Very High Cholesterol – Ongoing efforts seek to better identify and treat familial hypercholesterolemia, a leading cause of early heart attacks.

Some 35 million Americans have cholesterol values that put them at high risk for heart disease. The vast majority likely have dozens of different genetic mutations, each of which raises cholesterol by a little bit. Coupled with an unhealthy diet and not enough exercise, cholesterol creeps up slowly over time in these people.

But a small minority — about one of every 250 adults — have a genetic condition called familial hypercholesterolemia (FH). Most have a mutation in one of three key genes that provide instructions that help remove excess “bad” LDL cholesterol from the bloodstream. When one of these genes doesn’t operate properly, LDL cholesterol levels can skyrocket as high as 350 milligrams per deciliter (mg/dL) — more than three times higher than the desirable level of less than 100 mg/dL. Their total cholesterol levels (which includes LDL cholesterol plus other lipids) may reach 500 mg/dL or higher.

“Familial hypercholesterolemia is just as common as better-known -genetic conditions such as type 1 diabetes and cystic fibrosis,” says Dr. Pradeep Natarajan, director of preventive cardi-ology at Harvard-affiliated -Massachusetts -General Hospital. But many people have never even heard of FH, despite the fact that it’s a leading cause of premature (early) heart attacks — that is, those that occur in men before age 55 and in women before age 65.

Lifelong exposure to high LDL

People with untreated FH can succumb to a heart attack in their 30s or even earlier, which probably reflects the constant exposure to high LDL cholesterol levels starting at birth, says Dr. Natarajan. Because the condition remains underrecognized, experts have explored various strategies to identify people with FH at younger ages, as described in a recent study (see “Screening blood donors for inherited high cholesterol”).

But identifying people with FH is just part of the problem. Guidelines recommend testing children and adolescents at least once between ages 9 and 11 and again between ages 17 and 21. However, such testing doesn’t always happen. And even when testing reveals abnormally high LDL cholesterol, physicians often hesitate to prescribe potentially lifelong medications to young people with no symptoms, says Dr. Natarajan. “That’s unfortunate, because heart disease risk from FH is highly modifiable when the condition is recognized and managed early,” he adds.

Premature heart disease or very high cholesterol in a close family member (father, mother, brother, or sister) is a red flag for FH. Genetic testing isn’t always necessary, because high LDL cholesterol is reliable sign of heart disease risk in everybody, including those with FH, says Dr. Natarajan. In children, an LDL cholesterol level of 160 mg/dL or higher suggests FH; in adults, an LDL of 190 mg/dL or higher raises suspicion.

Screening blood donors for inherited high cholesterol

A study published online May 22 by JAMA Cardiology explored the notion of screening for familial hypercholesterolemia (FH) in blood donors at one of the country’s largest blood donation programs, Carter BloodCare, based in Texas. Here’s a summary of the findings:

  • Who: More than 1.1 million blood donors ages 16 and older, with a median age of 32 years.
  • When: In 2017, researchers reviewed total cholesterol values from blood donations given from 2002 to 2016.
  • How: For diagnosing FH, they used total cholesterol threshold values, which ranged from 270 mg/dL to 360 mg/dL or higher, depending on a person’s age.
  • Key findings: The median cholesterol value from all the blood donations was 183 mg/dL. But nearly 3,500 donors met the criteria for FH, based on their total cholesterol values. (The median value for this group was 332 mg/dL.)
  • What’s next: Screening blood donors could be a novel and potentially cost-effective way to identify FH, especially in younger people, who are less likely to see doctors regularly, according to the authors. They’re planning to follow up with donors flagged as having FH and connect them with appropriate medical care, including family screening.

Treating FH

The latest cholesterol treatment guidelines emphasize the importance of lowering excessively high cholesterol. For people with FH, that usually means high-intensity statin therapy. Many also need a second drug, such as ezetimibe (Zetia), which helps inhibit cholesterol absorption in the gut, and one of the newer injectable drugs known as a PCSK9 inhibitor, either alirocumab (Praluent) or evolocumab (Repatha), which work by helping to remove excess LDL from the blood. Other heart-healthy habits, as outlined in the American Heart Association’s Simple 7 (www.health.harvard.edu/simple7), are also very important, Dr. Natarajan says.

Source: https://www.health.harvard.edu/heart-health/when-very-high-cholesterol-runs-in-the-family

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