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The same N-terminal pro-B-type natriuretic peptides (NT-proBNP) concentration could mean drastically different absolute risks of heart failure (HF) for different demographics, according to a cohort study suggesting the importance of sex and race in interpreting risk for people free of HF at baseline.

In the longitudinal Atherosclerosis Risk in Communities (ARIC) cohort, Black men, compared with white women, had up to a seven-fold higher risk of incident HF or death in midlife than predicted based on the same guideline-recommended threshold for NT-proBNP, reported Amil Shah, MD, MPH, of Brigham and Women's Hospital in Boston, and colleagues.

Thresholds of midlife NT-proBNP associated with a 10% 5-year risk of incident HF or death varied for different groups:

• Black men: 76 pg/mL (95% CI 53-107)

• White men: 116 pg/mL (95% CI 95-125)

• Black women: 188 pg/mL (95% CI 142- 250)

• White women: 402 pg/mL (95% CI 312-597)

Absolute differences in risk between groups widened at higher NT-proBNP concentrations, and the results were replicated in a cohort of people from the Cardiovascular Health Study, Shah's group showed in a paper .

"Prevailing clinical practice guidelines establish singular thresholds for biomarker elevations that signal higher risk for HF, but how well does a one-size-fits-all threshold work across different sex and self-described racial groups?" asked Clyde Yancy, MD, MSc, and Sadiya Khan, MD, MSc, both of Northwestern University Feinberg School of Medicine in Chicago and both JAMA Cardiology editors.

"Use of the singular standards set in the guidelines fails to accurately discriminate risk and may underestimate risk in men of African ancestry. Tailored NT-proBNP thresholds, perhaps based on these ARIC data, may refine risk calculation and advance incorporation of sex- and ancestry-specific biomarker thresholds into more comprehensive risk assessment models that may enhance opportunities to prevent disease," Yancy and Khan wrote in an .

Shah and colleagues suggested using these thresholds as part of the decision-making around preventive therapies for HF, similar to the recommended system for primary prevention of coronary artery disease.

In the study, among ARIC participants in midlife and late life, Black men consistently had the lowest NT-proBNP concentrations (30 pg/mL and 74 pg/mL, respectively), whereas white women had the highest concentrations (70 pg/mL and 154 pg/mL, respectively).

Sex and race differences in NT-proBNP concentration persisted after accounting for known physiologic determinants, including age, income, education, area deprivation index, cardiovascular diseases, left ventricular (LV) structure, LV function, LV wall stress, weight and fat mass, and estimated glomerular filtration rate.

Black men are known to be more prone to heart failure even after accounting for established cardiovascular risk factors.

"Differences in circulating NP [natriuretic peptide] concentrations by sex and race and ethnicity are well recognized, and contributions from sex hormones and genetic ancestry have been proposed," Shah and colleagues wrote.

"Future studies incorporating detailed measures of the range of social drivers of health to explain interindividual differences in NP concentrations offer promise of a precision medicine approach to using NPs for risk prediction. Until such data are available, interpreting NT-proBNP values in the context of sex and race may improve the uniformity of predicted HF risk across important demographic subgroups in the population," the investigators proposed.

is an ongoing prospective community-based cohort study that enrolled people in 1987-1989. Shah's group relied on data from study visit 2 (1990-1992) and study visit 5 (2011-2013) for the present analysis. The authors included people free of HF in midlife and late life, respectively, at those visits.

The 5,191 individuals from visit 5 averaged 76.0 years of age. Men and Black people each accounted for 41% and 20%, respectively, of the overall cohort.

The relatively low number of Black individuals was a limitation of the study, as was the fact that not all surviving ARIC participants attended visits 2 and 5, the researchers noted.

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