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Chlorthalidone vs. Hydrochlorothiazide for Hypertension–Cardiovascular Events

Author/s: 
Ishani, A., Cushman, W. C., Leatherman, S. M., R. A., Woods, P., Glassman, P. A., Taylor, A. A., Hau, C., Klint, A., Huang, G. D., Brophy, M. T., Fiore, L. D., Ferguson, R. E., Diuretic Comparison Project Writing Group

Background: Whether chlorthalidone is superior to hydrochlorothiazide for preventing major adverse cardiovascular events in patients with hypertension is unclear.

Methods: In a pragmatic trial, we randomly assigned adults 65 years of age or older who were patients in the Department of Veterans Affairs health system and had been receiving hydrochlorothiazide at a daily dose of 25 or 50 mg to continue therapy with hydrochlorothiazide or to switch to chlorthalidone at a daily dose of 12.5 or 25 mg. The primary outcome was a composite of nonfatal myocardial infarction, stroke, heart failure resulting in hospitalization, urgent coronary revascularization for unstable angina, and non-cancer-related death. Safety was also assessed.

Results: A total of 13,523 patients underwent randomization. The mean age was 72 years. At baseline, hydrochlorothiazide at a dose of 25 mg per day had been prescribed in 12,781 patients (94.5%). The mean baseline systolic blood pressure in each group was 139 mm Hg. At a median follow-up of 2.4 years, there was little difference in the occurrence of primary-outcome events between the chlorthalidone group (702 patients [10.4%]) and the hydrochlorothiazide group (675 patients [10.0%]) (hazard ratio, 1.04; 95% confidence interval, 0.94 to 1.16; P = 0.45). There were no between-group differences in the occurrence of any of the components of the primary outcome. The incidence of hypokalemia was higher in the chlorthalidone group than in the hydrochlorothiazide group (6.0% vs. 4.4%, P<0.001).

Conclusions: In this large pragmatic trial of thiazide diuretics at doses commonly used in clinical practice, patients who received chlorthalidone did not have a lower occurrence of major cardiovascular outcome events or non-cancer-related deaths than patients who received hydrochlorothiazide. (Funded by the Veterans Affairs Cooperative Studies Program; ClinicalTrials.gov number, NCT02185417.).

Keywords 
hypertension cardiovascular events heart failure veterans infarction

Effects of salt substitutes on clinical outcomes: a systematic review and meta-analysis

Author/s: 
Yin, X., Rodgers, A., Perkovic, A., Huang, L., Li, K., Yu, J., Wu, Y., Wu, J. H. Y., Marklund, M., Huffman, M. D., Miranda, J. J., Di Tanna, G. L., Labarthe, D., Elliott, P., Tian, M., Neal, B.

Objectives The Salt Substitute and Stroke Study (SSaSS) recently reported blood pressure-mediated benefits of a potassium-enriched salt substitute on cardiovascular outcomes and death. This study assessed the effects of salt substitutes on a breadth of outcomes to quantify the consistency of the findings and understand the likely generalisability of the SSaSS results.

Methods We searched PubMed, Embase and the Cochrane Library up to 31 August 2021. Parallel group, step-wedge or cluster randomised controlled trials reporting the effect of salt substitute on blood pressure or clinical outcomes were included. Meta-analyses and metaregressions were used to define the consistency of findings across trials, geographies and patient groups.

Results There were 21 trials and 31 949 participants included, with 19 reporting effects on blood pressure and 5 reporting effects on clinical outcomes. Overall reduction of systolic blood pressure (SBP) was −4.61 mm Hg (95% CI −6.07 to −3.14) and of diastolic blood pressure (DBP) was −1.61 mm Hg (95% CI −2.42 to −0.79). Reductions in blood pressure appeared to be consistent across geographical regions and population subgroups defined by age, sex, history of hypertension, body mass index, baseline blood pressure, baseline 24-hour urinary sodium and baseline 24-hour urinary potassium (all p homogeneity >0.05). Metaregression showed that each 10% lower proportion of sodium choloride in the salt substitute was associated with a −1.53 mm Hg (95% CI −3.02 to −0.03, p=0.045) greater reduction in SBP and a −0.95 mm Hg (95% CI −1.78 to −0.12, p=0.025) greater reduction in DBP. There were clear protective effects of salt substitute on total mortality (risk ratio (RR) 0.89, 95% CI 0.85 to 0.94), cardiovascular mortality (RR 0.87, 95% CI 0. 81 to 0.94) and cardiovascular events (RR 0.89, 95% CI 0.85 to 0.94).

Conclusions The beneficial effects of salt substitutes on blood pressure across geographies and populations were consistent. Blood pressure-mediated protective effects on clinical outcomes are likely to be generalisable across population subgroups and to countries worldwide.

Keywords 
hypertension meta-analysis stroke Salt Substitutes blood pressure

Screening for Hypertension in Adults

Author/s: 
U.S. Preventative Services Task Force

IMPORTANCE Hypertension is a prevalent condition that affects approximately 45% of the adult US population and is the most commonly diagnosed condition at outpatient office visits. Hypertension is a major contributing risk factor for heart failure, myocardial infarction, stroke, and chronic kidney disease. OBJECTIVE To reaffirm its 2015 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of screening for hypertension in adults, the accuracy of office blood pressure measurement for initial screening, and the accuracy of various confirmatory blood pressure measurement methods. POPULATION Adults 18 years or older without known hypertension. EVIDENCE ASSESSMENT Using a reaffirmation deliberation process, the USPSTF concludes with high certainty that screening for hypertension in adults has substantial net benefit. RECOMMENDATION The USPSTF recommends screening for hypertension in adults 18 years or older with office blood pressure measurement. The USPSTF recommends obtaining blood pressure measurements outside of the clinical setting for diagnostic confirmation before starting treatment. (A recommendation)

Keywords 
hypertension heart failure myocardial infarction chronic kidney disease

The Unrecognized Prevalence of Primary Aldosteronism

Author/s: 
Brown, JM, Siddiqui, M, Calhoun, DA, Carey, RM, Hopkins, PN, Williams, GH, Vaidya, A

Background:

Primary aldosteronism is a nonsuppressible renin-independent aldosterone production that causes hypertension and cardiovascular disease.

 

Objective:

To characterize the prevalence of nonsuppressible renin-independent aldosterone production, as well as biochemically overt primary aldosteronism, in relation to blood pressure.

 

Design:

Cross-sectional study.

 

Setting:

4 U.S. academic medical centers.

 

Participants:

Participants with normotension (n = 289), stage 1 hypertension (n = 115), stage 2 hypertension (n = 203), and resistant hypertension (n = 408).

 

Measurements:

Participants completed an oral sodium suppression test, regardless of aldosterone or renin levels, as a confirmatory diagnostic for primary aldosteronism and to quantify the magnitude of renin-independent aldosterone production. Urinary aldosterone was measured in participants in high sodium balance with suppressed renin activity. Biochemically overt primary aldosteronism was diagnosed when urinary aldosterone levels were higher than 12 µg/24 h.

 

Results:

Every blood pressure category had a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher blood pressure, kaliuresis, and lower serum potassium levels. Mean adjusted levels of urinary aldosterone were 6.5 µg/24 h (95% CI, 5.2 to 7.7 µg/24 h) in normotension, 7.3 µg/24 h (CI, 5.6 to 8.9 µg/24 h) in stage 1 hypertension, 9.5 µg/24 h (CI, 8.2 to 10.8 µg/24 h) in stage 2 hypertension, and 14.6 µg/24 h (CI, 12.9 to 16.2 µg/24 h) in resistant hypertension; corresponding adjusted prevalence estimates for biochemically overt primary aldosteronism were 11.3% (CI, 5.9% to 16.8%), 15.7% (CI, 8.6% to 22.9%), 21.6% (CI, 16.1% to 27.0%), and 22.0% (CI, 17.2% to 26.8%). The aldosterone–renin ratio had poor sensitivity and negative predictive value for detecting biochemically overt primary aldosteronism.

 

Limitation:

Prevalence estimates rely on arbitrary and conventional thresholds, and the study population may not represent nationwide demographics.

 

Conclusion:

The prevalence of primary aldosteronism is high and largely unrecognized. Beyond this categorical definition of primary aldosteronism, there is a prevalent continuum of renin-independent aldosterone production that parallels the severity of hypertension. These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of “essential” hypertension.

 

Primary Funding Source:

National Institutes of Health.

Keywords 
primary aldosteronism hypertension cardiovascular disease

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial

Author/s: 
Hermida, R.C., Crespo, J.J., Domínguez-Sardiña, M, Otero, A., Moyá, A., Ríos, M.T., Sineiro, E., Castiñeira, M.C., Callejas, P.A., Pousa, L., Salgado, J.L., Durán, C., Sánchez, J.J., Fernández, J.R., Mojón, A., Ayala, D.E., Hygia Project Investigators

AIMS:

The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.

METHODS AND RESULTS:

In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].

CONCLUSION:

Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

TRIAL REGISTRATION:

ClinicalTrials.gov, number NCT00741585.

Keywords 
antihypertensives blood pressure hypertension medication

Yoga as Antihypertensive Lifestyle Therapy: A Systematic Review and Meta-analysis

Author/s: 
Wu, Yin, Johnson, Blair T., Acabchuk, Rebecca L., Chen, Shiqi, Lewis, Holly K., Livingston, Jill, Park, Crystal L., Pescatello, Linda S.

OBJECTIVE:

To investigate the efficacy of yoga as antihypertensive lifestyle therapy and identify moderators that account for variability in the blood pressure (BP) response to yoga.

METHODS:

We systematically searched 6 electronic databases from inception through June 4, 2018, for articles published in English language journals on trials of yoga interventions that involved adult participants, reported preintervention and postintervention BP, and had a nonexercise/nondiet control group. Our search yielded 49 qualifying controlled trials (56 interventions). We (1) evaluated the risk of bias and methodological study quality, (2) performed meta-regression analysis following random-effects assumptions, and (3) generated additive models that represented the largest possible clinically relevant BP reductions.

RESULTS:

On average, the 3517 trial participants were middle-aged (49.2±19.5 years), overweight (27.9±3.6 kg/m2) adults with high BP (systolic BP, 129.3±13.3 mm Hg; diastolic BP, 80.7±8.4 mm Hg). Yoga was practiced 4.8±3.4 sessions per week for 59.2±25.0 minutes per session for 13.2±7.5 weeks. On average, yoga elicited moderate reductions in systolic BP (weighted mean effect size, -0.47; 95% CI, -0.62-0.32, -5.0 mm Hg) and diastolic BP (weighted mean effect size, -0.47; 95% CI, -0.61 to -0.32; -3.9 mm Hg) compared with controls (P<.001 for both systolic BP and diastolic BP). Controlling for publication bias and methodological study quality, when yoga was practiced 3 sessions per week among samples with hypertension, yoga interventions that included breathing techniques and meditation/mental relaxation elicited BP reductions of 11/6 mm Hg compared with those that did not (ie, 6/3 mm Hg).

CONCLUSION:

Our results indicate that yoga is a viable antihypertensive lifestyle therapy that produces the greatest BP benefits when breathing techniques and meditation/mental relaxation are included.

Keywords 
yoga hypertension blood pressure mindfulness meditation

Association Between Use of Sodium-Glucose Cotransporter 2 Inhibitors, Glucagon-like Peptide 1 Agonists, and Dipeptidyl Peptidase 4 Inhibitors With All-Cause Mortality in Patients With Type 2 Diabetes

Author/s: 
Zheng, Sean L., Roddick, Alistair J., Aghar-Jaffar, Rochan, Shun-Shin, Matthew J., Francis, Darrel, Oliver, Nick, Meeran, Karim

IMPORTANCE:

The comparative clinical efficacy of sodium-glucose cotransporter 2 (SGLT-2) inhibitors, glucagon-like peptide 1 (GLP-1) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors for treatment of type 2 diabetes is unknown.

OBJECTIVE:

To compare the efficacies of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on mortality and cardiovascular end points using network meta-analysis.

DATA SOURCES:

MEDLINE, Embase, Cochrane Library Central Register of Controlled Trials, and published meta-analyses from inception through October 11, 2017.

STUDY SELECTION:

Randomized clinical trials enrolling participants with type 2 diabetes and a follow-up of at least 12 weeks were included, for which SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors were compared with either each other or placebo or no treatment.

DATA EXTRACTION AND SYNTHESIS:

Data were screened by 1 investigator and extracted in duplicate by 2 investigators. A Bayesian hierarchical network meta-analysis was performed.

MAIN OUTCOMES AND MEASURES:

The primary outcome: all-cause mortality; secondary outcomes: cardiovascular (CV) mortality, heart failure (HF) events, myocardial infarction (MI), unstable angina, and stroke; safety end points: adverse events and hypoglycemia.

RESULTS:

This network meta-analysis of 236 trials randomizing 176 310 participants found SGLT-2 inhibitors (absolute risk difference [RD], -1.0%; hazard ratio [HR], 0.80 [95% credible interval {CrI}, 0.71 to 0.89]) and GLP-1 agonists (absolute RD, -0.6%; HR, 0.88 [95% CrI, 0.81 to 0.94]) were associated with significantly lower all-cause mortality than the control groups. SGLT-2 inhibitors (absolute RD, -0.9%; HR, 0.78 [95% CrI, 0.68 to 0.90]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.86 [95% CrI, 0.77 to 0.96]) were associated with lower mortality than were DPP-4 inhibitors. DPP-4 inhibitors were not significantly associated with lower all-cause mortality (absolute RD, 0.1%; HR, 1.02 [95% CrI, 0.94 to 1.11]) than were the control groups. SGLT-2 inhibitors (absolute RD, -0.8%; HR, 0.79 [95% CrI, 0.69 to 0.91]) and GLP-1 agonists (absolute RD, -0.5%; HR, 0.85 [95% CrI, 0.77 to 0.94]) were significantly associated with lower CV mortality than were the control groups. SGLT-2 inhibitors were significantly associated with lower rates of HF events (absolute RD, -1.1%; HR, 0.62 [95% CrI, 0.54 to 0.72]) and MI (absolute RD, -0.6%; HR, 0.86 [95% CrI, 0.77 to 0.97]) than were the control groups. GLP-1 agonists were associated with a higher risk of adverse events leading to trial withdrawal than were SGLT-2 inhibitors (absolute RD, 5.8%; HR, 1.80 [95% CrI, 1.44 to 2.25]) and DPP-4 inhibitors (absolute RD, 3.1%; HR, 1.93 [95% CrI, 1.59 to 2.35]).

CONCLUSIONS AND RELEVANCE:

In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

Keywords 
SGLT-2 inhibitors GLP-1 agonists hypertension

2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task F

Author/s: 
Whelton, Paul K., Aronow, Wilbert S., Casey, Donald E., Jr., Collins, Karen J., Himmelfarb, Charyl Dennison, DePalma, Sondra M., Gidding, Samuel, Jamerson, Kenneth A., Jones, Daniel W., MacLaughlin, Eric J., Muntner, Paul, Ovbiagele, Bruce, Smith, Sidney C., Jr., Spencer, Crystal C., Stafford, Randall S., Taler, Sandra J., Thomas, Randal J., Williams, Kim A., Williamson, Jeff D., Wright, Jackson T., Jr.

Preamble

Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory Council recommended that the NHLBI focus specifically on reviewing the highest-quality evidence and partner with other organizations to develop recommendations.P-1,P-2 Accordingly, the ACC and AHA collaborated with the NHLBI and stakeholder and professional organizations to complete and publish 4 guidelines (on assessment of cardiovascular risk, lifestyle modifications to reduce cardiovascular risk, management of blood cholesterol in adults, and management of overweight and obesity in adults) to make them available to the widest possible constituency. In 2014, the ACC and AHA, in partnership with several other professional societies, initiated a guideline on the prevention, detection, evaluation, and management of high blood pressure (BP) in adults. Under the management of the ACC/ AHA Task Force, a Prevention Subcommittee was appointed to help guide development of the suite of guidelines on prevention of cardiovascular disease (CVD). These guidelines, which are based on systematic methods to evaluate and classify evidence, provide a cornerstone for quality cardiovascular care. The ACC and AHA sponsor the development and publication of guidelines without commercial support, and members of each organization volunteer their time to the writing and review efforts. Guidelines are official policy of the ACC and AHA.

Keywords 
hypertension
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