Associations between conventional cardiovascular risk factors and risk of peripheral artery disease in men.

CONTEXT Previous studies have examined the associations of individual clinical risk factors with risk of peripheral artery disease (PAD), but the combined effects of these risk factors are largely unknown. OBJECTIVE To estimate the degree to which the 4 conventional cardiovascular risk factors of smoking, hypertension, hypercholesterolemia, and type 2 diabetes are associated with the risk of PAD among men. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 44,985 men in the United States without a history of cardiovascular disease at baseline in 1986; participants in the Health Professionals Follow-up Study were followed up for 25 years until January 2011. The presence of risk factors was updated biennially during follow-up. MAIN OUTCOME MEASURE Clinically significant PAD defined as limb amputation or revascularization, angiogram reporting vascular obstruction of 50% or greater, ankle-brachial index of less than 0.90, or physician-diagnosed PAD. RESULTS During a median follow-up of 24.2 years (interquartile range, 20.8-24.7 years), there were 537 cases of incident PAD. Each risk factor was significantly and independently associated with a higher risk of PAD after adjustment for the other 3 risk factors and confounders. The age-adjusted incidence rates were 9 (95% CI, 6-14) cases/100,000 person-years (n = 19 incident cases) for 0 risk factors, 23 (95% CI, 18-28) cases/100,000 person-years (n = 99 incident cases) for 1 risk factor, 47 (95% CI, 39-56) cases/100,000 person-years (n = 176 incident cases) for 2 risk factors, 92 (95% CI, 76-111) cases/100,000 person-years (n = 180 incident cases) for 3 risk factors, and 186 (95% CI, 141-246) cases/100,000 person-years (n = 63 incident cases) for 4 risk factors. The multivariable-adjusted hazard ratio for each additional risk factor was 2.06 (95% CI, 1.88-2.26). Men without any of the 4 risk factors had a hazard ratio of PAD of 0.23 (95% CI, 0.14-0.36) compared with all other men in the cohort. In 96% of PAD cases (95% CI, 94%-98%), at least 1 of the 4 risk factors was present at the time of PAD diagnosis. The population-attributable risk associated with these 4 risk factors was 75% (95% CI, 64%-87%). The absolute incidence of PAD among men with all 4 risk factors was 3.5/1000 person-years. CONCLUSION Among men in this cohort, smoking, hypertension, hypercholesterolemia, and type 2 diabetes account for the majority of risk associated with development of clinically significant PAD.

[1]  N. Cook,et al.  High-Molecular-Weight and Total Adiponectin Levels and Incident Symptomatic Peripheral Artery Disease in Women: A Prospective Investigation , 2011, Circulation.

[2]  C. Meyer,et al.  Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease. , 2011, Journal of the American College of Cardiology.

[3]  J. Beckman,et al.  Secondary Prevention and Mortality in Peripheral Artery Disease: National Health and Nutrition Examination Study, 1999 to 2004 , 2011, Circulation.

[4]  Douglas P. Zipes,et al.  Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 2-Volume Set, 10th Edition , 2011 .

[5]  E. Tuzcu,et al.  Peripheral arterial disease and progression of coronary atherosclerosis. , 2011, Journal of the American College of Cardiology.

[6]  P. Libby,et al.  Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 2-Volume Set, 9th Edition Expert Consult Premium Edition €“ Enhanced Online Features , 2011 .

[7]  M. M. Joosten,et al.  Changes in Alcohol Consumption and Subsequent Risk of Type 2 Diabetes in Men , 2010, Diabetes.

[8]  Deepak L. Bhatt,et al.  Cardiovascular risk factor control and outcomes in peripheral artery disease patients in the Reduction of Atherothrombosis for Continued Health (REACH) Registry. , 2009, Atherosclerosis.

[9]  Y. Béjot,et al.  Comparative epidemiology of stroke and acute myocardial infarction: the Dijon Vascular project (Diva) , 2009, Journal of Neurology, Neurosurgery & Psychiatry.

[10]  L. Ferrucci,et al.  Associations of borderline and low normal ankle-brachial index values with functional decline at 5-year follow-up: the WALCS (Walking and Leg Circulation Study). , 2009, Journal of the American College of Cardiology.

[11]  A Hofman,et al.  Ankle brachial index combined with Framingham Risk Score to predict cardiovascular events and mortality: a meta-analysis. , 2008, JAMA.

[12]  J. Beckman,et al.  Serum Total Bilirubin Level and Prevalent Lower-Extremity Peripheral Arterial Disease: National Health and Nutrition Examination Survey (NHANES) 1999 to 2004 , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[13]  B. Gersh One-Year Cardiovascular Event Rates in Outpatients With Atherothrombosis , 2008 .

[14]  M. Al-Omran,et al.  Commentary: one-year cardiovascular event rates in outpatients with atherothrombosis. Steg PG, Bhatt DL, Wilson PW, et al; REACH Registry Investigators. JAMA. 2007;297: 1197-1206. , 2007, Perspectives in vascular surgery and endovascular therapy.

[15]  Honglei Chen,et al.  Hypertension, hypercholesterolemia, diabetes, and risk of Parkinson disease , 2007, Neurology.

[16]  R. Langer,et al.  Ethnic-specific prevalence of peripheral arterial disease in the United States. , 2007, American journal of preventive medicine.

[17]  D. Mukherjee,et al.  Peripheral arterial disease: Epidemiology, natural history, diagnosis and treatment , 2007, The International journal of angiology : official publication of the International College of Angiology, Inc.

[18]  John V. White,et al.  Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). , 2007, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[19]  L. Norgren,et al.  Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). , 2007, Journal of vascular surgery.

[20]  D. Spiegelman,et al.  Point and interval estimates of partial population attributable risks in cohort studies: examples and software , 2007, Cancer Causes & Control.

[21]  Beatrice A. Golomb,et al.  Peripheral Arterial Disease: Morbidity and Mortality Implications , 2006, Circulation.

[22]  E. Rimm,et al.  Healthy Lifestyle Factors in the Primary Prevention of Coronary Heart Disease Among Men: Benefits Among Users and Nonusers of Lipid-Lowering and Antihypertensive Medications , 2006, Circulation.

[23]  Rodney A. White,et al.  ACC/AHA 2005 Practice Guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and abdominal aortic): a collaborative report from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular Angiography , 2006, Circulation.

[24]  J. Polak,et al.  Risk factors for declining ankle-brachial index in men and women 65 years or older: the Cardiovascular Health Study. , 2005, Archives of internal medicine.

[25]  Luigi Ferrucci,et al.  Functional decline in peripheral arterial disease: associations with the ankle brachial index and leg symptoms. , 2004, JAMA.

[26]  E. Rimm,et al.  Effect of type 2 diabetes and its duration on the risk of peripheral arterial disease among men , 2004 .

[27]  Daniel W. Jones,et al.  Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. , 2003, Hypertension.

[28]  A. Dyer,et al.  Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. , 2003, JAMA.

[29]  A. Dyer,et al.  Major Risk Factors as Antecedents of Fatal and Nonfatal Coronary Heart Disease Events , 2003 .

[30]  Eric J Topol,et al.  Prevalence of conventional risk factors in patients with coronary heart disease. , 2003, JAMA.

[31]  N J Wald,et al.  Quantifying effect of statins on low density lipoprotein cholesterol, ischaemic heart disease, and stroke: systematic review and meta-analysis , 2003, BMJ : British Medical Journal.

[32]  P. Mehler,et al.  Intensive Blood Pressure Control Reduces the Risk of Cardiovascular Events in Patients With Peripheral Arterial Disease and Type 2 Diabetes , 2003, Circulation.

[33]  R. Holman,et al.  UKPDS 59: hyperglycemia and other potentially modifiable risk factors for peripheral vascular disease in type 2 diabetes. , 2002, Diabetes care.

[34]  G A Colditz,et al.  Physical activity and television watching in relation to risk for type 2 diabetes mellitus in men. , 2001, Archives of internal medicine.

[35]  T. Lumley,et al.  Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study. , 2001, Archives of internal medicine.

[36]  M. Criqui,et al.  Peripheral arterial disease detection, awareness, and treatment in primary care. , 2001, JAMA.

[37]  J. Mckenney,et al.  Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). , 2001, JAMA.

[38]  P. Wahl,et al.  Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. , 2000, American journal of epidemiology.

[39]  LOW RISK-FACTOR PROFILE AND LONG-TERM CARDIOVASCULAR AND NON-CARDIOVASCULAR MORTALITY AND LIFE EXPECTANCY , 2000 .

[40]  A. Dyer,et al.  Low risk-factor profile and long-term cardiovascular and noncardiovascular mortality and life expectancy: findings for 5 large cohorts of young adult and middle-aged men and women. , 1999, JAMA.

[41]  G. Lowe,et al.  Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study. , 1999, European heart journal.

[42]  E. Rimm,et al.  Reproducibility and Validity of a Self‐Administered Physical Activity Questionnaire for Male Health Professionals , 1996, Epidemiology.

[43]  I. Sartori Aspirin Use and the Risk for Colorectal Cancer and Adenoma in Male Health Professionals. , 1996 .

[44]  J. Manson,et al.  Smoking Cessation and Time Course of Decreased Risks of Coronary Heart Disease in Middle-Aged Women , 1994 .

[45]  B Rosner,et al.  Smoking cessation and decreased risk of stroke in women. , 1993, JAMA.

[46]  E. Rimm,et al.  A Prospective Study of Nutritional Factors and Hypertension Among US Men , 1989, Circulation.

[47]  B Rosner,et al.  Alcohol intake in relation to diet and obesity in women and men. , 1991, The American journal of clinical nutrition.

[48]  E. Rimm,et al.  The assessment of alcohol consumption by a simple self-administered questionnaire. , 1991, American journal of epidemiology.

[49]  R B D'Agostino,et al.  Relation of pooled logistic regression to time dependent Cox regression analysis: the Framingham Heart Study. , 1990, Statistics in medicine.

[50]  E. Rimm,et al.  Validity of Self‐Reported Waist and Hip Circumferences in Men and Women , 1990, Epidemiology.

[51]  W. Whitehouse Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality: Jonason T, Bergstrom R. Acta Med Scand 1987;221:253–260 , 1988 .

[52]  R. Bergström,et al.  Cessation of smoking in patients with intermittent claudication. Effects on the risk of peripheral vascular complications, myocardial infarction and mortality. , 2009, Acta medica Scandinavica.

[53]  W. Kannel,et al.  Update on Some Epidemiologic Features of Intermittent Claudication: The Framingham Study , 1985, Journal of the American Geriatrics Society.

[54]  E. Braunwald Heart Disease: A Textbook of Cardiovascular Medicine , 1992, Annals of Internal Medicine.