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Original Research |

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

David Conen, MD, MPH; Brendan M. Everett, MD, MPH; Tobias Kurth, MD, ScD; Mark A. Creager, MD; Julie E. Buring, ScD; Paul M Ridker, MD, MPH; and Aruna D. Pradhan, MD, MPH
[+] Article, Author, and Disclosure Information

From University Hospital, Basel, Switzerland; Brigham and Women's Hospital, Harvard Medical School, Harvard School of Public Health, and Veterans Affairs Boston Medical Center, Boston, Massachusetts; and INSERM Unit 708–Neuroepidemiology and University Pierre et Marie Curie, Paris, France.

Note: Drs. Conen and Everett contributed equally to this work.

Grant Support: By the National Heart, Lung, and Blood Institute (grants HL-043851, HL-080467, HL-082740, and HL-075771), National Cancer Institute (grant CA-047988), and Donald W. Reynolds Foundation.

Potential Conflicts of Interest: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2772.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Pradhan (e-mail, apradhan@partners.org).

Requests for Single Reprints: Aruna D. Pradhan, MD, MPH, Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215; e-mail, apradhan@partners.org.

Current Author Addresses: Dr. Conen: Department of Medicine, University Hospital, Petersgraben 4, 4031 Basel, Switzerland.

Drs. Everett, Buring, Ridker, and Pradhan: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, MA 02215.

Dr. Kurth: INSERM Unit 708-Neuroepidemiology, Hôpital de la Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.

Dr. Creager: Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115.

Author Contributions: Conception and design: D. Conen, B.M. Everett, P.M Ridker, A.D. Pradhan.

Analysis and interpretation of the data: D. Conen, B.M. Everett, T. Kurth, A.D. Pradhan.

Drafting of the article: D. Conen, B.M. Everett, A.D. Pradhan.

Critical revision of the article for important intellectual content: D. Conen, B.M. Everett, T. Kurth, M.A. Creager, J.E. Buring, P.M Ridker, A.D. Pradhan.

Final approval of the article: D. Conen, B.M. Everett, T. Kurth, J.E. Buring, P.M Ridker, A.D. Pradhan.

Statistical expertise: D. Conen, B.M. Everett.

Obtaining of funding: M.A. Creager, J.E. Buring, A.D. Pradhan.

Administrative, technical, or logistic support: J.E. Buring, P.M Ridker, A.D. Pradhan.

Collection and assembly of data: D. Conen, B.M. Everett, J.E. Buring, P.M Ridker, A.D. Pradhan.

Ann Intern Med. 2011;154(11):719-726. doi:10.7326/0003-4819-154-11-201106070-00003
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This article has been corrected. For original version, click "Original Version (PDF)" in column 2.

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.


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Appendix Figure.
Cumulative incidence of PAD, by pack-years of smoking.

PAD = peripheral artery disease.

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Hazard ratio for incident PAD.

Hazard ratios are adjusted for age, hypertension, diabetes, hypercholesterolemia, body mass index, alcohol consumption, and physical activity. Current smokers are the reference group. PAD = peripheral artery disease.

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Submit a Comment/Letter
Women , smoking and peripheral vascular disease
Posted on June 17, 2011
Sabino G Echebarria Mendieta
Conflict of Interest: None Declared

The studies relating migraine headache and cardiovascular Health in women : Kurth et al ( Women's Health Study - WHS ) and Amed B et al ( Women Ischemia Syndrome Evaluation-WISE ) showed , that after a 10 years and 4.4 years of follow-up , respectively ( 27,840 and 905 participants ) significative association appeared with the former ( HR 2.15 ) . Migraine with aura may be associated with an increased burden of CV risk factors , including prothrombotic and vasoactive factors .Additionally , the gender difference in antiplatelet effects among vascular beds is unknown but the study of low-dose aspirin in primary prevention in women , showed 24 % risk reduction in ischemic stroke and MI risk in men. (Ridker PM. NEJM 2005 ; 352: 1293).This would explain the physiopathologic effects of smoking and gender difference : endothelial dysfunction , with concentration decrease in NO and prostacyclin , effect of cLDL , fibrinogen , viscosity and white blood cells count may be explained in these contexts ( Haemostatic and rheological facts in intermittent claudication : the influence of smoking and extent of arterial disease . Br J Haematol 1996 ; 92: 226-30 ). -Khusla S . Cardiovascular effects of nicotine : relation to deleterious effects of cigarette smoking.Am Heart J 1994; 127: 1669-72

Conflict of Interest:

None declared

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Summary for Patients

Smoking and Peripheral Artery Disease in Women

The full report is titled “Smoking, Smoking Cessation, and Risk for Symptomatic Peripheral Artery Disease in Women. A Cohort Study.” It is in the 7 June 2011 issue of Annals of Internal Medicine (volume 154, pages 719-726). The authors are D. Conen, B.M. Everett, T. Kurth, M.A. Creager, J.E. Buring, P.M Ridker, and A.D. Pradhan.


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