Elevated remnant-like particles in heterozygous familial hypercholesterolemia and response to statin therapy.
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.


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.
de Sauvage Nolting
Pernette R W
PR
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. p.desauvagenolting@amc.uva.nl
Twickler
Marcel B
MB
Dallinga-Thie
Geesje M
GM
Buirma
Rudolf J A
RJ
Hutten
Barbara A
BA
Kastelein
John J P
JJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002784:Cholesterol / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005799:Genes, Dominant / Q000187:drug effects; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D012307:Risk Factors; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D008074:Lipoproteins; D014280:Triglycerides; C112017:remnant-like particle cholesterol; D002784:Cholesterol; D019821:Simvastatin