Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Background: The atherogenic index of plasma (AIP), calculated from triglyceride and high-density lipoprotein cholesterol levels, is associated with atherosclerosis and coronary artery disease (CAD). However, evidence concerning the impact of the AIP on CAD severity remains limited. This study aims to assess the correlation between AIP and the severity of CAD. Methods: This study included 19,929 hospitalized participants diagnosed with CAD. After excluding participants with missing data, aged >75 years, or diagnosed with chronic kidney disease or cancer, a total of 2561 individuals were included. The 2561 participants were divided into three AIP tertile groups: AIP1 (AIP <0.016, n = 854), AIP2 (0.016 ≤ AIP < 0.216, n = 853), and AIP3 (AIP ≥0.216, n = 854). In this study, CAD severity was determined by the count of coronary arteries exhibiting stenosis of 50% or greater. Multivessel CAD was defined as ≥50% stenosis in two or more major coronary arteries. The relationship between AIP and CAD severity was assessed using logistic regression models. Results: Results indicate that the AIP independently predicts CAD severity, with an odds ratio of 1.700 (95% confidence interval (CI): 1.160–2.491; p = 0.007). The AIP3 group demonstrated a significantly higher risk of multivessel CAD compared to the AIP1 group (odds ratio (OR), 1.441; 95% CI: 1.124–1.848; p = 0.004), particularly in patients without diabetes mellitus (OR, 1.421; 95% CI: 1.030–1.962; p = 0.033). Conclusions: The AIP was significantly associated with CAD severity, suggesting that it could be a convenient and valuable marker for severity stratification in patients with CAD in clinical practice.