Sudden cardiac death is the single largest cause of mortality in maintenance dialysis patients, accounting for over 25% of all deaths, said principal investigator Christiane Drechsler, MD, from the University of Würzburg in Germany. One risk factor for this could be poor glycemic control, which we know in the general population leads to the onset of cardiovascular comorbidities.

She explained that poor glycemic control can affect the development of comorbidities, electrolyte balance, the function of potassium and calcium channels, and sympathetic activity, all of which are relevant to arrhythmogenesis.

The 4D study aimed to determine the risk for sudden cardiac death and all-cause mortality on the basis of HbA1c levels.

Data were analyzed from 1255 hemodialysis patients with type 2 diabetes who were participants in the 4D study. Mean baseline HbA1c for the population was 6.7% ± 1.3%. Patients were divided into the following categories: normal HbA1c levels (<6%); elevated HbA1c levels (= 6% and < 8%); and high HbA1c levels (=8%).

During follow-up, at 4 years, a total of 617 patients died, 160 from sudden cardiac death and 200 from myocardial infarction.

Baseline HbA1c, as a continuous variable, was found to be significantly associated with the occurrence of sudden death, with a hazard ratio (HR), after adjustment for confounders, of 1.20 (95% confidence interval [CI], 1.06 – 1.37; P < .01). HbA1c levels were not, however, linked to the occurrence of myocardial infarction (HR, 0.95; 95% CI, 0.84 – 1.06; P = .43), Dr. Drechsler reported.

In categorical analyses, patients with elevated HbA1c levels (between 6% and 8%) were 83% more likely to die of sudden death (HRadj, 1.83; 95% CI, 1.21 – 2.78), and patients with high HbA1c levels (=8%) had a greater than 2-fold risk for sudden death, compared with those with normal HbA1c levels (<6%) (HRadj, 2.25; 95% CI, 1.32 -3.81).

The incidence of sudden death per 100 patient-years was 3.0 for patients with normal HbA1c levels, 5.0 for those with elevated HbA1c levels, and 6.3 for those with high HbA1c levels.

Furthermore, the risk for all-cause mortality significantly increased by 9% for every 1% increase in HbA1c levels (P = .02), Dr. Drechsler added.

It was noted that the ACCORD study found no benefit of intensive glycemic control in the prevention of cardiovascular events. Whether interventions achieving tight glycemic control in these patients will decrease sudden death is an issue that needs to be evaluated in future studies, Dr. Drechsler remarked.

Charles Herzog, MD, director of the Cardiovascular Special Studies Center of the US Renal Data System, and professor of medicine at the University of Minnesota in Minneapolis reported that factors affecting sudden death in dialysis patients are likely to be multifactorial, and glycemic control may be one of them. He was not involved in the study. He said other possible factors include ischemic heart disease, abnormalities in myocardial structure and function, left ventricular hypertrophy, and electrolyte shifts. Serum potassium, in particular, could be a factor, and the 4D investigators plan to analyze these patterns.

One of the main lessons of 4D is that some factors are treatable and some are not. There may be a point when things that could be treatable early on cross the tipping point and become untreatable, told Dr. Herzog. There is evidence from this and other studies that the main mechanism of sudden death in dialysis patients is not coronary heart disease, which has a different meaning in dialysis patients. Interventions that work in the general population, such as statins, do not work as well in dialysis.