Aortic valve stenosis is the most common valvular heart disease in the Western world. Lipoprotein(a) (Lp(a)) is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). The aim of this study was to assess the role of Lp(a) and its autoantibodies [autoAbs] in CAVS in patients with and without CHD. We included 250 patients (mean age 69 ± 3 years, males 42%) and divided them into three groups. There were two groups of patients with CAVS depending on the presence (group 1) or absence of CHD (group 2). The control group included the patients without CHD or CAVS. According to logistic regression analysis, levels of Lp(a), IgM autoAbs to oxidized Lp(a) (oxLp(a)), and age were independent predictors of CAVS. A concomitant increase in Lp(a) level (≥30 mg/dL) and a decrease in IgM autoAbs concentration (<9.9 lab. Units) are associated with CAVS with an odds ratio (OR) of 6.4, p < 0.01, and with CAVS and CHD with an OR of 17.3, p < 0.001. IgM autoantibodies to oxLp(a) are associated with calcific aortic valve stenosis regardless of Lp(a) concentration and other risk factors. Higher Lp(a) and lower IgM autoantibodies to oxLp(a) levels are associated with a much higher risk of calcific aortic valve stenosis.
Background
Lipoprotein(a) [Lp(a)] is an independent risk factor of coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). It has been recently shown that autotaxin (ATX), which breaks down lysophosphatidylcholine, derived from oxidized phospholipids, to lysophosphatidic acid, was strongly associated with CAVS.
Purpose
The aim of the study was to investigate the role of Lp(a) and ATX in CHD patients with and without CAVS.
Methods
The study included 438 patients (average age 66±11 years, men 310), 332 had CHD with ≥50% stenosis in at least one coronary artery according to angiography. CAVS was diagnosed with ultrasound. The control group consisted of 106 patients without CHD and CAVS. The concentrations of Lp(a), ATX, lipids and blood cells were measured for all the patients.
Results
CHD without CAVS (group I) was diagnosed in 287 patients, 45 patients had CHD and CAVS (group II). Patients in both groups were older than patients in the control group (75±8, 66±10 and 61±13 years respectively). ATX level was lower in group I (median [25; 75%]: 493 [406; 583] ng/ml) than in control group (544 [412; 655] ng/ml, p=0.02) or group II (553 [475; 609] ng/ml, p=0.003). Lp(a) was lower in control group (14.5 [5.5; 36.0] mg/dl) than in group I (25.6 [9.7; 58.5] mg/dl, p=0.0004) and group II (23.8 [9.9; 79.1] mg/dl, p=0.02). Elevated level of ATX was positively associated with CAVS in CHD patients, but negatively with CHD in patients without CAVS. We have shown that age, glucose level and neutrophil-lymphocytes index (NLI) could be predictors of CAVS in patients with CHD according to results of logistic regression analysis.
Odds ratio of high (QIV) vs. low (QI) Odds ratio (95% confidence interval) Groups Autotaxin Lipoprotein(a) Neutrophil-lymphocytes index I vs. control 0.5 (0.3–0.9)* 2.7 (1.3–5.2)** 2.4 (1.3–4.6)* II vs. control 8.6 (1.1–70.1)* 3.4 (1.2–9.4)* 6.2 (2.2–16.9)** II vs. I 16.6 (2.1–131.1)** 1.3 (0.5–3.2) 2.5 (1.0–6.37)* *p<0.05, **p<0.005.
Conclusion
Elevated Lp(a) level is a predictor of CHD regardless of calcific aortic valve stenosis, whereas elevated concentration of autotoxin in CHD patients was associated with calcific aortic valve stenosis.
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