An analysis of a randomized trial identified three biomarkers that were associated with adverse cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease or multiple cardiovascular risk factors.

The biomarkers were elevated levels of high-sensitivity troponin T (hsTnT), N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity C-reactive protein (hsCRP).

Lead researcher Benjamin M. Scirica, MD, MPH, of Brigham and Women’s Hospital in Boston, and colleagues published their results online in JAMA Cardiology on Sept. 28.

The researchers evaluated the SAVOR-TIMI 53 trial, which found that patients with type 2 diabetes who received saxagliptin had reductions in HbA1c level but did not have a reduced risk of the primary composite endpoint of cardiovascular death, MI or ischemic stroke. The patients in the saxagliptin group also had a significant 27 percent increased relative risk of hospitalization for heart failure.

This analysis included 12,310 patients from the trial who had concentrations of hsTnT, NT-proBNP and hsCRP measured at baseline. The study had a few limitations, according to the researchers, including that it did not assess left ventricular function. They also did not measure baseline lipid levels.

Still, the researchers found that elevated levels of each of the biomarkers were associated with significant increased risk for all the primary composite endpoint as well as the individual endpoints of cardiovascular death, MI, ischemic stroke and hospitalization for heart failure.

They added that the association was stronger for elevated levels of hsTnT and NT-proBNP and weaker for elevated levels of hsCRP. In addition, the association between the biomarkers and increased risk of cardiovascular outcomes was similar in patients with cardiovascular disease and those with multiple risk factors but no cardiovascular disease. They also noted that small elevations in the three biomarkers helped predict outcomes.

“Biomarker risk stratification thus challenges the traditional differentiation between primary and secondary prevention that is based simply on a history of a clinically recognized cardiovascular event,” the researchers wrote. “For example, the risk of cardiovascular death in a patient with clinical risk factors alone but with an elevated hsTnT level is higher (3.7 percent) than in a patient with established cardiovascular disease and a low hsTnT level (1.4 percent). Integration of these biomarkers into routine screening and risk stratification algorithms of patients with type 2 diabetes can more accurately assess risk and thereby target patients in whom modification or intensification of diagnostic and treatment strategies, as well as the frequency of follow-up, might reduce future complications.”