NTproBNP levels differ by race, but association of NTproBNP levels and mortality does not
Racial Differences in Plasma Levels of N-Terminal Pro–B-Type Natriuretic Peptide and Outcomes The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Literature - Bajaj NS, Gutierrez OM, Arora G, et al. - JAMA Cardiol. 2018;3(1):11Background
Natriuretic peptide (NP) deficiency has been found in obese persons and in individuals with common genetic variants, but data on the association between race and NP levels are conflicting [1]. Two recent studies suggested that black individuals have lower NTproBNP levels compared with white individuals [2,3], which could lead to a higher risk of hypertension and HF in black individuals. In this analysis of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study [4], the plasma N-terminal pro-B-type NP (NTproBNP) levels were compared in black versus white healthy individuals, and the associations between racial differences in NP levels and all-cause mortality, CV mortality, non-CV mortality, and incident hypertension were evaluated.
For the present analysis, a random cohort of 4415 REGARDS participants was selected for NTproBNP measurement using an electrochemiluminescence immunoassay. Hispanic participants, those with missing NTproBNP levels, as well as those with prevalent CV or cerebrovascular disease, atrial fibrillation, or renal dysfunction were excluded, leaving a cohort of 1998 healthy participants, who were stratified by age, gender, and race. The NTproBNP differences were compared and pooled with published results from the Dallas Heart Study (DHS) and the Atherosclerosis Risk in Communities (ARIC) study [2,3].
Main results
- In all 3 cohorts, NTproBNP levels in black participants were significantly lower compared with white participants: median NTproBNP in REGARDS 46 pg/mL vs. 60 pg/mL; in DHS 24 pg/mL vs. 32 pg/mL; in ARC 43 pg/mL vs. 68 pg/mL.
- In the REGARDS study, NTproBNP levels in black participants were 21% lower in an unadjusted linear regression model (β: -0.24; 95%CI: -0.32 to -0.17; P<0.001), and 27% lower after multivariate adjustment (β: -0.32; 95%CI: -0.40 to -0.24; P<0.001).
- In all 3 cohorts together, the multivariable-adjusted NTproBNP was 35% lower in black compared with white participants (95%CI: -42.31 to -26.66; P<0.001).
- In the REGARDS study, during a median follow-up of 8.4 years (IQR: 6.9-10.7), for every 1-SD increment in log NTproBNP levels, there was a 87% increase in the risk of death for the overall population (HR:1.87; 95%CI:1.64-2.13, P<0.001) and the risk was increased by 31% in the adjusted model (HRadj: 1.31; 95%CI: 1.11-1.54; P=0.001).
- After multivariable adjustment for established risk factors, incident rates of all-cause mortality, CV mortality, and non-CV mortality were similar in black participants as compared with white participants. No interaction between race and NTproBNP levels on all-cause mortality, CV mortality, and non-CV mortality was seen.
- There was no difference in the risk of incident hypertension in black compared with white participants, nor was there an association or racial interaction between NTproBNP and change in systolic or diastolic BP.
Conclusion
Healthy black adults have significantly lower NTproBNP levels compared with white individuals. This difference between the groups did not modify the association between baseline NTproBNP levels and the risk of all-cause and CV mortality.
Editorial comment
In his editorial article [5], Wang explains the pathophysiological importance of natriuretic peptides as protective cardio-renal and cardio-metabolic hormones, although they are primarily used as biomarker in the clinical setting: ‘Physicians are accustomed to thinking of BNP as a bad thing because elevated BNP is seen in patients with overt heart failure and frequently portends a poor prognosis. Of course, the problem is not the BNP itself, but the condition that causes the BNP to be elevated. Indeed, natriuretic peptide production is an important component of the body’s defense against cardiac overload.’
Moreover, he discusses potential pharmacologic and non-pharmacologic specific therapeutic approaches for individuals with natriuretic peptide deficiency and he concludes: ‘Endocrine therapies are administered to individuals with specific evidence of endocrine dysfunction, not to capture short-term beneficial effects. For instance, thyroid hormone is given only to patients in whom hypothyroidism is demonstrated, not based on its metabolic actions. Studies are warranted to determine whether a similar strategy for the heart’s endocrine system can advance the prevention and treatment of cardiometabolic disease.’