Differential associations of lipoprotein(a)-associated cholesterol and triglycerides with coronary plaque burden and vulnerability: a PROSPECT II substudy
S Tsimikas, L Lin, M Maeng, T Engstrom, O Ben-yehuda, O Frobert, J Persson, O Bleie, E Omerovic, R Rylence, S James, Z Ali, A Maehara, D Erlinge, G StoneAbstract
Background
Lipoprotein(a) [Lp(a)] is a causal risk factor for atherosclerotic cardiovascular disease, but the relative contributions of its cholesterol and triglyceride content to coronary plaque burden and vulnerability are unknown.
Methods
In 873 patients with recent acute myocardial infarction from the PROSPECT II cohort, non-culprit coronary segments were imaged with near-infrared spectroscopy-intravascular ultrasound. Lp(a)-associated cholesterol [Lp(a)-C] and triglycerides [Lp(a)-TG] were measured using validated immune-isolation assays. Associations with pan-coronary plaque volume (PPV), pan-coronary lipid burden, maximum 4-mm lipid core burden index (maxLCBI₄mm), and a combined high-risk plaque phenotype (plaque burden ≥70% and maxLCBI₄mm ≥324.7) were assessed by multivariable linear and logistic regression, adjusted for age, sex, smoking, hypertension, diabetes category, prior PCI, STEMI vs NSTEMI presentation, baseline statin use, and analyzed segment length.
Results
In multivariable analyses, the highest Lp(a)-C tertile was modestly associated with greater pan-coronary plaque volume compared with the lowest tertile (β = 1.36; 95% CI 0.00 to 2.72; p = 0.050). Continuous or log-transformed Lp(a)-C showed similar directional trends without reaching statistical significance. Neither Lp(a)-C nor Lp(a)-TG was independently associated with pan-coronary lipid burden or isolated maxLCBI₄mm ≥324.7. In contrast, log-transformed Lp(a)-TG was independently associated with the combined high-risk plaque phenotype (adjusted odds ratio 1.13; 95% CI 1.00 to 1.29; p = 0.048), whereas Lp(a)-C showed no association with this endpoint.
Conclusions
Cholesterol-enriched and triglyceride-enriched Lp(a) particles exhibit differential associations with coronary plaque characteristics in PROSPECT II. These hypothesis-generating findings suggest Lp(a) lipid composition influences plaque phenotype beyond particle concentration alone.