BACKGROUND: Remnant lipoproteins (RLP-C) are considered important in atherogenesis. Hence, this study was designed to assess RLP-C levels and the effect of statin therapy in patients with familial hypercholesterolemia (FH). Elevated RLP-C levels have been associated with the presence and progression of atherosclerotic disease, and their presence in FH patients has been proposed but never established in a large cohort, nor has their response to statin therapy been confirmed. METHODS AND RESULTS: FH patients were recruited from 36 lipid clinics. After a washout period of 6 weeks, all patients were started on monotherapy with 80 mg of simvastatin for 2 years. RLP-C levels were assessed by an immune-separation assay. In 327 FH patients, RLP-C measurements could be performed before and after treatment. Mean total cholesterol (10.55+/-2.17 mmol/L), mean LDL cholesterol (8.40+/-2.13 mmol/L), and median RLP-C (0.47 mmol/L) levels were all severely elevated at baseline. After treatment, RLP-C levels were reduced by 49% (0.24 mmol/L; P<0.0001). Even patients with normal triglyceride levels had elevated RLP-C levels at baseline, and those with high RLP-C levels were generally characterized by a very atherogenic lipoprotein profile. CONCLUSIONS: Baseline RLP-C levels are severely elevated in FH patients and are reduced by simvastatin but do not return to normal. These elevated RLP-C levels could be the consequence of impaired function of the LDL receptor in FH. RLP-C levels in FH contribute to an atherogenic lipoprotein profile and could identify patients who require additional treatment.
BACKGROUND: Remnant lipoproteins (RLP-C) are considered important in atherogenesis. Hence, this study was designed to assess RLP-C levels and the effect of statin therapy in patients with familial hypercholesterolemia (FH). Elevated RLP-C levels have been associated with the presence and progression of atherosclerotic disease, and their presence in FHpatients has been proposed but never established in a large cohort, nor has their response to statin therapy been confirmed. METHODS AND RESULTS:FHpatients were recruited from 36 lipid clinics. After a washout period of 6 weeks, all patients were started on monotherapy with 80 mg of simvastatin for 2 years. RLP-C levels were assessed by an immune-separation assay. In 327 FHpatients, RLP-C measurements could be performed before and after treatment. Mean total cholesterol (10.55+/-2.17 mmol/L), mean LDL cholesterol (8.40+/-2.13 mmol/L), and median RLP-C (0.47 mmol/L) levels were all severely elevated at baseline. After treatment, RLP-C levels were reduced by 49% (0.24 mmol/L; P<0.0001). Even patients with normal triglyceride levels had elevated RLP-C levels at baseline, and those with high RLP-C levels were generally characterized by a very atherogenic lipoprotein profile. CONCLUSIONS: Baseline RLP-C levels are severely elevated in FHpatients and are reduced by simvastatin but do not return to normal. These elevated RLP-C levels could be the consequence of impaired function of the LDL receptor in FH. RLP-C levels in FH contribute to an atherogenic lipoprotein profile and could identify patients who require additional treatment.
Authors: Hans L Mooij; Sophie J Bernelot Moens; Philip L S M Gordts; Kristin I Stanford; Erin M Foley; Marjolein A W van den Boogert; Julia J Witjes; H Carlijne Hassing; Michael W Tanck; Michiel A J van de Sande; J Han Levels; John J P Kastelein; Erik S G Stroes; Geesje M Dallinga-Thie; Jeff D Esko; Max Nieuwdorp Journal: J Lipid Res Date: 2015-01-07 Impact factor: 5.922
Authors: Rutger Verbeek; Federico Oldoni; R Preethi Surendran; Ailko H Zwinderman; Kay T Khaw; Erik S G Stroes; Nick J Wareham; S Matthijs Boekholdt; Geesje M Dallinga-Thie Journal: J Clin Lipidol Date: 2019-02-25 Impact factor: 4.766