Obesity paradox, hyperlipoproteinemia(a), autotaxin concentration and stenotic atherosclerosis of different vascular territories

Abstract Background Controversial data have recently emerged about the role of obesity in the development of cardiovascular diseases, otherwise known as “Obesity paradox”. Autotaxin (ATX) hydrolyzes lysophosphatidylcholine to lysophosphatidic acid, a lipid mediator involved in pathological processes, including obesity. Purpose To investigate the association between obesity and stenotic atherosclerosis of different vascular territories. Methods The study included 1225 patients with results of instrumental examination of coronary, carotid and lower limbs arteries. Stenotic atherosclerosis (≥50%) in any vascular bed was diagnosed in 889 patients. Results The patients were divided into two groups depending on body mass index (BMI) (table). The groups were comparable on age, lipids and frequency of CHD. The obesity negatively associated with lower extremity artery disease (LEAD) (odds ratio (OR) 0.51; 95% CI 0.36–0.72, p<0.01) adjusted for gender, age, smoking, type 2 diabetes, lipids and Lp(a). Multifocal atherosclerosis was also negatively associated with obesity (OR 0.44; 95% CI 0.28–0.71, p<0.01). ATX level was lower in patients with LEAD (median [25; 75%]: 492 [418; 573] ng/ml) vs. patients without LEAD (520 [424; 618] ng/ml, p<0.05). The similar results for ATX concentration were shown for patients with multifocal atherosclerosis vs. without stenotic atherosclerosis: 478 [414; 571] ng/ml vs. 551 [412; 678] ng/ml, p<0.05. The corresponding trend was observed in patients with and without coronary heart disease (CHD) (502 [421; 594] vs. 545 [425; 638] ng/ml, p=0.05). ATX level was associated with BMI (r=0.34, p<0.01) and negatively correlated with LEAD and multifocal atherosclerosis in obesity patients (r=−0.2, p<0.05 in both cases). Characteristics of study groups Parameters Control, BMI <30 kg/m2, n=846 Obesity, BMI ≥30 kg/m2, n=379 Hypertension 585 (69%) 316 (83%)*** Type 2 diabetes 133 (16%) 115 (30%)*** Lipoprotein(a), mg/dl 23.9 [9.0; 54.7] 18.0 [6.6; 49.2]* Lipoprotein(a) ≥30 mg/dl 372 (44%) 137 (36%)* Autotaxin, ng/ml 513.5±137.3 528.4±140.1 Carotid atherosclerosis 293 (35%) 127 (33%) CHD 539 (64%) 206 (54%)** LEAD 224 (26%) 66 (17%)*** *p<0.05, **p<0.005, ***p<0.0005 compare with control group. Conclusion “Obesity paradox” was observed in the patients with LEAD, CHD and multifocal atherosclerosis and it could be associated with lysophosphatidic acid pathway.