Association between Statin use and Incident Peripheral Artery Disease According to Race, Age, and Presence of Depression in the Multi-Ethnic Study of Atherosclerosis

Abstract

BackgroundPeripheral artery disease (PAD) is associated with high morbidity and mortality and has been commonly described as a coronary heart disease equivalent. Statin medications are recommended for primary prevention of atherosclerotic cardiovascular disease (ASCVD) among other indications. Therefore, understanding the longitudinal relationship of incident PAD is necessary to inform future research on how to prevent disease. Depression complicates cardiovascular disease (CVD) patients’ ability to properly adhere to their medications, yet the effect of depression on the relationship between statin use and incident PAD is understudied. People with PAD have a higher incidence of depressive symptoms than people without PAD. Black American and Hispanic populations are disproportionately affected by both PAD and depression yet research on the modifying effect of either race or depression on the relationship between statin use and onset of PAD is minimal. While statin utilization is highest for ages 75–84, there is minimal evidence of favorable risk–benefit balance. Consequently, in this project, we examined the relationship between statin use and incident peripheral artery disease and whether this relationship is modified by race/ethnicity, depressive symptoms, or age. MethodsWe used data on participants from the Multi-Ethnic Study of Atherosclerosis (MESA) from visit 1 (2000) through study visit 6 (2020) who had three separate measurements of the ankle-brachial index (ABI) taken at visit 1, visit 3, and visit 5. Incident PAD was defined as 1) incident lower extremity amputation or revascularization or 2) ABI less than 0.90 coupled with ABI decrease greater than 0.15 over the follow-up period. Statin use was noted on the study visit prior to incident PAD diagnosis while depressive symptoms were measured at exam 1, visit 3, and visit 5. Propensity score matching was implemented to create balance between the participants in the two treatment groups, i.e., statin treated and statin untreated groups to reduce the problem of confounding by indication. Propensity scores were calculated using multivariate logistic regression model to estimate the probability of receiving statin treatment. We used Cox proportional hazards regression to investigate the relationship between time-dependent statin use as well as other risk factors with incident PAD, overall and stratified by 1) race,2) depression status, and 3) age ResultsA total 4,210 participants were included in the final matched analytic cohort. There were 810 (19.3%) incident cases of PAD that occurred over an average (mean) of 11.3 (SD=5.7) years of follow-up time. In the statin treated group, and with the average follow-up time of 12.5 (SD=5.6) years. there were 281 (13.4%) cases of incident PAD with the average follow-up time of 10.1 (SD=5.5), whereas in the statin untreated group, there were 531 (25.2%) cases (p<0.001). Results demonstrate a lower risk of PAD event in statin treated group compared to untreated group (hazard ratio [HR] 0.45, 95% confidence interval [CI] 0.33-0.62) over the span 18.5 years. The interactions between 1) depression and 2) race with statin use for incident PAD were not significant. However other risk factors which were significant included Black American race that had approximately 30% lower hazard of PAD compared to non-Hispanic White (HR=0.70, 95% CI: 0.58-0.84); Age-stratified models were also fitted, and stain use was still a significant treatment factor for ages 45-54 (HR 0.45, 95% CI: 0.33-0.63), 55-64 (HR 0.61, 95% CI 0.46-0.79), and 65-74 years (HR 0.61, 95% CI: 0.48-0.78) but not for 75-84 years. ConclusionStatin use was associated with a decreased risk of incident PAD for those under age 75. Neither race nor depression significantly modified the relationship between statin use and incident PAD however risk of incident PAD was lower among Blacks Americans. These findings highlight that the benefit of statin may wane for those over the age 75. Findings also suggest statin use may not be compromised in those living with depression.