Statistically significant linear associations were found between increasing ABI and gender, race, age, height, smoking status, hypertension, diabetes, HDL- and LDL-cholesterol, and intermittent claudication (Table ). With increasing ABI, the mean age and LDL-cholesterol, proportions of African Americans and current smokers, and proportions with hypertension, diabetes, and intermittent claudication tended to decrease. HDL-cholesterol and also mean carotid IMT were lower in those with ABI ≤ 0.90. The proportion of men and mean height were higher in those with ABI ≤ 0.80 and also at ABI levels > 1.20.
Baseline characteristics of participants without prevalent coronary heart disease by ABI category, the ARIC study, 1987–1989*
A total of 686 of the 10028 white participants and 278 of the 3560 African American participants experienced an incident CHD event. In both men and women and in whites and African Americans, CHD incidence was higher for those with ABI-defined PAD than for those without PAD (Table ), as has been previously reported for ARIC data [26
]. White men with PAD, defined as an ABI < 0.90, had an incidence of 21.8 per 1000 person-years, while those without PAD had an incidence of 8.0 per 1000 person-years. Use of multiple ABI categories revealed an increase in CHD incidence with decreasing ABI, from 5.7 per 1000 person-years among white men with an ABI 1.20–1.30 to 24.2 per 1000 person-years for those with an ABI ≤ 0.80. White women with PAD also had a higher CHD incidence (6.9 per 1000 person-years) than those without (3.4 per 1000 person-years). Multiple ABI categories in white women suggested little if any increase in CHD incidence with ABI decreasing from the category 1.20–1.30 (2.3 per 1000 person-years) to 0.80–0.90 (2.9 per1000 person-years), with a notable increase in CHD incidence with an ABI ≤ 0.80 (27.1 1000 person-years). CHD incidence at ABI levels > 1.30 was similar to that estimated for the ABI category 1.20–1.30.
Sample size, number of incident CHD events, and age- and field-center adjusted incidence rates (per 1,000 person-years) by gender, race, and ABI level: the ARIC study, 1987–2001*
A separate model for African Americans estimated generally higher CHD incidence rates than for whites and similar patterns of increasing CHD risk with decreasing ABI. African American men with PAD, defined as an ABI < 0.90, had a much higher CHD incidence (40.7 per 1000 person-years) than those without PAD (8.9 per 1000 person-years). African American women with PAD had a CHD incidence of 11.4 per1000 person-years, and those without PAD had an incidence of 5.0 per 1000 person-years.
To explore whether gender differences existed in the association of PAD with incident CHD, race-specific hazard ratios (HRs) adjusted for age and field center were estimated from Cox regression models (Table ). In whites, those with PAD (ABI < 0.90) had twice the hazard of a CHD event than those without, with a HR of 2.81 for men and 2.05 for women; there was no statistically significant effect modification by gender (P = 0.39). In African Americans, the HR was higher for men (4.86) than for women (2.34), with marginally statistically significant effect modification by gender (P = 0.09). As expected, lowering the ABI cutpoint to define PAD to 0.85 for women increased the estimated HR to 3.31 in white women and 2.76 in black women; the statistical significance of the gender difference in HR decreased in both whites (P = 0.69) and blacks (P = 0.22).
Age- and field-center-adjusted CHD incidence hazard ratios for various ABI categories from Cox models for white and African American participants: the ARIC study, 1987–2001*
In both whites and African Americans, modeling the ABI as ordered categories (Table ) demonstrated a generally increasing CHD hazard with decreasing ABI category. Effect modification of the association of ABI category with incident CHD by gender was statistically significant in whites (P = 0.05 whites, P = 0.19 blacks), suggesting a gender difference in the shape of the ABI-CHD risk relationship across the spectrum of ABI up to 1.30.
Modeling these associations in whites and blacks (Figure ) as smooth curves using restricted cubic spline functions of the ABI demonstrate generally monotonic increases in CHD risk with decreasing ABI. Wide confidence intervals at ABI values < 0.8 (data not shown) reflect the degree of uncertainty regarding these functions at ABI values of clinical interest. Men and women did not differ significantly regarding the association of ABI, as a continuous spline function, with incident CHD in either whites (P = 0.22) or African Americans (P = 0.92). Models without the gender-by-ABI interaction showed that the departure from linearity (on the natural log scale) was not statistically significant in either whites (P = 0.12) or blacks (P = 0.92). However, in separate models by sex and race, white women did demonstrate a statistically significant non-log-linear relationship (P = 0.04). The figure suggests that the risk of CHD may fail to decline above ABI values of about 1.2 in this population of white women. Modeled as a continuous, linear effect, a 0.10 lower ABI increased the CHD hazard by 25% in white men, by 20% in white women, by 34% in African American men, and by 32% in African American women (Table ). Adjustment for traditional cardiovascular disease risk factors, excluding hypertension, decreased these hazard ratios by 5 to 9% across race-sex subgroups. The addition of hypertension among the risk factors additionally reduced the estimated HRs by 2% or less. Race-specific estimates of the HRs for a 0.1-unit increase in the ABI, modeled as a linear term, were increased by about 8% in whites and 14% in blacks after adjustment for ABI measurement error in models without covariate adjustment (Table ). Adjustment for measurement error increased HRs by approximately the same magnitude in models including age and field center as covariates, but had slightly less effect in models additionally including cardiovascular risk factors.
Figure 1 Hazard rate ratio (HRR) relative to an ankle-brachial index of 1.0 for incident coronary heart disease (CHD) by gender for white and African American ARIC participants, 1987–2001. White men (A), white women (B), African American men (C), African (more ...)
CHD hazard ratios estimated from Cox regression for a decrement of 0.10 in ABI modelled as a linear, continuous term: uncorrected and corrected for ABI reliability