Hemoglobin A1c levels and risk of sudden cardiac death: A nested case-control study
Ravi B Patel1, M V Moorthy2, Stephanie E Chiuve3
1Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Insights
Higher hemoglobin A1c (HbA1c) levels are linked to increased risk of sudden cardiac death (SCD), especially in individuals without known cardiovascular disease. These findings suggest hyperglycemia contributes to SCD risk in diabetic patients.
Area of Science:
- Cardiology
- Endocrinology
- Epidemiology
Background:
- Sudden cardiac death (SCD) is a primary manifestation of cardiovascular disease (CVD), lacking effective preventive strategies.
- Diabetic patients are a high-risk group for SCD, but the role of glycemic control in risk stratification is unclear.
Purpose of the Study:
- To investigate the association between hemoglobin A1c (HbA1c) levels and the risk of SCD.
Main Methods:
- A case-control analysis was conducted using data from 6 prospective cohort studies.
- HbA1c levels were measured in 482 SCD cases and 914 matched controls.
- Conditional logistic regression and fixed-effects meta-analysis were employed.
Main Results:
- HbA1c levels showed a linear association with SCD risk over an 11.3-year follow-up (P <.001).
- Each 1% increase in HbA1c correlated with a 32% increased hazard ratio (HR) for SCD (HR 1.32; 95% CI 1.16-1.50).
- The association was more pronounced in individuals without known CVD compared to those with known CVD (P interaction = .009).
- Even after controlling for diabetes status, HbA1c remained a significant predictor of SCD (HR 1.29; 95% CI 1.07-1.55), while diabetes status alone showed attenuated association.
Conclusions:
- Elevated HbA1c levels are independently associated with increased SCD risk, particularly in individuals without diagnosed CVD.
- These findings support the role of hyperglycemia in mediating SCD risk among patients with diabetes.
Background:
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.
Objective:
The purpose of this study was to examine the association between hemoglobin A1c (HbA1c) and SCD.
Methods:
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.
Results:
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).
Conclusion:
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.
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Published on: June 10, 2025
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