Effects of Simvastatin on Augmentation Index Are Transient: Outcomes From a Randomized Controlled Trial

BACKGROUND: Statins improve endothelial function, but their effects on arterial stiffness and aortic blood pressure in middle‐aged adults are uncertain. METHODS AND RESULTS: This was a prospective, randomized, double‐blind, placebo‐controlled trial of middle‐aged (40‐72 years old) adults who were randomly assigned to receive simvastatin 40 mg (n=44) or placebo (n=44) daily for 18 months to evaluate impact on dementia‐related biomarkers (primary end points) and measures of vascular health (secondary end points). This analysis focuses on the predetermined secondary end points of changes in central aortic blood pressure, aortic augmentation index, and brachial artery flow‐mediated dilation. Measurements were performed at baseline and after 6, 12, and 18 months. Multivariable models were used to identify predictors of these prespecified vascular end points. Study groups were similar at baseline; low‐density lipoprotein cholesterol declined in the statin group but not in the placebo group (P<0.01). There were no significant differences in changes in central blood pressure parameters or flow‐mediated dilation (all P>0.2). After 12 months, augmentation index decreased from baseline in the statin group compared with the placebo group (−2.3% [5.5%] versus 1.2% [5.7%], P=0.007), but by 18 months the response in both groups trend toward baseline (−1.1% [5.8%] versus 0.2% [4.8%], P=0.3). Low‐density lipoprotein cholesterol was not associated with changes in augmentation index at any time point. CONCLUSIONS: Statin therapy led to a short‐term reduction in augmentation index after 12 months, but this effect did not persist after 18 months despite continued reduction in low‐density lipoprotein cholesterol levels. These findings suggest that statins may have a transient effect on aortic stiffness. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00939822.