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Supplemental Digital Content is available in the text. [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated the usefulness of stenting for the prevention of major adverse renal and cardiovascular events. People with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease were examined. Findings found no significant benefit from renal-artery stenting with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy.

Combination therapy with benazepril 40 mg and amlodipine 10 mg (BDA) has been shown to be more effective than benazepril 40 mg and hydrochlorothiazide (HCTZ) 25 mg (BDH) in reducing cardiovascular (CV) events in high-risk patients with stage 2 hypertension with similar blood pressure reductions. In the present post hoc analysis, we evaluated whether BDA is more effective than BDH for reducing CV events in patients with known coronary artery disease (CAD) at baseline in a subgroup analysis of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) study. The main trial randomized 11,506 patients. Of those, 5,744 received BDA and 5,762 received BDH. Of the 11,506 patients, 5,314 (46%) were classified as having CAD at baseline. The mean patient follow-up period was 35.7 months for the BDA group and 35.6 months for the BDH group. The primary end point was the interval to the first event of composite CV morbidity and mortality. At baseline, significant differences were present between the 5,314 with CAD and the 6,192 without CAD. The patients with CAD had a lower systolic blood pressure and heart rate, a lower incidence of diabetes, and greater incidence of dyslipidemia. However, no baseline differences were found between the randomized BDA and BDH groups. In the patients with CAD, an 18% reduction occurred in the hazard ratio for CV events (primary end point) with BDA versus BDH (p [ 0.0016). In a prespecified secondary analysis of the composite end point, including only CV death, myocardial infarction, and stroke, the hazard ratio in the patients with CAD was reduced by 25% (p[0.0033) in the BDA group compared with the BDH group. BDA was more effective than BDH at comparable blood pressure reductions for reducing CV events in patients, regardless of the presence of CAD. In conclusion, our findings suggest that the combination of BDA should be preferentially used for older patients with high-risk, stage 2 hypertension. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Randomized controlled trials in hypertension demonstrate cardiovascular benefits when systolic blood pressures are reduced from higher values to<160 mm Hg. The value of lower targets has not been fully defined, although major guidelines recommend achieving systolic blood pressures of<140 mm Hg. This study was conducted to explore cardiovascular outcomes at differing on-treatment blood pressure levels. Methods: On the basis of a prespecified plan to explore relationships between clinical outcomes and systolic blood pressures, the pooled cohort of high-risk hypertensive patients (N=10,705) in the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension trial were divided into 4 strata of systolic blood pressure levels: >140 mm Hg, 130 to <140 mm Hg, 120 to <130 mm Hg, and 110 to <120 mm Hg. The primary end point was cardiovascular death or nonfatal myocardial infarction or stroke. Outcomes comparisons between the blood pressure groups were by Cox regression. Results: The mean patient age was 68 years, and the study duration was 35.7 months. The primary end point occurred in 171 of 3429 patients (5.0%) with systolic blood pressure in the 10 mm Hg range<140 and in 179 of 2354 patients (7.6%) with systolic blood pressure≥140 mm Hg (hazard ratio [HR], 0.62; 95% CI, 0.50-0.77; P =.0001). Likewise, cardiovascular death decreased by 36% (P =.0147), total myocardial infarction (fatal+nonfatal) decreased by 37% (P =.0028), and stroke decreased by 47% (P =.0002). Cardiovascular event rates in those with systolic blood pressure<130 mm Hg were not different from those with systolic blood pressure<140 mm Hg. However, compared with systolic blood pressure<130 mm Hg, stroke incidence in those with systolic blood pressure<120 mm Hg was lower (HR, 0.60; 95% CI, 0.35-1.01; P =.0529), but myocardial function was higher (HR, 1.52; 95% CI, 1.00-2.29; P =.0437), as were composite coronary events (myocardial infarction, hospitalized angina, or sudden death) (HR, 1.63; 95% CI, 1.18-2.24; P =.0023). The renal end point of a sustained>50% increase in serum creatinine was significantly lower in those with systolic blood pressure<140 mm Hg than in any of the other higher or lower blood pressure ranges. Conclusions: In high-risk hypertensive patients, major cardiovascular events are significantly lower in those with systolic blood pressures<140 mm Hg and<130 mm Hg than in those with levels>140 mm Hg. There are stroke benefits at levels<120 mm Hg, but they are offset by increased coronary events. Renal function is best protected in the 130 to 139 mm Hg range. [Copyright &y& Elsevier]

A high heart rate (HR) predicts future cardiovascular events. We explored the predictive value of HR in patients with high-risk hypertension and examined whether blood pressure reduction modifies this association. The participants were 15,193 patients with hypertension enrolled in the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial and followed up for 5 years. The HR was assessed from electrocardiographic recordings obtained annually throughout the study period. The primary end point was the interval to cardiac events. After adjustment for confounders, the hazard ratio of the composite cardiac primary end point for a 10-beats/min of the baseline HR increment was 1.16 (95% confidence interval 1.12 to 1.20). Compared to the lowest HR quintile, the adjusted hazard ratio in the highest quintile was 1.73 (95% confidence interval 1.46 to 2.04). Compared to the pooled lower quintiles of baseline HR, the annual incidence of primary end point in the top baseline quintile was greater in each of the 5 study years (all p <0.05). The adjusted hazard ratio for the primary end point in the highest in-trial HR heart rate quintile versus the lowest quintile was 1.53 (95% confidence interval 1.26 to 1.85). The incidence of primary end points in the highest in-trial HR group compared to the pooled 4 lower quintiles was 53% greater in patients with well-controlled blood pressure (p <0.001) and 34% greater in those with uncontrolled blood pressure (p = 0.002). In conclusion, an increased HR is a long-term predictor of cardiovascular events in patients with high-risk hypertension. This effect was not modified by good blood pressure control. It is not yet known whether a therapeutic reduction of HR would improve cardiovascular prognosis. [Copyright &y& Elsevier]

Background: In observational studies, the relationship between blood pressure and end-stage renal disease (ESRD) is direct and progressive. The burden of hypertension-related chronic kidney disease and ESRD is especially high among black patients. Yet few trials have tested whether intensive blood-pressure control retards the progression of chronic kidney disease among black patients. Methods: We randomly assigned 1094 black patients with hypertensive chronic kidney disease to receive either intensive or standard blood-pressure control. After completing the trial phase, patients were invited to enroll in a cohort phase in which the blood-pressure target was less than 130/80 mm Hg. The primary clinical outcome in the cohort phase was the progression of chronic kidney disease, which was defined as a doubling of the serum creatinine level, a diagnosis of ESRD, or death. Follow-up ranged from 8.8 to 12.2 years. Results: During the trial phase, the mean blood pressure was 130/78 mm Hg in the intensive-control group and 141/86 mm Hg in the standard-control group. During the cohort phase, corresponding mean blood pressures were 131/78 mm Hg and 134/78 mm Hg. In both phases, there was no significant between-group difference in the risk of the primary outcome (hazard ratio in the intensive-control group, 0.91; P=0.27). However, the effects differed according to the baseline level of proteinuria (P=0.02 for interaction), with a potential benefit in patients with a protein-to-creatinine ratio of more than 0.22 (hazard ratio, 0.73; P=0.01). Conclusions: In overall analyses, intensive blood-pressure control had no effect on kidney disease progression. However, there may be differential effects of intensive blood-pressure control in patients with and those without baseline proteinuria. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center on Minority Health and Health Disparities, and others.) N Engl J Med 2010;363:918-29. [ABSTRACT FROM AUTHOR]

The article discusses a study which investigated the effects of antihypertensive therapy with benazepril plus amlodipine and benazepril plus hydrochlorothiazide on progression of chronic kidney disease. The study is a prespecified secondary analysis of a randomised controlled trial involving patients with systolic hypertension undertaken in several countries, including the U.S., Sweden and Norway. The researchers concluded that benazepril plus amlodipine is more effective in patients with hypertension at high risk for cardiovascular events.

Abstract: Recruitment of diverse populations into clinical trials remains challenging but is needed to fully understand disease processes and benefit the general public. Greater knowledge of key factors among ethnic and racial minority populations associated with the decision to participate in clinical research studies may facilitate recruitment and enhance the generalizibility of study results. Therefore, during the recruitment phase of the African American Study of Kidney Disease and Hypertension (AASK) trial, we conducted a telephone survey, using validated questions, to explore potential facilitators and barriers of research participation among eligible candidates residing in seven U.S. locations. Survey responses included a range of characteristics and perceptions among participants and non-participants and were compared using bivariate and step-wise logistic regression analyses. One-hundred forty-one respondents in the one-hundred forty (70 trial participants and 71 non-participants) completed the survey. Trial participants and non-participants were similar in multiple demographic characteristics and shared similar views on discrimination, physician mistrust, and research integrity. Key group differences were related to their perceptions of the impact of their research participation. Participants associated enrollment with personal and societal health benefits, while non-participants were influenced by the health risks. In a step-wise linear regression analysis, the most powerful significant positive predictors of participation were acknowledgement of health status as important in the enrollment decision (OR=4.54, p =0.006), employment (OR=3.12, p = 0.05) and healthcare satisfaction (OR=2.12, p <0.01). Racially-based mistrust did not emerge as a negative predictor and subjects'' decisions were not influenced by the race of the research staff. In conclusion, these results suggest that health-related factors, and not psychosocial perceptions, have predominant influence on research participation among African Americans. [Copyright &y& Elsevier]

Context: Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD. Objective: To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension. Design: Randomized 3 × 2 factorial trial with enrollment from February 1995 to September 1998. Setting and Participants: A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m[sup 2]) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years. Interventions: Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a β-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals. Main Outcome Measures: Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or ≥25 mL/min per 1.73 m[sup 2]) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol. Results: Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m[sup 2] per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m[sup 2] per year; P = .24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95%... [ABSTRACT FROM AUTHOR]

A letter is presented in response to the article "Effects of Body Size and Hypertension Treatments on Cardiovascular Event Rates: Subanalysis of the ACCOMPLISH Randomised Controlled Trial" by M. A. Weber et al. in the February 16, 2013 issue.

Background: Acute declines in estimated glomerular filtration rate (eGFR) occur commonly after starting angiotensin-converting enzyme inhibitors. Whether declines in eGFR that occur after simultaneously starting angiotensin-converting enzyme inhibitors with other antihypertensive agents modifies the benefits of these agents on cardiovascular outcomes is unclear., Methods and Results: We identified predictors of acute declines in eGFR (>15% over 3 months) during randomization to benazepril plus amlodipine versus benazepril plus hydrochlorothiazide in the ACCOMPLISH (Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension) trial. We then determined the relation between declines in eGFR (treated as a binary variable, ≤15% versus >15% and separately, as a restricted spline variable) and the composite risk of fatal and nonfatal cardiovascular events using Cox proportional hazards models. We included 10 714 participants (median age 68 years [Q1 63, Q3 73]), of whom 1024 reached the trial end point over median follow-up of 2.8 years. Predictors of acute declines in eGFR>15% over 3 months included assignment to hydrochlorothiazide (versus amlodipine) and higher baseline albuminuria. Overall, declines in eGFR ≥15% (versus <15%) were associated with a 26% higher hazard of cardiovascular outcomes (95% CI, 1.07-1.48). In spline-based analysis, risk for cardiovascular outcomes was higher in the hydrochlorothiazide arm at every level of decline in eGFR compared with the same magnitude of eGFR decline in the amlodipine arm., Conclusion: Combined use of benazepril and amlodipine remains superior to benazepril and hydrochlorothiazide for cardiovascular outcomes, regardless of the magnitude of the decline in eGFR that occurred with initiation of therapy.

Competing Interests: Disclosures R.D. Brook is a consultant for Alnylam Pharmaceuticals. The other authors report no conflicts.

Rationale & Objective: In FIDELITY, finerenone improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). This analysis explored the efficacy and safety of finerenone in Black patients., Study Design: Subanalysis of randomized controlled trials., Setting & Participants: Patients with T2D and CKD., Intervention: Finerenone or placebo., Outcomes: Composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; composite of kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline from baseline maintained for ≥4 weeks, or renal death., Results: Of the 13,026 patients, 522 (4.0%) self-identified as Black. Finerenone demonstrated similar effects on the cardiovascular composite outcome in Black (HR, 0.79 [95% CI, 0.51-1.24]) and non-Black patients (HR, 0.87 [95% CI, 0.79-0.96; P  = 0.5 for interaction]). Kidney composite outcomes were consistent in Black (HR, 0.71 [95% CI, 0.43-1.16]) and non-Black patients (HR, 0.76 [95% CI, 0.66-0.88; P  = 0.9 for interaction]). Finerenone reduced urine albumin-to-creatinine ratio by 40% at month 4 (least-squares mean treatment ratio, 0.60 [95% CI, 0.52-0.69; P  < 0.001]) in Black patients and 32% at month 4 (least-squares mean treatment ratio, 0.68 [95% CI, 0.66-0.70; P  < 0.001]) in non-Black patients, versus placebo. Chronic eGFR decline (month 4 to end-of-study) was slowed in Black and non-Black patients treated with finerenone versus placebo (between-group difference, 1.4 mL/min/1.73 m 2 per year [95% CI, 0.33-2.44; P  = 0.01] and 1.1 mL/min/1.73 m 2 per year [95% CI, 0.89-1.28; P < 0.001], respectively). Safety outcomes were similar between subgroups., Limitations: Small number of Black patients; analysis was not originally powered to determine an interaction effect based on Black race., Conclusions: The efficacy and safety of finerenone appears consistent in Black and non-Black patients with CKD and T2D., Funding: Bayer AG., Trial Registration: ClinicalTrials.gov NCT02540993, NCT02545049., Plain-Language Summary: Diabetes is a major cause of chronic kidney disease (CKD), affecting more Black adults than White adults. Most adults with CKD ultimately die from heart and vascular complications (eg, heart attack and stroke) rather than kidney failure. This analysis of 2 recent trials shows that the drug finerenone was beneficial for patients with diabetes and CKD. Along with reducing kidney function decline and protein in the urine, it also decreased heart and vascular issues and lowered blood pressure in both Black and non-Black adults with diabetes and CKD. These findings have promising implications for slowing the progression of CKD and protecting against cardiovascular problems in diverse populations., (© 2023 The Authors.)

Background: Cardiovascular diseases (CVD) are rapidly increasing in low-middle income countries (LMICs). Accurate risk assessment is essential to reduce premature CVD by targeting primary prevention and risk factor treatment among high-risk groups. Available CVD risk prediction models are built on predominantly Caucasian risk profiles from high-income country populations, and have not been evaluated in LMIC populations. We aimed to compare six existing models for predicted 10-year risk of CVD and identify high-risk groups for targeted prevention and treatment in Haiti., Methods: We used cross-sectional data within the Haiti CVD Cohort Study, including 1345 adults ≥ 40 years without known history of CVD and with complete data. Six CVD risk prediction models were compared: pooled cohort equations (PCE), adjusted PCE with updated cohorts, Framingham CVD Lipids, Framingham CVD Body Mass Index (BMI), WHO Lipids, and WHO BMI. Risk factors were measured during clinical exams. Primary outcome was continuous and categorical predicted 10-year CVD risk. Secondary outcome was statin eligibility., Results: Sixty percent were female, 66.8% lived on a daily income of ≤ 1 USD, 52.9% had hypertension, 14.9% had hypercholesterolemia, 7.8% had diabetes mellitus, 4.0% were current smokers, and 2.5% had HIV. Predicted 10-year CVD risk ranged from 3.6% in adjusted PCE (IQR 1.7-8.2) to 9.6% in Framingham-BMI (IQR 4.9-18.0), and Spearman rank correlation coefficients ranged from 0.86 to 0.98. The percent of the cohort categorized as high risk using model specific thresholds ranged from 1.8% using the WHO-BMI model to 41.4% in the PCE model (χ 2  = 1416, p value < 0.001). Statin eligibility also varied widely., Conclusions: In the Haiti CVD Cohort, there was substantial variation in the proportion identified as high-risk and statin eligible using existing models, leading to very different treatment recommendations and public health implications depending on which prediction model is chosen. There is a need to design and validate CVD risk prediction tools for low-middle income countries that include locally relevant risk factors., Trial Registration: clinicaltrials.gov NCT03892265 ., (© 2022. The Author(s).)

The greater antihypertensive responses to initial therapy with calcium channel blockers (CCBs) or thiazide-type diuretics than renin-angiotensin system blockers as initial therapy in non-Hispanic Black (NHB) adults was recognized in the US High BP guidelines from 1988 to 2003. The 2014 Report from Panel Members Appointed to the Eighth Joint National Committee (2014 aJNC8 Report) and the 2017 American College of Cardiology/American Heart Association High Blood Pressure Guideline were the first to recommend CCBs or thiazide-type diuretics rather than renin-angiotensin system blockers as initial therapy in NHB. We assessed the temporal relationship of these recommendations on self-reported CCB or thiazide-type diuretics monotherapy by NHB and NHW adults with hypertension absent compelling indications for β-blockers or renin-angiotensin system blockers in National Health and Nutrition Examination Surveys 2015 to 2018 versus 2007 to 2012 (after versus before 2014 aJNC8 Report). CCB or thiazide-type diuretics monotherapy was unchanged in NHW adults (17.1% versus 18.1%, P =0.711) and insignificantly higher after 2014 among NHB adults (43.7% versus 38.2%, P =0.204), although CCB monotherapy increased (29.5% versus 21.0%, P =0.021) and renin-angiotensin system blocker monotherapy fell (44.5% versus 31.0%, P =0.008). Although evidence-based CCB monotherapy increased among NHB adults in 2015 to 2018, hypertension control declined as untreated hypertension and monotherapy increased. While a gap between recommended and actual monotherapy persists, evidence-based monotherapy appears insufficient to improve hypertension control in NHB adults, especially given evidence for worsening therapeutic inertia. Initiating treatment with single-pill combinations and timely therapeutic intensification when required to control hypertension are evidence-based, race-neutral options for improving hypertension control among NHB adults.

COVID-19 has had a substantial impact on clinical care and lifestyles globally. The State of Michigan reports over 80,000 positive COVID-19 tests between March 1, 2020 and July 29, 2020. We surveyed 8,041 Michigan Medicine biorepository participants in late June 2020. We found that 55% of COVID-19 cases reported no known exposure to family members or to someone outside the house diagnosed with COVID-19. A significantly higher rate of COVID-19 cases were employed as essential workers (45% vs 19%, p = 9x10-12). COVID-19 cases reporting a fever were more likely to require hospitalization (categorized as severe; OR = 4.4 [95% CI: 1.6-12.5, p = 0.005]) whereas respondents reporting rhinorrhea was less likely to require hospitalization (categorized as mild-to-moderate; OR = 0.16 [95% CI: 0.04-0.73, p = 0.018]). African-Americans reported higher rates of being diagnosed with COVID-19 (OR = 4.0 [95% CI: 2.2-7.2, p = 5x10-6]), as well as higher rates of exposure to family or someone outside the household diagnosed with COVID-19, an annual household income < $40,000, living in rental housing, and chronic diseases. During the Executive Order in Michigan, African Americans, women, and the lowest income group reported worsening health behaviors and higher overall concern for the potential detrimental effects of the pandemic. The higher risk of contracting COVID-19 observed among African Americans may be due to the increased rates of working as essential employees, lower socioeconomic status, and exposure to known positive cases. Continued efforts should focus on COVID-19 prevention and mitigation strategies, as well as address the inequality gaps that result in higher risks for both short-term and long-term health outcomes., Competing Interests: We disclose that Dr. Willer’s spouse works for Regeneron Pharmaceuticals Inc., and that Dr. Brummett is a consultant for Heron Therapeutics and Alosa Health. These disclosures do not alter our adherence to PLOS ONE policies on sharing data and materials.

Background and Objectives: Previous studies suggest that tobacco, alcohol, and illicit drug use is associated with CKD. We examined the associations of substance use with CKD progression and all-cause mortality among patients with CKD., Design, Setting, Participants, & Measurements: The Chronic Renal Insufficiency Cohort Study is a prospective, longitudinal cohort study among 3939 participants with CKD in the United States. Self-reported tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug (cocaine, heroin, or methamphetamine) use were obtained at baseline and annual follow-up visits. CKD progression was defined as incident ESKD or halving of eGFR. Substance use was modeled as the cumulative average exposure to capture both recent and long-term use in multivariable time-dependent Cox regression., Results: Over a median 5.5-year follow-up, 1287 participants developed CKD progression, and 1001 died. Baseline proportions of tobacco smoking, alcohol drinking, marijuana use, and hard illicit drug use were 13%, 20%, 33%, and 12%, respectively. Compared with nonsmoking throughout follow-up, multivariable-adjusted hazard ratios for persistent tobacco smoking were 1.02 (95% confidence interval, 0.86 to 1.21) for CKD progression and 1.86 (95% confidence interval, 1.54 to 2.24) for all-cause mortality. Compared with nondrinking throughout follow-up, multivariable-adjusted hazard ratios for persistent alcohol drinking were 1.06 (95% confidence interval, 0.88 to 1.29) for CKD progression and 0.73 (95% confidence interval, 0.58 to 0.91) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent marijuana use were 0.94 (95% confidence interval, 0.82 to 1.07) for CKD progression and 1.11 (95% confidence interval, 0.96 to 1.30) for all-cause mortality. Compared with nonuse throughout follow-up, multivariable-adjusted hazard ratios for persistent hard illicit drug use were 1.25 (95% confidence interval, 1.00 to 1.55) for CKD progression and 1.41 (95% confidence interval, 1.10 to 1.81) for all-cause mortality., Conclusions: Hard illicit drug use is associated with higher risk of CKD progression and all-cause mortality, tobacco smoking is associated with higher risk of all-cause mortality, and alcohol drinking is associated with lower risk of all-cause mortality among patients with CKD., (Copyright © 2018 by the American Society of Nephrology.)

The magnitude of decline in renal function that should be tolerated during intensive BP lowering and its association with risk of ESRD are unclear. To determine whether the acute declines in kidney function in the intensive BP lowering arm of two trials in CKD associated with higher risk of ESRD, we performed a retrospective study of 899 African American Study of Kidney Disease and Hypertension (AASK) and 761 Modification of Diet in Renal Disease (MDRD) Trial participants previously randomized to strict versus usual BP control. The predictor was the percentage decline in eGFR (<5%, 5% to <20%, or ≥20%) between randomization and months 3 and 4 of the trial (time to achieve BP goals). ESRD was the outcome of interest. Compared with a <5% eGFR decline in the usual BP arm, a 5% to <20% eGFR decline during intensive BP lowering did not associate with a higher risk of ESRD in the AASK (adjusted hazard ratio [aHR], 1.19; 95% confidence interval [95% CI], 0.84 to 1.68) or the MDRD Trial (aHR, 1.08; 95% CI, 0.84 to 1.40). However, a 5% to <20% eGFR decline in the usual BP arm associated with higher risk of ESRD in AASK (aHR, 1.83; 95% CI, 1.30 to 2.57) and MDRD Trial (aHR, 1.62; 95% CI, 1.25 to 2.11). A ≥20% eGFR decline associated with higher risk of ESRD in both strict and usual BP arms. Thus, acute eGFR declines ≥20% during intensive BP lowering identified a subset of patients at higher risk for adverse outcomes., (Copyright © 2017 by the American Society of Nephrology.)

Randomized clinical trials have not shown an additional clinical benefit of renal artery stent placement over optimal medical therapy alone. However, studies of renal artery stent placement have not examined the relationship of albuminuria and treatment group outcomes. The CORAL study (Cardiovascular Outcomes in Renal Atherosclerotic Lesions) is a prospective clinical trial of 947 participants with atherosclerotic renal artery stenosis randomized to optimal medical therapy with or without renal artery stent which showed no treatment differences (3(5.8% and 35.1% event rate at mean 43-month follow-up). In a post hoc analysis, the study population was stratified by the median baseline urine albumin/creatinine ratio (n=826) and analyzed for the 5-year incidence of the primary end point (myocardial infarction, hospitalization for congestive heart failure, stroke, renal replacement therapy, progressive renal insufficiency, or cardiovascular disease- or kidney disease-related death), for each component of the primary end point, and overall survival. When baseline urine albumin/creatinine ratio was ≤ median (22.5 mg/g, n=413), renal artery stenting was associated with significantly better event-free survival from the primary composite end point (73% versus 59% at 5 years; P=0.02), cardiovascular disease-related death (93% versus 85%; P≤ 0.01), progressive renal insufficiency (91% versus 77%; P=0.03), and overall survival (89% versus 76%; P≤0.01), but not when baseline urine albumin/creatinine ratio was greater than median (n=413). These data suggest that low albuminuria may indicate a potentially large subgroup of those with renal artery stenosis that could experience improved event-free and overall-survival after renal artery stent placement plus optimal medical therapy compared with optimal medical therapy alone. Further research is needed to confirm these preliminary observations., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00081731., (© 2016 American Heart Association, Inc.)

For people enrolled in Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL), we sought to examine whether variation exists in the baseline medical therapy of different geographic regions and if any variations in prescribing patterns were associated with physician specialty. Patients were grouped by location within the United States (US) and outside the US (OUS), which includes Canada, South America, Europe, South Africa, New Zealand, and Australia. When comparing US to OUS, participants in the US took fewer anti-hypertensive medications (1.9 ± 1.5 vs. 2.4 ± 1.4; P < .001) and were less likely to be treated with an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (46% vs. 62%; P < .001), calcium channel antagonist (37% vs. 58%; P < .001), and statin (64% vs. 75%; P < .05). In CORAL, the identification of variations in baseline medical therapy suggests that substantial opportunities exist to improve the medical management of patients with atherosclerotic renal-artery stenosis., (Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)

Purpose: To describe the experience and results from the roll-in phase of the Cardiovascular Outcomes with Renal Atherosclerotic Lesions (CORAL) study., Materials and Methods: The CORAL roll-in database was used to describe the baseline characteristics of the patients in the roll-in cohort, all of whom underwent renal artery stent placement; to evaluate CORAL site performance; to compare estimates of lesion (stenosis) severity made by site interventionalists with the central CORAL angiographic core laboratory readings; and to report outcomes after renal artery stent placement. During the roll-in phase, 239 patients (mean age, 70.2 y ± 9.0; 49% male) underwent renal artery stent procedures. Angiographic core laboratory analysis of renal arteriograms was done, and participants were followed at 1 month and 9 months., Results: Major angiographic complications were identified in 28 (13%) subjects. Kidney function remained unchanged at the short (2-4 weeks) follow-up interval. Improvement in systolic blood pressure with use of distal embolic protection devices (n = 161) did not show any clinical benefit over nonuse of such devices (n = 78) in this small series. At 9 months, there were significantly more endpoints reported by site in subjects with bilateral renal artery stenosis (P = .01) and prior history of stroke (P = .03)., Conclusions: In the roll-in phase of the CORAL study, a significant number of angiographic complications were identified. No effect was seen on estimated glomerular filtration rate after renal artery stent placement, but systolic blood pressure decreased significantly., (© 2013 Published by SIR on behalf of The Society of Interventional Radiology.)

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommended a thiazide-like diuretic, alone or in combination with other antihypertensive drug classes, as initial therapy for hypertension. JNC 7, however, did not specify preferred combinations. The Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial was completed five years after the JNC 7 and demonstrated a 20 % advantage in cardiovascular risk reduction when blood pressure was lowered using the single-pill combination of benazepril-amlodipine compared to benazepril-hydrochlorothiazide (Jamerson et al. 359(23):2417-28 [1]). This new and significant finding provided compelling evidence that the long-standing preference for diuretics as initial therapy could be refuted, but it may also be relevant to the lower-than-expected reduction in coronary disease related events (compared to stroke) observed for decades prior to the ACCOMPLISH approach to therapy. The JNC 8 panel members recently published their recommendations, and while the group did not recommend benazepril-hydrochlorothiazide over other combinations, they did highlight the findings of ACCOMPLISH, rating the primary ACCOMPLISH paper as "good." The American Society of Hypertension position paper and the European Hypertension Society guidelines endorse such combinations as a first-line agent for patients with stage 2 hypertension. We review the current position of ACCOMPLISH in the guidelines regarding treatment of stage 2 hypertension.

Objectives: Added-risk hypertensive patients with co-morbidities such as diabetes and metabolic syndrome often require two or more antihypertensives to achieve blood pressure (BP) targets. The aim of this sub-analysis was to determine the efficacy and safety of telmisartan 40 or 80 mg plus amlodipine 5 or 10 mg in patients with hypertension, stratified according to certain criteria such as type 2 diabetes mellitus and metabolic syndrome., Methods: Patients were treated for 8 weeks with telmisartan 20-80 mg plus amlodipine 2.5-10 mg. This post-hoc analysis included patients treated with higher doses, and stratified according to a number of sub-populations (age, race, diabetes, obesity, metabolic syndrome, elevated baseline systolic BP (SBP), renal impairment)., Results: Eight weeks' treatment with telmisartan plus amlodipine combinations provided consistent reductions in mean SBP/diastolic BP (DBP) across the different sub-populations, similar to the overall population. SBP/DBP reductions ranged from -13.5 to -34.7/-12.6 to -26.1 mmHg and BP goal rates (<140/90 mmHg) ranged from 29.8-100% for the four key dose combinations of telmisartan plus amlodipine. For the highest dose combination of telmisartan 80 mg plus amlodipine 10 mg, SBP/DBP reduction ranged from -19.1 to -34.7/-16.4 to -22.8 mmHg and goal attainment rate from 66.7% to 87.0%. Across the sub-populations, high SBP and DBP response rates were seen with combination treatment (83.3-97.7% and 75.0-95.7%, respectively, with telmisartan 80 mg plus amlodipine 10 mg). The combination was safe and well tolerated across all sub-populations and the incidence of peripheral oedema with telmisartan 40-80 mg plus amlodipine 10 mg was generally lower than with A10 monotherapy., Conclusions: Despite small patient numbers in some sub-populations and the post-hoc nature of the analysis, this does show that the combination of telmisartan plus amlodipine provides an effective, safe and well-tolerated antihypertensive treatment for added-risk hypertensive patients.

Background: Epidemiological studies typically diagnose heart failure (HF) at the time of hospitalization, and have not evaluated the prevalence of HF symptoms in CKD patients without a prior HF diagnosis., Methods and Results: We modified the Kansas City Cardiomyopathy Questionnaire (KCCQ) to detect and quantify symptoms characteristic of HF (dyspnea, edema, and fatigue) among 2883 chronic kidney disease (CKD) patients without diagnosed heart failure in the Chronic Renal Insufficiency Cohort (CRIC). The KCCQ is a 23-item instrument that quantifies the impact of dyspnea, fatigue, and edema on physical, social, and emotional functions (scored 0 to 100). The median KCCQ score was 92, and 25% had KCCQ scores <75. Compared with cystatin C‑based estimated glomerular filtration rate >50 mL·min·1.73 m(2) (reference), estimated glomerular filtration rate 40 to 50, 30 to 40, and <30 were independently associated with lower KCCQ scores (<75); adjusted odds ratios and (95% CI): 1.38 (1.06-1.78), 1.39 (1.09-1.82), and 2.15 (1.54-3.00), respectively. Lower hemoglobin (Hb) levels also had independent associations with KCCQ <75: Hb >14 g/dL (reference), Hb 13 to 14 g/dL (1.03; 0.76-1.40), Hb 12 to 13 g/dL (1.41; 1.04-1.91), Hb 11 to 12 g/dL (1.56; 1.12-2.16); and Hb <1 g/dL (1.65; 1.15-2.37)., Conclusion: CKD patients without diagnosed HF have a substantial burden of symptoms characteristic of HF, particularly among those with lower estimated glomerular filtration rate and hemoglobin levels., (Published by Elsevier Inc.)

Hypertension is a worldwide risk factor for premature death and disability from heart disease, stroke, peripheral vascular disease, and kidney failure. Much is known about the role of elevated blood pressure as a contributor to diseases of the heart and brain, but the risk it confers specifically to the development and progression of kidney disease is less well appreciated. The kidney is unique among the target organs of elevated blood pressure because it both suffers damage and still contributes to the pathophysiologic sustenance of hypertension through many avenues. In this overview, we discuss high blood pressure from an epidemiologic standpoint, placing it in a nephrologic perspective and discuss some of the known and speculative mechanisms that link it to kidney damage., (2011 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is significantly elevated in patients with kidney disease and is a potential risk factor for cardiovascular disease. Here, we tested whether human whole blood (WB), as in rodent blood, can accumulate free ADMA and whether this accumulation is a function of disease burden., Methods: In 16 healthy control subjects (CO), 18 patients with ESRD and 18 matched hypertensive patients with normal renal function (HTN), we compared using high-pressure liquid chromatography baseline plasma and WB supernatant (WBSUP) ADMA and symmetrical dimethylarginine (SDMA) concentrations and accumulation during a 5-h incubation. We measured protein turnover in incubated WBSUP to determine if proteolytic processes drive ADMA accumulation., Results: Elevated plasma ADMA was confirmed in ESRD and HTN populations while basal WBSUP ADMA was significantly higher in ESRD subjects than controls (P = 0.05 versus CO; P = 0.02 versus HTN). Plasma SDMA followed a similar pattern. Incubation of WBSUP resulted in ADMA release from protein-incorporated stores while SDMA was unaffected. ADMA accumulation in ESRD samples was significantly greater than that in HTN (P = 0.03). CO and HTN men showed significantly greater ADMA accumulation than women (P = 0.01 and P = 0.003, respectively) but no gender difference was observed in the ESRD group (P = 0.26). ADMA accumulation correlated with ex vivo protein turnover (R = 0.76, P < 0.0001)., Conclusions: Human blood is capable of releasing physiologically significant quantities of ADMA via proteolytic pathways. Dysregulated ADMA release from WB reservoirs may contribute to the distinctly high plasma ADMA levels in ESRD populations.

Background: The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting-enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic., Methods: In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization., Results: The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril-amlodipine group and 132.5/74.4 mm Hg in the benazepril-hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril-amlodipine group (9.6%) and 679 in the benazepril-hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril-amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001). For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P=0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs., Conclusions: The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.), (2008 Massachusetts Medical Society)

Background: Chronic kidney disease, undiagnosed in a significant number of adults, is a public health problem. Given the systemic inflammatory response to periodontal disease, we hypothesized that periodontal disease could be associated with chronic kidney disease., Study Design: Cross-sectional., Setting & Participants: We identified 12,947 adults 18 years or older with information for kidney function and at least one risk factor in the Third National Health and Nutrition Examination Survey., Predictor: The main predictor was periodontal status. Other nontraditional and traditional risk factors included socioeconomic status, health status, health behavior, biomarker levels, anthropometric assessment, and health care utilization., Outcomes & Measurements: Chronic kidney disease was defined using the Kidney Disease Outcomes Quality Initiative stages 3 and 4 with a moderate to severe decrease in kidney function (glomerular filtration rate, 15 to 59 mL/min/1.73 m(2)). Univariable and multivariable logistic regression models assessed the associations between chronic kidney disease and periodontal disease and other nontraditional risk factors., Results: Chronic kidney disease prevalence was 3.6%; periodontal disease prevalence was 6.0%; and edentulism prevalence was 10.5%. Adults with periodontal disease and edentulous adults were twice as likely to have chronic kidney disease (adjusted odds ratio, 1.60; 95% confidence interval, 1.16 to 2.21; adjusted odds ratio, 1.85; 95% confidence interval, 1.34 to 2.56, respectively) after simultaneously adjusting for other traditional and nontraditional risk factors., Limitations: Temporal association is unknown., Conclusions: Periodontal disease and its severe consequence, edentulism, were independently associated with chronic kidney disease after adjusting for other traditional and nontraditional risk factors. This model could contribute to identifying individuals at risk of chronic kidney disease and reduce its burden.

Background: Atherosclerotic renal artery stenosis is a problem with no consensus on diagnosis or therapy. The consequences of renal ischemia are neuroendocrine activation, hypertension, and renal insufficiency that can potentially result in acceleration of atherosclerosis, further renal dysfunction, myocardial infarction, heart failure, stroke, and death. Whether revascularization improves clinical outcomes when compared with optimum medical therapy is unknown., Methods: CORAL is a randomized clinical trial contrasting optimum medical therapy alone to stenting with optimum medical therapy on a composite cardiovascular and renal end point: cardiovascular or renal death, myocardial infarction, hospitalization for congestive heart failure, stroke, doubling of serum creatinine, and need for renal replacement therapy. The secondary end points evaluate the effectiveness of revascularization in important subgroups of patients and with respect to all-cause mortality, kidney function, renal artery patency, microvascular renal function, and blood pressure control. We will also correlate stenosis severity with longitudinal renal function and determine the value of stenting from the perspectives of quality of life and cost-effectiveness. The primary entry criteria are (1) an atherosclerotic renal stenosis of > or = 60% with a 20 mm Hg systolic pressure gradient or > or = 80% with no gradient necessary and (2) systolic hypertension of > or = 155 mm Hg on > or = 2 antihypertensive medications. Randomization will occur in 1080 subjects. The study has 90% power to detect a 28% reduction in primary end point hazard rate., Conclusions: CORAL represents a unique opportunity to determine the incremental value of stent revascularization, in addition to optimal medical therapy, for the treatment of atherosclerotic renal artery stenosis.

Hypertension treatment and control is of paramount importance in the prevention of premature cardiovascular disease. African Americans present a special challenge to the clinician due, in part, to their earlier age of onset,greater prevalence, and increased rates of untoward events. A review of the recent studies of genetic epidemiology has not revealed unique genotypes that explain human hypertension or the disparate impact suffered by African Americans. Moreover, a clear message has emerged that environmental factors predominate in their effect on cardiovascular risk and are mutable. These findings suggest that to have an immediate and substantial impact on the ethnic disparity of hypertension, resources and research should be directed toward social and behavioral factors. Prompt and aggressive control of blood pressure is an effective global strategy for cardiovascular risk reduction. In most cases, this approach requires multiple interventions including lifestyle modification and an antihypertensive regimen that is tailored to the individual under the current guidelines and not stipulated by race.

Hypertension is a major risk factor for chronic kidney disease (CKD), cardiovascular disease, cerebrovascular events, and premature death. However, certain groups are known to be at higher risk for hypertensive end-organ damage, including diabetic patients, older patients with isolated systolic hypertension, and specific ethnic populations. Coexistent diabetes and hypertension dramatically increase the risk of developing CKD and other target-organ complications. The prevalence of hypertension, left ventricular hypertrophy, CKD, hypertensive renal disease, and end-stage renal disease (ESRD) is far greater in African Americans compared with white Americans. Identification of patients at increased risk for CKD offers the potential to prevent or delay ESRD and the cardiovascular events associated with CKD. Data from completed and ongoing controlled clinical hypertension trials will assist clinicians in creating optimal antihypertensive regimens for patients at increased risk for CKD.

We measured health-related quality of life (HRQL) by using the Medical Outcomes Study 36-Item Short-Form (SF-36) in a cross-sectional study of 1,094 African American men and women with mild to moderate chronic renal insufficiency (mean glomerular filtration rate, 45.7 mL/min/1.73 m2) caused by hypertension before randomization onto the African American Study of Kidney Disease and Hypertension (AASK) Trial. Scales contributing to physical health and a summary measure, the Physical Component Summary (PCS) score (mean, 43.4 +/- 10.9 [SD]), were significantly lower than scales relating to mental health and the Mental Component Summary (MCS) score (51.3 +/- 10.3). All scales (except Role-Physical) and the PCS and MCS were significantly higher in men (44.3 +/- 10.9 and 51.8 +/- 10.0, respectively) than women (41.9 +/- 10.8 and 50.5 +/- 10.6, respectively). In multivariate analysis, employment status, education level, household income, body mass index, comorbid medical conditions, years of hypertension, number of antihypertensive drugs prescribed, exercise status, and male sex were significant independent predictors of PCS. Fewer factors predicted MCS and included employment status, marital status, current smoking, age, comorbid medical conditions, and male sex. In the entire AASK cohort, mean scores for individual scales, except Mental Health, and the PCS were lower, but the mean MCS score was slightly higher than values for the US general population. Values for individual scales of the SF-36 and the PCS were substantially higher among AASK participants compared with African-American hemodialysis patients. Six of the eight scales were lower in the AASK cohort compared with groups of racially mixed and exclusively African-American hypertensive subjects. We conclude that physical aspects of quality of life are substantially reduced compared with mental components among AASK participants, and a number of demographic and clinical characteristics significantly impact on HRQL., (Copyright 2002 by the National Kidney Foundation, Inc.)