Familial Hypercholesterolemia Underdiagnosed and Undertreated
David J. Strobl, D.O., FNLA
Professor Director, Cardiovascular Medicine Department of Academic Programs
Michigan State University College of Osteopathic Medicine
Director, Heart Disease Prevention Clinic Thoracic and Cardiovascular Institute
Sparrow Hospital System
FH - Prevalence
• Relatively high Prevalence • Heterozygous FH: 1: 200 – 1: 500 • Homozygous FH: 1: 1,000,000
• Recent estimates as high as 1: 300,000 • More common in certain ethnicities and groups
• French Canadian • Finnish • Christian Lebanese • South African
FH - Awareness
• Doesn’t appear to be high • Less than 1/3 of Cardiologists felt comfortable
making the diagnosis or are able to recognize a typical case
• Approximately one million FH patients in the U.S. • Less than 10% carry a diagnosis of FH
• Less than 1% of patients with FH are aware of their condition
• Up to 25% of diagnosed FH patients are not treated to the recommended target LDL-C of less than 100 mg/dl
FH – Most Common Genetic Mutations
FH – Cardiac Manifestations
• High LDL-cholesterol • Clinical Manifestations
• Extensor Tendon Xanthomata • Corneal Arcus • Achilles Tendon Xanthomas • Xantheloamatas
• Signs of Premature Atherosclerosis • Carotid Bruit – Carotid Artery Disease • Diminished Pulses – PVD • Exertional Angina
• Signs of Aortic Stenosis • Systolic Ejection Outflow Murmur
FH – Clinical Criteria
• Two well-established sets • Simon Broome • Dutch Lipid Clinic
• Label as possible, probable, and definite • All not applicable to Pediatric Population • Often miss mild FH forms since there is an overlap
between mutation positive and mutation negative individuals
All established clinical criteria take into consideration a combination of the following: • Untreated LDL levels (>190 mg/dl; >155 mg/dl if < 16 yo • Family history (LDL-C ↑; premature CHD+) • Clinical history (premature CHD+) • Physical examination
• Xanthomas • Corneal Arcus
• DNA analysis
FH – Clinical Criteria
FH – Overlap with High LDL-C (polygenic or common)
FH – Impact of Mutation Status on CAD According to LDL Cholesterol Level
Homozygous FH - Treatment
• More challenging • Begin with same drugs as for HeFH • Consider Mipomersin / Lomitapide • Lipoprotein Apheresis • Liver transplantaion / partial ileal bypass
• Rate of surgical approach declining because of the emergence of more potent medications
FH – Treatment Guidelines
FH – Treatment Algorithm
FH – Approach to Screening and Genetic Testing
FH – The Strobl Approach
• Screen all patients in your practice for individuals with a baseline LDL-C > 190 mg/dl
• Assume any of those individuals may have FH • Treat all primary hyperlipidemic patients
aggressively • LDL-C < 130 mg/dl • LDL-C < 100 mg/dl if family history of CAD • LDL-C < 70 mg/dl if any evidence of atherosclerosis
• Ask for all suspected patients to contact their first degree relatives to be screened
