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Role of Inflammation and Oxidant Stress

Giovanni Davì, MD; Maria Teresa Guagnano, MD; Giovanni Ciabattoni, MD; Stefania Basili, MD; Angela Falco, MD; Marina Marinopiccoli, MD; Michele Nutini, PhD; Sergio Sensi, MD; Carlo Patrono, MD

JAMA. 2002;288:2008-2014.

Context  Obesity, in particular abdominal adiposity, is associated with increased cardiovascular morbidity and mortality through mechanisms possibly linking the metabolic disorder to platelet and vascular abnormalities.

Objective  To investigate the clinical and biochemical determinants of lipid peroxidation and platelet activation in obese women.

Design, Setting, and Participants  Cross-sectional comparison, conducted between September 1999 and September 2001, of urinary 8-iso prostaglandin F₂ (8-iso PGF₂) and 11-dehydrothromboxane B₂ (11-dehyhdro-TxB₂) excretion levels in 93 women: 44 with a body mass index (BMI) higher than 28 and a waist-to-hip ratio (WHR) of 0.86 or higher, android obesity; 25 with a BMI higher than 28 and a WHR lower than 0.86, gynoid obesity; and 24 nonobese women with a BMI lower than 25. An additional study was conducted to determine the short-term effects of weight loss in 20 of the 44 women with android obesity.

Intervention  During a 12-week period, 20 women with android obesity followed a weight loss program to reduce caloric intake to about 1200 kcal/d.

Main Outcome Measures  Plasma C-reactive protein, insulin and leptin levels, and urinary 8-iso PGF₂ (marker of in vivo lipid peroxidation) and 11-dehyhdro-TxB₂ (marker of in vivo platelet activation) excretion. Weight loss was defined as successful when the initial body weight decreased by at least 5 kg after a 12-week period of caloric restriction.

Results  Women with android obesity had higher levels of 8-iso PGF₂ (median [interquartile range {IQR}] 523 [393-685] vs 187 [140-225] pg/mg creatinine) and 11-dehyhdro-TxB₂ (median [IQR], 948 [729-1296] vs 215 [184-253] pg/mg creatinine) than nonobese women (P<.001). Both 8-iso PGF₂and 11-dehyhdro-TxB₂ were higher in women with android obesity than women with gynoid obesity (P<.001). Based on multiple regression analysis, C-reactive protein levels and WHRs of 0.86 or higher predicted the rate of 8-iso PGF₂ excretion independently of insulin and leptin levels. Of 20 women with android obesity, 11 achieved successful weight loss, which was associated with statistically significant reductions in C-reactive protein (median change, 23%; P<.05), 8-iso PGF₂ (median change, 32%; P = .04) and 11-dehydro-TxB₂ (median change, 54%; P = .005).

Conclusions  Android obesity is associated with enhanced lipid peroxidation and persistent platelet activation. These abnormalities are driven by inflammatory triggers related to the degree of abdominal adiposity and are, at least in part, reversible with a successful weight-loss program.

Author Affiliations: Center of Excellence on Aging (Drs Davì, Falco, Marinopiccoli, and Nutini) and Departments of Medicine (Drs Guagnano and Sensi) and Drug Sciences (Dr Ciabattoni), "G. D'Annunzio" University Schools of Medicine and Pharmacy, Chieti; and University of Rome "La Sapienza," Rome (Drs Basili and Patrono), Italy.

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