Abstract
Background and Aims: Lipoprotein (a) [Lp(a)] has been identified as a risk factor for cardiovascular disease (CVD). We examined whether Lp(a) predicts subclinical atherosclerosis, extent of coronary artery disease and modifies discrimination and risk reclassification of CVD beyond conventional risk factors. Methods: Plasma Lp(a) and CVD risk factors were assessed in a random community-based cohort (Carotid Ultrasound Disease Assessment Study, CUDAS) and a cohort with premature angiographically defined coronary artery disease (CAD) (Carotid Ultrasound in Patients with Ischemic Heart Disease, CUPID). Carotid intima media thickness (IMT) and focal plaque were assessed by carotid B-mode ultrasound in both cohorts. The extent and severity of CAD was determined by the modified Gensini and Coronary Artery Stenosis ≥20% (CAGE) scores in CUPID. Results: In pooled analyses of 1414 individuals (830 men and 584 women) aged 20 to 70 years, Lp(a) was associated with risk of myocardial infarction and/or stroke [Odds Ratio (95% Confidence Intervals)][1.14 (1.05, 1.24)] and presence of focal plaque [1.08 (1.01, 1.16)], independent of age, gender and cardiometabolic risk factors (including body mass index, triglycerides, smoking, diabetes, hypertension, hypercholesterolemia and family history of CVD). Lp(a) was not associated with IMT. In CUPID, Lp(a) was an independent determinant of the Gensini score and in CUPID men, the CAGE ≥20% score (all P<0.01). The addition of Lp(a) to the basic model (age, gender and cardiometabolic risk factors) improved the C-statistics, integrated discrimination index and category-free net reclassification improvement for myocardial infarction and/or stroke. Conclusions: Lp(a) predicts risk of myocardial infarction and/or stroke, carotid plaque and extent of CAD. The addition of Lp(a) improves discrimination and risk reclassification of myocardial infarction and/or stroke beyond conventional risk factors.
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