Smoking, Smoking Cessation, and Risk for Symptomatic Peripheral Artery Disease in Women

BACKGROUND: Smoking has a well-documented detrimental effect on risk for myocardial infarction and stroke, but less information is available regarding peripheral artery disease (PAD), particularly among women. OBJECTIVE: To prospectively assess the association of current smoking status, cumulative smoking exposure, and smoking cessation with incident symptomatic PAD in women. DESIGN: Prospective cohort study. SETTING: U.S. female health care professionals in the Women's Health Study. PARTICIPANTS: 39,825 women with no cardiovascular disease who were prospectively followed for a median of 12.7 years. MEASUREMENTS: Incidence of symptomatic PAD. Cox proportional hazards models were used to compare PAD risk across smoking categories. RESULTS: 178 confirmed PAD events occurred. Across the 4 smoking categories (never, former, <15 cigarettes/d, and ≥15 cigarettes/d), age-adjusted incidence rates were 0.12, 0.34, 0.95, and 1.63 per 1000 person-years of follow-up, respectively. Multivariate adjustment had little effect on this relationship (adjusted hazard ratios HRs, 3.14 95% CI, 2.01 to 4.90, 8.93 CI, 5.02 to 15.89, and 16.95 CI, 10.77 to 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 risk estimates (HR, 5.58 CI, 2.61 to 11.93 for smoking <15 cigarettes/d and 9.52 CI, 5.17 to 17.53 for smoking ≥15 cigarettes/d). Lifetime exposure showed a strong dose-response relationship; fully adjusted HRs for smoking abstinence of fewer than 10, 10 to 29, and 30 or more pack-years were 2.52 (CI, 1.49 to 4.25), 6.75 (CI, 4.33 to 10.52), and 11.09 (CI, 6.94 to 17.72), respectively. Compared with current smokers, the adjusted HRs for fewer than 10 years, 10 to 20 years, more than 20 years, or lifelong abstinence were 0.39 (CI, 0.24 to 0.66), 0.28 (CI, 0.17 to 0.46), 0.16 (CI, 0.10 to 0.26), and 0.08 (CI, 0.05 to 0.12), respectively. LIMITATION: The use of symptomatic PAD as the a priori primary end point excludes asymptomatic disease. CONCLUSION: Among initially healthy women, smoking is a potent risk factor for symptomatic PAD and was associated with subclinical inflammation. Smoking cessation substantially reduces risk for PAD, but an increased occurrence of PAD persists even among former smokers who maintain abstinence. PRIMARY FUNDING SOURCE: The National Heart, Lung, and Blood Institute and National Cancer Institute.