Plasma Adiponectin and the Risk of Hypertension in White
and Black Postmenopausal Women
Lu Wang,1*JoAnn E. Manson,1,2J. Michael Gaziano,1,3,4Simin Liu,5Barbara Cochrane,6Nancy R. Cook,1
Paul M Ridker,1,7Nader Rifai,8and Howard D. Sesso1,2,3
BACKGROUND: Adiponectin may have a protective role
in the development of obesity-related metabolic and
vascular disorders, including hypertension. We con-
ducted a prospective, nested case control study to in-
vestigate the relation between baseline plasma adi-
METHODS: We selected 400 white and 400 black post-
cident hypertension during 5.9-year follow-up and an
Women’s Health Initiative Observational Study. We
measured plasma concentrations of total adiponectin
in their baseline blood samples.
RESULTS: In crude matched models, plasma adiponec-
tin was inversely associated with risk of hypertension
among both white and black women. The association
appeared to be nonlinear in white women but dose
related in black women. Adjustment for lifestyle fac-
tors, measures of obesity, and obesity-related clinical
factors attenuated these associations. The multivari-
able relative risk (95% CI) of hypertension across in-
creasing quartiles of plasma adiponectin were 1.00,
0.98 (0.66–1.46), 0.63 (0.41–0.97), and 0.92 (0.60–
1.42) in white women (Ptrend: 0.38) and 1.00, 0.96
(0.64–1.46), 0.83 (0.53–1.29), and 0.58 (0.36–0.94) in
black women (Ptrend: 0.02). Further adjustment for in-
flammatory markers and endothelial markers elimi-
nated the association in white, but not black, women.
CONCLUSIONS: In this prospective, nested case control
adiponectin and risk of hypertension in white and
tions of adiponectin in white women whereas it was
© 2012 American Association for Clinical Chemistry
Obesity is a modifiable risk factor for hypertension.
Measures of obesity such as high body mass index
(BMI)9are consistently associated with increases in
blood pressure (BP) and a greater risk of hypertension
(1–3). Conversely, weight loss among overweight and
obese individuals has shown BP-lowering benefits
(4, 5). The mechanisms underlying these observations
of biologically active compounds. These compounds,
collectively known as adipokines, have profound ef-
fects on metabolism and vasculature, and potentially
play important roles in the pathogenesis of obesity-
related disorders, including hypertension (6).
secreted exclusively by adipocytes (7). Concentrations
Laboratory studies show that adiponectin suppresses
including insulin resistance, endothelial dysfunction,
inflammation, and atherosclerosis (7). Epidemiologic
studies have provided evidence for hypoadiponectine-
mia as an independent risk factor for type 2 diabetes
(10, 11) and coronary heart disease (12). Despite sev-
inverse association between plasma adiponectin and
BP levels or hypertension status (13–16), prospective
1Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA;
2Department of Epidemiology, Harvard School of Public Health, Boston, MA;
3Division of Aging, Brigham and Women’s Hospital, Boston, MA;4Massachu-
setts Veterans Epidemiology Research and Information Center, VA Boston
Healthcare System, Jamaica Plain, MA;5Departments of Epidemiology and
Medicine, Center for Metabolic Disease Prevention, University of California Los
Angeles, Los Angeles, CA;
Seattle, WA;7Division of Cardiovascular Medicine, Brigham and Women’s
Hospital, Boston, MA;8Department of Laboratory Medicine, Boston Children’s
Hospital, Boston, MA.
6University of Washington School of Nursing,
* Address correspondence to: Brigham and Women’s Hospital, 900 Common-
wealth Ave., Boston MA 02215. Fax 617-731-3843; e-mail firstname.lastname@example.org.
Received June 8, 2012; accepted July 11, 2012.
Previously published online at DOI: 10.1373/clinchem.2012.191080
9Nonstandard abbreviations: BMI, body mass index; BP, blood pressure; WHI-OS,
Women’s Health Initiative-Observational Study; SBP, systolic BP; DBP, diastolic
BP; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6; sICAM-1,
soluble intercellular adhesion molecule-1; RR, relative risk.
Clinical Chemistry 58:10
Evidence-Based Medicine and Test Utilization
13. Iwashima Y, Katsuya T, Ishikawa K, Ouchi N,
Ohishi M, Sugimoto K, et al. Hypoadiponectine-
mia is an independent risk factor for hyperten-
sion. Hypertension 2004;43:1318–23.
14. Adamczak M, Wiecek A, Funahashi T, Chudek J,
Kokot F, Matsuzawa Y. Decreased plasma adi-
ponectin concentration in patients with essential
hypertension. Am J Hypertens 2003;16:72–5.
15. Huang KC, Chen CL, Chuang LM, Ho SR, Tai TY,
Yang WS. Plasma adiponectin levels and blood
pressures in nondiabetic adolescent females.
J Clin Endocrinol Metab 2003;88:4130–4.
16. Yamamoto Y, Hirose H, Saito I, Tomita M,
Taniyama M, Matsubara K, et al. Correlation of
the adipocyte-derived protein adiponectin with
insulin resistance index and serum high-density
lipoprotein-cholesterol, independent of body
mass index, in the Japanese population. Clin Sci
17. Chow WS, Cheung BM, Tso AW, Xu A, Wat NM,
Fong CH, et al. Hypoadiponectinemia as a pre-
dictor for the development of hypertension: a
5-year prospective study. Hypertension 2007;49:
18. Imatoh T, Miyazaki M, Momose Y, Tanihara S,
Une H. Adiponectin levels associated with the
development of hypertension: a prospective
study. Hypertens Res 2008;31:229–33.
19. Asferg C, Mogelvang R, Flyvbjerg A, Frystyk J,
Jensen JS, Marott JL, et al. Leptin, not adiponec-
tin, predicts hypertension in the Copenhagen city
heart study. Am J Hypertens 2010;23:327–33.
20. Burt VL, Whelton P, Roccella EJ, Brown C, Cutler
JA, Higgins M, et al. Prevalence of hypertension
in the us adult population. Results from the Third
National Health and Nutrition Examination Sur-
vey, 1988–1991. Hypertension 1995;25:305–13.
21. Chaturvedi N, McKeigue PM, Marmot MG. Rest-
ing and ambulatory blood pressure differences in
Afro-Caribbeans and Europeans. Hypertension
22. Hulver MW, Saleh O, MacDonald KG, Pories WJ,
Barakat HA. Ethnic differences in adiponectin lev-
els. Metabolism 2004;53:1–3.
23. Cohen SS, Gammon MD, North KE, Millikan RC,
Lange EM, Williams SM, et al. Adipoq, adipor1,
and adipor2 polymorphisms in relation to serum
adiponectin levels and BMI in black and white
women. Obesity 2011;19:2053–62.
24. Anderson GL, Manson J, Wallace R, Lund B, Hall
D, Davis S, et al. Implementation of the women’s
health initiative study design. Ann Epidemiol
25. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki
H, Uchida S, et al. Adiponectin stimulates glucose
utilization and fatty-acid oxidation by activating
amp-activated protein kinase. Nat Med 2002;8:
26. Ikeda T, Gomi T, Hirawa N, Sakurai J, Yoshikawa
N. Improvement of insulin sensitivity contributes
to blood pressure reduction after weight loss in
hypertensive subjects with obesity. Hypertension
27. Ferrier KE, Muhlmann MH, Baguet JP, Cameron
JD, Jennings GL, Dart AM, Kingwell BA. Intensive
cholesterol reduction lowers blood pressure and
large artery stiffness in isolated systolic hyperten-
sion. J Am Coll Cardiol 2002;39:1020–5.
28. Chen H, Montagnani M, Funahashi T, Shimomura
I, Quon MJ. Adiponectin stimulates production of
nitric oxide in vascular endothelial cells. J Biol
29. Matsuda M, Shimomura I, Sata M, Arita Y,
Nishida M, Maeda N, et al. Role of adiponectin in
preventing vascular stenosis. The missing link of
adipo-vascular axis. J Biol Chem 2002;277:
30. Yokota T, Oritani K, Takahashi I, Ishikawa J,
Matsuyama A, Ouchi N, et al. Adiponectin, a new
member of the family of soluble defense colla-
gens, negatively regulates the growth of myelo-
monocytic progenitors and the functions of mac-
rophages. Blood 2000;96:1723–32.
31. Motoshima H, Wu X, Mahadev K, Goldstein BJ.
Adiponectin suppresses proliferation and su-
peroxide generation and enhances eNOS activ-
ity in endothelial cells treated with oxidized
LDL. Biochem Biophys Res Commun 2004;315:
32. Mallamaci F, Zoccali C, Cuzzola F, Tripepi G,
Cutrupi S, Parlongo S, et al. Adiponectin in es-
sential hypertension. J Nephrol 2002;15:507–11.
33. Lovejoy JC, de la Bretonne JA, Klemperer M,
Tulley R. Abdominal fat distribution and meta-
bolic risk factors: effects of race. Metabolism
34. Kanaya AM, Wassel Fyr C, Vittinghoff E, Havel PJ,
Cesari M, Nicklas B, et al. Serum adiponectin and
coronary heart disease risk in older Black and
White Americans. J Clin Endocrinol Metab 2006;
35. Ukkola O, Santaniemi M, Rankinen T, Leon AS,
Skinner JS, Wilmore JH, et al. Adiponectin poly-
morphisms, adiposity and insulin metabolism:
HERITAGE family study and Oulu diabetic study.
Ann Med 2005;37:141–50.
36. Whelton PK, He J, Appel LJ, Cutler JA, Havas S,
Kotchen TA, et al. Primary prevention of
hypertension: clinical and public health advisory
from The National High Blood Pressure Education
Program. JAMA 2002;288:1882–8.
37. Chobanian AV, Bakris GL, Black HR, Cushman
WC, Green LA, Izzo JL Jr, et al. The Seventh
Report of the Joint National Committee on Pre-
vention, Detection, Evaluation, and Treatment of
High Blood Pressure: the JNC 7 report. JAMA
38. Frohlich ED, Susic D. Mechanisms underlying obe-
sity associated with systemic and renal hemody-
namics in essential hypertension. Curr Hypertens
39. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S,
Kita S, et al. Impaired multimerization of human
adiponectin mutants associated with diabetes.
Molecular structure and multimer formation of
adiponectin. J Biol Chem 2003;278:40352–63.
40. Glintborg D, Frystyk J, Hojlund K, Andersen KK,
Henriksen JE, Hermann AP, et al. Total and high
molecular weight (HMW) adiponectin levels and
measures of glucose and lipid metabolism follow-
ing pioglitazone treatment in a randomized
placebo-controlled study in polycystic ovary syn-
drome. Clin Endocrinol 2008;68:165–74.
Plasma Adiponectin and Hypertension Risk
Clinical Chemistry 58:10 (2012)