CVD risk increased in monogenic familial hypercholesterolemia
MIAMI — Patients with monogenic familial hypercholesterolemia had a higher risk for CVD compared with those without the familial hypercholesterolemia-causing variant or patients with polygenic familial hypercholesterolemia, according to the third-place oral poster winner presentation at the National Lipid Association Scientific Sessions.
Liam Brunham, MD, PhD, assistant professor in the department of medicine at the University of British Columbia in Vancouver, Canada, and colleagues analyzed data from 626 patients (mean age, 46 years; 51% women) with possible (n = 170), probable (n = 227) or definite familial hypercholesterolemia (FH; n = 229) based on Dutch Lipid Clinic Network criteria. Targeted sequencing was performed for genes that have been shown to cause FH and common variants that influence LDL. Researchers also calculated polygenic risk scores.
“If we identified a variant in one of those genes that’s annotated in ClinVar as being either pathogenic or likely pathogenic, then that was considered monogenic FH,” Brunham said during the presentation. “Alternatively, we identified novel variants and we had an approach to predict pathogenicity of those variants, so if we identified a novel variant in the LDL receptor gene that was predicted to be deleterious in a number of different approaches, that would also meet our criteria for designating a patient as having monogenic FH.”
CV events included in this study were MI, premature unstable angina, stroke and CV revascularization.
Variants that cause FH were found in 8.2% of patients with possible FH, 25.6% of those with probable familial hypercholesterolemia and 51% of patients with definite FH. There were 33.5% of patients who had a high polygenic risk score, defined as greater than the 80th percentile. Compared with patients without the variant, those with the variant had significantly higher LDL levels.
Significantly greater risk for CVD was linked to a monogenic cause of FH. The risk for CVD was not significantly different in patients with polygenic FH and in those who did not have a genetic variant that caused FH.
Patients with monogenic FH had more of an increased risk for CVD if they had a high LDL polygenic risk score.
“These results support the clinical benefit of genetic testing for patients with FH to confirm diagnosis, enable cascade screening and stratify risk,” Brunham said during the presentation. – by Darlene Dobkowski
Brunham L. Session VII: Clinical Pearls. Presented at: National Lipid Association Scientific Sessions; May 16-19, 2019; Miami.
Disclosures: The authors report no relevant financial disclosures.