Elevated platelet microparticle levels in nonvalvular atrial fibrillation: relationship to p-selectin and antithrombotic therapy.
BACKGROUND
Platelet microparticles (PMPs), are procoagulant membrane vesicles that are derived from activated platelets, the levels of which are elevated in patients with hypertension, coronary artery disease (CAD), diabetes, and stroke, all of which are conditions that lead to (and are associated with) atrial fibrillation (AF). We hypothesized the following: (1) PMP levels are elevated in patients with AF compared to levels in both healthy control subjects (ie, patients without cardiovascular diseases who are in sinus rhythm) and disease control subjects (ie, patients with hypertension, CAD, diabetes or stroke, but who are in sinus rhythm); (2) PMP levels correlate with levels of soluble P-selectin (sP-selectin) [a marker of platelet activation]; and (3) PMP levels are related to the underlying factors in patients with AF that contribute to the overall risk of stroke secondary to AF.


METHODS
We performed a case-control study of 70 AF patients, 46 disease control subjects and 33 healthy control subjects. Peripheral venous levels of PMP and sP-selectin were analyzed by flow cytometry and enzyme-linked immunosorbent assay, respectively.


RESULTS
Both AF patients and disease control subjects had significantly higher levels of PMPs (p < 0.001) and sP-selectin (p = 0.001) compared to healthy control subjects, but there was no difference between AF patients and disease control subjects. There was no difference in PMP levels between patients with paroxysmal and permanent AF (p = 0.581), and between those receiving therapy with aspirin and warfarin (p = 0.779). No significant correlation was observed between PMP and sP-selectin levels (p = 0.463), and the clinical characteristics that contribute to increased stroke risk in patients with AF. On stepwise multiple regression analysis in the combined cohort of AF patients plus disease control subjects, the presence/absence of AF was not an independent determinant of PMP and sP-selectin levels.


CONCLUSIONS
There is evidence of platelet activation (ie, high PMP and sP-selectin levels) in AF patients, but this is likely to be due to underlying cardiovascular diseases rather than the arrhythmia per se.
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.
Blann
Andrew D
AD
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; D001241:Aspirin / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000097:blood / Q000188:drug therapy*; D016022:Case-Control Studies; D002462:Cell Membrane / Q000378:metabolism; D002544:Cerebral Infarction / Q000097:blood / Q000188:drug therapy; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005434:Flow Cytometry; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D019007:P-Selectin / Q000097:blood*; D010316:Particle Size; D015539:Platelet Activation / Q000187:drug effects*; D012016:Reference Values; D012307:Risk Factors; D013223:Statistics as Topic; D014859:Warfarin / Q000627:therapeutic use*
D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D019007:P-Selectin; D014859:Warfarin; D001241:Aspirin