title: Familial combined hyperlipidemia and hyperlipoprotein(a) as phenotypic mimics of familial hypercholesterolemia: Frequencies, associations and predictions.
abstract: A significant proportion of index cases presenting with phenotypic familial hypercholesterolemia (FH) are not found to have a pathogenic mutation and may have other inherited conditions.
  
  
  
  Familial combined hyperlipidemia (FCHL) and elevated lipoprotein(a) [Lp(a)] may mimic FH, but the frequency and correlates of these disorders among mutation-negative FH patients have yet to be established.
  
  
  
  The frequency of FCHL and elevated Lp(a) was investigated in 206 FH mutation-negative index cases attending a specialist lipid clinic. An FCHL diagnostic nomogram was applied to each index case; a positive diagnosis was made in patients with a probability score exceeding 90%. Plasma Lp(a) concentration was measured by immunoassay, with an elevated level defined as ≥0.5 g/L. Clinical characteristics, including coronary artery disease (CAD) events, were compared between those with and without FCHL and hyper-Lp(a).
  
  
  
  Of mutation-negative FH patients, 51.9% had probable FCHL. These patients were older (P = .002), had a higher BMI (P = .019) and systolic (P = .001) and diastolic blood pressures (P = .001) compared with those without FCHL. Elevated Lp(a) was observed in 44.7% of cases, and there were no significant differences in clinical characteristics with Lp(a) status. The presence of elevated Lp(a) (P = .002), but not FCHL, predicted CAD events. This association was independent of established CAD risk factors (P = .032).
  
  
  
  FCHL and elevated Lp(a) are common disorders in patients with mutation-negative FH. Among such patients, FCHL co-expresses with components of the metabolic syndrome, and elevated Lp(a) is the major contributor to increased CAD risk.
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Katrina L
authors.initials: KL
authors.lastname: Ellis
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Pang
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Dick C
authors.initials: DC
authors.lastname: Chan
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia; School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Hooper
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia.
authors.forename: Damon A
authors.initials: DA
authors.lastname: Bell
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital and Fiona Stanley Hospital Network, Perth, Australia; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia.
authors.forename: John R
authors.initials: JR
authors.lastname: Burnett
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Lipid Disorders Clinic, Department of Cardiology, Royal Perth Hospital, Perth, Australia. Electronic address: gerald.watts@uwa.edu.au.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D001055:Apolipoproteins B / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003324:Coronary Artery Disease / Q000209:etiology; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology; D006938:Hyperlipoproteinemia Type II / Q000150:complications* / Q000175:diagnosis* / Q000453:epidemiology; D017270:Lipoprotein(a) / Q000097:blood*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D014280:Triglycerides / Q000097:blood
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D017270:Lipoprotein(a); D014280:Triglycerides
keywords: Coronary artery disease; Familial combined hyperlipidemia; Familial hypercholesterolemia; Lipoprotein(a); Mutation negative