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Title: Smoking, smoking cessation, and risk of symptomatic peripheral artery disease in women

Authors: D Conen, B Everett, T Kurth, M Creager, et al.

Reference: Ann Intern Med 2011; 154(11):719-726
http://bit.ly/nJrnim

Reviewer: Joaquin Barnoya, MD, MPH, Contributing Editor, ProCor; Research Assistant, Professor of Surgery, Washington University in St. Louis, Missouri, USA; Director, Research and Education, Unidad de Cirugia Cardiovascular de Guatemala, Guatemala

Reviewer comments: Peripheral artery disease (PAD) is another disease markedly increased in smokers compared to non-smokers. However, as with most diseases, the risk is greatly reduced after cessation. Not surprisingly, the longer the abstinence, the larger the decrease in risk. This study, however, might be an underestimate of the risk as only symptomatic PAD was assessed. In addition to the strong dose-response relationship, it is worth highlighting the higher risk among pre-menopausal women compared to post-menopausal women.

Purpose of study: To assess the relationship between smoking and smoking cessation with symptomatic PAD defined as intermittent claudication or lower-extremity artery revascularization.

Location of study: US

Methods: Participants were part of the Women´s Health Study, a completed randomized clinical trial that evaluated the risk and benefits of low-dose aspirin and vitamin E in the primary prevention of cardiovascular disease and cancer. Healthy women (39,876) were recruited beginning in 1993 and followed up every six months during the first year and every 12 months thereafter. Self-reported PAD was systematically confirmed by both participant interviews and medical record reviews. Smoking status included average number of cigarettes per day and years smoking (to calculate pack-year of cigarette smoking). Laboratory analysis included cholesterol level and inflammatory markers. PAD events were assessed annually via the Edinburgh Claudication Questionnaire. Multivariate analysis was adjusted for age, history of hypertension, diabetes, or hypercholesterolemia; body mass index; alcohol consumption; and physical activity.

Results: At baseline, 20,336 women (51%) were never smokers, 14,263 (36%) were former smokers, and 1967 (5%) smoked fewer than 15 cigarettes per day, and 3259 (8%) smoked 15 or more cigarettes per day. During a median follow-up of 12.7 years, 178 symptomatic PAD events occurred. Never smokers had the lowest incidence of PAD (0.12 events per 1000 person-years of follow-up) whereas the risk among those who smoked ≥15 cigarettes per day was more than 10-fold higher (1.63 events per 100 person-years of follow-up). Former smokers experienced a higher rate than never smokers but lower than current smokers. Multivariate adjustment had little effect on these findings. Analysis by menopausal status at baseline found that the risk for PAD was stronger among pre-menopausal than among post-menopausal women. Adding inflammatory markers to the model (e.g. hsCRP) attenuated the risk of PAD from smoking, however, smoking <15 cigarettes per day was still associated with more than a five-fold increase risk during follow-up. Furthermore, there was a strong dose-response relationship. Regarding smoking cessation, former smokers had a lower risk compared to continuing smokers. The longer the abstinence, the lower the risk. Among those that had quit fewer than 10 years ago, the risk had already decreased by 60%.