The effects of atorvastatin (10 mg) on systemic inflammation in heart failure.

In observational studies, statins are associated with lower mortality in patients with heart failure (HF), including those with nonischemic HF. Such benefits could be related to anti-inflammatory effects; however, the effects of statins on systemic inflammation in HF are not well-established. We conducted a 16-week, single-center, randomized, double-blind, placebo-controlled, crossover clinical trial of the effects of atorvastatin 10 mg/day on concentrations of systemic inflammatory markers in 22 patients with HF (including 20 with nonischemic HF) with New York Heart Association class II or III symptoms and left ventricular ejection fraction of <40%. The absolute and percentage of changes in inflammatory marker levels were evaluated using analysis of variance. Statin treatment reduced the concentrations of soluble tumor necrosis factor receptor-1 by 132 pg/ml (p = 0.04) and 8% (p = 0.056), C-reactive protein by 1.6 mg/L (p = 0.006) and 37% (p = 0.0002), and, after adjustment for treatment order, endothelin-1 by 0.21 pg/ml (p = 0.007) and 17% (p = 0.01). In post hoc analyses, the reduction in tumor necrosis factor receptor-1 levels was highest among patients with elevated levels at baseline (at or higher than the median of 1,055 pg/ml, p interaction = 0.001), among whom statin therapy reduced the levels by 306 pg/ml (p <0.001) and 22% (p <0.001). Statin treatment did not significantly affect the levels of other inflammatory markers, including interleukin-6 and brain natriuretic peptide. In conclusion, short-term atorvastatin therapy reduced the levels of several important inflammatory markers in patients with HF.

Hemodynamic effects of the angiotensin-converting enzyme inhibitor, ramipril, in patients with mild to moderate aortic stenosis and preserved left ventricular function.

BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitor use is presumed to be contraindicated in patients with aortic stenosis (AS). We determined the hemodynamic effects of ACE inhibitors in patients with mild to moderate aortic stenosis (AS) and preserved left ventricular function. METHODS: Thirteen elderly patients (mean [SD] age = 65 [17] years), with mild to moderate AS (aortic jet velocity 2.5-4.0 m/s), normal left ventricular and renal function, and no clinical coronary artery disease, were enrolled in a single-center, open-label trial comparing the hemodynamic effects at baseline and following titration of ramipril to a maximum dose of 7.5 mg twice daily. Patients were identified from echocardiography laboratory logs. Despite a presumed contraindication to ACE inhibitor use in AS patients, 30% (71 of 235) of patients otherwise meeting inclusion or exclusion criteria were excluded owing to current ACE inhibitor use. Patients were monitored with weekly clinic visits, biweekly laboratory tests, and monthly echocardiograms. RESULTS: There were no significant changes from baseline to week 8 in echocardiographic parameters, including mean (SD) aortic jet velocity [2.9 (0.4) vs 2.9 (0.4) m/s], calculated aortic transvalvular gradient [18 (6) vs 18 (6) mm Hg], or cardiac output [5.5 (1.2) vs 6.0 (2.1) L/min], or significant changes in blood pressure or heart rate. Early discontinuations were for asymptomatic low blood pressure (one patient) or a reversible creatinine increase of 0.3 mg/dL (one patient). CONCLUSIONS: Short-term treatment with up to 7.5 mg twice daily of ramipril was well tolerated in patients with mild to moderate AS and preserved left ventricular function. A surprisingly high proportion of patients with documented AS were already receiving ACE inhibitors.