The association of lipoprotein(a) and coronary artery calcium in asymptomatic patients: a systematic review and meta-analysis

Aims: Lipoprotein(a) [Lp(a)] is an atherogenic lipid particle associated with increased risk for coronary heart disease (CHD) events. Coronary artery calcium (CAC) score is a tool to diagnose subclinical atherosclerosis and guide clinical decision-making for primary prevention of CHD. Studies show conflicting results concerning the relationship between Lp(a) and CAC in asymptomatic populations. We conducted a meta-analysis to evaluate the association of Lp(a) and CAC in asymptomatic patients.

Methods and results: We systematically searched PubMed, Embase, and Cochrane until April 2023 for studies evaluating the association between Lp(a) and CAC in asymptomatic patients. We evaluated CAC > 0 Agatston units, and CAC ≥ 100. Lp(a) was analysed as a continuous or dichotomous variable. We assessed the association between Lp(a) and CAC with pooled odds ratios (OR) adopting a random-effects model. A total of 23 105 patients from 18 studies were included in the meta-analysis with a mean age of 55.9 years, 46.4% female. Elevated Lp(a) increased the odds of CAC > 0 [OR 1.31; 95% confidence intervals (CI) 1.05-1.64; P = 0.02], CAC ≥100 (OR 1.29; 95% CI 1.01-1.65; P = 0.04; ), and CAC progression (OR 1.43; 95% CI 1.20-1.70; P < 0.01; ). For each increment of 1 mg/dL in Lp(a) there was a 1% in the odds of CAC > 0 (OR 1.01; 95% CI 1.01-1.01; P < 0.01).

Conclusion: Our findings of this meta-analysis suggest that Lp(a) is positively associated with a higher likelihood of CAC. Higher Lp(a) levels increased the odds of CAC >0. These data support the concept that Lp(a) is atherogenic, although with high heterogeneity and a low level of certainty.

Protocol registration: CRD42023422034.

Key findings: Asymptomatic patients with elevated Lp(a) had 31% higher chances of having any coronary calcification (CAC > 0) and 29% higher chances of having more advanced calcification (CAC > 100). It increased the chances of having progression of coronary calcification over time by 43%. For each 1 mg/dL of Lp(a) there was an increment of 1% chance of having coronary calcification.