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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 © 2013 Elsevier Inc. All rights reserved.)

Background: In previous clinical trials in high-risk hypertensive patients, paradoxically higher cardiovascular event rates have been reported in patients of normal weight compared with obese individuals. As a prespecified analysis of the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial, we aimed to investigate whether the type of hypertension treatment affects patients' cardiovascular outcomes according to their body size., Methods: On the basis of body-mass index (BMI), we divided the full ACCOMPLISH cohort into obese (BMI ≥30, n=5709), overweight (≥25 to <30, n=4157), or normal weight (<25, n=1616) categories. The ACCOMPLISH cohort had already been randomised to treatment with single-pill combinations of either benazepril and hydrochlorothiazide or benazepril and amlodipine. We compared event rates (adjusted for age, sex, diabetes, previous cardiovascular events, stroke, or chronic kidney disease) for the primary endpoint of cardiovascular death or non-fatal myocardial infarction or stroke. The analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00170950., Findings: In patients allocated benazepril and hydrochlorothiazide, the primary endpoint (per 1000 patient-years) was 30·7 in normal weight, 21·9 in overweight, and 18·2 in obese patients (overall p=0·0034). However, in those allocated benazepril and amlodipine, the primary endpoint did not differ between the three BMI groups (18·2, 16·9, and 16·5, respectively; overall p=0·9721). In obese individuals, primary event rates were similar with both benazepril and hydrochlorothiazide and benazepril and amlodipine, but rates were significantly lower with benazepril and amlodipine in overweight patients (hazard ratio 0·76, 95% CI 0·59-0·94; p=0·0369) and those of normal weight (0·57, 0·39-0·84; p=0·0037)., Interpretation: Hypertension in normal weight and obese patients might be mediated by different mechanisms. Thiazide-based treatment gives less cardiovascular protection in normal weight than obese patients, but amlodipine-based therapy is equally effective across BMI subgroups and thus offers superior cardiovascular protection in non-obese hypertension., Funding: Novartis Pharmaceuticals., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The ACCOMPLISH trial (Avoiding Cardiovascular events through Combination therapy in Patients Living with Systolic Hypertension) was a 3-year multicenter, event-driven trial involving patients with high cardiovascular risk who were randomized in a double-blinded manner to benazepril plus either hydrochlorothiazide or amlodipine and titrated in parallel to reach recommended blood pressure goals. Of the 8125 participants in the United States, 1414 were of self-described Black ethnicity. The composite kidney disease end point, defined as a doubling in serum creatinine, end-stage renal disease, or death was not different between Black and non-Black patients, although the Blacks were significantly more likely to develop a greater than 50% increase in serum creatinine to a level above 2.6 mg/dl. We found important early differences in the estimated glomerular filtration rate (eGFR) due to acute hemodynamic effects, indicating that benazepril plus amlodipine was more effective in stabilizing eGFR compared to benazepril plus hydrochlorothiazide in non-Blacks. There was no difference in the mean eGFR loss in Blacks between therapies. Thus, benazepril coupled to amlodipine was a more effective antihypertensive treatment than when coupled to hydrochlorothiazide in non-Black patients to reduced kidney disease progression. Blacks have a modestly higher increased risk for more advanced increases in serum creatinine than non-Blacks.

OBJECTIVE -- To evaluate whether in hypertensive patients the risk of cardiovascular disease is greater in association with the metabolic syndrome (MetS) or the sum of its individual components. RESEARCH DESIGN AND METHODS -- Cox regression analysis models were developed to assess the influence of age, sex, ethnicity, and the individual components of MetS on risk associated with the MetS (using several definitions) of coronary outcomes, stroke, and all-cause mortality. RESULTS -- MetS was significantly associated with coronary outcomes, stroke, and all-cause mortality after adjusting for age, sex, and ethnicity. However, when the model was further adjusted for the individual components, MetS was associated with significantly increased risk of stroke (hazard ratio 1.34 [95% CI 1.07-1.68]) and all-cause mortality (1.35 [1.16-1.58]) but not coronary outcomes (fatal coronary heart disease plus nonfatal myocardial infarction 1.16 [0.95-1.43] and total coronary events 1.06 [0.91-1.24]). CONCLUSIONS- MetS, independent of its individual components, is associated with increased risk of stroke and all-cause mortality but not coronary outcomes. [ABSTRACT FROM AUTHOR]