New Risk Factors Identified for Sudden Cardiac Death in Type 2 Diabetes

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Biomarkers, baseline HbA1c, and amputation predicted sudden cardiac death.
Biomarkers, baseline HbA1c, and amputation predicted sudden cardiac death.

New insights from the SAVOR-TIMI 53 Trial indicate that unexpected sudden cardiac death is a common cause of death in patients with type 2 diabetes, representing slightly less than one-third of all deaths. Additionally, researchers found that specific biomarkers may help identify patients with diabetes who are at high risk for sudden cardiac death.

Study results were presented at the American College of Cardiology's (ACC) 65th Scientific Sessions.

“Sudden cardiac death represents a public health burden responsible for approximately 4 000 000 deaths every year in the world,” said lead study author Ilaria Cavallari, MD, a postdoctoral research fellow and member of the TIMI Study Group at Brigham and Women's Hospital in Boston.

“Different epidemiological studies have shown that type 2 diabetes is associated with a 2-to-3-fold increased risk for sudden cardiac death. The most recent estimates suggest of 400 000 sudden cardiac deaths each year in the United States, approximately 80 000 involve diabetic patients. All together, these numbers are expected to increase according to the increasing prevalence of diabetes worldwide and strengthen the importance of early detection of additional modifiable risk factors.”

Until now the actual risk factors for sudden cardiac death in patients with type 2 diabetes have not been well described, noted Dr Cavallari.

She and colleagues mined data from SAVOR-TIMI 53, a randomized trial of patients with type 2 diabetes and established cardiovascular disease (CVD) or multiple risk factors. In this trial, deaths were adjudicated by a blinded events committee.

The researchers analyzed the association between baseline features and cause of death using a competing-risk analysis (cause-specific hazard models). Sudden cardiac death was defined as a death that occurred unexpectedly in a previously stable patient.

Of 16 492 randomized patients, 798 died during a median follow-up of 2.1 years. Of these, 30.1% (n=240) were sudden cardiac deaths, 36.2% (n=289) were other CV deaths, and 33.7% (n=269) were non-CV deaths.

Dr Cavallari reported that 2-year cumulative incidence rates were 1.41% for sudden cardiac death, 1.64% for other CV death, and 1.46% for non-CV deaths.

Data showed that patients with sudden cardiac death, as compared with those who did not die, were more likely to be older, have longer duration of type 2 diabetes, higher baseline HbA1c, and be on insulin (P<.05 for all). Furthermore, rates of macrovascular and microvascular complications were higher in those with sudden cardiac death.

The investigators also found that prior heart failure, albuminuria, estimated glomerular filtration rate (eGFR) ≤ 50 mL/min, peripheral artery disease, and age were the strongest correlates of sudden cardiac death when biomarkers were not included in the models. Nevertheless, biomarkers N-terminal of prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) were found to be strong and independent correlates of all causes of death, including sudden cardiac death.

“After multivariable adjustment, the significant independent correlates of sudden cardiac death were prior heart failure, albuminuria, eGFR ≤ 50 mL/min, peripheral artery disease, age, HbA1c, coronary artery disease and prior myocardial infarction, male sex, and heart rate. Sudden cardiac death and other causes of CV death shared similar predictors except for male sex that was found to be associated to sudden cardiac death and not to other CV deaths,” Dr Cavallari told Endocrinology Advisor.

“When biomarkers NT-proBNP, hsTnT, and C-reactive protein (CRP) were tested in the models, they were found to be strong predictors of all causes of death, including sudden cardiac death.”

The study demonstrated that a majority of sudden cardiac deaths occurred out of hospital (81.2%) and medical resuscitation was attempted in 28.7% of the patients.

The study was limited by the fact that for most of the deaths, detailed information was missing. However, new or worsening symptoms within 24 hours were reported in 28.3% of patients, and the most common worsening symptoms were chest pain followed by dyspnea and nausea or vomiting.

“When treating patients with diabetes, endocrinologists should take into account the results of this analysis for mortality risk stratification. Biomarkers, especially NT-proBNP and hsTnT, could be useful tools to identify diabetic patients at high risk for death,” said Dr Cavallari. “These high-risk patients might derive benefit from close monitoring and aggressive treatment of modifiable risk factors.”


  1. Cavallari I, Patel R, Bhatt D, et al. Clinical Factors Associated With Sudden Cardiac Death in Type 2 Diabetes: Insights From the SAVOR-TIMI 53 Trial. Presented at: ACC 65th Scientific Sessions; April 2-4, 2016; Chicago, IL.
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