Relation of lower-extremity amputation to all-cause and cardiovascular disease mortality in American Indians: the Strong Heart Study

OBJECTIVE: To compare risk of all-cause and cardiovascular disease (CVD) mortality in people with a lower-extremity amputation (LEA) attributable to diabetes and people without an LEA. RESEARCH DESIGN AND METHODS: The Strong Heart Study is a study of CVD and its risk factors in 13 American-Indian communities. LEA was ascertained at baseline by direct examination of the legs and feet. Mortality surveillance is complete through 2000. RESULTS: Of 2,108 participants with diabetes at baseline, 134 participants (6.4%) had an LEA. Abnormal ankle-brachial index (53%), albuminuria (87%), and long diabetes duration (mean 19.8 years) were common among diabetic subjects with LEA. Mean diabetes duration among diabetic participants without LEA and in those with toe and below-the-knee amputations was 11.9, 18.6, and 21.1 years, respectively. During 8.7 (+/-2.9) years of follow-up, 102 of the participants with LEA (76%) died from all causes and 35 (26%) died from CVD. Of the 1,974 diabetic participants without LEA at baseline, 604 (31%) died from all causes and 206 (10%) died from CVD. The unadjusted hazard ratios (HRs) for all-cause and CVD mortality in diabetic participants with LEA compared with those without were 4.0 and 4.1, respectively. Adjusting for known and suspected confounders, LEA persisted as a predictor of all-cause (HR 2.2, 95% CI 1.7-2.9) and CVD mortality (HR 1.9, 95% CI 1.3-2.9). We observed a significant interaction between baseline LEA and sex on CVD mortality, with female sex conferring added risk of CVD mortality. CONCLUSIONS: LEA is a potent predictor of all-cause and CVD mortality in diabetic American Indians. The combination of female sex and LEA is associated with greater risk of CVD mortality than either factor alone.