on April 20, 2006
Published online before print April 20, 2006, doi: 10.1161/01.ATV.0000222908.78873.36
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 25, 2006
Accepted on April 3, 2006
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
Anders Mälarstig ;
From the Department of Medical Sciences, Clinical Chemistry (A.M., A.S.), Cardiology, Uppsala Clinical Research Centre (B.L., L.W.), Uppsala University, Sweden.
* To whom correspondence should be addressed. E-mail: agneta.siegbahn{at}akademiska.se.
Objectives--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).
Methods and 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
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.
Key words: ACS • CD40L • myocardial infarction • outcome • SNP • thrombosis
This article has been cited by other articles:
 |
|
 |
|
  C. Antoniades, C. Bakogiannis, D. Tousoulis, A. S. Antonopoulos, and C. Stefanadis The CD40/CD40 ligand system: linking inflammation with atherothrombosis. J. Am. Coll. Cardiol., August 18, 2009; 54(8): 669 - 677. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Jiang, C. Y. Liu, Q. F. Yang, P. Wang, and W. Zhang Plasma Level of Growth Arrest-Specific 6 (GAS6) Protein and Genetic Variations in the GAS6 Gene in Patients With Acute Coronary Syndrome Am J Clin Pathol, May 1, 2009; 131(5): 738 - 743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Yang, Z. Fang, Y. Liu, H. Zhang, X. Shi, Q. Ji, Q. Lin, and R. Lin Protective Effects of Chinese Traditional Medicine Buyang Huanwu Decoction on Myocardial Injury Evid. Based Complement. Altern. Med., February 8, 2009; (2009) nep013v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Welch, Y. Sun, B. J. Arey, V. Lemaitre, N. Sharma, M. Ishibashi, S. Sayers, R. Li, A. Gorelik, N. Pleskac, et al. Spontaneous Atherothrombosis and Medial Degradation in Apoe-/-, Npc1-/- Mice Circulation, November 20, 2007; 116(21): 2444 - 2452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Koenig and N. Khuseyinova Biomarkers of Atherosclerotic Plaque Instability and Rupture Arterioscler Thromb Vasc Biol, January 1, 2007; 27(1): 15 - 26. [Abstract] [Full Text] [PDF]
|
|