In patients with diabetes and high cardiovascular risk, hemoglobin A1c (HbA1c) is strongly associated with cardiovascular outcomes, according to study results published in the Journal of the American Heart Association.

While diabetes is associated with a significantly increased risk for cardiovascular morbidity and mortality, several trials have suggested that strict glucose control may not improve the risk for macrovascular complications. HbA1c is used for the diagnosis of diabetes and monitoring response to treatment, but its utility as a marker of risk in optimally treated patients at high cardiovascular risk is unknown.

In the current subanalysis of data from the Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High Risk for Vascular Outcomes (ACCELERATE) trial, the researchers assessed the relationship between baseline HbA1c and cardiovascular risk in patients with diabetes and high-risk vascular disease, including patients with recent acute coronary syndrome, peripheral arterial disease, and cerebrovascular disease.

Of the 12,092 patients in the ACCELERATE trial, 8145 had established diabetes and a baseline measurement of HbA1c. The researchers calculated Kaplan-Meier events rates, stratified by increasing baseline HbA1c levels censored at 30 months.

Increasing baseline levels of HbA1c were strongly associated with the occurrence of the primary composite end point of cardiovascular death, nonfatal myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina with a Kaplan-Meier estimate of 12.6 with HbA1c <6.0%, 14.5 with HbA1c 6.0% to <6.5%, 14.0 with HbA1c 6.5% to <7.0%, 16.1 with HbA1c 7.0% to <7.5%, 16.3 with HbA1c 7.5% to <8.0%, and 18.2 with HbA1c ≥8.0% (P <.001).

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Increasing baseline HbA1c levels were also associated with a triple end point of cardiovascular death, nonfatal myocardial infarction, and stroke, with Kaplan-Meier estimates increasing from 7.8 with HbA1c <6.0% to 11.3 with HbA1c ≥8.0% (P =.003). A similar trend was evident for the individual end points of nonfatal myocardial infarction (Kaplan-Meier estimates, 3.1-7.0; P <.001), hospitalization for unstable angina (Kaplan-Meier estimates, 1.8-5.0, respectively; P =.003), and need for coronary revascularization (Kaplan-Meier estimates, 7.3-11.1; P =.001), but not for nonfatal stroke.

Rates of cardiovascular mortality (P =.21) and all-cause mortality (P =.21) were similar regardless of baseline HbA1c levels.

In a multivariable model, baseline HbA1c was an independent predictor for the primary composite end point (hazard ratio, 1.06; 95% CI, 1.02-1.11; P =.003).

The researchers acknowledged several study limitations, including missing data on important variables such as duration of diabetes and changes in glycemic control over time, as well as data on the use of novel antiglycemic agents, particularly those that influence cardiovascular outcomes.

“In a contemporary population of patients with [diabetes] and established coronary artery  disease on optimum medical therapy, HbA1c was found to be an independent predictor for major adverse cardiac events in the ACCELERATE trial. No associated increase in mortality with decreasing HbA1c levels was noted,” concluded the researchers.

Disclosure: This clinical trial was supported by Eli Lilly. Please see the original reference for a full list of authors’ disclosures.

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Reference

Menon V, Kumar A, Patel DR, et al. Impact of baseline glycemic control on residual cardiovascular risk in patients with diabetes mellitus and high-risk vascular disease treated with statin therapy. J Am Heart Assoc. 2020;9(1):e014328.