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Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:434-439
Published online before print January 30, 2003, doi: 10.1161/01.ATV.0000058402.34138.11
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:434.)
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Atherosclerosis and Lipoproteins

Obesity and Systemic Oxidative Stress

Clinical Correlates of Oxidative Stress in The Framingham Study

John F. Keaney, Jr; Martin G. Larson; Ramachandran S. Vasan; Peter W.F. Wilson; Izabella Lipinska; Diane Corey; Joseph M. Massaro; Patrice Sutherland; Joseph A. Vita; Emelia J. Benjamin

From the Evans Memorial Department of Medicine (J.F.K. R.S.V., P.W.F.W., J.A.V., E.J.B.), Whitaker Cardiovascular Institute (J.F.K., I.L., J.A.V.), and Department of Preventive Medicine (R.S.V., E.J.B.), Boston University School of Medicine; Department of Epidemiology and Biostatistics (J.M.M.), Boston University School of Public Health; and the National Heart, Lung, and Blood Institute Framingham Study (M.G.L., R.S.V., P.W.F.W., D.C., J.M.M., P.S., E.J.B.), Framingham, MA.

Correspondence to J.F. Keaney, Jr, Boston University School of Medicine, Whitaker Cardiovascular Institute, 715 Albany St, Rm W507, Boston, MA 02118. E-mail jkeaney{at}bu.edu

Objective— To determine the clinical conditions associated with systemic oxidative stress in a community-based cohort. Information regarding cardiovascular risk factors associated with systemic oxidative stress has largely been derived from highly selected samples with advanced stages of vascular disease. Thus, it has been difficult to evaluate the relative contribution of each cardiovascular risk factor to systemic oxidative stress and to determine whether such risk factors act independently and are applicable to the general population.

Methods and Results— We examined 2828 subjects from the Framingham Heart Study and measured urinary creatinine–indexed levels of 8-epi-PGF2{alpha} as a marker of systemic oxidative stress. Age- and sex-adjusted multivariable regression models were used to assess clinical correlates of oxidative stress. In age- and sex-adjusted models, increased urinary creatinine–indexed 8-epi-PGF2{alpha} levels were positively associated with female sex, hypertension treatment, smoking, diabetes, blood glucose, body mass index, and a history of cardiovascular disease. In contrast, age and total cholesterol were negatively correlated with urinary creatinine–indexed 8-epi-PGF2{alpha} levels. After adjustment for several covariates, decreasing age and total/HDL cholesterol ratio, sex, smoking, body mass index, blood glucose, and cardiovascular disease remained associated with urinary 8-epi-PGF2{alpha} levels.

Conclusions— Smoking, diabetes, and body mass index were highly associated with systemic oxidative stress as determined by creatinine-indexed urinary 8-epi-PGF2{alpha} levels. The effect of body mass index was minimally affected by blood glucose, and diabetes and may suggest an important role of oxidative stress in the deleterious impact of obesity on cardiovascular disease.


Key Words: oxidative stress • isoprostanes • diabetes • obesity • cardiovascular disease




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Am. J. Physiol. Endocrinol. Metab.Home page
G. E. Alvarez, B. M. Davy, T. P. Ballard, S. D. Beske, and K. P. Davy
Weight loss increases cardiovagal baroreflex function in obese young and older men
Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E665 - E669.
[Abstract] [Full Text] [PDF]


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J DAIRY SCIHome page
U. Bernabucci, B. Ronchi, N. Lacetera, and A. Nardone
Influence of Body Condition Score on Relationships Between Metabolic Status and Oxidative Stress in Periparturient Dairy Cows
J Dairy Sci, June 1, 2005; 88(6): 2017 - 2026.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
K. L. Moreau, K. M. Gavin, A. E. Plum, and D. R. Seals
Ascorbic Acid Selectively Improves Large Elastic Artery Compliance in Postmenopausal Women
Hypertension, June 1, 2005; 45(6): 1107 - 1112.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. P. Gardner, S. Li, S. R. Srinivasan, W. Chen, M. Kimura, X. Lu, G. S. Berenson, and A. Aviv
Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition
Circulation, May 3, 2005; 111(17): 2171 - 2177.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
A. Mohn, M. Catino, R. Capanna, C. Giannini, M. Marcovecchio, and F. Chiarelli
Increased Oxidative Stress in Prepubertal Severely Obese Children: Effect of a Dietary Restriction-Weight Loss Program
J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2653 - 2658.
[Abstract] [Full Text] [PDF]


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CirculationHome page
D. D. Christou, C. L. Gentile, C. A. DeSouza, D. R. Seals, and P. E. Gates
Fatness Is a Better Predictor of Cardiovascular Disease Risk Factor Profile Than Aerobic Fitness in Healthy Men
Circulation, April 19, 2005; 111(15): 1904 - 1914.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
A. F. Dominiczak, D. Graham, M. W. McBride, N. J.R. Brain, W. K. Lee, F. J. Charchar, M. Tomaszewski, C. Delles, and C. A. Hamilton
Cardiovascular Genomics and Oxidative Stress
Hypertension, April 1, 2005; 45(4): 636 - 642.
[Abstract] [Full Text] [PDF]


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Nephrol Dial TransplantHome page
E. M. Stuveling, S. J. L. Bakker, H. L. Hillege, P. E. de Jong, R. O. B. Gans, and D. de Zeeuw
Biochemical risk markers: a novel area for better prediction of renal risk?
Nephrol. Dial. Transplant., March 1, 2005; 20(3): 497 - 508.
[Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. D. Morrow
Quantification of Isoprostanes as Indices of Oxidant Stress and the Risk of Atherosclerosis in Humans
Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 279 - 286.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
I. S. Young
Oxidative Stress and Vascular Disease: Insights from Isoprostane Measurement
Clin. Chem., January 1, 2005; 51(1): 14 - 15.
[Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
N. R. Madamanchi, A. Vendrov, and M. S. Runge
Oxidative Stress and Vascular Disease
Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 29 - 38.
[Abstract] [Full Text] [PDF]


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CirculationHome page
J. A. Vita, J. F. Keaney Jr, M. G. Larson, M. J. Keyes, J. M. Massaro, I. Lipinska, B. T. Lehman, S. Fan, E. Osypiuk, P. W.F. Wilson, et al.
Brachial Artery Vasodilator Function and Systemic Inflammation in the Framingham Offspring Study
Circulation, December 7, 2004; 110(23): 3604 - 3609.
[Abstract] [Full Text] [PDF]


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FASEB J.Home page
P. MONTUSCHI, P. J. BARNES, and L. J. ROBERTS II
Isoprostanes: markers and mediators of oxidative stress
FASEB J, December 1, 2004; 18(15): 1791 - 1800.
[Abstract] [Full Text] [PDF]


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CirculationHome page
M. Juonala, J. S.A. Viikari, T. Laitinen, J. Marniemi, H. Helenius, T. Ronnemaa, and O. T. Raitakari
Interrelations Between Brachial Endothelial Function and Carotid Intima-Media Thickness in Young Adults: The Cardiovascular Risk in Young Finns Study
Circulation, November 2, 2004; 110(18): 2918 - 2923.
[Abstract] [Full Text] [PDF]


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J. Clin. Endocrinol. Metab.Home page
B. Hansel, P. Giral, E. Nobecourt, S. Chantepie, E. Bruckert, M. J. Chapman, and A. Kontush
Metabolic Syndrome Is Associated with Elevated Oxidative Stress and Dysfunctional Dense High-Density Lipoprotein Particles Displaying Impaired Antioxidative Activity
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4963 - 4971.
[Abstract] [Full Text] [PDF]


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Physiol. Rev.Home page
R. Stocker and J. F. Keaney Jr.
Role of Oxidative Modifications in Atherosclerosis
Physiol Rev, October 1, 2004; 84(4): 1381 - 1478.
[Abstract] [Full Text] [PDF]


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CirculationHome page
F.-P. Xu, M.-S. Chen, Y.-Z. Wang, Q. Yi, S.-B. Lin, A. F. Chen, and J.-D. Luo
Leptin Induces Hypertrophy via Endothelin-1-Reactive Oxygen Species Pathway in Cultured Neonatal Rat Cardiomyocytes
Circulation, September 7, 2004; 110(10): 1269 - 1275.
[Abstract] [Full Text] [PDF]


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Diabetes CareHome page
S. Mustafa, T. Vukovich, T. Prikoszovich, C. Winzer, B. Schneider, H. Esterbauer, O. Wagner, and A. Kautzky-Willer
Haptoglobin Phenotype and Gestational Diabetes
Diabetes Care, September 1, 2004; 27(9): 2103 - 2107.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
H. Shibata, T. Nabika, H. Moriyama, J. Masuda, and S. Kobayashi
Correlation of NO Metabolites and 8-Iso-Prostaglandin F2a With Periventricular Hyperintensity Severity
Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1659 - 1663.
[Abstract] [Full Text] [PDF]


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CirculationHome page
C. Vassalle, M. G. Andreassi, E. Schwedhelm, R. Maas, R. H. Boger, J. Brummer, J. Berger, A. Bartling, H. Lenzen, D. Tsikas, et al.
8-Iso-Prostaglandin F2{alpha} as a Risk Marker in Patients With Coronary Heart Disease * Response
Circulation, August 3, 2004; 110(5): e49 - e50.
[Full Text] [PDF]


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EndocrinologyHome page
G. Xing, T. Shimosawa, T. Ogihara, H. Matsui, K. Itakura, X. Qingyou, T. Asano, K. Ando, and T. Fujita
Angiotensin II-Induced Insulin Resistance Is Enhanced in Adrenomedullin-Deficient Mice
Endocrinology, August 1, 2004; 145(8): 3647 - 3651.
[Abstract] [Full Text] [PDF]


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CirculationHome page
N. C. Ward, J. Rivera, J. Hodgson, I. B. Puddey, L. J. Beilin, J. R. Falck, and K. D. Croft
Urinary 20-Hydroxyeicosatetraenoic Acid Is Associated With Endothelial Dysfunction in Humans
Circulation, July 27, 2004; 110(4): 438 - 443.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
T. Matsumoto, H. Takashima, N. Ohira, Y. Tarutani, Y. Yasuda, T. Yamane, S. Matsuo, and M. Horie
Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin
J. Am. Coll. Cardiol., July 21, 2004; 44(2): 451 - 457.
[Abstract] [Full Text] [PDF]


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CirculationHome page
P. M Ridker, N. J. Brown, D. E. Vaughan, D. G. Harrison, and J. L. Mehta
Established and Emerging Plasma Biomarkers in the Prediction of First Atherothrombotic Events
Circulation, June 29, 2004; 109(25_suppl_1): IV-6 - IV-19.
[Full Text] [PDF]


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Am. J. Clin. Nutr.Home page
J. Gomez-Ambrosi, J. Salvador, and G. Fruhbeck
Is hyperleptinemia involved in the development of age-related lens opacities?
Am. J. Clinical Nutrition, May 1, 2004; 79(5): 888 - 889.
[Full Text] [PDF]


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Diabetes CareHome page
C. S. Fox, L. Sullivan, R. B. D'Agostino Sr, and P. W.F. Wilson
The Significant Effect of Diabetes Duration on Coronary Heart Disease Mortality: The Framingham Heart Study
Diabetes Care, March 1, 2004; 27(3): 704 - 708.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Renal Physiol.Home page
J. T. Lane
Microalbuminuria as a marker of cardiovascular and renal risk in type 2 diabetes mellitus: a temporal perspective
Am J Physiol Renal Physiol, March 1, 2004; 286(3): F442 - F450.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
T. L. Goodfriend and D. A. Calhoun
Resistant Hypertension, Obesity, Sleep Apnea, and Aldosterone: Theory and Therapy
Hypertension, March 1, 2004; 43(3): 518 - 524.
[Abstract] [Full Text] [PDF]


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CirculationHome page
E. Schwedhelm, A. Bartling, H. Lenzen, D. Tsikas, R. Maas, J. Brummer, F.-M. Gutzki, J. Berger, J. C. Frolich, and R. H. Boger
Urinary 8-iso-Prostaglandin F2{alpha} as a Risk Marker in Patients With Coronary Heart Disease: A Matched Case-Control Study
Circulation, February 24, 2004; 109(7): 843 - 848.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
T. L. Goodfriend, D. L. Ball, B. M. Egan, W. B. Campbell, and K. Nithipatikom
Epoxy-Keto Derivative of Linoleic Acid Stimulates Aldosterone Secretion
Hypertension, February 1, 2004; 43(2): 358 - 363.
[Abstract] [Full Text] [PDF]


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HeartHome page
R S Vasan
Cardiac function and obesity
Heart, October 1, 2003; 89(10): 1127 - 1129.
[Full Text] [PDF]


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HypertensionHome page
M. E. Widlansky, D. T. Price, N. Gokce, R. T. Eberhardt, S. J. Duffy, M. Holbrook, C. Maxwell, J. Palmisano, J. F. Keaney Jr, J. D. Morrow, et al.
Short- and Long-Term COX-2 Inhibition Reverses Endothelial Dysfunction in Patients With Hypertension
Hypertension, September 1, 2003; 42(3): 310 - 315.
[Abstract] [Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. V. Higdon and B. Frei
Obesity and Oxidative Stress: A Direct Link to CVD?
Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 365 - 367.
[Full Text] [PDF]


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Arterioscler. Thromb. Vasc. Bio.Home page
J. D. Morrow
Is Oxidant Stress a Connection Between Obesity and Atherosclerosis?
Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 368 - 370.
[Full Text] [PDF]