Familial hypercholesterolemia

Familial hypercholesterolemia is a disorder of high LDL ("bad") cholesterol that is passed down through families, which means it is inherited. The condition begins at birth and can cause heart attacks at an early age.

Alternative Names

Type II hyperlipoproteinemia; Hypercholesterolemic xanthomatosis; Low density lipoprotein receptor mutation

Causes

Familial hypercholesterolemia is a genetic disorder caused by a defect on chromosome 19.

The defect makes the body unable to remove low density lipoprotein (LDL, or "bad") cholesterol from the blood. This results in high levels of LDL in the blood. High levels of LDL cholesterol make you more likely to have narrowing of the arteries from atherosclerosis at an early age. Those with familial hypercholesterolemia are more likely to have a family history of high cholesterol and heart disease at a younger age than normal.

The condition is typically passed down through families in an autosomal dominant manner. That means you only need to get the abnormal gene from one parent in order to inherit the disease.

In rare cases, a child may inherit the gene from both parents.When this occurs, the increase in cholesterol levels is much more severe, greatly increasing the risk for heart attacks and heart disease.

Symptoms

Symptoms that may occur include:

·                        Fatty skin deposits called xanthomas over the elbows, knees, buttocks, tendons, and around the cornea of the eye

·                        Cholesterol deposits in the eyelids (xanthelasmas)

·                        Chest pain (angina) or other signs of coronary artery disease; may be present at a young age

Exams and Tests

A physical examination may reveal fatty skin growths called xanthomas and cholesterol deposits in the eye (corneal arcus).

The doctor will ask questions about your personal and family medical history. There may be:

·                        A strong family history of familial hypercholesterolemia or early heart attacks

·                        High levels of LDL in either or both parents

Individuals from families with a strong history of early heart attacks should have blood tests done to determine lipid levels.

Blood tests may show:

·                        High levels of total cholesterol

o                                      Greater than 300 mg/dL in adults

o                                      Greater than 250 mg/dL in children

·                        High LDL levels

o                                      Greater than 170-200 mg/dL in children

o                                      Greater than 220 mg/dL in adults

·                        Normal level triglycerides

Other tests that may be done include:

·                        Studies of cells called fibroblasts to see how the body absorbs LDL cholesterol

·                        Genetic test for the defect associated with this condition

Treatment

The goal of treatment is to reduce the risk of atherosclerotic heart disease. Those who inherit only one copy of the defective gene may respond well to diet changes combined with statin drugs.

LIFESTYLE CHANGES

The first step is to change what you eat. This is tried for several months before drug therapy is added. Diet changes include reducing total fat intake to less than 30% of the total calories you eat.

You can reduce your saturated fat intake by:

·                        Decreasing amounts of beef, chicken, pork, and lamb

·                        Substituting low-fat dairy products for full-fat ones

·                        Eliminating coconut and palm oils

You can reduce your the amount of cholesterol you eat by eliminating egg yolks and organ meats.

Dietary counseling is often recommended to help people make these adjustments to their eating habits. Weight loss and regular exercise may also aid in lowering cholesterol levels.

MEDICATIONS

If lifestyle changes do not change your cholesterol levels, your doctor may recommend medication. There are several types of drugs available to help lower blood cholesterol levels, and they work in different ways. Some are better at lowering LDL cholesterol, some are good at lowering triglycerides, while others help raise HDL cholesterol.

The most commonly used and effective drugs for treating high LDL cholesterol are called statins. The include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor).

Other cholesterol-lowering medicines include:

·                        Bile acid-sequestering resins

·                        Ezetimibe

·                        Fibrates (such as gemfibrozil)

·                        Nicotinic acid

Those with more severe forms of this disorder may need a treatment called extracorporeal apheresis. This is the most effective treatment. Blood or plasma is removed from the body. Special filters then remove the extra LDL-cholesterol, and the blood plasma is then returned.

Back to TopOutlook (Prognosis)

How well you do greatly depends on whether or not you follow your doctor's treatment recommendations. Diet changes, exercise, and medications can lower cholesterol levels for those with the milder form of this disorder, and may significantly delay a heart attack.

Men and women with familial hypercholesterolemia typically are at increased risk of early heart attacks.

Risk of death varies among patients with familial hypercholesterolemia. Persons who inherit two copies of the defective gene have a poorer outcome. That type of familial hypercholesterolemia causes early heart attacks and is resistant to treatment.

type of Lipid

Type of Lipid and their Functions

Physicians talk of the lipid profile, or lipid type while most patients want to know about their cholesterol.  We really are on the same team, looking for the same goals of reducing the risk of heart and artery disease caused by abnormally levels of the types of lipids that lead to atherosclerosis.  We just have different words we use.  The jargon physicians use can be confusion, and lipid type is a good example.  First some definitions:

Lipid: really another word for fat.  A lipid is a substance that disolves in alchohol but not in water.  Examples of lipids are wax, oil and other fats.

Cholesterol: a specific lipid that is used for many purposes in the body including cell membranes, hormones, vitamin D production and bile production.  It consists of a sterol carbohydrate ring with specific side chains.

Lipoprotein: a particle manufactured in the liver that consists of lipids and protein that circulates in the bloodstream.

Triglyceride: molecule made up of a three carbon molecule glycerin with three long carbon chain fatty acids attached, i.e. “tri” for three + glyceride. Practically these are the fatty particles in the blood stream that did not get packaged into lipoproteins in the first pass of the blood from the gut through the liver.

HDL cholesterol: (High density lipoprotein) Think good cholesterol here.  The HDL  lipoprotein particle consists of more proteins which are more dense, and less lipids which are less dense, so the lipoprotein is high in density.  There are several subsets of HDL, but in general a high HDL level is good.  HDL cholesterol functions in part to remove cholesterol from places it does not belong and return it to the liver to be repackaged and better used.

LDL cholesterol: (Low density lipoprotein) Think bad cholesterol here.  A lipoprotein that is higher in lipid and lower in protein making it low density.  In general high levels of LDL cholesterol are not good, as they increase the risk of atherosclerosis and heart disease.  LDL cholesterol is the primary vehicle for carrying cholesterol in the blood stream.  When present in large amounts cholesterol is often put where it can cause harm, like on the lining of blood vessels.

CRP: (C-reactive protein or hsCPR for highly sensitive CRP) is a marker of inflammation, and is used sometimes to assess risk of heart disease when the cardiovascular risk based on the rest of the lipid measurements and the other risk factors do not lead to a clear decision on lipid management.

Non-HDL cholesterol: This is simply calculated by subtracting the HDL cholesterol level from the total cholesterol level.  non-HCL cholesterol is a secondary target for treating lipids, after the LDL goal is met.

Direct LDL: usually the LDL level is calculated using the formula:

Total Cholesterol – HDL cholesterol – Triglycerides/5 = LDL cholesterol

This formula is quite accurate except when the triglyceride level is over 400-500.  High triglyceride levels make this calculation less accurate, so in those cases a more expensive test is used to measure the LDL cholesterol directly.

Physicians use these numbers along with a patients other risk factors to decide on whether to treat them with medication for abnormal lipid measurements.  In general the more risk factors for heart disease a patient has the more likely they are to warrant medication treatment.

The risk factors recommended by the National Institute of Health (through the NHBLI)  for this decision making include:

Table 3. Major Risk Factors (Exclusive of LDL Cholesterol) That Modify LDL Goals*

- Cigarette smoking

- Hypertension (BP ³140/90 mmHg or on antihypertensive medication)

-Low HDL cholesterol (<40 mg/dL)†

-Family history of premature CHD (CHD in male first degree relative <55 years; CHD in female first degree relative <65 years)

-Age (men ³45 years; women ³55 years)*

* In ATP III, diabetes is regarded as a CHD risk equivalent.

† HDL cholesterol ³60

(table from the NIH site)

The levels of cholesterol are broken down into categories:

Table 2. ATP III Classification of LDL, Total, and HDL Cholesterol (mg/dL)

LDL Cholesterol

<100                                       Optimal

100-129                                 Near optimal/above optimal

130-159                                 Borderline high

160-189                                 High

>190                                       Very high

Total Cholesterol

<200                                Desirable

200-239                          Borderline high

³240                                  High

HDL Cholesterol

<40                                    Low

>60                                     High

(table from the NIH site)

The recommendations for goal LDL cholesterol are as follows:

Three Categories of Risk that Modify LDL Cholesterol Goals

Risk Category LDL Goal (mg/dL)

CHD and CHD risk equivalents           <100

Multiple (2+) risk factors*                   <130

Zero to one risk factor                           <160

* Risk factors that modify the LDL goal are listed in Table 3

(from the NIH site)

Using these recommendations a woman age 67 who does not smoke, has a BP < 140/90 on no blood pressure medication, has an HDL cholesterol of 38, and has no coronary heart disease in her mother, father, or siblings would have 2 risk factors (age plus low HDL cholesterol) making her goal LDL <130.

Similarly a man age 40 who smokes, is on BP medication, and whose father had his first heart attack at age 50 with an HDL of 33 would have three risk factors (smoking, blood pressure and family history)  so his goal LDL cholesterol would be <130 unless his Framingham calculated risk of developing Coronary disease in the next 10 years is >20%.

Here is a link to the calculator provided by the NIH  to calculate Framingham Risk:

Framingham Risk Calculator

Using this calculator the 10 year risk of the man above would be 22% if his current systolic BP was 130 on medication, so he falls into the CHD equivalent category and has a goal of <100 for LDL cholesterol.

Treating LDL cholesterol is usually pretty straightforward.  We try to get patients to eat a diet low in total fat and saturated fat (primarily animal fat) to avoid trans fatty acids, and to lose weight.  If this is not adequate we usually add a medication in the statin family.  Many generic statins are available and can keep costs of treatment fairly low, and most patients tolerate statins well.  Some patients do not and red yeast rice is sometimes tolerated by those patients.  It has a statin-like effect.  Statins can lower LDL cholesterol by 25-55% in most patients.  If statins are not tolerated, or if you are a woman who may become pregnant (absolute contraindication to statins) then other medications are sometimes used.

Treating low HDL cholesterol is more difficult, and often slow release niacin is used for this purpose, but it is sometimes difficult to tolerate because of flushing and itching side effects.

Treating triglycerides is important if they are extremely high.  Levels >500 can put you at risk for pancreatitis, and need to be treated.  Levels between 150 and 500 are suboptimal, and are sometimes treated.

In general the goals for non-HCL cholesterol are the LDL goals + 30.