Abstract 10288: Lipoprotein(a) and Long-Term Risk of Atherosclerotic Cardiovascular Disease in a US Pooled Cohort

Background: Lipoprotein(a) [Lp(a)] is a common genetic factor associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). There are limited long-term follow-up data from large prospective primary prevention cohorts of the US population, including those with diabetes. Methods: We examined the relation of Lp(a) with ASCVD outcomes in a pooled cohort of five major US prospective studies: the Multiethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, Jackson, Framingham Offspring, and Atherosclerosis Risk in Communities. Lp(a) levels were examined continuously (per 50 mg/dL) and categorically as follows: <15 mg/dL (reference), 15-29 mg/dL, 30-49 mg/dL, 50-69 mg/dL, and > 70 mg/dL. Cox regression, adjusted for age, sex, race/ethnicity, LDL-C, and other risk factors, examined the relation of Lp(a) levels with total incident ASCVD events (non-fatal and fatal myocardial infarction, stroke, revascularization, and coronary heart disease death) in the pooled cohort overall and among those at low-intermediate (<20%) and high ( > 20%) 10-year risk and in those with diabetes. Results: We included 27,756 persons without prior ASCVD (mean age 51.3 + 12.4 years, 55.0% female, and 35.7% black participants) who had a mean follow-up of 21.1 + 9.9 years for ASCVD events. The table below shows the adjusted hazard ratios (HRs) and 95% confidence intervals for Lp(a) levels in relation to ASCVD events. In the overall sample, a 50 mg/dL increment in Lp(a) was associated with a 26% greater risk and compared to <15 mg/dL those with Lp(a) levels of 15-29 mg/dL, 30-40 mg/dL, 50-69 mg/dL, and > 70 mg/dL had 10%, 31%, 44%, and 30% greater risks of ASCVD events. Relationships were stronger in those with diabetes. Conclusions: Our results demonstrate in a large pooled cohort of US prospective studies relationships of increased ASCVD risk begin above Lp(a) levels of 15 mg/dL, especially in those with diabetes.