BARCELONA, SPAIN — High levels of serum probrain natriuretic peptide (proBNP) are associated with an increased risk of macrovascular events, independent of baseline coronary artery disease (CAD) status, in patients with and without type 2 diabetes [1].

These are the conclusions of an analysis presented today here at the European Association for the Study of Diabetes (EASD) 2013 Meeting by Dr Alexander Vonbank (Private University of Liechtenstein, Triesen). Overall, Vonbank said that patients with type 2 diabetes and low levels of serum proBNP were at a moderate risk of future events, whereas those patients with type 2 diabetes and high levels of proBNP, defined as >314 pg/mL, were "at an extremely high risk for cardiovascular events."

In both groups, those with diabetes and those without, proBNP was a strong predictor of cardiovascular events. "ProBNP in patients with diabetes, as well in those without diabetes, is useful for cardiovascular-risk stratification and provides prognostic information over and above the angiographically determined CAD status," said Vonbank.

Increasing Risk With Increasing proBNP Levels

Presenting the results during the EASD meeting, Vonbank said that proBNP is a broadly applied marker of cardiac distress and strongly predicts cardiovascular-event risk in the non–heart-failure patient population. However, the ability of the marker to predict cardiovascular events in patients with diabetes is not known, he explained, and this led to the group studying its prognostic ability in 720 consecutive patients undergoing coronary angiography for CAD or suspected CAD.

Of the 720 patients, 24% had diabetes mellitus. At baseline, the diabetic patients had higher levels of serum proBNP. The diabetic patients also were significantly more likely to have hypertension, more obesity, and more coronary disease. The average age in the entire cohort was 66 years, and 63% were male. Patients with acute coronary syndrome were excluded from the study.

After three years of follow-up, there were 119 major vascular events, including 24 deaths from cardiovascular causes, 18 nonfatal MIs, 12 nonfatal strokes, 37 coronary revascularizations, and 28 noncoronary revascularizations. Patients were stratified into four patient groups: no diabetes/low proBNP (<314 pg/dL), diabetes/low proBNP, no diabetes/high proBNP (>314 pg/mL), and diabetes/high proBNP.

In terms of event-free survival, there was a significant difference in risk among patients with no diabetes and low proBNP levels compared with patients with diabetes and high levels of proBNP, said Vonbank. Patients with diabetes and high levels of proBNP had the highest risk of cardiovascular events.

Overall, cardiovascular risk increased significantly with increasing proBNP levels in patients with diabetes. Per tertile, the risk of cardiovascular events was 6.3%, 24.1%, and 32.4%, respectively (p=0.004). Similar results were observed in the nondiabetic patients, with the risk of cardiovascular events per tertile being 11.5%, 11.4%, and 21.1%, respectively (p=0.012). When measured as a continuous variable, baseline proBNP levels were predictive of cardiovascular events in diabetics and nondiabetics (hazard ratio 1.40; p=0.003 and hazard ratio 1.19; p=0.003, respectively). Even when adjusted for angiographically confirmed CAD, the results were not attenuated.

Dr Naveed Sattar (University of Glasgow, Scotland), the session moderator, said that his group has performed an analysis of the ADVANCE data, currently awaiting publication, showing that proBNP is a very strong predictor of events. However, he pointed out that the researchers did not examine any reclassification improvement metrics, such as area-under-the-curve (AUC) or receiver-operating-characteristic (ROC) analyses, so it is difficult to yet claim these results aid in prognosis.

To heartwire , Sattar said proBNP has been shown to be a strong predictor of cardiovascular events in elderly patients without diabetes as well as in high-risk patients without prior cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS). "Again, proBNP seemed to improve risk prediction two to three times as well as [C-reactive protein] CRP did," said Sattar. "ProBNP is probably the biggest, hottest biomarker in terms of predicting cardiovascular disease that we need to look at right now. CRP has been canned."

Sattar said that in the general opinion of European and UK experts, CRP adds very little to cardiovascular risk stratification. For example, he cited data from the Emerging Risk Factors Collaboration , which included 52 studies and 246 669 individuals, that showed adding CRP to traditional risk factors yields only a net reclassification improvement of 1.52%, "which is insufficient to be clinically useful."

"So we now need to look at something else, and proBNP is the next biomarker," said Sattar. He that his group is currently working on a larger analysis that will examine the extent to which proBNP improves risk prediction.

The authors report no conflicts of interest.

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