Left atrial volume in patients with asymptomatic aortic valve stenosis (the Simvastatin and Ezetimibe in Aortic Stenosis study)

Left atrial (LA) size is known to increase with persistently increased left ventricular (LV) filling pressure. We therefore hypothesized that LA volume might reflect the severity of aortic valve stenosis (AS). Transthoracic echocardiography was performed in 1,758 patients with asymptomatic AS (transaortic Doppler velocity > or =2.5 and < or =4 m/s) in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. LA volume was measured in end-systole in the apical 4-chamber view in 1,503 patients (85%), and aortic valve area (AVA) was estimated by the continuity equation and indexed by body surface area. Mean values for age and AVA were 67 +/- 10 years and 1.27 +/- 0.5 cm2, respectively, and 574 were women (38%). Mean value for LA volume indexed (LAVI) was 36 +/- 13 ml/m2. Enlargement of LA volume (> or =32 ml/m2) was found in 57% of patients. AVA indexed was significantly correlated to LAVI (r = -0.1, p = 0.0002). Multivariate analysis showed that LAVI was significantly related to AVA indexed (beta = -4.1, p = 0.007) in a model that also included mitral regurgitation (beta = 2.8, p <0.0001), history of hypertension (beta = 2.2, p = 0.002), LV end-diastolic volume (beta = 0.05, p <0.0001), presence of LV hypertrophy (beta = 3.4, p <0.0001), and restrictive LV filling pattern (beta = 3.5, p = 0.01). Gender and LV ejection fraction were eliminated from the final model. In conclusion, LA volume is often enlarged in asymptomatic patients with AS. Furthermore, LA volume is related to AVA even when adjusting for other known risk factors for increased LA volume including of measurements of diastolic function.     

Effect of Low‐Density Lipoprotein Cholesterol Lowering by Ezetimibe/Simvastatin on Outcome Incidence: Overview,Meta‐Analyses,and Meta‐Regression Analyses of Randomized Trials

This analysis investigated the extent of different outcome reductions from low‐density lipoprotein cholesterol (LDL‐C) lowering following ezetimibe/simvastatin treatment and the proportionality of outcome to LDL‐C reductions. The authors searched PubMed between 1997 and mid‐June 2015 (any language) and the Cochrane Library to identify all randomized controlled trials comparing ezetimibe/simvastatin with placebo or less intensive LDL‐C lowering. Risk ratios (RR) and 95% confidence intervals (CIs), standardized to 20 mg/dL LDL‐C reduction, were calculated for 5 primary outcomes (fatal and nonfatal) and 4 secondary outcomes (non‐cardiovascular [CV] death, cancer, myopathy, and hepatopathy). Five ezetimibe/simvastatin RCTs (30 051 individuals) were eligible, 2 comparing ezetimibe/simvastatin vs placebo and 3 vs less intensive treatment. Outcomes reduced almost to the same extent were stroke (RR: ?13%, 95% CI: ?21% to ?3%), coronary heart disease (CHD; RR: ?12%, 95% CI: ?19% to ?5%), and composite of stroke and CHD (RR: ?14%, 95% CI: ?20% to ?8%). Absolute risk reductions: 5 strokes, 10 CHD events, and 16 stroke and CHD events prevented for every 1000 patients treated for 5 years. Residual risk was almost 7× higher than absolute risk reduction for all the above outcomes. All death outcomes were not reduced, and secondary outcomes did not differ between groups. Logarithmic risk ratios were not associated with LDL‐C lowering. Our meta‐analysis provides evidence that, in patients with different CV disease burden, major CV events are safely reduced by LDL‐C lowering with ezetimibe/simvastatin, while raising the hypothesis that the extent of LDL‐C lowering might not be accompanied by incremental clinical‐event reduction.