July 15, 1999 DALLAS, July 13 -- Cholesterol-lowering drugs may ward off a secondary complication of high blood cholesterol, according to a report in today's Circulation: Journal of the American Heart Association.
Cholesterol-lowering drugs reduce blood cholesterol, which can collect in the blood vessels, triggering a heart attack. New evidence suggests elevated cholesterol also can lead to a remodeling of the blood vessel wall that causes it to constrict, a condition called reduced myocardial vasodilation (MVD). However, the condition seems reversible with cholesterol-lowering treatment, say University of Tokyo researchers.
"Reduced MVD may be an early sign of coronary heart disease, because we were able to identify the condition in individuals with coronary heart disease who did not have extensive fatty deposits, or plaque, in their blood vessel. Our findings suggest that it is vital that this condition be treated in order to avoid a heart attack, and also that cholesterol-lowering drugs can help reverse this remodeling process," says lead author Ikuo Yokoyama, M.D., of the department of cardiovascular medicine at the University of Tokyo.
The researchers found that this reversal was also associated with improvements in blood pressure, both systolic (heart pumping) and diastolic (heart at rest).
"Reversing remodeling may result in a reduction in the development of plaque, which in turn can reduce the risk of a heart attack," says Yokoyama. However, further research is needed to confirm this idea.
The Japanese team did not set out to test the effectiveness of any particular cholesterol-lowering drug in improving blood flow to the heart muscle, and several drugs were used, often in combination.
Yokoyama and his team studied 27 people with high cholesterol, 17 men and 10 women, and compared them to 12 men and 4 women with normal cholesterol levels. The high cholesterol group had an average total cholesterol level of 263 milligrams per deciliter (mg/dl), compared to 197 mg/dl in the second group. There were no other significant differences between the two groups; they were similar in age, gender, body weight, height, blood pressure and smoking habits. Sixteen members of the high-cholesterol group had chest pain and other signs of coronary heart disease, but angiograms (an X-ray of the blood vessel) indicated that most of their blood vessels were normal. Twenty-five of those with high cholesterol were treated with a combination of medications and a low-cholesterol diet, and two by diet alone. The high cholesterol group saw their levels drop to an average of 197 mg/dl during the course of therapy.
The researchers measured myocardial (heart) blood flow using a technique called positron emission tomography (PET). Readings were made when the patients were at rest and when they were given dipyridamole, a drug used to determine how much the blood vessels dilate to allow blood flow. Blood vessels must dilate and constrict to respond to the daily stresses on the heart. The PET test provides a way to test this ability, by stressing the blood vessels and measuring how well they respond. The team measured blood flow again eight to 15 months after medication and/or dietary therapies were given.
Myocardial blood flow at rest as measured by PET was similar in the high-cholesterol patients and those with normal cholesterol levels, both at the beginning and end of the study. However, when people in the two groups were given the dilating drug to test their blood vessel's response, those with high cholesterol had significantly lower blood flow to the heart muscle than the healthy group.
After their course of cholesterol-lowering drug therapy, those with high cholesterol experienced a significant improvement in blood flow to their heart muscle. However, it was still lower than in the group with normal cholesterol levels.
Sixteen of the high-cholesterol patients also had high blood pressure, and five had diabetes, both of which can contribute to the remodeling of coronary blood vessels. When the Japanese team excluded these patients from their analysis, the results indicated that the cholesterol-lowering drugs led to a more complete reversal of MVD, and normalized the blood vessels of those with high cholesterol only.
Researchers say the "inclusion of those with high blood pressure or diabetes" may account for the variation in the response to the therapy.
Co-authors of the paper are Shin-ichi Momomura, M.D.; Tohru Ohtake, M.D.; Katsunori Yonekura, M.D.; Weidong Yang, M.D.; Naoshi Kobayakawa, M.D.; Teruhiko Aoyagi, M.D.; Seiryo Sugiura, M.D.; Nobuhiro Yamada, M.D.;Kuni Ohtomo, M.D.; Yasuhito Sasaki, M.D.; Masao Omata, M.D.; and YoshioYazaki, M.D.
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