Background-The associations of low (Ͻ0.90) and high (Ͼ1.40) ankle brachial index (ABI) with risk of all-cause and cardiovascular disease (CVD) mortality have not been examined in a population-based setting. Methods and Results-We examined all-cause and CVD mortality in relation to low and high ABI in 4393 American Indians in the Strong Heart Study. Participants had bilateral ABI measurements at baseline and were followed up for 8.3Ϯ2.2 years (36 589 person-years). Cox regression was used to quantify mortality rates among participants with high and low ABI relative to those with normal ABI (0.90 ՅABI Յ1.40). Death from all causes occurred in 1022 participants (23.3%; 27.9 deaths per 1000 person-years), and of these, 272 (26.6%; 7.4 deaths per 1000 person-years) were attributable to CVD. Low ABI was present in 216 participants (4.9%), and high ABI occurred in 404 (9.2%). Diabetes, albuminuria, and hypertension occurred with greater frequency among persons with low (60.2%, 44.4%, and 50.1%) and high (67.8%, 49.9%, and 45.1%) ABI compared with those with normal ABI (44.4%, 26.9%, and 36.5%), respectively (PϽ0.0001). Adjusted risk estimates for all-cause mortality were 1.69 (1.34 to 2.14) for low and 1.77 (1.48 to 2.13) for high ABI, and estimates for CVD mortality were 2.52 (1.74 to 3.64) for low and 2.09 (1.49 to 2.94) for high ABI. Conclusions-The association between high ABI and mortality was similar to that of low ABI and mortality, highlighting a U-shaped association between this noninvasive measure of peripheral arterial disease and mortality risk. Our data suggest that the upper limit of normal ABI should not exceed 1.40.

OBJECTIVE -Insulin resistance (IR) and the metabolic syndrome (MS) are associated with type 2 diabetes and adverse cardiovascular disease (CVD) risk factor profiles. Whether IR and MS predict CVD independently of diabetes and other CVD risk factors is not known. This study examines whether IR and/or presence of MS are independently associated with CVD in nondiabetic American Indians (AI).RESEARCH DESIGN AND METHODS -We examined 2,283 nondiabetic AI who were free of CVD at the baseline examination of the Strong Heart Study (SHS). CVD risk factors were measured, IR was quantified using the homeostasis model assessment (HOMA), and MS as defined by the National Cholesterol Education Program Adult Treatment Panel (ATP III) was assessed for each participant. Incident CVD and diabetes were ascertained during follow-up. RESULTS -MS was present in 798 individuals (35%), and 181 participants (7.9%) developed CVD over 7.6 Ϯ 1.8 years of follow-up. Age, BMI, waist circumference, and triglyceride levels increased and HDL cholesterol decreased across tertiles of HOMA-IR. Risk of diabetes increased as a function of baseline HOMA-IR (6.3, 14.6, and 30.1%; P Ͻ 0.001) and MS (12.8 vs. 24.5%). In Cox models adjusted for CVD risk factors, risk of CVD did not increase either as a function of baseline HOMA-IR or MS, but individual CVD risk factors predicted subsequent CVD.CONCLUSIONS -Among nondiabetic AI in the SHS, HOMA-IR and MS both predict diabetes, but neither predicts CVD independently of other established CVD risk factors.

OBJECTIVE -To determine whether non-HDL cholesterol, a measure of total cholesterol minus HDL cholesterol, is a predictor of CVD in patients with diabetes. RESEARCH DESIGN AND METHODS -The Strong HeartStudy, a population-based study of CVD and its risk factors in 13 American Indian communities in three geographic areas in the U.S. The baseline examination, conducted between July 1989 and January 1992, consisted of a personal interview, a physical examination, and laboratory tests. Of the 4,549 women and men aged 45Ϫ74 years participating in the study, 2,108 had diabetes but no CVD at baseline. Data on fatal and nonfatal CVD were collected during the follow-up period through 31 December 1998 (average 9 years).RESULTS -Multivariable analyses indicated that non-HDL cholesterol is a strong predictor of CVD in men and women with diabetes and is particularly indicative of coronary events. Hazard ratios for the highest tertile of non-HDL cholesterol in men and women with diabetes (2.23 and 1.80, respectively) were higher than those for either LDL cholesterol or triglycerides alone in both men and women and were higher than the ratio of total/HDL cholesterol in women. The utility of non-HDL cholesterol in predicting CVD extended over a wide range of triglyceride concentrations.CONCLUSIONS -This study suggests that non-HDL cholesterol index may be particularly useful in predicting CVD risk in patients with diabetes. Diabetes Care 26:16 -23, 2003C ardiovascular disease (CVD) is currently the primary cause of morbidity and mortality in patients with diabetes (1-4). Because individuals with diabetes have greatly increased CVD risk compared with nondiabetic individuals (5-9), it is important to identify factors that may increase CVD risk in diabetic patients.In type 2 diabetes, there is a characteristic dyslipidemia consisting of elevated triglycerides, decreased HDL cholesterol, and LDL particles of altered composition (10 -12). Previous studies (5-9,13-15) indicate that, in addition to LDL cholesterol level, this dyslipidemia is an important CVD risk factor in individuals with diabetes. Although the CVD risk associated with individual lipoproteins has been examined, it would be valuable to have a measure that reflects the combined risk of all lipoprotein changes observed in diabetes. Some investigators (16 -18) have recently suggested that a measure of non-HDL cholesterol, which reflects total cholesterol minus HDL cholesterol (i.e., all apolipoprotein Bcontaining atherogenic lipoproteins), might be a useful marker of this combined risk. A recent study conducted in a cohort containing both diabetic and nondiabetic individuals showed that non-HDL cholesterol was a somewhat better predictor of CVD than LDL cholesterol (19). Furthermore, the Adult Treatment Panel (ATP-III) of the National Cholesterol Education Program has recommended using non-HDL cholesterol in assessing CVD risk in patients with diabetes (20). However, there have been no populationbased studies evaluating the utility of non-HDL cholesterol as a predictor of...