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In modern clinical practice, less than half of patients with new-onset heart failure (HF) undergo ischemic evaluation and only a minority undergo revascularization. We aimed to assess the proportion of the effect of hypertension (antihypertensive treatment) on incident HF to be eliminated by prevention of coronary heart disease (CHD) event treated with or without revascularization, considering possible treatment-mediator interaction. The causal mediation analysis of Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) included 42,418 participants (age 66.9 ± 7.7, 35.6% black, 53.2% men). A new CHD event (myocardial infarction or angina) that occurred after randomization but before the incident HF outcome was the mediator. Incident symptomatic congestive HF (CHF) and hospitalized/fatal HF (HHF) were the primary and secondary outcomes, respectively. Logistic regression (for mediator) and Cox proportional hazards regression (for outcome) were adjusted for demographics, cardiovascular disease history, and risk factors. During a median 4.5-year follow-up, 2,785 patients developed CHF, including 2,216 HHF events. Participants who developed CHD events had twice the higher incidence rate of CHF than CHD-free (28.5 vs 13.9 events/1,000 person-years). The proportion of reference interaction indicating direct harm because of a CHD event for lisinopril (234% for CHF, 355% for HHF) and amlodipine (244% for CHF, 468% for HHF) was greater than for chlortalidone (143% for CHF, 269% for HHF). In patients with revascularized CHD events, chlortalidone and amlodipine eliminated 21% to 24% and lisinopril eliminated -45% of HHF. Antihypertensive treatment could not eliminate harm from CHD events treated without revascularization. In conclusion, the antihypertensive drugs (chlortalidone, lisinopril, and amlodipine) prevent HF not principally by preventing CHD events but by way of other pathways. HF is moderated but not mediated by CHD events. Revascularization of CHD events is paramount for HF prevention., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: High fruit and vegetable diets are associated with reduced chronic kidney disease and cardiovascular disease but are infrequently used in hypertension treatment. Low acid diets are also associated with reduced chronic kidney disease and cardiovascular disease, and fruits and vegetables or oral sodium bicarbonate (NaHCO 3 ) lowers dietary acid., Methods: We randomized 153 hypertensive macroalbuminuric patients receiving pharmacologic chronic kidney disease and cardiovascular disease protection to get fruits and vegetables, oral NaHCO 3 , or Usual Care. We assessed the course of kidney disease progression and cardiovascular disease risk indices over five years., Results: Chronic kidney disease progression was slower in participants receiving fruits and vegetables or oral NaHCO 3 than Usual Care [mean (SE)] [-1.08 (0.06) and -1.17 (0.07) vs. -1.94 (0.11) mL/min/1.73m 2 / year, respectively, P's< .001). Yet, systolic blood pressure was lower, and cardiovascular disease risk indices improved more in participants receiving fruits and vegetables than in those receiving NaHCO 3 or Usual Care. These cardiovascular benefits of fruits and vegetables were achieved despite lower doses of pharmacologic chronic kidney disease and cardiovascular disease protection., Conclusion: The trial supports fruits and vegetables as foundational hypertension treatment to reduce chronic kidney disease progression and cardiovascular disease risk., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The purpose of this research was to assess overall medication adherence as an indicator for emergency room (ER) visits, hospitalizations, and mortality among elderly patients., Methods: The study included individuals aged 75-90 years, diagnosed with diabetes or hypertension, who were treated with at least 1 antihypertensive, or antidiabetic medication in 2017. We determined personal adherence rates by calculating the mean adherence rates of the medications prescribed to each individual. We retrieved information on all ER visits and hospitalizations in internal medicine and surgical wards from 2017 to 2019 and mortality in 2019., Results: Of the 171,097 individuals included in the study, 60% were women. The mean age was 81.2 years. 93% had hypertension, 46% had diabetes, and 39% had both diabetes and hypertension. In 2017, 61,668 (36.0%) patients visited the ER, 44,910 (26.2%) were hospitalized in internal medicine wards, and 13,305 (7.8%) were hospitalized in surgical wards. Comparing the highest adherence quintile to the lowest, ORs were 0.69 (0.63, 0.76) for ER visits, 0.40 (0.36, 0.45) for hospitalization in internal medicine wards, and 0.61 (0.52, 0.72) for hospitalization in surgery wards. ORs were similar for the 3 consecutive years 2017, 2018, and 2019. The adjusted OR for all-cause mortality in 2019 comparing the highest adherence quintile to the lowest was 0.60 (0.54, 0.66)., Conclusions: Better medication adherence was associated with fewer ER visits and hospitalizations among elderly patients with diabetes and hypertension and lower mortality rates. Overall medication adherence is an indicator for health outcomes unrelated to the patient's underlying health status., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Serial blood pressure and heart rate measurements, particularly obtained by the patients at home, are currently recommended for the management of patients., Methods: Home blood pressure and heart rate measurements were obtained by an 81-year old husband and his 74-year old wife in the morning and evening, over the course of an entire month., Results: Morning and evening systolic blood pressure (129.9 ± 5.5, 125.9 ± 10.2, respectively), and diastolic blood pressure (69.2 ± 4.0, 70.1 ± 5.3) were not different (P > .05), heart rate (61.2 ± 2.9, 69.0 ± 5.5) was higher in the evening (P = .00001) in the husband, while systolic blood pressure (134.7 ± 9.6, 119.0 ± 12.0) and diastolic blood pressure (78.6 ± 5.6, 72.1 ± 7.3) were higher in the morning (P = .00001, P = .00031), and heart rate (62.7 ± 4.7, 68.2 ± 4.6) was higher in the evening (P = .00017) in the wife., Conclusions: Patient-generated serial home blood pressure and heart rate logs provide essential data for the patients' management and could potentially be useful in research; circadian variation of blood pressure and heart rate calls for implementation of chronotherapeutic principles for the time of drug administration., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: This study aimed to evaluate the efficacy and tolerability of irbesartan (IRB) and amlodipine (AML) combination therapy in patients with essential hypertension whose blood pressure (BP) was not controlled by IRB monotherapy., Methods: Two multicenter, randomized, double-blind, placebo-controlled, phase III studies were conducted in Korea (the I-DUO 301 study and the I-DUO 302 study). After a 4-week run-in period with either 150 mg IRB (I-DUO 301 study) or 300 mg IRB (I-DUO 302 study), patients with uncontrolled BP (ie, mean sitting systolic BP [MSSBP] ≥140 mmHg to <180 mmHg and mean sitting diastolic BP <110 mmHg) were randomized to the placebo, AML 5 mg, or AML 10 mg group. A total of 428 participants were enrolled in the 2 I-DUO studies. In the I-DUO 301 study, 271 participants were randomized in a 1:1:1 ratio to receive either IRB/AML 150/5 mg, IRB/AML 150/10 mg, or IRB 150 mg/placebo. In the I-DUO 302 study, 157 participants were randomized in a 1:1 ratio to receive IRB/AML 300/5 mg or IRB 300 mg/placebo. The primary endpoint was the change in MSSBP from baseline to week 8. Tolerability was assessed according to the development of treatment-emergent adverse events (TEAEs) and clinically significant changes in physical examination, laboratory tests, pulse, and 12-lead electrocardiography., Findings: In I-DUO 301, the mean (SD) changes of MSSBP at week 8 from baseline were -14.78 (12.35) mmHg, -21.47 (12.78) mmHg, and -8.61 (12.19) mmHg in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively. In I-DUO 302, the mean (SD) changes of MSSBP at week 8 from baseline were -13.30 (12.47) mmHg and -7.19 (15.37) mmHg in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively. In both studies, all combination groups showed a significantly higher reduction in MSSBP than the IRB monotherapy groups (P < 0.001 for both). TEAEs occurred in 10.00%, 10.99%, and 12.22% of participants in the IRB/AML 150/5 mg, IRB/AML 150/10 mg, and IRB 150 mg/placebo groups, respectively, in I-DUO 301 and in 6.33% and 10.67% of participants in the IRB/AML 300/5 mg and IRB 300 mg/placebo groups, respectively, in I-DUO 302, with no significant between-group differences. Overall, there was one serious adverse event throughout I-DUO study., Implications: The combination of IRB and AML has superior antihypertensive effects compared with IRB alone over an 8-week treatment period, with placebo-like tolerability., Clinical Trial Registration: ClinicalTrials.gov identifier: NCT05476354 (I-DUO 301), NCT05475665 (I-DUO 302)., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: Cardiovascular adverse events (CVAEs) are common adverse effects of first-generation Bruton tyrosine kinase inhibitors (BTKis) and limit their use considerably. This led to the development of second-generation BTKis-acalabrutinib and zanubrutinib-which are more selective, potent, and presumed to have better safety profiles than the previous group of medications. However, there have been sporadic reports of CVAEs associated with second-generation BTKis in clinical practice. To address this issue, a comprehensive meta-analysis to pool the documented CVAEs was performed, including major hemorrhage, any bleeding, atrioventricular block, atrial fibrillation/flutter, pericardial effusion, pericarditis, heart failure, cardiac arrest, myocardial infarction, hypertension, hypotension, and stroke. This meta-analysis incorporated 8 studies. Among these, 6 were Phase III trials and 2 were Phase II trials. These studies collectively enrolled a total of 2938 patients., Methods: Multiple databases, including PubMed, MEDLINE, Cochrane Library, Scopus, and EMBASE, were systematically searched for relevant clinical trials from inception through January 14, 2023. The effect measure used was odds ratio (OR) and 95% CI., Findings: Of a total of 1774 studies identified during the initial database search, 8 were included in the meta-analysis. The incidence of overall and cardiovascular mortality was comparable between the 2 groups. There were no significant differences observed for cardiovascular mortality (OR = 0.36; 95% CI, 0.08-1.65; n = 2588; I 2 = 45%; P = 0.19). Similar results were found for all-cause mortality (OR = 0.85; 95% CI, 0.67-1.07), any bleeding (OR = 1.90; 95% CI, 0.88-4.09), major bleeding (OR = 1.07; 95% CI, 0.65-1.76), atrioventricular block (OR = 0.74; 95% CI, 0.15-3.68), atrial fibrillation/flutter (OR = 0.74; 95% CI, 0.37-1.50), and other CVAEs associated with second-generation BTKis., Implications: Based on the available evidence, there is no indication of worse cardiovascular outcomes or superiority of second-generation BTKis compared with standard treatments in terms of safety profile. However, additional large-scale controlled trials are needed to provide robust support for the superior tolerability of new-generation BTKis., Competing Interests: Declaration of Competing Interest The authors declare that there were no study sponsors involved in the design of the study, collection, analysis and the interpretation of data, the writing of the manuscript, or the decision to submit the manuscript for publication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Hypertension stands as a prominent risk factor for cardiovascular disease, making it of utmost importance to address. Studies have shown that L-carnitine supplementation may lower blood pressure (BP) parameters in different populations. Therefore, we have conducted a systematic review and dose-response meta-analysis of published Randomized Controlled Trials (RCTs), including the most recent articles on the effect of L-carnitine supplementation on BP., Methods: PubMed, ISI Web of Science, Cochrane databases, and Scopus were used to collect RCT studies published up to October 2022 without limitations in language. Inclusion criteria were adult participants and recipients of L-carnitine in oral supplemental forms. The funnel plot test, Begg's test, and Egger's test were used to examine publication bias., Findings: After the search strategy, 22 RCTs (n = 1412) with 24 effect sizes fulfilled the criteria. It was found L-Carnitine supplementation did not have a significant effect on systolic blood pressure (SBP) (mm Hg) (weighted mean difference [WMD] = -1.22 mm Hg, 95% CI: -3.79, 1.35; P = 0.352; I 2 = 85.0%, P < 0.001), and diastolic blood pressure (mm Hg) (WMD = -0.50 mm Hg, 95% CI: -1.49, 0.48; P = 0.318; I 2 = 43.4%, P = 0.021) in the pooled analysis. Subgroup analyses have shown that L-carnitine supplementation had no lowering effect on SBP in any subgroup. However, there was a significant reduction in diastolic blood pressure in participants with a baseline body mass index >30 kg/m 2 (WMD = -1.59 mm Hg; 95% CI: -3.11, -0.06; P = 0.041; I 2 = 41.3%, P = 0.164). There was a significant nonlinear relationship between the duration of L-carnitine intervention and changes in SBP (coefficients = -6.83, P = 0.045)., Implications: L-carnitine supplementation in adults did not significantly affect BP. But anyway, more studies should be done in this field on different individuals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Apparent resistant hypertension, defined as uncontrolled office blood pressure despite ≥ 3 antihypertensive medications including a diuretic or use of ≥ 4 medications regardless of blood pressure, occurs in ≤ 15% of treated hypertensives. Apparent refractory hypertension, defined as uncontrolled office pressure despite use of 5 or more medications including a diuretic, occurs in ≤ 10% of resistant cases. Both are associated with increased comorbidity and enhanced cardiovascular risk. To rule out pseudo-resistant or pseudo-refractory hypertension, employ guideline-based methodology for obtaining pressure, maximize the regimen, rule out white-coat effect, and assess adherence. True resistant hypertension is characterized by volume overload and aldosterone excess, refractory by enhanced sympathetic tone. Spironolactone is the preferred agent for resistance, with lower doses. Spironolactone, potassium binders, or both, are preferred if the estimated glomerular filtration rate is below 45. If significant albuminuria, finerenone is indicated. The optimal treatment of refractory hypertension is unclear, but sympathetic inhibition (α-β blockade, centrally acting sympathoinhibitors, or both) seems reasonable. Renal denervation has shown minimal benefit for resistance, but its role in refractory hypertension remains to be defined., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Intensive blood pressure lowering prevents major adverse cardiovascular events, but some patients experience serious adverse events. Examining benefit-harm profiles may be more informative than analyzing major adverse cardiovascular events and serious adverse events separately., Methods: We analyzed data from the Systolic Blood Pressure Intervention Trial (n = 9361), comparing intensive treatment (systolic blood pressure target <120 mm Hg) to standard treatment (<140 mm Hg). A 4-year hierarchical outcome profile was defined for each participant: 1) alive with neither major adverse cardiovascular events nor serious adverse events (most desirable); 2) alive with serious adverse events only; 3) alive with major adverse cardiovascular events only; 4) alive with both events; and 5) deceased (least desirable). We compared 4-year outcome profiles between the treatment groups in the entire population and by frailty subgroups defined using physical frailty phenotype (non-frail, pre-frail, and frail)., Results: The proportion who died were lower with intensive treatment than standard treatment (5% vs 6%). A higher proportion of the intensive treatment group was alive with serious adverse events and no major adverse cardiovascular events (36% vs 33%), and a lower proportion were alive with both events (6% vs 5%) than the standard treatment group. The outcome profiles were more favorable among those with physical frailty phenotype who were treated with intensive treatment vs standard treatment, but outcome profiles were similar between the treatment groups among non-frail or pre-frail participants., Conclusions: This post hoc proof-of-concept analysis demonstrates the utility of the outcome profile analysis that simultaneously examines the benefit and harm of the treatment., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Albuminuria and left ventricular hypertrophy (LVH) are independent predictors of heart failure (HF); however, to the best of our knowledge, their combined effect on the risk of HF has not yet been explored. Therefore, we examined the joint associations of albuminuria and electrocardiographic-LVH with incident acute decompensated HF (ADHF), and whether albuminuria/LVH combinations modified the effects of blood pressure control strategy in reducing the risk of ADHF. A total of 8,511 participants from the Systolic Blood Pressure Intervention Trial (SPRINT) were included. Electrocardiographic-LVH was present if any of the following criteria were present: Cornell voltage, Cornell voltage product, or Sokolow-Lyon. Albuminuria was defined as urine albumin/creatinine ratio ≥30 mg/g. ADHF was defined as hospitalization or emergency department visit for ADHF. Cox proportional hazard models were used to examine the association of neither LVH nor albuminuria (reference), either LVH or albuminuria, and both (LVH + albuminuria) with incident ADHF. Over a median follow-up of 3.2 years, 182 cases of ADHF occurred. In adjusted models, concomitant albuminuria and LVH were associated with greater risk of ADHF than either albuminuria or LVH in isolation (hazard ratio [95% confidence interval]: 4.95 [3.22 to 7.62], 2.04 [1.39 to 3.00], and 1.47 [0.93 to 2.32], respectively, additive interaction p = 0.01). The effect of intensive blood pressure in reducing ADHF was attenuated in participants with coexisting albuminuria and LVH without any interaction between treatment group assignment and albuminuria/LVH categories (interaction p = 0.26). In conclusion, albuminuria and LVH are additive predictors of ADHF. The effect of intensive blood pressure control in reducing ADHF risk did not vary significantly across albuminuria/LVH combinations., Competing Interests: Declaration of Competing Interest Dr. Chen receives funding from the National Heart, Lung, and Blood Institute (R01 HL141288, R01 HL126637, K24 HL155813). The remaining authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hypertensive patients with heart failure (HF), with reduced or preserved ejection fraction, belong to a vulnerable subset with high mortality risks. In HF patients, the current clinical guideline recommends attaining a systolic blood pressure (BP) <130 mm Hg. However, levels of BP control and their correlates in this subgroup are not well understood. Our study aimed at establishing levels of BP control and its associated factors in a geographically, racially diverse population of hypertensive patients with HF. Our study involved 10,802 patients within a large health system in the Charlotte metropolitan area in 2019. We documented a high prevalence of systolic BP ≥130 mm Hg, 48.1% (95% confidence interval 47.4% to 48.8%), and of BP ≥130/80 mm Hg, 57.6% (57.0% to 58.3%). From a multivariate logistic regression model, systolic BP ≥130 mm Hg was associated with race-ethnicity (p <0.0001), gender (p = 0.0001), insurance (p <0.0001), attribution with a primary care physician (p = 0.0001). Non-Hispanic Blacks (vs non-Hispanic Whites odds ratio [OR] 1.38, 1.28 to 1.48), women (OR 1.12, 1.06 to 1.19), and uninsured patients (vs privately insured OR 1.43, 1.20 to 1.72) had a higher risk of systolic BP ≥130 mm Hg; patients with primary care physician attribution had a lower risk of systolic BP ≥130 mm Hg (OR 0.87, 0.81 to 0.94). Similar results were found with the outcome BP ≥130/80 mm Hg. Overall, further efforts are needed to optimize treatment in hypertensive patients with HF and improve health equity across patient communities., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Incorporating technology such as home blood pressure monitoring (HBPM) into the clinical routine generates opportunities to improve BP monitoring and control in primary health care. It is also important to prevent overtreatment. However, the combination of HBPM with collaborative drug therapy management (CDTM) has not yet been studied. This study aimed to assess the efficacy of combining HBPM with CDTM to optimize hypertension treatment for older patients., Methods: This open-label, parallel-group, randomized clinical trial was conducted between June 2021 and August 2022 in a Brazilian community pharmacy and included older patients (aged ≥60 years) with hypertension. Those who were classified as poorly adherent or nonadherent to the prescribed drug treatment or who were unable to perform HBPM were excluded. In the control group, participants received a BP monitor and instructions on how to perform HBPM. A general practitioner, who was provided a report with the obtained BP values, determined any changes to the treatment protocol. In the intervention group, a pharmacist enrolled participants in a drug therapy management protocol and provided the general practitioner with suggestions to optimize the antihypertensive drug therapy, in addition to the report with the BP values. The following outcomes were considered: the proportion of participants receiving deprescriptions of antihypertensive drugs, other treatment adjustments, and the difference in mean BP between the groups 45 days after performing HBPM. The study used a t test combined with Levene's test to calculate mean intergroup differences in BP, the paired t test to calculate mean intragroup differences in BP, and Pearson's χ 2 test to determine intergroup differences in changes in drug therapy., Findings: In each group, 161 participants completed the trial. Antihypertensive agents were deprescribed for 31 (19.3%) participants in the intervention group versus 11 (6.8%) in the control group (P = 0.01). In addition, 14 (8.7%) participants were prescribed antihypertensive drugs in the intervention group versus 11 (6.8%) in the control group (P = 0.52). The mean office systolic BP and HBPM values were lower in the intervention group (P = 0.22 and P = 0.29, respectively)., Implications: Combining HBPM with a CDTM protocol effectively optimized antihypertensive treatment for older patients in a primary health care setting., Clinicaltrials: gov identifier: NCT04861727., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The optimal timing for administering antihypertensive medications remains a topic of debate. This review examines the effectiveness of nighttime vs daytime administration of antihypertensive medications in controlling blood pressure (BP). The MAPEC and Hygia trials suggest that nighttime dosing achieves better BP control and significantly lowers cardiovascular events. However, concerns about methodology and generalizability have been raised. In contrast, the HARMONY and TIME trials found no significant difference in BP control nor cardiovascular outcomes between daytime and nighttime dosing. Current research suggests that the timing of antihypertensive medication administration may not be a crucial factor. Therefore, the decision about the timing of antihypertensive medications administration should be individualized, taking into account patient preference and clinical context, in order to promote consistent compliance., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Health systems have been quickly adopting telemedicine throughout the United States, especially since the onset of the COVID-19 pandemic. However, there are limited data on whether adding pharmacist-led home blood pressure (BP) telemonitoring to office-based usual care improves BP. We searched PubMed/MEDLINE and Embase for randomized controlled trials from January 2000 until April 2022, comparing studies on pharmacist-led home BP telemonitoring with usual care. Six randomized controlled trials, including 1,550 participants, satisfied the inclusion criteria. There were 774 participants in the pharmacist-led telemonitoring group and 776 in the usual care group. The addition of pharmacist-led telemonitoring to usual care was associated with a significant decrease in systolic BP (mean difference -8.09, 95% confidence interval -11.15 to -5.04, p <0.001, I 2  = 72%) and diastolic BP (mean difference -4.19, 95% confidence interval -5.58 to -2.81, p <0.001, I 2  = 42%) compared with usual care. In conclusion, this meta-analysis showed that adding pharmacist-led home BP telemonitoring to usual care achieves better BP control than usual care alone., Competing Interests: Declaration of Competing Interest Dr. Volgman reports as Sanofi (consulting), Pfizer (consulting), Merck (Consulting), Janssen (consulting), Bristol Myers Squibb Foundation Diverse Clinical Investigator Career Development Program (DCICDP), National Advisory Committee (NAC), Novartis and NIH Clinical Trials, Apple Inc. stock. Dr. Mitchell reports grants from Pfizer, Abbott Laboratories, Myocardial Solutions, and Children's Discovery Institute. Modest consulting from Pfizer and BridgeBio, unrelated to the contents of the manuscript. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Renal denervation is not a cure for hypertension. Although more recent sham-controlled trials were positive, a significant minority of patients in each trial were unresponsive. The optimal patient or patients need to be defined. Combined systolic/diastolic hypertension appears more responsive than isolated systolic hypertension. It remains uncertain whether patients with comorbidities associated with higher adrenergic tone should be targeted, including obesity, diabetes, sleep apnea, and chronic kidney disease. No biomarker can adequately predict response. A key to a successful response is the adequacy of denervation, which currently cannot be assessed in real time. It is uncertain what is the optimal denervation methodology: radiofrequency, ultrasound, or ethanol injection. Radiofrequency requires targeting the distal main renal artery plus major branches and accessory arteries. Although denervation appears to be safe, conclusive data on quality of life, improved target organ damage, and reduced cardiovascular events/mortality are required before denervation can be generally recommended., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Fimasartan, one of the newest angiotensin receptor blockers (ARBs) available worldwide, has been investigated extensively since its initial development. Our study group conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating fimasartan and comparators for their blood pressure (BP)-lowering effect. Moreover, we employed a cross-inference (frequentist and Bayesian inference) system, which has never been used in the medical field, to confirm the results of our study. In addition, a quality management system was integrated throughout the study for data quality., Methods: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, ClinicalKey, and ClinicalTrial.gov were searched for RCT studies from March 1998 to March 2022. In each study, the mean differences (MD s ) and 95% CIs were identified for reductions in clinic sitting systolic and diastolic BP (SiSBP/SiDBP) or 24-hour mean systolic BP and diastolic BP by ambulatory BP monitoring (ASBP/ADBP) from baseline between the fimasartan and comparator groups, followed by meta-analysis. A subsequent meta-analysis was performed with frequentist and Bayesian inference as a tool in the cross-checking system., Findings: Eleven RCTs with a total of 2459 subjects were included in the study. The clinic SiSBP/SiDBP-lowering effect of fimasartan was significantly greater relative to those of comparators (MD for clinic SiSBP, -2.58 mm Hg [95% CI, -4.35 to -0.81; P = 0.004]; MD for clinic SiDBP, -2.13 mm Hg [95% CI, -2.96 to -1.30; P = 0.00001]). The ASBP/ADBP-lowering effect of fimasartan was also significantly greater relative to those of comparators (MD for ASBP, -3.58 mm Hg [95% CI, -5.74 to -1.43; P = 0.001]; MD for ADBP, -1.99 mm Hg [95% CI, -3.34 to -0.63; P = 0.004])., Implications: Fimasartan seems to be more effective in lowering BP than its comparators, including other ARBs. Although there is a limited amount of data and a minuscule number of study subjects available, the results of cross-inference (frequentist + Bayesian) were fairly consistent with the meta-analysis results through our quality management system., Competing Interests: Declaration of Interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Renal denervation (RD) has been investigated as an invasive blood pressure (BP) lowering treatment for hypertension (HTN). Resistant HTN (RHTN) has been defined as uncontrolled BP despite use of 3 antihypertensive medications of different classes, including a diuretic, at maximum tolerated doses. The impact of RD on RHTN remains under investigation. Ten sham-controlled trials testing RD were included in this trial-level analysis. A prespecified subgroup analysis was conducted to test whether efficacy of RD differed in patients with and without RHTN. The primary end points were change in 24-hour ambulatory systolic (SBP) and diastolic (DBP) using raw mean difference (RMD) between sham control and RD. Ten studies (6 RHTN and 4 nonresistant HTN) were identified that included 1,544 participants (1,001 RHTN and 543 essential HTN) with cumulative mean age (±SD) of 57 years (±3). Cochran risk of bias assessment showed 69% of the domains to be at low risk of bias. The RMD for 24-hour SBP between RD and sham control was statistically significant for nonresistant HTN trials (-4.19 mm Hg; 95% confidence interval [CI] -6.07 to -2.30) but was not statistically significant for RHTN trials (-1.86 mm Hg; 95% CI - 3.89 to 0.16). Despite the numerical difference in the subgroups, the interaction between subgroups failed to reach statistical significance (p = 0.10). The RMD for 24-hour DBP between RD and sham control was statistically significant for nonresistant HTN trials (-2.60 mm Hg; 95% CI -3.79 to -1.42) but was not statistically significant for RHTN trials (-0.67 mm Hg; 95% CI -1.84 to 0.50). The interaction between subgroups was statistically significant (p = 0.02). Our analysis indicates RD is a less effective intervention for patients with RHTN. These data may be beneficial for clinicians to consider when assessing patients with RHTN for RD., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients with systemic lupus erythematosus have a higher incidence of cardiovascular disease than the general population. Antihypertensive drugs that modify the renin-angiotensin system (RAS) are used to protect renal function in lupus nephritis and may also have extrarenal effects that lower cardiovascular disease risk due to their anti-inflammatory properties. In this study, we compared the effects of RAS vs non-RAS antihypertensive drugs on cardiovascular disease incidence in patients with lupus., Methods: Using a medical insurance claims dataset, 220,168 patients with lupus were identified, of which 31,647 patients (4018 patients prescribed RAS drugs, 27,629 patients prescribed non-RAS drugs) were eligible for the study. Patients had a mean age of 46.1 years, were 93.0% female, and healthy (96.9% Charlson Comorbidity Index score 0-4). Patients in the 2 drug groups were propensity score matched using demographic data, risk factors, and comorbidities., Results: Use of RAS vs non-RAS drugs lowered the relative risk (RR) of diagnosis of cardiovascular disease (RR 0.80; 95% confidence interval [CI], 0.74-0.87), which was more pronounced after propensity score matching (RR 0.62; 95% CI, 0.57-0.68). The decreased risk in cardiovascular disease occurred regardless of lupus nephritis status (with lupus nephritis: RR 0.51; 95% CI, 0.39-0.65; without lupus nephritis: RR 0.65; 95% CI, 0.59-0.72). RAS-modifying therapies significantly increased cardiovascular disease-free survival probability over a 5-year period (86.0% vs 78.3% probability)., Conclusions: RAS-modifying drugs reduced the risk of cardiovascular disease in patients with systemic lupus erythematosus in this dataset. These findings have the potential to impact clinical decision-making with regards to hypertension management in patients with lupus., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Heart failure (HF) is a risk factor for incident stroke. However, less is known about the independent nature of this association and to what extent various baseline characteristics may mediate this risk. Of the 5,795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5,448 were free of baseline stroke, of whom 229 had baseline HF. We used a multivariable-adjusted Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for centrally adjudicated incident stroke associated with HF. Participants had a mean age of 73 years, 58% were women, and 15% were African-American. During 23 years of follow-up, incident stroke occurred in 18.8% and 19.3% of those with and without HF, respectively, but the time to first stroke was shorter in those with HF (age-gender-race-adjusted HR 1.64, 95% CI 1.21 to 2.25). The association remained essentially unchanged after adjustments for tobacco, alcohol, and physical activity (HR 1.63, 95% CI 1.21 to 2.24), attenuated after adjustment for hypertension, atrial fibrillation, myocardial infarction, and diabetes mellitus (HR 1.26, 95% CI 0.92 to 1.72), and further attenuated after additional adjustment for 10 baseline functional and subclinical variables (HR 1.05, 95% CI 0.76 to 1.46). In conclusion, despite a similar 23-year stroke incidence, time to first stroke was shorter in older adults with HF than without. However, this extra risk appears to be mediated primarily by 4 cardiovascular diseases that are also risk factors for HF. These findings highlight the importance of the primary prevention of these HF risk factors to reduce the extra risk of stroke in HF., Competing Interests: Disclosures Dr. Fonarow reports consulting with Abbott, Amgen, Astra Zeneca, Bayer, cytokinetics, Edwards, Janssen, Medtronic, Merck, and Novartis. The other authors have no conflicts of interest to declare. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Veterans Affairs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The optimal target blood pressure in the treatment of hypertension is undefined. Whether more intense therapy is better than standard, typically <140/90 mm Hg, is controversial. The most recent American guidelines recommend ≤130/80 mm Hg for essentially all adults. There have been at least 28 trials targeting more versus less intensive therapy, including 13 aimed at reducing cardiovascular events and mortality, 11 restricted to patients with chronic kidney disease, and 4 with surrogate endpoints. We review these trials in a narrative fashion due to significant heterogeneity in targets chosen, populations studied, and primary endpoints. Most were negative, although some showed significant benefit to more intense therapy. When determining the optimal pressure for an individual patient, additional factors should be considered, including age, frailty, polypharmacy, baseline blood pressure, and the diastolic blood pressure J-curve. We discuss these modifying factors in detail. Whereas the tenet "lower is better" is generally true, one size does not fit all, and blood pressure control must be individualized., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Hypertension is an independent risk factor for thromboembolic events in patients with atrial fibrillation (AF). However, the association between blood pressure (BP) control and thromboembolic events remains under-evaluated in patients with AF. We aimed to identify the relation between BP control and the risk of ischemic stroke and systemic embolism in hypertensive patients with AF. Data on 13,712 consecutive patients with AF (9,505 with and 4,207 without hypertension) were retrospectively analyzed. The hypertensive group was divided into quartiles according to the initial BP, linearly interpolated mean BP, variability independent of the mean of the BP, and time in therapeutic range (&lt;130 mm Hg for systolic BP [SBP] and &lt;80 mm Hg for diastolic BP) during follow-up. The primary outcome was ischemic stroke and systemic embolism. The mean follow-up duration of the study population was median 2.7 years (interquartile range 1.1 to 4.9 years), and the median number of BP measurements was 14 (interquartile range 6 to 25) times. Strictly controlled initial and interpolated mean BP and low variability in controlled BP (variability independent of the mean) were associated with a lower risk of ischemic stroke and systemic embolism for both SBP and diastolic BP. A similar risk was observed in patients with strictly controlled SBP (time in therapeutic range under 130 mm Hg &gt;94%) and those without hypertension. In conclusion, continuous and strict maintenance of SBP under 130 mm Hg with low variability at outpatient clinic follow-up reduces the risk of ischemic stroke and systemic embolism in patients with hypertension and AF., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The most important factor in treating hypertension is assessing an individual patient's true blood pressure load, the cornerstone being research-grade office determination. Office blood pressure should be supplemented with out-of-office measurement, including home and ambulatory monitoring (if available), which we consider complementary and not interchangeable. Controversy remains for initiation of treatment of white coat hypertension, where cardiovascular risk lies between normotension and sustained hypertension; antihypertensive therapy should be considered unless low cardiovascular risk, wherein pressures should be followed for progression to sustained hypertension. Available data do not support intensification of therapy for the white coat effect due to the similar cardiovascular risk to controlled hypertension. Given the higher cardiovascular risk of the masked effect, initiation of therapy for masked hypertension and intensification for masked uncontrolled hypertension are indicated, acknowledging the dearth of supporting data. Optimally, randomized controlled trials are needed to determine the benefit of treating the 4 incongruous phenotypes between office and out-of-office measurements, that is, those with white coat or masked effects. We make no recommendations regarding chronotherapy pending results of ongoing trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Angiotensin receptor blockers (ARBs), which are commonly used antihypertensives, have been proposed to lower the risk of Parkinson disease by reducing oxidative stress based on animal and in vitro studies. Thus, this study aimed to test this association in patients with newly diagnosed hypertension., Methods: This retrospective cohort study enrolled 107,207 patients with newly diagnosed hypertension between 2001 and 2013. The hazard ratios for Parkinson disease were calculated for ARB treatment compared with those who never used ARBs and among the 5 subgroups receiving different cumulative ARB dosages., Results: We identified 527 (1.1%) Parkinson disease cases among patients with ARB treatment in a median observation period of 8.4 years compared to the 1,255 (2.2%) Parkinson disease cases among those without ARB treatment in a median observation period of 6.8 years. Overall, risk for developing Parkinson disease was statistically lower in the ARB-treated group with a hazard ratio of 0.56 (95% confidence interval: 0.51-0.63) than those without ARB., Conclusions: ARB treatment was associated with a statistically important reduction of Parkinson disease risk in patients with newly diagnosed hypertension. Therefore, ARB may constitute an effective neuroprotective strategy to lower Parkinson disease risk in such patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Blood pressure control has been shown to reduce risk of vascular events and mortality after an ischemic stroke or transient ischemic attack (TIA). Yet, questions remain about effectiveness, timing, and targeted blood pressure reduction., Methods: We analyzed data from a retrospective cohort of 18,837 veterans cared for 12 months prior and up to 12 months after an emergency department visit or inpatient admission for stroke or TIA. Latent class growth analysis was used to classify patients into systolic blood pressure trajectories. With Cox proportional hazard models, we examined relationships between blood pressure trajectories, intensification of antihypertensive medication, and stroke (fatal or non-fatal) and all-cause mortality in 12 months following the index event., Results: The cohort was classified into 4 systolic blood pressure trajectories: 19% with a low systolic blood pressure trajectory (mean systolic blood pressure = 116 mm Hg); 65% with a medium systolic blood pressure trajectory (mean systolic blood pressure = 136 mm Hg); 15% with a high systolic blood pressure trajectory (mean systolic blood pressure = 158 mm Hg), and 1% with a very high trajectory (mean systolic blood pressure = 183 mm Hg). After the stroke or TIA, individuals in the high and very high systolic blood pressure trajectories experienced a substantial decrease in systolic blood pressure that coincided with intensification of antihypertensive medication. Patients with very low and very high systolic blood pressure trajectories had a significantly greater (P < .05) hazard of mortality, while medication intensification was related significantly (P < .05) to lower hazard of mortality., Conclusions: These findings point to the importance of monitoring blood pressure over multiple time points and of instituting enhanced hypertension management after stroke or TIA, particularly for individuals with high or very high blood pressure trajectories., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The effects of vitamin D (Vit-D) deficiency and Vit-D treatment (VDT) on atrial fibrillation (AF) remain inconclusive. This study sought to determine the effects of VDT and nontreatment on AF risk in Vit-D-deficient patients without a previous history of AF. In this nested case-control study, 39,845 individuals with low 25-hydroxy-Vit-D ([25-OH]D) levels (<20 ng/ml) were divided into group-A (untreated, levels ≤20 ng/ml), group-B (treated, levels 21 to 29 ng/ml), and group-C (treated, levels ≥30 ng/ml). The risk of AF was compared utilizing propensity score-weighted Cox proportional hazard models. Among the individuals receiving VDT for ≥6 months, the risk of AF was significantly lower in group-B (hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80 to 0.98, p = 0.03] and group-C (HR 0.84, 95% CI 0.73 to 0.0.95, p = 0.007] than in group-A. A subgroup analysis of men >65 years showed individuals with hypertension had a significantly lower risk of AF in group-C than in group-B (HR 0.79, CI 0.65 to 0.94, p = 0.02) and group-A (HR 0.78, CI 0.64 to 0.96, p = 0.012). A similar result was found in men >65 years with diabetes mellitus in group-C compared with group-B (HR 0.69, CI 0.51 to 0.93, p = 0.012) and group-A (HR 0.63, CI 0.47 to 0.84, p = 0.002). In what is, to best of our knowledge, the largest observational study to date of patients with Vit-D deficiency and no previous history of AF, (25-OH)D level of >20 ng/ml with VDT for ≥6 months was associated with a significantly lower risk of AF. Additionally, men >65 years with hypertension or diabetes mellitus had a further decrease in AF risk when the (25-OH)D levels were ≥30 ng/ml., (Published by Elsevier Inc.)

Whether blood pressure (BP) classification using the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) BP guideline can identify patients at high risk for proteinuria remains unknown. We examined the association of BP classification using the 2017 ACC/AHA guideline with the subsequent risk for the development of proteinuria. This is an observational cohort study using the JMDC Claims Database. We analyzed 914,786 participants with negative proteinuria assessed using urine dipstick tests at the initial health check-ups, not taking BP-lowering medications, and who underwent repeated urine dipstick tests within 4 years. Based on the 2017 ACC/AHA guideline, each participant was categorized as having normal BP (n = 487,020), elevated BP (n = 134,798), stage 1 hypertension (n = 197,618), or stage 2 hypertension (n = 95,350). The primary outcome was incident proteinuria. We investigated the association of BP based on the 2017 ACC/AHA guideline category with incident proteinuria using multivariable analyses. We used restricted cubic spline functions to identify the relation between systolic BP (SBP) and the risk for proteinuria. The median age was 45 years, and 59.4% were men. Multivariable analysis demonstrated that stage 1 hypertension (relative risk 1.14, 95% confidence interval 1.11 to 1.17), and stage 2 hypertension (relative risk 1.48, 95% confidence interval 1.43 to 1.52) were associated with a higher incidence of proteinuria than normal BP. The restricted cubic spline demonstrated that the risk for proteinuria increased linearly with SBP after SBP exceeded 120 mm Hg. Not only stage 2 hypertension but also stage 1 hypertension was associated with a greater risk for proteinuria, suggesting the importance of establishing the management strategy for stage 1 hypertension., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The present United States and European treatment guidelines recommend that antihypertensive therapy be initiated with a combination of agents from different classes to facilitate the achievement of control of blood pressure (BP). This prospective, randomized, open-label study was conducted at 3 tertiary hospitals in India to evaluate the effects of combination therapy with an angiotensin receptor blocker and a calcium antagonist on office BP and central hemodynamic parameters in patients with untreated hypertension or uncontrolled BP (>130/>80 mm Hg) during treatment with antihypertensive monotherapy. Patients were randomized to treatment with telmisartan 40 mg/day + amlodipine 5 mg/day or telmisartan 40 mg/day + cilnidipine 10 mg/day. Change from baseline to 8 weeks of treatment was assessed for seated office BP, ambulatory BP monitoring, and seated central hemodynamics (central BP, aortic augmentation index, central aortic augmentation pressure, and pulse wave velocity). A total of 94 of 96 enrolled patients completed the study. From baseline to 8 weeks a significant decrease was observed in both telmisartan + amlodipine and telmisartan + cilnidipine groups for mean BP (148.0 ± 12.80 to 124.0 ± 10.4 and 144.5 ± 10.2 to 123.0 ± 10.0 mm Hg, respectively; both p <0.001); in only telmisartan + amlodipine group for mean central aortic systolic and diastolic BP (131.1 ± 19.1 to 119.7 ± 14.9 mm Hg [p <0.001] and 93.3 ± 12.0 to 89.2 ± 14.6 mm Hg [p = 0.0008], respectively) and for central aortic pulse wave velocity (7.6 ± 1.4 to 7.2 ± 1.3 m/s, p = 0.0011); in only telmisartan + cilnidipine group for aortic augmentation index (27.5 ± 14.6 to 22.3 ± 12.2; p = 0.0178). Heart rate was unchanged in both treatment groups. Combination therapy with an angiotensin receptor blocker and a calcium antagonist effectively reduced BP to below the new <130/80 mm Hg target and had favorable effects on central hemodynamics., Competing Interests: Disclosures Drs. C. Venkata S. Ram, S. Ray, U. Jadhav, J. P. S. Sawhney, G. Unni, and N. Desai are consultants for clinical research at Mankind Pharma. The remaining authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Uncontrolled hypertension is an important cardiovascular risk factor and therefore requires effective approaches to patient management. This study assessed approaches to the management of patients with Stage 2 hypertension by cardiologists in India. This was a retrospective, multicenter, observational, case-based questionnaire study. Data on demographic characteristics, risk factors associated with Stage 2 hypertension, use of antihypertensive medications, side effects, and approaches to education for 2,540 patients were extracted from questionnaire responses provided by 508 cardiologists. The study population of patients with Stage 2 hypertension had a mean age of 55.0 years. Most of the patients (62.6%) were aged 30 to 60 years and diabetes mellitus was the most prevalent comorbidity (48.9%). Triple antihypertensive therapy was being used by 760 patients, and 634 and 1,146 patients were receiving 4 and 5 different antihypertensive medications, respectively. Telmisartan, amlodipine, chlorthalidone, hydrochlorothiazide, spironolactone, metoprolol, and prazosin were the commonly prescribed drugs. Ankle edema (27.7%) was the most frequent side effect of therapy. Pharmacotherapy was supported by patient education and lifestyle modifications for better blood pressure control. The standardized approach to the collection and assessment of these contemporary data provides useful insights into the characteristics and treatment of patients with Stage 2 hypertension in India., Competing Interests: Disclosures Dr. Mahesh Abhyankar and Dr. Santosh Revankar are employees of USV Pvt Ltd. All other authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Given the concern that beta-blocker use may be associated with an increased risk for heart failure (HF) in populations with normal left ventricular systolic function, we evaluated the association between beta-blocker use and incident HF events, as well as loop diuretic initiation in the Systolic Blood Pressure Intervention Trial (SPRINT). SPRINT demonstrated that a blood pressure target of <120 mm Hg reduced cardiovascular outcomes compared with <140 mm Hg in adults with at least one cardiovascular risk factor and without HF. The lower rate of the composite primary outcome in the 120 mm Hg group was primarily driven by a reduction in HF events. Subjects on a beta blocker for the entire trial duration were compared with subjects who never received a beta blocker after 1:1 propensity score matching. A competing risk survival analysis by beta-blocker status was performed to estimate the effect of the drug on incident HF and was then repeated for a secondary end point of cardiovascular disease death. Among the 3,284 propensity score-matched subjects, beta-blocker exposure was associated with an increased HF risk (hazard ratio 5.86; 95% confidence interval 2.73 to 13.04; p <0.001). A sensitivity analysis of propensity score-matched cohorts with a history of coronary artery disease or atrial fibrillation revealed the same association (hazard ratio 3.49; 95% confidence interval 1.15 to 10.06; p = 0.028). In conclusion, beta-blocker exposure in this secondary analysis was associated with increased incident HF in subjects with hypertension without HF at baseline., Competing Interests: Disclosures Dr. Meyer has licensed patents on the use of pacemakers to prevent and treat heart failure with preserved ejection fraction; the relationship is modest. The remaining authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

Background: Thiazide diuretics are a mainstay in the management of hypertension and often associated with dyselectrolytemias. We investigated the prevalence of and risk factors for hyponatremia and hypokalemia in thiazide users, substance-specific differences, and the association of thiazides with syncope and falls., Methods: In this cross-sectional analysis all patients admitted to an interdisciplinary emergency department in Switzerland between January 1, 2017, and December 31, 2018, with measurements of serum sodium and potassium were included. Data regarding serum electrolytes and creatinine were analyzed to classify for dysnatremias, dyskalemias, and acute kidney injury. Chart reviews were performed to screen for syncope or falls., Results: A total of 1604 patients (7.9%) took thiazides. Acute kidney injury was significantly more common in thiazide users (22.1 vs 7%, P < .0001). Hyponatremia (22.1 vs 9.8%, P < .0001) and hypokalemia (19 vs 11%, P < .0001) were more frequent with thiazides. Thiazide use together with higher age and female sex were independent predictors of hyponatremia and hypokalemia. A dose-dependent effect was found for electrolyte disorders, and there was a variance in risk between the investigated substances with chlorthalidone bearing the highest and hydrochlorothiazide the lowest risk. Patients taking thiazide diuretics had significantly more episodes of syncope and falls., Conclusions: Thiazide use is a clear risk factor for hyponatremia and hypokalemia. The effect appears to be dose-dependent and highly variable depending on the substance. Syncope and falls seem to be causally related to thiazide use. Especially in patients who are elderly, female, and prone to falls, the use of thiazide diuretics should be thoroughly questioned., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Chlorthalidone is recommended over hydrochlorothiazide (HCTZ) as the preferred thiazide, but the supporting evidence is not robust at routinely used doses, or in whites vs blacks, in whom differences in response to thiazides are well known. We compare the efficacy and safety of HCTZ and chlorthalidone as first-line therapies for white and black hypertensive patients., Methods: We compared treatment-related outcomes between the HCTZ arm (12.5 mg for 2-3 weeks; 25 mg for additional 6 weeks) of the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR, n = 376) and chlorthalidone arm (15 mg for 2 weeks; 25 mg for additional 6 weeks) of PEAR-2 (n = 326) clinical trials, in 17-65-year-old mild-moderate uncomplicated hypertensive whites and blacks., Results: Mean systolic/diastolic blood pressure (SBP/DBP) reduction with HCTZ vs chlorthalidone: 8 ± 8/4 ± 5 vs 12 ± 9/7 ± 5 mm Hg in whites (P < 10 -6 SBP and DBP); 12 ± 10/7 ± 6 vs 15 ± 10/9 ± 6 in blacks (P = .008 SBP, P = .054 DBP). Treatment with HCTZ vs chlorthalidone in whites resulted in significantly fewer patients achieving target BP (<140/90 mm Hg) (44% vs 57%, P = .018) and clinical response rate (≥10 mm Hg DBP reduction); and significantly higher nonresponse rate (<6 mm Hg DBP reduction); but no significant differences in rates among blacks (eg, target-BP rate: 56% vs 63%, P = .31). HCTZ treatment led to significantly lower rates of hypokalemia and hyperuricemia in whites and blacks, vs chlorthalidone, and significantly lower odds of requiring potassium supplementation among blacks (odds ratio 0.16; 95% confidence interval, 0.07-0.37; P = 3.4e -7 )., Conclusion: Compared with HCTZ, chlorthalidone showed greater blood pressure lowering and adverse metabolic effects in whites, but similar blood pressure lowering and greater adverse effects in blacks; suggesting that the recent guideline recommendations to choose chlorthalidone over HCTZ may not be warranted in blacks., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Effect of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) among hypertensive patients with coronavirus disease 2019 (COVID-19) is debated. The aim of the COVIDECA study was to assess the outcome of ACEI and ARB among hypertensive patients presenting with COVID-19. We reviewed from the Assistance Publique-Hôpitaux de Paris healthcare record database all patients presenting with confirmed COVID-19 by RT-PCR. We compared hypertensive patients with ACEI or ARB and hypertensive patients without ACEI and ARB. Among 13,521 patients presenting with confirmed COVID-19 by RT-PCR, 2,981 hypertensive patients (mean age: 78.4 ± 13.6 years, 1,464 men) were included. Outcome of hypertensive patients was similar whatever the use or non-use of ACEI or ARB: admission in ICU (13.4% in patients with ACEI or ARB versus 14.8% in patients without ACEI/ARB, p = 0.35), need of mechanical ventilation (5.5% in patients with ACEI or ARB vs 6.3% in patients without ACEI/ARB, p = 0.45), in-hospital mortality (27.5% in patients with ACEI or ARB vs 26.7% in patients without ACEI/ARB, p = 0.70). In conclusion, the use of ACEI and ARB remains safe and can be maintained in hypertensive patients presenting with COVID-19., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: Antihypertensive agents are frequently prescribed in kidney transplant recipients (KTRs). However, the frequency and patterns of prescribing antihypertensive agents remain uncharacterized in KTRs in China. Therefore, this investigation was carried out., Methods: Retrospective prescription data dated 2011 to 2018 from KTRs in China were accessed using the Hospital Prescription Analysis Program database. Information about sex, birth date, and identification number of the patient; city, date, and department of the medical visit; major diagnoses; and the generic names, specifications, quantities, and usage of prescribed drugs were collected. Antihypertensive agents were grouped into 5 classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics. The frequency and patterns of prescribing these antihypertensive agents were analyzed., Findings: Prescriptions from 174,749 KTRs (67.2% male; mean age, 42.5 [9.4] years) were obtained, and 58.2% of the patients were prescribed antihypertensive agents. The percentage of patients who received antihypertensive treatment increased from 52.9% in 2011 to 61.6% in 2018 and varied by city. Cyclosporine was associated with higher prescription frequency of antihypertensive agents than was tacrolimus (71.7% vs 63.4%; P < 0.0001). During the 8-year study period, CCBs were most frequently prescribed (39.0%), followed by ARBs (31.9%), BBs (14.3%), ACEIs (11.6%), and diuretics (3.2%). The mean (SD) number of antihypertensive drugs prescribed per KTR was 1.7 (0.8). Almost half of KTRs (51.2%) received just 1 antihypertensive drug. Co-administration of 2 or more antihypertensive drugs presented an obviously upward trend. The most commonly prescribed 2-drug combination was CCB + ARB (44.8%), followed by CCB + BB (20.1%) and CCB + ACEI (13.0%). In the patients who received 3 antihypertensive drugs, the 2 most frequently prescribed combinations were CCB + ARB + BB (37.5%) and CCB + ARB + ACEI (32.7%). Specific data varied by both year and city., Implications: The prescribing patterns of antihypertensive agents in KTRs varied by city even within same country. Hence, more high-quality research studies on the use of antihypertensive agents in KTRs are needed., Competing Interests: Disclosures The authors have indicated that they have no conflicts of interest with regard to the content of this article., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We sought to determine if the absence of hypertension in older adults can be used to identify those at lower risk of atherosclerotic cardiovascular disease (ASCVD). We identified participants ≥75 years old free of cardiovascular disease (CVD) in the National Institutes of Health Pooled Cohorts with and without hypertension. We assessed the association between systolic blood pressure (BP), diastolic BP, and cardiovascular events using multivariable modeling. The association between predicted ASCVD risk and observed events was compared. Of 2,667 adults aged ≥75 years, 67.9% had hypertension. Lower systolic BP correlated with lower CVD event rates. ASCVD predicted risk score and systolic BP were both independently associated with ASCVD event rates. Among adults with similar ASCVD predicted risk estimates, those without (vs with) hypertension had lower observed event rates across the predicted risk spectrum. The absence of hypertension may help refine the risk stratification of older adults, particularly those with intermediate predicted risk., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Although calcium channel blockers (CCBs) are now commonly prescribed to treat hypertension as a first-line drug therapy, their impact on prostate cancer (PCa) is unclear. This systematic review and meta-analysis was conducted to determine the association between CCB use and the overall risk of PCa., Methods: PubMed, EMBASE, and Cochrane were searched up to December 26, 2019, stratified according to statistical method of outcome [odd ratios (ORs), relative ratios (RRs), hazard ratios (HRs)] and cumulative duration of CCB use. The quality assessment of included studies was evaluated by using the Newcastle-Ottawa Scale. Fixed effects models were used to study the association between CCB use and the risk of PCa. Between-study heterogeneity was quantified by using Cochran's Q-statistic and I 2 statistics. Sensitivity analysis was performed by excluding the studies one by one, and publication bias was analyzed by using funnel plots., Findings: Nineteen studies with 1,418,407 patients were identified for inclusion in the meta-analysis, which was based on the comparison of cohort studies, nested case-control studies, and case-control studies. Pooled estimates showed a RR of 1.08 (95% CI, 1.05-1.11; P < 0.00001) and a HR of 1.07 (95% CI, 1.02-1.13; P = 0.008) for association between CCB use and the risk of PCa. In addition, the results of subgroup analysis showed that CCB users of <5 years had an 8% increased overall risk of PCa (RR, 1.08; 95% CI, 1.04-1.12; P = 0.0001), and CCB users of 5-10 years had a 13% increased overall risk of PCa (RR, 1.13; 95% CI, 1.04-1.23; P = 0.003)., Implications: CCB use had a tendency to increase the overall risk of PCa, and cumulative duration of CCB use might also be positively correlated with the overall risk of PCa., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The 2017 American blood pressure (BP) guidelines recommended a personalized risk-based approach to treatment in stage 1 hypertension. We sought to establish the utility of coronary artery or thoracic aortic calcium (CAC or TAC) as additional risk modifiers in this setting. We included 1859 Multiethnic Study of Atherosclerosis participants with stage 1 hypertension. We compared adjusted HR for the composite outcome of incident atherosclerotic cardiovascular disease or heart failure across predefined categories of either CAC or TAC (0, 1 to 100, or >100) in: (1) the full sample; (2) 4 high-risk subgroups recommended for pharmacotherapy to a BP goal <130/80 mm Hg, and (3) low-risk subgroup not eligible for pharmacotherapy. We also estimated the 10-year number-needed-to-treat (NNT 10 ) to a systolic BP <130 mm Hg as extrapolated from meta-analyses. Mean age was 62.8 ± 9.4 years, 46% were female and there were 300 events over a median follow-up of 13.8 years. The absolute event rate was 4.1 to 10.8 per 1,000 person-years among high-risk participants with CAC = 0, but 28.4 among low-risk participants with CAC >100. CAC >100 was independently associated with a higher relative risk of events compared with CAC = 0 (e.g., adjusted HR [9.5 (1.8 to 18.7)] in the low-risk subgroup). NNT 10 for CAC = 0 were 3 to 5 times higher than those for CAC >100 in all analyses. TAC was not a reliable risk modifier in our study. In conclusion, CAC, but not TAC, can further guide risk-based allocation of treatment in stage 1 hypertension and should be considered as a risk modifier in future guidelines., Competing Interests: Conflicts of Interest SSM has served on scientific advisory boards of Amgen, Sanofi, Regeneron, Esperion, Novo Nordisk, Quest Diagnostics, and Akcea Therapeutics, and has received research support from Apple, Google, iHealth, Nokia, NIH, the Maryland Innovation Initiative, American Heart Association, Aetna Foundation, PJ Schafer Memorial Fund, and David and June Trone Family Foundation. He is a co-inventor on a pending patent filed by Johns Hopkins University for a system of LDL-C estimation. MJB has received grant support from General Electric. All other authors report no conflicts of interest., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: The goal of this study was to review recent clinical studies of azilsartan medoxomil (AZL-M) and chlorthalidone (CLD), a combined angiotensin receptor blocker and thiazide-like diuretic, and its role in recently published guidelines. This review explores the role of AZL-M/CLD in treating patients with hypertension., Methods: A systematic review of literature published from 1990 to 2018 was performed by using the following key words: Edarbyclor, azilsartan, chlorthalidone, pharmacokinetic, and hypertension. Available English-language data from reviews, abstracts, presentations, and clinical trials regarding the use of AZL-M/CLD therapy specifically detailing effects of lowering blood pressure (BP) and outcomes on cardiovascular disease in humans and rats were reviewed., Findings: One study compared a single-pill combination of AZL-M/CLD with co-administration of AZL-M and hydrochlorothiazide and found a greater reduction in clinic systolic BP with AZL-M/CLD (-35.1 mm Hg vs -29.5 mm Hg) than for AZL-M and hydrochlorothiazide. Another study of 153 patients with chronic kidney disease who received AZL-M/CLD or other single-pill combination agents found that AZL-M/CLD was more effective in lowering BP, achieving superior adherence. According to new guidelines, an increase in the prevalence of resistant hypertension can occur as a result of trying to lower target BP., Implications: A powerful and effective medication that can increase patient compliance is essential to reduce the incidence of resistant hypertension. AZL-M/CLD is a powerful and safe antihypertensive medication that has been thoroughly studied in patients with hypertension., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: The goal of this study was to evaluate the concurrent control rate of hypertension and dyslipidemia by fimasartan and rosuvastatin in patients who were concomitantly prescribed both drugs., Methods: This single-center, cross-sectional study was conducted in 536 patients with hypertension and dyslipidemia who were taking fimasartan and rosuvastatin together for at least 12 weeks. Patients were enrolled from October 2016 to March 2018 at a tertiary hospital in the Republic of Korea. The primary end point was the concurrent control rate of blood pressure (<140/90 mm Hg) and LDL-C. As a secondary end point, the target blood pressure <130/80 mm Hg was adopted in all patients or in high-risk patients with atherosclerotic cardiovascular diseases. Target LDL-C and non-HDL-C levels followed the domestic guidelines. Correlation between blood pressure control and lipid profile was also evaluated. All parameters were assessed in a clinic by board-certified physicians., Findings: Of the total 536 patients, 69% (n = 368) had very high (n = 308) or high (n = 60) cardiovascular risk, with an average age of 65 years; 57% were male. When the target blood pressure was set at 140/90 mm Hg, the proportion of patients meeting the targeting LDL-C level was 40.3% (95% CI, 36.2-44.5; P < 0.001). When applied to the revised blood pressure criteria targeting 130/80 mm Hg, the concurrent control rate dropped by one half to 20.3% (95% CI, 17.2-24.0; P < 0.001). To apply the new blood pressure criteria, more intensive management is mandatory in patients with high or very high cardiovascular risk. There was no positive correlation between the controlled rate of hypertension and dyslipidemia., Implications: Fimasartan and rosuvastatin were shown to have effects on target diseases, but there was no synergistic effect when administered in combination. The higher the cardiovascular risk of the patients, the lower the rate of concurrent control when fimasartan and rosuvastatin were administered simultaneously. More active treatment is therefore required in high-risk patients., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)