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Improvement in endothelium-dependent brachial artery flow-mediated vasodilation with low-density lipoprotein cholesterol levels <100 mg/dl

  • Michael Shechter
    Correspondence
    Dr. Shechter’s address is: Preventive & Rehabilitative Cardiac Center, Cedars-Sinai Medical Center, 444 San Vicente Boulevard, Suite 901, Los Angeles, California 90048
    Affiliations
    Preventive & Rehabilitative Cardiac Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, California,USA
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  • Michael Sharir
    Affiliations
    Preventive & Rehabilitative Cardiac Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, California,USA
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  • Maura J Paul Labrador
    Affiliations
    Preventive & Rehabilitative Cardiac Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, California,USA
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  • James Forrester
    Affiliations
    Preventive & Rehabilitative Cardiac Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, California,USA
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  • C.Noel Bairey Merz
    Affiliations
    Preventive & Rehabilitative Cardiac Center, Division of Cardiology, Department of Medicine, Cedars-Sinai Medical Center and the UCLA School of Medicine, Los Angeles, California,USA
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      Hypercholesterolemia is associated with impaired endothelial function,
      • Vita J.A.
      • Treasure C.B.
      • Yeung A.C.
      • Vekshtein V.I.
      • Fantasia G.M.
      • Fish R.D.
      • Ganz P.
      • Selwyn A.P.
      Patients with evidence of coronary endothelial dysfunction as assessed by acetylcholine infusion demonstrate marked increase in sensitivity to constrictor effects of catecholamines.
      ,
      • Chowienczyk P.J.
      • Watts G.F.
      • Cockcroft J.R.
      • Ritter J.M.
      Impaired endothelium-dependent vasodilation of forearm resistance vessels in hypercholesterolemia.
      and animal
      • Kroon A.A.
      • Stalenhoef A.F.
      • Buikema H.
      • Demacker P.N.
      • de Wilde P.C.
      • Leijten P.A.
      • van Gilst W.H.
      The effect of cholesterol reduction on the endothelial function and progression of atherosclerisis in WHHL rabbits.
      ,
      • Osborne J.A.
      • Siegman M.J.
      • Sedar A.W.
      • Mooers S.U.
      • Lefer A.M.
      Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterol-fed rabbits.
      and human
      • Treasure C.B.
      • Klein J.L.
      • Weintraub W.S.
      • Talley J.D.
      • Stillabower M.E.
      • Kosinski A.S.
      • Zhang J.
      • Boccuzzi S.J.
      • Cedarholm J.C.
      • Alexander R.W.
      Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease.
      ,
      • Leung W.H.
      • Lau C.P.
      • Wong C.K.
      Beneficial effect of cholesterol-lowering therapy on coronary endothelium-dependent relaxation in hypercholesterolemic patients.
      ,
      • Stroes E.S.
      • Koomans H.A.
      • de Bruin T.W.
      • Rabelink T.J.
      Vascular function in the forearm of hypercholesterolemic patients off and on lipid-lowering medication.
      studies indicate that lipid-lowering improves endothelial function. Current National Cholesterol Education Program (NCEP) Adult Treatment Panel II guidelines consider desirable low-density lipoprotein (LDL) cholesterol levels in patients with coronary artery disease (CAD) to be ≤100 mg/dl,
      Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults
      Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II).
      although recent trials using statin lipid-lowering treatment in patients with CAD have suggested there is no longitudinal benefit of lipid lowering among patients with baseline LDL cholesterol <125 mg/dl.
      • Sacks F.M.
      • Pfeffer M.A.
      • Moye L.A.
      • Rouleau J.R.
      • Rutherford J.D.
      • Cole T.G.
      • Brown L.
      • Wornica J.W.
      • Arnold J.M.O.
      • Wun C.C.
      • Davis B.R.
      • Braunwald E.
      The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators.
      ,
      Long-Term Intervention with Pravastatin in Ischemic (LIPID) Study Group
      Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and broad range of initial cholesterol levels.
      Although coronary angiographic trials suggest that more intensive intervention (i.e., LDL cholesterol <100 mg/dl) is associated with improved results in terms of the regression or arrest of progression of coronary lesions compared with more moderate LDL cholesterol reduction,
      Post Coronary Artery Bypass Graft Trial Investigators
      The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts.
      no trial has directly assessed whether there is mortality benefit from lowering LDL cholesterol levels to the NCEP goal of 100 mg/dl. To determine whether achievement of the current NCEP cholesterol recommendations are consistent with beneficial endothelium-dependent vasodilatation, we assessed endothelium-dependent brachial artery vasoreactivity noninvasively in stable CAD patients. We hypothesized that achievement of LDL cholesterol ≤100 mg/dl would be associated with more beneficial endothelial vasoreactivity than LDL cholesterol >100 mg/dl in patients with CAD.
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