AimsThe aim was to determine whether the effect of smoking on the development of peripheral or coronary artery disease might be mediated by other cardiovascular risk factors, including dietary antioxidant vitamin intake, serum low and high density lipoproteins, blood pressure, plasma fibrinogen, blood viscosity and markers of endothelial disturbance and fibrin turnover.Methods and Results 1592 men and women aged 55-74 years were selected at random from 11 general practices in Edinburgh, Scotland and followed-up for 5 years. The incidences of peripheral arterial disease and coronary artery disease were 5·1% and 11·1%, respectively. Both conditions were more common in moderate and heavy smokers than in never smokers; cigarette smoking was a stronger risk factor for peripheral arterial disease than for coronary artery disease. Smoking was associated with reduced dietary antioxidant vitamin intake, serum high density lipoprotein cholesterol and diastolic blood pressure and with increased alcohol intake, serum triglycerides, blood viscosity, plasma fibrinogen, and markers of endothelial disturbance (tissue plasminogen activator and von Willebrand factor antigens). Simultaneous adjustment for these risk factors reduced the relative risk of peripheral arterial disease only slightly, from 3·94 (95% CI 2·04, 7·62) to 2·72 (95% CI 1·13, 6·53) in heavy smokers and from 1·87 (95% CI 0·91, 3·85) to 1·70 (95% CI 0·72, 3·99) in moderate smokers. Similar adjustment also had little effect on the risk of coronary artery disease associated with smoking. ConclusionThe combined effect of smoking on the cardiovascular risk factors studied may explain part of its influence on peripheral and coronary arterial disease, but the majority of the effect appears to be due to other mechanisms. (Eur Heart J 1999; 20: 344-353)

Elevations in rheologic factors may have important effects on further reduction of blood flow in the legs of patients with claudication and promote worsening ischemia and clinical progression of symptoms.