Uptick in Natriuretic Peptides at Serial Testing Predicts New HF


A jump in natriuretic peptide levels over several years in middle-aged adults points to worsened long-term risks for incident heart failure (HF) and death. But their predicted long-term survival improves if serial testing shows a drop in those levels, suggests a new analysis based on a well-known longitudinal study cohort.

The findings support the risk-stratification potential of serial natriuretic peptide testing, which may improve on individual assays for predicting future HF. Such serial assays might also be useful for guiding therapy aimed at preventing, for example, progression to clinical HF, researchers speculate on the basis of the current study,

The analysis of almost 1000 members of the ARIC (Atherosclerosis Risk in Community) cohort had been free of clinical HF at the first of two NT-proBNP assays, which were performed 6 years apart. Their 20-year clinical risk was linked to the trajectory of NT-proBNP levels across the two earlier assays.

For example, adjusted risk of incident HF more than doubled for participants with NT-proBNP levels exceeding 125 pg/mL on both assays, compared to levels that stayed under the cut point at both assays. Their mortality risk climbed by about two thirds.

Risk for incident HF and of death climbed 86% and 32%, respectively, if NT-proBNP levels rose over the 6 years from less than to greater than 125 pg/mL. But long-term survival improved if serial assays showed a drop from the higher to the lower level.

Rising NT-proBNP levels over several years probably reflect ongoing exposure to risk factors such as hypertension or diabetes. Conversely, decreasing NT-proBNP levels likely reflect some success at keeping such risk factors under control, propose the authors of the analysis published February 8 in JAMA Cardiology. The study was led by Xiaoming Jia, MD, Baylor College of Medicine, Houston.

The findings raise the possibility that reducing NT-proBNP levels through risk-factor modification, tracked by serial assays, may potentially improve long-term risk for death or incident HF.

Such therapy, guided by natriuretic peptides, might prove especially useful in asymptomatic adults with modifiable HF risk factors but without known NT-proBNP elevation or cardiac structural changes, so-called stage A HF, senior author Vijay Nambi, MD, PhD, also of Baylor, observed for theheart.org | Medscape Cardiology.

The best populations for serial NT-proBNP assays to guide therapy, Nambi said, should become clear “as more data emerges.” But the threshold for ordering such tests would probably be lower for people in stage A, who could potentially be reclassified to stage B, also called pre-HF, if NT-proBNP levels rise substantially.

In such cases, he speculated, intensified therapy of HF risk factors such as uncontrolled hypertension or diabetes — prompted by greater NT-proBNP levels at serial testing — might possibly avert progression to clinical HF.

“These investigators have nicely demonstrated that one measurement of the biomarker may not be sufficient, that maybe it under-captures the true burden of people who eventually will develop heart failure,” Muthiah Vaduganathan, MD, MPH, told theheart.org | Medscape Cardiology.

The study raises the possibility “that the serial natriuretic peptide strategy may be more efficient and more comprehensive in identifying those who will eventually progress,” said Vaduganathan, of Brigham and Women’s Hospital and Harvard Medical School, Boston, who was not associated with the ARIC analysis.

An open question, he added, is whether the predicted risk is modifiable. “If you are able to provide the biomarker information to treating clinicians, can they do something to attenuate the risk?”

The outlook is hopeful, given contemporary therapies “that can slow and even prevent heart failure in at-risk populations,” Vaduganathan said. For example, “The selective allocation of SGLT2 inhibitors to those with elevated natriuretic peptide levels, perhaps as captured in serial measurements, would be of great interest.”

The analysis included 9776 adults (56.5% women, 21.3% Black) without HF who underwent NT-proBNP testing at the second and — about 6 years later — the fourth scheduled clinical visits in the ARIC study, which had enrolled persons aged 45 to 64 from four diverse communities from across the US.

Adjusted hazard ratios (HRs) for incident HF according to NT-proBNP changes from the first to second assays relative to 125 pg/dL were as follows:

  • 1.86 (95% CI, 1.60 – 2.16) when levels rose to higher than the cut point

  • 2.40 (95% CI, 2.00 – 2.88) when both levels were exceeded the cut point

The corresponding adjusted HRs for death from any cause were as follows:

  • 1.32 (95%CI, 1.19 1.47) when levels rose to higher than 125 mg/dL

  • 1.68 (95% CI, 1.47 1.91) when both levels were above the cut point

The risks for incident HF and for death rose significantly by 6% and 5%, respectively, per standard deviation NT-proBNP increase from the first to second assay.

Risks for HF and mortality for participants whose NT-proBNP levels declined from greater than to less than 125 pg/mL were similar to those whose levels remained low at both assays.

Cost-effectiveness would be another issue when implementing a strategy that calls for multiple biomarker assays, Vaduganathan observed.

“Surely, we would want to demonstrate that the laboratory measurement costs are offset by downstream prevention of heart failure events that could be averted by use of effective medical therapy, such SGLT2 inhibitors.”

ARIC has been funded by the National Institutes of Health and Department of Health and Human Services. Nambi discloses receiving grants from the National Institutes of Health during the conduct of the study; support from Amgen; and stocks from Abbott Laboratories. Disclosures for the other authors are in the report. Vaduganathan has disclosed receiving grants or serving on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, Novartis, Pharmacosmos, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; speaking for AstraZeneca, Novartis, and Roche Diagnostics; and serving on trial committees for studies sponsored by Galmed, Novartis, Bayer AG, Occlutech, and Impulse Dynamics.

JAMA Cardiol. Published online February 8, 2023. Full text

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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