Hemoglobin A1c levels andriskofsuddencardiac death: A nested case-control study

BACKGROUND Sudden cardiac death(SCD) is often the first manifestation ofcardiovascular 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. OBJECTIVE The purpose of this study was to examine the association between hemoglobin A(1c) (HbA1c) and SCD. METHODS We performed a case-control analysis among individuals enrolled in 6 prospective cohor tstudies. HbA(1c) levels were determined for 482 cases of SCD and 91 matched controls. Conditiona logistic regression with fixed effects meta-analysis was used for analysis. RESULTS In multivariable models, HbA(1c) levels were linearly associated with SCD risk over follow-up of 11.3years (P <. 001). Each 1% increment in HbA(1c) was associated with a hazard ratio (HR) of 1.32 (95% confidence interval [CI] 1.16-1.50). Th emagnitude of the association was greater in subjects without vs those with known CVD [HRper1% 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 fordiabetes status and HbA(1c), the association between HbA(1c) and SCD remained significant (HR1.29,95% CI1.07-1.55, P = .01), where as the association between diabetes and SCD was attenuated (relative risk 1.21,95% CI 0.64-2.27, P = .56). CONCLUSION In these prospective cohorts, HbA(1c) 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.