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Clinical Science (2008) 114, (449–455) (Printed in Great Britain)

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Association of low-grade inflammation and platelet activation in patients with hypertension with microalbuminuria

Patrizia FERRONI*, Maria Teresa GUAGNANO†, Angela FALCO†, Vincenzo PAOLETTI‡, Maria Rosaria MANIGRASSO†, Noemi MICHETTI†, Francesca SANTILLI†, Fiorella GUADAGNI*, Stefania BASILI‡ and Giovanni DAV̆

*Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy, †Center of Excellence on Aging,“G. d'Annunzio” University Foundation and Department of Medicine and Aging, University of Chieti“G. d'Annunzio”, Chieti-Pescara, Italy, and ‡Department of Medical Therapy, University of Rome“La Sapienza”, Rome, Italy

Key words: hypertension, inflammation, microalbuminuria, platelet activation, soluble CD40 ligand (sCD40L), thrombosis.

Abbreviations: ADMA, asymmetric dimethylarginine; AER, albumin excretion rate; BMI, body mass index; BP, blood pressure; CD40L, CD40 ligand; CRP, C-reactive protein; EH, essential hypertension; HDL, high-density lipoprotein; HS, healthy subjects with normotension; LDL, low-density lipoprotein; MA, microalbuminuria; EH, essential hypertension without MA; MH, essential hypertension with MA; sCD40L, soluble CD40L; sP-selectin, soluble P-selectin; TNF-a, tumour necrosis factor-a; vWF, von Willebrand factor.

Correspondence: Professor Giovanni Davì (email gdavi@unich.it).

Increased levels of sCD40L (soluble CD40 ligand) have been associated with enhanced in vivo platelet activation, and may represent a molecular link between inflammation and a prothrombotic state. The aim of the present study was to analyse the relationship between platelet activation, endothelial dysfunction, low-grade inflammation and sCD40L in patients with hypertension with or without MA (microalbuminuria). A cross-sectional comparison of sCD40L levels was performed in 25 patients with MH (essential hypertension with MA) pair-matched for gender and age with 25 patients with EH (essential hypertension) and 25 HS (healthy subjects with normotension). Circulating levels of CRP (C-reactive protein), a marker of inflammation, sP-selectin (soluble P-selectin), a marker of in vivo platelet activation, and ADMA (asymmetric dimethylarginine) and vWF (von Willebrand factor), markers of endothelial dysfunction, were analysed in each subject. sCD40L levels were increased in patients with MH compared with either patients with EH (P<0.001) or HS (P<0.0001). A highly significant correlation between plasma sCD40L and sP-selectin (P<0.0001), vWF (P<0.001) or CRP levels (P<0.05) was observed in patients with MH. Multivariate regression analysis showed that sP-selectin was the strongest independent predictor of sCD40L levels (P<0.0001) in patients with MH. Patients with hypertension with both vWF and CRP levels above the median had the highest sCD40L levels (P<0.0001). Factorial ANOVA of all of the patients with hypertension confirmed that only patients with MH with low-grade inflammation had elevated levels of sCD40L. In conclusion, sCD40L levels appear to discriminate a subset of patients characterized by MA and low-grade inflammation, suggesting that inhibition of the CD40/CD40L system may represent a potential therapeutic target in subjects with hypertension at a high risk of cardiovascular events.

Received 31 August 2007/31 October 2007; accepted 7 November 2007

Published as Immediate Publication 7 November 2007, doi:10.1042/CS20070307

© The Authors Journal compilation © 2008 Biochemical Society