Heredity plays big role in heart disease risk factors

October 14, 2005

Heredity plays a major role in determining the blood lipid profile and heart rate variability of blacks and whites, two major risk factors for coronary artery disease, researchers say.

"There are some interesting ethnic differences in cardiovascular risk factors, including the fact that blacks tend to have higher HDL (high-density lipoprotein) and lower triglycerides, which is an advantage, and we suspect it is due to genetic influences," says Dr. Catherine L. Davis, clinical health psychologist at the Medical College of Georgia.

Coronary artery disease rates in the United States are similar or lower in blacks yet blacks have higher mortality rates.

Dr. Davis and her colleagues at MCG's Georgia Prevention Institute examined heritability - the percentage of a variable attributable to genes - to better understand the influence of genetics and environment on heart health.

Heritability studies were enabled by data MCG is collecting on 500 pairs of twins - blacks and whites, identical and fraternal - to determine whether environmental stress is a risk factor for cardiovascular disease. Identical twins have identical genes and fraternal twins share about 50 percent of their genes, much like normal siblings.

"Any differences between identical twins must be due to the environment," says Dr. Harold Snieder, genetic epidemiologist. "So you can quantify the part that is due to genetics," he says, noting that heritability provides an aggregate look at the effect of genes, many of which may still be unknown.

Across both races they found that lipid levels, which include so-called good cholesterol, HDL, and bad cholesterol, LDL, as well as triglycerides, are 60 percent to 80 percent determined by genetics.

A separate study found heart rate variability - the heart's ability to respond to changing demands - was heritable and equally so, about 70 percent, among young blacks and whites, Dr. Snieder says.

"We also were able to confirm that blacks indeed showed a more favorable pattern of heart rate variability," he says. "If you have a lot of variability, it means your heart is able to cope well with changing demands. The heart needs to adapt all the time in real life," says Dr. Snieder.

"It's a paradox," Dr. Davis says. "It's the opposite direction you would expect given the disparities in health outcomes."

"We would have expected environmental influences to be more important in blacks," adds Dr. Snieder. "We did not find that."

What they did find they hope will provide new insight and possibly new, more targeted treatment strategies for a cross section of people with heart disease.

"What we are very interested in is how these risk factors for cardiovascular disease develop over time and to what extent the development is influenced by genes and environment," says Dr. Snieder, who plans on gathering longitudinal data on an even larger percentage of the twins he's following.

"Even having these genes doesn't make blacks into long-lived healthy people necessarily," says Dr. Davis. "But maybe that link could help scientists develop medicines that target the protein that gene encodes, to help people who have high triglycerides try to correct them or try to help them raise their HDL."

The lipid study, published in the October issue of Twin Research and Human Genetics, included 106 black twins and 106 white twins. The heart rate variability study, published in the October issue of the American Journal of Cardiology, looked at 166 adolescents, 104 pairs of twins and 11 individual twins.

A related candidate gene study, published in the October issue of Ethnicity and Disease, looked at a handful of genes linked to obesity and implicated in lipid metabolism in mostly unrelated individuals: 413 health adolescents and young adults who were 44 percent black and 53 percent male. Researchers wanted to explore the relationship between these genes and lipid levels - in general, lipid levels worsen when weight increases - as well as any racial differences, Dr. Davis says.

They found whites were much more likely to have a variation of the LDL receptor gene that raises triglycerides. A mutation in a second candidate gene, ApoB, seemed to predict total cholesterol but the total varied with body mass index: heavier people were more affected by the gene. Those under age 18 with the same ApoB variant had a higher total cholesterol. The effect of that variant wasn't seen in adults, making researchers suspect its activity might be tied to puberty. Also, a variant of TNFĄ gene was linked to a lower HDL in men. "Women are known to have higher HDL levels than men," Dr. Davis says. "This gene might be interacting with sex hormones to influence men's HDL levels and make them a bit lower."
-end-
Co-authors on the studies include Dr. Xiaoling Wang, Dr. Snieder's postdoctoral fellow; Dr. Frank A. Treiber, MCG vice president for research and vice chair of basic research for the Department of Pediatrics; Dr. Julian F. Thayer, Emotions and Quantitative Psychophysiology Section, National Institute on Aging, Gerontology Research Center, Baltimore; and Dr. Anastasia Illiadou, Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm.

Medical College of Georgia at Augusta University

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