Balance of non–Lp(a) apoB and Lp(a) with Coronary Plaque Phenotypes and MACE: Insights from PROSPECT II and CASABLANCA
Sotirios Tsimikas, James L Januzzi, Michael Maeng, Thomas Engstrøm, Lars Kjøller-Hansen, Ori Ben-Yehuda, Mitsuaki Matsumura, Hans Erik Bøtker, Ole Fröbert, Jonas Persson, Rune Wiseth, Alf I Larsen, Lisette O Jensen, Jan E Nordrehaug, Øyvind Bleie, Elmir Omerovic, Claes Held, Rebecca Rylance, Yuxi Liu, Stefan K James, Ziad A Ali, Akiko Maehara, Gregg W Stone, David ErlingeAbstract
Aims
Apolipoprotein B (apoB)-containing lipoproteins contribute heterogeneously to atherosclerosis. While apoB particles are major determinants of plaque burden, Lp(a) has been linked to plaque inflammation and instability. We investigated the associations of non–Lp(a) apoB, Lp(a), and their relative balance with coronary plaque burden and vulnerability.
Methods and results
Among 854 patients with recent myocardial infarction enrolled in the PROSPECT II near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) study, total apoB was converted to nmol/L and non–Lp(a) apoB calculated by subtracting Lp(a) in nmol/L. The non–Lp(a) apoB/Lp(a) ratio was used to characterize the relative predominance of these lipoprotein classes. Higher non–Lp(a) apoB was independently associated with greater plaque burden (plaque percentage volume; β = 0.19, 95% confidence interval [CI] 0.05-0.33; P = 0.009), but not with lipid core burden index. In contrast, lower non–Lp(a) apoB/Lp(a) ratio tertile were associated with higher odds of plaque burden ≥70% (odds ratio [OR] 1.47, 95% CI 1.04-2.07; P = 0.029) and the composite vulnerability endpoint of plaque burden ≥70% and maxLCBI4mm ≥324.7 (OR 1.62, 95% CI 1.12-2.33; P = 0.011). In an exploratory external cohort from the CASABLANCA study, lower ratios identified an Lp(a)- and oxidized phospholipid-enriched phenotype and were associated with higher unadjusted cardiovascular risk.
Conclusions
Non–Lp(a) apoB and Lp(a) demonstrate distinct associations with coronary plaque burden and vulnerability. Differentiating Lp(a)-associated from non–Lp(a)-associated apoB particle pools provides complementary information on coronary plaque phenotype, and the non–Lp(a) apoB/Lp(a) ratio summarizes their relative predominance.