Autosomal Recessive Hypercholesterolemia
Long-Term Cardiovascular Outcomes
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.
|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|
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