A peptide used as the “gold standard” for diagnosis heart failure loses predictive ability in African Americans. A new study published in JCI Insight by University of Alabama at Birmingham researchers shows that the ability to predict the risk of heart failure using N-terminal pro-B-type natriuretic peptide (NTproBNP) levels is reduced in African Americans with obesity or impaired kidney function. NTproBNP is a peptide which is widely used clinically to predict heart failure.
Nirav Patel, M.D., a heart failure fellow in the Division of Cardiovascular Disease, explained that the human heart is an endocrine organ and produces hormones called natriuretic peptides. Natriuretic peptides, especially NTproBNP, are routinely used as “gold-standard” biomarkers for diagnosis and prognosis of cardiovascular diseases such as heart failure in clinical practice.
In the current study, authors tested the hypothesis that the association between NTproBNP and incident heart failure differ by race, and further explore whether the risk of incident heart failure predicted by NTproBNP levels across body mass index and kidney function categories differ by race.
To investigate, Patel and his team examined racial differences in NTproBNP levels in in more than 30,000 American adults age 45 or older enrolled in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study — an ongoing NIH-sponsored observational study of stroke risk factors assessed by region and race.
Patel, first author of the JCI Insight study, designed and conducted the analyses for the study. He said the REGARDS study offers a unique opportunity to examine the race-specific risk associated with NTproBNP for incident heart failure, including in subgroups who are obese or have impaired kidney function in a large, biracial population of United States adults.
Race, increasing age, sex, obesity, and impaired kidney function affect circulating natriuretic peptide levels,” Patel said. “However, there is little known about the relationship of NTproBNP with incident heart failure across BMI and kidney function categories among African-American individuals, a key racial group at risk for heart failure.”
The researchers found that higher NTproBNP was strongly associated with incident heart failure independent of sociodemographic and clinical risk factors. The risk of heart failure predicted by NTproBNP levels was preserved across BMI and kidney function categories among Caucasians. However, the predictive ability of NTproBNP for incident heart failure was diminished among African Americans with obesity or impaired kidney function.
“We speculate that African-American individuals, when exposed to increased wall stress such as pressure and volume overload, may not able to mount an appropriate natriuretic peptide response as compared with Caucasians,” said senior author Pankaj Arora M.D., an assistant professor in UAB’s Division of Cardiovascular Disease. “This may be a reason behind the marked underrepresentation of African Americans in the clinical trials where recruitment was based on natriuretic peptide levels.”
Arora also stressed that the decrease in the predictive ability of NTproBNP in African Americans with severe obesity and impaired kidney function suggest that race-specific cutoff values — the upper limit for normal natriuretic peptide levels — for the diagnosis of heart failure and when NTproBNP is used to drive enrollment in clinical trials may be necessary.
“Currently, the guidelines provide only age-stratified NTproBNP cutoff values for the diagnosis and prognosis of heart failure,” Arora said. “In an era of precision medicine, our study suggests that to improve the accuracy of risk prediction models using NTproBNP levels for incident heart failure, we need to account for other factors that can affect natriuretic peptide levels, such as race, BMI, and kidney function.”