How Do Your Genes Shape Your Risk of Heart Disease?

Heart disease reflects an interaction between genes and environment. Large population studies estimate that 40 to 60 percent of coronary artery disease risk is inherited. A family history of early heart disease roughly doubles risk, even after accounting for cholesterol, blood pressure, smoking, and diabetes.

Most inherited risk is polygenic. This means it comes from many small genetic variants rather than a single mutation. When combined into a polygenic risk score, these variants can identify people with nearly double the lifetime risk of heart attack, even when standard labs look normal. This explains why some patients with good cholesterol still develop premature disease.

Some genetic risks are more discrete and powerful. Lipoprotein(a), or Lp(a), is a cholesterol like particle that is almost entirely genetically determined. High Lp(a) increases risk of heart attack, stroke, and aortic valve disease. Diet and exercise have little effect on it, which is why measuring it once in adulthood is so important.

Genetic testing is now routine for many inherited cardiac conditions. It is used to confirm diagnoses, guide treatment, and screen family members. This process, called cascade testing, allows us to identify relatives who carry the same mutation before disease develops.

Familial hypercholesterolemia is a clear example. It affects about 1 in 250 people and causes lifelong very high LDL cholesterol due to mutations in genes like LDLR or APOB. Untreated, it leads to early heart attacks, often decades earlier than expected. When identified early, aggressive LDL lowering can reduce risk by roughly 80 percent. This is why familial hypercholesterolemia is considered a public health priority.

Hypertrophic cardiomyopathy is another common inherited condition. It is caused by mutations in sarcomere proteins that make heart muscle contract. The result is thickened, stiff heart muscle and a higher risk of arrhythmias and sudden cardiac death. Genetic testing allows us to monitor affected family members, guide exercise recommendations, and decide who may benefit from medications or implanted defibrillators.

Genetics also shapes treatment. PCSK9 inhibitors were developed after researchers discovered people with natural PCSK9 loss of function mutations had very low LDL and low heart disease risk. New therapies now target PCSK9 directly, and early human trials using gene editing have shown large LDL reductions after a single treatment. In hypertrophic cardiomyopathy, new myosin inhibitors directly counteract the hypercontractile state caused by sarcomere mutations.

Importantly, genes are not destiny. Multiple studies show that healthy lifestyle choices can cut genetic risk nearly in half. Physical activity, not smoking, maintaining metabolic health, and controlling ApoB remain powerful even in people with high inherited risk.

The practical takeaway is simple. Genetics help us identify risk earlier, not replace traditional prevention. When we combine genetic insight with aggressive risk factor control, we move from reactive cardiology to true prevention.