic BP cuff and randomized 2:1 to MyBP vs treatment-as-usual (control). Engagement with MyBP was defined as the proportion of BP reading prompts for which a reading was submitted, tracked over successive 2-week monitoring periods. Preliminary measures of efficacy included BP readings from phone-supervised home measurements and a self-efficacy questionnaire. Sixty-two participants (40 women, 33 Blacks, mean age 66, mean office BP 164/91) were randomized to MyBP (n = 41) or a control group (n = 21). Median follow-up was 22.9 (SD = 6.7) weeks. In the MyBP group, median engagement with HBPM was 82.7% (Q1 = 52.5, Q3 = 89.6) and sustained over time. The decline in systolic [12 mm Hg (SD = 17)] and diastolic BP [5 mm Hg (SD = 7)] did not differ between the two treatment groups. However, participants with higher baseline systolic BP assigned to MyBP had a greater decline compared to controls [interaction effect estimate −0.56 (−0.96, −0.17)]. Overall hypertension self-efficacy improved in the MyBP group. In conclusion, trial results show that older hypertensive adults with substantial minority representation had sustained engagement with this digital self-monitoring program and may benefit clinically.
Analytical framework of population coverage interventions in the hypertension control cascade
Status quo intervention refers to keeping the status quo level of probabilities unchanged in subsequent cascade levels. Best practice intervention refers to setting probabilities as those of better performing health systems in the subsequent cascade levels.
Comparison of uncontrolled hypertension prevalence outcomes status-quo and best practice population coverage interventions at different cascade levels
The dashed lines are showing estimates using zero elasticity, meaning treatment and control rate are constant for any additional aware and treated individuals. Status quo intervention refers to keep the status quo level of probabilities unchanged in subsequent cascade levels. Best practice intervention refers to setting probabilities as those of better performing health systems in the subsequent cascade levels. The baseline refers to 2018 Bangladesh National STEPS survey’s estimate of hypertension prevalence (WHO, 2018).
Effective control of hypertension at the population level is a global public health challenge. This study shows how improving population coverages at different hypertension care cascade levels could impact population-level hypertension management. We developed an analytical framework and a companion Excel model of multi-level hypertension care cascade entailing awareness, treatment, and control. The model estimates the prevalence of uncontrolled hypertension for different level of population coverages at certain cascade levels. We applied the model to data from Bangladesh and reported prevalence estimates associated with coverage interventions at different cascade levels. The model estimated that if 50% of the unaware hypertensive patients became aware of their hypertensive condition, the prevalence of uncontrolled hypertension would decrease by 1.8 and 1.3 percentage points (8.2% and 5.8% relative reduction), respectively, for constant and variable rates in the status quo setting. When 50% of the aware, but untreated individuals received treatment, the prevalence would decrease by around 0.7 percentage points (3.3% relative reduction). A 50% decrease in the share of treated individuals who did not have hypertension under control, would result in decreasing the prevalence by 2.8 percentage points (12.7% relative reduction). By providing an analytical tool that demonstrates the probable impact of population coverage interventions at certain hypertension care cascade levels, our study endows public health practitioners with vital information to identify gaps and design effective policies for hypertension management.
Unadjusted means of the RAAS components for black (A) and white (B) women not using contraception, using the combination pill, and receiving the injection/implant. Error bars are standard deviation and significance at P ≤ 0.05 level, respectively.
Exogenous estrogens and progestins may affect the components of the renin–angiotensin–aldosterone system (RAAS). Changes in ventricular blood volume are associated with increased secretion of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP), which may also be affected by hormonal contraceptives. In this study, we aimed to compare components of the RAAS and NT-proBNP between groups using different hormonal contraceptives, including the combination pill, the injection or implant, and controls (no contraception) in black and white women of fertile age (20 – 30 years). Secondly, we determined whether blood pressure and NT-proBNP are associated with the RAAS components. We included 397 black and white women not using contraceptives, 120 using the combination pill, and 103 receiving an injection/implant. RAAS Triple-A analysis was carried out with LC-MS/MS quantification, and blood pressure measurements (ABPM) taken over 24 h. We found that serum aldosterone was higher (475.7 vs. 249.2 pmol/L; p < 0.001) in the combination pill group than in the no contraception group of white women. The aldosterone-angiotensin II ratio (AA2) was higher (5.4 vs. 2.5; p < 0.001) in the combination pill group than in the no contraception group. In the black women using the combination pill, we found a borderline-positive and borderline-negative association between 24-h systolic blood pressure and NT-proBNP with equilibrium (eq) Ang II, respectively. In white women using the combination pill, only CRP contributed positively and independently to NT-proBNP. To conclude, activation of RAAS by different hormonal contraceptives may increase future risk for the development of hypertension in young black and white women.
Venn diagram of preeclampsia and aspirin targets
There are 1463 preeclampsia associated targets and 160 aspirin associated targets. 90 intersecting targets of preeclampsia and aspirin were obtained.
Top 20 biological processes and KEGG signaling pathways of the intersecting targets
A Biological processes. X-axis represents gene ratio, Y-axis represents biological process. The number of genes involved in biological processes is represented by the size of the bubble. The adjusted p value is represented by color, and the darker the color, the smaller the adjusted p value. B KEGG signaling pathways. X-axis represents gene ratio, Y-axis represents signaling pathway. Bubble size represents the number of genes involved in the KEGG signaling pathway. The adjusted p value is represented by color, and the darker the color, the smaller the adjusted p-value.
Protein–protein interaction network and hub targets
A Protein–protein interaction network. B Hub targets.
Molecular docking of aspirin and proteins
Black arrows point to aspirin. A Molecular docking of aspirin and TP53. B Molecular docking of aspirin and CXCL8. C Molecular docking of aspirin and MAPK3. D Molecular docking of aspirin and MAPK1. E Molecular docking of aspirin and MAPK14. F Molecular docking of aspirin and EGFR. G Molecular docking of aspirin and ESR1. H Molecular docking of aspirin and PTGS2.
This study aimed to reveal the key targets and molecular mechanisms of aspirin in preventing preeclampsia. We used bioinformatics databases to collect the candidate targets for aspirin and preeclampsia. The biological functions and signaling pathways of the intersecting targets were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Then, the hub targets were identified by cytoscape plugin cytoHubba from the protein–protein interaction network. We collected 90 targets for aspirin in preventing preeclampsia. The biological processes of the intersecting targets are mainly involved in xenobiotic metabolic process, inflammatory response, negative regulation of apoptotic process, and protein phosphorylation. The highly enriched pathways were FoxO signaling pathway, circadian rhythm, insulin resistance, arachidonic acid metabolism, and drug metabolism-cytochrome P450. The hub targets for aspirin in preventing preeclampsia were tumor protein p53 (TP53), C–X–C motif chemokine ligand 8 (CXCL8), mitogen-activated protein kinase 3 (MAPK3), mitogen-activated protein kinase 1 (MAPK1), mitogen-activated protein kinase 14 (MAPK14), epidermal growth factor receptor (EGFR), estrogen receptor (ESR1), and prostaglandin-endoperoxide synthase 2 (PTGS2). Molecular docking results showed good bindings between the proteins and aspirin. In conclusion, these findings highlight the key targets and molecular mechanisms of aspirin in preventing preeclampsia.
Categorical association between CRF and hypertension risk
CRF cardiorespiratory fitness, RR risk relative, CI confidence interval. A High versus low CRF in total population; B Moderate versus low CRF in total population.
Dose–response association between CRF and hypertension risk
A RR of hypertension for per 1-MET increase in CRF in total population. B Dose–response relation of CRF and hypertension in the total population. C RR of hypertension for per 1-MET increase in CRF in men. D Dose–response relation of CRF and hypertension in men). CRF cardiorespiratory fitness, RR risk relative, CI confidence interval, MET metabolic equivalent of task.
Association between CRF increase and hypertension risk
CRF cardiorespiratory fitness, RR risk relative, CI confidence interval.
Established evidence has indicated a negative correlation between cardiorespiratory fitness (CRF) and hypertension risk. In this study, we performed a meta-analysis to investigate the categorical and dose–response relationship between CRF and hypertension risk and the effects of CRF changes on hypertension risk reduction. The PubMed, Web of Science, and Embase databases were searched for relevant studies. The summarized relative risk (RR) and 95% confidence interval (95% CI) were estimated using the DerSimonian and Laird random effect model, and the dose–response relationship between CRF and hypertension risk was characterized using generalized least-squares regression and restricted cubic splines. Nine cohorts describing 110,638 incident hypertension events among 1,618,067 participants were included in this study. Compared with the lowest category of CRF, the RR of hypertension was 0.63 (95% CI: 0.56–0.70) for the highest CRF category and 0.85 (95% CI: 0.80–0.91) for the moderate category of CRF. For a 1-metabolic equivalent increment in CRF, the pooled RR of hypertension was 0.92 (95% CI: 0.90–0.94) in the total population. The RR of hypertension was 0.71 (95% CI: 0.64–0.79) for participants with CRF increased compared with those whose CRF was decreased over time. In conclusion, our meta-analysis supports the widely held notion of a negative dose-dependent relationship between CRF and hypertension risk.
Flow chart of study participants
14,083 participants who did not use antihypertensive drugs.
Association between WHtR and HTN, ISH, IDH, and SDH
A WHtR and HTN; B WHtR and ISH; C WHtR and IDH; D WHtR and SDH. Adjusted for sex, age, area, smoking, drinking, education status, occupation, family history of hypertension, and sleep duration on workday and non-workday.
Data regarding the association of the waist-to-height ratio (WHtR) with hypertension (HTN) are conflicting. Moreover, little information is available on the association between WHtR and HTN subtypes. Therefore, we aimed to investigate the associations between WHtR and the prevalence of HTN and its subtypes in a Chinese population. In the cross-sectional analysis, 13,947 adults from the China Hypertension Survey study were analysed. We examined the relationship between WHtR and the prevalence of HTN and its subtypes (isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH) and systodiastolic hypertension (SDH)) using multivariate logistic regression analysis. A generalized additive model (GAM) and smooth curve fitting (penalized spline method) were also used. Overall, the mean WHtR was 0.50. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for HTN, ISH, IDH and SDH for each standard deviation (SD) increase in WHtR were 1.53 (1.45−1.61), 1.36 (1.28−1.44), 1.41 (1.20−1.65) and 1.47 (1.36−1.59), respectively. The fully adjusted smooth curve fitting revealed a linear association between WHtR and HTN, ISH, IDH, and SDH. Moreover, the positive associations between WHtR and HTN and its subtypes were more strong among younger adults (<60 compared with ≥60 years, P values for interaction <0.001). These findings suggested that WHtR was positively associated with HTN and its subtypes, especially among younger adults (<60 years) in southern China.
Adjusted HRs for incident hypertension according serum uric acid concentration by restricted cubic spline model in Jinchang Cohort population
SUA serum uric acid. Adjusted for age (<30, 30–59, ≥60), sex (male, female), education level (primary school or illiterate, middle school, junior college, bachelor’s degree or above), smoking index (0, 0–6.60, 6.61–15.00, 15.01–25.00, ≥25.01), alcohol index (0, 0–53.50, 53.51–129.52, 129.53–295.65, ≥295.66), TC (<4.00, 4.01–4.50, 4.51–5.10, ≥5.11), TGs (<1.00, 1.00–1.40, 1.41–2.10, ≥2.11), exercise (no, yes), family history of hypertension (no, yes) and diabetes (no, yes). The median of SUA was used as the reference value. Four knots of the restricted cubic spline model were 5th, 25th, 75th and 95th.
Sex subgroups analysis of SUA quartiles distribution and hazard ratios (HRs) of hypertension incidence in Jinchang Cohort population
SUA serum uric acid. Quartile distribution was stratified based on the SUA distribution on the nonhypertension population; crude HRs without adjustment for confounding; adjusted for age (<30, 30–59, ≥60), education level (primary school or illiterate, middle school, junior college, bachelor’s degree or above), exercise (no, yes), TGs (<1.00, 1.00–1.40, 1.41–2.10, ≥2.11), family history of hypertension (no, yes) and diabetes (no, yes) in adjusted model; P for trend: The median of each group of SUA was treated as continuous variable into the model for trend test.
Age subgroups analysis of SUA quartiles distribution and hazard ratios (HRs) of hypertension incidence in Jinchang Cohort population
SUA serum uric acid. Quartile distribution was stratified based on the SUA distribution on the nonhypertension population. Crude HRs without adjustment for confounding. Adjusted for sex (male, female), smoking index (0, 0–6.60, 6.61–15.00, 15.01–25.00, ≥25.01), TGs (<1.00, 1.00–1.40, 1.41–2.10, ≥2.11), exercise (no, yes), family history of hypertension (no, yes) in adjusted model. P for trend: The median of each group of SUA was treated as continuous variable into the model for trend test.
Mediation effects of baseline insulin resistance (TyG) on the association between baseline SUA and follow-up hypertension in Jinchang Cohort population
SUA serum uric acid, TyG triglyceride glucose product index, βMed βmediation. A Total population. B Male population. C Female population. #P < 0.05.
Many studies have demonstrated that elevated serum uric acid independently increases the risk of developing hypertension. However, the role of insulin resistance in the relationship between serum uric acid and hypertension is still unelucidated. Based on a prospective cohort study, we aimed to examine the longitudinal link between serum uric acid and hypertension and whether this relationship was mediated by insulin resistance. Overall, 21,999 participants without hypertension or gout at baseline with a mean age of 46 ± 13 years in the Jinchang Cohort were included in our study. Adjusted Cox-regression analyses and mediation analyses were performed to assess the risk of hypertension by serum uric acid quartile distribution and whether insulin resistance mediated the association between serum uric acid and hypertension. During the first follow-up period, 3080 participants developed hypertension. After controlling for covariates, compared with the lowest quartile of serum uric acid, the risk of hypertension in the highest quartile was 1.21 (1.06, 1.38) in the overall population. The risks for males and females were 1.14 (1.00–1.29) and 1.30 (1.08–1.56), respectively. The correlation between serum uric acid and hypertension was especially observed in younger people (<30 years). The mediating effects of insulin resistance were 0.058 (0.051, 0.065), 0.030 (0.025, 0.036) and 0.056 (0.047, 0.065), and the proportions mediated were 39.73, 36.59 and 38.62% in the overall, male and female populations, respectively. Elevated serum uric acid levels are associated with an increased risk of incident hypertension, and insulin resistance may play a mediating role in the relationship between serum uric acid and hypertension.
WC trajectories during young adulthood
WC waist circumference.
Gender-specific WC trajectories during young adulthood
a WC trajectories of males. b WC trajectories of females. WC waist circumference.
Single measurements of waist circumference (WC) can predict the incident hypertension, while dynamic change patterns of WC during young adulthood and their association with the incidence of hypertension are poorly demonstrated. This study aimed to identify the longitudinal WC trajectories during young adulthood and explore their association with the risk of incident hypertension. We utilized the data from the China Health and Nutrition Survey (1993–2015) and included 6604 participants aged 18–50 years with repeated WC measurements of 3–8 times and information on incident hypertension. The group-based trajectory model was used to identify WC trajectories. Cox proportional hazard model was conducted to evaluate the association of WC trajectories with the risk of incident hypertension. We identified four distinct WC trajectories during young adulthood. Participants with the low-increasing and the moderate-increasing trajectories had increasing but normal WC, while those with the high-increasing and the sharp-increasing trajectories developed from non-abdominal obesity to abdominal obesity. Compared with the low-increasing trajectory, the adjusted hazard ratios (95% confidence intervals) were 1.48 (1.16–1.89), 2.50 (1.84–3.40), and 3.86 (2.40–6.21) for the moderate-increasing, the high-increasing, and the sharp-increasing trajectories, respectively. After further excluding participants with obesity at baseline, this association did not alter substantially. The gender-specific trajectory analyses yielded similar results. WC trajectories during young adulthood were significantly associated with the risk of incident hypertension in Chinese. Moreover, even the increasing WC trajectory within the normal range during young adulthood might increase the risk of hypertension.
PRISMA flow chart of the studies included for the present meta-analysis.
Forest plots of cardiovascular variables including the change of resting systolic blood pressure (A), resting diastolic blood pressure (B), and resting heart rate (C) after exercise with blood flow restriction compared to the same exercise with no blood flow restriction.
The purpose of this meta-analysis was to examine the effects of blood flow restriction training on resting blood pressure and heart rate. A meta-analysis was completed in May 2020 including all previously published papers on blood flow restriction and was analyzed using a random effects model. To be included, studies needed to implement a blood flow restriction protocol compared to the same exercise protocol without restriction. A total of four studies met the inclusion criteria for quantitative analysis including four effect sizes for resting systolic blood pressure, four effect sizes for resting diastolic blood pressure, and three effect sizes for resting heart rate. There was evidence of a difference [mean difference (95 CI)] in resting systolic blood pressure between training with and without blood flow restriction [4.2 (0.3, 8.0) mmHg, p = 0.031]. No significant differences were observed when comparing resting diastolic blood pressure [1.2 (−1, 3.5) mmHg p = 0.274] and resting heart rate [−0.2 (−4.7, 4.1) bpm, p = 0.902] between chronic exercise with and without blood flow restriction. These results indicate that training with blood flow restriction may elicit an increase in resting systolic blood pressure. However, lack of data addressing this topic makes any conclusion speculative. Based on the results of the present study along with the overall lack of long-term data, it is suggested that future research on this topic is warranted. Recommendations include making changes in resting blood pressure a primary outcome and increasing the sample size of the interventions.
Carotid wall layers
Illustrative images of carotid intima (1), media (2), and intima-media (3) thickness from three different participants. The images were zoomed in to provide a more illustrative view of carotid wall layers.
Relationship between carotid plaques and wall layers
A Logistic regression analysis between carotid plaques and wall layers adjusted for age, sex, creatinine, glycated hemoglobin, and triglycerides. AIC Akaike information criterion. B Receiver-operating characteristic (ROC) curves for the prediction of carotid plaques. AUC area under curve. *p < 0.05 compared with intima thickness.
Relationship between left ventricular hypertrophy (LVH) and carotid wall layers
A Logistic regression analysis between left ventricular hypertrophy (LVH) and carotid wall layers adjusted for age, sex, systolic blood pressure, spironolactone use, and central alpha2 agonist use. AIC Akaike information criterion. B Receiver-operating characteristic (ROC) curves for the prediction of LVH. AUC area under curve.
Carotid intima-media thickness (cIMT) is considered a marker of subclinical atherosclerosis and is related to target-organ damage in hypertensive patients. However, increased cIMT may be due to increases in the thickness of intima (cIT) and media (cMT) layers. This study evaluated whether cIMT layers (cIT and cMT) had a greater association with carotid atherosclerotic plaques and left ventricular hypertrophy (LVH) than cIMT in hypertensive subjects. We cross-sectionally evaluated clinical, carotid, and echocardiography characteristics of 186 hypertensive patients followed at an outpatient clinic. High-resolution images of common carotid arteries were obtained by ultrasonography equipped with 10-MHz transducers, and cIT, cMT, and cIMT were manually measured using an image-processing software. Among all participants (n = 186; age = 60.8 ± 10.9 years, 43% males), there were 58% with carotid plaques and 58% with LVH. Mean cIT, cMT, and cIMT values were 0.267 ± 0.060, 0.475 ± 0.107, and 0.742 ± 0.142 mm, respectively. In logistic regression analysis adjusted for relevant covariates, carotid plaques showed stronger association with cIT than with cMT and cIMT. Furthermore, cIT showed greater area under the ROC curve (0.92; 95% CI 0.87−0.96) than cIMT (0.79; 95% CI 0.72−0.85) and cMT (0.64; 95% CI 0.56−0.72) to identify plaques. Conversely, cIT, cMT, and cIMT had modest association and accuracy to identify LVH (area under the ROC curve = 0.61, 0.57, and 0.60, respectively). In conclusion, cIT is a more accurate marker of atherosclerosis than cMT or cIMT, while cIT and cMT provide no incremental value in identifying LVH when compared with cIMT among hypertensive subjects.
Forest plots for all studies with available data of (A) the area under the receiver operating characteristic curve (AUC) and (B) the ratio of observed to expected complete resolution of hypertension after unilateral adrenalectomy for PA.
Forest plots of stratum-specific likelihood ratios for patients classified as low (ARS 0–1), moderate (ARS 2–3) and high probability (ARS 4–5) for complete resolution of hypertension by the ARS predictive model.
The Aldosteronoma Resolution Score (ARS) is the most studied scoring system for predicting the high likelihood of hypertension cure after adrenalectomy for unilateral primary aldosteronism (PA). However, the ARS’s accuracy in PA patients worldwide is uncertain. We aimed to perform a meta-analysis of the accuracy, discrimination, and calibration of the ARS using stratum-specific likelihood ratios (SSLR) by organizing available data from cohort studies. We searched PubMed, Embase (Ovid), the Cochrane CENTRAL, Web of Science to November 2021 according to PRISMA statement. The quality assessment used adapted TRIPOD and PROBAST criteria. Thirteen studies comprising 2158 PA patients from North America (43%), Europe (32%), Asia (22%), and other continents, were included. The pooled estimate of the area under the receiver operating characteristic curve for all studies was 0.77 (95% CI: 0.73–0.81), and the ratio of the observed to expected complete resolution of hypertension (CRH) for all studies was 0.9 (95% CI: 0.8–1.0). The summary estimates of the SSLR for all studies were 0.31, 0.89, and 3.1, for the low (ARS 0–1), medium (ARS 2–3), and high-likelihood group (ARS 4–5) of CRH, respectively. However, substantial heterogeneity existed among studies. Follow-up period, and adrenalectomy AVS (adrenal vein sampling)-guided served as potential sources of heterogeneity for quantitative studies, which were measurement and reference standard for qualitative studies selection. In conclusion, in patients with unilateral PA, the ARS is currently an accurate prediction tool, the easiest and cheapest, for identifying long-term high likelihood of CRH after adrenalectomy, particularly when the adrenalectomy is AVS-guided.
Prevalence of hypertension by age group and child marriage and adolescent childbearing
Estimates were obtained using complex survey weights. Vertical lines across the markers illustrates 95% confidence intervals.
Hypertension in reproductive age women, particularly in low-and-middle income countries (LMICs) is an area that is less explored. This study assesses the risk of hypertension in relation to two critical women’s health issues in the LMICs – child marriage and adolescent childbearing. The health consequences of these issues have been primarily studied in the context of reproductive health. There is a dearth of evidence on the long-term health outcomes associated with these early life events. The current study, by linking child marriage and adolescent motherhood with hypertension in young adult and early middle-aged women, is commensurate with the body of literature that examines the link between potentially early adversity and later life risk of chronic health outcomes. Using the most recent data on 582,358 women aged 20 to 49 years from India, this study examined whether child brides and adolescent mothers at age 20 s, 30 s, and 40 s had a higher risk of having hypertension compared to women who were not married before age 18 years or did not give birth by age 19 years in respective age groups. Estimating multivariable logistic regressions, we found that child brides and adolescent mothers were about 1.2 times more likely to have hypertension later in life. The elevated risk of hypertension among child brides and adolescent mothers were evident at every age group. These results were robust after controlling for various sociodemographic, anthropometric, and behavioral characteristics as well as across urban and rural, and poor and non-poor subgroups.
Survival curves of participants stratified by tertiles of baseline NLR
Survival curves of participants stratified by tertiles of baseline NLR without (A) or with (B) adjustment for covariates including age, gender, smoking history, BMI, BUN, DBP, FBG, PLR, PLT, SBP, TBil, WBC, hypertension, diabetes, and dyslipidemia (Tertile1: NLR >1.56, Tertile2: 2.17>NLR≥1.56, Tertile3: NLR ≥2.17).
Variable selections using the LASSO binary logistic regression
After LASSO regression selection, 18 variables were reduced to 10 variables with nonzero coefficients. BMI body mass index, BP blood pressure, BUN blood urea nitrogen, FBG fasting blood glucose, NLR neutrophil-to-lymphocyte ratio, PLR platelet-to-lymphocyte ratio, PLT platelet, TBil total bilirubin, WBC white blood count.
Based on a cohort in Tianjin, China, we explore the relationship between neutrophils-to-lymphocyte ratio (NLR) and the risk of cardiovascular diseases (CVDs). From January 2010 to December 2019, 4667 eligible participants aged more than 40 years old, CVDs-free, and registered in two community health service centers were recruited and followed up. The values of NLR collected at baseline were included in Cox proportional hazards model to evaluate its association with the incidence risk of CVDs. Hazard ratio (HR) and 95% confidence interval (CI) were calculated before and after adjustment for potential confounding factors selected by LASSO regression. During a total of 13,691 person-years of follow-up among all participants (median, 2.0 years; interquartile range, 1.7–2.5), 150 (3.42%) newly diagnosed CVDs events occurred, with the incidence density of CVDs of 10.96/1000 person-year. The incidence density in subgroups categorized by tertiles of baseline NLR was 8.08/1000, 11.74/1000, and 13.24/1000, respectively (p trend = 0.019). COX models revealed that after adjustment for potential confounders, NLR (as a continuous variable) was significantly related to the risk of total CVDs (HR 1.10, 95% CI: 1.04, 1.17), myocardial infarction (HR 1.12, 95% CI: 1.05, 1.20), and ischemic stroke (HR 1.21, 95% CI: 1.10, 1.33). When NLR was categorized into tertiles, participants in the top tertile had a significantly higher risk of CVDs (HR 1.61, 95% CI: 1.06, 2.44) and myocardial infarction (HR 1.88, 95% CI: 1.09, 3.27) relative to those in the bottom tertile.
Correlation between COVID-19-related concern and fear of COVID-19.
Correlation between fear of COVID-19 and medication adherence.
The study was conducted to identify the impact of the pandemic on hypertensive older people’s COVID-19 fear, blood pressure control, and medication adherence. In this descriptive, correlational study, mean medication adherence was taken as 45.6 ± 6.06% based on the literature, with a 5% margin of error, and the sample size was determined as 292 with 95% confidence interval and 80% power. Data were collected from 419 older individuals using a sociodemographic information form, an infodemic-related questionnaire, Fear of COVID-19 Scale, and Medication Adherence Self-Efficacy Scale via Google Forms. The data were analyzed using IBM SPSS Statistics 23 software via independent sample t test, one-way variance analysis, χ2 analysis, and the Pearson correlation coefficient. It was found that, rather than avoiding hospitals during a pandemic, one out of two older people had had their blood pressure checked. One out of every five had abnormal/uncontrolled blood pressure during the pandemic. The infodemic was found to increase concern levels, and those with high fear scores had abnormal/uncontrolled levels of blood pressure. Moreover, a low-level positive correlation was found between medication adherence and the level of fear of COVID-19. As the pandemic continues, older people with hypertension need support in terms of monitoring blood pressure and medication adherence as well as increased awareness about the pandemic.
Increased blood pressure variability (BPV) is strongly associated with cardiovascular events in end-stage kidney disease patients. Male hemodialysis patients present higher cardiovascular risk compared with females. The aim of this study is to investigate sex differences in short-term BPV in hemodialysis patients. 129 male and 91 female hemodialysis patients that underwent 48-h ABPM were included in this analysis. Standard deviation (SD), weighted SD (wSD), coefficient of variation (CV), and average real variability (ARV) of SBP and DBP were calculated with validated formulas. Age, dialysis vintage and history of major comorbidities did not differ between men and women. 48-h SBP/DBP (137.2 ± 17.4/81.9 ± 12.1 mmHg vs 132.2 ± 19.2/75.9 ± 11.7 mmHg, p = 0.045/<0.001) was significantly higher in men than women. During the 48-h period, all systolic BPV indices were similar between men and women (48-h SBP-ARV: 12.0 ± 2.9 vs 12.1 ± 3.2 mmHg, p = 0.683); 48-h DBP-SD, DBP-wSD and DBP-ARV (9.1 ± 1.6 vs 8.4 ± 1.8 mmHg, p = 0.005) were higher in men. In conclusion, short-term diastolic BPV indices are higher in male than female hemodialysis patients. Increased BPV may impact on the higher incidence of cardiovascular events observed in male hemodialysis patients.
The aim of the HEARTS in the Americas initiative is to promote the adoption of global best practices in the prevention and control of cardiovascular diseases, and improve the control of hypertension. HEARTS is being implemented in 21 countries and a diverse set of actions and measures are in progress to improve exclusive access in primary health care facilities to automated blood pressure measuring devices that have been validated for accuracy. The purpose of this manuscript is to illustrate these efforts, mainly in the regulatory and public procurement arena, and to present information on common challenges and solutions identified. Examples from six countries confirm the need for not only a robust regulatory framework to increase availability of validated automated blood pressure measuring devices but also a comprehensive strategic approach that involves relevant stakeholders, includes a multi-pronged approach and is associated with a national program to prevent and control non communicable diseases.
The flow diagram of the patients’ allocation
Patients were allocated based on hypertension status in the first phase and then the status of taking antihypertensive medications was considered. in the last phase, the type of antihypertensive medications were important.
The frequency of comorbidities among the patients admitted for COVID-19
Some of the patients reported more than a comorbidity.
The frequency of antihypertensive medications taken by the patients
Some of patients reported more than one medication.
In Covid-19 pandemic, specific comorbidities are associated with the increased risk of worse outcomes and increased severity of lung injury and mortality. the aim of this study was to investigate the effects of antihypertensive medications on the severity and outcomes of hypertensive patients with COVID-19. This retrospective observational study conducted on patients with COVID-19 who referred to Afzalipour Hospital, Kerman, Iran during the six months from 19 February 2020 to 20 July 2020. The data were collected through medical chart reviews. We assessed 265 patients with Covid-19 and they stratified based on hypertension and type of antihypertension medications. The data were described and Student’s t-test, Mann–Whitney U and Fisher exact test were run to compare the patients ‘demographical and clinical information. The qualitative variables were compared using the by SPSS software version 23. The results of the present study showed that hypertension was a prevalent comorbidity among patients with COVID-19 and hypertensive patients compared to other patients without any comorbidity who were older (P-value: 0.03). The oxygen saturation was higher for the patients in the control group than hypertensive patients (P-value: 0.01). The severity of COVID-19 and its outcome were not different between the patients who took or did not take antihypertensive medications and also the type of antihypertensive medications. Hypertensive patients did not show any significant difference in survival, hospital stay, ICU admission, disease severity, and invasive medical ventilation in other normotensive patients with COVID-19.
Choices regarding drug treatment initiation in untreated hypertensive patients. ARB angiotensin receptor blockers, ACEi angiotensin-converting enzyme inhibitors, CCB calcium channel blockers.
Blood pressure control rates. Percentage of uncontrolled and controlled hypertension among 2350 treated hypertensive patients according to office blood pressure targets recommended by 2018 European guidelines (<130/80 mmHg in <65 years; <140/80 mmHg in ≥65 years).
The HYPEDIA study aimed at evaluating the implementation of the 2018 European guidelines for treating hypertension in primary care. A nationwide prospective non-interventional cross-sectional study was performed in consecutive untreated or treated hypertensives recruited mainly in primary care in Greece. Participants’ characteristics, office blood pressure (BP) (triplicate automated measurements, Microlife BPA3 PC) and treatment changes were recorded on a cloud platform. A total of 3,122 patients (mean age 64 ± 12.5 [SD] years, 52% males) were assessed by 181 doctors and 3 hospital centers. In 772 untreated hypertensives (25%), drug treatment was initiated in the majority, with monotherapy in 53.4%, two-drug combination in 36.3%, and three drugs in 10.3%. Angiotensin receptor blocker (ARB) monotherapy was initiated in 30%, ARB/calcium channel blocker (CCB) 20%, ARB/thiazide 8%, angiotensin converting enzyme inhibitor (ACEi)-based 19%. Of the combinations used, 97% were in single-pill. Among 977 treated hypertensives aged <65 years, 79% had BP ≥ 130/80 mmHg (systolic and/or diastolic), whereas among 1,373 aged ≥65 years, 66% had BP ≥ 140/80 mmHg. ARBs were used in 69% of treated hypertensives, CCBs 47%, ACEis 19%, diuretics 39%, beta-blockers 19%. Treatment modification was decided in 53% of treated hypertensives aged <65 years with BP ≥ 130/80 mmHg and in 62% of those ≥65 years with BP ≥ 140/80 mmHg. Renin-angiotensin system blocker-based therapy constitutes the basis of antihypertensive drug treatment in most patients in primary care, with wide use of single-pill combinations. In almost half of treated uncontrolled hypertensives, treatment was not intensified, suggesting suboptimal implementation of the guidelines and possible physician inertia.
Although there has been a dramatic increase in visibility and recognition of transgender and gender-diverse populations, remarkably little has been published on prevalence rates of hypertension within these populations. In addition to summarizing the limited data on prevalence rates, this review compares the prevalence rates with those of cisgender populations and explores whether gender-affirming hormone therapy affects blood pressure and hypertension rates. The studies show that hypertension affects a significant proportion of transgender and gender-diverse people and support the practice of routinely monitoring blood pressure in transgender and gender-diverse people, especially after the initiation of gender-affirming hormone therapy. The two largest studies both found that estrogen plus an antiandrogen was associated with a decrease in systolic blood pressure and that testosterone was associated with an increase in systolic blood pressure.
Clinically validated, automated arm-cuff blood pressure measuring devices (BPMDs) are recommended for BP measurement. However, most BPMDs available for purchase by consumers globally are not properly validated. This is a problem because non-validated BPMDs are less accurate and precise than validated ones, and therefore if used clinically could lead to misdiagnosis and mismanagement of BP. In response to this problem, several validated device lists have been developed, which can be used by clinicians and consumers to identify devices that have passed clinical validation testing. The purpose of this review is to describe the resources that are available for finding validated BPMDs in different world regions, to identify the differences between validated device lists, and describe current gaps and challenges. How to use validated BPMDs properly is also summarised.
Doppler ultrasound imaging
Blood flow velocity waveforms recorded, A for the common carotid artery, (B) the subclavian artery, (C) the internal thoracic artery, (D) the renal artery, (E) the epigastric artery, (F) the common femoral artery and (G) the abdominal aorta, (H) top, multidetector computed tomography angiography with three-dimensional reconstructed images before endovascular treatment; bottom, schematic representation of the end of the aorta, the epigastric artery, the iliac and femoral arteries. Blood flow velocity waveforms were normal in the common carotid and subclavian arteries, but displayed a “tardus-parvus” pattern in the abdominal aorta, as in the renal and common femoral arteries. Blood flow velocities were high in the internal thoracic and epigastric arteries, epigastric arteries presented reverted flows towards the common femoral arteries. Yellow arrows indicate the direction of blood flows in the internal thoracic and epigastric arteries.
In developed countries, aortic coarctation (AC) is generally diagnosed by fetal echocardiography during the third trimester of pregnancy, or during the neonatal period based on the absence of femoral pulses or the presence of a left supraclavicular systolic murmur. However, AC may be diagnosed late, such as in adult migrants arriving from developing countries without documented medical history although they may require healthcare support during their stay. We report three cases of the incidental diagnosis of thoracic aortic malformations in adults (27, 38 and 43 years) referred for the management of uncontrolled high blood pressure, with major cerebrovascular events for the two oldest. Doppler ultrasound imaging indicated for suspected renal artery stenosis and atheroma lesions revealed abnormal lower-body and normal upper-body arterial blood flow velocity waveforms constitutive of a pathognomonic hemodynamic pattern of AC, a diagnostic which was in all three cases confirmed by multidetector computed tomography-angiography. None of these patients had undergone complete cardiovascular examination, particularly with effective peripheral pulse palpation, during the period preceding the occurrence of major cardiovascular events or at any other time after birth. Our observation suggests that a simple medical examination could have prevented diagnostic wandering and, possibly, the occurrence of severe cerebrovascular complications in two of these three patients.
Hypertension Mediated Organ Damage in the different Blood Pressure group
Pulse Wave Velocity (A), Intima-Media Thickness (B), Left Ventricular Mass Index/BSA (C) and Left Ventricular Mass Index/h2.7 (D). In boxplots the inner line indicates the median; the whiskers are located at the maximum and minimum observation (outside observations indicated with dots are those out of the 1.5 × interquartile range).
Odds Ratio from unadjusted and adjusted logistic regression models of the Hypertension Mediated Organ Damage variables
Pulse Wave Velocity > 10 (A), Intima-Media Thickness > 0.9 (B) and Carotid Plaque (C).
Purpose of our study was to assess the prevalence of hypertension mediated organ damage (HMOD) in healthy subjects with high-normal Blood Pressure (BP) comparing them with subjects with BP values that are considered normal (<130/85 mmHg) or indicative of hypertension (≥140/90 mmHg). Seven hundred fifty-five otherwise healthy subjects were included. HMOD was evaluated as pulse wave velocity (PWV), left ventricular mass index (LVMI), and carotid intima-media thickness (IMT) and plaque. When subjects were classified according to BP levels we found that the high-normal BP group showed intermediate values of PWV and higher values of IMT. This corresponds to intermediate prevalence of arterial stiffness, while there were no differences for increased IMT or carotid plaque. No subjects showed left ventricular hypertrophy. At multivariable analysis, the odds of having arterial stiffness or carotid HMOD in the high-normal group resulted not different to the normal group. In conclusion, in our otherwise healthy population, high-normal BP values were not related to aortic, carotid or cardiac HMOD.
Life table analysis for the incidence of coronary artery disease
Separate lines are for patients with LVH and without LVH. CAD, coronary artery disease; LVH, left ventricular hypertrophy.
In treated hypertensive patients, there is a substantial residual cardiovascular (CV) risk that cannot be assessed by the available prediction models. This risk can be associated with subclinical organ damage, such as increased left ventricular mass (LVM) and arterial stiffness. However, it remains unknown which of these two CV markers better predicts coronary artery disease (CAD). A prospective cohort study was used to answer the above question. The study sample consisted of 1033 patients with hypertension (mean age 55.6 years, 538 males) free of CAD at baseline, who were followed for a mean period of 6 years. At baseline, all subjects underwent a complete echocardiographic study and pulse wave velocity (PWV) measurement. Hypertensive individuals who developed CAD (2.8%) compared to those without CAD at follow-up, had a higher baseline LVM index (by 16.7 g/m², p < 0.001), higher prevalence of left ventricular hypertrophy (LVH) (21% greater, p = 0.027) and greater prevalence of high PWV levels at baseline (21% greater, p = 0.019). Multivariate Cox regression analysis revealed that baseline age >65 years (HR = 2.067, p = 0.001), male gender (HR = 3.664, p = 0.001), baseline chronic kidney disease (HR = 2.020, p = 0.026), baseline diabetes mellitus (HR = 1.952, p = 0.015) and baseline LVH (HR = 2.124 p = 0.001) turned out to be independent predictors of CAD, whereas high PWV levels were not. LVH proved to be an independent prognosticator of CAD in contrast to arterial stiffness that was not related to CAD after accounting for established confounders. Therefore, LVM can reliably help physicians to identify high-risk hypertensives in whom an intensified therapeutic management is warranted.
Top-cited authors
Bryan Williams
  • University College London
Francesco Cappuccio
  • The University of Warwick
Feng J He
  • Queen Mary, University of London
Peter Sever
  • Imperial College London
Christopher Bulpitt
  • Imperial College London