BIRMINGHAM, AL — In a cohort free of cardiovascular disease, serum levels of the commonly used diagnostic biomarker N-terminal pro–B-type natriuretic peptide (NT-proBNP) were 27 % lower in African Americans than in whites[1].
However, as levels of this biomarker increased, the risk of dying during follow-up increased in both racial groups, new REGARDS data show.
“This finding suggests that higher NT-proBNP levels are associated with similar increases in the risk of all-cause mortality in black and white individuals even though black individuals on average have lower NT-proBNP levels than white individuals,” Dr Navkaranbir S Bajaj (University of Alabama, Birmingham) and colleagues summarize in their study, published online November 22, 2017 in JAMA Cardiology.
Previous studies have shown that levels of this biomarker are low in obese patients, and now this research suggests that African Americans have a natriuretic peptide deficiency, senior author Dr Pankaj Arora (University of Alabama) told theheart.org | Medscape Cardiology.
The group found similar racial differences in NT-proBNP in a pooled analysis of data from REGARDS, the Dallas Heart Study, and the ARIC study.
Clinicians need to be aware that an African American patient with heart failure “wouldn’t be able to bump up their numbers to a level where somebody with an adequate natriuretic peptide system would,” Arora said.
“If you measure a BNP level in someone who’s obese or someone who’s African American, their levels may be lower than you would expect,” Dr Thomas J Wang (Vanderbilt University, Nashville, TN) echoed in a comment to theheart.org | Medscape Cardiology. Wang wrote an editorial that accompanies the article[2].
“Collectively, the data from REGARDS and other studies provide persuasive evidence that racial/ethnic differences in circulating natriuretic peptides are real,” he notes.
Cardiac wall stress should trigger increased natriuretic peptide production. However, if African Americans have a relative natriuretic peptide deficiency, this would make them more prone to hypertension, salt overload, and left ventricular hypertrophy; and individuals who are both African American and obese may be particularly susceptible to these adverse consequences.
Natriuretic Peptide Deficiency in African Americans?
BNP, a hormone synthesized by the heart in response to increased myocardial wall stress, is a “gold-standard” biomarker and used extensively for the diagnosis and prognosis of cardiovascular disease, especially heart failure, said Arora.
BNP has a number of beneficial effects, said Wang, including diuresis, vasodilation, and cardiac remodeling. However, recent studies have suggested that the BNP system may be suppressed in African Americans who are free of prevalent cardiovascular disease, and this may be tied to mortality outcomes.
To investigate this, the researchers analyzed data from REGARDS, a national sample of 4415 healthy participants age 45 and older. They identified 1998 participants (mean age 63 years) who did not have prevalent cardiovascular disease, defined as coronary artery disease, stroke, transient ischemic attack, atrial fibrillation, peripheral vascular disease, aortic aneurysm, heart failure, or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2.
Just under half the participants were female (49%), 35% were obese, and 49% were black. The median NT-proBNP was 53 pg/mL, determined by an immunoassay.
Compared with white participants, African American participants had a higher median systolic blood pressure (129 vs 121 mm Hg) and body-mass index (BMI; 29 vs 27 kg/m2). They were more likely to have type 2 diabetes (24% vs 11%) and to smoke (17% vs 11%), but less likely to be current alcohol drinkers (45% vs 64%).
The median NT-proBNP level was significantly lower in African Americans than in whites (46 vs 60 pg/mL; P<0.001).
The NT-proBNP level was 27% lower in African Americans than in whites (P<0.001), after adjustment for age, sex, income, college education, exercise, smoking, alcohol, BMI, systolic blood pressure, antihypertensive medications, aspirin use, hyperlipidemia, diabetes, and eGFR.
The median NT-proBNP level was 46, 24, and 43 pg/mL in the 1998 participants in REGARDS, 2575 participants in the Dallas Heart Study, and 9137 participants in ARIC, respectively, who were all free of CVD.
In this pooled cohort, the median adjusted NT-proBNP level was 35% lower in African Americans than in whites (P<0.001).
During a median follow-up of 8.4 years in REGARDS, 155 black patients and 124 white patients died.
For every one-standard-deviation higher log NT-proBNP, there was a 31% increased adjusted risk of death (hazard ratio [HR] 1.31; P=0.001), which was driven by an increase in CV mortality (HR 1.69; P=0.004).
NT-proBNP levels were not associated with changes in hypertension.
Future Research Directions
The group plans to investigate whether the effects of sacubitril/valsartan (Entresto, Novartis), which augments natriuretic peptide and was approved in the US in 2015 for treating heart failure, are different in people who are deficient in natriuretic peptide, including those with genetic variance, obese people, and African Americans.
NP-proBNP production is known to increase with exercise, so “a key piece of missing information” is whether the response to exercise is the same in African Americans and whites, Arora said.
In a number of clinical heart-failure trials, especially heart failure with preserved ejection fraction, patients with NT-proBNP levels below a certain cut point were excluded, Wang noted. “People who design trials should recognize that this might have the unintended consequence of including fewer African Americans, because they tend to have lower levels.”
The study was supported by grants from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Department of Health and Human Services. The authors and Wang have no relevant financial relationships .
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