Soluble CD40L levels are regulated by the -3459 A>G polymorphism and predict myocardial infarction and the efficacy of antithrombotic treatment in non-ST elevation acute coronary syndrome.
OBJECTIVE
Current evidence suggests the CD40-CD40L pathway as a key process in the development, progression, and outcome of acute coronary syndrome (ACS). The aim was to investigate the prognostic importance of soluble (s) CD40L levels, single nucleotide polymorphisms (SNP) in the CD40LG gene, and the relation between sCD40L and SNPs in patients with acute coronary syndromes (ACS).


RESULTS
Samples were obtained on admission from 2359 patients with non-ST elevation ACS randomized to an early invasive versus a conservative and to placebo controlled long-term dalteparin treatment in the FRISC-II study. The -3459 A>G SNP was identified as a novel regulator of sCD40L levels (P = 0.001). In the placebo-treated group, sCD40L levels above median were associated with a 2.5-fold increased risk of myocardial infarction (MI) (P < or = 0.001) but not with raised mortality. In the dalteparin treated group, sCD40L showed no association with MI (P = 0.75). Consequently, dalteparin treatment was effective in reducing the risk of MI only in patients with sCD40L levels above median. A combined assessment of troponin-T and sCD40L complemented the prognostic information on risk of MI.


CONCLUSIONS
We identified a SNP in the CD40LG gene as a novel regulator of sCD40L plasma concentrations. Soluble CD40L levels above median reflect a prothrombotic state, which can be managed with the use of intense anti-thrombotic treatments.
Mälarstig
Anders
A
Department of Medical Sciences, Clinical Chemistry, Uppsala University, S-751 85 Uppsala, Sweden.
Lindahl
Bertil
B
Wallentin
Lars
L
Siegbahn
Agneta
A
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D023201:CD40 Ligand / Q000097:blood* / Q000737:chemistry / Q000235:genetics*; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D017985:Dalteparin / Q000627:therapeutic use*; D004562:Electrocardiography; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology* / Q000517:prevention & control; D009994:Osmolar Concentration; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012995:Solubility; D016019:Survival Analysis; D013577:Syndrome; D016896:Treatment Outcome; D020107:Troponin T / Q000097:blood
D015415:Biomarkers; D005343:Fibrinolytic Agents; D020107:Troponin T; D023201:CD40 Ligand; D017985:Dalteparin