Genetic Evidence Linking Lipoprotein(a) to Cardiovascular Disease and the Potential Role of Aspirin: A Mendelian...

Many studies have revealed the observational associations between lipoprotein(a) (Lp(a)) concentrations and the incidence of cardiovascular diseases (CVDs). However, the causal associations remain unclear.

Public summary data were analyzed using a Mendelian randomization (MR) design to assess the causal associations between Lp(a) levels and risks of nine CVDs and evaluate the potential impact of aspirin on Lp(a) levels. The principal analysis was conducted employing the random-effects inverse-variance weighted (IVW) method. Furthermore, the weighted median and MR-Egger approaches were used as the sensitivity analysis. Additionally, the significantly associated single nucleotide polymorphisms (SNPs) in salicylic acid (INTERVAL and EPIC-Norfolk, n = 14,149) were chosen to assess the potential effects of aspirin on lowering Lp(a) levels.

The IVW analysis showed that the per standard deviation (SD) increment in Lp(a) level was causally associated with a higher risk of coronary artery disease (odds ratio (OR), 1.237; 95% confidence interval (CI), 1.173-1.303), atrial fibrillation (OR, 1.030; 95% CI, 1.011-1.050), heart failure (OR, 1.074; 95% CI, 1.053-1.096), hypertension (OR, 1.006; 95% CI, 1.004-1.008), and peripheral artery disease (OR, 1.001; 95% CI, 1.001-1.001) (all p < 0.001). The investigation did not reveal any significant heterogeneities or instances of horizontal pleiotropy. Furthermore, for each SD increase in salicylic acid concentration, there was a corresponding 5.4% reduction in Lp(a) levels (OR: 0.946, 95% CI: 0.900-0.993; p = 0.022).

A causal nexus was discerned between Lp(a) levels and an increased risk of conditions including coronary artery disease, atrial fibrillation, heart failure, hypertension, and peripheral artery disease. Furthermore, administering aspirin may be a potential therapeutic to reduce these CVD risks among individuals with elevated Lp(a) levels.