What is FH?

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Diagram courtesy of Sanofi.

Hypercholesterolemia in an excess of cholesterol in the bloodstream that increases the risk of heart disease and stroke. Familial hypercholesterolemia is when the excess of cholesterol is caused by an inherited condition. It is an autosomal dominant genetic disease, which means that siblings and children of a person with FH have a 50% risk of getting the defect. The condition may be discovered if you have a routine health check. People with FH have high cholesterol levels from birth and this leads to an early development of atheroma (fatty lumps within the arteries) and associated cardiovascular diseases (angina, heart attack, stroke, transient ischaemic attack and peripheral vascular diseases).

Causes of FH

Familial hypercholesterolemia is caused by a defect in a few genes responsible for the way cholesterol is handled in the body. The cholesterol is transported in the bloodstream within specific transporters called low-density lipoproteins (LDL), also called “bad cholesterol”. People with familial hypercholesterolemia have high levels of LDL-cholesterol because they cannot effectively remove the LDL particles from the bloodstream, which causes the development of atheroma and premature cardiovascular diseases. Generally, the defective gene is inherited from one parent (heterozygous inheritance), which affects about 1 in 500 people. If you inherit it from both parents (homozygous inheritance), the condition is more severe. The homozygous condition is rare, occurring with a frequency of 1:1,000,000.

Symptoms

Familial Hypercholesterolemia may be an asymptomatic disease with its first presentation being an acute myocardial infarction.

Clinical Findings

Possible signs of familial hypercholesterolemia include:

  • High levels of total cholesterol and LDL cholesterol, dating back to childhood.
  • Development of cardiovascular disease at a young age, in some people as young as 20 years old.
  • A strong family history of high levels of total and LDL cholesterol and/or early heart attack.
  • Elevated and therapy-resistant levels of LDL in either or both parents.
  • Presence of xanthomas –fatty cholesterol-rich deposits in the skin– usually found around the elbows, knees, buttocks and tendons.
  • Xanthelasmas – cholesterol deposits in the eyelids.
  • Corneal Arcus – a white ring around the cornea of the eye.
  • bodyImage_1
    Tendinous xanthomas in an untreated adult patient with heterozygous familial hypercholesterolemia
    Courtesy of Dr Jacques Genest
  • bodyImage_2
    Xanthelasmas around the eyes in an untreated adult patient with heterozygous familial hypercholesterolemia
    Courtesy of Dr Jacques Genest
  • bodyImage_3
    Corneal arcus in a patient with heterozygous familial hypercholesterolemia
    Courtesy of Dr Jean Davignon and Dr Robert Dufour
  • bodyImage_4
    Xanthomas in the knees in a patient with heterozygous familial hypercholesterolemia
    Courtesy of Dr Jean Davignon and Dr Robert Dufour
  • bodyImage_5
    Normal (left) versus xanthomatous Achilles tendons (right) and their radiological assessment
    Courtesy of Dr Jean Davignon and Dr Robert Dufour

Diagnosis

Familial hypercholesterolemia is a disease that is both underdiagnosed and undertreated. The aim of the FH Canada registry is to improve the detection and management of individuals and families with FH in Canada. The project will identify those affected by FH with the aim of lowering their high blood cholesterol and thus preventing early cardiovascular disease such as heart attack and stroke.

You may have been diagnosed by chance if you had a health screening check or noticeable fatty deposits on the skin or around the eyes. Or you may have been advised to have yourself checked when a member of your family was diagnosed with familial hypercholesterolemia or had a heart attack before the age of 50.

The diagnosis of familial hypercholesterolemia is based on physical examination and laboratory testing. A physical exam will be conducted by your physician and will help identify any types of fatty deposits or lesions that have developed as a result of the elevated cholesterol levels (xanthomas, xanthelasmas and corneal arcus). Your physician will also ask about your personal medical history, as well as your family medical history. Laboratory testing mainly includes a blood test for cholesterol levels. Familial hypercholesterolemia is diagnosed in the presence of increased cholesterol levels in the absence of secondary causes of hypercholesterolemia (diabetes, hypothyroidism, renal dysfunction, hepatic disease, some drugs such as oral contraceptives and adrenal steroids, alcohol, systemic lupus erythematosus, obesity and cigarette smoking). In adults, familial hypercholesterolemia is suspected if your blood total cholesterol level is 7.5 mmol/L or greater, or if your LDL-cholesterol levels are 4.9 mmol/L or greater. In children, the levels are 6.7 mmol/L and 4.0 mmol/L respectively. In some clinics, studies of heart function (stress test) and genetic testing may be included.

If you have FH, then each of your close family members has a 50% chance of also having FH, including parents, siblings, children, aunts, uncles, and cousins. This means that if you are diagnosed with FH, your whole family should get tested.

Treatment

The overall goal of treatment is to lower the risk for atherosclerotic heart disease by lowering the LDL cholesterol levels in the blood stream.

Lifestyle:

Being a genetic disorder, familial hypercholesterolemia is not caused by an unhealthy lifestyle. However, keeping yourself in the best physical condition will help prevent future problems.

A healthy lifestyle includes:

  • Eating healthily – diet should reduce the total amount of fat eaten to 30 percent of the total daily calories. You will almost certainly be referred to a dietitian to help you to make these changes in your eating habits.
  • Exercise.
  • Avoiding smoking.
  • Maintaining a normal weight.
  • Stress management

Medication:

You will be offered medication to help bring your cholesterol level down. The first and more effective choice are drugs called “statin” (HMG-CoA-reductase inhibitors). The most common statins used in Canada are atorvastatin, rosuvastatin and simvastatin. If the level of cholesterol does not come down, another medicine called ezetimibe, which decreases cholesterol absorption in the small intestine, is sometimes added. Bile acid binding resins, nicotinic acid (niacin), gemfibrozil, fenofibrate and estrogen replacement therapy in postmenopausal women can also be prescribed. Some patients with extreme levels of cholesterol, such as the homozygous patients, may need apheresis, a treatment which filters LDL cholesterol out of the blood.

Your general practitioner or family doctor may want to discuss referring you to a specialist. A specialist can advise you about your treatment and arrange the testing of close members of your family. You may also refer to the list of FH Canada Registry participating clinics.

The prognosis for people with familial hypercholesterolemia is usually good if you maintain a healthy lifestyle, have regular checks and take your medication without fail. The most significant complication is heart disease or another cardiovascular disease that may develop at a younger age than usual.

Lifestyle is the cornerstone of preventive strategies in children, and all children with a presumptive diagnosis of FH should undergo 6 to 12 months of extensive lifestyle changes including diet, exercise and a tobacco-free environment. As in adults, if drug treatment is required, statins should be used as first-line therapy with ezetimibe as a second-line agent. Bile acid binding resins should be considered third-line therapy.