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This Article Full Text (PDF) All Versions of this Article: chest.07-2745v1 134/3/574    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Personal Article Archive Download to citation manager Google Scholar Articles by Choudhury, A. Articles by Lip, G. Y. PubMed PubMed Citation Articles by Choudhury, A. Articles by Lip, G. Y.

SOLUBLE CD40L, PLATELET SURFACE CD40L AND TOTAL PLATELET CD40L IN ATRIAL FIBRILLATION: Relationship to soluble P-selectin, stroke risk factors and risk factor intervention

Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England, UK

g.y.h.lip{at}bham.ac.uk

Abstract

BackgroundAbnormal levels of sCD40L have been reported in hypertension, coronary artery disease (CAD), diabetes mellitus, heart failure and stroke –all conditions that are associated with) nonvalvular atrial fibrillation(AF). We hypothesised the following: (i) CD40L related indices [that is, platelet surface expressed CD40L, sCD40L and total amount of CD40L per platelet (pCD40L)] are elevated in AF compared to controls; (ii) these indices correlate with soluble P-selectin (sP-selectin, an established platelet marker); and (iii) these indices differentiate ‘high-risk' from ‘low-risk' subjects.

MethodsWe performed a case-control study of 121 AF patients, 71 ‘disease controls' and 56 ‘healthy controls'. Peripheral venous levels of platelet surface expressed CD40L were analyzed by flow cytometry, whilst levels of sCD40L, pCD40L and sP-selectin were measured by ELISA.

ResultsAF patients had significantly higher sCD40L levels compared to ‘healthy controls' (p=0.042), with no difference in platelet surface CD40L and pCD40L levels. A positive correlation was noted between levels of sCD40L and pCD40L, and not with sP-selectin. CD40L related indices failed to distinguish between ‘high-risk' and ‘low-risk' AF patients. AF patients on optimal anti-thrombotic therapy had significantly lower pCD40L levels (p<0.001) compared to controls. Optimised AF management also resulted in significant reductions of sCD40L (p=0.023) and pCD40L (p<0.001) levels.

ConclusionCD40L related indices are not useful in the risk stratification of AF patients, and abnormal sCD40L levels can be reduced by intense multifactorial risk management. Whilst there is significant, albeit modest, excess of platelet activation in AF (as measured by sCD40L levels) compared to ‘healthy controls', this is not in excess of that seen with underlying cardiovascular diseases.

Key Words: Platelet activation • CD40L • soluble CD40 • platelet lysate • atrial fibrillation