Physical signs and atherosclerotic cardiovascular disease in familial hypercholesterolemia: the HELLAS-FH Registry

Area of Science:

• Cardiology
• Genetics
• Dermatology

Background:

• Heterozygous familial hypercholesterolemia (heFH) is a genetic disorder.
• Physical signs such as tendon xanthomas, corneal arcus, and xanthelasma are associated with heFH.
• The prevalence and clinical significance of these signs in current heFH populations are not well understood.

Purpose of the Study:

• To determine the frequency of physical signs in contemporary heFH individuals.
• To investigate the association between these physical signs and prevalent atherosclerotic cardiovascular disease (ASCVD) in heFH patients.

Main Methods:

• Utilized data from the Hellenic Familial Hypercholesterolemia Registry.
• Diagnosed heFH using the Dutch Lipid Clinic Network Score.
• Employed multivariate logistic regression to analyze the association between physical signs and ASCVD.

Main Results:

• Included 2156 adult heFH patients (mean age 50 years).
• 14.5% exhibited at least one heFH-related physical sign.
• Corneal arcus before 45 (6.6%), tendon xanthomas (5.3%), and xanthelasmas (5.8%) were observed.
• Corneal arcus before 45 was the only sign independently associated with premature coronary artery disease (CAD).
• No association found between physical signs and total CAD, stroke, or peripheral artery disease.
• Patients with physical signs received more intensive lipid-lowering therapy but rarely achieved optimal lipid targets.

Conclusions:

• Physical signs are infrequently present in today's heFH patient cohort.
• Corneal arcus appearing before age 45 is an independent predictor of premature CAD in heFH.