Abstract 10882: Homozygous Familial Hypercholesterolemia: Luck Meets Opportunity Meets Knowledge

Abstract

Introduction: Homozygous familial hypercholesterolemia (HoFH) is an inherited autosomal co-dominant disorder characterized by severely elevated circulating low-density lipoprotein (LDL). Monoclonal antibodies are now a treatment focus. Inhibition of proprotein convertase subtilisin kexin type 9 (PCSK9) increases the number of LDL receptors. Inhibition of angiopoietin-like 3 (ANGPTL3) inhibitor is associated with hypolipidemia and reduced risk of cardiovascular disease. We present the case of one of the oldest living patients with HoFH. Case Description: The patient is a 67-year-old black woman diagnosed with corneal arcus senilis and xanthomas at the age of 11, with total cholesterol (TC) levels >1000 mg/dL. At age 12, she underwent a partial ileal bypass (PIB) that lowered her TC by 39%. At age 32, she began statin therapy (Lovastatin, intensified to Atorvastatin at age 43). Despite concomitant dietary changes, her LDL levels remained elevated (>400 mg/dL). At age 34, multivessel coronary artery disease was detected and she initiated lipoprotein apheresis. Her LDL-C was reasonably well-controlled over the 20 years on LDL apheresis and high intensity statin therapy. Combined therapy with PCSK9 inhibitors (Evolocumab at age 61, replaced by Alirocumab at age 67) and ANGPTL3 inhibitor Evinacumab (age 67) lowered her LDL-C significantly. Genetic analysis confirmed two LDLR mutations: c.1846-1G>A and c.907C>T. Conclusion: Elevated cholesterol levels are linked to a higher risk of premature myocardial infarction and stroke. We report a case of HoFH with successful lowering of LDL levels on dual antibody and high intensity statin therapy along with PIB. Unlike PCSK9 inhibitors, ANGPTL3 inhibitors work independently of LDLRs by stimulating lipoprotein & endothelial lipase. This case offers insight into early surgical and combination drug therapy in HoFH and describes one of the longest living patients with HoFH illustrating treatment evolution.