This study attempted to assess whether coronary risk factors are associated with endothelial
dysfunction in the systemic arteries of asymptomatic men and women.
Endothelial dysfunction is present in adults with established atherosclerosis. It
is not known whether risk factors interact to produce endothelial dysfunction in clinically
well subjects early in the natural history.
Using high resolution ultrasound, we measured arterial diameter at rest, after reactive
hyperemia (with increased flow causing endothelium-dependent dilation) and after sublingual
nitroglycerin (an endothelium-independent dilator). Arterial responses were studied
noninvasively in 500 clinically well, nonhypertensive subjects (252 men, 248 women;
mean [+/- SD] age 36 +/- 15 years, range 5 to 73), including 179 current and former
smokers. The superficial femoral artery was studied in 46 subjects and the brachial
artery in 454.
Flow-mediated dilation ranged from -1% to +17%. All arteries dilated in response to
administration of nitroglycerin (17 +/- 6%), suggesting an abnormality of endothelial
function in subjects with impaired flow-mediated dilation. On univariate analysis,
reduced flow-mediated dilation was significantly related to hypercholesterolemia,
cigarette smoking, higher blood pressure, male gender, older age, family history of
premature vascular disease and larger vessel size (p < 0.01). By multiple stepwise
regression analysis, reduced flow-mediated dilation was independently associated with
cigarette smoking, older age, male gender and larger vessel size (p < 0.005) but not
with total cholesterol level, blood pressure or family history. A composite risk factor
score was independently related to flow-mediated dilation (r = -0.30, p < 0.0001),
suggesting risk factor interaction.
Loss of endothelium-dependent dilation in the systemic arteries occurs in the preclinical
phase of vascular disease and is associated with interaction of the same risk factors
known to predispose to atherosclerosis and its complications in later life.