N-Terminal Pro-B-Type Natriuretic Peptide Concentrations Vary Substantially by Sex and Race

Biological research
Biological research
A study was conducted to determine if physiologic determinants of NT-proBNP concentrations account for sex and race differences.

The absolute risk of heart failure (HF) associated with a given value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration varies substantially by sex and race, according to a study published in JAMA Cardiology.

Researchers assessed the extent to which interpreting NT-proBNP concentrations with sex and race may better predict absolute HF risk in these subgroups in midlife and late life.

In the ongoing prospective Atherosclerosis Risk in the Communities (ARIC) study, 12,750 participants without HF (aged mean 57.3±5.7 years; 45% men; 25% Black) at study visit 2 (1990-1992) were included for analysis in midlife. A total of 5191 participants without HF (aged mean 76.0±5.2 years; 41% male; 20% Black) at visit 5 (2011-2013) were included for analysis in late life.

The primary outcome was incident HF among participants who were alive in the 5 years of follow-up after visits 2 and 5. All statistical analysis was performed from June 2018 to October 2021.

The investigators also assessed the generalizability of their findings in 3920 participants from the Cardiovascular Health Study (CHS) without HF and who had NT-proBNP measurements during their 1992 to 1993 study visit (aged mean 74.5±5.2 years; 61% women, 17% Black).

The 5191 participants at visit 5 had a median NT-proBNP concentration of 124 pg/mL (IQR, 64-239). At visit 5, the NT-proBNP level was 19% (95% CI, 14%-24%) lower in men compared with women (P <.001). After the investigators accounted for known determinants of NT-proBNP, the NT-proBNP concentrations were 39% (95% CI, 35%-45%) lower in men vs women (P <.001).

Black race was associated with a 30% (95% CI, 24%-36%) lower NT-proBNP concentration in multivariable models that accounted for known determinants of NT-proBNP and included an interaction between race and left ventricular volume.

Of the 12,750 participants at visit 2, the median (IQR) concentration of NT-proBNP was 30 (14-67) pg/mL for Black men, 46 (23-86) pg/mL for Black women, 39 (22-72) pg/mL for White men, and 70 (42-111) pg/mL for White women.

Of this group, 622 (4.9%) developed HF or died during the 5-year follow-up (incidence rate, 1.02 per 100 person-years [95% CI, 0.94-1.10]; 324 incident HF and 601 died). The incidence rate per 100 person-years was 1.72 (95% CI, 1.41-2.10) for Black men, 1.27 (95% CI, 1.13-1.43) for White men, 1.21 (95% CI, 1.01-1.46) for Black women, and 0.57 (95% CI, 0.48-0.67) for White women.

Increased concentrations of NT-proBNP were associated with a greater risk for incident HF or death after adjustment for age, sex, race, comorbidities, blood pressure, BMI, and estimated glomerular filtration rate (hazard ratio [HR] per doubling, 1.60; 95% CI, 1.52-1.68; P <.001). Stronger associations were found in White participants (HR, 1.71; 95% CI, 1.60-1.83) vs Black participants (HR, 1.49; 95% CI, 1.38-1.61; P for interaction =.02).

The predicted risk corresponding with a given NT-proBNP concentration varied substantially between sex- and race-based categories. A guideline-recommended NT-proBNP threshold was associated with a 6.7-fold (95% CI, 4.6-9.9) difference in predicted rate of incident HF or death for White women compared with Black men. The differences in absolute predicted risk between sex- and race-based categories were greater for higher NT-proBNP concentrations.

For the CHS participants without HF, NT-proBNP levels greater than guideline-recommended thresholds were associated with a 4-fold lower difference in the incidence rate of HF or death for White women compared with Black men (incidence rate per 100 person-years, 2.8 [95% CI, 2.4-3.3] vs 11.0 [95% CI, 7.8-15.6]; rate ratio, 4.0; 95% CI, 2.7-5.8), with intermediate incidence rates among Black women and White men.

Among several study limitations, the number of Black participants was limited, and the population included participants in a community-based prospective cohort. In addition, the researchers did not have measurements of biologically active NPs, such as B-type NP and A-type NP.

“Important sex- and race-based differences in risk of HF or death exist and NT-proBNP is not a reliable equalizer of risk across these important demographic subgroups,” the investigators concluded. “Consideration of NT-proBNP values in the context of sex and race allows for more uniform prediction of absolute risk across sexes and races.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Myhre PL, Claggett B, Yu B, et al. Sex and race differences in N-terminal pro–B-type natriuretic peptide concentration and absolute risk of heart failure in the community. JAMA Cardiol. Published online April 27, 2022. doi: 10.1001/jamacardio.2022.0680