Biomarkers Sharpen, May Best Clinical CV Risk Assessment in Diabetics

Larry Hand

September 28, 2016

BOSTON, MA — To improve cardiovascular risk stratification in patients with stable type 2 diabetes, incorporation of biomarker data, particularly for high-sensitivity troponin T (hs-TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP), into standard algorithms should be considered, according to a secondary analysis of the SAVOR-TIMI 53 clinical-trial results[1].

The results were published online September 28, 2016 in JAMA Cardiology.

"I think the biomarkers, in particular the high-sensitivity troponin and NT-proBNP, are better at risk stratifications in patients with stable diabetes than many of the clinical variables or characteristics that we use," Dr Benjamin M Scirica (Brigham and Women's Hospital, Boston, MA) told heartwire from Medscape.

"For example, a person who has an elevated high-sensitivity troponin level but no history of a myocardial infarction is actually at higher subsequent risk than somebody who had a history of myocardial infarction but a normal or low high-sensitivity troponin," he said.

Scirica and colleagues analyzed whether widely used biomarkers would provide prognostic value in risk stratification based on data in the SAVOR-TIMI 53 trial, in which researchers evaluated the cardiovascular effects of the diabetes therapy saxagliptin (Onglyza, AstraZeneca) when added to standard care.

They included hs-TnT, NT-proBNP, and high-sensitivity C-reactive protein (hs-CRP) in their analysis, using samples collected during the study, which ran from May 10, 2010 to June 15, 2013. They found that in samples collected from 12,310 patients who either had confirmed cardiovascular disease or had multiple CVD risk factors, elevated levels of all three biomarkers were significantly associated with increased risk for cardiovascular end points.

Elevated Biomarkers and Risk for Cardiovascular End Points

Biomarker/outcome Adjusted hazard ratio (95% CI) P
Cardiovascular death 3.07 (2.35–4.02) <0.001
MI 2.13 (1.69–2.67) <0.001
Hospitalization for heart failure 3.85 (2.82–5.27) <0.001
Cardiovascular death 3.09 (2.46-3.89) <0.001
MI 1.95 (1.51-2.53) <0.001
Hospitalization for heart failure 3.92 (3.11-4.92) <0.001
Cardiovascular death 1.49 (1.22-1.82) <0.001
Hospitalization for heart failure 1.47 (1.20-1.81) <0.001

Results were consistent across patients with and without established CVD.

"Compared with clinical variables, these biomarkers really do identify high- and low-risk patients in a much better manner than what we're doing in clinical practice," Scirica told heartwire . "If you are seeing a patient in front of you who you are wondering what's their overall risk, these biomarkers would tell you if the patient is high or low risk.

"If you're doing research, you could identify these patients and then think about some type of intervention, whether it's specific therapy or whether it's lifestyle changes, you name it," he said.

Whether in patients with type 2 diabetes with CVD present or with multiple CVD risk factors, the biomarkers work "and need to be integrated into the typical risk-stratification algorithm within the guidelines," he concluded.

He said a test for NT-proBNP is available worldwide, while high-sensitivity troponin assays are widely used in Europe and outside the US but still not approved for use in the US.

Dr Mikhail Kosiborod (St Luke's Mid-America Heart Institute, Kansas City, MO), who was not involved in the current analysis, told heartwire , "I think this study really addresses an important clinical need, because we don't have great ways of differentiating risk in patients with type 2 diabetes. We know that, on average, patients with type 2 diabetes are a higher-risk group, but they are not a homogeneous group—some are at high risk, and some are not. This study certainly moves us in the right direction—in terms of our ability to do a better job with risk prediction."

"Two biomarkers were clearly identified in this analysis that are really important, that have really excellent ability to predict outcomes in a relatively short term, not 10 to 15 years but 2 or 3 years," Kosiborod said.

"A large proportion of patients had abnormal biomarkers at baseline. It was such a significant proportion of patients, even among those who didn't have manifest cardiovascular disease. And patients without established disease but who had elevated biomarkers had as high as or even higher risk than those with established disease and low levels of biomarkers. That is a very important insight," he concluded.

The SAVOR-TIMI 53 trial was sponsored by AstraZeneca and Bristol-Myers Squibb. Scirica reported receiving research funds from AstraZeneca, Eisai, Merck, and Poxel and consulting fees from AstraZeneca, Biogen Idec, Boehringer Ingelheim, Covance, Dr Reddy's Laboratory, Elsevier Practice Update Cardiology, Forest Laboratory, GE Healthcare, GlaxoSmithKline, Health[at]Scale, Lexicon, Merck Sanofi, St Jude's Medical, and the University of Calgary. Disclosures for the coauthors are listed in the article.

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