Association Between HbA1c Levels and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Cardiovascular Disease: A Secondary Analysis of the TECOS Randomized Clinical Trial

AIMS Whether glycemic control is associated with cardiovascular outcomes in patients with type 2 diabetes (T2D) is unclear. Consequently, we assessed the relationship between glycated hemoglobin (HbA1c ) and cardiovascular outcomes in a placebo-controlled randomized trial which demonstrated no cardiovascular effect of sitagliptin in patients with T2D and atherosclerotic vascular disease. METHODS AND RESULTS Secondary analysis of 14,656 TECOS participants with time to event analyses using multivariable Cox proportional hazard models. During a median 3.0 (IQR 2.3-3.8) year follow-up, 456 (3.1% of 14,656) patients had first hospitalization for heart failure (HF), 1084 (11.5%) died, 1406 (9.6%) died or were hospitalized for HF, and 1689 (11.5%) had a non-HF cardiovascular event (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, or hospitalization for unstable angina). Associations between baseline or time-varying HbA1c and cardiovascular outcomes were U-shaped, with the lowest risk when HbA1c was around 7%. Each one-unit increase in the time-varying HbA1c above 7% was associated with an adjusted HR of 1.21 (95%CI 1.11-1.33) for first HF hospitalization, 1.11 (1.03-1.21) for all-cause death, 1.18 (1.09-1.26) for death or HF hospitalization, and 1.10 (1.02-1.17) for non-HF cardiovascular events. Each one-unit decrease in the time-varying HbA1c below 7% was associated with an adjusted HR of 1.35 (95% CI 1.12-1.64) for first HF hospitalization, 1.37 (1.16-1.61) for death, 1.42 (1.23- 1.64) for death or HF hospitalization, and 1.22 (95% CI 1.06-1.41) for non-HF cardiovascular events. CONCLUSION HbA1c exhibits a U-shaped association with cardiovascular outcomes in patients with T2D and atherosclerotic vascular disease, with nadir around 7%. This article is protected by copyright. All rights reserved.