Glycemia (hemoglobin A1c) and incident venous thromboembolism in the Atherosclerosis Risk in Communities cohort study

Diabetes has been inconsistently associated with increased risk of venous thromboembolism (VTE) and there is little direct evidence on the associations of glycemia levels with VTE. We used data from the Atherosclerosis Risk in Communities study to test the hypothesis that glycemia, as measured by hemoglobin A1c (A1c), is positively associated with VTE. Participants aged 45-64 years (n = 12,298) had A1c measured in 1990 and were followed for incident VTE (n = 345) through 2005. Because A1c is affected by diabetes treatment, analyses were stratified by history of diagnosed diabetes. Owing to evidence of non-linearity, we categorized A1c according to clinical cut-points: <5.7, 5.7-6.4, and ≥6.5% in those with no diagnosed diabetes; <7.0 and ≥7.0% in those with diagnosed diabetes. After adjustment for potential confounders, the hazard ratios (95% CIs) for VTE across increasing A1c categories were 1 (referent), 1.02 (0.77, 1.35) and 0.72 (0.41, 1.29) for those without diagnosed diabetes, and 1.30 (0.77, 2.17) and 1.41 (0.95, 2.09) for those with diagnosed diabetes. To explore the relation, we employed various models to adjust for potential confounding variables and modeled A1c as tertiles. We consistently found elevated hazard ratios in those with diagnosed diabetes, though the association was not statistically significant in every model. Hazard ratios in those without diagnosed diabetes were close to 1. In conclusion, our results are mildly suggestive that diagnosed diabetes and high levels of glucose, per se, may increase the risk of VTE. Elevated glucose was not related to VTE in those without diagnosed diabetes.