Open AccessEnhanced Lipid Peroxidation and Platelet Activation as Potential Contributors to Increased Cardiovascular Risk in the Low‐ HDL Phenotype
Author(s) -
Vazzatale,
Ganci Antonina,
Cefalù Angelo Baldassare,
Lattanzio Stefano,
Noto Davide,
Santoro Nicole,
Saggini Raoul,
Puccetti Luca,
Averna Maurizio,
Davì Giovanni
Publication year - 2013
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.113.000063
Subject(s) - medicine , platelet activation , endocrinology , oxidative stress , creatinine , lipid peroxidation , high density lipoprotein , lipoprotein , platelet , urinary system , gastroenterology , cholesterol , cardiology
Background Low high‐density lipoprotein ( HDL ) levels are major predictors of cardiovascular ( CV ) events, even in patients on statin treatment with low‐density lipoprotein ( LDL ) at target. In animal models HDL s protect LDL from oxidation and blunt platelet activation. Our study aimed to examine whether HDL levels are related to in vivo oxidative stress and platelet activation, as determinants of atherothrombosis. Methods and Results Urinary 8‐iso‐PGF 2α and 11‐dehydro‐TXB 2 , in vivo markers of oxidative stress and platelet activation, respectively, were measured in 65 coronary heart disease (CHD) normocholesterolemic patients with HDL ≤35 mg/ dL , and in 47 CHD patients with HDL >35 mg/ dL . The 2 eicosanoids were also measured before and after an intensive exercise program in sedentary people (n=18) and before and after fenofibrate treatment in otherwise healthy subjects with low HDL (n=10). Patients with HDL ≤35 mg/ dL showed significantly higher urinary 8‐iso‐PGF 2α (median [25th to 75th percentiles]: 289 [189 to 380] versus 216 [171 to 321] pg/mg creatinine, P =0.019) and 11‐dehydro‐TXB 2 (563 [421 to 767] versus 372 [249 to 465] pg/mg creatinine, P =0.0001) than patients with higher HDL. A direct correlation was found between urinary 8‐iso‐PGF 2α and 11‐dehydro‐TXB 2 in the entire group of patients (ρ=0.77, P <0.0001). HDL levels were inversely related to both 8‐iso‐PGF 2α (ρ=−0.32, P =0.001) and 11‐dehydro‐TXB 2 (ρ=−0.52, P <0.0001). On multiple regression, only 8‐iso‐PGF 2α (β=0.68, P <0.0001) and HDL level (β=−0.29, P <0.0001) were associated with urinary 11‐dehydro‐TXB 2 excretion, independent of sex, age, smoking, hypertension, diabetes, previous myocardial infarction, total cholesterol, LDL, and triglycerides. Both intensive exercise and fenofibrate treatment significantly reduced the 2 eicosanoids in healthy subjects, in parallel with an HDL increase. Conclusions A low HDL phenotype, both in CHD patients and in healthy subjects, is associated with increased lipid peroxidation and platelet activation. These data provide novel insight into the mechanisms linking low HDL with increased CV risk.