Soluble CD40 ligand, platelet surface CD40 ligand, and total platelet CD40 ligand in atrial fibrillation: relationship to soluble P-selectin, stroke risk factors, and risk factor intervention.
BACKGROUND
Abnormal levels of soluble CD40 ligand (sCD40L) have been reported in patients with hypertension, coronary artery disease, diabetes mellitus, heart failure, and stroke, all of which are conditions that are associated with nonvalvular atrial fibrillation (AF). We hypothesized the following: (1) CD40 ligand (CD40L)-related indexes (ie, platelet surface expressed CD40L, the soluble fragment of CD40L [sCD40L], and the total amount of CD40L per platelet [pCD40L]) are elevated in patients with AF compared to control subjects; (2) these indexes correlate with soluble P-selectin (sP-selectin), which is an established platelet marker; and (3) these indexes differentiate "high-risk" from "low-risk" subjects.


METHODS
We performed a case-control study of 121 AF patients, 71 "disease control subjects," and 56 "healthy control subjects." Peripheral venous levels of platelet surface-expressed CD40L were analyzed by flow cytometry, while levels of sCD40L, pCD40L, and sP-selectin were measured by enzyme-linked immunosorbent assay.


RESULTS
AF patients had significantly higher sCD40L levels compared to healthy control subjects (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 indexes failed to distinguish between high-risk and low-risk AF patients. AF patients receiving optimal antithrombotic therapy had significantly lower pCD40L levels (p < 0.001) compared to control subjects. Optimized AF management also resulted in significant reductions in the levels of sCD40L (p = 0.023) and pCD40L (p < 0.001).


CONCLUSIONS
CD40L-related indexes are not useful in the risk stratification of AF patients, and abnormal sCD40L levels can be reduced by intense multifactorial risk management. While there is a significant, albeit modest, excess of platelet activation in AF patients (as measured by sCD40L levels) compared to healthy control subjects, this is not in excess of that seen in patients with underlying cardiovascular diseases.
Choudhury
Anirban
A
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Chung
Irene
I
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Panja
Nimai
N
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Patel
Jeetesh
J
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Lip
Gregory Y H
GYH
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK. Electronic address: g.y.h.lip@bham.ac.uk.
D000368:Aged; D001281:Atrial Fibrillation / Q000097:blood* / Q000188:drug therapy; D001792:Blood Platelets / Q000378:metabolism*; D023201:CD40 Ligand / Q000097:blood*; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*
D005343:Fibrinolytic Agents; D019007:P-Selectin; D023201:CD40 Ligand