Impact of Social Determinants of Health and Lifestyle on Association Between Lipoprotein(a) and Cardiovascular Events

Background In European cohorts, healthier lifestyle either attenuated or associated with lower cardiovascular risk despite elevated lipoprotein(a) [Lp(a)]. Objectives The purpose of this study was to test if social determinants of health (SDOH) and Life’s Simple 7 (LS7) scores impact the association of Lp(a) with cardiovascular events in U.S. cohorts. Methods We performed a sequential multivariable Cox proportional hazard analysis using the ARIC (Atherosclerosis Risk In Communities) and MESA (Multi-Ethnic Study of Atherosclerosis) cohorts. We first adjusted for age, gender, non-high-density lipoprotein-cholesterol, race, and ethnicity, then sequentially added SDOH and LS7 scores. The primary outcomes were time until first myocardial infarction (MI) or stroke. Results ARIC (n = 15,072; median Lp(a) = 17.3 mg/dL) had 16.2 years and MESA (n = 6,822; median Lp(a) = 18.3 mg/dL) had 12.3 years of average follow-up. In age, gender, race, and ethnicity, and non-high-density lipoprotein-cholesterol adjusted analyses, Lp(a) was associated with MI in ARIC (HR: 1.10, P < 0.001) and MESA (HR: 1.11, P = 0.001), and stroke in ARIC (HR: 1.07, P < 0.001) but not MESA (HR: 0.97, P = 0.53). In models with SDOH and LS7, associations of Lp(a) remained similar with MI (ARIC, HR: 1.08, P < 0.001; MESA, HR: 1.10, P = 0.001) and stroke (ARIC, HR: 1.06, P = 0.002; MESA, HR: 0.96, P = 0.37). Each additional SDOH correlated positively with MI (ARIC, HR: 1.04, P = 0.01; MESA, HR: 1.08, P = 0.003) and stroke in ARIC (HR: 1.08, P = 0.00) but not MESA (HR: 1.03, P = 0.41). Each additional LS7 point correlated negatively with MI (ARIC, HR: 0.88, P < 0.001; MESA, HR: 0.85, P < 0.001) and stroke (ARIC, HR: 0.91, P < 0.001; MESA, HR: 0.86, P < 0.001). Conclusions SDOH and lifestyle factors associated with risk for MI and stroke but did not largely impact the association between Lp(a) and cardiovascular events.