The Association of Lipoprotein(a), Apolipoprotein(a) Phenotypes and Autoantibodies to Lipoprotein(a) With Lower Extremity Artery Disease

Abstract

Lipoprotein(a) [Lp(a)] and low molecular weight (LMW) apolipoprotein(a) [apo(a)] phenotype are risk factors of сoronary heart disease and stroke. Data about the role of Lp(a) and phenotypes apo(a) in the development of lower extremity artery disease (LEAD) isscarce. The aim of our study was to assess the association of Lp(a), apo(a) phenotypes and autoantibodies to apolipoprotein B100 (apoB100) lipoproteins with LEAD. The study included 622 patients (386 male and 236 female, average age 61±12years), examined in the Department of Atherosclerosis of National Medical Research Center of Cardiology. Patients were divided into 2groups: themain group included 284 patients with LEAD, 338 patients without significant atherosclerosis ofcoronary, carotid and lower limbs arteries formed the control group. LEAD was diagnosed as atherosclerotic lesions with at least one stenosis of low limb artery ≥50 % and ankle-brachial index ≤0.9. The concentration of Lp(a), lipids was measured in blood serum ofallthepatients, level of autoantibodies toapoB100 lipoproteins was measured in 247 patients, and apo(a) phenotypes were determined in389patients. Patients with LEAD were older, were more frequently male, and had a greater prevalence of risk factors including hypertension, type 2 diabetes, smoking than thecontrol group patients (p<0.001 in all the cases). The level of Lp(a) was significantly higher in the main group compared to control group: 35[14; 67] mg / dl vs. 14 [5; 32] mg / dl, p<0,001. ROC analysis demonstrated that the level of Lp(a) ≥26 mg / dl was associated with LEAD (sensitivity 61 %, specificity 70 %). The prevalence ofLp(a) ≥26 mg / dl and LMW apo(a) phenotype were higher inthe main group in comparison with the control group: 61 % vs. 30 % and 48 % vs. 26 % respectively (p<0.001 in the both cases). Theodds ratio ofLEAD inthepresence ofLp(a) ≥26 mg / dl was 3.7 (95 % confidence interval (CI), 2.6-5.1, p<0.001) and in the presence ofLMW apo(a) phenotype was 2.6 (95 % CI, 1.7-4.0, p<0.001). Inlogistic regression analysis adjusted for age, sex, hypertension, smoking, diabetes, both Lp(a) and LMW apo(a) phenotype were independent predictors of LEAD when included separately. The level of IgM autoantibodies toLp(a) was significantly higher inthecontrol group compared tothe patients with LEAD (p=0.01). Concentration of IgG autoantobodies toLp(a) and LDL in the plasma did not differ essentially in the both groups. The level of Lp(a) ≥26 mg / dl and LMW apo(a) phenotype are independent predictors ofLEAD, whereas the contribution of autoantobodies to Lp(a) in LEAD development is controversial.