title: Genetically determined apo B levels and peak LDL density predict angiographic response to intensive lipid-lowering therapy.
abstract: OBJECTIVE
  Lipid-lowering therapy (LL-Rx) reduces coronary artery disease (CAD) but the response varies amongst individuals. We investigated the contribution of three genetic forms of dyslipidaemia characterized by elevated plasma apo B, familial hypercholesterolaemia (FH), familial combined hyperlipidaemia (FCHL), and elevated Lp(a), to the angiographic response with LL-Rx.
  
  
  RESULTS
  Fifty-one men, with premature CAD and elevated plasma apo B, were selected in whom a genetic diagnosis was based on lipid phenotypes in relatives. Subjects received conventional (diet +/- colestipol) or intensive LL-Rx (niacin or lovastatin plus colestipol). Clinical parameters and CAD severity were measured before and after 2 years of treatment. Twenty-seven patients had FCHL, 12 FH and 12 elevated Lp(a). Regression of coronary stenosis was dependent on the effect of therapy (P < 0.001), genetic form of dyslipidaemia (P = 0.004) and the interaction between the two variables (P = 0.02). Significant regression of coronary stenosis occurred only in FCHL and Lp(a) (P = 0.03, vs. control groups); CAD progression was only slowed in FH.
  
  
  CONCLUSIONS
  Three genetic forms of dyslipidaemia were associated with different angiographic outcomes during intensive LL-Rx. Different forms of dyslipidaemia therefore may require different lipid-lowering strategy. Patients with FH and buoyant LDL require more aggressive reduction of LDL cholesterol whilst those with either FCHL or elevated Lp(a) with dense LDL need LDL cholesterol reduction as well as therapies aimed at reduction of the small, dense LDL particles.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195-6426, USA.
authors.forename: A
authors.initials: A
authors.lastname: Zambon
authors.forename: B G
authors.initials: BG
authors.lastname: Brown
authors.forename: J E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: A G
authors.initials: AG
authors.lastname: Motulsky
authors.forename: J D
authors.initials: JD
authors.lastname: Brunzell
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001055:Apolipoproteins B / Q000097:blood*; D003084:Colestipol / Q000627:therapeutic use; D017023:Coronary Angiography; D023921:Coronary Stenosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000235:genetics*; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood*; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000627:therapeutic use; D010597:Pharmacogenetics; D016896:Treatment Outcome
chemical_list: D001055:Apolipoproteins B; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D009525:Niacin; D008148:Lovastatin; D003084:Colestipol