Hemoglobin A1c levels and risk of sudden cardiac death: A nested case-control study

Abstract

Sudden cardiac death (SCD) is often the first manifestation of cardiovascular disease (CVD), and preventive strategies within this broad population are lacking. Patients with diabetes represent a high-risk subgroup, but few data exist regarding whether measures of glycemia mediate risk and/or add to SCD risk stratification. The purpose of this study was to examine the association between hemoglobin A1c (HbA1c) and SCD. We performed a case-control analysis among individuals enrolled in 6 prospective cohort studies. HbA1c levels were determined for 482 cases of SCD and 914 matched controls. Conditional logistic regression with fixed effects meta-analysis was used for analysis. In multivariable models, HbA1c levels were linearly associated with SCD risk over follow-up of 11.3 years (P <.001). Each 1% increment in HbA1c was associated with a hazard ratio (HR) of 1.32 (95% confidence interval [CI] 1.16-1.50). The magnitude of the association was greater in subjects without vs those with known CVD [HR per 1% increment 1.64 (95% CI 1.31-2.06) vs 1.15 (95% CI 0.99-1.33), P interaction = .009]. In models simultaneously controlling for diabetes status and HbA1c, the association between HbA1c and SCD remained significant (HR 1.29, 95% CI 1.07-1.55, P = .01), whereas the association between diabetes and SCD was attenuated (relative risk 1.21, 95% CI 0.64-2.27, P = .56). In these prospective cohorts, HbA1c levels associated with SCD risk, particularly among those without known CVD, even after controlling for diabetes status. These data support the hypothesis that hyperglycemia mediates SCD risk among patients with diabetes.