Chronic kidney disease (CKD) is associated with increased risk for cardiovascular disease morbidity and mortality, but its association with incident venous thromboembolism (VTE) in non-dialysis-dependent patients has not been evaluated in a community-based population. With the use of data from the Longitudinal Investigation of Thromboembolism Etiology (LITE) study, 19,073 middle-aged and elderly adults were categorized on the basis of estimated GFR, and cystatin C (available in 4734 participants) was divided into quintiles. During a mean follow-up time of 11.8 yr, 413 participants developed VTE. Compared with participants with normal kidney function, relative risk for VTE was 1.28 (95% confidence interval [CI] 1.02 to 1.59) for those with mildly decreased kidney function and 2.09 (95% CI 1.47 to 2.96) for those with stage 3/4 CKD, when adjusted for age, gender, race, and center. After additional adjustment for cardiovascular disease risk factors, an increased risk for VTE was still observed in participants with stage 3/4 CKD, with a multivariable adjusted relative risk of 1.71 (95% CI 1.18 to 2.49). There was no significant association between cystatin C and VTE. In conclusion, middle-aged and elderly patients with CKD (stages 3 through 4) are at increased risk for incident VTE, suggesting that VTE prophylaxis may be particularly important in this population.

Chronic kidney disease (CKD) is associated with an increased risk for cardiovascular disease, but its association with peripheral arterial disease (PAD) is unclear. With the use of data from the Atherosclerosis Risk in Communities (ARIC) Study, 14,280 middle-aged adults were categorized on the basis of estimated GFR >90, 60 to 89, and 15 to 59 ml/min per 1.73 m 2 for normal kidney function, mildly decreased kidney function, and stages 3 to 4 CKD, respectively. Incident PAD was defined as a new onset of ankle-brachial index <0.9 assessed at regular examinations, new intermittent claudication assessed by annual surveillance, or PAD-related hospital discharges. Incidence rates and relative risks (RR) for PAD were compared across these categories. During a mean follow-up time of 13.1 yr (186,616 person-years), 1016 participants developed PAD. The incidence rates per 1000 person-years were 4.7, 4.9, and 8.6 for the normal kidney function, mildly decreased kidney function, and CKD groups, respectively. Compared with participants with normal kidney function, the age-, gender-, race-, and ARIC field center-adjusted RR for PAD was 1.04 (95% confidence interval [CI] 0.91 to 1.18) for those with mildly decreased kidney function and 1.82 (95% CI 1.34 to 2.47) for those with CKD. After additional adjustment for cardiovascular disease risk factors, an increase in risk for incident PAD still was observed in participants with CKD, with a multivariable adjusted RR of 1.56 (95% CI 1.13 to 2.14). Patients with CKD are at increased risk for incident PAD. Development of strategies for screening and prevention of PAD in this high-risk population seems warranted.

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OBJECTIVE -To assess the relation between HbA 1c (A1C) and incident peripheral arterial disease (PAD) in a community-based cohort of diabetic adults from the Atherosclerosis Risk in Communities (ARIC) study. A second aim was to investigate whether the association was stronger for severe, symptomatic disease compared with PAD assessed by low ankle-brachial index (ABI). RESEARCH DESIGN AND METHODS-This was a prospective cohort study of 1,894 individuals with diabetes using ARIC visit 2 as baseline (1990 -1992) with follow-up for incident PAD through 2002. We assessed the relation between A1C and incident PAD, defined by intermittent claudication, PAD-related hospitalization, or a low ABI (Ͻ0.9).RESULTS -During a mean follow-up of 9.8 years, the crude incidence rates were 2.1 per 1,000 person-years for intermittent claudication (n ϭ 41), 2.9 per 1,000 person-years for PAD-related hospitalization (n ϭ 57), and 18.9 per 1,000 person-years for low ABI at visit 3 or 4 (n ϭ 123). The relative risk (RR) (95% CI) of an incident PAD event comparing the second and third tertiles of A1C to the first, respectively, after adjustment for cardiovascular risk factors was strongest for severe, symptomatic forms of disease, e.g., PAD-related hospitalization (RR ϭ 4.56 [1.86 -11.18] for the third A1C tertile compared with the first, P trend Ͻ0.001) than for low ABI (RR ϭ 1.64 [0.94 -2.87], P trend ϭ 0.08).CONCLUSIONS -We found a positive, graded, and independent association between A1C and PAD risk in diabetic adults. This association was stronger for clinical (symptomatic) PAD, whose manifestations may be related to microvascular insufficiency, than for low ABI. Our results suggest that efforts to improve glycemic control in persons with diabetes may substantially reduce the risk of PAD. Diabetes Care 29:877-882, 2006P eripheral arterial disease (PAD) is more than twice as common among diabetic compared with nondiabetic individuals (1,2) and is a strong predictor of subsequent cardiovascular morbidity and mortality (3-5). Chronic hyperglycemia may contribute to the development of atherosclerosis and subsequent macrovascular events, including PAD, in persons with diabetes, but this relation is controversial. HbA 1c (A1C), a measure of long-term glycemic control, is used to monitor and guide clinical treatment in persons with diabetes. Chronic hyperglycemia, as measured by A1C, is an established risk factor for diabetes-associated microvascular disease (6,7). Recent studies have also suggested that A1C may be associated with incident large-vessel disease (coronary heart disease, stroke, and PAD) in persons with diabetes (8 -10).There have been few prospective studies that have examined the association between A1C and PAD in persons with diabetes (11-13). Three previous studies in the literature have shown a positive association between A1C and incident PAD. However, these studies did not consistently adjust for known cardiovascular disease risk factors, including smoking, lipids, and adiposity (8). There is currently no consensus re...

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