CIGARETTE-SMOKING IS ASSOCIATED WITH DOSE-RELATED AND POTENTIALLY REVERSIBLE IMPAIRMENT OF ENDOTHELIUM-DEPENDENT DILATION IN HEALTHY-YOUNG ADULTS

Background. Cigarette smoking is the most important modifiable risk fa ctor for atherosclerosis. Endothelial dysfunction is an early event in atherogenesis, and we hypothesized that smoking might be associated w ith endothelial damage in the systemic arteries of otherwise healthy y oung adults. Methods and Results. We studied noninvasively the brachia l arteries of 200 subjects aged 15 to 57 years, all normotensive, nond iabetic with cholesterol level less-than-or-equal-to 240 mg/dL and no family history of premature vascular disease: 80 control subjects aged 16 to 56 years (mean, 35), 80 current smokers aged 15 to 55 years (me an, 33), and 40 former smokers aged 25 to 57 years (mean, 38). Total l ifetime amount smoked varied from 1 to 75 pack years in the smokers. U sing high-resolution ultrasound, vessel diameter was measured at rest, during reactive hyperemia (with flow increase causing endothelium-dep endent dilation), and after sublingual glyceryl trinitrate (GTN, an en dothelium-independent vasodilator). Flow-mediated dilation (FMD) was o bserved in all the control subjects (10+/-3.3%; range, 4% to 22%) but was impaired or absent in the smokers (4+/-3.9%; range, 0% to 17%; P<. 0001). FMD in the smokers was inversely related to lifetime dose smoke d (6.6+/-4.0% in very light smokers, 4.0+/-3.1% in light smokers, 3.2/-3.2% in moderate smokers, and 2.6+/-1.2% in heavy smokers; P<.01). F MD for the former smokers was 5.1+/-4.1% (range, 0% to 15%). In a mult ivariate model adjusting for age, sex, cholesterol, smoking history, a nd vessel size, former smoking was associated with a higher FMD than c urrent smoking (P=.07); when only male former and current smokers were considered, the higher FMD was significant (P=.0001) but not for fema le smokers (P=.24). GTN caused dilation in all subjects (control subje cts, 20+/-5.2%; smokers, 17+/-5.8%; former smokers, 17.4+/-5.4%). Vess el diameter, baseline flow, and degree of reactive hyperemia (Doppler estimated) were similar in all groups. Conclusions:Cigarette smoking i s associated with dose-related and potentially reversible impairment o f endothelium-dependent arterial dilation in asymptomatic young adults , consistent with endothelial dysfunction.