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Management

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  • Management is aimed at lowering LDL levels by at least 50% to reduce risk for atherosclerosis.  
  • Lowering LDL to 100mg/dl (or 130 mg/dl in children) has been proposed as an alternate goal in those Familial hypercholesterolemia patients without known coronary artery disease (CAD). 
  • If CAD has already been documented the LDL goal is 70 mg/dl.

First Steps after Confirming Diagnosis

Find a lipid specialist through the National Lipid Association.

Children
Consideration should be given to starting treatment at age 8 years (or earlier in those with evidence of disease, homozygous familial hypercholesterolemia, additional risk factors, or family history of very early onset atherosclerosis).

  • Initiate lifestyle changes to lower LDL levels (see Diet, Exercise, and Lifestyle Interventions)
  • Initiate statin therapy in children for whom lifestyle modification does not achieve 50% reduction in LDL or LDL levels <130 mg/dL (see Medications).
  • Consult with, or refer to, a lipid specialist for all patients with heterozygous familial hypercholesterolemia. In patients with homozygous familial hypercholesterolemia, elevated lipids should be directly managed by a lipid specialist if possible as therapy often involves the use of LDL apheresis

Adults

  • Initiate lifestyle changes to lower LDL levels (see Diet, Exercise, and Lifestyle Interventions)
  • Initiate statin therapy for all familial hypercholesterolemia individuals (see Medications).
  • Most familial hypercholesterolemia patients will require more than one medication to achieve LDL goals.
  • Additional risk factors such as smoking, diabetes, and hypertension should be aggressively treated.
  • Consult with, or refer to, a lipid specialist for all patients with heterozygous familial hypercholesterolemia. In patients with homozygous familial hypercholesterolemia, elevated lipids should be directly managed by a lipid specialist if possible. Homozygous FH usually requires LDL apheresis or medications that are FDA-approved only for the treatment of adult patients with homozygous FH (lomitapide, mipomersen)  

Diet, Exercise, and Lifestyle Interventions

  • Smoking cessation is critical: smoking dramatically accelerates CVD in individuals with familial hypercholesterolemia , especially men.
  • Diet: referral to a registered dietician or other qualified nutritionist is recommended.
    • Total fat 25-35% of energy intake
    • Saturated fatty acids <7% of energy intake
    • Dietary cholesterol < 200 mg/d
    • Limiting caloric intake to maintain healthy body weight
    • plant stanol or sterol esters 2g/d.
    • soluble fiber 10-20 g/d.
  • Physical activity to maintain healthy body weight and aerobic health
  • Limitation of alcohol consumption per AHA guidelines to 1-2 drinks per day.

Longitudinal care

Follow up testing/screening/monitoring.

  • Lipid panels should be assessed every several months until the patient is at their goal LDL and then periodically especially if there is a change in medications or clinical status.
  • Blood pressure should be maintained at <140/90 (<130/80 in diabetic patients).
  • Routine stress tests or cardiac catheterization are not usually indicated.

Care team members

Required

  • Lipid specialist
    • Consult with, or refer to, a lipid specialist for all patients with heterozygous familial hypercholesterolemia. In patients with homozygous familial hypercholesterolemia, elevated lipids should be directly managed by a lipid specialist.
    • Find a lipid specialist through the National Lipid Association.
  • Primary care
  • Registered dietician or other medical nutritional therapist
  • Cardiologist

As Needed

  • Endocrinologist
  • Psychology/counseling
  • Genetic counselor

Physical/occupational/speech/developmental therapy

Not applicable

Psychology/Counseling

Counseling may be indicated for:

  • Compliance with treatment recommendations
  • Adaptation to lifestyle changes
  • Appreciation of and coping with increased cardiovascular risk
  • Coping with burden of increased medical management
  • Family communication and support of lifestyle changes
  • Unresolved grief surrounding early family deaths

Medications

Indicated:

  • Statin (high potency statins are preferred e.g., simvastatin, atorvastatin, rosuvastatin)
  • Intensify drug treatment  with higher doses of statins or the addition of other medications, in patients for whom initial treatment does not achieve at least 50% reduction in LDL or preferably levels < 100 mg/dL. For higher risk patients (as below) a goal LDL of < 70 mg/dL should be considered and will often require additional medications.
    • Higher risk patients are those with
      • clinically evident coronary heart disease,
      • atherosclerotic cardiovascular disease,
      • diabetes,
      • family history of very early cardiovascular disease (CVD),
      • current smokers, or
      • high lipoprotein-a (>50 mg/dL using an isoform insensitive assay).
  • Combination drug therapy is generally required though may have higher cost and potential for adverse effects and decreased adherence.
  • When statins are poorly tolerated or contraindicated, alternatives include:
    • Every-other day or even weekly dosing of high-potency statin therapy
    • Low-potency statin (often inadequate LDL-lowering effect)
    • Ezetimibe
    • Bile acid sequestrants (colesevelam)
    • Niacin
    • LDL apheresis (see section on Surgery and/or Procedures)
  • Low dose aspirin for those with radiological evidence or clinical evidence of coronary artery disease is standard of care.  Low dose aspirin is also standard of care for middle-aged men (> 50 yo) regardless of FH status. While broader low dose aspirin is still considered controversial for the general population, low dose aspirin should be considered for middle-aged FH patients as all FH patients are considered “high risk” by national guidelines from the National Lipid Association .
  • If triglyceride levels are > 500mg/dl consider high dose omega-3 fatty acids, niacin or fibrate. 

Contraindicated/Use with caution:

  • As for all patients, fibrates (ie. gemfibrozil) increase risk for statin-induced myositis .  However, fibrates may be used with caution alongside statins, especially when a patient with familial hypercholesterolemia has concurrent elevated triglyceride levels.

Surgery and/or procedures

  • LDL apheresis if inadequate response after 6 months of maximum tolerated drug therapy.
    • LDL apheresis is indicated according to these guidelines:
    • Homozygous FH with LDL >300 mg/dL
    • Heterozygous familial hypercholesterolemia  with:
      • LDL>300 mg/dL AND 0-1 CVD risk factors
      • LDL>200mg/dL AND 2+ CVD risk factors or high lipoprotein (a)
        • LDL>160mg/dL AND established CVD or other very high risk factors (i.e. diabetes)
  • Portacaval anastomosis may be indicated for homozygous FH.
  • Ileal bypass may be rarely indicated in very hard to manage patients.
  • Liver transplantation may be rarely indicated in very hard to manage patients.

Other interventions

N/A

Treatments and interventions to avoid

N/A

Reproductive implications

Effect of the condition on fertility

There is no direct evidence that FH impacts fertility

Effect of the condition on pregnancy, delivery and/or the post-partum period

  • Statins, ezetimibe and niacin should not be used during pregnancy or lactation. Alternative medications such as bile acid binding resins are generally considered safe for pregnancy (Class B).
  • LDL apheresis may be considered during pregnancy if significant atherosclerotic disease is present, or if a patient has homozygous familial hypercholesterolemia.

Effect of pregnancy on manifestations of the condition

Serum lipid levels including total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides rise during pregnancy

Prognosis

Penetrance

  • The prevalence of FH approaches 100%, thus essentially all individuals with familial hypercholesterolemia have elevated cholesterol, starting from birth.
  • Risk for cardiovascular events increases with age.
  • If left untreated, men with heterozygous FH have a 50% chance of CVD by age 50 and women have a 30% chance by age 60.

Factors affecting expression (variable expressivity)

  • Homozyogotes have substantially higher LDL levels (usually > 500 mg/dl) and earlier and more severe onset of disease than heterozygotes.
  • Heterozygous males have earlier and more severe onset of disease than heterozygous females.
  • Homozygotes have the same disease risk regardless of gender.
  • Certain gene mutations may retain some degree of LDL receptor function (see “How do genetic test results alter prognosis”).
  • Atherosclerotic disease is significantly accelerated in smokers.

Effect on longevity/lifespan

  • Mean age of cardiovascular events in untreated familial hypercholesterolemia is early 40s in men and early 50s in women.

Effect on function and quality of life

Little systematic data is available to evaluate this issue.

Expected response to therapy

  • Early and long-term drug therapy can substantially lower CHD risk to levels that approach that of the general population.

How do genetic test results alter prognosis?

  • Individuals in families with a known mutation who test negative for the known familial mutation do not have familial hypercholesterolemia and are at population risk for cardiovascular disease.
  • Homozygotes require earlier and more aggressive treatment.
  • Certain gene mutations may retain some degree of LDL receptor function, influencing expected response to treatment, though no consensus currently exists on genotype-based guidelines.

Presymptomatic or Asymptomatic Patients

  • Children <18 years old with FH should consult with a pediatric lipid specialist to discuss initiation of therapy which depends on lipid levels, family history and personal medical history
  • Adults > 18 yo should consult with a lipid specialist but should generally initiate statin based therapy (unless pregnant or trying to become pregnant) to lower LDL by at least 50% to prevent the deleterious long term effects of FH on CVD risk.

Consensus Statements and Guidelines

National Lipid Association Expert Panel on Familial Hypercholesterolemia. Goldberg et al. 2011. Familial Hypercholesterolemia: Screening, Diagnosis, and Management of Pediatric and Adult Patients. Journal of Clinical Lipidology, 5(3S): S1-S51.