Journal of Human Hypertension

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Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth restriction. These conditions are jointly termed placental syndromes as they are characterised by impaired placentation and early placental vascularization. Placental syndromes are associated with an increased maternal risk of progression to hypertension and cardiovascular disease (CVD) in later life. Women affected by both a clinical placental syndrome and with evidence of placental maternal vascular malperfusion (MVM) have a particularly high risk of hypertension and CVD. Yet whether placental impairment and clinical syndromes are causes or consequences of higher blood pressure in women remains unclear. In this review, we address the relationship between blood pressure and maternal health in pregnancy. We conclude that there is a pressing need for studies with a range of detailed measures of cardiac and vascular structure and function taken before, during and after pregnancy to solve the ‘chicken and egg’ puzzle of women’s blood pressure and pregnancy health, and to inform effective precision medicine prevention and treatment of both placental syndromes and chronic hypertension in women.
 
Number of nocturnal voids
The number of nocturnal voids is shown (no voids: n = 2381 [55.2%]; 1 void: n = 847 [19.7%]; ≥2 voids per night: n = 1082 [25.1%]).
Previous studies have reported a significant relationship between hypertension and nocturia. However, the underlying pathophysiology associated with pulse rate (PR) remains unclear. In the Japan Morning Surge-Home Blood Pressure Study, a self-administered nocturia questionnaire and evening home blood pressure (BP) and PR measurements (taken on a mean of 11.2 days) were performed on 4310 patients with one or more cardiovascular risk factors (mean: 64.9 years old; 47% male). According to the number of nighttime voids, the study population was divided into three groups (no voids: n = 2382; 1 void: n = 847; ≥2 voids per night: n = 1082). In the multinomial logistic regression analysis adjusted for confounders, diuretic use (OR, 1.23; 95%CI, 1.01–1.50; p < 0.05) was significantly associated with one nocturnal void, whereas evening home systolic BP (SBP) (OR per 1 SD, 1.14; 95%CI, 1.05–1.24; p < 0.01) and evening home PR (OR per 1 SD, 1.12; 95%CI: 1.02–1.24; p < 0.05) were significantly associated with multiple nocturnal voids. In the younger group (<65 years), only evening home PR was significantly related to multiple nighttime voids (p < 0.01), whereas in the older group (≥65 years), only evening home SBP was significantly related to multiple nighttime voids (p = 0.02). In this study, both higher evening home PR and higher evening home SBP were associated with multiple nighttime voids, with the former playing a greater role in the younger participants, and the latter more often associating the older group. An age-stratified approach to reduce the burden of BP or PR might be important to improve sleep quality.
 
Overview of treatment synergies and differences in adverse effects.
Antihypertensive treatment is equally beneficial for reducing cardiovascular risk in both men and women. Despite this, the drug treatment, prevalence and control of hypertension differ between men and women. Men and women respond differently, particularly with respect to the risk of adverse events, to many antihypertensive drugs. Certain antihypertensive drugs may also be especially beneficial in the setting of certain comorbidities – of both cardiovascular and extracardiac nature – which also differ between men and women. Furthermore, hypertension in pregnancy can pose a considerable therapeutic challenge for women and their physicians in primary care. In addition, data from population-based studies and from real-world data are inconsistent regarding whether men or women attain hypertension-related goals to a higher degree. In population-based studies, women with hypertension have higher rates of treatment and controlled blood pressure than men, whereas real-world, primary-care data instead show better blood pressure control in men. Men and women are also treated with different antihypertensive drugs: women use more thiazide diuretics and men use more angiotensin-enzyme inhibitors and calcium-channel blockers. This narrative review explores these sex-related differences with guidance from current literature. It also features original data from a large, Swedish primary-care register, which showed that blood pressure control was better in women than men until they reached their late sixties, after which the situation was reversed. This age-related decrease in blood pressure control in women was not, however, accompanied by a proportional increase in use of antihypertensive drugs and female sex was a significant predictor of less intensive antihypertensive treatment.
 
The accuracy of Omron 10 Series BP7450 (HEM-7342T-Z), Omron Platinum BP5450 (HEM-7343T-Z), Walmart Equate Premium 8000 Series UA-8000WM, Walgreens Premium 15+ WGNBPA-960BT, and CVS Series 800 BP3MW1-4YCVS were assessed in an adult general population compared to a mercury sphygmomanometer standard according to the ISO 81060-2:2018/AMD 1:2020 validation procedure. Omron selected the monitors and included three non-Omron monitors because they were from large retail vendors in the United States and these monitors did not have accessible results from validation testing. The BP7450, N = 85, passed both criteria for the standard. Mean (SD) differences in paired SBP and DBP determinations between the test device and reference were 0.5 (7.7) and 2.5 (6.8) mm Hg. The BP5450, N = 86, passed both criteria. Mean (SD) differences in paired SBP and DBP determinations were 1.9 (7.0) and 3.6 (6.4) mm Hg. The UA-8000WM, N = 85, did not meet the first criterion for the standard. Mean (SD) differences in paired SBP and DBP determinations were 2.5 (8.0) and 5.1 (6.4) mm Hg. The WGNBPA-240BT, N = 85, did not meet the first criterion for the standard. Mean (SD) differences in paired SBP and DBP determinations were 7.9 (8.5) and 5.5 (6.7) mm Hg. The BP3MW1-4YCVS, N = 85, did not meet the first criterion for the standard. Mean (SD) differences in paired SBP and DBP determinations were 5.8 (8.7) and 3.1 (5.6) mm Hg. These findings emphasize the importance of verifying the validation status of home blood pressure monitors before use by consumers.
 
This paper reviews 11 current and previous international and some selected national hypertension guidelines regarding sex and gender-related differences. Those differences can be attributed to biological sex and to gender differences that are determined by socially constructed norms. All reviewed guidelines agree on a higher hypertension prevalence in men than in women. They also concur that evidence does not support different blood pressure thresholds and targets for treatment between men and women. Differences refer in addition to the differences in epidemiological aspects to differences in some morphometric diagnostic indices, e.g., left ventricular mass or the limits for daily alcohol intake. Concerning practical management, there are hardly any clear statements on different procedures that go beyond the consensus that blockers of the renin–angiotensin system should not be used in women of childbearing age wishing to become pregnant. Some further sex-specific aspects are related to differences in tolerability or drug-specific side effects of BP-lowering drugs. There is also a consensus about the need for blood pressure monitoring before and during the use of contraceptive pills. For management of pregnancy, several guidelines still recommend no active treatment in pregnant women without severe forms of hypertension, despite a wide consensus about the definition of hypertension in pregnancy. A disparity in treatment targets when treating severe and non-severe hypertension in pregnancy is also observed. Overall, sex-specific aspects are only very sparsely considered or documented in the evaluated guidelines highlighting an unmet need for future clinical research on this topic.
 
Elevated blood pressure ranks among the most important modifiable risk factors for premature death, and disability from hypertension mediated organ damage in the world. Many studies attest to the value of lifestyle adjustments and pharmacologic therapy in improving outcomes in patients with hypertension. Since blood pressure is a dynamic vitals sign, variability in visit-to-visit measurements is expected. While guidelines recommend a goal blood pressure, increasing attention is centered on how often a patient’s blood pressure is found to be not only below the recommended goal value, but also how much of the time the blood pressure is below what is considered a safe lower goal threshold for blood pressure. In this Perspective we review a relatively new technique in addressing adequacy of blood pressure treatment, the time in therapeutic range, and provide examples supporting the clinical relevance of this novel metric.
 
Intradialytic hypotension and intradialytic hypertension are complications of hemodialysis (HD) associated with a higher risk of cardiovascular disease (CVD) and death. Blood pressure (BP) normally fluctuates in a circadian pattern, but whether the risk of intradialytic hypotension and intradialytic hypertension varies according to the time of the HD session is unknown. We analyzed two cohorts of thrice-weekly maintenance HD (N = 1838 patients/n = 64,503 sessions from the Hemodialysis [HEMO] Study, and N = 3302 patients/n = 33,590 sessions from Satellite Healthcare). Random effects logistic regression models examined the association of HD start time (at or before 9:00 a.m. [early AM], between 9:01 a.m. and 12:00 p.m. [late AM], and at or after 12:01 p.m. [PM]) with intradialytic hypotension (defined as nadir intra-HD systolic BP (SBP) < 90 mmHg if pre-HD SBP < 160 mmHg, or <100 mmHg if pre-HD SBP ≥ 160 mmHg) and intradialytic hypertension (SBP increase ≥ 10 mmHg from pre-HD to post-HD). Compared to early AM, late AM and PM were associated with an 8% (aOR 0.92, 95% CI 0.83–1.02) and a 16% (aOR 0.84, 95% CI 0.75–0.95) lower risk of intradialytic hypotension in HEMO, respectively. Conversely, compared to early AM, a monotonic higher risk of intradialytic hypertension was observed for late AM (aOR 1.23, 95% CI 1.12–1.35) and PM (aOR 1.41, 95% CI 1.27–1.56) in HEMO. These findings were consistent in Satellite. In two large cohorts of maintenance HD, we observed a monotonic lower risk of intradialytic hypotension and a monotonic higher risk of intradialytic hypertension with later dialysis start times. Whether HD treatment allocation to certain times of the day in hypotensive-prone or hypertensive-prone patients improves outcomes deserves further investigation.
 
Flow chart.
ROC curve QKDh and cardiovascular events.
Variations of sensitivity and specificity to predict cardiovascular events according to QKDh values.
Event free survival curves for patents with normal or reduced QKDh (mulyivariate Cox model).
Arterial stiffness, most often assessed with carotido-femoral pulse wave velocity predicts cardiovascular events but its use in clinical practice remains limited. The 24 h ambulatory monitoring of Blood pressure and timing of Korotkoff sounds (QKD interval) allows an automatic assessment of arterial stiffness and is an independent predictor of cardiovascular events in hypertensive patients. The long term follow up of our cohort of hypertensive patients gave us the opportunity to test the consequences of increased arterial stiffness on the incidence of all causes deaths and to define the populations who could benefit of this measurement beyond risk scores. The sample includes 930 patients (502 males, age 53 ± 13 years, baseline risk SCORE2-OP = 6.70 ± 4.97%) with an average follow up of 12.11 ± 7.4 years (0.3–30). In this population 169 cardiovascular events and 155 deaths were recorded. SCORE2-OP, 24 h Systolic Blood Pressure and arterial stiffness (QKDh) as a continuous or discontinuous variable (normal or reduced) were significantly and independently linked to the occurrence of cardiovascular events or all cause deaths in multivariate Cox model. ROC curves analysis show that measuring arterial stiffness with QKD method offers the best predictive value in patients with low or very low risk scores.
 
Nephroangiosclerosis (NAS) associated with hypertension continues to be one of the most causes of end stage renal diseases in Europe, but it is still poorly studied. The prevalence of NAS shows a large variability due to the difference among different countries regarding clinical presentations and the indication to perform renal biopsy. The study aimed to investigate the prevalence in biopsy-proven NAS patients and the association with hypertension and/or glomerulonephritis (GN). We included all patients referred for native kidney biopsy between 2003–2021 at Policlinic Umberto I of Rome. From 837 patients who underwent renal biopsy NAS was diagnosed in 80 (10.5%) patients. Serum creatinine was significantly higher in NAS [2.07 mg/dl (IQR 1.13–5.2) vs 1.1 mg/dl (IQR 0.8–2.1), p < 0.001] compared to patients without NAS. Hypertension was present in 45% of patients with NAS. Proteinuria was significantly higher in patients with mild-moderate NAS compared to patients with severe NAS [2.6 g/die (IQR 1–5) vs 1.5 g/die (IQR 0.86–2.3), p < 0.05]. We did not find any significant differences, including histological features, between NAS patients with hypertension and NAS patients without hypertension (p > 0.05). IgA nephropathy, focal segmental glomerulosclerosis and membranous nephropathy were the most frequent GN associated. In conclusion no specific histological features are reported in NAS with and without hypertension. More information on the phenotype, clinical presentation and markers are needed to improve histological and clinical diagnostics.
 
Correlation matrix of Cardiovascular and blood pressure parameters
All studied participants (Panel A), and separately by normotension and hypertension groups (Panels B and C). Colour and colour intensity indicate r values i.e., direction and strength of correlation (red negative correlation, blue positive), as per X axis. *P < 0.05 **P < 0.01 ***P < 0.001. BMI body mass index; CIMT carotid intima media thickness, DBP diastolic blood pressure, SD standard deviation, DCP diastolic central pressure, AI@75% AIx adjusted for heart rate, FMD% percent flow-mediated dilatation, HR heart rate, IDQ interheart diet score, IPAQ International Physical Activity Questionnaire, LnRHI logarithmic transformation of reactive hyperaemia index, PWV pulse wave velocity, PWA pulse wave analysis, AIx augmentation index, SBP systolic blood pressure, SCP systolic central pressure.
Cluster analyses of the hypertensive group
Spectral Biclustering with three subgroups of patients and eight groups of features (Panel A). Boxplots of key features discriminating bicluster groups (Panel B). Both panels: Group 0 ‘arterially stiffened’ hypertension, Group 1 ‘vasoprotected’ hypertension, Group 2 ‘non-dippers’. SBP24, 24 h average systolic BP; DBP24, 24 h average diastolic BP; SBP SD standard deviation i.e., variability of systolic BP; DBP SD, standard deviation i.e., variability of diastolic BP; FMD flow mediated dilatation, BMI body-mass index, dip percentage reduction from day to night BP, LnRHI logarithmic reactive hyperaemia index, AIx EndoPAT-2000-derived augmentation index, AI@75% AIx adjusted for heart rate, HR range day daytime heart rate range, PWV pulse wave velocity, PWA pulse wave analysis, SCP systolic central pressure, DCP diastolic central pressure.
The study characterises vascular phenotypes of hypertensive patients utilising machine learning approaches. Newly diagnosed and treatment-naïve primary hypertensive patients without co-morbidities (aged 18–55, n = 73), and matched normotensive controls (n = 79) were recruited (NCT04015635). Blood pressure (BP) and BP variability were determined using 24 h ambulatory monitoring. Vascular phenotyping included SphygmoCor® measurement of pulse wave velocity (PWV), pulse wave analysis-derived augmentation index (PWA-AIx), and central BP; EndoPAT™-2000® provided reactive hyperaemia index (LnRHI) and augmentation index adjusted to heart rate of 75bpm. Ultrasound was used to analyse flow mediated dilatation and carotid intima-media thickness (CIMT). In addition to standard statistical methods to compare normotensive and hypertensive groups, machine learning techniques including biclustering explored hypertensive phenotypic subgroups. We report that arterial stiffness (PWV, PWA-AIx, EndoPAT-2000-derived AI@75) and central pressures were greater in incident hypertension than normotension. Endothelial function, percent nocturnal dip, and CIMT did not differ between groups. The vascular phenotype of white-coat hypertension imitated sustained hypertension with elevated arterial stiffness and central pressure; masked hypertension demonstrating values similar to normotension. Machine learning revealed three distinct hypertension clusters, representing ‘arterially stiffened’, ‘vaso-protected’, and ‘non-dipper’ patients. Key clustering features were nocturnal- and central-BP, percent dipping, and arterial stiffness measures. We conclude that untreated patients with primary hypertension demonstrate early arterial stiffening rather than endothelial dysfunction or CIMT alterations. Phenotypic heterogeneity in nocturnal and central BP, percent dipping, and arterial stiffness observed early in the course of disease may have implications for risk stratification.
 
Indication for renal artery intervention. Multiple indications expressed by adjoining lines.
Change in blood pressure and serum creatinine following renal artery stent.
Renal artery stenosis manifests as poorly-controlled hypertension, impaired renal function or pulmonary oedema, therefore the success of treatment is dependent on indication. This study aims to determine the outcomes of patients undergoing renal artery stenting (RASt) based on therapeutic aim compared to criteria used in the largest randomised trial. Retrospective case-note review of patients undergoing RASt between 2008–2021 ( n = 74). The cohort was stratified by indication for intervention (renal dysfunction, hypertension, pulmonary oedema) and criteria employed in the CORAL trial, with outcomes and adverse consequences reported. Intervention for hypertension achieved significant reduction in systolic blood pressure and antihypertensive agents at 1 year (median 43 mmHg, 1 drug), without detrimental impact on renal function. Intervention for renal dysfunction reduced serum creatinine by a median 124 μmol/L, sustained after 6 months. Intervention for pulmonary oedema was universally successful with significant reduction in SBP and serum creatinine sustained at 1 year. Patients who would have been excluded from the CORAL trial achieved greater reduction in serum creatinine than patients meeting the inclusion criteria, with equivalent blood pressure reduction. There were 2 procedure-related mortalities and 5 procedural complications requiring further intervention. 5 patients had reduction in renal function following intervention and 7 failed to achieve the intended therapeutic benefit. Renal artery stenting is effective in treating the indication for which it has been performed. Previous trials may have underestimated the clinical benefits by analysis of a heterogenous population undergoing a procedure rather than considering the indication, and excluding patients who would maximally benefit.
 
Bland Altman plot for differences in full ABPM and 2–10PM per participant
Bland Altman plot for differences in full ABPM and 2PM–10PM per participant. Graph 1a- shows the difference of the systolic blood pressure in the time segment 2PM–10PM. Graph 1b shows the difference of the diastolic blood pressure in the time segment 2PM–10PM.
Ambulatory blood pressure monitoring (ABPM) is considered the most reliable and accurate measurement of blood pressure (BP). However, the use of ABPM has some limitations, which make it difficult to complete for the entire 24 h. We aimed to establish in which part of the day BP measurements are in highest correlation with full ABPM (over 24 h) results. We performed a retrospective cross-sectional study which included 3113 full ABPM. Each ABPM was divided into 6- and 8-hour segments, and mean BP in each time segment was calculated. Linear mix models for describing BP by BP in each time segment were performed. A total of 3113 ABPM measurements carried out on 2676 patients (mean age 57.78 ± 14.74) were included in the study. Linear mix models demonstrated significant association between mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) in full ABPM, and SBP and DBP between 2–10 PM, respectively (SBP: β = 0.902, p < 0.001; DBP: β = 0.839, p < 0.001), adjusted for gender, age, season, and relevant interactions. This section had higher coefficient correlations than other sections which were examined. The study findings indicate high correlation between BP between 2–10 PM, and BP in full-ABPM, by each season. This time segment may be ideal for short-term BP monitoring as an initial screening test and for patients who are unable to complete full ABPM. However, since this time segment does not include nighttime hours, there is a risk of underdiagnosis of non-dipper.
 
Hypertension cascade of care in Gaza
Percentages are indicated with as denominator the atotal study population (n = 4576) and bhypertensive population (n = 2586).
Effect modification of age and sex on the hypertension cascade
Effect modification of age and sex is shown on the prevalence (A), diagnosis (B) and control (C) of hypertension.
Although hypertension constitutes a substantial burden in conflict-affected areas, little is known about its prevalence, control, and management in Gaza. This study aims to estimate the prevalence and correlates of hypertension, its diagnosis and control among adults in Gaza. We conducted a representative, cross-sectional, anonymous, household survey of 4576 persons older than 40 years in Gaza in mid-2020. Data were collected through face-to-face interviews, anthropometric, and blood pressure measurements. Hypertension was defined in anyone with an average systolic blood pressure ≥140 mmHg or average diastolic blood pressure ≥90 mmHg from two consecutive readings or a hypertension diagnosis. The mean age of participants was 56.9 ± 10.5 years, 54.0% were female and 68.5% were Palestinian refugees. The prevalence of hypertension was 56.5%, of whom 71.5% had been diagnosed. Hypertension was significantly higher among older participants, refugees, ex-smokers, those who were overweight or obese, and had other co-morbidities including mental illnesses. Two-thirds (68.3%) of those with hypertension were on treatment with one in three (35.6%) having their hypertension controlled. Having controlled hypertension was significantly higher in females, those receiving all medications for high blood pressure and those who never or rarely added salt to food. Investing in comprehensive but cost-effective initiatives that strengthen the prevention, early detection and timely treatment of hypertension in conflict settings is critical. It is essential to better understand the underlying barriers behind the lack of control and develop multi-sectoral programs to address these barriers.
 
Reliable clinical signs associated with recent brain injuries during malignant hypertension crisis are lacking. In this single-center study we compared the prevalence of brain MRI injuries between fully asymptomatic patients and those with headache; we found no significant differences, suggesting that headache is not associated with recent brain injuries during malignant hypertension.
 
Changes in the mean systolic and diastolic blood pressure between baseline and last visits.
Blood pressure control after the implementation of hypertension management protocol based on HEARTS technical package according to blood pressure at the baseline.
The majority of patients with hypertension in Jordan have uncontrolled blood pressure. This study aimed to adapt and implement the hypertension management protocol (a module in the HEARTS technical package) in health care centers in Jordan and evaluate its effectiveness on hypertension management and control. The hypertension management protocol was adapted and implemented in six health centers followed by training of the healthcare staff on the adapted protocol. Patients above 18 years old who attended health centers during the study period were recruited consecutively. The blood pressure of 852 patients was monitored over 4 months, using an individual patient treatment card. At the baseline visit, the proportion of patients with uncontrolled blood pressure was 71.5%. After 4 months of the implementation of the protocol, the proportion of patients with uncontrolled blood pressure decreased to 29.1%. Of all studied characteristics, age was the only significant predictor of achieving blood pressure control. Patients aged ≤50 had a higher rate of controlled blood pressure readings after 4 months of implementation of the protocol compared to patients older than 60 years (OR = 1.98, 95% CI: 1.07, 3.67; P value = 0.028). In conclusion, the implementation of the HEARTS hypertension management protocol has successfully achieved better control of the blood pressure of the enrolled patients after 4 months of implementation. To achieve better control of hypertension in the general population, integrating evidence-based strategies for hypertension control that are listed in the HEART technical package into routine care is strongly recommended.
 
Form factors and pulse wave shape: influence of arterial site, amplification, and augmentation (SphygmoCor)
Left panels (dark background) taken from a random SphygmoCor study showing typical morphological differences between peripheral and central waveforms. The radial tonogram (left panel) was scaled to brachial SBP and DBP and subjected to a generalized transfer function to yield a central (aortic) pressure waveform (second panel). Morphological differences in arterial contour between arterial locations are typical as are the corresponding FF values. In this individual, PPA is 12 mmHg, PPA ratio is 1.17, and central augmentation index (AI) is 121%. Right panels are scatterplots showing close correlations between brachioradial FF and both PPA ratio and central AI (p < 0.000 each).
Central and forearm form factors with different devices
Upper and lower scatterplots demonstrate marked differences in FF relationships at two different arterial sites for SphygmoCor and Mobil-O-Graph. With both devices, central FF was higher than forearm arterial FF. With SphygmoCor (upper panel), central and peripheral FF values were highly correlated (p < 0.000) and normally distributed (95% CI values included on scatterplots). With Mobil-O-Graph, brachial FF was fixed (0.46) and about 34% higher than SphygmoCor brachioradial FF (0.34, p < 0.000); Mobil-O-Graph central FF was about 26% higher than SphygmoCor.
Matched pairs analysis of MAP and central SBP with SphygmoCor (SPG) and Mobil-O-Graph (MOB)
Upper panel: means (bars) and SDs (verticals) for SBP, DBP, MAP and central (c) SBP by device (see Table 3). Middle panel: matched pairs Bland-Altman-type analysis of MAP. Although MOB-MAP was 6.3 mmHg higher than SPG-MAP at the midpoint, the inter-device difference decreased at higher MAP values (negative systematic bias, regression equation on scatterplot). Lower panel: matched pairs Bland-Altman-type analysis of central (c) SBP. MOB-cSBP was higher than SPG-cSBP at the midpoint (2.2 mmHg). Due to negative systematic bias, for MAP values below 120 mmHg, MOB values were higher than SPG but for MAP values above 120 mmHg, SPG values were higher than MOB.
Mean arterial pressure (MAP) is often estimated from cuff systolic (S) and diastolic (D) blood pressure (BP) using a fixed arterial form factor (FF, usually 0.33). If MAP is measured directly, a true FF can be calculated: FF = [MAP–DBP]/[SBP–DBP]. Because waveform shapes vary, true FF should also vary and MAP accuracy will be affected. We studied factors affecting FF using radial tonography (SphygmoCor, n = 376) or brachial oscillometry (Mobil-O-Graph, n = 157) and to compare devices, 101 pairs were matched precisely for SBP and DBP. SphygmoCor brachioradial FF correlated strongly with central FF (r2 = 0.75), central augmentation index (cAI, r2 = 0.39), and inversely with pulse pressure amplification (PPA) ratio (r2 = 0.44) [all p < 0.000]; brachioradial FF was lower than central (c) FF (0.34 vs. 0.44, 95% CI’s [0.23,0.46] and [0.34,0.54], p < 0.000). On forward stepwise regression, brachioradial FF correlated with PPA ratio, age, heart rate, and cAI (multiple-r2 0.63, p < 0.000). With Mobil-O-Graph: brachial FF was fixed, lower than the corresponding cFF [mean(SD)] 0.46(0.00098) vs. 0.57(0.048), p < 0.000], and uncorrelated with clinical characteristics; MAP and cSBP were higher than SphygmoCor by 6.3 and 2.2 mmHg (p < 0.005) at the midpoint with systematic negative biases. We conclude that FF derived from radial tonometry (SphygmoCor) varies with pulse wave morphology within and between individuals and by measurement site, age, and heart rate. With oscillometry (Mobil-O-Graph), brachial FF was fixed and high and unrelated to other clinical variables; MAP and cSBP were higher than tonometry, with systematic negative biases.
 
Psoriasis is associated with increased cardiovascular risk. Endothelial, platelet, and erythrocyte microvesicles (MVs) are novel biomarkers of endothelial dysfunction and thromboinflammation. We explored whether MVs of different cell types are elevated in patients with psoriasis, and investigated potential associations with disease severity and macrovascular function. Endothelial, platelet and erythrocyte MVs were measured using a standardized flow cytometry protocol in psoriasis patients and controls free from established cardiovascular disease. Carotid intima-media thickness (IMT) and pulse wave velocity (PWV) were measured as markers of subclinical atherosclerosis and arterial stiffness. Psoriasis severity was assessed with PASI (Psoriasis Area Severity Index). Both platelet (p < 0.001) and erythrocyte MVs (p = 0.046), yet not endothelial MVs, were significantly increased in patients with psoriasis (n = 41) compared with controls (n = 41). Patients with higher PASI (≥10) presented significantly higher levels of ErMVs compared to those with lower PASI (<10) (p = 0.047). Carotid IMT and PWV were comparable between psoriasis patients and controls and did not significantly correlate with MVs. In the multivariate analysis, psoriasis was identified as an independent predictor of both platelet (p < 0.001) and erythrocyte MVs (p = 0.043), while hypertension was independently associated with endothelial MVs (p < 0.001). Increased formation of platelet and erythrocyte MVs may be evident in psoriasis patients and is indicative of prothrombotic, proinflammatory microenvironment, even in the absence of subclinical macrovascular dysfunction and before the clinical onset of overt cardiovascular complications. Potential mechanistic links and prognostic implications of increased MVs in psoriasis warrant further investigation.
 
Multiple linear regression model for systolic blood pressure changes from baseline to six months of follow-up in participants who received integrated HIV and hypertension care at the Mulago ISS clinic.
Globally, people living with HIV on antiretroviral therapy have an increased risk of cardiovascular disease. Hypertension is the most important preventable risk factor for cardiovascular disease and is associated with increased morbidity. We conducted an exploratory survey with hypertensive persons living with HIV who received integrated HIV and hypertension care in a large clinic in Uganda between August 2019 and March 2020 to determine factors associated with blood pressure control at six months. Controlled blood pressure was defined as <140/90 mmHg. Multivariable logistic regression was used to determine baseline factors associated with blood pressure control after 6 months of antihypertensive treatment. Of the 1061 participants, 644 (62.6%) were female. The mean age (SD) was 51.1 (9.4) years. Most participants were overweight (n = 411, 38.7%) or obese (n = 276, 25.9%), and 98 (8.9%) had diabetes mellitus. Blood pressure control improved from 14.4% at baseline to 66.1% at 6 months. Comorbid diabetes mellitus (odds ratio (OR) = 0.41, 95% confidence interval (CI) = 0.26–0.64, p < 0.001) and HIV status disclosure (OR = 0.73, 95% CI = 0.55–0.98, p = 0.037) were associated with the absence of controlled blood pressure at 6 months. In conclusion, comorbid diabetes mellitus and the disclosure of an individual’s HIV status to a close person were associated with poor blood pressure control among persons living with HIV who had hypertension. Therefore, subpopulations of persons living with HIV with hypertension and comorbid diabetes mellitus may require more thorough assessments and intensive antihypertensive management approaches to achieve blood pressure targets.
 
There are very few studies in Africans investigating the association between early life exposure to malnutrition and subsequent hypertension in adulthood. We set out to investigate this potential association within an adult cohort who were born around the time of the Biafran War (1968–1970) and subsequent famine in Nigeria. This was a retrospective analysis of Abia State Non-Communicable Diseases and Cardiovascular Risk Factors (AS-NCD-CRF) Survey, a community-based, cross-sectional study that profiled 386 adults (47.4% men) of Igbo ethnicity born in the decade between January 1965 and December 1974. Based on their date of birth and the timing of the famine, participants were grouped according to their exposure to famine as children (Child-Fam) or in-utero fetus/infant (Fet-Inf-Fam) or no exposure (No-Fam). Binomial logit regression models were fitted to determine the association between famine exposure and hypertension in adulthood. Overall, 130 participants had hypertension (33.7%). Compared to the No-Fam group (24.4%), the prevalence of hypertension was significantly elevated in both the Child-Fam (43% - adjusted OR 2.47, 95% CI 1.14–5.36) and Fet-Inf-Fam (44.6% - adjusted OR 2.54, 95% CI 1.33–4.86) groups. The risk of hypertension in adulthood was highest among females within the Child-Fam group. However, within the Fet-Inf-Fam group males had a equivalently higher risk than females. These data suggest that early life exposure to famine and malnutrition in Africa is associated with a markedly increased risk of hypertension in adulthood; with sex-based differences evident. Thus, the importance of avoiding armed conflicts and food in-security in the region cannot be overstated. The legacy effects of the Biafran War clearly show the wider need for ongoing programs that support the nutritional needs of African mothers, infants and children as well as proactive surveillance programs for the early signs of hypertension in young Africans.
 
Timeline of the study design: Tehran Lipid and Glucose Study, Iran, 2002–2018.
The impact of 3-year change in glycemic state on the risk of hypertension among Tehranian adults aged ≥20 years was assessed. The study population included 1679 men and 2348 women who were non-diabetic normotensive at enrollment. The following categories were defined both at baseline visit and three years later (second visit): normoglycemia [normal fasting glucose (NFG) and normal glucose tolerance (NGT)] and prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)]. Changes in the categories, i.e., regression to normoglycemia, remaining in previous status, and progression to diabetes were assessed. Changes in fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) categories were also considered separately. We used the Cox models adjusted for traditional hypertension risk factors to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During a median follow-up of 9.4 years, 485 men and 589 women developed hypertension. Among men, considering both FPG and 2hPG, compared to individuals remaining normoglycemic, changing from prediabetes to normoglycemia had a HR of 1.30 (95% CI: 0.98–1.71; P-value: 0.064). Defining changes by 2hPG showed that compared to remaining NGT, incident IGT (progression from NGT to IGT) had a significant association with increased risk of hypertension development by a HR of 1.61 (1.13–2.30). Among women, on the other hand, change in glycemic state generally didn’t show a significant association with incident hypertension. To sum up, change in glycemic state hadn’t a significant association with hypertension development among women; however, compared to remaining NGT, men with incident IGT had a significant higher risk.
 
Study selection flowchart. Flowchart detailing study selection process as per the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. n = Number of records.
Cardiovascular related deaths account for over 40% of the excess mortality in Turner syndrome (TS). Hypertension, a modifiable risk factor for both aortic dilatation and dissection, is more commonly encountered in TS during childhood and adolescence. Treatment of hypertension is currently recommended beyond the age of 16 years in TS to help reduce the risk of aortic dissection. This study aims to determine the prevalence of hypertension in paediatric patients with TS and explore the associated methodologies of blood pressure evaluation reported in these studies. Three online databases were searched (Medline, Embase and Web of Science) for literature which reported a prevalence, or allowed calculation of prevalence, of hypertension in patients with TS who were 18 years of age or younger. Seventeen studies which met the primary eligibility criteria, with a total of 1948 patients, were included. The estimated pooled prevalence of hypertension in children and adolescents with TS was 16% (95% CI: 8.9–24.6%). There was significant heterogeneity detected between the studies. The prevalence of hypertension in those studies which assessed 24-h Ambulatory Blood Pressure Monitoring (ABPM) was 21.1% (95% CI: 15.2–27.6%) compared those which used another method of blood pressure measurement which was 13.5% (95% CI: 5.2–24.4%). Given the impact of hypertension with long-term health outcomes and the reversibility of these same outcomes by addressing abnormal blood pressure, prompt and early diagnosis of hypertension in young girls with TS should be prioritised. We recommend the use of 24-h ABPM in screening for hypertension in the paediatric TS population.
 
Consort diagram of included and excluded articles.
Given that cardiovascular diseases remain a primary cause of mortality and morbidity, there is a need to consider preventative strategies to improve vascular function from early in life. The aims of this study were therefore to investigate which interventions may improve endothelial function, intima media thickness and arterial stiffness in children and young people and to assess whether these interventions differ in boys and girls. A systematic literature search of Science Direct, Pubmed, Google Scholar and the Cochrane Library by two independent reviewers was performed to source articles. Inclusion criteria were any studies including any child ≤18 years of age receiving an intervention, which measured vascular function other than blood pressure. Exclusion criteria were studies assessing children with chronic medical conditions. A total of 72 studies were identified, which met the inclusion criteria. A measurable change in outcome was more likely to be reported in studies investigating endothelial function (p = 0.03). Interventions which improved vascular function included physical activity and dietary programmes. Under 10% of studies considered sex differences. In conclusion, school-based physical activity interventions are most likely to result in improvements in vascular function. Endothelial function may be the first variable of vascular function to change secondary to an intervention. Standardisation of reporting of differences between the sexes is essential to be able to ensure interventions are equally effective for boys and girls.
 
Hypertension (HTN) is a critical primary modifiable risk factor for the development of cardiovascular diseases, with recognized sex-based differences. While sex refers to one’s biological genetic makeup and attributes, gender encompasses the individual’s psycho-socio-cultural characteristics, including their environment and living conditions. The impact of each gendered variable may differ amongst men and women with respect to HTN. Applying a sex and gender-based lenses to inform our understanding of HTN has the potential to unveil important contributors of HTN-related cardiovascular outcomes. For instance, increased life stressors, work related anxiety and depression, typically have more pronounced effect on women than men with HTN. The impact of social surrounding including marital status and social support on HTN also differs amongst men and women. While married men are less likely to have higher blood pressure, single women, and those who never married are less likely to have HTN. Additionally, the beneficial role of social support is more pronounced in more historically marginalized cultural groups compared to majority. Finally, socioeconomic status, including education level and income have a linear and inverse relationship in blood pressure control in more resource-rich countries. The aim of this review is to summarize how sex and gender interact in shaping the clinical course of HTN demonstrating the importance of both sex and gender in HTN risk and its treatment. Hence, when investigating the role of gendered factors in HTN it is imperative to consider cultural, and social settings. In this narrative we found that employment and education play a significant role in manifestation and control of HTN particularly in women.
 
Systolic and diastolic blood pressure (BP) at rest, during exercise (left panel) and recovery from exercise (right panel)
Data are means (SD). *p < 0.05 vs. Rest, †p < 0.05 vs. Immediately preceding stage, ‡p < 0.05 vs. Reference, §p < 0.05 vs. All other methods at the same stage.
Association of systolic and diastolic blood pressure (BP) between the Fukuda monitor and the reference (the observer using a stethoscope)
Pearson correlation analysis of systolic and diastolic blood pressure are shown in (A and B). Bland-Altman analysis of agreement plots with mean difference ±2 standard deviations are shown in (C and D).
Blood pressure (BP) measurement plays a critical role in cardiac stress testing and is most commonly assessed manually. The emphasis of social distancing during the COVID-19 pandemic has renewed the interest in and the need for an automated BP device for incremental exercise stress testing. We assessed the accuracy of a new automated blood pressure device specifically manufactured for cardiac stress testing. Thirty-five adults aged 35 ± 16 years were studied during an incremental stress test on the cycle ergometer. Three observers measured BP simultaneously, two listening to Korotkoff sounds using a dual-headed stethoscope and one using headphones to listen to sounds generated by an automated BP device. With increasing workload, systolic BP increased progressively without significant differences in BP readings between any observer compared with the automated monitor at any stage during exercise. Systolic BP obtained with the BP machine was strongly correlated with those obtained by the stethoscope observers (r = 0.96) and the observer with headphones (r = 0.95). Diastolic BP obtained with the BP machine was moderately and significantly associated with those obtained by the stethoscope observers (r = 0.75) and the observer with headphones (r = 0.75). The automated BP monitor specifically made for cardiac stress testing accurately measured both systolic and diastolic blood pressure during exercise.
 
UMOD rs4293393 association with estimated glomerular filtration rate (eGFR): overall and sex stratified cross-sectional analysis
P = 0.003 (post hoc analysis) comparing mean values of heterozygous AG (n = 297) with homozygous AA (n = 668) individuals. Mean eGFR value for GG genotype was not significantly different from that of AA and AG groups. Data were analyzed by analysis of covariance, adjusted for sex in the overall analysis.
UMOD rs4293393 association with decline in estimated glomerular filtration rate (eGFR): overall and sex stratified longitudinal analysis
P > 0.05 across all groups. Data were analyzed by analysis of covariance, adjusted for sex, follow-up time and baseline eGFR values in the overall analysis and for follow-up time and baseline values eGFR in the sex-subgroup analysis.
Genetic variants in UMOD associate with kidney function and hypertension. These phenotypes are also linked to sex-related differences and impairment in cognitive and physical function in older age. Here we evaluate longitudinal associations between a common UMOD rs4293393-A>G variant and changes in estimated glomerular filtration rate (eGFR), blood pressure (BP), cognitive and physical function parameters in older participants in the BASE-II after long-term follow-up as part of the GendAge study. Overall, 1010 older participants (mean age 75.7 ± 3.7 years, 51.6% women) were analyzed after follow-up (mean 7.4 years) both in cross-sectional analysis and in longitudinal analysis as compared to baseline. In cross-sectional analysis, heterozygous G–allele carriers exhibited significantly higher eGFR values (AA, 71.3 ml/min/1.73 m2, 95% CI, 70.3–72.3 vs. AG, 73.5 ml/min/1.73 m2, 95% CI, 72.1–74.9, P = 0.033). Male heterozygous G-allele carriers had lower odds of eGFR < 60 mL/min/1.73 m2 (OR 0.51, 95% CI, 0.28–0.95, P = 0.032) and in Timed Up and Go-Test ≥ 10 s (OR 0.50, 95% CI, 0.29–0.85, P = 0.011) whereas women were less likely to have hypertension (OR 0.58, CI, 0.37–0.91, P = 0.018). UMOD genotypes were not significantly associated with longitudinal changes in any investigated phenotype. Thus, while the impact of UMOD rs4293393 on kidney function is maintained in aging individuals, this variant has overall no impact on longitudinal changes in BP, kidney, cognitive or functional phenotypes. However, our results suggest a possible sex-specific modifying effect of UMOD on eGFR and physical function in men and hypertension prevalence in women.
 
Association of serum markers of inflammation and endothelial function with AT1AA
Scatter plot of correlation between serum levels of AT1AA and markers of inflammation CRP, SAA (A, B) and endothelial function, sVCAM and sICAM (C, D) at baseline; p-value of Spearman rank correlation test, and “r” is the linear correlation coefficient.
Association of serum dicarbonyls and AGEs with AT1AA
Scatter plot of correlation between serum levels of AT1AA and dicarbonyls MGO, GO and 3-DG at baseline (A); Scatter plot of correlation between serum levels of AT1AA and free and protein-bound (PB) AGEs CML, CEL and 3-DG at baseline (B, C); p-value of Spearman rank correlation test, and “r” is the linear correlation coefficient.
Serum levels of dicarbonyls and AGEs before and after adrenalectomy
Serum levels of MGO, GO and 3-DG before (Pre) and 1-month after adrenalectomy (Post) (A); serum levels of free and protein-bound (PB) AGEs CML, CEL and 3-DG before (Pre) and 1-month after adrenalectomy (Post) (B, C). The estimation plots show the mean difference between pre and post adrenalectomy of the compound analyzed.
Patients with an aldosterone-producing adenoma (APA) carry a higher risk of cardiovascular disease and commonly have high levels of autoantibodies (AT1AA) that may activate the angiotensin II type 1 receptor (AT1R). AT1R activation is linked to an increase of the glucose metabolite methylglyoxal (MGO), a potential precursor of advanced glycation endproducts (AGEs) and driver of vascular inflammation. We investigated whether serum AT1AA levels are associated with serum MGO and AGE levels in APA patients. In a case series of 26 patients with APA we measured levels of dicarbonyls MGO, glyoxal (GO) and 3-deoxyglucosone (3-DG), and dicarbonyl-derived AGEs 5-hydro-5-methylimidazolone (MG-H1), Nε-(carboxyethyl)lysine (CEL) and Nε-(carboxymethyl)lysine (CML) with UPLC-MS/MS. We also measured AT1AA by ELISA. These measurements were repeated 1-month after adrenalectomy in a subset of 14 patients. Panels of inflammation and endothelial function were also measured by immunoassays. Although baseline higher AT1AA levels tended to be correlated with higher baseline serum MGO, GO and 3-DG levels (r = 0.18, p = 0.38; r = 0.20, p = 0.33; r = 0.23, p = 0.26; respectively), these correlations were not statistically significant. We observed no obvious correlations between higher AT1AA levels and protein-bound and free MG-H1, CEL and CML levels, and markers of inflammation and endothelial function. No decrease was observed in any of the dicarbonyls, protein-bound AGE levels and markers of inflammation and endothelial function after adrenalectomy. In patients with APA the serum levels of AT1AA were not significantly correlated with serum dicarbonyls, protein-bound and free AGE levels. Increased signalling of the AT1AA receptor may therefore be unlikely to overtly increase systemic dicarbonyl levels.
 
Y- axis level of self-care in percent and X- axis show the components of self-care
The level of self-care practice of hypertensive patients who were attending follow up care at East Gojjam Zone, North West Ethiopia, 2021.
Uncontrolled hypertension leads to cardiovascular complications and organ damage. Self-care practice is crucial for the prevention and management of hypertension by improving quality of life, preventing complications and decreasing health care expenditure. The study aimed to assess self-care practice and its associated factors among hypertensive follow up patients at East Gojjam Zone public hospitals; in Northwest Ethiopia. Quantitative cross-sectional study design and qualitative phenomenological approach were applied. The quantitative result was supported by in-depth interview. Out of 480 patients included in the study, 49% have good self-care practices. Out of the total participants 44.6% have poor in antihypertensive medication adherence, 92.5% have low in diet management, 82.8% were poorly practiced physical activity and 62.5% poor practice to weight management. Participants who cannot read and write (AOR = 3.1, 95% CI: 1.6–5.9), and have no comorbidity (AOR = 0.4, 95% CI: 0.2–0.6), uncontrolled blood pressure status (AOR = 2.1, 95% CI: 1.2–3.6), poor social support status (AOR = 2.5, 95% CI: 1.5–4.3) and unfavorable attitude (AOR = 3.1, 95% CI: 1.9–5.2) are the factors for poor self-care practice. During interview; family meal preparation habits, inadequate information about self-care practice during follow-up time, inconvenient working environment, pressure during social events to share food, negligence, and poor self-efficacy were highly described as challenges for practicing and sustaining self- care. The level of hypertension self-care practices was found to be low. Therefore, hypertension self-care practices should be strengthened throughout their follow-up time, and creating awareness in the community is highly encouraged.
 
GAM plots demonstrating univariable associations of hs-CRP with systolic and diastolic blood pressure in 46–49 years old women and men in the Hordaland Health Study
The solid lines indicate blood pressure and the shaded areas 95% confidence intervals. Density plots indicate distributions, and the vertical white lines indicate the 5th, 20th, 50th, 80th and 95th percentiles of hs-CRP. CRP high-sensitive C-reactive protein.
Associations of four circulating markers of inflammation (hs-CRP, neopterin, PAr index and KTR) with systolic and diastolic blood pressure in 46–49 years old women and men in the Hordaland Health Study
Red (women) and blue (men) diamonds indicate standardized beta coefficients and lines 95% confidence intervals from univariable linear regression analysis, respectively. pp for interaction between biomarker and sex, CRP high-sensitive C-reactive protein, PAr the ratio plasma 4-pyridoxic acid: (pyridoxal + pyridoxal-5’-phosphate), KTR kynurenine:tryptophan ratio.
Our aim was to test sex-specific associations of circulating markers of inflammation with blood pressure (BP) and incident hypertension in midlife. Participants in the Hordaland Health study (n = 3280, 56% women, mean age 48 years) were examined at baseline and followed for 6 years. Circulating levels of inflammatory markers including high-sensitive C-reactive protein (hs-CRP), neopterin, and pyridoxic acid ratio (PAr) index were measured at follow-up. The associations with systolic/diastolic BP and incident hypertension were tested in sex-specific linear- or logistic-regression analyses adjusted for body mass index, serum triglycerides, creatinine, physical activity, smoking and diabetes. At follow-up, women had lower mean BP than men (124/72 vs. 130/78 mmHg, p < 0.001). Higher hs-CRP was significantly associated with greater systolic and diastolic BP (standardized β = 0.07 and β = 0.09, both p < 0.01) in women, but not in men. Higher neopterin was associated with higher diastolic BP in women and higher PAr index was associated with higher diastolic BP in women and higher systolic and diastolic BP in men (all p < 0.01). Compared to hs-CRP < 1 mg/l, higher levels of hs-CRP 1–<3 mg/l and hs-CRP ≥ 3 mg/l were associated with new-onset hypertension only in women (odds ratio (OR) 1.74, 95% CI 1.20–2.53 and OR 1.87, 95% CI 1.20–2.90). Sex-interactions were found for hs-CRP and neopterin in models on incident hypertension and diastolic BP, respectively (both p < 0.05). Higher levels of circulating markers of inflammation were associated with higher BP and incident hypertension in a sex-specific manner. Our results suggest a sex-specific interaction between cardiovascular inflammation and BP in midlife.
 
Flow chart of the study design
Flowchart of the selection of randomized controlled trials included in this systematic review.
Effect after isometric handgrip exercise (IHGE) in individuals with hypertension (MVC: 30%)
A systolic blood pressure (SBP); (B): diastolic blood pressure (DBP).
Effect after isometric handgrip exercise (IHGE) in individuals with hypertension (MVC: 50%)
A systolic blood pressure (SBP); (B): diastolic blood pressure (DBP).
Effect after isometric handgrip training (IHGT) in individuals with hypertension
A systolic blood pressure (SBP); (B): diastolic blood pressure (DBP). *Ambulatory blood pressure monitoring (ABPM).
Aerobic exercise is a leading strategy for the prevention/management of systemic arterial hypertension, but other modalities of exercise have also been explored. Thus, we examined the acute effect of isometric handgrip exercise (IHGE) and the chronic effect of isometric handgrip training (IHGT) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in individuals with hypertension without comorbid conditions. We conducted a systematic review with meta-analysis of randomized controlled trials (RCTs) involving adults with hypertension. We searched the electronic databases MEDLINE (PubMed), Cochrane, Web of Science, LILACS, EMBASE and PEDro. We used random-effects model for the analyses, RoB2 tool to assess the risk of bias, and GRADE to assess the strength of evidence. A total of 9 RCTs (2 for IHGE and 7 for IHGT) were selected. Compared to a control condition, IHGE did not have any effect on SBP/DBP. Unlike, the pooled mean effect of IHGT showed SBP was reduced by 6.7 mmHg (95% CI –10.3 to –3.4 mmHg) and DBP by 4.5 mmHg (95% CI –7.3 to –1.7 mmHg) in individuals with hypertension. Also, the 95% prediction interval (95% PI) of IGHT was –10.9 to –2.5 mmHg for SBP and –10.2 to +1.2 mmHg for DBP. In conclusion, while IHGE did not produce post-exercise hypotension in the population studied, IHGT reduced SBP/DBP in individuals with hypertension with clinically important reductions in SBP (–6.7 mmHg) and DBP (–4.5 mmHg). This review was registered in the International Prospective Register of Systematic Reviews (PROSPERO) (CRD 42021217958).
 
Longitudinal measures of blood pressure separated by sex
(a) Systolic and (b) diastolic blood pressure plotted against age. (c) Systolic and (d) diastolic blood pressure plotted against Tanner stage. Data are presented as mean ± standard error. Mixed model estimates and p-values are provided. Asterisks denote a significant sex difference (p < 0.05).
Longitudinal measures of urinary Na:K separated by sex
Changes in urinary Na:K are plotted against (a) age and (b) Tanner stage, and presented as mean ± standard error. Mixed model estimates and p-values are provided for the linear or quadratic terms for age and Tanner stage, based on significance of the terms. Asterisks denote a significant sex difference (p < 0.05).
Blood pressure (BP) rises rapidly at puberty. While this is partly due to normal development, factors like excess adiposity and a high intake of dietary sodium relative to potassium may contribute to a true increase in hypertension risk. This study aimed to assess the relative impact of growth, gonadal hormones, adiposity and the sodium-to-potassium ratio (Na:K) on longitudinal BP measures at puberty. This study analysed data from a three-year longitudinal cohort study of pubertal adolescents. Anthropometry, body composition (bio-electrical impedance), serum testosterone and oestradiol (mass spectrometry) were measured annually. Na:K was measured from three-monthly urine samples. These variables were used to predict annual BP measures using mixed modelling and ordinal regression. Data from 325 adolescents (11.7 ± 1.0 y; 55% male) were analysed, showing typical growth patterns at puberty. Systolic BP increased over time in both sexes (p < 0.01), with boys exhibiting a significantly steeper rise compared to girls. Adiposity variables (BMI z-score, percent body fat, fat mass, waist-to-height ratio) strongly and consistently predicted systolic and diastolic BP in both sexes (all p < 0.05). Systolic BP was also significantly and positively related to height (p < 0.05). No associations with BP were identified in either sex for gonadal hormones or Na:K. Similar results were obtained when BP was classified into hypertension categories. Relative to other developmental and diet-related variables tested, adiposity was found to be the strongest most consistent predictor of BP in pubertal adolescents. Findings highlight the importance of dedicated youth obesity management interventions and policy measures for reducing long-term hypertension and cardiovascular disease risks. Australian New Zealand Clinical Trials Registry ACTRN12617000964314.
 
Hypertension remains the primary contributor in the development of cardiovascular disease which is rapidly increasing worldwide. High blood pressure affects men and women differently and understanding these sex differences is the ultimate unmet need for researchers in this field. Due to the inherent differences in hypertension prevalence, control and outcomes between men and women, novel research needs to be carried out to tackle these disparities and improve targeted treatment. Animal models of hypertension have provided valuable insights into the sexual dimorphism of blood pressure mechanisms. The availability of genetic and non-genetic hypertensive strains allows the opportunity to study diverse environmental and genetic factors that affect blood pressure, therefore presenting a valuable tool for researchers. Sex differences are present before birth and throughout life, which presents a challenge for the study of disease development in humans, but these complexities can be resolved with the use of in vivo models that display similarities to human disease. The aim of the present review is to provide an overview of the different available animal models of hypertension that present sexual dimorphisms and to discuss their relevance to humans.
 
Workflow of transcriptomics. Transcriptomics analysis begins with the extraction of DNA from plasma. Reverse transcriptase is then used to obtain complementary DNA fragments. The DNA library is then loaded into the sequencer and analysed. Gene expression can be visualised in heatmaps.
Proteomics analysis. For top-down proteomics where intact proteins are resolved by 2D PAGE and individually characterised later. In bottom up, proteins are digested by proteolytic enzymes and the separated peptides are analysed by MS (Figure modified from Kennani et al. [111]).
Hypertension, characterised by a constant high blood pressure, is the primary risk factor for multiple cardiovascular events and a major cause of death in adults. Excitingly, innovations in high-throughput technologies have enabled the global exploration of the whole genome (genomics), revealing dysregulated genes that are linked to hypertension. Moreover, post-genomic biomarkers, from the emerging fields of transcriptomics, proteomics, glycomics and lipidomics, have provided new insights into the molecular underpinnings of hypertension. In this paper, we review the pathophysiology of hypertension, and highlight the multi-omics approaches for hypertension prediction and diagnosis.
 
A framework for diagnosis and management of hypertensive emergencies, malignant hypertension (accelerated hypertension), and acute severe hypertension. a Approach and diagnosis of management of hypertensive emergencies, malignant hypertension (accelerated hypertension), and acute severe hypertension. b Management framework for acute severe hypertension. c Management framework for malignant hypertension and hypertensive emergencies.
Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.
 
Cardiovascular disease (CVD) is the leading cause of death globally for men and women. Premenopausal women have a lower incidence of hypertension and other cardiovascular events than men of the same age, but diminished sex differences after menopause implicates 17-beta-estradiol (E2) as a protective agent. The cardioprotective effects of E2 are mediated by nuclear estrogen receptors (ERα and ERβ) and a G protein-coupled estrogen receptor (GPER). This review summarizes both established as well as emerging estrogen-mediated mechanisms that underlie sex differences in the vasculature during hypertension and CVD. In addition, remaining knowledge gaps inherent in the association of sex differences and E2 are identified, which may guide future clinical trials and experimental studies in this field.
 
Hypertension is a major public health challenge in low- and middle-income countries (LMICs) and calls for large-scale effective hypertension control programs. Adoption of drug and dose-specific treatment protocols recommended by the World Health Organization-HEARTS Initiative is key for hypertension control programs in LMICs. We estimated the annual medication cost per patient using three such protocols (protocol-1 and protocol-2 with Amlodipine, Telmisartan, using add-on doses and different drug orders, adding Chlorthalidone; protocol-3 with a single-pill combination (SPC) of Amlodipine/Telmisartan with dose up-titration, and addition of Chlorthalidone, if required) in India. The medication cost was simulated with different hypertension control assumptions for each protocol and calculated based on prices in the public and private sectors in India. The estimated annual medication cost per patient for protocol-1 and protocol-2 was $33.88–58.44 and $51.57–68.83 for protocol-3 in the private sector. The medication cost was lower in the generic stores ($5.78–9.57 for protocol-1 and protocol-2, and $7.35–9.89 for protocol-3). The medication cost for patients was the lowest ($2.05–3.89 for protocol-1 and protocol-2, and $2.94–3.98 for protocol-3) in the public sector. At less than $4 per patient per annum, scaling up a hypertension control program with specific treatment protocols is a potentially cost-effective public health intervention. Expanding low-cost generic retail networks would extend affordability in the private sector. The cost of treatment with SPC is comparable with non-SPC protocols and can be adopted in a public health program considering the advantage of simplified logistics, reduced pill burden, improved treatment adherence, and blood pressure control.
 
Exposure-relationship between TV and BP
Lag days with the smallest AIC were selected to analyze. For daily temperature variability (DTV) and BP, Lag03 day, Lag00 day, Lag06 day, and Lag01 day were used for SBP, DBP, PP, and MAP, respectively. For hourly temperature variability (HTV) and BP, Lag03 day, Lag00 day, Lag06 day, and Lag02 day were used for SBP, DBP, PP, and MAP. All models were adjusted for age, gender, education level, marital status, occupation, income, smoking, drinking, BMI, diseases history, mean temperature, relative humidity and season.
BP changes associated with per 1 °C increase in DTV and HTV in different lag days
A for SBP, (B) for DBP, (C) for PP, and (D) for MAP. The slid dots are the effect estimates and the error bars represent the 95% confidence intervals. All models were adjusted for age, gender, education level, marital status, occupation, income, smoking, drinking, BMI, diseases history, mean temperature, relative humidity and season.
Estimated effects in BP per 1 °C increase in TV among people with different blood pressure
Models were adjusted for age, gender, education level, marital status, occupation, income, smoking, drinking, BMI, diseases history, drug use, mean temperature, relative humidity and season. *There were statistical differences compared with people with normal blood pressure.
Blood pressure has been shown to change by outdoor temperature, but whether intra- and inter-day temperature variability (TV) will bring higher effect on BP is not clear. Based on a prospective cohort study, the mixed effect model was selected to estimate the relationship between TV (daily temperature variability (DTV) and hourly temperature variability (HTV)) and BP (systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), and mean arterial pressure (MAP)) after adjusting for confounding variables. We found that there was a positive linear correlation between TV and BP. The results of DTV and HTV were basically consistent, but the effect estimates of HTV seemed to be larger. Gender, age, BMI, education level and BP status may modify the relationship between TV and BP. The effect of TV on BP was greater in non-heating season than in heating season. Our work contributes to a further macro mechanism evidence for the TV-CVDs association.
 
Flow chart of the study
Flow chart of the study including the classification of pregnant women before 20 weeks of gestation using ambulatory blood pressure monitoring.
The objectives of this study were 1—to evaluate the prevalence of masked chronic hypertension in pregnant women classified as gestational hypertension 2—to compare the risks of developing preeclampsia in true gestational hypertension vs those women classified as having gestational hypertension but who had had masked hypertension in the first half of pregnancy. We conducted a cohort study in consecutive high-risk pregnancies who were evaluated before 20 weeks of gestation. Women who developed gestational hypertension (normotension in the office before 20 weeks of gestation and office BP ≥ 140/90 mmHg and/or antihypertensive treatment in the second half of gestation) were divided, according to an ABPM performed before 20 weeks of pregnancy, in two subgroups: subgroup 1—if their ABPM was normal, and subgroup 2—if they had masked chronic hypertension. Risks for preeclampsia (PE) were estimated and compared with normotensive women. Before 20 weeks of gestation, 227 women were evaluated (age 32 ± 6 years, median gestation age 15 weeks); 67 had chronic hypertension (29.5%). Of the remaining 160, 39 developed gestational hypertension (16 in subgroup 1 and 23 insubgroup 2. Compared with normotensive pregnant women, subgroup 1 of women with gestational hypertension did not increase the risk of developing PE (OR = 0.76, 95% CI = 0.16–6.65). Conversely, subgroup 2 of gestational hypertension increased the risk of PE more than 4 times (0R = 4.47 CI = 1.16–12.63). Risk estimation did not change substantially after the adjustment for multiple possible confounders. In conclusion, the59% of women initially diagnosed as gestational hypertensive according to current recommendations had masked chronic hypertension and a very high risk of developing PE.
 
Comparison of central stiffness and retrograde flow profile between the two groups
A Incremental Elastic modulus was significantly higher in patients with ischemic heart disease as compared to healthy subjects (Mann–Whitney test). B Carotid compliance was significantly lower in patients of ischemic heart disease compared to healthy subjects (Mann–Whitney test). C Retrograde blood flow velocity (mean -AUC) was comparable between the two groups (Mann–Whitney test). D Retrograde shear stress (mean—AUC) was comparable between the two groups (Mann–Whitney test) (*** indicates p < 0.0001, ** indicates p < 0.05).
Association of retrograde and oscillatory flow profile with central and peripheral vascular factors in healthy subjects and patients
Upper panel (A–C) shows correlations in healthy subjects and lower panel (D–F) shows correlation in patients with ischemic heart disease (A). A significant positive correlation was seen between retrograde blood flow velocity (mean -AUC) (RBFVAUC) with augmentation index in healthy subjects (Pearson’s correlation) (B). A significant positive correlation was seen between RBFVAUC and incremental elastic modulus in healthy subjects (Spearman Correlation) (C). A significant negative correlation was seen between oscillatory shear index and forearm vascular conductance in healthy subjects (Spearman Correlation) (D). A significant positive correlation was seen between RBFVAUC and Ejection fraction in patients with ischemic heart disease (Spearman Correlation) (E). A significant negative correlation was seen between RBFVAUC and forearm vascular conductance in patients with ischemic heart disease (Spearman Correlation) (F). A significant positive correlation was seen between RBFVAUC and cf/cr pulse wave velocity ratio (Spearman Correlation).
Association of retrograde flow profile with endothelial function and sub-clinical atherosclerosis in healthy subjects (A) and patients (B, C)
A A significant negative correlation was seen between retrograde blood flow velocity (max) and Low flow mediated constriction (LFMC) in healthy subjects (Pearson’s Correlation) B A significant negative correlation was seen between Retrograde blood flow velocity (mean-AUC) (RBFVAUC) and Flow mediated dilation (FMD) (Spearman Correlation). C A significant positive correlation was seen between RBFVAUC and carotid-intima media thickness (CIMT) (Spearman Correlation).
of the central, peripheral, and composite vascular factors associated with retrograde flow
Parameters in bold dark gray were majorly found to be associated with retrograde flow patterns in healthy subjects. Parameters in bold black were majorly found to be associated with retrograde flow patterns in patients with ischemic heart disease. Parameter in italics was found to be associated with retrograde flow in both healthy subjects and patients with ischemic heart disease. Non-bolded parameters in light gray were not found to be associated with retrograde flow patterns in either group.
Retrograde flow in endothelial cell cultures has been shown to induce a pro-atherogenic phenotype. Despite its potential role as a pathophysiological link between cardiovascular risk factors and atherosclerotic disease, resting retrograde flows between patients with cardiovascular disease and healthy subjects have not been compared. Further, the vascular characteristics governing retrograde flow in human arteries have not been systematically investigated. Association of central and peripheral vascular characteristics with retrograde flow profile was investigated in 32 healthy subjects and 47 patients with ischemic heart disease. Endothelial dysfunction was assessed by brachial ultrasound-based calculation of flow-mediated dilation (FMD) and sub-clinical atherosclerosis was estimated from carotid-intima media thickness (CIMT). Retrograde blood flow velocity (RBFV) and shear rate were comparable between the two groups (RBFV 1.82(0.97–3.32) vs 1.78(1.24–2.65) cm/s p = 0.79). Augmentation index was a significant determinant of retrograde flow in both patients and healthy subjects. Carotid artery incremental elastic modulus was an independent determinant of retrograde flow patterns in healthy subjects while ejection fraction, cf/cr PWV ratio and forearm vascular conductance emerged as independent determinants in patients. Retrograde flow patterns were also associated with FMD (RBFV r = −0.43, p = 0.004) and CIMT (r = 0.30, p = 0.041) in patients. The results of the study suggest a difference in the determinants of retrograde flow in patients and healthy subjects, with central arterial stiffness being a major contributor in healthy subjects while interaction between central, peripheral, and cardio-arterial factors influence retrograde flow in patients with ischemic heart disease.
 
Accurate blood pressure (BP) assessment is essential for the optimal diagnosis and management of hypertension. Contemporary clinical practice guidelines strongly endorse use of automated cuff blood pressure measuring devices (BPMD) as the preferred means of measuring and monitoring BP in the office, at home and with ambulatory blood pressure monitoring. To ensure that they are accurate, automated BPMDs should undergo clinical validation testing, performed using an established clinical validation standard. Unfortunately, most BPMDs sold on the global market have not been clinically validated. Furthermore, in the last thirty years, several different clinical validation protocols have been published, with major differences apparent between these standards, causing controversy with respect to which standard is considered acceptable for clinical validation. Complexly worded standards, multiple revisions, and firewalled access also contribute to a lack of understanding and use of clinical validation standards and the number of expert centers performing clinical validations is small. Recently, joint society collaborations have led to creation of the AAMI/ESH/ISO universal standard for the clinical validation of automated cuff BPMDs. Not only is this unified standard a necessary step, but oversight from regulators and influential stakeholders to ensure that only clinically validated BPMDs can be marketed is additionally needed.
 
Trajectories of ambulatory blood pressure and pulse rate by neurologic status at discharge
a Ambulatory systolic blood pressure; b ambulatory diastolic blood pressure; c ambulatory pulse rate.
Odds ratio functions of ambulatory blood pressure and pulse rate profiles on neurologic disability
a Neurologic disability at discharge; b neurologic disability at 3-months follow-up. ABPM ambulatory blood pressure monitoring, SBP systolic blood pressure, DBP diastolic blood pressure, PR pulse rate, CI confidence interval. Odds ratio functions are shown as solid lines, and confidence bands dotted lines.
This study aims to assess the associations of functional outcomes following acute ischemic stroke (IS) with ambulatory pulse rate (PR) and characterize the time-variant properties of the associations. The prospective cohort consisted of 1831 patients who had ambulatory blood pressure (BP) and PR monitoring following acute IS, and neurologic status evaluated at discharge and 3-month follow-up. The neurologic disability was defined as modified Rankin Scale ≥3. Logistic regression and generalized penalized functional regression models were used to examine the associations of ambulatory BP and PR with neurologic disability. Adjusting for covariates, the neurologic disability at discharge and 3-month was associated with high average 24-h, daytime, and nocturnal PR (odds ratio, OR = 1.20–1.34; p < 0.05 for all), high standard derivation of nocturnal PR (OR = 1.19 and 1.32; p < 0.05 for both), and low nocturnal PR decline (OR = 0.76 and 0.76; p < 0.05 for both). The OR functions of ambulatory PR on neurologic disability were “W-shaped” from 0 a.m. to 12 p.m., with ORs >1 in the wee hours and at noon, and ORs <1 before dawn and at night. The ambulatory BP profiles were not associated with neurologic disability at discharge or 3-month. The ambulatory PR is associated with the risk of short-term neurologic disability of stroke patients, with four different phases in a 24-h cycle. Ambulatory PR monitoring, especially nocturnal PR monitoring, has significant clinical implications for the prevention of short-term neurologic disability in stroke inpatients.
 
Arterial hypertension is a major public health issue. Non-pharmacological approaches like Mindfulness-Based Stress Reduction (MBSR) might be a promising addition to conventional therapy. This systematic review and meta-analysis aim to evaluate the effects of MBSR on systolic (SBP) and diastolic blood pressure (DBP) among individuals with prehypertension or hypertension. We searched Medline/PubMed, Scopus and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized controlled trials (RCTs) from their inception until August 1st 2021. RCTs were included that compared MBSR to any control intervention in participants with diagnosed prehypertension (120-139/80-89 mmHg) or hypertension (≥140/≥90 mmHg). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Risk of Bias was assessed using the Cochrane tool. Seven RCTs with 429 participants were included. Very low quality of evidence was found for positive effects of MBSR on SBP (MD = -11.26 mmHg, 95%CI = -20.24 to -2.29, p = 0.01) but no evidence for effects on DBP levels (MD = -3.62 mmHg, 95%CI = -8.52 to 1.29, p = 0.15) compared to waitlist control. Compared to active control, very low quality of evidence was found for positive effects on DBP (MD = -5.51 mmHg, 95%CI = -10.93 to -0.09, p = 0.05) but no effects on SBP levels (MD = -4.33 mmHg, 95%CI = -12.04 to 3.38, p = 0.27). Overall, the studies showed a high degree of heterogeneity. The effects found were robust against selection, detection, and attrition bias. Only one RCT reported safety data. MBSR may be an option for lowering blood pressure in people with prehypertension to hypertension. More and larger high-quality studies are needed to substantiate our findings.
 
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.
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.
 
Pharmacogenetics play an important role in determining the anti-hypertensive effects of blood pressure-lowering medications and have the potential to improve future patient care. Current literature on the topic, however, has a heavy focus on Caucasians and may not be generalisable to the Asian populations. Therefore, we have conducted this systematic review to summarise and evaluate the literature of the past decade. PubMed, Embase, and the Cochrane Register of Controlled Trials were searched for relevant studies from 1 January 2011 to 23 July 2021. The outcome of interest was the response to anti-hypertensive treatment in Asians according to each genetic polymorphism. A total of 26 studies with a total of 8837 patients were included in our review, covering five classes of anti-hypertensive agents—namely, angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), beta-blockers (BB), calcium channel blockers (CCB), and thiazide-like diuretics. Response to ACEI therapy was most susceptible to genotypic variations, while the efficacy of ARB and CCB were affected by pharmacogenetic differences to varying extent. For BB, only variations in the ADRB1 genotype significantly affects therapeutic response, while the therapeutic efficacy of thiazide-like diuretics was correlated with genotypic variations in the REN and ACE. This systematic review evaluated the impact of pharmacogenetic variations on the therapeutic efficacy of anti-hypertensive treatment in Asians and has described numerous drug-gene pairs that are potentially clinically important. Future prospective studies with larger sample sizes and longer follow-up periods are needed to better elucidate the impact of these drug-gene pairs.
 
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.
 
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