Diabetes and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of sudden and/or arrhythmic death (SAD) and other causes of death in patients with coronary artery disease (CAD) and left ventricular ejection fraction (LVEF) of more than 30% to 35%, according to study findings published in JACC: Clinical Electrophysiology.

The study was the multicenter, observational PRE-DETERMINE trial, which included 5764 patients with CAD or prior myocardial infarction and an LVEF of either  more than 35% or 30% to 35% with New York Heart Association (NYHA) functional class I heart failure symptoms. None of the patients in the study met criteria for implantable cardioverter-defibrillator (ICD) implantation for primary SAD prevention.

In this cohort, researchers compared the absolute and relative risks of SAD vs death from other causes (non-SAD) stratified by diabetes status and HbA1c levels. The researchers also sought to determine risk factors for SAD among patients with diabetes (n=1782; mean age, 65±10 years).


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Compared with people without diabetes (n=3762; mean age, 64±11 years), those with diabetes had a significantly higher median HbA1c level (5.6% vs 6.7%, respectively).

Over a median 6.8-year follow-up period, a total of 184 cases of SAD and 758 cases of non-SAD were recorded in the study. Most non-SADs were attributable to noncardiac causes (n=561) vs cardiac causes (n=142). The estimated 7-year cumulative incidence of SAD was 4.8% (95% CI, 3.8% to 5.9%) in patients with diabetes vs 2.8% (95% CI, 2.2% to 3.3%) in patients without diabetes.

The estimated 7-year cumulative incidence of non-SAD was 4-fold higher than SAD in patients with diabetes (19.2%; 95% CI, 17.3% to 21.2%) and patients without diabetes (11.5%; 95% CI, 10.5% to 12.6%). Fine-Gray models showed an association between diabetes and SAD (hazard ratio [HR], 1.50; 95% CI, 1.10-2.04; P =.010) as well as non-SAD (HR, 1.65; 95% CI, 1.41-1.93; P <.001).

For each 1% increment in HbA1c, there was associated HR of 1.12 (95% CI, 1.01-1.25; P =.038) for SAD and 1.24 (95% CI, 1.16-1.32; P ≤.001) for non-SAD. Diabetes and HbA1c were strongly associated with non-SAD cardiac death compared with SAD in a Fine-Gray analysis and competing risk Cox proportional hazards models (cause-specific HR for diabetes, 2.73 [95% CI, 1.92-3.87] vs 1.59 [95% CI, 1.17-2.17], respectively; P =.024; cause-specific HR for HbA1c: 1.39 [95% CI, 1.23-1.56] vs 1.15 [95% CI, 1.03-1.29], respectively; P =.026).

Fine-Gray analysis revealed 3 factors significantly associated with an increased risk of SAD in patients with diabetes: low LVEF (<50%), atrial fibrillation, and high electrocardiogram score (P ≤.05 for all comparisons).

The findings from this study may be limited in their generalizability, given the predominance of White participants (85.9% for diabetes and 90.8% for no diabetes) and men (73.1% for diabetes and 77.8% for no diabetes) in the study cohort.

The researchers wrote the “data underscore the need for better SAD risk stratification of patients with diabetes and CAD, ideally by identifying risk factors and/or biomarkers that can discriminate between SAD and non-SAD risk.”

The researchers wrote that the findings warrant additional research that can better identify patients with diabetes “who are specifically at higher risk for SAD” in an effort “to guide more tailored ICD recommendations and advance medical interventions.”

Disclosure: This research was supported by Roche Diagnostics. Please see the original reference for a full list of disclosures.

Reference

Venkateswaran RV, Moorthy MV, Chatterjee NA, et al. Diabetes and risk of sudden death in coronary artery disease patients without severe systolic dysfunction. JACC Clin Electrophysiol. Published online July 21, 2021. doi:10.1016/j.jacep.2021.05.014