Hypercholesterolemia: The Daily PANCE Blueprint

Familial Hypercholesterolemia: The Daily PANCE Blueprint

A 45-year-old obese Caucasian gentleman arrives at your clinic for a routine check-up after having some blood work done during a workplace health screening. He is found to have an LDL cholesterol level of 720 mg/dL. He states that his father and brother had high cholesterol and both died at a young age from a heart attack. He has a follow-up appointment with his cardiologist because of some occasional chest pain and abnormalities seen on his EKG. Additionally, you notice that he has well-demarcated yellow deposits around his eyes. He is started on high dose statin and his LDL at 12 weeks is 350 mg/dL. What is the next best step in this patient's management?

A. Continue high dose statin, the patient's LDL is at goal
B. Add niacin 100 mg three times daily
C. Add ezetimibe 10 mg daily
D. Add a PCSK9 inhibitor
E. Refer to a lipid specialist

Answer and topic summary

The answer is C: add ezetimibe 10 mg

If LDL-C is not at goal after 6-12 weeks the next best step for the treatment of familial hypercholesterolemia is to add ezetimibe 10 mg daily and check again in 6-12 weeks. If at that time the patient’s LDL is still not at goal (ideally < 150) refer to lipid specialist to consider adding a PCSK9 inhibitor.

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Pearls

  • Familial hypercholesterolemia (FH) is the most common autosomal dominant genetic disease. The clinical syndrome (phenotype) is characterized by extremely elevated levels of low-density lipoprotein cholesterol (LDL-C) and a propensity to early-onset atherosclerotic cardiovascular disease. In general, homozygotes manifest the disease at a much earlier age than heterozygotes and the disease is more severe.
  • Homozygous FH patients are rare and have an estimated prevalence of approximately 1:300,000 to 1:400,000
  • Heterozygous FH is estimated to occur in 1 in 200 to 250 individuals in the United States.
  • It is estimated that about 7 percent of American adults have an untreated lipoprotein cholesterol ≥190 mg/dL but only 1.7 percent carry an FH mutation
  • Patients with undiagnosed homozygous familial hypercholesterolemia (FH) develop severe, premature, atherosclerotic cardiovascular disease and die before age 20 in many cases.
  • In patients with a negative or unknown family history, an untreated LDL-C level of ≥190 mg/dL (4.9 mmol/L) suggests FH. This value is greater than the 90th percentile for age and sex.

Diagnosis

  • The diagnosis of heterozygous familial hypercholesterolemia (FH) is made with genetic testing or clinical criteria. A causative mutation in the LDLR, APOB, or PCSK9 gene(s) secures this diagnosis
  • When genetic testing is not available or not felt to be necessary, you can use the Dutch Lipid Clinic Network criteria, which assigns points based on low density lipoprotein cholesterol (LDL-C) levels, personal history of early atherosclerotic cardiovascular disease (ASCVD), family history of early ASCVD, or high cholesterol in a first-degree relative, and personal and physical examination finding

Treatment

  • Patients with homozygous familial hypercholesterolemia (FH) – intensive LDL-C lowering, which targets a minimal value of <150 mg/dL (3.9 mmol/L)
  • In addition to a high-dose statin (atorvastatin 80 mg daily or rosuvastatin 40 mg daily), most homozygous patients will require additional therapies such as ezetimibe, a PCSK9 inhibitor, or potentially LDL-C apheresis

Smarty PANCE Content Blueprint Review:

Covered under ⇒ PANCE Blueprint Cardiology (13%) ⇒Lipid disorders (PEARLS) ⇒ Hypercholesterolemia