JACC: Combining biomarkers, risk factors helps predict mortality

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Adding a multiple biomarker model to established risk factors—diabetes, hypertension, systolic blood pressure, heart rate, among others—can improve the prediction of mortality in STEMI patients undergoing primary PCI, according to a study published in the Jan. 4 issue of the Journal of the American College of Cardiology.

“Several demographic, electrocardiographic and percutaneous coronary intervention (PCI)-related characteristics have been identified as important prognostic factors regarding mortality in patients with STEMI,” the authors wrote. Novel biomarkers have previously been associated with an increased risk of mortality in STEMI patients because they may reflect left ventricular dysfunction, glucose metabolism, renal function and MI cell damage, the authors noted.

To better understand whether multiple biomarkers can improve the prediction of mortality, either alone or in combination with established risk factors, Peter Damman, MD, of the Academic Medical Center in Amsterdam, and colleagues evaluated 1,034 STEMI patients who underwent primary PCI between Jan. 1, 2005, and Jan. 5, 2007.

Of the patient cohort, the mean age was 62 years and 73 percent were male.

The researchers developed a risk score to assess whether combining N-terminal pro-brain natriuretic peptide (NT-proBNP), glucose, C-reactive protein, estimated glomerular filtration rates and cardiac troponin T (cTnT) could improve the prediction of mortality.

The risk score was based on the strongest predicting biomarkers to established prognostic factors such as age, body weight, diabetes, hypertension, systolic blood pressure, heart rate, anterior MI and time to treatment, which were all assessed in a multivariable Cox regression.

The results showed that during the 901-day median follow-up, 120 of the 1,034 patients died. The researchers found that glucose, glomerular filtration rates and NT-proBNP were the strongest predictors of mortality.

Glomerular filtration rates of less than 60 ml/min were linked to a 2.80 increased mortality hazard, while glucose levels equal to 10 mmol/l or more were associated with higher mortality. A two-fold increase in mortality was seen when NT-proBNP values were 600 ng/l or higher.

The researchers said that the increase in mortality occurred early and offered that additional therapies to improve outcomes should be started as soon as possible—during or immediately following primary PCI.

“The main advantage of this multimarker score is its simplicity and strong discriminative capacity. When confirmed by other independent cohorts, our multimarker score may be useful in identifying patients eligible for adjuvant therapies during or after PCI,” the authors wrote. “This is particularly important in view of the number of new treatments investigated in STEMI patients, such as ticagrelor and delta-protein kinase C inhibitors, potentially leading to resource-limited treatment options.”

In an accompanying JACC editorial, Luigi M. Biasucci, MD, and Roberta Della Bona, MD, of the Catholic University of the Sacred Heart in Rome, wrote that biomarkers are useful for troublesome diagnosis, therapeutic and strategic decision marking, long-term prognostication and a better understanding of complex pathophysiological mechanisms.

However, Biasucci and Della Bona urged that Damman et al's findings should be interpreted with caution and in their own context, due to the fact that only a few trials have addressed the topic.

“The authors' hypothesis that use of a biomarker score may help to address the best therapies may seem consequential,” the authors wrote. "However, this may represent a dangerous oversimplification: The step from higher nonspecific risk to more aggressive specific therapy is long and should not be considered until definitive data are provided.”

Biasucci and Della Bona said that no new treatments address any of the biomarkers mentioned in the study. In addition, because renal function is a marker of increased ischemic and hemorrhagic risk, the authors said that antithrombotic and antiplatelet agents should be chosen on the bases of evidence and tests.

In addition, Biasucci and Della Bona wrote, "The study provides important pathophysiological information confirming the common roots of ACS, either ST-segment elevation or NSTE, and promising clinical improvements in STEMI treatment.

“Although their efforts fell short of the objectives, we hope that they will contribute to a more accurate and individualized prognostication