Impaired Endothelium-Dependent Dilatation Precedes Early Arterial Wall Change in Symptom-Free Smokers

Abstract

Smoking is one of the known risk factors associated with atherosclerosis. Endothelial cell dysfunction is an early event in the development of atherosclerosis, and diminished nitric oxide production has been found to be a marker of this dysfunction. The aim of this study was to investigate the effect of smoking on the endothelial function before the development of early atherosclerotic wall changes.

Twenty symptom-free smokers (> 10 cigarettes per day) and 22 symptom-free, ageand sex-matched volunteers were included into the study. Subjects with diabetes, hypertension, a known history of cardiovascular disease, or those who had a plaque (isolated irregular luminal lesion > 1.5 mm thick) or an intima-media thickness > 0.8 mm in the carotid bifurcation were excluded. By means of high-resolution ultrasound, the diameter of the brachial artery at rest, during reactive hyperemia (endothelium-dependent dilatation), and after sublingual glycerin trinitrate (endothelium-independent dilatation; five controls and five smokers) were measured. All the tests were performed with acclimatized subjects in the supine position. The entire test was recorded on super VHS video. Diameter measurements (average diameter of five cardiac cycles), incident with the R wave on the electrocardiogram, were taken from the near to far wall. Reproducibility measurements in eight subjects (five volunteers and three smokers) showed a coefficient of variation ranging from 1.6% to 3.2% for intraobserver and 1.8% to 3.9% for interobserver variability. Brachial artery endothelium-dependent dilatation was present in all the symptom-free volunteers (10.8 ±3.4%, range 3.4 to 18.2) and reduced or abolished in smokers (3.5 ± 2.9%, range 0 to 7.6; p > 0.001). Glycerin trinitrate induced comparable dilatation in both smokers and controls, indicating that the dysfunction is endothelium dependent. Endothelial dysfunction is present prior to arterial wall changes in smokers, suggesting early arterial damage.

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