Genes May Leave Short People Prone to Heart Disease

WEDNESDAY, April 8, 2015 (HealthDay News) -- Short people may be more likely to have heart
disease, and that increased risk could be linked to the genetics that also determine height, a Britishled research team suggests.

A person's risk of heart disease increases about 13.5 percent for every 2.5 inches of difference in
height, the scientists said. That means a 5-foot-tall person has an average 32 percent higher risk of
heart disease than a person who's 5-foot 6-inches tall, according to the researchers.
An in-depth genetic analysis of more than 18,000 people revealed a number of genes linked to
human growth and development that likely play a role in the increased risk for heart disease.
"We found that people who carry those genetic variants that lower your height and make you shorter
are more likely to develop coronary heart disease," said Dr. Nilesh Samani, a professor of cardiology
and head of the department of cardiovascular sciences at the University of Leicester in England.
However, while the current study was able to show an association between genetics, height and a
higher risk of heart disease, it wasn't able to prove a cause-and-effect relationship.
The study is published online April 8 in the The New England Journal of Medicine.
Heart disease occurs when the arteries that supply blood to the muscles of the heart become
narrowed, as a result of fatty plaques that build up along the artery walls. If a blood clot forms
within a plaque-narrowed section of artery, it can block blood flow to the heart muscle and cause a
heart attack.

But researchers found that only a third of the increased genetic risk they observed comes from
genes related to levels of "bad" LDL cholesterol and triglycerides in the body.
That means most of the heart disease risk related to shortness of stature is tied to other genetic
factors that are as yet poorly understood, said Dr. Ronald Krauss, director of atherosclerosis
research at Children's Hospital Oakland Research Institute in California.
"The genetic data is sufficiently strong to argue there's something else going on," Krauss said. "What
that might be is still conjectural."
Some genes identified by researchers could influence heart disease risk by affecting the growth of
cells in the artery walls and the heart, Krauss and Samani said.
"These variants could affect the arterial walls in a way that makes them more likely to develop
atherosclerosis," the medical term for narrowed or hardened arteries, Samani said.
Other genes appear to be linked to inflammation in the body, which is another risk factor for heart
disease, Krauss said.
It's been known for more than 60 years that people who are shorter run a higher risk of heart
disease, but this is the first study to suggest that genetics are a primary cause, Samani said.
Up to now, doctors have been unable to rule out other possible explanations, he said. For example,
one theory has held that people grow up shorter due to poor nutrition, which also predisposes them
to heart disease.
To better understand the heart risks associated with short stature, researchers pooled data from two
recent international research efforts into the human genome, one of which explored the genetics of
height and the other the genetics of heart disease, said study co-author Dr. Christopher O'Donnell,
associate director of the Framingham Heart Study for the U.S. National Heart, Lung, and Blood
Institute.
The research team first tested the association between a change in height and risk of coronary
artery disease by examining 180 different height-associated genetic variants in nearly 200,000
people, and concluded there's a relative 13.5 percent increase in heart disease risk for every 2.5
inches shaved off a person's height.
They then drilled down to very specific individual genetic data from a smaller pool of more than
18,000 people. They identified a number of pathways by which genes related to height could also
influence heart disease risk.
Interestingly, the effect of height on heart disease risk may be gender-specific. "We found a clear-cut
effect in men, but we didn't see a clear-cut effect in women," Samani said, adding that significantly
fewer women in the study could have affected the statistics.
Samani, Krauss and O'Donnell all said that these results are preliminary, and don't indicate that
short people need to do anything other than what's already recommended for everyone to lower
heart disease risk, such as eat a healthy diet and get regular exercise.
"We have an abundance of evidence that every person should look at their modifiable risk factors
and speak with their doctors," O'Donnell said. "It's not clear what one can do about their height, but

it's very clear there are a lot of behaviors one can change to improve their health overall."
SOURCES: Nilesh Samani, M.D., professor, cardiology, and head, department of cardiovascular
sciences, University of Leicester, U.K.; Ronald Krauss, M.D., director, atherosclerosis research,
Children's Hospital Oakland Research Institute; Christopher O'Donnell, M.D., M.P.H., associate
director, Framingham Heart Study, U.S. National Heart, Lung, and Blood Institute; April 8, 2015,
New England Journal of Medicine, online
http://www.nlm.nih.gov/medlineplus/news/fullstory_151905.html