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RESEARCH PRODUCT
Enhanced lipid peroxidation and platelet activation as potential contributors to increased cardiovascular risk in the low-HDL phenotype
Stefano LattanzioG. DaviNicole SantoroA. GanciNatale VazzanaLuca PuccettiRaoul SagginiMaurizio AvernaAngelo B. CefalùDavide Notosubject
MaleSettore MED/09 - Medicina InternaCoronary DiseaseDinoprostmedicine.disease_causeLipid peroxidationchemistry.chemical_compoundFenofibrateHDL cholesterolRisk FactorsCoronary Heart Diseaseoxidative stressMyocardial infarctionOriginal ResearchHypolipidemic AgentsplateletHypoalphalipoproteinemiasFenofibrateMiddle AgedAged; Arachidonic Acids; Case-Control Studies; Cholesterol HDL; Coronary Disease; Cross-Sectional Studies; Dinoprost; Exercise; Exercise Therapy; Female; Fenofibrate; Humans; Hypoalphalipoproteinemias; Hypolipidemic Agents; Lipid Peroxidation; Male; Middle Aged; Oxidative Stress; Phenotype; Platelet Activation; Risk Factors; Sedentary Lifestyle; Thromboxane B2; Cardiology and Cardiovascular MedicineExercise TherapyCholesterolPhenotypeSedentary LifestyleFemalelipids (amino acids peptides and proteins)exercise HDL cholesterol oxidative stress plateletCardiology and Cardiovascular Medicinemedicine.drugmedicine.medical_specialtyHDLArachidonic AcidsDiabetes mellitusInternal medicinemedicineHumansPlatelet activationExerciseAgedCreatininebusiness.industryCholesterol HDLCase-control studyPlatelet Activationmedicine.diseaseThromboxane B2Cross-Sectional StudiesEndocrinologychemistryCase-Control StudiesLipid PeroxidationSedentary BehaviorbusinessOxidative stressLipoproteindescription
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.
year | journal | country | edition | language |
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2013-04-01 | European Heart Journal |