Lipoprotein(a), Cholesterol, Triglyceride Levels, and Vulnerable Coronary Plaques A PROSPECT II Substudy

BACKGROUND Although lipoprotein(a) (Lp[a]) has been associated with acute myocardial infarction (MI), the relationship between Lp(a) and the presence of high-risk "vulnerable" coronary plaques has not been studied. OBJECTIVES The aim of this study was to investigate whether specific lipoproteins are associated with pancoronary plaque volume and lipid deposition vs the development of non-flow-limiting high-risk vulnerable plaques. METHODS In PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) II, 3-vessel coronary artery imaging was performed with a combined near-infrared spectroscopy and intravascular ultrasound catheter after treatment of all flow-limiting lesions in patients with recent MI. The relationships of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (HDL-C), HDL-C, Lp(a), and triglycerides to pancoronary plaque volume, pancoronary lipid core burden index (LCBI), and the presence of focal vulnerable plaques (plaque burden >= 70% and maximum LCBI over any 4-mm segment >= 324.7) were assessed in 865 patients. RESULTS By multivariable analysis, TC, LDL-C, and non-HDL-C (but not Lp[a]) were associated with pancoronary plaque volume and pancoronary LCBI (P < 0.01 for all), but not with the presence of vulnerable plaque. Conversely, Lp(a) (but not TC, LDL-C, or non-HDL-C) was associated with the presence of focal vulnerable plaques (P 1/4 0.01). CONCLUSIONS In PROSPECT II, elevated TC, LDL-C, and non-HDL-C were strongly associated with pancoronary atherosclerosis and lipid deposition, whereas elevated Lp(a) was strongly associated with the presence of focal vulnerable plaques. These findings may explain the association between high Lp(a) levels and future MI and suggest a unique role for Lp(a) role in atherosclerosis progression and plaque vulnerability. (PROSPECT II & PROSPECT ABSORB-An Integrated Natural History Study and Randomized Trial; NCT02171065) (JACC. 2025;85:2011-2024) (c) 2025 by the American College of Cardiology Foundation.