Smoking, Smoking Status, and Risk for Symptomatic Peripheral Artery Disease in Women: A Cohort Study

Study Questions:

How are current smoking status, cumulative smoking exposure, and/or smoking cessation associated with incident symptomatic peripheral arterial disease (PAD) in women?


This was a prospective cohort study of female health care professionals residing in the United States and enrolled in the Women’s Health Study. Women with no apparent cardiovascular disease at baseline were followed for a median of 12.7 years. Women were classified as never-smokers, former smokers, current smokers who smoked fewer than 15 cigarettes per day, or current smokers who smoked 15 or more cigarettes per day. Current smokers were queried about the average number of cigarettes they smoked per day at study entry (none, 1-4, 5-14, 15-24, 25-35, 36-44, or ≥45 cigarettes/day). Participants were asked how many total years they had smoked (<5, 5-9, 10-19, 20-29, 30-39, 40-49, or ≥50 years) and the number of cigarettes they had smoked per day across eight age categories, ranging from younger than 15 years to 70 years or older. Pack-years of cigarette smoking were calculated by multiplying the midpoint of the “total number of years smoked” category by the average number of cigarettes smoked per day on the baseline questionnaire. Participants answered the same questionnaire again at months 12, 24, 48, 72, and 96; at the end of the randomized portion of the study; and three more times during the observational follow-up study. Participants were surveyed annually for health outcomes including symptomatic PAD including intermittent claudication, and PAD interventions.


A total of 39,825 women were included in this analysis, of which 20,336 women were never smokers, 14,263 were former smokers, and 1,967 smoked <15 cigarettes per day, and 3,259 smoked 15 or more cigarettes per day. During follow-up, 178 confirmed PAD events were identified. Across the four smoking categories (never, former, <15 cigarettes/day, and ≥15 cigarettes/day), age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1,000 person-years of follow-up, respectively. Adjustment for traditional potential confounders had little effect on this relationship (hazard ratios [HRs], 3.14; 95% confidence interval [CI], 2.01-4.90; HR, 8.93; 95% CI, 5.02-15.89; and HR, 6.95; 95% CI, 10.77-26.67, respectively vs. women who never smoked). Additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 levels among women with available blood samples (28,314 participants, 117 events) attenuated the risk estimates (HR, 5.58; 95% CI, 2.61-11.93 for smoking <15 cigarettes/day, and HR, 9.52; 95% CI, 5.17-17.53 for smoking ≥15 cigarettes/day). A strong dose–response relationship was observed for lifetime exposure. Compared with current smokers, the adjusted HRs for fewer than 10 years of smoking, 10-20 years of smoking, more than 20 years of smoking, or lifelong abstinence were 0.39 (95% CI, 0.24-0.66), 0.28 (95% CI, 0.17-0.46), 0.16 (95% CI, 0.10-0.26), and 0.08 (95% CI, 0.05-0.12), respectively.


The investigators concluded that among initially healthy women, smoking is a significant risk factor for symptomatic PAD. Smoking cessation reduced the risk for PAD; however, increased occurrence of PAD persisted even among former smokers who maintained abstinence.


These data suggest that although smoking cessation reduced the risk for PAD, being a lifelong nonsmoker carries the lowest risk of symptomatic PAD. Given the rates of smoking among young adults, including women, efforts to prevent initiation of smoking carry significant public health ramifications.

Clinical Topics: Prevention, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Smoking

Keywords: Incidence, Follow-Up Studies, Women's Health, Peripheral Arterial Disease, Risk Factors, Smoking Cessation, Smoking, United States

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