Effect of gemfibrozil +/- niacin +/- cholestyramine on endothelial function in patients with serum low-density lipoprotein cholesterol levels <160 mg/dl and high-density lipoprotein cholesterol levels <40 mg/dl.
We studied endothelial function using the brachial artery ultrasound model in 100 subjects from the Armed Forces Regression Study, a placebo-controlled, angiographic regression trial in subjects with normal or modestly elevated low-density lipoprotein (LDL) cholesterol and low levels of high-density lipoprotein (HDL) cholesterol treated for 30 months with gemfibrozil and (if necessary) niacin and/or cholestyramine to raise HDL by 25% and lower LDL to < 110 mg/dl. Although the treatment group had highly significant improvements in LDL and HDL cholesterol, there was no difference between the 2 groups in flow-mediated dilation (treatment vs control 6.9 +/- 6.5% vs 6.3 +/- 7.3%) or nitroglycerin-induced dilation (12.4 +/- 9.6% vs 11.9 +/- 7.4%, all p = NS). Treatment and control subjects without a history of hypertension had flow-mediated dilation similar to that of a normal reference population (10.6 +/- 8.3% vs 8.4 +/- 4.5%), whereas subjects with a history of systemic hypertension had markedly impaired flow-mediated dilation that was not significantly improved with treatment (treatment vs control, 6.0 +/- 5.5% vs 4.3 +/- 5.9%, p = 0.2). Thus, nonhypertensive subjects with angiographic coronary disease and low HDL cholesterol had normal endothelial function in the brachial artery model. Patients with a history of hypertension had marked endothelial dysfunction despite blood pressure treated to normal levels, and this dysfunction is not attenuated by pharmacologic therapy for dyslipidemia.
Andrews
T C
TC
Department of Cardiology, Wilford Hall Medical Center, Lackland Air Force Base, San Antonio, Texas, USA.
Whitney
E J
EJ
Green
G
G
Kalenian
R
R
Personius
B E
BE
D000368:Aged; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002792:Cholestyramine Resin / Q000494:pharmacology* / Q000627:therapeutic use; D003327:Coronary Disease / Q000150:complications / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D015248:Gemfibrozil / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000494:pharmacology* / Q000627:therapeutic use; D012016:Reference Values; D014664:Vasodilation / Q000187:drug effects*
D000960:Hypolipidemic Agents; D002792:Cholestyramine Resin; D009525:Niacin; D015248:Gemfibrozil