Natriuretic Peptide Deficiency Uncovered

Natriuretic Peptide Deficiency Uncovered
Unexpectedly low levels could mask heart failure risk.

Patients presenting with heart failure, atypical hemodynamics, or abnormal cardiac function may not have B-type natriuretic peptide (BNP) elevations as expected, according to new research led by Katherine N. Bachmann, M.D., an endocrinologist at Vanderbilt University Medical Center and Nashville VA Medical Center.

Two decades of EHR data suggest some patients may simply be deficient in the hormones that help compensate for acute myocardial stretch and strain. The findings were recently published in the Journal of the American College of Cardiology: Heart Failure.

“This is the first time to our knowledge that anyone has looked at three clinical populations we expect to have high levels of BNPs and found that some people instead have inappropriately low levels,” Bachmann said. “This is really strong evidence that a deficiency of natriuretic peptide hormones may exist in humans.”

A Novel Deficiency

In contrast to other hormones, such as insulin, thyroid hormone and cortisol, where states of deficiency or excess are well established, it is not clear whether such states exist for natriuretic peptides, Bachmann says. Endocrine feedback loops add to an already complicated regulatory landscape for natriuretic peptides in the heart.

“The existence of deficiencies for other hormones are so well defined. Natriuretic peptides are hormones we know some things about, but we are just starting to understand that deficiencies could exist, which raises so many interesting questions,” Bachmann said.

While Bachmann and colleagues previously quantified sex-specific differences in natriuretic peptide levels, mechanisms behind these differences remain unknown.

Unexpectedly Low BNP

In the recent study, researchers identified 47,970 adults with BNP measurements in Vanderbilt’s Synthetic Derivative EHR database. This included 13,613 patients with at least one condition in which elevated BNP would be expected.

Among these patients, the researchers found extremely low BNP (under 50 pg/ml) in 4.9, 14, and 16.3 percent of patients with heart failure, abnormal cardiac structure or function, or abnormal hemodynamics, respectively. Dozens of patients had completely undetectable BNP levels. Obese patients were most likely to have unexpectedly low or undetectable BNP.

“Natriuretic peptides are hormones we know some things about, but we are just starting to understand that deficiencies could exist.”

A small genetic subanalysis did not immediately reveal alterations in the gene encoding BNP that might explain the deficiency. However, the researchers were able to rule out any genetic variations that might have precluded BNP detection in the patients.

Clinical Consequences 

The study is the first to describe a natriuretic peptide deficiency in a clinical population. This novel deficiency could have clinical consequences, said study coauthor Deepak Gupta, M.D., director of Vanderbilt’s Translational and Clinical Cardiovascular Research Center.

“Natriuretic peptides are compensatory hormones that promote diuresis and vasodilation in the setting of increased cardiac stress,” he said. “People with a natriuretic peptide deficiency may be more susceptible to volume or pressure overload. Relatively low natriuretic peptide levels in some patients may also pose challenges to accurately diagnosing heart failure; therefore, we also need to be aware of this when interpreting lab results.”

Next, the researchers plan to study whether low levels of natriuretic peptides may increase susceptibility to cardiometabolic disease and affect outcomes.

“Perhaps a relative deficiency of natriuretic peptide hormones contributes to the higher rates of hypertension and cardiometabolic disease in certain populations,” Bachmann said.