Current US heart failure guidelines that use a single cut point for natriuretic peptides (NPs) can underestimate the risk for the disease for people with obesity, according to a study published recently in Circulation: Heart Failure.

The 2022 joint guidelines from the American Heart Association, the American College of Cardiology, and the Heart Failure Society of America added NP as a biomarker for higher risk, with a threshold of 125 pg/mL to up-classify individuals from stage A (at-risk) to stage B (pre-heart failure).

But concentrations of the proteins typically are lower in people with obesity, said Jennifer Ho, MD, a cardiologist at Harvard Medical School in Boston, so she wondered whether clinicians who follow the recommendations might be underestimating the risk for heart failure in their patients with obesity.

Lower Classification Rates in Obesity

Using the pooled data from more than 32,000 people without heart failure enrolled in community-based cohorts, Ho and her colleagues classified their risk for heart failure using both the 2013 guidelines, which did not include NP levels, and the 2022 guidelines, taking into account their obesity status.

They found the single cut point resulted in fewer individuals with obesity being up-classified to stage B heart failure than normal-weight individuals. The proportion up-classified to stage B using the NP levels was 62% among those with normal weight, 51% among those who were overweight, 47% among individuals with obesity class 1, and 42% among those with obesity class 2/3.

“The majority of the discrepancy is because of the reclassification on the basis of NP levels,” Ho said. “This suggests patients with obesity need a lower threshold to capture their risk.”

The optimal cut point to assess the risk for future heart failure was lower in people with obesity (80 pg/mL) than in people of normal weight (109 pg/mL), the study found.

Guideline Implications

Paul Heidenreich, MD, a cardiologist at Stanford University in Stanford, California, and a coauthor of the 2022 guidelines, said the guideline committee was aware of this issue and mentioned it in the document. But without solid data on how thresholds should differ, they felt they should include a general number, with the caveat that some people would likely have different thresholds.

“Whenever you give a number, some people will latch on to it too strongly, but it is better to have something than nothing, even if it is not perfect for everyone,” said Heidenreich, who was not involved in the new research.

Ho’s study is helpful, he added, because it provides a starting point for developing new thresholds that could be incorporated into the next set of guidelines. He said he expects future guidelines will include a matrix of NP thresholds, adjusted not just for obesity but for kidney disease and other conditions that can change levels of the protein.

In the meantime, Heidenreich urged clinicians to keep in mind that NPs are far from the only things that affect the risk for heart failure. “You need to think about all the other characteristics that might influence that threshold,” he said.

Ho and Heidenreich reported having no financial conflicts of interest.

Brian Owens is a freelance writer in New Brunswick, Canada.