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Relation of Inflammation to Peripheral Arterial Disease in the National Health and Nutrition Examination Survey, 1999–2002

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The relation between inflammation and peripheral arterial disease (PAD) is not well characterized. This study examined this relation and its consistency across important subgroups in a cross-sectional, nationally representative sample of the adult United States population. C-reactive protein (CRP), fibrinogen, leukocyte count, and PAD were assessed in a sample of 4,787 participants aged ≥40 years in the National Health and Nutrition Examination Survey 1999–2002. PAD was defined as an ankle-brachial blood pressure index <0.9. Graded relations were present between inflammatory markers and PAD. The multivariate adjusted odds ratios of PAD associated with the highest versus the lowest quartile of CRP, fibrinogen, and leukocyte count were 2.14 (95% confidence interval [CI] 1.41 to 3.25), 2.49 (95% CI 1.27 to 4.85), and 1.67 (95% CI 0.84 to 3.31), respectively (each p trend <0.05 across quartiles). Associations between inflammation and PAD were similar across gender, obesity, and diabetic subgroups. However, the odds ratios of PAD for the highest CRP quartile versus the 3 lowest quartiles were 3.10 (95% CI 1.76 to 5.45) for non-Hispanic blacks versus 1.50 (95% CI 0.98 to 2.28) for non-Hispanic whites and 1.11 (95% CI 0.57 to 2.17) for Mexican Americans (p interaction = 0.049) and 5.59 (95% CI 1.82 to 17.17) for patients aged 40 to 54 years versus 2.01 (95% CI 1.13 to 3.58) for patients aged 55 to 69 years and 0.98 (95% CI 0.65 to 1.48) for patients aged ≥70 years (p interaction = 0.018). Odds ratios of PAD for the highest fibrinogen quartile versus the lowest 3 quartiles were 3.26 (95% CI 1.69 to 6.28) for current smokers versus 0.83 (95% CI 0.51 to 1.35) for never smokers (p interaction = 0.006). In conclusion, in the general United States adult population, inflammation is independently associated with PAD.

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Study participants

The National Health and Nutrition Examination Survey (NHANES) 1999–2002 was a nationally representative sample of the United States noninstitutionalized, civilian population. As described in detail on the Web site of the National Center for Health Statistics,1 NHANES 1999–2002 included the oversampling of non-Hispanic blacks and Mexican Americans to provide stable estimates for these groups. Ankle-brachial index (ABI) measurements were obtained on the subsample of patients aged ≥40 years.

ABI measurement and PAD definition

For

Results

The mean ABI was 1.10 (SE 0.003), and the prevalence of PAD (ABI <0.9) was 4.90% (SE 0.33). Patients in lower ABI categories were more likely to have a number of traditional cardiovascular disease risk factors (Table 1). Additionally, geometric mean CRP, fibrinogen, and leukocyte count were incrementally greater with each successively lower ABI category.

Graded, positive associations were present between quartiles of all 3 inflammatory markers and PAD prevalence (Figure 1). Associations remained

Discussion

These data provide evidence of strong, graded, positive associations between inflammation and PAD. Even after adjustment for traditional cardiovascular disease risk factors, patients in the highest quartile of CRP, fibrinogen, or leukocyte count had approximately 2 times greater odds of having PAD than those in the lowest quartile. Additionally, these data showed inflammation to maintain a stronger association with PAD in non-Hispanic blacks, current smokers, and middle-aged patients.

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    Drs. Wildman and Chen received partial support for the analysis and interpretation of these data from the National Institutes of Health, Bethesda, Maryland (Grant 1 K12 HD43451-01).

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