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INTRODUCTION
Familial hypercholesterolemia (FH), also known as familial hyperlipoproteinemia type 2 or Fredrickson class 2a hyperlipidemia, is an autosomal dominant-inherited genetic disorder that leads to elevated blood cholesterol levels. Typically, the patient inherits only 1 of the defective genes, making him heterozygous. Rarely, the patient inherits an abnormal gene from both parents, making him homozygous; being homozygous for FH causes extremely elevated blood cholesterol levels. Most of the time, a mutation of the low density lipoprotein (LDL) receptor gene is the culprit. However, other genetic mutations have been identified, including those that affect apolipoprotein B (ApoB) structure and proprotein convertase subtilisin kexin type 9 (PCSK9) gain-of-function mutations. The International FH Foundation and the National Institute for Health and Care Excellence (formerly the National Institute of Health and Clinical Excellence) have published recommendations for the detection, evaluation, and treatment of FH to help guide clinicians responsible for treating FH patients. 1, 2
FH may present as severely elevated total cholesterol and LDL cholesterol (LDL-C) levels or as premature coronary heart disease (CHD). An estimated 5% of myocardial infarctions (MIs) in patients <60 years and 20% of MIs in patients <45 years are attributable to FH. 3 Men with FH have a 50% chance of having CHD by the age of 50, and women with FH have a 30% chance of having CHD by the age of 60. 3 The homozygous form of FH, although rare, is particularly devastating. In patients with homozygous FH, atherosclerosis develops during childhood, and CHD may appear before the age of 20. Therefore, routine cholesterol screening is recommended at various ages based on risk. The discovery of FH should lead to cascade testing (the systematic method of testing family members) to identify other family members with the condition.
Patients identified as having FH should be counseled about therapeutic lifestyle changes and should take high-dose potent statins to attain 50% LDL-C reductions. Patients with severe FH may benefit from add-on therapy with other cholesterol-lowering medications and LDL apheresis. Children with homozygous FH and extremely elevated LDL-C levels may be candidates for orthotopic liver transplantation.
EPIDEMIOLOGY AND GENETICS
FH is a common genetic disorder with autosomal dominant inheritance. The heterozygous FH form is estimated to occur at a rate of 1:300-1:500. 3 However,...