New statin use and left ventricular structure: estimating long-term associations in the Multi-Ethnic Study of Atherosclerosis (MESA)

Thesis (Master's)--University of Washington, 2016-08Recent treatment guidelines in the United States have increased the number of statin-eligible individuals. While statin use is associated with a modest reduction in heart failure hospitalizations in meta-analyses of statin trials, the mechanism is unclear. Only small and short-term studies have evaluated statins in relation to changes in heart structure. We estimated the association of new statin use with 10-year remodeling of the left ventricle. The Multi-Ethnic Study of Atherosclerosis (MESA) collected data on statin use at five clinic exams over about 10 years, and conducted cardiac magnetic resonance (CMR) imaging at both baseline and the 10-year exam. Participants were free of known cardiovascular disease (CVD) and we excluded statin users at baseline. Cumulative statin use and statin dose were estimated between exam intervals for each positive report of current use. Primary outcomes were the change in left ventricular mass index (LVMI; % predicted by height, weight and sex relative to a healthy population) and mass-to-volume ratio (MVR). Associations were estimated in multivariable linear regression analyses, adjusting for baseline age, race, sex, traditional CVD risk factors, anti-hypertensive medication, exercise, health insurance, and coronary artery calcium. A total of 3113 participants (53% female; 40% white, 25% African-American, 22% Hispanic, 13% Chinese-American) had a valid CMR scan and no statin use at baseline; 2431 returned for a follow-up CMR after a median of 9.4 years. Statin therapy (moderate dose in 76%) was started by 36% of participants (N=872) and the duration of use ranged from 1.5-8 years among new users (median: 3.25 years). We excluded 42 participants with an incident myocardial infarction during follow-up. Each additional year of statin use was had a marginal association with 10-year progression in LVMI (-0.30, 95%CI: -0.59, -0.02, p=0.04) but not MVR (-0.002, 95%CI: -0.006, 0.002, p=0.42). A modest dose response was observed where higher statin doses were associated with less progression of LVMI (p=0.004, test for trend); association with LVMI was statistically significant only for moderate dose vs. never use (-1.64, 95%CI: -2.95, -0.33, p=0.01). Techniques to account for missing data did not appreciably alter estimates. We found no robust or substantive associations between statin use and indices of left ventricular remodeling over 10 years in a diverse population without clinical CVD at baseline