Racial differences in circulating natriuretic peptide levels: the atherosclerosis risk in communities study

Deepak K Gupta, Brian Claggett, Quinn Wells, Susan Cheng, Man Li, Nisa Maruthur, Elizabeth Selvin, Josef Coresh, Suma Konety, Kenneth R Butler, Thomas Mosley, Eric Boerwinkle, Ron Hoogeveen, Christie M Ballantyne, Scott D Solomon, Deepak K Gupta, Brian Claggett, Quinn Wells, Susan Cheng, Man Li, Nisa Maruthur, Elizabeth Selvin, Josef Coresh, Suma Konety, Kenneth R Butler, Thomas Mosley, Eric Boerwinkle, Ron Hoogeveen, Christie M Ballantyne, Scott D Solomon

Abstract

Background: Natriuretic peptides promote natriuresis, diuresis, and vasodilation. Experimental deficiency of natriuretic peptides leads to hypertension (HTN) and cardiac hypertrophy, conditions more common among African Americans. Hospital-based studies suggest that African Americans may have reduced circulating natriuretic peptides, as compared to Caucasians, but definitive data from community-based cohorts are lacking.

Methods and results: We examined plasma N-terminal pro B-type natriuretic peptide (NTproBNP) levels according to race in 9137 Atherosclerosis Risk in Communities (ARIC) Study participants (22% African American) without prevalent cardiovascular disease at visit 4 (1996-1998). Multivariable linear and logistic regression analyses were performed adjusting for clinical covariates. Among African Americans, percent European ancestry was determined from genetic ancestry informative markers and then examined in relation to NTproBNP levels in multivariable linear regression analysis. NTproBNP levels were significantly lower in African Americans (median, 43 pg/mL; interquartile range [IQR], 18, 88) than Caucasians (median, 68 pg/mL; IQR, 36, 124; P<0.0001). In multivariable models, adjusted log NTproBNP levels were 40% lower (95% confidence interval [CI], -43, -36) in African Americans, compared to Caucasians, which was consistent across subgroups of age, gender, HTN, diabetes, insulin resistance, and obesity. African-American race was also significantly associated with having nondetectable NTproBNP (adjusted OR, 5.74; 95% CI, 4.22, 7.80). In multivariable analyses in African Americans, a 10% increase in genetic European ancestry was associated with a 7% (95% CI, 1, 13) increase in adjusted log NTproBNP.

Conclusions: African Americans have lower levels of plasma NTproBNP than Caucasians, which may be partially owing to genetic variation. Low natriuretic peptide levels in African Americans may contribute to the greater risk for HTN and its sequalae in this population.

Keywords: ancestry informative markers; deficiency; hypertension; natriuretic peptide; race.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Cumulative distribution plot of log NTproBNP levels according to race in ARIC. Natural log NTproBNP values are lower in African Americans, as compared to Caucasians (P<0.001). For example, the frequency of natural log NTproBNP levels ≤4 (NTproBNP=54.6 pg/mL) is ≈60% in African Americans, compared to 40% of Caucasians. The lower limit of the natural log of NTproBNP is truncated at 0.92 based upon the lowest value of NTproBNP of 2.5 pg/mL. ARIC indicates Atherosclerosis Risk in Communities; NTproBNP, N-terminal pro B-type natriuretic peptide.
Figure 2
Figure 2
Forest plot of percent difference in log NTproBNP levels in African Americans, compared to Caucasians, overall and across subgroups of ARIC participants. African-American race is significantly associated with lower NTproBNP levels, as compared to Caucasians, in the overall study population and within subgroups. Values shown are from multivariable adjusted linear regression analyses (see Methods for covariates). For the insulin-resistant subgroups, HOMA-IR was included as an additional covariate in the multivariable adjusted analyses. ARIC indicates Atherosclerosis Risk in Communities; HOMA-IR, homeostatic model for assessment of insulin resistance; NTproBNP, N-terminal pro B-type natriuretic peptide.
Figure 3
Figure 3
The relationship between genetically determined percent European ancestry and plasma NTproBNP levels among self-reported African Americans in ARIC. Among self-reported African Americans, with increasing proportion of European ancestry, there is a significant increase in plasma NTproBNP levels. ARIC indicates Atherosclerosis Risk in Communities; NTproBNP, N-terminal pro B-type natriuretic peptide.

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