Not long ago, one's lipid profile was a simple number produced by adding together the levels of high-density lipoproteins (HDL) and low-density lipoproteins (LDL), the so-called "good" and "bad" forms of cholesterol. However, researchers have now identified five subclasses of HDL, four subclasses of LDL, as well six subclasses of very low density lipoproteins (VLDL), as well as intermediate-density lipoprotein (IDL). In addition to the levels of the lipoproteins, also critical is the size of the particles they form in the blood.
In a study that takes these new subclasses into account, the Duke researchers have found that there are racial and gender differences in the sizes and numbers of the particles of these lipoproteins. Furthermore, they said, these differences can determine one's risk of developing cardiovascular disease. These differences help explain why two people with the same overall cholesterol level can have markedly different degrees of cardiovascular disease, the researchers said.
"It is important to know these differences, because the commonly used lipid profiles do not always tell the complete story," said Johanna Johnson, Duke exercise physiologist and first author of a paper published in the October, 2004, issue of the journal Atherosclerosis. "Generally speaking, African-American women have the best lipoprotein distribution, while white men have the worst profile.
"Our data would suggest that the subclass profile of the women in our study would place them at reduced risk for heart disease, even though their total cholesterol and LDL levels are higher than men," she continued. "Additionally, the significant racial difference seen among the LDL and VLDL subclasses would appear to put whites at more risk. These gender and racial differences would not be apparent in traditional lipid profiles."
The Duke team studied 285 sedentary and overweight men and women without a history of heart disease or diabetes as a part of one of the first large-scale clinical trials designed to measure the effects of differing amounts and intensities of exercise on the average American couch potato.
The trial, led by Duke cardiologist William Kraus, M.D., was support by a $4.3 million grant from the National Heart, Lung and Blood Institute. Dubbed STRRIDE (Studies of Targeted Risk Reduction Interventions through Defined Exercise), the five-year trial began in 1998.
"While others studies have suggested that in terms of lipid profiles, African-Americans are better off than whites and women are better off than men, what has not been known before is the distribution of the different particle size and number," Kraus said. "No matter how we look at it, white men have the higher risk of developing metabolic syndromes, diabetes and cardiovascular disease. When it comes to lipids, white men are cesspools."
Cholesterol and triglycerides are energy-rich fats, or lipids, that must "attach" to protein particles in order to circulate throughout the bloodstream and nourish tissues. Abnormal levels of these lipoprotein units have been linked to the progression of atherosclerosis and heart disease.
"It is known that small, dense LDL particles are associated with increased risk for cardiovascular disease, and our study found that men have higher levels of these particles compared to women, and that whites have higher levels than African-Americans," Johnson said. "Additionally, the white men in our study had 2.5 times higher levels of these small dense particles than any other group."
While the researchers found no difference between African-American and white men in terms of LDL particle concentration, they did find that African-American women tended to have larger LDL particle sizes with lower amounts of small LDL particles than white women.
In terms of HDL, which is known to protect against cardiovascular disease, the researchers found that women not only had higher levels of HDL cholesterol compared to men, but also had higher amounts of the large HDL particles with a greater percentage of their total HDL being larger. While there were no significant racial differences, there was a tendency for African-Americans to have a greater percentage of their HDL being large particles.
"Larger HDL particles appear to have a greater protective effect against cardiovascular disease," Johnson said. "The African-Americans in our study had a significantly larger average HDL size than whites. With the lowest average concentration of large HDL particles, the white men displayed the least desirable profile."
High levels of IDL have recently been appreciated as a possible predictor of cardiovascular disease progression. In the current study, the Duke team found no gender differences, but they did see IDL levels three times higher in whites than African-Americans.
The researchers also looked at the levels of small HDL and large VLDL particles, which are known risk factors for coronary artery disease. They found that men have higher amounts of both particles, and whites have significantly higher levels of large VLDL than African-Americans.
"Taken together, the findings from this study suggest that whites, particularly white men, are at a greater risk for cardiovascular disease, yet when you look at their standard lipid profile, there are no significant differences," Johnson said.
Amongst other findings, the STRRIDE trial demonstrated that aerobic exercise can have a positive effect on cholesterol levels by making the particles larger and fluffier. The results of that study were published in the New England Journal of Medicine in November, 2002. The Duke researchers are currently enrolling patients in the STRRIDE II trial, supported by a recent $3.1 million NIH grant, to measure the effects of resistance training of cardiovascular risk factors.
Joining Johnson were Duke colleagues Cris Slentz, Ph.D., Brian Duscha, and Gregory Samsa, M.D., as well as Joseph Houmard, Ph.D., and Jennifer McCartney, East Carolina State University.
Journal
Atherosclerosis