Oregon Health & Science University
  • Sergio Fazio, M.D., Ph.D. Sergio Fazio, M.D., Ph.D.
    OHSU Knight Cardiovascular Institute
    Dr. Fazio is the director of OHSU’s Center for Preventive Cardiology. He is professor of medicine and is board-certified in clinical lipidology. His clinical expertise includes genetic and acquired lipid disorders and alternative therapies for people unable to tolerate lipid drugs.

Familial hypercholesterolemia

Do you have a patient whose cholesterol remains high even with statins? If LDL remains over 150 despite medication, dietary changes and exercise, you may consider familial hypercholesterolemia, or FH. This life-threatening genetic syndrome is underdiagnosed, but manageable when identified early.

What is familial hypercholesterolemia?

Familial hypercholesterolemia is a genetic disorder with heterozygous and homozygous forms characterized by high LDL cholesterol from birth. The major risk is very early coronary heart disease and myocardial infarction (the youngest patient with FH-related MI was six). On average, untreated patients with FH may expect a loss of 15 to 20 years of life expectancy.
FH is not rare. In the United States, between 600,000 and 2 million people have it, and worldwide prevalence ranges from 1 in 200/500 for the heterozygous form to 1 in 1 million for the homozygous form.

Why diagnosing FH is critical

With timely diagnosis and appropriate treatment, patients with FH can live an essentially normal life span. However, just five percent of those with LDL over 190 are diagnosed with FH, and approximately 90 percent of patients with FH go undiagnosed.
For patients with FH, the risk of MI depends on LDL levels, which vary by severity of genotype.

Severity of FH genotype LDL without treatment Myocardial infarction may occur as early as:

(1 in 200/500 –
FH mutation from one parent)

Untreated, >190 mg/dL

40s and 50s

(1 in 1 million –
FH mutation from both parents)

Untreated, >350 mg/dL

20s and 30s

How is FH diagnosed?

A lipid panel and family medical history are sufficient for clinical diagnosis. The main characteristics include:

  • High LDL at any age — 190 or above (not on statin)
  • Premature CHD
  • History of FH or early CHD in first degree relatives
  • Tendon xanthomata — Fatty deposits on the tendons
  • Arcus corneae — A cloudy ring around the iris of the eye

Which patients need screening?

All patients with family history of early CHD or MI and first-degree family members (parents, siblings and children) of patients with FH.

Patient characteristics to prompt FH screening

Family history of CHD before age 50

LDL cholesterol above 190, or above 150 with medication, dietary changes and exercise

Tendon xanthomata

Premature sudden cardiac death in family member

Arcus corneae in young patients — These fatty corneal deposits are associated with normal aging, but should raise suspicion of FH in patients from childhood to early middle age (<50).

Treating FH

Nearly 100 percent of FH patients require statins. Generic statins are an excellent way to protect patients who have already had an MI, but patients with FH generally require higher doses of the two higher-potency statins (one of which is branded). Many FH patients require double or triple therapy to bring LDL into a safe range. Some primary providers and other non-cardiac specialists are less comfortable with combination therapy regimes for patients already taking high-intensity statins.

The OHSU Center for Preventive Cardiology at the Knight Cardiovascular Institute partners with providers to find the best regimen and assist with management of patients with FH.

New, adjunct and alternative FH therapies

In the last two years, the U.S. Food and Drug Administration approved two new drugs for homozygous FH: lopitamide (Juxtapid) and mipomersen (Kynamro). The OHSU Center for Preventive Cardiology is experienced in prescribing and monitoring these drugs for the appropriate patients (homozygous FH) when other therapies are not effective. Good candidates are patients with LDL above 350 mg/dL, which should be evaluated for homozygous FH by a lipid specialist. The OHSU Center for Preventive Cardiology is also the only place in the state offering LDL apheresis (cholesterol dialysis), an FDA-approved procedure that extends the life of CAD patients with very severe LDL elevations. Insurance covers the procedure for post-MI patients whose LDL remains above 200 even with medication. Patients with no MI, but an LDL above 300 with medication, also qualify.

For patients who do not respond well to, do not want to take, or do not tolerate statins, we support a holistic approach including alternative and complementary therapies. An approach based exclusively on dietary supplements is available for those who cannot accept standard therapy.

OHSU clinical trials and FH registry

The Knight Cardiovascular Institute is committed to clinical trials of promising drugs for FH and other lipid disorders. We are among the few institutions nationwide with an FH registry.

Your partner for diagnosing and treating FH

Patients with FH have multiple treatment options and often require combination, novel, alternative, experimental or invasive therapies. We are always available to consult or assist you in helping your patients. The OHSU Center for Preventive Cardiology is composed of five expert providers and a full-time dietitian.

Contact us

To refer a patient or consult with our team, call the OHSU Physician Consult & Referral Service at 800 245-6478.

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