Publication:

Association between elevated lipoprotein(a) levels and cardiovascular risk

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle implicated in atherosclerotic cardiovascular disease (ASCVD). Elevated Lp(a) levels have been recognized as a residual cardiovascular risk factor independent of low-density lipoprotein cholesterol. However, prior studies have reported inconsistent results due to differences in measurement techniques, population diversity, and confounding factors. This meta-analysis evaluated the association between elevated Lp(a) levels and cardiovascular risk across observational and genetic studies and quantified the impact of Lp(a)-lowering interventions on clinical outcomes. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library up to October 20, 2025, following PRISMA 2020 guidelines. Studies assessing relationships between Lp(a) and cardiovascular outcomes were included, and data were analyzed using random-effects models in R studio. Heterogeneity was measured using the I² statistic, and risk of bias was evaluated using the Newcastle-Ottawa scale (NOS) and ROBINS-I tool. Twenty-five studies encompassing 95,206 participants were included. Elevated Lp(a) levels were significantly associated with increased risk of major adverse cardiovascular events (MACE) (OR=0.81; 95% CI: 0.68-0.98; I²=54.9%), myocardial infarction (OR=0.86; 95% CI: 0.75-0.99), ischemic stroke (OR=0.87; 95% CI: 0.76-0.99), and cardiovascular mortality (OR=0.89; 95% CI: 0.87-0.91). PCSK9 inhibitors reduced Lp(a) by a pooled mean difference of -15.58 mg/dL, and anti-inflammatory therapies by -11.21 mg/dl. Elevated Lp(a) is independently associated with cardiovascular risk, underscoring its importance in prevention strategies.