Why is it that some people can smoke, eat cheeseburgers for lunch and steak for dinner, never exercise and still not develop heart disease, while others who follow a strict, low-fat diet and exercise every day can't avoid it? Genes make the difference, said Dr. Helen Hobbs, chief of clinical genetics at UT Southwestern and holders of the 1995 Dallas Heart Ball Chair in Cardiology Research.

Dr. Hobbs spoke on "Good Genes, Bad Genes: How Can You Tell?" at the fourth autumn women's luncheon for the Friends of the Center for Human Nutrition. Different genetic traits contribute to whether a person develops heart disease directly or indirectly, Dr. Hobbs said. Sometimes a healthy lifestyle can counterbalance a genetic predisposition to heart disease, while for other individuals, having good genes that protect against heart disease can outweigh an unhealthy lifestyle.

Using four well-known, yet diverse, men--Hindu nationalist leader and social reformer Mahatma Gandhi, actor/comedian John Candy, tennis star Arthur Ashe and former British Prime Minister Winston Churchill, she illustrated her point."Some people fulfill all of our expectations of who is going to get heart disease and who is not," she said. "Gandhi was a vegetarian, very thin and physically active. He had no evidence of heart disease when he was tragically murdered by a religious zealot at the age of 73. In contrast, John Candy died of a heart attack at the young age of 43. But many of us were not really surprised when he died. He lived the life and had the physique of someone we'd expect to have heart disease. His favorite foods were pizzas, hoagies and hot dogs, and he did not exercise at all."

But there are others whose lives do not follow these predictable patterns."Arthur Ashe died of AIDS, but he got AIDS because he had coronary artery disease and had heart attacks in his 30s despite being thin, physically active and consuming a good diet," she explained.During a bypass surgery he received a blood transfusion tainted with the AIDS virus."Actually, he indirectly died of heart disease," she said. "Winston Churchill did everything we tell our patients not to do," she said. "He loved to eat--the richer the food the better, never exercised, drank heavily and had an ever-present cigar hanging from his mouth. And yet he lived to the ripe old age of 90 and had no evidence of heart disease when he died."

Using the analogy that each person is dealt a hand of cards when they're born representing his or her genetic makeup, Dr. Hobbs illustrated what kinds of card these four prominent men might have been holding.Imaging that black cards are protective genes, red cards are genes predisposing a person to heart disease and a joker represents a single unknown gene with a strong predisposition to heart disease. For Ashe--a joker and black cards. "It turns out he had very high plasma LDL (low-density lipoprotein) cholesterol," Dr. Hobbs said. "This probably was responsible for his having heart attacks at an early age. He is an example of a person who inherited a pretty good hand but because of one bad card suffered the ravages of heart disease."

For Churchill--all black cards. "He inherited a good hand of cards, so no matter what he did, he did fine because he had a lucky hand," she said.For Gandhi and Candy--a fairly well distributed hand of red and black cards."Because Gandhi lived an exemplary life when it comes to heart-disease risk factors, he may have overcome any genetic disposition," she said. "But with Candy, we find that he not only lived a non-exemplary lifestyle but also inherited genes that predisposed him to heart disease. His father died of heart disease at 34."

Since researchers can't really see what kinds of genetic cards a person holds, Dr. Hobbs and her colleagues at UT Southwestern are trying to determine who will develop heart disease, who won't and why.There are known risk factors for heart disease: age (men over the age of 45 and women over 55) smoking, hypertension, diabetes, obesity, high cholesterol and a family history. "About 50 percent of heart disease can be attributed to genes and about 50 percent to environmental factors," she said. "Most of us have a nice balance. If we haven't inherited bad genes but smoke and eat bad foods our risk is increased. Alternately, if we try to adhere to a heart-healthy lifestyle, sometimes we can minimize the environmental factors and compensate for inherited genetic predisposition to develop heart disease."

Her research focuses on defining the genetic factors that contribute to high cholesterol. UT Southwestern researchers currently are studying 150 families in an attempt to identify which genes increase cholesterol levels. A direct correlation exists between high LDL, the "bad cholesterol," and the incidence of coronary artery disease. People with high levels of HDL, high-density lipoproteins or the "good cholesterol," are protected from heart disease. For example when total cholesterol increases from 150 to 200 milligrams per deciliter, there is a slight increased risk of coronary artery disease. But when it goes from 200 to 250 mg/dL or from 250 to 300 mg/dL, there is a dramatic increase in risk. "If we could find the genes responsible, we may figure out ways to modify their expression and hopefully change cholesterol levels," she said.