Familial hypercholesterolemia (FH), a group of genetic defects that cause elevations in cholesterol levels, is associated with preventable, premature cardiovascular disease (CVD), and can be broken down into heterozygous and homozygous forms (Table 1). Early and accurate diagnosis and treatment are crucial in avoiding cardiovascular events and death. “FH is very treatable,” says Anne C. Goldberg, MD, FNLA, FACP, FAHA, “and is one of the more common genetic disorders in which treatment can decrease the risk of early cardiovascular disease.”

The National Lipid Association (NLA) released clinical practice recommendations on the screening, diagnosis, and management of patients with FH, focusing heavily on early recognition and treatment. The recommendations were published in the June 2011 Journal of Clinical Lipidology. “Most clinical guidelines for cholesterol treatment have discussed the importance of cholesterol levels and cholesterol as a risk factor for CVD but don’t really address FH in any great detail,” explains Dr. Goldberg, who was the chair of the writing group that developed the recommendations. “As such, the NLA recommendations may contribute by helping physicians to recognize FH in particular and then manage these patients appropriately based on the available scientific evidence.”

Be Suspicious of FH Among Children

Among the key recommendations made by the NLA is for universal cholesterol screening for elevated serum cholesterol. All children aged 9 to 11 should be screened. Healthcare providers should suspect FH among children and adolescents under the age of 20 with LDL cholesterol of 160 mg/dL or higher or non-HDL cholesterol of 190 mg/dL or higher and in anyone aged 20 or older who has LDL cholesterol levels of 190 mg/ dL or higher and/or non-HDL cholesterols of 220 mg/dL or higher (Table 2). “The first signs of atherosclerosis can occur about when puberty starts,” explains Dr. Goldberg. “Cholesterol levels in FH are elevated from birth and are at least double the levels you see in ‘normal’ children.”

“Cholesterol levels in FH are elevated from birth and are at least double the levels you see in ‘normal’ children.”

Screening for FH is recommended even for children as young as 2 who have a strong family history of premature coronary disease or hypercholesterolemia. “Cholesterol levels tend to fluctuate until the age of 2,” says Dr. Goldberg. “Age 2 is also when most children start eating ‘real’ food. At this age, children who have the heterozygous form of FH should avoid highsaturated fat foods, be encouraged to exercise, and avoid second-hand smoke.” Dr. Goldberg adds that the NLA recommendations do not call for medications at age 2.

Diet, Exercise, and Sometimes Statins

Although diets low in saturated fat and cholesterol along with exercise are recommended as first-line therapy for all patients with FH, Dr. Goldberg says these interventions usually will not be enough to achieve a substantial drop in LDL-cholesterol levels. “For those whose LDL-cholesterol or non-HDL cholesterol remains elevated after lifestyle interventions— including children aged 9 to 11—statin therapy is recommended. This is a little different for children when compared with adults. In adults, the use of a potent statin at a moderate dose may be more appropriate. Clinicians should aim to achieve an LDL-cholesterol decrease of at least 50% in adults. In some adults, however, a high dose of a potent statin may not be enough to get a significant drop in LDL-cholesterol. In these cases, combination therapy may be necessary.” For children as young as 8 with heterozygous FH and LDL-cholesterol levels of 190 mg/dL or higher, medication is recommended. Five of the currently available statins have been approved by the FDA for these types of children at age 10. Currently, only one of the available statins is approved for use at age 8 in children with FH.

Special Considerations for Certain Patients

Dr. Goldberg says it is important to screen as many family members as possible for FH. “People need to be aware of their family cholesterol history,” she says. “It’s important to find and treat people before they develop disease so that they can further prevent premature death.”

While statins are the drug of choice for treating FH, they are not approved for use in pregnant women. “Discussing childbearing plans with young women is important when FH is suspected,” says Dr. Goldberg. “In these cases, treatment should begin in the adolescent years and early 20s so that they will have received treatment for a length of time before they stop taking cholesterol medications (eg, statins). We recommend stopping statins at least 4 weeks before women stop taking birth control pills once they are planning to become pregnant.”

Dr. Goldberg cautions against using the Framingham risk scoring in patients with FH. “Men with FH can start developing coronary disease in their 30s and 40s, and women in their 40s and 50s,” she explains. “These age ranges can become even younger if patients smoke or have untreated hypertension or diabetes. Applying the Framingham risk scoring may underestimate risks in these scenarios.”



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Young J, Molyneux S, Reinheimer A, et al. Relationship between plasma coenzyme Q10, asymmetric dimethylarginine and arterial stiffness in patients with phenotypic or genotypic familial hypercholesterolemia on long-term statin therapy. Atherosclerosis. 2011 May 5 [Epub ahead of print]. Available atwww.sciencedirect.com/science/article/pii/S0021915011003807.

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