High baseline lipoprotein(A) Level as a risk factor for coronary artery calcification progression: Sub-analysis of a prospective multicenter trial

Abstract

L ipoprotein(a), or Lp(a), is a low-density lipoprotein (LDL)-like particle. Apolipoprotein B is covalently linked to apolipoprotein(a) by a single disulfide bond [1]. Circulating concentrations of Lp(a) vary widely across individuals and ethnic subgroups, mediated in large part by genetic variations at the LPA gene locus [2]. A meta-analysis of 126,634 participants in 36 prospective studies found that Lp(a) was an independent risk factor for coronary heart disease and stroke [3]. Mendelian randomization studies have linked Lipoprotein(a), or Lp(a), is a low-density lipoprotein-like particle largely independent of known risk factors for, and predictive of, cardiovascular disease (CVD). We investigated the association between baseline Lp(a) levels and the progression of coronary artery calcification (CAC) in patients with hypercholesterolemia undergoing statin therapy. This study was a sub-analysis of a multicenter prospective study that evaluated the annual progression of CAC under intensive and standard pitavastatin treatment with or without eicosapentaenoic acid in patients with an Agatston score of 1 to 999, and hypercholesterolemia treated with statins. We classified the patients into 3 groups according to CAC progression. A total of 147 patients (mean age, 67 years; men, 54%) were analyzed. The proportion of patients with Lp(a) > 30 mg/dL significantly increased as CAC progressed (non-progression; 5.4%, 0 < CAC progression ≦100; 7.7%, and CAC progression > 100; 23.6%). Logistic regression analysis showed that Lp(a) > 30 mg/dL was an independent predictor of the annual change in Agatston score > 100 (OR: 5.51; 95% CI: 1.28-23.68; p = 0.02), even after adjusting for age, sex, hypertension, diabetes mellitus, current smoking, body mass index, and lipid-lowering medications. Baseline Lp(a) > 30 mg/dL was a predictor of CAC progression in this population of patients with hypercholesterolemia undergoing statin therapy.