Relation of Visceral Adiposity to Circulating Natriuretic Peptides
in Ambulatory Individuals
Susan Cheng, MD
a,b,f
, Caroline S. Fox, MD, MPH
a,g,h
, Martin G. Larson, ScD
a,i
,
Joseph M. Massaro, PhD
a,i
, Elizabeth L. McCabe, MS
a,b
, Abigail May Khan, MD
b
,
Daniel Levy, MD
a,h,j
, Udo Hoffmann, MD
c
, Christopher J. O’Donnell, MD
a,b,h
,
Karen K. Miller, MD
d
, Christopher Newton-Cheh, MD, MPH
a,b,e,l
, Andrea D. Coviello, MD, MS
a,j,k
,
Shalender Bhasin, MD
k
, Ramachandran S. Vasan, MD
a,j
, and Thomas J. Wang, MD
a,b,
*
Natriuretic peptides have important roles in the regulation of vasomotor tone, salt homeo-
stasis, and ventricular remodeling. Lower natriuretic peptide levels observed in obese
individuals may underlie the greater cardiovascular risk associated with obesity. Thus the
aim of this study was to determine whether lower natriuretic peptide levels in obesity are
attributable to differences in regional fat distribution. We investigated the relation of
plasma N-terminal pro–B-type natriuretic peptide (NT–pro-BNP) to regional adiposity in
1,873 community-based individuals (46% women, mean age 45 years). Subcutaneous
adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured by multi-
detector computed tomography. In gender-specific multivariable analyses adjusting for age
and blood pressure, log NT–pro-BNP was inversely associated with VAT in men (beta
؊0.11 per standard deviation increment, p <0.001) and women (beta ؊0.19, p <0.001).
Log NT–pro-BNP was inversely associated with SAT in women only (beta ؊0.14, p
<0.001). In models containing VAT and SAT, only VAT was significantly associated with
log NT–pro-BNP (men, beta ؊0.137, p <0.001; women, beta ؊0.184, p <0.001). VAT
remained associated with log NT–pro-BNP even after adjustment for body mass index and
waist circumference (beta ؊0.119, p <0.001) and in analyses restricted to nonobese patients
(beta ؊0.165, p <0.001). Adjustment for insulin resistance attenuated the associations of
NT–pro-BNP with VAT and SAT. In conclusion, this study demonstrates that circulating
NT–pro-BNP is related to variations in regional and particularly visceral adiposity. These
findings suggest that excess visceral adiposity and concomitant hyperinsulinemia may
contribute to the natriuretic peptide “deficiency” observed in obesity. © 2011 Elsevier Inc.
All rights reserved. (Am J Cardiol 2011;108:979 –984)
It is uncertain whether the link between obesity and
natriuretic peptides is attributable to differences in fat mass
because most studies have used anthropometric measure-
ments to characterize obesity. One previous study has noted
that B-type natriuretic peptide (BNP) levels are inversely
correlated with lean body mass as measured by dual energy
x-ray absorptiometry.
1
Other studies have proposed that
factors such as increased renal clearance of BNP
2
or con-
founding by clinical characteristics
3
may account for the
low natriuretic peptide levels in obesity. Furthermore, it is
unknown whether differences in regional fat distribution are
related to circulating natriuretic peptide levels. The 2 major
fat compartments are subcutaneous and visceral, with the
latter recognized as the more metabolically active and,
hence, pathogenic fat depot.
4
Thus we investigated cross-
sectional relations between plasma N-terminal pro-BNP
(NT–pro-BNP) and visceral and subcutaneous adiposities in
a large community-based sample. Regional adiposity was
assessed using multidetector computed tomography, which
can reliably characterize subcutaneous adipose tissue (SAT)
and visceral adipose tissue (VAT) volumes.
4
Methods
Beginning in 2002 third-generation study participants
(n ϭ 4,095) of the Framingham Heart Study who had Ն1
parent in the Framingham Offspring Study were enrolled
and underwent standard clinic examinations. A subset of
a
Framingham Heart Study, Framingham, Massachusetts;
b
Cardiology
Division,
c
Radiology Department,
d
Neuroendocrine Unit, and
e
Center for
Human Genetic Research, Massachusetts General Hospital, Harvard Med-
ical School, Boston, Massachusetts; Divisions of
f
Cardiovascular Medicine
and
g
Endocrinology, Metabolism and Diabetes, Department of Medicine,
Brigham and Women’s Hospital, Harvard Medical School, Boston, Mas-
sachusetts;
h
Center for Population Studies, National Heart, Lung, and
Blood Institute, Bethesda, Maryland;
i
Department of Mathematics and
Statistics, Boston University, Boston, Massachusetts;
j
Preventive Medicine
and Cardiology Sections, Department of Medicine, and
k
Section of Endo-
crinology, Diabetes and Nutrition, Boston University School of Medicine,
Boston, Massachusetts;
l
Program in Medical and Population Genetics,
Broad Institute of Harvard University and the Massachusetts Institute of
Technology, Cambridge, Massachusetts. Manuscript received March 23,
2011; revised manuscript received and accepted May 25, 2011.
This work was supported in part by Contracts N01-HC-25195 and R01-
HL-086875 from the National Heart, Lung, and Blood Institute of the National
Institutes of Health, Bethesda, Maryland (Dr. Wang and Dr. Newton-Cheh)
and the Ellison Foundation, Bethesda, Maryland (Dr. Cheng).
*Corresponding author: Tel: 617-724-6158; fax: 617-726-4105.
E-mail address: tjwang@partners.org (T.J. Wang).
0002-9149/11/$ – see front matter © 2011 Elsevier Inc. All rights reserved. www.ajconline.org
doi:10.1016/j.amjcard.2011.05.033