Although myocardial infarction (MI, or heart attack) and atherothrombotic ischemic stroke are thought to be caused by rupture of vulnerable atherosclerotic plaques, they are recognized to be complex disorders that likely result from multifaceted interactions between an individual's genetic makeup and environmental factors, according to background information in the article. The relation between COX-2 variations and the risk of MI and stroke has not been clear.
Francesco Cipollone, M.D., of the G. d'Annunzio University of Chieti and G. d'Annunzio University Foundation, Chieti, Italy and colleagues conducted a study to determine if there was a relationship between a variation in the COX-2 gene (termed the "-765G-C polymorphism") and clinically evident plaque rupture. The study was conducted between March 2002 and October 2003 among 864 patients with first MI or atherothrombotic ischemic stroke and 864 hospitalized controls. The groups were matched for age, sex, body mass index, smoking, hypertension, hypercholesterolemia, and diabetes.
The researchers found that the prevalence of this specific genetic variation (-765GC) was 2.41 times higher among the controls than among the MI and stroke patients. The prevalence of a different variant (-765CC) was 5.81 times higher among the controls than among the MI and stroke patients. Patients with the -765GC or -765CC genotype had a reduction in relative risk of MI and ischemic stroke of 52 percent and 67 percent, respectively, after adjustment for age, sex, smoking status, body mass index, hypercholesterolemia, hypertension, and diabetes.
"We found that the -765GC polymorphism of the COX-2 gene is associated with a reduction in the risk of MI and stroke, suggesting that this [variation] may offer protection against clinical events related to atherosclerotic plaque rupture," the authors write.
(JAMA. 2004;291:2221-2228. Available post-embargo at JAMA.com)
Editor's Note: This study was supported in part by grants from the Italian Ministry of Research and Education and the Italian Ministry of Health.
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JAMA