AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress.

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Whether visit-to-visit blood pressure variability (BPV) is associated with adverse outcomes in patients with heart failure (HF) with preserved ejection fraction is unclear. We assessed these associations in 3184 patients with HF (51.0% women; mean age, 68.6 years) with preserved ejection fraction (≥45%) enrolled in the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist). BPV indexes were the SD, variability independent of the mean, and average real variability. The primary end point consisted of total mortality, myocardial infarction, stroke, and hospitalized HF. We computed hazard ratios for the risks associated with 1-SD increase in BPV indexes, using multivariable Cox regression to adjust for the BP level and confounders. In the placebo group (n=1577), the primary composite end point, stroke, and hospitalized HF were significantly associated with systolic and diastolic BPV (hazard ratios, ≥1.28; P ≤0.008) and total mortality with systolic BPV (hazard ratios ≥1.20; P ≤0.010). In the spironolactone group (n=1607), the primary end point and hospitalized HF were associated with both systolic and diastolic BPV (hazard ratios ≥1.17; P ≤0.006). Sensitivity analyses stratified by sex, median age, and region generated confirmatory results. Most of the interactions between randomized group and BPV indexes were not significant. In conclusion, in patients with HF with preserved ejection fraction, greater systolic and diastolic BPV were associated with adverse health outcomes over and beyond the BP level.

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