Abstract 228: Lipoprotein(a), Apolipoprotein(a) Size Polymorphism, and Cardiovascular Risk in Chronic Kidney Disease: Findings in the Sugar Study

An elevated level of lipoprotein(a) [Lp(a)] is a genetically regulated, casual, and prevalent risk factor for cardiovascular disease (CVD). A few non-genetic factors including chronic kidney disease (CKD) influence Lp(a) levels. In this cross-sectional study, we evaluated associations of CKD, defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m 2 , with Lp(a) level and its major genetic regulator—apolipoprotein(a) [apo(a)] Kringle (K) repeats—in non-diabetic, non-dialysis patients with CKD (n=54) and healthy controls (n=39) enrolled in the Study of Glucose and Insulin in Renal Disease. The mean age of participants was 63 years (SD=14), 48% were women and 77% were of European descent. The mean eGFR was 37 and 89 mL/min/1.73 m 2 in the CKD and the control groups, respectively. Lp(a) concentration was higher in participants with CKD vs controls [median (IQR): 14 (5; 44) vs 11 (4; 30) mg/dL]. Notably, this increase in Lp(a) level was observed for both smaller and larger apo(a) sizes (i.e., independent of number of K repeats). Across the eGFR groups using common cut-offs of ≥90, 60-89, 30-59, <30 mL/min/1.73 m 2 , the median (IQR) Lp(a) concentration was 12 (3; 29), 11 (6; 31), 8 (4; 44), and 20 (8; 71) mg/dL, respectively, with a similar distribution of apo(a) K repeats across the eGFR groups. Among CKD patients, Lp(a) concentration was higher in those with CVD (n=17) vs without CVD (n=37) [median (IQR): 26 (4; 73) vs 11 (4; 43) mg/dL). In conclusion, among persons without diabetes, severe kidney impairment is characterized by markedly higher Lp(a) levels compared to those without it. Among persons with CKD, prevalent CVD is associated with higher Lp(a) levels. Mechanisms underlying CKD-induced increases in Lp(a) levels unrelated to apo(a) size polymorphism and their relevance in CVD risk warrant further investigations.