CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Anne Paxton
August 2018—For diabetes type 2 patients with cardiovascular disease, findings of a new study support clinicians’ use of serial measures of NT-proBNP concentrations to make critical treatment decisions easier by basing them on risk of major cardiovascular events, including heart failure.
Researchers analyzed differences between baseline and later NT-proBNP (N-terminal B-type natriuretic peptide) test results along with outcomes in the population with diabetes type 2 who were enrolled in the EXAMINE trial. They found a “strong graded relationship” between increasing baseline and six-month NT-proBNP concentration and the incidence of future major cardiovascular events.
NT-proBNP at baseline was independently associated with development of major cardiovascular events—in particular, hospitalization for heart failure (Jarolim P, et al. Diabetes Care. 2018;41[7]:1510–1515).
In a cohort of patients singled out by the study, “the risk of heart failure was really dramatic,” says lead author Petr Jarolim, MD, PhD, director of clinical laboratories at Dana-Farber Cancer Institute and medical director of clinical chemistry and director of the biomarker research and clinical trials laboratory at Brigham and Women’s Hospital. Dr. Jarolim presented the study at the Heart Failure 2018 conference in Vienna, Austria, in May. The study was also featured in the closing session highlights of the meeting.
“When we teased out high-risk patients” (those with persistently high NT-proBNP or newly high NT-proBNP at six months) from the quartiles in which patients were stratified according to their NT-proBNP results, “we showed that the risk of heart failure for them is very significant. For this group of patients—about 10 percent of the population of type 2 diabetes patients—the risk we identified is very high,” Dr. Jarolim says.
‘We found that NT-proBNP concentration of 400 pg/mL as the point between so-called high and low NT-proBNP worked very well.’
—Petr Jarolim, MD, PhD
Evidencing the strong correlation with risk, the hazard ratios shown in the study—the ratio of the hazard rates corresponding to the conditions described by two levels of a variable—“were on the order of five to 10 in those patients seen by a clinician and marked as abnormal,” he says. This signifies that the high-risk group was five to 10 times as likely as the others (those with persistently low NT-proBNP or an NT-proBNP that declined to a low level over six months) to be hospitalized for heart failure.
The model used for this study adjusted for important potential confounders, including age, sex, BMI, type of qualifying acute coronary syndrome event and time since the event, history of heart failure, hypertension, and estimated glomerular filtration rate.
The study is another in a string of recent papers on serial changes in biomarkers such as troponin relating to treatment of cardiovascular disease. “It didn’t come out of the blue,” says Dr. Jarolim, whose research laboratory worked on several earlier studies. Troponin and NT-proBNP have solid predictive value, he says. “The reason we focused here on NT-proBNP is that there is a lot of discussion about the potential benefits of new antidiabetic medications for cardiovascular disease.”
The FDA mandated about a decade ago that each new antidiabetic medication have sizable post-marketing studies addressing the safety of the drug, he notes. “Although no studies show there is a risk in using these new medications, one of the initial concerns was possible increased hospitalizations for heart failure and whether they could be predicted.”
Use of the high-risk patients in the EXAMINE trial (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care), who were enrolled after a clinical presentation of acute coronary syndrome, was one of the limitations of the study. The rate of major cardiovascular events in a stable diabetic patient population is relatively low, so the size of any study has to be large if patients are not high-risk patients. “However, we believe our findings can be applied to lower-risk patient populations,” Dr. Jarolim says.
“What may eventually be needed is actually a similar study to ours in patients who are not pre-selected as high-risk patients, who are just your standard type 2 diabetes patients without active CV disease yet. That’s important to show this effect is the same or similar in the general population with type 2.”