Smoking is Associated with Dose-Related Increase of Intima-Media Thickness and Endothelial Dysfunction

Cigarette smoking is firmly established as a risk factor for atherosclerosis. However, the exact mechanism causing smoking-related damage to the arterial wall and its relation to the atherosclerotic process is not known. Also unknown is the time delay between the start of smoking and the sequence of functional and morphologic changes occurring in the arterial wall caused by smoking and their interrelationship. Therefore, the aim of this study was to evaluate the acute and chronic effects of smoking on endothelium-dependent (flow-mediated) dilation (FMD) of the peripheral arteries, the effects of dose and duration of chronic smoking on intima-media thickness (IMT) of the carotid arteries, and their interrelationship. The study encompassed two groups of smokers. In group A there were 40 subjects of both sexes, who smoked on average 17.6 +/- 6.5 cigarettes per day, for 5 to 15 years (mean 8.95 +/- 4.0 years), mean age 28.1 years. Group B consisted of 42 smokers of both sexes who smoked 21.15 +/- 8.2 cigarettes/day for more than 15 years (mean 21.15 +/- 3.4 years), mean age 39.5 years. The control group consisted of 40 healthy subjects without major risk factors of atherosclerosis, mean age 29.1 years. By means of high-resolution ultrasound the brachial artery diameter was measured at rest and during reactive hyperemia (after release of a forearm tourniquet) and the flow-mediated, endothelium-dependent dilation was calculated. The IMT of the carotid arteries was determined in all subjects by use of B-mode ultrasonography. Resting blood flow in the brachial arteries was significantly less in the smokers' groups than in controls (78.8 +/- 31.9 vs 134.9 +/- 45.0 mL/min, p<0.0001). This decrease was much more evident in female than in male smokers. Female smokers also had significantly smaller brachial artery diameter at rest. In smokers the FMD of the brachial artery was reduced (11 +/- 4% vs 7 +/- 4%, p<0.004) and the mean IMT was significantly greater than in controls (0.68 +/- 0.13 vs 0.59 +/- 0.04 mm, p<0.001). Impairments of FMD and IMT increase were related to the duration and to the number of cigarettes smoked. In all subjects IMT was significantly correlated with total and LDL cholesterol, fibrinogen, lipoprotein(a) concentration, body mass index, and age of the subjects, but multivariate analysis showed that only total dose smoked and fibrinogen concentration were independently related to IMT. The results of this study show that smoking is associated with dose-related impairment of FMD and increased IMT of the carotid arteries. Impairment of FMD occurs in smokers very early and is the earliest detectable event, preceding morphologic changes of the vessel wall. Some harmful effects of smoking on the vessel wall are gender related.