Author + information
- Received April 5, 2000
- Revision received June 28, 2000
- Accepted August 31, 2000
- Published online December 1, 2000.
- Adnan Kastrati, MD∗,* (, )
- Werner Koch, PhD∗,
- Peter B Berger, MD†,
- Julinda Mehilli, MD∗,
- Katherine Stephenson, PhD‡,
- Franz-Josef Neumann, MD∗,
- Nicolas von Beckerath, MD∗,
- Corinna Böttiger, MD∗,
- Gordon W Duff, MD, PhD§ and
- Albert Schömig, MD∗
- ↵*Reprint requests and correspondence: Dr. Adnan Kastrati, Deutsches Herzzentrum, München, Lazarettstrasse 36, 80636 München, Germany
To test the hypothesis that interleukin-1 receptor antagonist (IL-1ra) gene polymorphism contributes to the risk of restenosis after coronary stenting.
Cytokines of the interleukin-1 (IL-1) family play a central role in regulating inflammatory responses. There is strong evidence to support IL-1 involvement in smooth muscle cell mitogenesis and extracellular matrix metabolism. The IL-1ra counters the proinflammatory effects of IL-1. The interleukin-1 receptor antagonist gene (IL-1RN) contains several well-characterized polymorphic sites that correlate with altered IL-1ra levels.
In 1,850 consecutive patients, clinical and angiographic measures of restenosis were evaluated over one year after coronary stent placement. Repeat angiography at six months was achieved in 84% of the patients; angiographic restenosis was defined ≤50% diameter stenosis at follow-up. Genotyping for an exon 2 polymorphism (+2,018) of IL-1RN (alleles 1 and 2) was based on a polymerase chain reaction technique.
Allele 2 frequency was 0.28. Carriers of allele 2 had a significantly lower risk for angiographic restenosis, odds ratio (OR) of 0.78 (95% confidence interval, 0.63 to 0.97) and target vessel revascularization, OR of 0.73 (0.58 to 0.92) compared with noncarriers. Risk reduction was especially significant in patients <60 years (n = 696), with OR of 0.63 (0.43 to 0.91) for angiographic restenosis and 0.55 (0.39 to 0.78) for target vessel revascularization.
Allele 2 of the IL-1ra gene was associated with a lower incidence of restenosis after coronary stenting, particularly in younger patients. This finding supports a role of inflammation in the development of restenosis after stent placement.
- Received April 5, 2000.
- Revision received June 28, 2000.
- Accepted August 31, 2000.
- American College of Cardiology