Elsevier

The American Journal of Cardiology

Volume 136, 1 December 2020, Pages 38-48
The American Journal of Cardiology

Cardiovascular Outcome of Pediatric Patients With Bi-Allelic (Homozygous) Familial Hypercholesterolemia Before and After Initiation of Multimodal Lipid Lowering Therapy Including Lipoprotein Apheresis

https://doi.org/10.1016/j.amjcard.2020.09.015Get rights and content

Twenty-four patients with bi-allelic familial hypercholesterolemia commencing chronic lipoprotein apheresis (LA) at a mean age of 8.5 ± 3.1 years were analysed retrospectively and in part prospectively with a mean follow-up of 17.2 ± 5.6 years. Mean age at diagnosis was 6.3 ± 3.4 years. Untreated mean LDL-C concentrations were 752 mg/dl ± 193 mg/dl (19.5 mmol/l ± 5.0 mmol/l). Multimodal lipid lowering therapy including LA resulted in a mean LDL-C concentration of 184 mg/dl (4.8 mmol/l), which represents a 75.5% mean reduction. Proprotein convertase subtilisin/kexin type 9-antibodies contributed in 3 patients to LDL-C lowering with 5 patients remaining to be tested. After commencing chronic LA, 16 patients (67%) remained clinically stable with only subclinical findings of atherosclerotic cardiovascular disease (ASCVD), and neither cardiovascular events, nor need for vascular interventions or surgery. In 19 patients (79%), pathologic findings were detected at the aortic valve (AV), which in the majority were mild. AV replacement was required in 2 patients. Mean Lipoprotein(a) concentration was 42.4 mg/dl, 38% had >50 mg/dl. There was no overt correlation of AV pathologies with other ASCVD complications, or Lipoprotein(a) concentration. Physicochemical elimination of LDL particles by LA appears indispensable for patients with bi-allelic familial hypercholesterolemia and severe hypercholesterolemia to maximize the reduction of LDL-C. In conclusion, in this rare patient group regular assessment of both the AV, as well as all arteries accessible by ultrasound should be performed to adjust the intensity of multimodal lipid lowering therapy with the goal to prevent ASCVD events and aortic surgery.

Section snippets

Methods

Inclusion criteria for this open, observational retrospective and partially prospective multicenter study were the genetically proven diagnosis of hoFH or c-hetFH, the initiation of chronic LA as pediatric patients, that is, before the age of 18 years, and written informed consent of parents or legal guardians of the participating children and adolescents. There were no exclusion criteria, if these criteria were met. Fourteen specialized nephrological treatment centers including 8 departments

Results

Twenty-four patients (10 female) with genetically proved hoFH or c-hetFH commencing chronic LA before the age of 15 were enrolled, representing all patients meeting the inclusion criteria in the participating centers. Since birth mean follow-up was 17.2 ± 5.6 years with a range of 9.1 years to 32.2 years. Mean age at time of diagnosis of FH was 6.3 ± 3.4 years (Figure 1). In these, 21 were diagnosed due to clinical findings of lipid deposition in xanthomas or xanthelasmas. Three patients (#4,

Discussion

Severe hypercholesterolemia and likelihood of premature death from ASCVD complications still make bi-allelic FH, that is, hoFH or c-hetFH a therapeutic challenge. Twenty-four patients were included in this retrospective and partly prospective investigation, who commenced regular LA treatment before the mean age of 9 years. Long-term clinical profiles were analysed with a mean follow-up of 17.2 years since birth. The diagnosis of FH in general is classified as high-risk morbid condition by the

Authors cobtribution

Christina Taylan: Conceptualization, Methodology, Resources, Formal analysis, Investigation, Writing - Original Draft, Writing - Review & Editing.

Joenna Driemeyer: Resources, Writing - Review & Editing.

Claus P. Schmitt: Resources, Writing - Review & Editing.

Lars Pape: Resources, Writing - Review & Editing.

Rainer Büscher: Resources, Writing - Review & Editing.

Matthias Galiano: Resources, Writing - Review & Editing.

Jens König: Resources, Writing - Review & Editing.

Carsten Schürfeld: Resources,

Conflict of Interest Statement

Andreas Heibges and Reinhard Klingel are employees of Apheresis Research Institute, which received research grants from Diamed, Cologne Germany, and Asahi Kasei Medical, Tokyo Japan. For all other authors none conflict of interest is declared.

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