Background: Autosomal recessive hypercholesterolemia (ARH) is a rare lipid disorder characterized by premature atherosclerotic cardiovascular disease (ASCVD). There are sparse data for clinical management and cardiovascular outcomes in ARH. Objectives: Evaluation of changes in lipid management, achievement of low-density lipoprotein cholesterol (LDL-C) goals and cardiovascular outcomes in ARH.
Methods: Published ARH cases were identified by electronic search. All corresponding authors and physicians known to treat these patients were asked to provide follow-up information, using a standardized protocol.
Results: We collected data for 52 patients (28 females, 24 males; 31.1 ± 17.1 years of age; baseline LDL-C: 571.9 ± 171.7 mg/dl). During a mean follow-up of 14.1 ± 7.3 years, there was a significant increase in the use of high-intensity statin and ezetimibe in combination with lipoprotein apheresis; in 6 patients, lomitapide was also added. Mean LDL-C achieved at nadir was 164.0 ± 85.1 mg/dl (−69.6% from baseline), with a better response in patients taking lomitapide (−88.3%). Overall, 23.1% of ARH patients reached LDL-C of <100 mg/dl. During follow-up, 26.9% of patients had incident ASCVD, and 11.5% had a new diagnosis of aortic valve stenosis (absolute risk per year of 1.9% and 0.8%, respectively). No incident stroke was observed. Age (≥30 years) and the presence of coronary artery disease at diagnosis were the major predictors of incident ASCVD.
Conclusions: Despite intensive treatment, LDL-C in ARH patients remains far from targets, and this translates into a poor long-term cardiovascular prognosis. Our data highlight the importance of an early diagnosis and treatment and confirm the fact that an effective treatment protocol for ARH is still lacking.

Additional Metadata
Keywords atherosclerotic cardiovascular disease, autosomal recessive hypercholesterolemia, follow-up, lipid-lowering therapies, retrospective analysis
Persistent URL dx.doi.org/10.1016/j.jacc.2017.11.028, hdl.handle.net/1765/104546
Journal Journal of the American College of Cardiology
Citation
D'Erasmo, L. (Laura), Minicocci, I. (Ilenia), Nicolucci, A, Pintus, P. (Paolo), Roeters van Lennep, J.E, Masana, L, … Arca, M. (Marcello). (2018). Autosomal Recessive Hypercholesterolemia. Journal of the American College of Cardiology, 71(3), 279–288. doi:10.1016/j.jacc.2017.11.028