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A relative's age at heart attack
Someone who reports that both grandfathers had heart attacks may find, on a closer look, that their first events came at 87 and 92. That is not premature heart disease. A first heart attack or stroke at a young age is, and it sets how aggressive a lifetime of prevention will be.
Family history can't be modified, but it raises awareness and carries across generations. For those with significant family histories, prevention strategies may start earlier, and so may testing, much as cancer screening begins younger for the children and grandchildren of people who had cancer. Heart disease genetics work the same way.
Why does the age of onset matter so much?
A heart attack at a young age suggests a strong inherited contribution, since a lifetime of ordinary wear has had less time to build up. American cardiology guidelines define premature heart disease in a first-degree relative as occurring before 55 in men and before 65 in women. A relative's heart attack at 90 mostly reflects age. A heart attack at 45 points to something in the family's biology.
How can genes drive heart disease?
Familial hypercholesterolemia is an inherited condition caused by mutations in genes such as LDLR, which clears LDL cholesterol from the blood. It affects roughly 1 in 250 people, according to population studies, and it leaves LDL cholesterol high from birth. People with it can develop heart disease in their 30s and 40s. Many other genes each add a small amount of risk, and researchers combine them into polygenic risk scores.