Association of lipoprotein(a) with coronary artery calcium in Individuals without atherosclerotic cardiovascular disease

Abstract

Aim . To evaluate the association between lipoprotein(a) [Lp(a)] levels and the presence and severity of coronary artery calcium (CAC) in patients without clinically established atherosclerotic cardiovascular disease (ASCVD). Material and methods . The study included1,777 outpatients without clinical manifestations of ASCVD who underwent routine preventive examination in the MEDSI clinic network (Moscow and Moscow region) between 2021 and 2025. Eligible patients had both noncontrast computed tomography with quantitative CAC scoring and laboratory measurement of Lp(a). Patients were classified according to CAC values: 0, >0, >100, >300 Agatston units. Lp(a) was evaluated as a continuous variable and according to clinically relevant thresholds >30, >50 and >70 mg/dL. Results . The median age of participants was 47 [41; 55] years, and 43.2% were women. Coronary calcification (CAC >0) was detected in 30.6% of patients. Compared with individuals without calcification, patients with CAC >0 were older (54 vs 45 years; p <0.001), more frequently had arterial hypertension (58.9% vs 39.1%; p <0.001) and diabetes mellitus (7.7% vs 2.4%; p <0.001). Median Lp(a) levels were significantly higher in patients with CAC >0 — 25 [8; 87] mg/dL versus 15 [6; 59] mg/dL in those with CAC=0 (p <0.001). In multivariable logistic regression, Lp(a) remained significantly associated with the presence of CAC >0 (adjusted odds ratio [AOR] 1.007 per 1 mg/dL; 95% confidence interval [CI] 1.004-1.009; p <0.001). The association persisted when using clinical thresholds: for Lp(a) >30 mg/dL AOR was 1.81, for >50 mg/dL — 1.89, and for >70 mg/dL — 2.06 (all p <0.001). Higher Lp(a) values were more prevalent among patients with calcification: in those with CAC >0, the proportions of Lp(a) >30, >50 and >70 mg/dL were 47.8%, 38.4% and 29.8%, respectively. Severe calcification (CAC >300) was found in 2.4% of individuals without ASCVD. Conclusion . Elevated Lp(a) levels are independently associated with subclinical atherosclerosis defined by CAC, even after adjustment for traditional risk factors. Combined assessment of Lp(a) and CAC helps identify patients at “hidden” very high cardiovascular risk and design strategies for early preventive and therapeutic interventions.