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

Abstract

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.

Figure 1

Hazard ratios (HRs) for incident peripheral artery disease (PAD) according to individual and joint clinical risk factors. HRs are adjusted for age, height, aspirin use, parental history of myocardial infarction at age 60 years or younger, geographical region, body mass index, physical activity, alcohol consumption and each of the other three clinical risk factors. The reference group for each of the individual risk factors was the remainder of the cohort without the individual risk factor. Population attributable risks percent (PAR%) for each individual risk factor were calculated using pooled logistic regression models and were adjusted for the same factors mentioned above. The linear trend for the joint risk factors was obtained by treating the number of risk factors as a continuous variable. Abbreviations: HT, Hypertension; HC, hypercholesterolemia; T2D, type 2 diabetes.

Figure 2

Hazard ratios (HRs) for incident peripheral artery disease (PAD) according to smoking status (A) and pack-years of smoking (B). HRs are adjusted for age, height, positive history of type 2 diabetes, hypertension and hypercholesterolemia, aspirin use, parental history of myocardial infarction at age 60 years or younger, geographical region, body mass index, physical activity and alcohol consumption. Data on pack-years of smoking was missing for 6.0% of person-years during follow-up.

Figure 3

Hazard ratios (HRs) for incident peripheral artery disease (PAD) according to duration of hypertension (A), hypercholesterolemia (B) and diabetes (C). HRs are adjusted for age, height, smoking status, history of diabetes, hypertension and hypercholesterolemia, aspirin use, parental history of myocardial infarction at age 60 years or younger, geographical region, body mass index, physical activity and alcohol consumption. Linear trends are based only on participants with the disease and are tested by using the median of each duration category as a continuous variable. Abbreviations: HT, Hypertension; HC, hypercholesterolemia; T2D, type 2 diabetes.