OBJECTIVES: To investigate whether novel risk factors, including C-reactive protein (CRP), fibrinogen, lipoprotein(a) [Lp(a)], and homocysteine levels, are associated with the ankle brachial index (ABI) in African American and non-Hispanic white populations and whether novel risk factors account for ethnic differences in peripheral arterial disease (PAD). PARTICIPANTS AND METHODS: Between December 2000 and October 2004, original participants in the Genetic Epidemiology Network of Artericpathy study returned for a second study visit to undergo measurement of risk factors and ABI. The CRP, Lp(a), and homocysteine levels were log transformed to reduce skewnees. Multivariable regression analyses were used to assess whether a novel risk factor was associated with ABI after adjustment for conventional risk factors and whether ethnicity was associated with PAD (ABI, ≤0.95) after adjustment for conventional and novel risk factors. RESULTS: Of 2229 study participants, the ABI was determined in 1395 African American participants (mean ± SD age, 63±9 years; 71% women) and 834 white participants (mean ± SD age, 58±9 years; 62% women) whc belonged to hypertensive sibships. The mean ABI was lower in African American than in white individuals (0.99±0.1 vs 1.13±0.1; P<.001). In both ethnic groups, higher levels of CRP, fibrinogen, and homocysteine were each associated with a lower ABI after adjustment for conventional risk factors. In African American participants, the Lp(a) level was also significantly associated with the ABI. African American ethnicity was associated with the presence of PAD after adjustment for conventional risk factors (men: odds ratio [OR], 3.04; 95% confidence interval [CI], 1.80-5.15; woman: OR, 2.82; 95% CI, 1.85-4.29), but the risk was significantly attenuated after additional adjustment for novel risk factors (men: OR, 2.11; 95% CI, 1.21-3.70; women: OR, 1.98; 96% CI, 1.26-3.11). CONCLUSION: Novel risk factors are associated with interindividual variation in ABI in African American and non-Hispanic white populations and partly account for the increased risk of PAD associated with African American ethnicity.
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