Relationship of low-density lipoprotein-cholesterol and lipoprotein(a) to cardiovascular risk: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background and aims: Plasma low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) are both associated with coronary heart disease (CHD). This study investigated whether elevated plasma Lp(a) concentration was associated with increased CHD risk when LDL-C was low (≤100 mg/dL) in individuals not on statin therapy. Methods: Participants from the Multi-Ethnic Study of Atherosclerosis (MESA) (n = 4,585) were categorized into four groups: Group 1: LDL-C ≤ 100 mg/dL, Lp(a) < 50 mg/dL; Group 2: LDL-C > 100 mg/dL, Lp(a) < 50 mg/dL; Group 3: LDL-C ≤ 100 mg/dL, Lp(a) ≥ 50 mg/dL; and Group 4: LDL-C > 100 mg/dL, Lp(a) ≥ 50 mg/dL. The relationship of Lp(a) and LDL-C with time to CHD events was assessed with Kaplan Meier curves and multivariable Cox proportional hazard models. Results: Participants were followed for a mean of 13.4 years and a total of 315 CHD events occurred. Compared to participants with LDL-C ≤ 100 mg/dL and Lp(a) < 50 mg/dL, those with LDL-C > 100 mg/dL and Lp(a) < 50 mg/dL (Group 2) demonstrated no increased risk for CHD events (HR: 0.92; 95% CI: 0.69, 1.21). However, participants with LDL-C ≤ 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 3) and those with LDL-C > 100 mg/dL and Lp(a) ≥ 50 mg/dL (Group 4) exhibited significantly increased risk of CHD events compared to Group 1 (HR: 1.83; 95% CI: 1.02, 3.27) and Group 2 (HR: 1.61; 95% CI: 1.15, 2.26), respectively. Conclusions: When Lp(a) was elevated, risk of CHD events increased, regardless of baseline LDL-C.