NT-proBNP Level May Influence HF Risk Among Blacks vs Whites, Men vs Women

Significant differences in the risk of incident heart failure (HF) or death, when stratifying that risk by race and sex, were seen according to N-terminal pro–B-type natriuretic peptide concentration (NT-proBNP) levels in a new subanalysis of data from the Atherosclerosis Risk in the Communities (ARIC), which is an ongoing epidemiologic prospective community-based cohort study.

The findings from this investigation, published online today in JAMA Cardiology, resulted from the authors’ wanting to explore the potential of NT-proBNP as a predictive biomarker for HF. The circulating biomarker is already an established biomarker for HF diagnosis and prognosis, they noted, adding, “There is increasing interest in using circulating biomarkers to predict risk of developing HF, particularly given the emergence of agents that appear particularly efficacious for HF prevention.”

Their primary question they wanted to answer was, are there physiologic determinants of NT-proBNP concentrations that account for sex and race differences in HF risk and the primary outcome, incident HF among the participants who remained alive over the 5-year follow-up.

Levels of the biomarker were evaluated in ARIC study participants during their second study visit (n = 12,750; mean [SD] age, 57.3 [5.7] years), which took place between 1990 and 1992, and their fifth study visit (n = 5191; mean age, 76.0 [5.2] years), which took place between 201 and 2013. Also during the fifth visit, clinical, anthropometric, echocardiographic, and laboratory parameters that may have influenced differences in NT-proBNP concentration were measured.

At both visits, for which the participants had to be free of HF, Black men had the lowest median (IQR) NT-proBNP concentrations and White women had the highest:

• Visit 2:
  • Black men: 30 (14-67) pg/mL
  • White women: 70 (42-111) pg/mL
• Visit 5:
  • Black men: 74 (34-153) pg/mL
  • White women: 154 (82-268) pg-mL

Plus, the authors of the current study highlight that the FDA has NT-proBNP thresholds of below 125 pg/mL for persons 75 years or younger and below 450 pg/mL for persons 75 years and older that should be used to rule out chronic HF. Female vs male sex is also associated with significantly higher concentrations of circulating NT-proBNP.

The median overall NT-proBNP concentration at visit 5 was 124 (64-239) pg/mL.

Older age, White race, female sex, lower socioeconomic status, lower body mass index (BMI),cardiovascular comorbidities, lower estimated glomerular filtration rate (eGFR), greater left ventricular (LV) mass, worse LV function (systolic and diastolic), and higher LV wall stress were shown to be associated with higher NT-proBNP concentration.

In addition, no matter the NT-proBNP concentration, differences persisted among the races and sexes evaluated in this analysis. For Black men, at visit 2, the risk was 7-fold greater (rate ratio [RR], 6.7; 95% CI, 4.6-9.9), and at visit 5, 3-fold greater (RR, 2.7; 95% CI, 1.7-4.1).

For this study, race was self-reported; medical history, participant interview, and medication use helped define hypertension, diabetes, coronary artery disease, and atrial fibrillation; the 2009 Chronic Kidney Disease Epidemiology Collaboration equation calculated eGFR; echocardiography assess heart function; NT-proBNP levels were analyzed from serum samples; and active surveillance was used to capture cardiovascular events.

Additional study findings include the following:

• 19% lower NT-proBNP levels among men vs women from visit 5
• 39% lower NT-proBNP levels in men vs women after accounting for potential confounders (age, race, social determinants of health [SDOH], comorbidities, blood pressure, BMI, fat mass, diabetes, eGFR, LV structure and function) at visit 5
• 38% lower NT-proBNP levels among Blacks vs Whites at visit 5
• 30% lower NT-proBNP levels associated with Black race
• When considering HF risk in midlife:
  • Black men had a higher incident rate vs White men (1.72 vs 1.27 per 100-person years) and Black women had a higher incident rate vs White women (1.21 vs 0.57)
  • Each doubling of NT-proBNP concentration was associated with a 60% higher risk of incident HF or death (HR, 1.60; 95% CI, 1.52-1.68)
  • 4.9% developed HF or died during follow-up
• When considering HF risk in late life:
  • Black men had a higher incident rate vs White men (4.54 vs 3.50) and Black women had a slightly higher incident rate vs White women (2.67 vs 2.65)
  • Each doubling of NT-proBNP concentration was associated with a 55% higher risk of incident HF or death (HR, 1.55; 95% CI, 1.46-1.65)
  • 13.7% developed HF or died

The authors note that a major strength of their results is that they were replicated among 3920 participants in the Cardiovascular Health Study. Moving forward, they do not recommend using a sole NT-proBNP cut point for estimating risk of HF, as this could underestimate risk in Black men and overestimate risk in White women.

“Measurement of NT-proBNP is not a reliable equalizer of risk across these important demographic subgroups [age and sex],” the authors noted. “Consideration of sex and race in interpreting NT-proBNP values allows for more uniform prediction of absolute risk across sexes and races.”

Future studies should investigate how SDOH may influence interindividual differences in NP concentrations, they concluded, which in turn could enable a precision medicine approach for risk prediction in the HF space, as the differences they saw by sex and race “were not fully explained by known physiologic determinates of NT-proBNP.”

Reference

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