Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease, but its impact on long-term coronary plaque progression remains unclear. This study synthesizes evidence from CCTA, IVUS, and Show more
Lipoprotein(a) [Lp(a)] is a causal risk factor for cardiovascular disease, but its impact on long-term coronary plaque progression remains unclear. This study synthesizes evidence from CCTA, IVUS, and OCT to clarify the relationship between high-risk Lp(a) and coronary plaque burden and high-risk plaque features. We conducted a comprehensive search of multiple databases up to July 2025 for studies evaluating Lp(a) and atherosclerotic plaque progression. Statistical analysis was performed using a random-effects model in RevMan 5.4, reporting odds ratios (OR) and mean differences (MD) with 95% confidence intervals (CI). The protocol is registered in PROSPERO (CRD420251113955). Our final analysis included 16 studies comprising 19,822 participants with a mean age of 62 years and a median imaging follow-up ranging from 10 months to 10.2 years. On analysis, high-risk Lp(a) levels were significantly associated with the presence of coronary plaque (OR 1.53; 95% CI, 1.03-2.29; p = 0.04) compared with low Lp(a) levels. Additionally, patients with elevated Lp(a) exhibited significantly greater progression in percent atheroma volume (ΔPAV) than those with low levels (MD 4.31%; 95% CI, 1.08-7.53; p = 0.009). Subgroup analysis by plaque phenotype revealed a statistically significant increase in low-attenuation plaque (LAP) presence among individuals in the high-risk Lp(a) category (OR 1.92; 95% CI, 1.13-3.27; p = 0.02). High-risk Lp(a) is associated with greater coronary plaque prevalence, accelerated progression, and increased LAP. These findings underscore Lp(a) as a driver of high-risk, rupture-prone plaques and a critical biomarker and potential therapeutic target in cardiovascular risk management. Show less