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The inflammatory status of the kidneys, vasculature, and perivascular adipose tissue (PVAT) has a significant influence on blood pressure and hypertension. Numerous micronutrients play an influential role in hypertension-driving inflammatory processes, and recent reports have provided bases for potential targeted modulation of these micronutrients to reduce hypertension. Iron overload in adipose tissue macrophages and adipocytes engenders an inflammatory environment and may contribute to impaired anticontractile signalling, and thus a treatment such as chelation therapy may hold a key to reducing blood pressure. Similarly, magnesium intake has proven to greatly influence inflammatory signalling and concurrent hypertension in both healthy animals and in a model for chronic kidney disease, demonstrating its potential clinical utility. These findings highlight the importance of further research to determine the efficacy of micronutrient-targeted treatments for the amelioration of hypertension and their potential translation into clinical application., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Arterial hypertension is a major risk factor for cardiovascular morbidity and mortality, and highly prevalent in older age, underscoring the importance of its appropriate management. The population is ageing at an increasing rate, with those aged 80+ years being the fastest growing population characterized by high heterogeneity in terms of functionality and autonomy. The prevalence of hypertension rises with increasing age, due to a significant increase in SBP largely as a result of age-related stiffening of the aorta and other large arteries, affecting almost 80% of those aged 80+ years. Appropriate management of blood pressure in this population is a priority for clinicians. Frailty is a condition characterized by marked vulnerability to adverse health outcomes and is common among older adults including those with hypertension. Hypertension increases frailty level and at the same time, individuals with increasing frailty present with more drug-related adverse effects meaning they are less tolerant to blood pressure lowering by medication. Thus, frailty is a factor that should be integrated when treating hypertension in this population. The European Society of Hypertension 2023 Guidelines on the management of Hypertension are the first international guidelines to integrate the concept of adapting blood pressure management in older adults according to their frailty/functionality level, and to propose practical tools for the application of this concept in the daily practice of physicians and other healthcare professionals. The present article prepared by the European Society of Hypertension Working Group on Hypertension in Older Adults aims to further address some important aspects mentioned concisely in the 2023 European Society of Hypertension guidelines, in order to help physicians and other healthcare professionals including those practicing in primary care. To this end, this study discusses 12 'hot questions' which are answered with the help of the 2023 European Society of Hypertension Guidelines. We hope the present article and Working Group's actions will contribute to understanding and applying the ideal management of hypertension in this most vulnerable population., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hypertension and cancers are the most common causes of death in humans, as well as common co-diseases among elderly population. Studies have shown that hypertension is associated with carcinogenesis. The renin-angiotensin-aldosterone system (RAAS) is a crucial regulatory system of blood pressure, fluid, and electrolyte homeostasis, which plays an essential role in the pathogenesis of hypertension, whose mechanism is relatively clear. Studies have indicated that RAAS also widely exists in cancer tissues of different systems, which can affect the risk of cancers by stimulating cancer angiogenesis, participating in cancer-related oxidative stress, and regulating cancer-related immunity. Therefore, inhibiting RAAS activity seems beneficial to decreasing the risk of cancers. As one of the most commonly used antihypertensive drugs, RAAS inhibitors have been widely used in clinical practice. However, the conclusions of clinical studies on the relationship between RAAS inhibitors and cancers are not entirely consistent, which has been widely concerned by clinicians. The latest findings suggest that while RAAS inhibitors may reduce the risk of digestive cancers, respiratory cancers, urological cancers, gynecological cancers, and skin cancers, ACEIs may increase the risk of lung cancer, endometrial cancer, basal cell carcinoma, and squamous cell carcinoma. This article comprehensively reviews animal experiments, clinical studies, and meta-analyses on the relationship between RAAS inhibitors and cancers, to provide references for related studies in the future., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Since the effects of once-daily antihypertensive (HT) medications are more pronounced within the first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, no relevant meta-analysis has been conducted in patients with nocturnal HT. This meta-analysis included randomized controlled trials involving patients with elevated mean nocturnal blood pressure (BP) and compared evening anti-HT administration with morning administration. Multiple databases, including grey literature (e.g. clincialtrial.gov), were searched. Study selection and data extraction were conducted by two independent authors. Risk of bias assessment and overall quality of evidence were conducted using Cochrane risk-of-bias tool and GRADE by two independent authors. A total of 107 studies were included, 76 of which were investigated in China and had not been identified in previous reviews. Only one trial was ranked low risk-of-bias. Evening administration of anti-HT medications was effective in reducing nocturnal systolic BP (4.12-9.10 mmHg; I2 = 80.5-95.2%) and diastolic BP (3.38-5.87 mmHg; I2 = 87.4-95.6%). Subgroup analyses found that the effectiveness of evening administration was contributed by data from the Hermida group and China. Evening administration did not provide additional nocturnal/daytime/24-h BP reduction in non-Hermida/non-China studies (I2 = 0) and in meta-analyses that included studies with unclear or low risk of bias. The effectiveness of nocturnal BP reduction was similar across different types, doses, and half-lives of medications. Evening administration of anti-HT medications may reduce proteinuria, left ventricular hypertrophy (LVH), nondipping and morning surge. The overall quality of evidence was ranked as very low to low. Our results highlight the scarcity of low risk-of-bias studies and emphasize the need for such trials to evaluate the efficacy of evening dosing of anti-HT medications as a standard treatment for patients with nocturnal HT across diverse populations., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To assess the impact of personalized feedback on therapy adherence testing results on quality of life and beliefs about medication in patients with resistant hypertension, as well as to identify patient-oriented predictors of therapy adherence., Methods: This study was a prespecified post hoc analysis of the multicenter randomized controlled trial Resistant HYpertension: MEasure to ReaCh Targets (RHYME-RCT). Patients were randomized to a personalized feedback conversation on measured antihypertensive drug levels additional to standard-of-care, or standard-of-care only. The primary outcomes consisted of EuroQol EQ-5D-5L and Beliefs about Medicine Questionnaire (BMQ) scores at 12 months., Results: A total of 56 patients with median age 61.5 [25th-75th percentile: 55.8-69.3] years (21.4% women) were included. Mean blood pressure ±SD was 149.8/84.1 ± 14.9/13.8 mmHg while being on a median of 5.6 [4.8-7.3] defined daily dosages (DDD) of antihypertensive drugs. At 12 months, no differences were observed in EQ-5D-5L index (0.81 [0.69-0.89] vs. 0.89 [0.73-1.00]; P  = 0.18) and visual analogue scale score on general patient-perceived health (70 [60-80] vs. 70 [60-82]; P  = 0.53) between the intervention-arm and the standard-of-care only-arm. Likewise, individual EQ-5D-5L domain scores and BMQ scores did not differ between both arms. Irrespective of the intervention, independent positive predictors of the percentage adherence were patient age, EQ-5D-5L index score, BMQ-specific necessity score and concern score, whereas the total number of drugs prescribed was a negative predictor., Conclusion: Within this prespecified subanalysis of the randomized RHYME-RCT trial, implementation of a personalized feedback conversation targeting therapy adherence did not improve health-related quality-of-life and beliefs about medication in patients with resistant hypertension., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hypertension, a risk factor for developing cardiovascular disease, is becoming increasingly prevalent worldwide. Digital health is now widely utilized for hypertension management, and numerous studies have assessed its effectiveness., Objective: The review aims to analyse the effectiveness of digital health (i.e., mobile health (mHealth), telehealth, and the combination of mHealth & telehealth) on hypertensive patients, concerning three key areas: clinical outcomes, medication adherence, and adherence to lifestyle changes, as compared to standard care., Methods: The review followed the PRISMA framework. Eight electronic databases were scanned for randomized control trials focusing on the effects of mHealth or telehealth on hypertensive patients, published between 2010 and 2023. All processes were conducted by the first two authors independently. A meta-analysis was conducted for quantitative data, while a narrative synthesis was conducted for qualitative data., Results: In total, 74 studies involving 92 686 participants were identified. The meta-analysis favoured the interventions, revealing a significant decrease in systolic blood pressure and diastolic blood pressure for mHealth, telehealth and mHealth & telehealth groups. Nevertheless, medication adherence showed improvement only in the mHealth group, while blood pressure control showed improvement in both mHealth and mHealth & telehealth groups, and BMI showed improvement only in the mHealth group. Evidence for adherence to physical activity and DASH diet/salt intake remained inconclusive., Conclusion: In general, mHealth and telehealth have demonstrated their merits in improving the clinical outcomes of hypertensive patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Real-life management of hypertensive patients with chronic kidney disease (CKD) is unclear., Methods: A survey was conducted in 2023 by the European Society of Hypertension (ESH) to assess management of CKD patients referred to ESH-Hypertension Excellence Centres (ESH-ECs) at first referral visit. The questionnaire contained 64 questions with which ESH-ECs representatives were asked to estimate preexisting CKD management quality., Results: Overall, 88 ESH-ECs from 27 countries participated (fully completed surveys: 66/88 [75.0%]). ESH-ECs reported that 28% (median, interquartile range: 15-50%) had preexisting CKD, with 10% of them (5-30%) previously referred to a nephrologist, while 30% (15-40%) had resistant hypertension. The reported rate of previous recent (<6 months) estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR) testing were 80% (50-95%) and 30% (15-50%), respectively. The reported use of renin-angiotensin system blockers was 80% (70-90%). When a nephrologist was part of the ESH-EC teams the reported rates SGLT2 inhibitors (27.5% [20-40%] vs. 15% [10-25], P  = 0.003), GLP1-RA (10% [10-20%] vs. 5% [5-10%], P  = 0.003) and mineralocorticoid receptor antagonists (20% [10-30%] vs. 15% [10-20%], P  = 0.05) use were greater as compared to ESH-ECs without nephrologist participation. The rate of reported resistant hypertension, recent eGFR and UACR results and management of CKD patients prior to referral varied widely across countries., Conclusions: Our estimation indicates deficits regarding CKD screening, use of nephroprotective drugs and referral to nephrologists before referral to ESH-ECs but results varied widely across countries. This information can be used to build specific programs to improve care in hypertensives with CKD., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Primary aldosteronism is the most common cause of secondary hypertension, which is caused by increased aldosterone secretion in the adrenal cortex and contains many subtypes, among which familial hyperaldosteronism is relatively rare. Familial hyperaldosteronism can be divided into four subtypes based on its clinical manifestations and mutated genes: FH-I , FH-II , FH-III , and FH-IV . This article reports on three patients with FH-IV: a mother and her two sons. They were diagnosed with hypertension in other hospitals, and hypokalemia was found during hospitalization in our department. Diltiazem and terazosin were used for elution for 1 month. Renin and aldosterone levels in standing or supine positions improved, and the aldosterone-to-renin ratio was positive. Primary aldosteronism was diagnosed based on improved saline and captopril inhibition tests. As the three patients were blood-related immediate family members, gene screening was performed, diagnosing them with FH-IV . This article reports the clinical characteristics of the three cases in combination with related literature to improve the understanding of FH-IV ., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Many studies have implemented and evaluated task-sharing interventions with community health workers (CHWs) to manage hypertension. To identify gaps in research, we conducted a scoping review. We searched original articles published in PubMed and EMBASE between 2010 and 2022 and found 122 articles meeting our inclusion criteria. Only seven articles were from low-income countries (LICs), most of which were qualitative studies or mixed methods studies. In the identified 122 articles, CHWs often performed health education (61.3%) and measured blood pressure (60.4%). Whereas CHWs carried out pharmacological treatment in only three studies. Participant homes (75.0%) were the most common setting for receiving interventions. Our study identified specific needs for future research, specifically, studies in LICs that are experimental in design and that collect relevant qualitative information, and studies in which CHWs do advanced task. In addition, publications of CHW studies should provide a more comprehensive list of intervention features., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Overestimation of blood pressure (BP) resulting from medial artery calcification (MAC) is a cause of pseudoresistant hypertension. In this condition, there is no noninvasive way to reliably assess the BP. We report the case of a 62-year-old man who had a four-limb MAC, hypertension despite five antihypertensive molecules, and significant orthostatic hypotension following the addition of the fifth drug. Hypotension symptoms resolved after discontinuation of two treatments. Subsequently, measurement of finger SBP (FSBP) by laser Doppler flowmeter (LDF) was used to estimate upper-limb SBP. While the brachial SBP was greater than 170 mmHg, the FSBP was always less than 140 mmHg. In the absence of upper-limb artery disease, by evidencing the discrepancy between FSBP and brachial SBP, LDF-obtained FSBP could be a reliable tool to ascertain pseudohypertension and monitor the antihypertensive treatment., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We aimed to determine the influence of coronavirus disease 2019 (COVID-19) pandemic on blood pressure (BP) control assessed by ambulatory blood pressure monitoring (ABPM)., Methods: Office BP and ABPM data from two visits conducted within a 9-15 months interval were collected from patients treated for hypertension. In the prepandemic group, both visits took place before, while in the pandemic group, Visit-1 was done before and Visit-2 during the pandemic period., Results: Of 1811 collected patients 191 were excluded because they did not meet the required ABPM time frames. Thus, the study comprised 704 patients from the pandemic and 916 from the prepandemic group. Groups did not differ in sex, age, duration of hypertension, frequency of first line antihypertensive drug use and mean 24 h BP on Visit-1. The prevalence of sustained uncontrolled hypertension was similar in both groups. On Visit-2 mean 24 h BP, daytime and nighttime systolic BP and diastolic BP were higher in the pandemic compared to the prepandemic group ( P  < 0.034). The prevalence of sustained uncontrolled hypertension on Visit-2 was higher in the pandemic than in the prepandemic group [0.29 (95% confidence interval (95% CI): 0.26-0.33) vs. 0.25 (95% CI: 0.22-0.28), P  < 0.037]. In multivariable adjusted analyses a significant difference in BP visit-to-visit change was observed, with a more profound decline in BP between visits in the prepandemic group., Conclusions: This study using ABPM indicates a negative impact of the COVID-19 pandemic on BP control. It emphasizes the need of developing strategies to maintain BP control during a pandemic such as the one induced by COVID-19., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The Action in Diabetes and Vascular disease: preterAx and diamicroN Controlled Evaluation (ADVANCE) trial investigated the effects of intensive blood pressure (BP) lowering using a fixed combination of perindopril-indapamide versus placebo in type 2 diabetes (T2D). The study showed that combination perindopril-indapamide had significant benefits in reducing cardiovascular, renal, and mortality events, with consistent relative risk reductions across different patient subgroups. Secondary analyses of ADVANCE have identified novel risk markers in T2D including cessation of BP lowering therapy, absent peripheral pulses and cardiac biomarkers to name a few. ADVANCE also shed light on practical aspects of hypertension management, including the limitations of office BP, tolerability of combination BP lowering therapy across the range of BP levels and the interpretation of changes in serum creatinine after treatment initiation. This review article summarizes the findings of ADVANCE and its subsequent substudies, which have been foundational in our understanding of BP management and the use of combination BP lowering therapy in T2D., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Diuretics, including thiazides and thiazide-like drugs, are commonly recommended for treating hypertension, though their precise mechanism of action is not fully understood. This study aimed to investigate the pharmacological effects of trichloromethiazide (TCM) in malignant stroke-prone spontaneously hypertensive rats (M-SHRSP)., Methods: M-SHRSPs were treated with varying doses of TCM. Prognosis, histological changes, and mRNA expression related to hypertension and stroke were assessed., Results: The high-dose TCM group (3%) exhibited significantly lower SBP compared with the untreated group, whereas the low-dose group (0.3%) did not show a significant reduction in SBP. The survival rate was 54% in the low-dose group, whereas all rats in the high-dose group survived without experiencing a stroke by 16 weeks of age. Organ weights in both TCM-treated groups were lower than those in the control group, without severe histological abnormalities, including stroke and sclerosis. Plasma levels of thiobarbituric acid-reactive substances (TBARS) were significantly reduced in both TCM-treated groups. Additionally, 20 genes related to tissue protection, repair, proliferation, maintenance, and function were significantly expressed., Conclusion: TCM administration in M-SHRSPs significantly modulated the expression of 20 genes associated with tissue protection and maintenance, and reduced plasma TBARS levels. These findings suggest that TCM, a thiazide diuretic, may protect against tissue impairment in hypertension by modulating gene expression and exhibiting antioxidant activity., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Hypertension is often linked with metabolic risk factors that share common pathophysiological pathways. Despite wide-spread availability of multiple drug classes, optimal blood pressure (BP) control remains challenging. Increased central sympathetic outflow is frequently neglected as a critical regulator of both circulatory and metabolic pathways and often remains unopposed therapeutically. Selective imidazoline receptor agonists (SIRAs) effectively reduce BP with a favorable side effect profile compared with older centrally acting antihypertensive drugs. Hard outcome data in hypertension, such as prevention of stroke, heart and kidney diseases, are not available with SIRAs. However, in direct comparisons, SIRAs were as effective as angiotensin-converting enzyme inhibitors, β-blockers, calcium channel blockers, and diuretics in lowering BP. Other beneficial effects on metabolic parameters in hypertensive patients with concomitant overweight and obesity have been documented with SIRAs. Here we review the existing evidence on the safety and efficacy of moxonidine, a widely available SIRA, compared with common antihypertensive agents and provide a consensus position statement based on inputs from 12 experts from Europe and Australia on SIRAs in hypertension management., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients in methadone maintenance treatment (MMT) may develop age-related medical problems, but hypertension (HTN) proportion and its occurrence during MMT have not been studied yet. We aimed to evaluate changes in blood pressure (BP) during MMT and characterize current HTN., Methods: Of all 1098 ever admitted MMT patients, those with ≥2 BP follow-up measures were included ( n  = 516), of them all current patients ( N  = 245) tested for HTN (systolic BP ≥140 mmHg or diastolic BP ≥90 were detected twice (one week apart) were considered as affected with HTN. Current and earliest during the first, and latest year in MMT of body mass index (BMI), BP, methadone dose and serum level, and drugs in urine were analyzed., Results: HTN was detected in 89(36.3%) of the current patients. The HTN and non-HTN groups did not differ by sex ( P  = 0.6), age ( P  = 0.2), and duration in MMT ( P  = 0.6), but had higher BMI (27.9 ± 5.2 vs. 25.6 ± 5.2, respectively, P  = 0.001) and fewer had positive urine test findings for any substance (31.5% vs. 44.9%, P  = 0.04). Comparing their earliest measures (before 11.9 ± 5.8 years), BP and BMI increased more among the hypertensive group, independent of methadone dose and serum levels, which significantly reduced over the years. No drug abuse was associated with increased BMI and BP., Conclusions: Weight gain was associated with BP elevation and characterized patients who succeeded in drug abstinence during MMT. Healthy nutrition education at admission to MMT may reduce the incidence of weight gain and HTN, therefore identifying HTN and offering treatment for this highly prevalent life-threatening condition among middle-age and older patients in MMT is recommended., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Blood pressure (BP) variability (BPV) can be assessed using office (OBP), home (HBP), or ambulatory BP (ABP) measurements. This analysis investigated the association and agreement between OBP, HBP, and ABP measurements for BPV assessment at baseline and 10 weeks after initiating antihypertensive drug therapy., Methods: Untreated hypertensive patients with elevated BPV were randomized to receive an angiotensin-converting enzyme inhibitor (ramipril) or a calcium channel blocker (nifedipine GITS) in a 10-week, open-label, blinded-end point study. BPV was assessed using standard deviation (SD) and coefficient of variation (CV) (reading-to-reading analyses)., Results: Data from 146 participants from three research centers (Athens/Greece; Milan/Italy; Shanghai/China) were analyzed [mean age 53 ± 10 (SD) years, male individuals 60%, baseline systolic OBP, HBP, and 24 h ABP 144 ± 9, 138 ± 10, and 143 ± 10 mmHg, respectively]. Post-treatment minus pre-treatment systolic CV difference was: OBP: 0.3%, P  = 0.28; HBP: -0.2%, P  = 0.20; 24 h ABP: 1.1%, P  < 0.001. Home and ambulatory (not office) BPV indices presented weak-to-moderate correlation, both before and during treatment (range of coefficients 0.04-0.33). The correlation coefficient between systolic HBP and awake ABP CV was 0.21 and 0.28 before and during treatment, respectively ( P  < 0.05/< 0.001, respectively). Home and ambulatory (not office) BPV indices presented slight-to-fair agreement (range 64-73%) in detecting participants with high systolic BPV (top quartile of respective distributions) both before and during treatment (kappa range 0.04-0.27)., Conclusion: These data showed a weak-to-moderate association between out-of-office (but not office) BPV indices both before and during BP-lowering treatment, with reasonable agreement in detecting individuals with high BPV. Out-of-office BP measurements provide more similar and consistent BPV information than office measurements., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: In China, the prevalence of hypertension is high and the use of combination antihypertensive therapy is low, which contributes to inadequate blood pressure (BP) control. The availability of simplified treatments combining complementary BP-lowering agents may help more patients achieve their goals., Methods: This Phase III, multicenter, randomized, double-blind, noninferiority study included Chinese adults with mild-to-moderate hypertension. Following a 1-month run-in on perindopril/indapamide bi-therapy, patients with uncontrolled systolic/diastolic BP (≥140/90 mmHg) were randomized to perindopril 5 mg/indapamide 1.25 mg/amlodipine 5 mg (Per/Ind/Aml) single-pill combination (SPC) or perindopril 4 mg/indapamide 1.25 mg plus amlodipine 5 mg (Per/Ind + Aml) for 6 months. Uptitration was permitted from month 2 onwards. The primary efficacy objective was the noninferiority of Per/Ind/Aml in lowering office systolic BP at 2 months. The secondary objectives included the effectiveness of SPC on diastolic BP, uptitration efficacy, and office BP control (systolic/diastolic <140/90 mmHg). A subgroup of patients participated in 24-h ambulatory BP monitoring (ABPM)., Results: A total of 532 patients were randomized: Per/Ind/Aml ( n  = 262) and Per/Ind + Aml ( n  = 269). Overall, the mean (±SD) age was 55.7 ± 8.8 years, 60.7% were male, and the mean office systolic/diastolic BP at baseline on Per/Ind was 150.4/97.2 mmHg. Systolic BP decreased in both groups at 2 months from baseline: -14.99 ± 14.46 mmHg Per/Ind/Aml versus -14.49 ± 12.87 mmHg Per/Ind +Aml. A predefined noninferiority margin of 4 mmHg was observed ( P  < 0.001). The effectiveness of the Per/Ind/Aml SPC was also demonstrated for all secondary endpoints. ABPM demonstrated sustained BP control over 24 h. Both treatments were well tolerated., Conclusions: Per/Ind/Aml is an effective substitute for Per/Ind + Aml, providing at least equivalent BP control over 24 h in a single pill, with comparable safety., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Isometric handgrip training (IHT) has been shown to reduce blood pressure (BP) in hypertensive patients. However, factors that predict responsiveness to IHT are largely unknown. The aim of this study was to investigate the patient characteristics associated with the antihypertensive response to IHT using a recommended statistical approach for evaluating interindividual responses., Methods: Data from four randomized controlled trials were combined, totaling 81 patients undergoing IHT (48.8% women; 60 ± 11 years) and 90 control patients (45.6% women; 62 ± 12 years). IHT consisted of 4 × 2 min isometric contractions at 30% of maximal voluntary contraction, performed three times/week for 8-12 weeks. BP was measured at baseline and following IHT and control interventions. The interindividual variation was assessed by the standard deviation of the individual responses (SD ir ), and linear regression analyses were conducted to explore response predictors., Results: IHT significantly decreased both SBP (-5.4; 95% confidence interval (CI) -9.5 to -1.3 mmHg) and DBP (-2.8; 95% CI -5.1 to -0.6 mmHg). The interindividual variation of BP change was moderate for systolic (SD ir  = 5.2 mmHg, 0.30 standardized units) and low for diastolic (SD ir  = 1.7 mmHg, 0.15 standardized units). Sex, age, and BMI were not associated with the antihypertensive effect of IHT. However, a higher baseline SBP ( b  = -0.467, P  < 0.001) and absence of dihydropyridine calcium channel blockers use ( b  = 0.340, P  = 0.001) were associated with greater BP reductions., Conclusion: IHT reduced BP in medicated hypertensive patients regardless of age, sex, and BMI. Patients with a higher baseline SBP and those not prescribed dihydropyridine calcium channel blockers were more responsive to IHT., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Drug allergy and intolerance are increasingly recognized as significant public health concerns, leading to adverse reactions in patients undergoing pharmacological treatments. Multiple drug intolerance syndrome (MDIS), characterized by adverse reactions to at least three different drug classes without a clear immunological mechanism, poses a substantial challenge, particularly in hypertensive patients. Despite its link to suboptimal adherence and uncontrolled blood pressure, MDIS in the context of hypertension remains insufficiently explored. This review synthesizes existing literature on MDIS, emphasizing clinical characteristics, pathogenesis, and psychiatric comorbidity. Furthermore, it delves into MDIS in the context of hypertension, highlighting the importance of a multidisciplinary approach in diagnosis and management, including innovative therapeutic strategies such as novel therapeutic algorithms or renal denervation. The review concludes by emphasizing the necessity for further research and clinical trials to enhance our understanding and address MDIS, especially in hypertensive patients., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adherence to antihypertensives is key for blood pressure control. Most people with hypertension have several comorbidities and require multiple medicines, leading to complex care pathways. Strategies for coordinating medicine use can improve adherence, but cumulative benefits of multiple strategies are unknown., Methods: Using dispensing claims for a 10% sample of eligible Australians, we identified adult users of antihypertensives during July 2018-June 2019 who experienced polypharmacy (≥5 unique medicines). We measured medicine use reflecting coordinated medicine management in 3 months before and including first observed dispensing, including: use of simple regimens for each cardiovascular medicine; prescriber continuity; and coordination of dispensings at the pharmacy. We measured adherence (proportion of days covered) to antihypertensive medicines in the following 12 months, and used logistic regression to assess independent associations and interactions of adherence with these measures of care., Results: We identified 202 708 people, of which two-thirds (66.6%) had simple cardiovascular medicine regimens (one tablet per day for each medicine), two-thirds (63.3%) were prescribed >75% of medicines from the same prescriber, and two-thirds (65.5%) filled >50% of their medicine on the same day. One-third (28.4%) of people experienced all three measures of coordinated care. Although all measures were significantly associated with higher adherence, adherence was greatest among people experiencing all three measures (odds ratio = 1.63; 95% confidence interval: 1.55-1.72). This interaction was driven primarily by effects of prescriber continuity and dispensing coordination., Conclusions: Coordinating both prescribing and dispensing of medicines can improve adherence to antihypertensives, which supports strategies consolidating both prescribing and supply of patients' medicines., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Blood pressure variability (BPV) is a risk factor for poor kidney function independent of blood pressure (BP) in chronic kidney disease (CKD). Little is known about the association between kidney function decline and BPV in hypertensive patients without CKD., Methods: A post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) was performed. BPV was measured as standard deviation (SD) and average real variability (ARV). Cox proportional hazard models were employed to explore the relationship between BPV and incident CKD and albuminuria., Results: A total of 5700 patients were included, with a mean age of 66.4 years old. During a median of 3.29 years follow-up, 150 (2.6%) patients developed CKD and 222 (7.2%) patients developed albuminuria. Patients were divided into four groups according to the quartiles of BPV. Compared with SBPV Q1, the incidence of CKD was higher in SBPV Q2-Q4; hazard ratios and 95% confidence interval were 1.81 (1.07-3.04), 1.85 (1.10-3.12) and 1.90 (1.13-3.19), respectively. The association between incident CKD and albuminuria with DBPV was less significant than SBPV. Similar results were found when measuring BPV as ARV and SD. No interaction was detected in BP-lowering strategy and SBPV on incident CKD and albuminuria ( P  > 0.05)., Conclusion: This study found that BPV was a risk factor for incident CKD and albuminuria in patients without CKD, especially SBPV. Although intensive BP control increased the risk of CKD, the association between SBPV and kidney function decline did not differ between the two treatment groups., Registration: URL: https://clinicaltrials.gov/ , Unique identifier: NCT01206062., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Visit-to-visit blood pressure (BP) variability associates with an increased risk of cardiovascular events. We investigated the role of seasonal BP modifications on the magnitude of BP variability and its impact on cardiovascular risk., Methods: In 25 390 patients included in the ONTARGET and TRANSCEND trials, the on-treatment systolic (S) BP values obtained by five visits during the first two years of the trials were grouped according to the month in which they were obtained. SBP differences between winter and summer months were calculated for BP variability quintiles (Qs), as quantified by the coefficient of variation (CV) of on-treatment mean SBP from the five visits. The relationship of BP variability with the risk of cardiovascular events and mortality was assessed by the Cox regression model., Results: SBP was approximately 4 mmHg lower in summer than in winter regardless of confounders. Winter/summer SBP differences contributed significantly to each SBP-CV quintile. Increase of SBP-CV from Q1 to Q5 was associated with a progressive increase in the adjusted hazard ratio (HR) of the primary endpoint of the trials, i.e. morbid and fatal cardiovascular events. This association was even stronger after removal of the effect of seasonality from the calculation of SBP-CV. A similar trend was observed for secondary endpoints., Conclusions: Winter/summer SBP differences significantly contribute to visit-to-visit BP variability. However, this contribution does not participate in the adverse prognostic significance of visit-to-visit BP variations, which seems to be more evident after removal of the BP effects of seasonality from visit-to-visit BP variations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: We examined haemodynamics, focusing on volume balance and forward and backward wave amplitudes, before and after 2.8 years of targeted treatment of primary aldosteronism. Patients with essential hypertension and normotensive individuals were examined for comparison ( n  = 40 in each group)., Methods: Recordings were performed using radial artery pulse wave analysis and whole-body impedance cardiography. Unilateral aldosteronism was treated with adrenalectomy ( n  = 20), bilateral aldosteronism with spironolactone-based medication ( n  = 20), and essential hypertension with standard antihypertensive agents., Results: Aortic SBP and DBP, forward and backward wave amplitudes, and systemic vascular resistance were equally elevated in primary aldosteronism and essential hypertension. All these haemodynamic variables were similarly reduced by the treatments. Primary aldosteronism presented with 1 litre (∼10%) extracellular water excess ( P  < 0.001) versus the other groups, and this excess was normalized by treatment. Initial pulse wave velocity (PWV) was similarly increased in primary aldosteronism and essential hypertension, but final values remained higher in primary aldosteronism ( P  < 0.001). In regression analyses, significant explanatory factors for treatment-induced forward wave amplitude reduction were decreased systemic vascular resistance ( β  = 0.380) and reduced extracellular water volume ( β  = 0.183). Explanatory factors for backward wave amplitude reduction were changes in forward wave amplitude ( β  = 0.599), heart rate ( β  = -0.427), and PWV ( β  = 0.252)., Conclusion: Compared with essential hypertension, the principal haemodynamic difference in primary aldosteronism was higher volume load. Volume excess elevated forward wave amplitude, which was subsequently reduced by targeted treatment of primary aldosteronism, along with normalization of volume load. We propose that incorporating extracellular water evaluation alongside routine diagnostics could enhance the identification and diagnosis of primary aldosteronism., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: A combination of four ultra-low-dose blood pressure (BP) medications lowered office BP more effectively than initial monotherapy in the QUARTET trial. The effects on average ambulatory BP changes at 12 weeks have not yet been reported in detail., Methods: Adults with hypertension who were untreated or on monotherapy were eligible for participation. Overall, 591 participants were randomized to either the quadpill (irbesartan 37.5 mg, amlodipine 1.25 mg, indapamide 0.625 mg, and bisoprolol 2.5 mg) or monotherapy control (irbesartan 150 mg). The difference in 24-h, daytime, and night-time systolic and diastolic ambulatory BP at 12 weeks along further metrics were predefined secondary outcomes., Results: Of 576 participants, 289 were randomized to the quadpill group and 287 to the monotherapy group. At 12 weeks, mean 24-h ambulatory SBP and DBP were 7.7 [95% confidence interval (95% CI) 9.6-5.8] and 5.3 (95% CI: 6.5-4.1) mmHg lower in the quadpill vs. monotherapy group ( P  < 0.001 for both). Similar reductions in the quadpill group were observed for daytime (8.1/5.7 mmHg lower) and night-time (6.3/4.0 mmHg lower) BP at 12 weeks (all P  < 0.001) compared to monotherapy. The rate of BP control (24-h average BP < 130/80 mmHg) at 12 weeks was higher in the quadpill group (77 vs. 50%; P  < 0.001). The reduction in BP load was also more pronounced with the quadpill., Conclusion: A quadruple quarter-dose combination compared with monotherapy resulted in greater ambulatory BP lowering across the entire 24-h period with higher ambulatory BP control rates and reduced BP variability at 12 weeks. These findings further substantiate the efficacy of an ultra-low-dose quadpill-based BP lowering strategy., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Originally, the beta-blockers were equally ranked alongside the other antihypertensive drug classes. Things changed when two major long-term randomized controlled trials, ASCOT-BPLA and LIFE showed that the patients receiving the beta-blockers based regimes suffered 25-30% more strokes than those receiving a calcium channel blocker based regime or an angiotensin receptor blocker based regime. The inferiority of the beta-blockers at stroke prevention was not due to differences in blood pressure control during the follow-up period in both trials. The 2023 European Society of Hypertension (ESH) guidelines still argue in favour of beta-blockers that their clinical inferiority was simply to lesser blood pressure reduction rather than class effect. The analysis argues that the return of beta-blockers as a first-line option for the management of uncomplicated hypertension by the ESH is a cause for concern and should be reconsidered., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Several recent guidelines have proposed the gradual reduction of antihypertensive drugs for patients with well controlled blood pressure (BP). However, no studies have examined alterations in BP variability (BPV) during the down-titration of antihypertensives. This study aims to investigate changes in home BPV during the down-titration of antihypertensives., Methods: We analyzed 83 hypertensive patients who underwent down-titration of antihypertensives and had available home BP data during the down-titration. Down-titration was performed when home SBP was less than 120 mmHg, regardless of the clinic SBP. Primary exposure variable was the standard deviation (SD) of home BP., Results: Among 83 patients (mean age 66.3 ± 11.9 years; 45.8% men), down-titration led to increase home SBP (from 110.5 to 118.7 mmHg; P  < 0.001), and home DBP (from 68.8 to 72.8 mmHg; P  = 0.001) significantly. There were no significant differences in SDs of SBP [from 6.02 ± 3.79 to 5.76 ± 3.09 in morning, P  = 0.570; from 6.13 ± 3.32 to 6.63 ± 3.70 in evening, P  = 0.077; and from 6.54 (4.80, 8.31) to 6.37 (4.65, 8.76) in home SBP, P  = 0.464] and SDs of DBP during the down-titration of antihypertensive drugs., Conclusion: Down-titration of antihypertensive drugs did not have notable impact on clinic BP and home BPV, while significantly increasing home BP. These findings provide important insights indicating that the potential concern related to an increase in BPV in the planned strategy of reducing antihypertensive drugs is not substantial., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hypertension control is suboptimal globally. Implementing evidence-based, simple, standardized treatment protocols (STPs) has been instrumental in effectively and efficiently improving treatment and control of hypertension. We aimed to identify, characterize, and critically appraise hypertension STPs., Methods: We defined STP as a series of steps for the pharmacological treatment of primary hypertension, with information on target population, BP threshold for treatment initiation, target BP, specific drugs/classes/doses, and follow-up frequency. STPs for adult patients were identified from the websites of relevant health organizations, Google search, and through expert consultations (until July 2023). STPs for secondary, gestational, or malignant hypertension or those that were templates/samples were excluded. Included STPs were critically appraised using HEARTS in the Americas Checklist for hypertension management in primary care and compared with the 2021 WHO hypertension management guideline recommendations., Results: Fifty STPs were identified. All STPs had a stepwise treatment approach, involved guideline-recommended first-line drugs, and 98% consisted of at least four steps. Majority (54%) recommended monotherapy with calcium channel blockers as first-line treatment. Only 44% STPs recommended treatment initiation with combination therapy, and 16% recommended single-pill combinations. Most (62%) had dose-intensification as the second step. Most (74%) STPs did not provide complete dosing information. Only one STP mentioned a target time for achieving BP control. On average, STPs scored a performance of 68% on the HEARTS Checklist., Conclusion: Several STPs are available globally; however, most of them have enormous scope for improvement through interventions aimed at alignment with the latest evidence-based guidelines and multistakeholder engagement., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Hypertension affects 50-90% of kidney transplant recipients and is associated with cardiovascular disease and graft loss. We aimed to evaluate the comparative benefits and harms of blood pressure lowering agents in people with a functioning kidney transplant., Methods: We conducted a systematic review with network meta-analysis of randomized controlled trials (RCTs). We searched MEDLINE, Embase, and CENTRAL through to October 2023. RCTs evaluating blood pressure lowering agents administered for at least 2 weeks in people with a functioning kidney transplant with and without preexisting hypertension were eligible. Two reviewers independently extracted data. The primary outcome was graft loss. Treatment effects were estimated using random effects network meta-analysis, with treatment effects expressed as an odds ratio (OR) for binary outcomes and mean difference (MD) for continuous outcomes together with their 95% confidence interval (CI). Confidence in the evidence was assessed using GRADE for network meta-analysis., Results: Ninety-four studies (7547 adults) were included. Two studies were conducted in children. No blood pressure-lowering agent reduced the risk of graft loss, withdrawal because of adverse events, death, cardiovascular or kidney outcomes compared with placebo/other drug class. Angiotensin-converting enzyme inhibitors and angiotensin receptor blocker therapy may incur greater odds of hyperkalemia compared with calcium channel blockers [odds ratio (OR) 5.48, 95% confidence interval (CI) 2.47-12.16; and OR 8.67, 95% CI 2.65-28.36; low certainty evidence, respectively)., Conclusion: The evidentiary basis for the comparative benefits and safety of blood pressure lowering agents in people with a functioning kidney transplant is limited to guide treatment decision-making., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of Vitamin D supplementation on SBP and DBP levels in individuals with hypertension and hypovitaminosis D. PubMed, Scopus, Web of Science, and SciELO were systematically searched for relevant publications until January 2023. The review has been registered at PROSPERO (CRD42023400035). To compare the effects of vitamin D with placebo, the mean differences with 95% confidence intervals (95% CIs) were pooled based on the random-effects model. Subgroup analyses were performed to identify the source of heterogeneity, and assessment of study quality was conducted using the GRADE approach. Publication bias was evaluated using funnel plots and Egger's tests. In total, 14 randomized controlled trials (RCTs) were included in this systematic review, and 11 trials were selected for meta-analysis. The data showed that Vitamin D significantly decreased SBP levels; however, it did not affect DBP levels. In subgroup analysis, Vitamin D supplementation significantly decreased in SBP in studies involving individuals over 60 years of age, with a dose greater than 400 000 IU, duration greater than 8 weeks, frequency of weekly supplementation in studies conducted in Asia. In addition, subgroup analysis revealed a significant reduction in DBP in the weekly frequency subgroups and in the studies carried out in Asia. This meta-analysis indicated that Vitamin D significantly reduced the SBP in individuals with hypertension and hypovitaminosis D. Further, well designed trials are necessary to validate these results., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The association of hypertension and diabetes mellitus is extremely common, increasing the mortality risk of patients, mainly by cardiovascular causes. Regarding the blood pressure (BP) targets to be achieved, most guidelines suggest levels of 130 mmHg for SBP and of 80 mmHg for DBP. Dietary modifications are quite effective, and many studies suggest that decreasing sodium intake and increasing potassium ingestion are both valuable practices for reducing BP. This can be achieved by stimulating the ingestion of lacteous products, vegetables, and nuts. As for the ideal pharmacologic treatment for hypertension, either calcium channel blockers, diuretics or angiotensin-system blockers can be the first class of drug to be used. In this review, we summarize the evaluation of patients with diabetes mellitus and hypertension, and discuss the available therapeutic approaches, with emphasis on evidence-based dietary recommendations., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hypertension is the leading cardiovascular risk factor worldwide. However, in Japan, only 30% of patients have their blood pressure controlled under 140/90 mmHg, and nonadherence to antihypertensives is thought to be a reason for the poor control of hypertension. We therefore sought to assess the adherence to hypertension treatment and to evaluate factors influencing patients' adherence in a large, representative sample of the Japanese population. To this end, we analyzed claims data from the LIFE Study database, which includes 112 506 Japanese adults with newly diagnosed hypertension. Medication adherence was measured for a year postdiagnosis using the proportion of days covered (PDC) method. Factors associated with adherence to antihypertensives were also assessed. Among the total 112 506 hypertensive patients, the nonadherence rate (PDC ≤ 80%) for antihypertensives during the first year after initiation of the treatment was 26.2%. Younger age [31-35 years: odds ratio (OR), 0.15; 95% confidence interval (95% CI), 0.12-0.19 compared with 71-74-year-old patients], male gender, monotherapy, and diuretics use [OR, 0.87; 95% CI, 0.82-0.91 compared with angiotensin II receptor blockers (ARBs)] were associated with poor adherence in the present study. Cancer comorbidity (OR, 0.84; 95% CI, 0.79-0.91 compared with no comorbidity), prescription at a hospital, and living in a medium-sized to regional city were also associated with poor adherence. Our present findings showing the current status of adherence to antihypertensive medications and its associated factors using claims data in Japan should help to improve adherence to antihypertensives and blood pressure control., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: Statins appear to have greater antihypertensive effects in observational studies than in randomized controlled trials. This study assessed whether more frequent treatment of hypertension contributed to better blood pressure (BP, mmHg) control in statin-treated than statin-eligible untreated adults in observational studies., Methods: National Health and Nutrition Examination Surveys 2009-2020 data were analyzed for adults 21-75 years ( N  = 3814) with hypertension (BP ≥140/≥90 or treatment). The 2013 American College of Cardiology/American Heart Association Cholesterol Guideline defined statin eligibility. The main analysis compared BP values and hypertension awareness, treatment, and control in statin-treated and statin-eligible but untreated adults. Multivariable logistic regression was used to assess the association of statin therapy to hypertension control and the contribution of antihypertensive therapy to that relationship., Results: Among adults with hypertension in 2009-2020, 30.3% were not statin-eligible, 36.9% were on statins, and 32.8% were statin-eligible but not on statins. Statin-treated adults were more likely to be aware of (93.4 vs. 80.6%) and treated (91.4 vs. 70.7%) for hypertension than statin-eligible adults not on statins. The statin-treated group had 8.3 mmHg lower SBP (130.3 vs. 138.6), and 22.8% greater control (<140/<90: 69.0 vs. 46.2%; all P values <0.001). The association between statin therapy and hypertension control [odds ratio 1.94 (95% confidence interval 1.53-2.47)] in multivariable logistic regression was not significant after also controlling for antihypertensive therapy [1.29 (0.96-1.73)]., Conclusion: Among adults with hypertension, statin-treated adults have lower BP and better control than statin-eligible untreated adults, which largely reflects differences in antihypertensive therapy., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The risk of cardiovascular disease (CVD) mortality in individuals with an alerting reaction, assessed by hypertension in the first blood pressure (BP) reading but normal BP in further readings, remains unknown in the general population., Methods and Results: In a sample of 11 146 adults (51.5% men and 48.5% women) with a mean age of 47.1 years (SD ± 12.3) from a German population-based cohort, we analyzed risk factors and CVD mortality risk associated with an alerting reaction. An alerting reaction was prevalent in 10.2% of the population and associated with sociodemographic, lifestyle, and somatic CVD risk factors. Within a mean follow-up period of 22.7 years (SD ± 7.05 years; max: 32 years; 253 201 person years), 1420 (12.7%) CVD mortality cases were observed. The CVD mortality rate associated with an alerting reaction was significantly higher than in normotension (64 vs. 32 cases/10 000 person-years), but lower than hypertension (118 cases/10 000 person-years). Correspondingly, the alerting reaction was associated with a 23% higher hazard ratio of CVD mortality than normal blood pressure [hazard ratio 1.23 (95% confidence interval 1.02-1.49), P  = 0.04]. However, adjustment for antihypertensive medication use attenuated this association [1.19 (0.99-1.44), P  = 0.06]., Conclusion: The results may warrant monitoring of an alerting reaction as a preventive measure of CVD mortality in untreated individuals with elevated first BP readings, as well as optimized treatment in treated individuals., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The proliferation, migration and phenotypic transformation of vascular smooth muscle cells contribute to vascular remodeling and hypertension. Resolvin D1 (RvD1) is a specialized pro-resolving lipid mediator that has been shown to have anti-inflammatory effects and can protect against different cardiovascular diseases. However, the role and mechanism of RvD1 in hypertension are not clear. The current study investigated the role of RvD1 in Ang II-induced hypertensive mice and Ang II-stimulated rat vascular smooth muscle cells. The results showed that RvD1 treatment significantly attenuated hypertension and vascular remodeling, as indicated by decreases in blood pressure, aortic media thickness and collagen deposition. In addition, RvD1 inhibited the proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) in vivo and in vitro . Notably, the protective effects of RvD1 were mediated by the Ras homolog gene family member A (RhoA)/mitogen-activated protein kinase (MAPK) signaling pathway. In conclusion, our findings demonstrated the potential benefits of RvD1 as a promising therapeutic agent in the treatment of vascular remodeling and hypertension., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: To estimate the national prevalence of chlorthalidone and hydrochlorothiazide use among adults diagnosed with hypertension by sociodemographic subgroup, healthcare access status, and clinical factors., Methods: Data was extracted from the National Health and Nutrition Examination Survey for 2009-2010 through 2017-2018 survey waves. Patients at least 20 years old, diagnosed with hypertension, and on hydrochlorothiazide or chlorthalidone were included. Uni-variable logistic regression models estimated the odds of being on chlorthalidone compared with hydrochlorothiazide use by sociodemographic and clinical factors. Analyses were adjusted for multi-stage complex survey design and are nationally representative., Results: Two thousand five hundred and eighty-five participants were included with 95.2% participants using hydrochlorothiazide and 4.8% using chlorthalidone. Participants over 65 years were more likely to be on chlorthalidone compared with younger counterparts [odds ratio (OR) 1.8; 95% confidence interval (CI) 1.12-2.88]. Participants with hypokalemia (OR 2.62; 95% CI 1.56-4.42) or hyponatremia [OR 2.298; 95% CI 1.23-4.30) were more likely to be using chlorthalidone compared with patients with normal levels., Conclusion: Chlorthalidone, a potent and effective first-line antihypertensive agent and thoroughly studied thiazide diuretic with substantial cardiovascular benefits, continues to be underutilized in patients with hypertension. Findings demonstrated that individuals receiving chlorthalidone were more likely to be 65 years or older and to experience hyponatremia or hypokalemia. Sociodemographic factors, healthcare access and use, clinical factors, and medical conditions did not appear to sway the choice in thiazide diuretic use., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: Whether bedtime versus morning administration of antihypertensive therapy is beneficial on outcomes is controversial. We evaluated the risk of total and cardiovascular mortality in a very large observational cohort of treated hypertensive patients, according to the timing of their usual treatment administration (morning versus evening)., Methods: Vital status and cause of death were obtained from death certificates of 28 406 treated hypertensive patients (mean age 62 years, 53% male individuals), enrolled in the Spanish Ambulatory Blood Pressure Monitoring (ABPM) Registry between 2004 and 2014. Among the 28 406 patients, most (86%) received their medication exclusively in the morning; whilst 13% were treated exclusively in the evening or at bedtime. Follow-up was for a median of 9.7 years and 4345 deaths occurred, of which 1478 were cardiovascular deaths., Results: Using Cox-models adjusted for clinical confounders and 24-h SBP, and compared with patients treated in the morning (reference group), all-cause mortality [hazard ratio 1.01; 95% CI 0.93-1.09) and cardiovascular mortality (hazard ratio 1.04; 95% CI 0.91-1.19) was not significantly different in those receiving evening medication dosing. The results were consistent in all the subgroups of patients analysed., Conclusion: In this very large observational study, morning versus bedtime dosing of antihypertensive medication made no difference to the subsequent risk of all-cause or cardiovascular mortality. These findings are in accordance with results from a recent randomized controlled trial and do not support the hypothesis of a specific beneficial effect of night-time antihypertensive treatment dosing on risk of all-cause or cardiovascular death., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: We report data regarding systolic BP monitoring in children aged <5 years performed over a 2-week period by parents at home using a hand-held doppler device and aneroid sphygmomanometer for SBP measurements (HDBPM). Our objectives were to compare health professional measured office systolic BP by doppler device (Office-SBP Doppler ) with parent measured home systolic BP using the same doppler device (Home-SBP Doppler ). We also report data evaluating reliability and optimal number of days of measurement required., Design and Methods: We taught parents to measure systolic BP and assessed their technique using a hand-held doppler device and aneroid sphygmomanometer. We requested parents to perform three consecutive BP measurements twice daily (ideally morning and evening around similar times) when the child was awake, settled and cooperative., Results: Over a 3-year period, data from 48 of 62 children who underwent HDBPM measurements were evaluated with median (IQR) age of 1.9 (0.9, 3.6) years, 27 (56%) boys and 14 (29%) on antihypertensive medication. Office-SBP Doppler was 2.9 ± 8.9 mmHg [95% confidence interval (CI), -14.4 to 20.4, P  = 0.026] higher than Home-SBP Doppler . Mean Home-SBP Doppler between Week-1 and Week-2 monitoring was similar -0.45 ± 3.5 mmHg (95% CI, -7.35 to 6.45, P  = 0.41). Morning HDBPM measurements were lower than evening with a mean difference of -2.77 ± 3.92 mmHg, P  < 0.001). Over Week-1, mean Home-SBP Doppler was closer to mean Office-SBP Doppler with increasing cumulative days of monitoring and with smaller standard deviations suggesting that readings become more reliable from day 4 onwards., Conclusions: HDBPM is a reliable method for measuring systolic BP in young children with BP levels measured by parents comparable to those performed by health professional in clinic. HDBPM technique described here and performed by parents over a 7-day period with a minimum of 4-days, offers a reliable and reproducible technique to measure blood pressure at home., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Prior studies have shown that treatment intensification for patients presenting with uncontrolled hypertension (HTN) rarely occurs, even during visits to the patient's own primary care physicians (PCPs). In this article, we identified predictors of treatment intensification for uncontrolled HTN., Methods: We conducted a cross-sectional study using nationally representative survey data on visits by patients aged 18 or above with uncontrolled HTN, defined as a recorded SBP at least 140 and/or a DBP at least 90 using data from the National Ambulatory Medical Care Survey (NAMCS) 2008-2018. Our outcome is treatment intensification defined as the addition of a new blood pressure medication., Results: We analyzed 22 559 visits to PCPs where uncontrolled HTN was noted, representing 801 023 786 visits nationally. Among these encounters, 2138 (10.3%) of the visits resulted in treatment intensification. Visits with the patient's own PCP had higher rates of treatment intensification than visits to another PCP (10.8 vs. 5.9%, P  < 0.0001). Visits for patients previously on antihypertensive medications had lower rates of treatment intensification (11% for no medications, 10.4% for one medication, 6.6% for ≥2 medications, P  < 0.0001), but there were no statistically significant differences in rates of intensification for those with relevant comorbidities (9.4% for no chronic conditions, 10.8% for one to two chronic conditions, 8.9% for at least three chronic conditions, P  = 0.12). Multivariable adjusted results were similar to the unadjusted findings., Conclusion: Visits for patients with uncontrolled HTN rarely result in treatment intensification. Substantial opportunity exists to improve management of HTN, particularly for patients on fewer medications or seen by a covering provider., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: In healthy older adults, the relationship between long-term, visit-to-visit variability in blood pressure (BP) and frailty is uncertain., Methods: Secondary analysis of blood pressure variability (BPV) and incident frailty in >13 000 participants ≥65-70 years enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) trial and its observational follow-up (ASPREE-XT). Participants were without dementia, physical disability, or cardiovascular disease at baseline. BPV was estimated using standard deviation of mean BP from three annual visits (baseline through the second annual follow-up). Frailty was defined using Fried phenotype and a frailty deficit accumulation index (FDAI). Participants with frailty during the BPV estimation period were excluded from the main analysis. Adjusted Cox proportional hazards regression evaluated the association between BPV and incident frailty, and linear mixed models for change in frailty scores, through a maximum of 9 years of follow-up., Results: Participants in the highest systolic BPV tertile were at higher risk of frailty compared to those in the lowest (referent) tertile of systolic BPV [Fried hazard ratio (HR) 1.17, 95% confidence interval (CI) 1.04-1.31; FDAI HR 1.18, 95% CI 1.07-1.30]. Findings were consistent when adjusted for multiple covariates and when stratified by antihypertensive use. Linear mixed models showed that higher systolic BPV was associated with increasing frailty score over time. Diastolic BPV was not consistently associated., Conclusions: High systolic BPV, independent of mean BP, is associated with increased risk of frailty in healthy older adults. Variability of BP across visits, even in healthy older adults, can convey important risk information beyond mean BP., Trial Registration: ClinicalTrials.gov NCT01038583 and ISRCTN83772183., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: In any treated hypertensive patient office blood pressure (BP) values may differ between visits and this variability (V) has an adverse prognostic impact. However, little information is available on visit-to-visit 24-h BPV., Methods: In 1114 hypertensives of the ELSA and PHYLLIS trials we compared visit-to-visit office and 24-h mean BPV by coefficient of variation (CV) of the mean systolic (S) and diastolic (D) BP obtained from yearly measurements during a 3-4 year treatment period. Visit-to-visit BPV during daytime and night-time were also compared., Results: Twenty-four-hour SBP-CV was about 20% less than office SBP-CV ( P  < 0.0001). SBP-CV was considerably greater for the night-time than for the daytime period (20%, P  < 0.0001). Results were similar for DBP and in males and females, older and younger patients, patients under different antihypertensive drugs or with different baseline or achieved BP values. In the group as a whole and in subgroups there was significant correlations between office and 24-h BP-CV but the correlation coefficients was weak, indicating that office SBP or DBP CV accounted for only about 1-4% of 24-h SBP or DBP-CV values., Conclusion: Twenty-four-hour mean BP across visits is more stable than across visit office BP. Visit-to-visit office and 24-h BPV are significantly related to each other, but correlation coefficients are low, making visit-to-visit office BP variations poorly predictive of the concomitant 24-h BP variations and thus of on-treatment ambulatory BP stability., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)