https://diabetes.acponline.org/archives/2016/10/07/2.htm

3 biomarkers may refine standard cardiovascular risk algorithms for diabetes

Elevations in high-sensitivity troponin T or N-terminal pro-B-type natriuretic peptide were significantly associated with risk of cardiovascular death, myocardial infarction, and hospitalization for heart failure, while C-reactive protein was a less significant predictor.


Three cardiac biomarkers may provide incremental value to predict risk of future cardiovascular events in patients with type 2 diabetes, a new analysis found.

Researchers conducted a secondary analysis of the SAVOR-TIMI trial, a randomized, double-blind, placebo-controlled clinical trial that evaluated the safety of saxagliptin in outpatients with type 2 diabetes with overt cardiovascular disease or multiple risk factors. In a secondary analysis, researchers evaluated high-sensitivity troponin T, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein continuously and at established cut points to learn whether they might provide incremental prognostic value in stratifying risk.

The study was performed from May 2010 to June 2013, with a median follow-up of 2.1 years (interquartile range, 1.8 to 2.3 years). Outcomes included cardiovascular death, myocardial infarction, ischemic stroke, and hospitalization for heart failure (HF). Results appeared in JAMA Cardiology on Sept. 28.

Researchers measured baseline biomarkers in 12,310 patients and found that elevated levels of each biomarker were associated significantly with increased risk for all cardiovascular end points. When added to clinical variables, these biomarkers significantly improved the discrimination and appropriate reclassification of risk.

Elevated high-sensitivity troponin T was associated with an increased risk of cardiovascular death (adjusted hazard ratio [AHR], 3.07; 95% CI, 2.35 to 4.02; P<0.001), myocardial infarction (AHR, 2.13; 95% CI, 1.69 to 2.67; P<0.001), and hospitalization for HF (AHR, 3.85; 95% CI, 2.82 to 5.27; P<0.001). Elevated N-terminal pro-B-type natriuretic peptide was associated with an increased risk of cardiovascular death (AHR, 3.09; 95% CI, 2.46 to 3.89; P<0.001), myocardial infarction (AHR, 1.95; 95% CI, 1.51 to 2.53; P<0.001), and hospitalization for HF (AHR, 3.92; 95% CI, 3.11 to 4.92; P<0.001). Elevated high-sensitivity C-reactive protein was more weakly associated with an increased risk of cardiovascular death (AHR, 1.49; 95% CI, 1.22 to 1.82; P<0.001) and hospitalization for HF (AHR, 1.47; 95% CI, 1.20 to 1.81; P<0.001).

When patients who had 1, 2, or 3 elevated biomarkers were compared with patients without any elevated biomarkers, there was a stepwise increase in the risk of cardiovascular events by cut point. In 481 patients (3.9%) with 3 elevated biomarkers, the 2-year rates were 17.3% for cardiovascular death, 11.7% for myocardial infarction, 4.7% for ischemic stroke, and 21.7% for hospitalization for HF. The corresponding rates in the patients without any elevated biomarkers (4,266 patients [34.7%]) were 1.0%, 1.9%, 1.0%, and 0.7%, respectively, and this stepwise increase in risk was apparent in patients with established cardiovascular disease or multiple risk factors alone.

The researchers noted that biomarker risk stratification challenges the traditional differentiation between primary and secondary prevention based simply on clinical history. Strategies to improve risk stratification in patients with type 2 diabetes, with or without cardiovascular disease, should consider incorporation of biomarker data into standard risk algorithms, they said.

“Although biomarkers clearly identified patients at increased cardiovascular risk, no biomarker identified a particular patient population that benefited or was harmed by treatment with saxagliptin,” the authors wrote. “Now that several different classes of diabetes drugs have been reported to improve cardiovascular outcomes, biomarkers may provide additional insight into the mechanism of action and identification of patients most likely to benefit from therapy.”