In a major challenge to the widely held belief that a "bad" form of cholesterol contributes to heart disease while another form helps to prevent it, U.S. and Soviet researchers have found that high levels of the supposedly "good" cholesterol offer no such protection to middle-aged Soviet men and are associated with an increase in the overall death rate.
The findings, involving about 8,000 Soviet men, are at odds with a long line of studies that show beneficial effects of so-called HDL cholesterol in the United States and Western Europe--including a parallel study of about 1,000 American men conducted by the same research team.
The findings, reported Tuesday at the American Heart Assn.'s scientific sessions in Anaheim, "wave a red flag" because they are the first "really that show HDL as being adverse," said Dr. Robert I. Levy of Columbia University's College of Physicians and Surgeons.
Earlier studies have led some physicians to encourage patients with high cholesterol to specifically increase their HDL levels, sometimes with medications, in addition to taking generally recommended steps to decrease the risk of heart disease. Just last week, such a recommendation was made by Finnish researchers after studying the drug gemfibrozil, which raises HDL levels.
The latest study shows that elevated HDL levels do not protect Soviet men against heart disease and contribute to their increased risk of death from other causes, primarily cancer.
It does not, however, explain the differences between the apparent protective role of HDL in Western nations and its seeming detrimental effects in the Soviet Union.
"With HDL increase taking a much more important role now in the United States, with the sinister relationship between HDL and disease seen in the Soviet Union, obviously the unraveling of this paradox is of tremendous public health importance to both our nations," Levy said.
HDL, or high-density lipoproteins, are one of three major classes of cholesterol-containing substances in the bloodstream.
The others are LDL, or low-density lipoproteins, which is a major cause of atherosclerosis (narrowing of the arteries), and the closely related very low-density lipoproteins. Between 60% and 70% of the cholesterol is found in LDL, the target of efforts to lower cholesterol through diet or drug therapy.
HDL usually contains 20% to 30% of the total cholesterol. Laboratory studies have suggested that HDL may reduce the accumulation of cholesterol in the arteries. In addition, some physicians have argued that further benefits can be obtained by raising the percentage of cholesterol in HDL through exercise, weight reduction or the use of drugs. But "categorical proof" of these beneficial effects is lacking, according to Dr. Basil M. Rifkind of the National Heart, Lung and Blood Institute.
The new HDL results are the latest findings of the U.S.-U.S.S.R. Lipid Research Clinics Study, an ongoing 15-year collaboration that has permitted extensive international health comparisons through strict adherence to common methods and quality-control procedures. The project is jointly directed by Levy and Dr. Anatoli N. Klimov of the Academy of Medical Sciences in Leningrad.
The HDL study involved 7,815 men, ages 40 to 59, in Moscow and Leningrad. They were selected at random and followed for an average of 7 1/2 years, according to Levy. In addition, a comparable group of 982 American men from throughout the country have been studied for an average of 8 1/2 years.
All the men have had repeated physical examinations and blood tests, including a variety of cholesterol determinations using sophisticated laboratory techniques, Levy said. Follow-up has been more than 99% complete.
On average, the Soviet men had HDL levels that were 18% higher than the American men--53 milligrams per deciliter compared to 45.
After accounting for other factors such as age, blood pressure, weight and total cholesterol, the Soviet men with high HDL levels and those with lower levels had similar heart disease death rates, the researchers found. But the men with high HDL levels still had higher death rates from non-cardiac causes, primarily cancer, than those with lower HDL levels.
By comparison, the American men with high HDL levels had lower death rates from heart disease and lower overall death rates than those with lower HDL levels.
In a related finding, the researchers found that Soviet men with extremely low total cholesterol levels had higher death rates from heart disease than those with average cholesterol levels, another result that contrasted with the results for American men.
The new HDL data comes at a time when heart disease and overall death rates are increasing in the Soviet Union while declining in the United States and most Western nations.
According to Levy, the "striking" differences may eventually be explained by environmental, dietary or genetic differences between Soviets and Americans.