Familial Hypercholesterolaemia and Lipoprotein(a) Phenotypes in a Community-Based Cohort: Associations with Carotid Intima-Media Thickness, Focal Plaque and Cardiovascular Outcomes

Familial hypercholesterolaemia (FH) and elevated lipoprotein(a) [Lp(a)] are associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). We assessed the frequencies of these disorders in individuals without overt cardiovascular disease at recruitment, and their predictive utility for subclinical carotid atherosclerosis and CVD events. Study participants (n = 977) were selected from the Perth Carotid Ultrasound Disease Assessment Study (CUDAS), a random survey of 20 to 70 year olds from the Western Australian electoral-roll. LDL-cholesterol was adjusted for lipid-lowering therapy and the cholesterol content of Lp(a). Phenotypic FH was defined as a Dutch Lipid Network Criteria Score of ≥5 (at least possible FH). Lp(a) concentration and KIV-2 copy number (an estimate of apo(a) isoform size) were estimated by immunonephelometry and quantitative PCR, respectively. Elevated Lp(a) was defined as levels ≥0.5 g/L. CVD events, including CVD death or hospital admission for CVD, were recorded for a median 9.3 years. Phenotypic FH was identified in 6.4% of individuals and elevated Lp(a) in 17.1%. Lp(a) concentration was inversely correlated with apo(a) isoform size (r = -0.37; p < 0.001). LDL-cholesterol was significantly associated with carotid intima-media thickness (cIMT) (p < 0.001); LDL-cholesterol (p < 0.001) and FH phenotype (p < 0.001) were associated with the presence of focal plaque. Neither Lp(a) concentration (p ≥ 0.850) nor apo(a) isoform size (p ≥ 0.466) were associated with cIMT or focal plaque. LDL-cholesterol predicted CVD events when adjusting for additional CVD risk factors (p = 0.03; ß = 1.32). LDL-cholesterol and FH phenotype were associated with subclinical atherosclerosis and subsequent CVD events in individuals free of overt CVD. Conversely, Lp(a) and apo(a) isoform size were not significant predictors.