Hyperlipoprotein(a) and the low-molecular-weight apoprotein(a) phenotype in patients with atherosclerotic cardiovascular diseases and their complications

Aim. To study the association between lipoprotein(a) [Lp(a)] and apoprotein(a) [apo(a)] phenotypes with atherosclerosis of various locations and a history of cardiovascular events. Material and methods . This cross-sectional, single-center study included 819 patients over 18 years of age with available paraclinical data on the coronary, carotid, and lower extremity arteries (LEA). Atherosclerosis was considered significant with stenosis of at least one main artery by more than 50%, as determined by carotid duplex ultrasound, LEA, and coronary angiography. Patients were divided into 4 following groups depending on their Lp(a) level and apo(a) phenotype: group 1 — Lp(a) <30 mg/dL and high-molecular-weight apo(a) phenotype (n=314); group 2 — Lp(a) <30 mg/dL and low-molecular-weight (LMW) apo(a) phenotype (n=122); group 3 — Lp(a) ≥30 mg/dL and high-molecularweight apo(a) phenotype (n=126); group 4 — Lp(a) ≥30 mg/dL and LMW apo(a) (n=257). In all patients, serum lipid and Lp(a) concentrations were determined, and apo(a) phenotyping was performed. Results. The study groups were comparable by age and sex. In the studied sample, as the concentration of Lp(a) and LMW apo(a) increased from group 1 to group 4, the proportion of individuals without significant atherosclerosis decreased (58, 36, 29 and 20%, respectively), and multifocal atherosclerosis incidence increased (16, 34, 44 and 45%, respectively). LMW apo(a) with Lp(a) <30 mg/dl (group 2) was associated with multifocal atherosclerosis with an odds ratio (OR) of 2,6 (95% confidence interval (CI): 1,6-4,3 (p<0,01)), while hyperlipoproteinemia(a) (Lp(a) concentration ≥30 mg/dL) was associated with a 4-fold increase in the odds of multifocal atherosclerosis (groups 3 and 4) when compared with group 1 — OR 4,0; 95% CI: 2,5-6,4 (p<0,01) and OR 4,0; 95% CI: 2,7-5,9 (p<0,01), respectively. Independent association of Lp(a) and LMW apo(a) levels with atherosclerotic cardiovascular diseases and history of myocardial infarction (MI) was confirmed by logistic regression analysis including age, sex, hypertension, type 2 diabetes, smoking status, and obesity in the model. The odds of coronary, carotid, and multifocal atherosclerosis and history of MI were highest with a combination of hyperlipoproteinemia(a) and LMW apo(a) as follows: OR 4,5; 95% CI: 3,0-6,8 (p<0,01), OR 3,5; 95% CI: 2,2-5,6 (p<0,01), OR 10,9; 95% CI: 5,8-20,5 (p<0,01), OR 2,9; 95% CI: 2,0-4,2 (p<0,01), respectively. No significant association was found between Lp(a) and LMW apo(a) levels with a history of ischemic stroke. Conclusion. Hyperlipoproteinemia(a) and LMW apo(a) are associated with significant coronary, carotid and LEA atherosclerosis, with isolated and multifocal atherosclerosis and a history of MI, independent of both conventional risk factors and each other. LMW apo(a) was associated with atherosclerotic cardiovascular disease and a history of MI, but not with ischemic stroke, regardless of Lp(a) levels.