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Japanese Researchers Get to the Heart of Atherosclerosis

June 05, 2006

SAN DIEGO, Calif.—Using positron emission tomography (PET), the medical isotope 15O-water and cold pressor tests, Japanese researchers were able to detect the beginnings of atherosclerosis—before the disease became clinically evident. These results were released during SNM's 53rd Annual Meeting June 3—7 in San Diego.

This revelation will allow physicians to advise high-risk patients—who show no cardiovascular symptoms—to make lifestyle changes modifications or to undergo medical treatment, said Masanao Naya, a physician at Hokkaido University Graduate School of Medicine in Sapporo, Japan. In addition, researchers determined that elevated levels of interleukin-6—one of the inflammatory chemicals produced by endothelial cells and that has been associated with an increased risk of heart disease—is "a major determinant" of coronary endothelial dysfunction, especially in individuals with high blood pressure.

Atherosclerosis is a slow, progressive disease that begins with damage to the innermost layer of the artery—the endothelium—and buildup of fatty substances, cholesterol and cellular waste products in the inner linings of arteries, which carry oxygen-rich blood to the heart, brain and other parts of the body. The endothelium can be damaged by such factors as elevated levels of cholesterol, high blood pressure (hypertension), smoking and obesity. Over time, plaques can narrow coronary arteries, allowing less blood to flow to the heart muscle. Rupture of these plaques may result in heart attack and death, said the co-author of "Determinants of Coronary Endothelial Dysfunction in Hypertensive Patients."

Coronary endothelial dysfunction—which occurs when blood vessels aren't flexible enough to expand in response to increased blood flow—is the central feature of this dreaded disease. Coronary endothelial dysfunction precedes cardiovascular events and is reversible, making its early detection important, said Naya. He explained, "We can select high-risk patients with endothelial dysfunction using blood sample analysis at an early stage of atherosclerosis, then start medical treatment or lifestyle modification." More than 71 million Americans have one or more forms of cardiovascular disease, the single leading cause of death in this country.

Coronary endothelial function is impaired at an early stage of atherosclerosis in hypertensive patients; however, the "magnitude" of dysfunction differs among individuals, said Naya. "We can assess the endothelial dysfunction in the human heart noninvasively using PET and evaluate factors that can determine endothelial dysfunction," he added.

In their study, researchers examined 27 untreated patients with high blood pressure. Myocardial blood flow was measured both at rest and during stimulation induced by a cold pressor test by using PET with 15O-water. The patient's feet were immersed in icy water for 4 minutes, and a person's risk for hypertension or high blood pressure was evaluated by observing blood pressure response.

Additional research needs to be done, said Naya. "We have been enrolling more patients and evaluating the relevance to the prognosis and the effect of medical treatments or life modification," he noted.

This is "quite revolutionary research," said Josef Machac, SNM's Scientific Program Committee cardiovascular vice chair. "By measuring the response of coronary blood flow to stress, these researchers were able to detect atherosclerosis before it became evident clinically," allowing patients the potential opportunity to make important lifestyle changes (such as reducing the amount of saturated fat and cholesterol in their diets and getting regular exercise) before medical intervention became necessary, added the director of the Clinical PET Center and Nuclear Medicine at Mount Sinai School of Medicine in New York City.

Society of Nuclear Medicine