To the surprise of researchers who had thought the very notion a joke, an international consortium of investigators reported on Wednesday that shorter stature increases the risk of heart disease. After gathering genetic data from nearly 200,000 men and women worldwide, the investigators found that each extra 2.5 inches of height brings a 13.5 percent reduction in heart disease risk. The relationship is present throughout the range of adult heights.
A person who is 5 feet tall has a 30 percent greater chance of developing heart disease than someone who is 5-foot-6, said a lead author of the new study, Sir Nilesh Samani, a professor of cardiology at the University of Leicester in England. Of course, the increased risk pales in comparison to that caused by smoking, which elevates the odds of getting heart disease by 200 to 300 percent.
There is nothing people can do about their height, but the researchers hope the finding will lead to the discovery of new links to heart disease. The paper was published in The New England Journal of Medicine.
No one was more surprised by the result than heart disease experts, although they have known about a purported association between height and heart disease for more than half a century. It was first pointed out in 1951 by Dr. Paul Dudley White, a cardiologist who was President Dwight D. Eisenhower's physician.
He observed that 97 men and three women who had a heart attack before age 40 and were admitted to Massachusetts General Hospital were 2 inches shorter on average than 146 healthy men.
Since then, experts have noted that shorter people are more likely to get heart disease in a variety of populations and ethnic groups, even after accounting for such risk factors as smoking and cholesterol, diabetes and obesity. But few researchers took the finding seriously. Height was just a marker for some other problem causing heart disease, most scientists said - perhaps a poor diet, or infectious diseases in childhood that led to a lifelong weakness of the heart.
"This idea that shorter stature is associated with coronary artery disease is something we would laugh about," said Dr. Michael Lauer, director of cardiovascular sciences at the National Heart, Lung and Blood Institute. "We would think about it as yet another example of epidemiology going amok."
Samani and his colleagues realized that if there was a real link, genetic variations that resulted in short stature would also result in a greater risk of heart disease.
Previous research had identified 180 genetic variants that control height. To find out if those variants also affected heart disease risk, Samani and his colleagues examined the genetic profiles of more than 200,000 people whose DNA had been analyzed in a variety of other studies.
People with the genetic variants were more prone to heart disease, the scientists found. But what was the connection? Did the genes controlling height also affect obesity, diabetes or blood pressure?
Samani and his colleagues found just one link, and it was a very small one: The genetic variants associated with shorter stature also were linked to slightly higher levels of LDL, the form of cholesterol that increases heart disease risk, and to slightly higher levels of triglycerides, blood fats that are also a risk.
But that was not enough to account for all of the increased risk, noted Dr. Sekar Kathiresan, an author of the paper and director of preventive cardiology at Massachusetts General Hospital. The rest, the researchers speculated, may come from poorly understood mechanisms, governed by height genes, that control the development of both blood vessels and bones.
Not everyone is impressed by the new report. Dr. Kari Stefansson, chief executive of deCODE Genetics, said the increase in heart disease risk was real but so small as to be not very meaningful. "It's a weak effect," he said.
Others, like Lauer, find the new report an exciting taste of the science to come. Until recently, heart disease research focused on factors that greatly increase risk, like cholesterol levels. Research into the genetic underpinnings of disease may point to more "low-hanging fruit" in "other orchards we haven't seen," Lauer said.
Studies of huge DNA databases, like the new research, show the power of genetics to resolve questions that had seemed unanswerable.
"The Achilles' heel of epidemiology has been the inability to distinguish between associations that are correlations and those that are causal," Lauer said. Until now, the only way to do that was through large, expensive and time-consuming randomized controlled clinical trials.
For example, the Women's Health Initiative studied whether taking hormones after menopause could reduce the risk of heart disease, which seemed well established. Thousands of women were told to take hormones after menopause, or not to. After years of study and millions of dollars, the result was clear: The hormones did not protect against heart disease.
No randomized trial can test whether height is linked to heart disease risk. But genetic variations are distributed at random in populations, and genes are not affected by lifestyle or environmental factors that have to be accounted for when researchers analyze data they get by simply observing populations.
In a sense, Lauer said, we are nature's random experiments.
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2015 New York Times News Service