title: Clinical impact of direct HDLc and LDLc method bias in hypertriglyceridemia. A simulation study of the EAS-EFLM Collaborative Project Group.
abstract: BACKGROUND
  Despite international standardization programs for LDLc and HDLc measurements, results vary significantly with methods from different manufacturers. We aimed to simulate the impact of analytical error and hypertriglyceridemia on HDLc- and LDLc-based cardiovascular risk classification.
  
  
  METHODS
  From the Dutch National EQA-2012 external quality assessment of 200 clinical laboratories, we examined data from normotriglyceridemic (∼ 1 mmol/l) and hypertriglyceridemic (∼ 7 mmol/l) serum pools with lipid target values assigned by the Lipid Reference Laboratory in Rotterdam. HDLc and LDLc were measured using direct methods of Abbott, Beckman, Siemens, Roche, Olympus, or Ortho Clinical Diagnostics. We simulated risk reclassification using HDL- and sex-specific SCORE multipliers considering two fictitious moderate-risk patients with initial SCORE 4% (man) and 3% (woman). Classification into high-risk treatment groups (LDLc >2.50 mmol/l) was compared between calculated LDLc and direct LDLc methods.
  
  
  RESULTS
  Overall HDLc measurements in hypertriglyceridemic serum showed negative mean bias of -15%. HDL-multipliers falsely reclassified 70% of women and 43% of men to a high-risk (SCORE >5%) in hypertriglyceridemic serum (P < 0.0001 vs. normotriglyceridemic serum) with method-dependent risk reclassifications. Direct LDLc in hypertriglyceridemic serum showed positive mean bias with Abbott (+16%) and Beckman (+14%) and negative mean bias with Roche (-7%). In hypertriglyceridemic serum, 57% of direct LDLc measurements were above high-risk treatment goal (2.50 mmol/l) vs. 29% of direct LDLc (33% of calculated LDLc) in normotriglyceridemic sera.
  
  
  CONCLUSIONS
  LDLc and HDLc measurements are unreliable in severe hypertriglyceridemia, and should be applied with caution in SCORE risk classification and therapeutic strategies.
authors: European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group (WG) Cardiac Markers; WG Guidelines, EFLM; Department of Laboratory Medicine, AZ St-Jan Bruges and Ghent University, B-8000 Bruges, Belgium. Electronic address: michel.langlois@azsintjan.be.
authors: Michel R
authors: MR
authors: Langlois
authors: Centre de Recherche Médicale de Jolimont, Hôpital de Jolimont, 7100 Haine Saint-Paul, Belgium.
authors: Olivier S
authors: OS
authors: Descamps
authors: Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
authors: Arnoud
authors: A
authors: van der Laarse
authors: Queen Beatrix Hospital, Winterswijk, The Netherlands.
authors: Cas
authors: C
authors: Weykamp
authors: European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group (WG) Cardiac Markers; Institut für Laboratoriumsmedizin, Mikrobiologie, Blutdepot und Krankenhaushygiene, Regionale Kliniken Holding RKH GmbH, Posilipostr. 4, D-71640 Ludwigsburg, Germany.
authors: Hannsjörg
authors: H
authors: Baum
authors: European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group (WG) Cardiac Markers; Department of Clinical Chemistry, University of Eastern Finland and Eastern Finland Laboratory Centre, P.O.B. 1700 FIN-70211 Kuopio, Finland.
authors: Kari
authors: K
authors: Pulkki
authors: Institute of Clinical Chemistry, University Hospital of Zurich, Rämistrasse 100, 8091 Zürich, Switzerland.
authors: Arnold
authors: A
authors: von Eckardstein
authors: Department of Public Health, Ghent University, B-9000 Ghent, Belgium.
authors: Dirk
authors: D
authors: De Bacquer
authors: Wallenberg Laboratory, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors: Jan
authors: J
authors: Borén
authors: Wallenberg Laboratory, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors: Olov
authors: O
authors: Wiklund
authors: European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group (WG) Cardiac Markers.
authors: Païvi
authors: P
authors: Laitinen
authors: WG Guidelines, EFLM.
authors: Wytze P
authors: WP
authors: Oosterhuis
authors: Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors: Christa
authors: C
authors: Cobbaert
mesh_terms: D015982:Bias; D002318:Cardiovascular Diseases / Q000209:etiology; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D003951:Diagnostic Errors / Q000517:prevention & control; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000175:diagnosis*; D008297:Male; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL
keywords: HDL-cholesterol; Hypertriglyceridemia; LDL-cholesterol; Risk classification; SCORE; Treatment goals