Abstract 3143: Association of PCSK9 Gene Variants with Longitudinal LDL-Cholesterol Levels: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Recent studies have shown that mutations of PCSK9 are associated cross-sectionally with plasma LDL cholesterol (LDL-C) levels in middle-aged adults. However, the longitudinal change with aging of LDL-C levels associated with PCSK9 variants is unknown. We examined data from 1750 black and 1828 white participants (ppts), 18 to 30 years old at baseline, in the CARDIA Study to determine the effect of 6 PCSK9 variants on LDL-C over 20 years. GEEs adjusting for sex, time-dependent BMI, and 6 examinations were used to assess differences between the gene variants in LDL-C levels with age. Ppts without any of these 6 variants were considered as the reference group for their race. For black ppts, 3 variants (L235F, C679X, and Y142X) were combined for data analysis due to the small number (2.7 %) with these variants. Ppts with the 3 gene variants and the A443T variant had significantly lower LDL-C levels at age 18, while participants with the E670G variant (7 %) had higher LDL-C levels compared with the reference group (see table⇓). For Blacks with the 3 gene variants, compared to the reference group, the difference in LDL-C levels widened by 0.25 mg/dl per year of age, while the E670G and A443T variants did not show a significant change in LDL-C levels with age. For white ppts, the R46L variant (3.3 %) was associated with lower LDL-C levels at age 18, and the difference narrowed with age. Furthermore, the 3 gene variants and the A443T variant in black men were associated with lower prevalence of coronary artery calcium in early middle age. Our results suggest that several variants of PCSK9 have persistently lower serum LDL-C levels than the reference group from young adulthood to middle age. Such long-term reduction in LDL-C levels is associated with reduced sub-clinical atherosclerosis burden, and may have considerable beneficial effects on coronary heart disease incidence.