Lipoprotein(a) and premature myocardial infarction: Mechanistic insights and implications for PCI-era residual risk

South Asians experience premature acute myocardial infarction (AMI) at disproportionately high rates compared with Western populations, often despite modest LDL-cholesterol levels and contemporary lipid-lowering therapy. Lipoprotein(a) [Lp(a)], a genetically determined and causally implicated atherosclerotic cardiovascular disease risk factor, may contribute through proatherogenic and prothrombotic mechanisms. We evaluated associations between Lp(a), premature AMI, coronary angiographic severity, and percutaneous coronary intervention (PCI) outcomes, with emphasis on South Asian populations.

A structured scoping review with quantitative meta-analytic components was conducted in accordance with PRISMA-ScR and PRISMA 2020 guidelines. PubMed, Scopus, and Web of Science were searched from inception through [Month Year]. Eligible studies included adult AMI or PCI cohorts reporting quantitative Lp(a) levels and relevant outcomes. Seventeen studies met inclusion criteria; three provided extractable data for exploratory random-effects meta-analysis using the DerSimonian-Laird method.

Elevated Lp(a) showed a pooled risk ratio of 1.16 (95% CI 0.93-1.43; I² = 24%) for major adverse cardiovascular events, with a consistent direction of effect. Qualitative synthesis linked higher Lp(a) to multivessel disease, higher SYNTAX score, greater thrombus burden, and recurrent post-PCI events. Mechanistic evidence supports roles in oxidized phospholipid transport and impaired fibrinolysis. South Asian cohorts showed higher Lp(a) levels and earlier disease onset.

Elevated Lp(a) may contribute to angiographic severity and adverse PCI-era outcomes in premature AMI, supporting risk assessment in high-risk South Asian populations.