A novel hormone deficiency may exist in humans, Vanderbilt investigators have discovered. In an analysis of two decades worth of electronic health records, the researchers found that some patients have unexpectedly low levels of natriuretic peptide hormone in clinical situations that should cause high levels of the hormone.
The findings were published in the journal JACC: Heart Failure.
Natriuretic peptides — a family of hormones including ANP and BNP — are produced by heart muscle cells in response to stress that occurs in conditions such as heart failure, high blood pressure and states of volume overload. The natriuretic peptides then promote excretion of salt and water into the urine and relax blood vessels to counter the stress on the heart.
In the clinical setting, natriuretic peptides are used as biomarkers for states of volume overload and may get a “bad rap” because they are elevated in patients with heart failure, said Katherine N. Bachmann, MD, MSCI, assistant professor of Medicine.
However, natriuretic peptide levels are elevated in such states because the heart is secreting these hormones in order to help improve and lessen the volume overload, she added.
Recent evidence suggests natriuretic peptides also may play beneficial roles in metabolism. Animal models with genetically higher levels of natriuretic peptides are protected against hypertension and insulin resistance. This raises the question of whether low levels of natriuretic peptides may increase susceptibility to cardiometabolic disease. Groups of people with lower levels of natriuretic peptides, such as obese individuals and African Americans, also have higher rates of hypertension and states of volume overload, Bachmann noted.
“Perhaps a relative deficiency of natriuretic peptide hormones contributes to the higher rates of hypertension and volume overload in certain populations,” she said.
But in contrast to other hormones, such as thyroid hormone and cortisol, where states of deficiency or excess have been well established, it is not clear whether such states exist for natriuretic peptide hormones.
“As an endocrinologist interested in hormones and metabolism, I found this intriguing,” Bachmann said.
Simply measuring natriuretic peptide levels to look for a deficiency is not reliable, however, because of complex endocrine feedback loops. Instead, the team, led by Bachmann and cardiologist Deepak Gupta, MD, MSCI, assistant professor of Medicine, decided to look for individuals who have unexpectedly low levels of natriuretic peptides when high levels should be present — because of a stimulus like heart failure.
The researchers used Vanderbilt’s database of de-identified electronic medical records (the “Synthetic Derivative”), which includes about 3 million records spanning 20 years. They identified three groups of patients who should have high BNP levels: patients with heart failure, patients with abnormal cardiac structure or function on echocardiograms, and patients with abnormal filling pressures on cardiac catheterization.
Among the 13,613 patients who had one of the three conditions, they quantified the frequency of low BNP levels. They found very low BNP levels in 4.9%, 14.0% and 16.3% of patients with heart failure, abnormal structure and abnormal pressure, respectively.
“This is the first time to our knowledge that anyone has looked at three clinical populations we expect to have high levels of BNP 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.”
The findings could have important implications, Bachmann said.
“If people cannot mount an appropriate natriuretic peptide hormone response to volume overload, that could lead to worse outcomes. That’s a question for future investigations.”
Among other open questions are how to diagnose a natriuretic peptide deficiency, how to treat it and whether treatments have beneficial outcomes. She also noted that the team’s evidence for a natriuretic peptide deficiency supports further study of how low levels might be contributing to higher rates of hypertension and poor cardiac outcomes in obese individuals and African Americans.
“The existence of deficiencies for other hormones are so well defined. Natriuretic peptides are hormones we knew some things about, but we are just starting to understand that deficiencies could exist, which raises so many interesting questions,” Bachmann said.
Also contributing to the research were Meng Xu, MS, Evan Brittain, MD, MSCI, Eric Farber-Eger, Pankaj Arora, MD, Sheila Collins, PhD, Quinn Wells, MD, PharmD, MSCI, and Thomas Wang, MD. The research was supported by the U.S. Department of Veterans Affairs Clinical Sciences Research and Development Program, Vanderbilt University Medical Center Faculty Research Scholars program and National Institutes of Health (grants HL109019, HL128928, HL146887, HL131532, HL146588, HL125212, HL140074, DK007061, TR000445).
