DALLAS, Feb. 11 -- Researchers may have pieced together part of the puzzle about why some individuals with many risk factors for atherosclerosis never develop heart disease and stroke while others with few risk factors do.
Their findings are reported this month's Arteriosclerosis, Thrombosis and Vascular Biology: Journal of the American Heart Association.
According to the study's lead author, Sharon L.R. Kardia, M.D., and colleagues at the University of Michigan, Ann Arbor, the gene responsible for regulating levels of certain fats in the bloodstream also appears to determine how much influence cholesterol and other risk factors have on atherosclerosis, the disease process that leads to heart attacks and strokes.
The gene that Kardia and her colleagues say affects the influence of risk factors is apolipoprotein E (Apo E). Apo E is a protein on the "good" cholesterol and "bad" cholesterol in the blood which helps deliver the cholesterol to the liver and elsewhere in the body.
"Whether a risk is really a risk factor for a particular individual may be determined in part by the form of their Apo E gene," she says. The findings are in line with the current understanding of the complexity of heart disease and stroke because not everyone with many risk factors develops cardiovascular disease.
Kardia, assistant professor of epidemiology, examined the relationship between risk factors, atherosclerosis, and the genetic makeup of 169 women and 160 men who were participants in the Rochester Family Heart Study.
Atherosclerosis is a disease in which calcium, along with fats and cholesterol, collect in the blood vessel to form plaques. The plaques can block blood flow to the heart or brain, triggering a heart attack or stroke. Participants had no prior signs of heart disease and had not suffered a stroke. All participants were under 60 years of age.
To detect early signs of atherosclerosis, researchers used electron-beam-computed tomography. This technique can detect calcium in plaques in individuals without symptoms of heart disease and stroke.
Different versions of the Apo E gene exist. They are E-2, E-3 and E-4. These combine to form six possible Apo E genotypes (3/2, 3/3, 4/3, etc.). E-3/3 is the most common genotype in the general population.
Kardia and her colleagues sought to determine the influence of specific Apo E genotypes in predicting the risk of developing early calcification of the arteries in the individuals studied. They were looking to determine which specific risk factors were associated with the development of early calcification.
The Apo E-4/3 genotype in women was associated with calcification if the women had an increased body mass index and increased blood levels of triglycerides. But, in contrast, the E-3/3 genotype was not associated with calcification in these risk groups. Body mass index (BMI) is a measure used to classify people on the basis of body density, which reflects fat levels. A BMI higher than 30 is considered obese. Obesity is a risk factor for heart disease. In men the E-4/3 genotype was associated with calcification if the men had increased body mass index, but not elevated cholesterol levels. In contrast those with the E-3/3 genotype had a lower risk.
"Although we do not have the knowledge of the biological mechanisms to explain why some genotypes are more at risk than others, we do know that disease susceptibility in individuals is a consequence of interactions between genetic and environmental factors," she says. "These kinds of studies might help explain some of that variation and have implications for treatment." According to Kardia, individuals with one type of Apo E may need to focus primarily on controlling their blood levels of cholesterol rather than other risk factors.
"However, before we can use this kind of information the way we use a cholesterol test, we need to have a large prospective study in which healthy individuals are followed over time to confirm these associations that we have found in our study on how the Apo E gene affects risk of heart disease and stroke," says Kardia.
Co-authors are M.B. Haviland, M.D.; C.F. Sing, M.D., University of Michigan, Ann Arbor; and R.E. Ferrell, University of Pittsburgh.
Media advisory: Dr. Kardia can be reached at 734-936-0866. (Please do not publish numbers)