title: Reduction in mortality in subjects with homozygous familial hypercholesterolemia associated with advances in lipid-lowering therapy.
abstract: BACKGROUND
  Homozygous familial hypercholesterolemia is an inherited disorder caused by mutations in both low-density lipoprotein receptor alleles, which results in extremely elevated plasma low-density lipoprotein cholesterol concentrations and very early morbidity and mortality due to cardiovascular disease.
  
  
  RESULTS
  To evaluate the impact of advances in lipid-lowering (predominantly statin) therapy on cardiovascular disease morbidity and mortality in a large cohort of patients with homozygous familial hypercholesterolemia, the records of 149 patients (81 females, 68 males) from 2 specialized lipid clinics in South Africa were evaluated retrospectively. Homozygous familial hypercholesterolemia was diagnosed by confirmation of mutations in genes affecting low-density lipoprotein cholesterol or by clinical criteria. A Cox proportional hazard model with time-varying exposure was used to estimate the risk of death and major adverse cardiovascular events among statin-treated patients compared with statin-naive patients. The hazard ratio for benefit from lipid therapy, calculated with the Cox proportional hazards model for the end point of death, was 0.34 (95% confidence interval 0.14-0.86; P=0.02), and for the end point of major adverse cardiovascular events, it was 0.49 (95% confidence interval 0.22-1.07; P=0.07). This occurred despite a mean reduction in low-density lipoprotein cholesterol of only 26.4% (from 15.9±3.9 to 11.7±3.4 mmol/L; P<0.0001) with lipid-lowering therapy.
  
  
  CONCLUSIONS
  Lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia.
authors: Carbohydrate & Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa. Frederick.raal@wits.ac.za
authors: Frederick J
authors: FJ
authors: Raal
authors: Gillian J
authors: GJ
authors: Pilcher
authors: Vanessa R
authors: VR
authors: Panz
authors: Hendrick E
authors: HE
authors: van Deventer
authors: Brigitte C
authors: BC
authors: Brice
authors: Dirk J
authors: DJ
authors: Blom
authors: A David
authors: AD
authors: Marais
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors