New Biomarker Predicts Increased Risk of Death in Heart Failure Patients

A new study from cardiologists at UCLA Medical Center how revealed a new biomarker that could help other physicians predict which patients with stable heart failure have a higher risk of dying within the next 3 years.

The study found patients with higher levels of neuropeptide Y(NPY) were 10 times more likely to die within 1 to 3 years when compared to their counterparts with lower levels of NPY.

In an effort to determine whether the adrenergic cotransmitter NPY could serve as a reliable biomarker for predicting which patients with stable heart failure were at a higher risk of dying, investigators carried out a prospective observational cohort study using data of 105 patients from the Biomarkers to Predict CRT Response in Patients with CHF (BIOCRT) study. For the purpose of the current study, investigators examined coronary sinus(CS) NPY levels in patients with stable heart failure at the time of elective cardiac resynchronization therapy (CRT) device implantation.

The primary outcome of the study was major adverse cardiovascular events (MACE), which investigators defined as death, cardiac transplant (OHT), or ventricular assist device (VAD) placement, and hospitalization for heart failure.

Of the 105 patients included in the study, the mean age was 68 years, 78% were men, and the mean left ventricular ejection fraction(LVEF) was 26%. Investigators noted that prior to CRT implantation 90% of participants were receiving beta-blockers and 95% were receiving an angiotensin-converting enzyme inhibitor, angiotensin receptor booker, or nitrate/hydralazine combination. Additionally, 25% of participants ere reeve ing an aldosterone antagonist prior to implantation.

In regard to NPY levels and their relationship to clinical characteristics, investigators found levels were significantly greater in women, patients with diabetes, and patients with hypertension. No associations were observed between NPY levels and NYHA functional class, ischemic cardiomyopathy, prior coronary artery bypass grafting surgery, or prior myocardial infarction.

During a follow-up period lasting 28.8 months, the composite endpoint of death, OHT, and VAD placement was observed in 19% (20 of 105) patients included in the study. Investigators established 130 pg/mL of CS NPY as the threshold for the analyses, as it was identified as an inflection point where the hazard ratio for the composite endpoint increased significantly.

Analyses revealed CS NPY levels greater than 130 pg/mL were associated with had worse outcomes than patients with lower levels (HR: 8.9; 95% CI, 3.1-25.7; P<0.001). These results were consistent in additional analyses adjusting for age, eGFR, and LVEF (HR: 9.5; 95% CI, 2.92-30.5; P<0.001). Investigators noted death (18 of 20) accounted for the majority of the events that occurred.

In analyses including heart failure hospitalizations in the composite endpoint, an increased risk for adverse events was noted in patients with elevated CS NPY levels(unadjusted HR: 5.3; 95% CI, 1.99-13.9; P<0.001). Investigators pointed out similar results were observed in additional analyses accounting for age, eGFR, and LVEF (HR: 9.34; 95% CI, 3.08-28.35; P<0.001). Heart failure hospitalizations (28) and deaths (8) accounted for the majority of events in the aforementioned analyses.

In an invited commentary published in JAMA Cardiology, Robin Shaw, MD, PhD, professor of cardiology at the University of Utah, wrote results of the current study could help move diagnostic techniques and suggest results indicate the need for follow-up studies.

“The authors are to be congratulated for a study that has the potential to advance diagnostic approaches to the level of cardiac neurohormonal stress, which directly affects cardiomyocyte pathogenesis,” Shaw wrote.

This study, titled “Coronary Sinus Neuropeptide Y Levels and Adverse Outcomes in Patients With Stable Chronic Heart Failure,” was published in JAMA Cardiology.