HbA1c level may predict cardiovascular events in high-risk patients with diabetes

Glycemic control as measured by HbA1c level remains strongly and independently associated with cardiovascular outcomes in high-risk patients with diabetes on statin therapy.


HbA1c levels are an independent predictor for future cardiovascular events in optimally treated patients with diabetes mellitus, a recent study found.

Researchers used data from the ACCELERATE (Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes) trial to determine whether HbA1c was an accurate marker of risk for a composite end point of cardiovascular death, nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and coronary revascularization in patients with diabetes and established coronary artery disease who were receiving optimal treatment. Results of the study, which was funded by Eli Lilly, were published Dec. 19, 2019, by the Journal of the American Heart Association.

All of the 8,145 included patients had diabetes and a measurement of HbA1c at baseline. Statistically significant trends were seen for age, sex, body mass index, current smoking, peripheral artery disease, and congestive heart failure with increasing levels of baseline HbA1c. Patients with increasing baseline HbA1c levels were also significantly more likely to be receiving treatment with a high-intensity statin and antiglycemic medications, especially sulfonylureas and insulin.

A strong association was seen between increasing baseline HbA1c level and the primary end point (Kaplan-Meier estimate, 12.6 to 18.2; P<0.001). Increasing baseline HbA1c level was also associated with a combined end point of death, nonfatal myocardial infarction, and stroke (Kaplan-Meier estimate, 7.8 to 11.3; P=0.003), as well as the individual end points of nonfatal myocardial infarction (Kaplan-Meier estimate, 3.1 to 7.0; P<0.001), hospitalization for unstable angina (Kaplan-Meier estimate, 1.8 to 5.0; P=0.003), and revascularization (Kaplan-Meier estimate, 7.3 to 11.1; P=0.001).

No association was seen between baseline HbA1c level and stroke (Kaplan-Meier estimate, 1.4 to 2.4; P=0.45), and rates of cardiovascular mortality (Kaplan-Meier estimate, 2.6 to 4.3; P=0.21) and all-cause mortality (Kaplan-Meier estimate, 4.8 to 5.9; P=0.21) were similar regardless of baseline HbA1c levels. After the researchers adjusted for relevant baseline characteristics, baseline HbA1c level was found to be an independent predictor of the primary end point (hazard ratio, 1.06; 95% CI, 1.02 to 1.11; P=0.003).

The researchers noted that their analysis could have been affected by confounding and that no data were available on such factors as diabetes duration and change in glycemic control over time, among other limitations. However, they concluded that in this population of patients with diabetes and established coronary artery disease who were receiving optimal medical therapy, HbA1c level was an independent predictor of major adverse cardiac events.

“The practical lessons arising from our observations are self-evident,” the authors wrote. “HbA1c levels remain strongly predictive of future cardiovascular events in patients with [diabetes mellitus], despite optimal lipid, blood pressure, and preventive strategies and despite recent outcomes data that may shift the focus away from glycemic control. Awareness of the HbA1c levels will enable clinicians to recognize residual risk and initiate or substitute proven medications that improve downstream cardiovascular outcomes in this vulnerable population.”