Association of Elevated Lipoprotein(a) levels with vulnerable plaque features assessed by multimodality coronary imaging in patients with coronary artery disease: A systematic review and Meta-analysis
TL;DR
This meta-analysis suggests that high Lp(a) levels are associated with several imaging-defined high-risk coronary plaque features, with the most robust evidence observed for OCT-derived TCFA and plaque rupture.
Abstract
Background Coronary artery plaques are the pathological basis of coronary artery disease (CAD), and the rupture of vulnerable plaques and thrombosis are important causes of major adverse cardiovascular events (MACE). Lipoprotein(a) is a lipid particle which has been proven to be related to the risk of MACE, but the association between its level and the specific imaging phenotype of vulnerable coronary artery plaques has not been clearly established. Methods We searched PubMed, Embase, and the Cochrane Library databases from inception to June 19, 2026, for observational studies evaluating the association between elevated serum Lp(a) levels and coronary plaque characteristics. For OCT-derived features, we compared the relationship between elevated serum Lp(a) levels and the formation of thin-cap fibroatheroma (TCFA), plaque rupture, maximum lipid arc, and minimum lumen area (MLA) in patients with coronary artery disease. Similarly, for CCTA-derived features, we compared the relationship between elevated serum Lp(a) levels and plaque burden, positive remodeling, spotty calcification, napkin ring sign, and low attenuation plaques (LAPs) in patients with CAD. Results This meta-analysis included 13 studies involving 6671 patients (7 studies used optical coherence tomography (OCT) and 6 studies used coronary computed tomography angiography). For the primary outcomes, a meta-analysis of 7 OCT studies (n = 1773 patients) showed that elevated Lp(a) was associated with a significantly increased risk of TCFA (OR 2.57; 95% CI 1.54–4.30; I2 = 61%; P = 0.0003). Conversely, a meta-analysis of 5 CCTA studies (n = 3581 patients) revealed no statistically significant difference in plaque burden between the high and normal Lp(a) groups (SMD 0.27; 95% CI -0.01 to 0.56; I2 = 90%; P = 0.06). For secondary outcomes, elevated Lp(a) was significantly associated with a higher risk of OCT-derived plaque rupture (4 studies; OR 1.71; 95% CI 1.25–2.34; I2 = 0%; P = 0.0008) and a larger maximum lipid arc (3 studies; SMD 0.84; 95% CI 0.31–1.38; I2 = 79%; P = 0.002). For CCTA-derived features, elevated Lp(a) was associated with an increased risk of spotty calcification (3 studies, OR 1.78; 95% CI 1.19–2.68; I2 = 14%; P = 0.005), napkin-ring sign (3 studies, OR 1.46; 95% CI 1.05–2.03; I2 = 0%; P = 0.02), and LAPs (3 studies, OR 1.52; 95% CI 1.06–2.17; I2 = 69%; P = 0.02). Conclusion This meta-analysis suggests that high Lp(a) levels are associated with several imaging-defined high-risk coronary plaque features, with the most robust evidence observed for OCT-derived TCFA and plaque rupture. By integrating evidence from both OCT and CCTA, our findings provide a comprehensive imaging-based characterization of the vulnerable plaque phenotype associated with elevated Lp(a), although several CCTA-derived findings should be interpreted cautiously. Further research is needed to determine whether Lp(a)-lowering therapy can modify high-risk coronary plaque features and reduce subsequent cardiovascular events.