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To the Editor: Davì et al¹ recently reported that android obesity is associated with enhanced lipid peroxidation and persistent platelet activation, both of which can be reduced by weight loss. In this context, enhanced circulating soluble CD40 ligand (CD40L) has recently been suggested to be associated with platelet activation.^2-4 CD40L is a trimeric, transmembrane protein of the tumor necrosis factor family that is cryptic in unstimulated platelets but is rapidly expressed on the platelet surface after platelet stimulation.³ Thus, increased levels of circulating soluble CD40L represent an index of platelet activation.^2-4 We assessed the relationship between central obesity and levels of circulating soluble CD40L and the effect of weight loss on this measure of platelet activation.

Methods
Participants were 36 obese white men (mean age, 53.4 [SD, 6.6] years) with body mass indexes (BMIs) greater than 30 and without additional cardiovascular risk factors, selected according to previously described criteria.⁵ All patients had android obesity^{1, 6} and were given a diet providing from 800 kcal/d to 1200 kcal/d, according to tailored agreements occurring between each patient and our medical staff. Circulating levels of soluble CD40L (R&D Systems Inc, Minneapolis, Minn) were assessed at baseline and after 16 weeks under caloric restriction. Concentrations of plasma 8-iso-prostaglandin F₂ (8-iso-PGF₂) (Assay Design Inc, Ann Arbor, Mich), a marker of lipid peroxidation, was also assessed in obese patients. Twenty-six healthy male volunteers (mean age, 51.2 [5.5] years) selected according to the same exclusion criteria used for obese patients but with a BMI less than 25 were studied as control group for baseline comparisons. The study was approved by our institutional review board.

Results
Baseline mean (SD) levels of circulating soluble CD40L and 8-iso-PGF₂ were significantly (P<.001) higher in obese vs nonobese patients (3.8 [0.7] vs 2.3 [0.8] ng/mL and 411.9 [59.3] vs 265.9 [39.0] pg/L, respectively). Baseline BMI among obese patients was signficantly related to initial concentrations of circulating soluble CD40L (r = 0.397, P = .02) and 8-iso-PGF₂ (r = 0.472, P = .004). Plasma levels of soluble CD40L were directly correlated with 8-iso-PGF₂ concentrations (r = 0.426, P<.01). After 16 weeks under caloric restriction, significant (P<.001) reductions of BMI (-3.5 [0.7]) and plasma levels of soluble CD40L (-1.3 [0.2] ng/mL) and 8-iso-PGF₂ (-142.2 [41.2] pg/L) were observed in the obese group. Changes in plasma levels of soluble CD40L in this group were directly correlated with changes in 8-iso-PGF₂ concentrations and BMI (Figure 1).

View larger version (32K): [in this window] [in a new window] Figure. Relationship Between Changes in Soluble CD40L Levels and Changes in Plasma 8-Iso-PGF2 Concentrations and BMI in 36 Obese Men After Weight Loss BMI indicates body mass index; CD40L, CD40 ligand; 8-iso-PGF2, 8-iso-prostaglandin F2. Body mass index is calculated by dividing weight in kilograms by the square of height in meters (kg/m2).

Comment
Enhanced oxidative stress, as indicated by the elevated concentrations of circulating 8-iso-PGF₂, may represent a link between obesity and platelet activation, as previously reported by Davì et al.¹ Similarly, we previously reported that obese patients manifest endothelial adhesion activation.⁵ This also could be consequent to increased oxidative stress and could augment the role of platelet activation in increasing the cardiovascular risk in obese patients.

Giovambattista Desideri, MD; Claudio Ferri, MD
Department of Internal Medicine and Public Health
University of L'Aquila
L'Aquila, Italy

1. Davì G, Guagnano MT, Ciabattoni G, et al. Platelet activation in obese women: role of inflammation and oxidant stress. JAMA. 2002;288:2008-2014. FREE FULL TEXT 2. Cipollone F, Mezzetti A, Porreca E, et al. Association between enhanced soluble CD40L and prothrombotic state in hypercholesterolemia: effects of statin therapy. Circulation. 2002;106:399-402. FREE FULL TEXT 3. Henn V, Steinbach S, Buchner K, Presek P, Kroczek RA. The inflammatory action of CD40 ligand (CD154) expressed on activated human platelets is temporally limited by coexpressed CD40. Blood. 2001;98:1047-1054. FREE FULL TEXT 4. Andrè P, Nannizzi-Alaimo L, Prasad SK, Phillips DR. Platelet-derived CD40L: the switch-hitting player of cardiovascular disease. Circulation. 2002;106:896-899. FREE FULL TEXT 5. Ferri C, Desideri G, Valenti M, et al. Early upregulation of endothelial adhesion molecules in obese hypertensive men. Hypertension. 1999;34(4 pt 1):568-573. FREE FULL TEXT 6. Crepaldi G, Belfiore F, Bosello O, et al. Italian Consensus Conference—overweight, obesity and health. Int J Obes. 1991;15:781-790. ISI | PUBMED

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2003;289:1781-1782.

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