Influence of smoking status on progression of ... - Wiley Online Library

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All measured coronary artery seg- ments (n = 202) ... University of Florida College of Medicine .... 10.0% for the all-segment and target-segment responses, re-.
Clin. Cardiol. 21, 331-334 (1998)

Clinical Investigations

Influence of Smoking Status on Progression of Endothelid Dysfunction CARL J. &PINE, M.D., JAYD. SCHLAIFER, M.D., G.B.JOHN MANCIM, M.D.,*BERTRAM Pm;M.D.,+BLAIRJ. O’NEILL, M.D.,$ HARRY E. HABER,M.P.H.,~ ON BEHALFOFTHETREND INVESTIGATORS

Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Gainesville, Florida, USA, *University of British Columbia, Vancouver, British Columbia,Canada; +Universityof Michigan, Ann Arbor, Michigan, USA; TDalhousie University, Halifax, Nova Scotia, Canada; gParke-DavisPharmaceutical Research, Ann Arbor, Michigan, USA

summary

Background: Cigarette smoking is a major risk factor for developing coronary artery disease and is associated with increased coronary morbidity and mortality in patients with established atherosclerosis.This report describes the influence of smoking on coronary endothelialfunction in normotensive patients with coronary artery disease, but without left ventricular dysfunction, severe hypercholesterolemia, or insulindependent diabetes mellitus. Methods: Placebo-treated patients (n = 54) from a larger study assessing coronary endothelial function were classified at baseline a?smokersor nonsmokers for this subgroupandysis. Patients underwent coronary angiography at baseline and again after 6-month follow-up. Results: At baseline, there was a trend for a greater decrease in target segment diameter (n = 54) in smokers compared with nonsmokers (-17.2 +. 5.3% vs. -8.0 +. 2.5%, acetylcholine lo4 mol/l). All measured coronary artery segments (n = 202) showed similar responses (-7.3 f 2.7% vs. -3.8 -+ I .3%, acetylcholine lo4 mmol/l, for smokers vs. nonsmokers, respectively).After 6 months, smokers showed an even greater vasoconstrictor response to acetylcholine

This study was supported in part by Parke-Davis Pharmaceutical Research. Address for reprints: Carl J. Pepine, M.D. Division of Cardiovascular Medicine University of Florida College of Medicine 1600 SW Archer Road Gainesville, FL 32610-0277. USA Received: October 14, 1997 Accepted with revision: February 26, 1998

whereas nonsmokers did not (-21.7 ~ t _5.3% vs. -8.3 +. 2.5%, acetylcholine lo4 mmol/l). The vasodilatory response to nitroglycerin was similar in smokers and nonsmokers. Conclusions: In current smokers, a marked decline in endothelium-dependent vasomotor response was observed over a 6-month period.

Key words: acetylcholine, angiography, coronary disea3e, endothelium, smoking, vasoconstriction

Introduction Cigarette smoking has long been recognized as a major risk factor for developing atheroscleroticcoronary artery disease (CAD).’ It also is associated with increased morbidity and mortality in patients with established coronary atheroscleros~s.*-~ Among the many proposed mechanisms for the adverse cardiovascular effects of cigarette smoke is endothelial dysfunction.&9Prospective serial angiographic studies to assess the effect of smoking on the development and progression of coronary endothelid dysfunction are lacking. The recently reported TREND (Trial on Reversing Endothelial Dysfunction) study demonstrated that the potent angiotensin-convertingenzyme inhibitor quinapril significantly improved endothelium-dependent vasomotor response in normotensive patients with CAD but without left ventricular dysfunction, severe hypercholesterolemi%or insulin-dependent diabetes mellitus.loThs report describes the influence of smoking status on coronary artery endothelial function at baseline and at short-term follow-up in the subset of patients who were randomized to placebo in the TREND study.

Methods The methods of the TRENDstudy, a double-blind,placebocontrolled trial, were previously reported in detail.’() In brief,

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patients who had a clinical need for nonsurgical revascularization with single- or double-vessel CAD (>50% diameter stenosis) and one adjacent major coronary artery with no or mild (