A1c Targets for Patients with Diabetes and Heart Disease

Relationship of A1c and mortality in heart failure patients with diabetes.

This study done by D. Aguilar, B. Bozkurt, K. Ramasubbu and A. Deswal examined an observational retrospective cohort of 5,815 patients with diabetes and heart failure, with electronic data from Veterans Affairs medical centers. Individuals were classified into quintiles of glycated hemoglobin (A1c) levels (measured within 1 year before or 2 weeks after the index visit), and followed for 2 years for the primary outcomes of time to death and time to hospitalization for heart failure. The investigators assessed the relationship between outcomes and quintiles of A1c after adjusting for up to 29 potential confounding variables with Cox proportional-hazards regressions. Variables included demographics; comorbidities, such as prior myocardial infarction, atrial fibrillation, and chronic obstructive pulmonary disease; clinical measures, such as body mass index, left ventricular ejection fraction, blood pressure, glomerular filtration rate, and cholesterol; and pharmacotherapies, including specific antihyperglycemic agents, angiotensin-converting enzyme inhibitors, beta-blockers, and statins.

The cohort was 94% men with a mean age of 69 years and a mean body mass index of 31.7 kg/m². Mean A1c was 7.75%, and the levels of A1c in each quintile were ≤ 6.4%, 6.4%-7.1%, 7.1%-7.8%, 7.8%-9.0%, and > 9%. As the A1c quintiles increased, there was a greater prevalence of diabetic complications; individuals were more likely to require a greater number of medications for glycemic control; and they were more likely to be receiving insulin therapy.

Compared with quintile 3, the other 4 quintiles had a significantly higher risk for death over 2 years, ranging from a risk-adjusted hazard ratio of 1.37 (95% confidence interval, 1.14-1.64) for quintile 1, to 1.31 (1.09-1.58) for quintiles 2 and 4, to 1.45 (1.20-1.76) for quintile 5. The risk of heart failure hospitalization increased with larger quintiles, but was not statistically significant after adjustment for potential confounders.

Until recently, the American Diabetes Association (ADA) has encouraged clinicians to attempt to achieve glycemic control that is as near to normal as possible to prevent complications. Even after the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial surprisingly reported that the intensive glycemic control group experienced a significant increase in mortality compared with the standard control group, the ADA maintained that “the general goal of [A1C] < 7% appears reasonable."

However, the current study raises the prospect that < 7% may be too low for patients with comorbid heart failure. Unfortunately, observational data can only demonstrate associations that require more rigorous studies to determine causality.

The current study differed from ACCORD in that it used a single baseline A1c level to predict mortality up to 2 years later, thus neither accounting for glycemic control at the time of death nor the glycemic burden that may have accumulated during follow-up. This is not trivial because the direction of the association between A1c and incident heart failure in patients with diabetes may differ depending on whether a single measure or a mean of many measures is used.

Furthermore, despite ACCORD and the results reported above, there are still good reasons to continue to optimize glycemic control in most patients, such as proven reductions in microvascular complications. Nevertheless, these findings suggest that glycemic targets should be carefully tailored to the individual patient. Minimizing complications in older and sicker individuals, such as those with heart failure, may be of less importance.

J Am Coll Cardiol.  2009; 54(5):422-8 (ISSN: 1558-3597