Non-fasting lipid profiles: implications for lipoprotein testing and reporting Consensus guideline of the European Atherosclerosis Society (EAS) and European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) presenter: Michel Langlois MD,PhD AZ St.-Jan Bruges & University of Ghent, Belgium Chair of EFLM Task & Finish Group – Laboratory Testing for Dyslipidemia EFLM webinar moderator: prof. Dr. Jerzy-Roch Nofer leader of the scientific Clinical Chemistry division at the University of Münster.
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Non-fasting lipid profiles: implications for lipoprotein testing and
reportingConsensus guideline of the European Atherosclerosis Society (EAS) and
European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)
presenter: Michel Langlois MD,PhD
AZ St.-Jan Bruges & University of Ghent, BelgiumChair of EFLM Task & Finish Group – Laboratory Testing for Dyslipidemia
EFLM webinar
moderator: prof. Dr. Jerzy-Roch Noferleader of the scientific Clinical Chemistry division at the University of Münster.
About Presenter• Professor at Ghent University, Department of Cardiovascular
Diseases• Vice-Director at the laboratory of AZ St-Jan hospital, Bruges• President of the Belgian Atherosclerosis Society• Past-president of the Royal Belgian Society of Laboratory Medicine• Chair of the EFLM-EAS Task and Finish Group on Laboratory
Testing for Dyslipidemia• Member of the EFLM WG-Guidelines• Corresponding member for the EFLM WG-Cardiac Markers and
B. NordestgaardA. VarboThe Lancet 2014; 384:626-635
A.Varbo et al. Copenhagen General Population Study, Copenhagen City Heart Study, & Copenhagen Ischemic Heart Disease Study. J Am Coll Cardiol 2013;61:427-36.
Remnant cholesterol is a direct, causal CVD risk factor
LDL-particles
Low LDL-C; underestimated risk
Misleading LDL-C
Atherogenic Dyslipidemia in Diabetes and the Metabolic Syndrome
Nordestgaard et al. EAS EFLM joint Consensus Panel. Eur Heart J 2016
Population-based studies N >300 000 non-fasting individuals
Statin trials N= 43 000 non-fasting individuals
Tromsø Heart Study Heart Protection Study
Norwegian National Health Service Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm
British Population Studies Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine
European Prospective Investigation of Cancer–Norfolk
Northwick Park Heart StudyApolipoprotein-related Mortality RiskCopenhagen City Heart StudyWomen's Health StudyNurses' Health StudyPhysicians' Health Study
National Health and Nutrition Examination Survey III
Circulatory Risk in Communities StudyCopenhagen General Population Study
INTERHEART study
Nordestgaard et al. EAS EFLM joint Consensus Panel. Eur Heart J 2016
• Potential for risk misclassification in hypertriglyceridemic samples!
Abbott Beckman Olympus Roche Siemens Ortho
1.3
1.2
1.1
1.0
0.9
0.8
0.7
0.6
Langlois M et al. The EAS-EFLM Collaborative Project. Atherosclerosis 2014; 233:83-90
1.08CDC Reference Laboratory,Rotterdam
EQA survey (n=197 labs) of hypertriglyceridemic serum (~7 mmol/l)
Risk cutpoint
In red: SCORE>5 % and LDL-C ³ 2.50 mmol/L: start statin therapy immediately In green: SCORE>5 % and LDL-C <2.50 mmol/L: not applicable for statin therapy.
Clinical simulation: effect of direct LDL-C method variation on treatment
= TC - HDLC
A.Varbo et al. Copenhagen General Population Study. J Am Coll Cardiol 2013;61:427-36.
Non-fasting non-HDLC includes ‘remnant-cholesterol’
Abbott Beckman Olympus Roche Siemens Ortho
5.3
5.1
4.9
4.7
4.5
4.3
Langlois M et al. The EAS-EFLM Collaborative Project. Atherosclerosis 2014; 233:83-90
EQA survey (n=197 labs) of hypertriglyceridemic serum
• Non-HDLC§ Calculated as TC – HDLC at no additional cost§ Includes ‘remnant-C’§ Not influenced by TG variability§ HDLC measurement errors!
• ApoB§ Simple, automated assay§ Single, well-defined measurand§ International standard SP3-08 (WHO / IFCC)§ LDL-particle number count
Non-fasting lipoprotein markers beyond LDLC
Comparison of 26 lipid fractions as predictors of first-ever cardiovascular events in apparently healthy women. Data are shown for the top versus bottom quintile of each lipid fraction.
The Lancet 2014;384:607 - 617
Paul M Ridker LDL cholesterol: controversies and future therapeutic directions
Relative Risk Ratios (RRR) for LDLC, non-HDLC, and apoBfrom 12 independent epidemiological studies
Sniderman A et al. Circ Cardiovasc Qual Outcomes 2011;4:337-345
From: Association of LDL Cholesterol, Non–HDL Cholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events Among Patients Treated With Statins: Meta-analysis of 8 Trials (N=38 153)
Boekholdt SM et al. JAMA. 2012;307:1302-1309.
Hazard ratios (HRs) and 95% CIs for risk of major cardiovascular events for 4 categories of statin-treated patients, based on whether or not they reached the LDL-C target of 100 mg/dL and the non–HDL-C target of 130 mg/dL. HRs were adjusted for sex, age, smoking, diabetes, systolic blood pressure, and trial.
Jepsen AK et al. Clin Chem 2016;62:593-604
Remnant cholesterol explains part of residual risk of mortalityin 5414 patients with ischemic heart disease
National Societies for cardiology, endocrinology, atherosclerosis, pediatrics, clinical chemistry, general practice etc.
Key university hospitals and reference centers
National Implementation Strategies
Journalists and key medias disseminate the story that fasting is no longer routinely required for lipid testing
Clinical chemistry laboratories no longer require fasting for lipid testing and use desirable concentration cutpoints for lipid test reporting and flagging
From EFLM: Michel Langlois (Belgium; EFLM co-chair)Hannsjörg Baum (Germany), Christa Cobbaert (The Netherlands), Kari Pulkki (Finland), Grazyna Sypniewska (Poland)From EAS: Børge Nordestgaard (Denmark; EAS co-chair)Jan Borén (Sweden), Olivier Descamps (Belgium), Arnold von Eckardstein (Switzerland), Olov Wiklund (Sweden)Invited expertsEric Bruckert (France), John Chapman (France), Pia Kamstrup (Denmark), Genovefa Kolovou (Greece), Florian Kronenberg (Austria), Anne Langsted (Denmark), Samia Mora (USA), Alan Remaley (USA), Nader Rifai (USA), Emilio Ros (Spain), Gerald Watts ( Australia)