ATLANTA, Nov. 10 -- Scientists in Japan may have found a genetic cause of coronary artery spasm, a condition that reduces blood supply to the heart causing chest pain or, in severe cases, even a heart attack. They reported their finding today at the American Heart Association Scientific Sessions.

A coronary artery spasm occurs when a coronary artery -- one of the blood vessels supplying blood to the heart -- constricts, then fails to re-open or dilate. Smoking can increase the risk for spasm, but the precise reason for coronary artery spasm has been largely unknown.

In genetic studies, researchers found that mutations in the endothelial nitric oxide synthase (eNOS) gene -- which controls nitric oxide production in the epithelium, or lining, of blood vessel walls -- were prevalent in patients with coronary artery spasm.

Nitric oxide is a key chemical in controlling blood vessel dilation. Varying levels of the chemical stimulate blood vessels to relax or constrict to meet the heart's increasing or decreasing demand for blood flow. "Given that the effects of the gene and smoking are potentially additive, individuals with the gene should be strongly cautioned against smoking," says Michihiro Yoshimura, M.D., Ph.D., and fellow researchers at Kumamoto University in Japan.

"In other studies, we found that nitric oxide activity was deficient in the coronary arteries of patients with coronary spasm," says Yoshimura, lead scientist on the study. "From there we decided to target the eNOS gene to find a genetic cause of coronary artery spasm."

In the study, Yoshimura and colleagues compared risk factors and genetic findings between 201 individuals diagnosed with coronary artery spasm and 345 healthy volunteers. The researchers revealed that the eNOS gene mutation is the most predictive risk factor for coronary artery spasm, followed by cigarette smoking.

Individuals with the gene mutation had twice the risk of having a spasm as individuals without the mutation. Spasms also occurred twice as often among smokers than nonsmokers.

Yoshimura says the gene mutations are useful for diagnosing coronary artery spasm, but won't replace the traditional method used to diagnose the condition. Spasm is diagnosed by imaging the blood vessels after injecting a substance that causes the vessels to constrict. An individual with spasm would have an abnormal constriction in response to the substance.

"However," he says, "because coronary artery spasm is sometimes difficult to diagnose, physicians could use the eNOS analysis in addition to other diagnostic methods. If a patient carries a mutation in this gene, he or she could be treated before the onset of chest pain."

Yoshimura also says that further study of the eNOS gene may allow people with coronary artery spasm to be treated with gene therapy. "The era might come when we are able to regulate the gene," says Yoshimura. Yoshimura and his colleagues are now involved in a cooperative study to investigate the incidence of the eNOS gene mutations in other countries.

The drug, nitroglycerin can relieve the symptoms of spasms, but other treatments such as calcium antagonists and nitrates are useful for preventing spasms.

"The impairment of the endothelium plays an important role in the cause of spasm, and since smoking contributes to spasm, it is important that we recommend cessation of smoking in patients with spasm," he says.

Smoking was also associated with spasm in individuals without the gene, which gives another reason for individuals not to smoke, he adds.

Co-authors are Hirofumi Yasue, M.D., Ph.D.; Masafumi Nakayama, M.D., Ph.D.; Yukio Shimasaki, M.D., Ph.D.; Yuji Mizuno, M.D.; Eisaku Harada, M.D.; Shota Nakamura, M.D.; Teruhiko Ito, M.D.; Kiyotaka Kugiyama, M.D., Ph.D.; Tomohiro Sakamoto, M.D., Ph.D; and Kazuwa Nakao, M.D., Ph.D.

Media Advisory: Dr. Yoshimura can be reached by phone at 81-9637-35175, or by fax at 81-9636-23256, or email at [email protected] (Please do not publish numbers.)