John Fixx works out every day. Most days he runs. Sometimes he uses an elliptical machine. He lifts weights and follows a low-fat diet. He has never smoked. At 56, he has lived longer than his father and grandfather, who both died of heart attacks.
“We can’t control the DNA we are given,” said Fixx, who heads the Country School in Madison, Conn. “But we can control what we put into our bodies, and whether we exercise, get enough sleep and manage stress.”
If Fixx’s name sounds familiar, there’s a reason. His father, Jim Fixx, wrote “The Complete Book of Running,” a 1977 bestseller that helped fuel the running craze. John was 23 when his father died of a heart attack at 52 while out on a run. Jim Fixx had taken up running in midlife, lost weight and quit smoking, but apparently it was too late to outrun his family history: his father, Calvin Fixx, suffered his first heart attack at 36, then had a second one seven years later that killed him.
Yet his family believes that the healthy habits he embraced added years to his life. Vermont’s chief medical examiner agreed. She told the family that “his heart was so strong from years of exercise that it was able to pump blood through the diminished arteries far longer than would otherwise have occurred,” John Fixx said.
Many cardiovascular experts agree that a family history of early heart disease is a warning and that vulnerable people can lessen their risk. Moreover, advances in drug therapy have made it easier to control or treat conditions that contribute to heart disease, such as hypertension, high cholesterol and diabetes.
Having bad genes “doesn’t necessarily mean you are fated to have heart disease,” said Cashell Jaquish, a genetic epidemiologist with the NHLBI. “Other factors, like not smoking, diet and exercise, can have a very large effect. Family history does increase your risk slightly, but not as much as [not doing] these other things.”
Heart disease is the leading cause of death in the United States for men and women, killing more than 600,000 people annually, said the Centers for Disease Control and Prevention. Heart attack risk increases for all men after age 45, but it is more worrisome for people whose fathers are diagnosed with heart disease before 55, said the National Heart, Lung, and Blood Institute (NHLBI).
About 735,000 Americans have a heart attack each year. Of these, 525,000 are a first heart attack, the CDC said. Family history is one of several risk factors, which — in addition to lifestyle and such conditions as diabetes, high cholesterol and hypertension — include age, race and ethnicity.
Equally important, families share more than genes. They also often share the same environment, the same diet and behaviors such as smoking. This can complicate efforts to tease out the role of genetics.
“When large studies are conducted, results suggest about a twofold risk if you had a mother or father with coronary heart disease,” said Eric B. Rimm, director of the cardiovascular epidemiology program at the Harvard T.H. Chan School of Public Health. “The younger your parent was when [he or she] suffered the first event, the higher the risk for the child. However, this is not all genetic, since parents and children share similar lifestyle habits, so it’s tough to disentangle completely.”
Iftikhar Kullo, a cardiovascular genetics researcher at the Mayo Clinic, agreed. “If you’re dealt a bad hand by your family, it doesn’t mean you are determined to have heart disease,” he says. “You can reduce that risk. … Risk is a scale that you can dial up or down.”
Studies suggest that there are at least 161 identified genetic variants that have been linked to heart disease, and most of us have one or more of them. “These are variants that have modest effects,” Kullo said. “Each variant raises your risk anywhere from 5 percent to 35 percent, depending on the variant. The more you have, the higher your risk.”
Genetic testing for heart disease risk now takes place only as part of research. But Mayo is developing a test that may become more widely available as early as this year, Kullo said. “There will be a time when people will have a good idea of their genetic risk. In the meantime, the surrogate genomic test is your family history.”
Kullo said he believes knowing your individual genetic risk profile could encourage behavior changes or a willingness to begin medication. He said, “You can reduce [genetic] risk by lifestyle changes and speaking to your doctor about the possibility of medications to treat cholesterol or hypertension. It could save your life.”
He conducted a 2015 study comparing the use of genetic information to the current conventional method of assessing heart disease risk, the Framingham Risk Score. The study found that people with high cholesterol who knew their personal genetic data had lower “bad” cholesterol (low-density lipoprotein cholesterol, or LDL) after six months than those in a control group.
The NHLBI’s Jaquish said she believes the biggest benefit from personal genetic information will be in pharmacogenetics, the study of how genes affect the way people respond to drugs. “We’ll be using genetics to predict which drugs will work and which ones won’t.”
For example, patients with a variant of the CYP2C19 gene associated with a platelet clotting disorder do not respond to the drug Plavix, which is frequently prescribed to prevent clot formation. If patients knew they carried this variant, “their doctors could consider a different drug strategy,” Jaquish said.