Smoking Increases Women's Risk for Peripheral Artery Disease

Laurie Barclay, MD

June 07, 2011

June 7, 2011 — Among initially healthy women, smoking for even a short time is a potent risk factor for symptomatic peripheral artery disease (PAD), according to the results of a prospective cohort study reported in the June 7 issue of the Annals of Internal Medicine.

"This study showed that—as has been previously shown for heart attacks and for lung cancer—that smoking is actually very harmful for the development of PAD," said senior author Aruna D. Pradhan, MD, MPH, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, in a news release. "This is significant because PAD is a disease that not only causes a lot of pain and discomfort with usual, daily activities but it also increases the risk of heart attack."

The goal of the study was to evaluate the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD among 39,825 US female healthcare professionals with no cardiovascular disease who were enrolled in the Women's Health Study and prospectively observed. The investigators compared PAD risk across smoking categories using Cox proportional hazards models.

During follow-up (median, 12.7 years), there were 178 confirmed PAD events. Across the 4 smoking categories (never, former, < 15 cigarettes/day, and ≥ 15 cigarettes/day), the age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1000 person-years of follow-up, respectively. This association was not changed much by multivariate adjustment. Compared with women who never smoked, the adjusted hazard ratios (HRs) were 3.14 (95% confidence interval [CI], 2.01 - 4.90) for former smoking, 8.93 (95% CI, 5.02 - 15.89) for smoking less than 15 cigarettes per day, and 16.95 (95% CI, 10.77 - 26.67) for smoking 15 or more cigarettes per day.

Blood samples were available for 28,314 participants, among whom 117 PAD events were reported. Among these women, risk estimates for PAD were attenuated by additional adjustment for high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 levels (HR, 5.58 [95% CI, 2.61 - 11.93] for smoking < 15 cigarettes per day and HR, 9.52 [95% CI, 5.17 - 17.53] for smoking ≥ 15 cigarettes per day).

There was a strong dose-response relationship between lifetime smoking exposure and PAD risk. Fully adjusted HRs for smoking abstinence of less than 10, 10 to 29, and 30 or more pack-years were 2.52 (95% CI, 1.49 - 4.25), 6.75 (95% CI, 4.33 - 10.52), and 11.09 (95% CI, 6.94 - 17.72), respectively. Adjusted HRs, compared with current smokers, for smoking abstinence of less than 10 years, 10 to 20 years, more than 20 years, 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.

"Among initially healthy women, smoking is a potent risk factor for symptomatic PAD and was associated with subclinical inflammation," the study authors write. "Smoking cessation substantially reduces risk for PAD, but an increased occurrence of PAD persists even among former smokers who maintain abstinence."

Study limitations include lack of generalizability to men or to persons with asymptomatic PAD and inability to assess the effect of exposure to secondhand smoke.

"In this large, prospective cohort study, smoking significantly increased the risk for symptomatic PAD in women in a dose-dependent manner," the study authors conclude. "...Women should be made aware that smoking increases their risk for PAD and that smoking cessation will reduce that risk."

The National Heart, Lung, and Blood Institute and National Cancer Institute supported this study. Disclosures of the study authors can be viewed at the Annals of Internal Medicine Web site .

Ann Intern Med. 2011;154:719-726. Abstract

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