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Canadian Journal of Cardiology

Canadian Society of Clinical Chemists Harmonized Clinical Laboratory Lipid Reporting Recommendations on the Basis of the 2021 Canadian Cardiovascular Society Lipid Guidelines

Published:April 01, 2022DOI:https://doi.org/10.1016/j.cjca.2022.03.019

      Abstract

      There is limited guidance on laboratory reporting and interpretation of lipids and lipoproteins used in cardiovascular risk stratification. This contributes to inconsistencies in lipid reporting across clinical laboratories. Recently, the Canadian Cardiovascular Society (CCS) published the 2021 CCS guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult. A subcommittee of the Working Group on Reference Interval Harmonization of the Canadian Society of Clinical Chemists has developed harmonized lipid reporting recommendations that are aligned with the 2021 CCS guidelines, to improve the standardization of lipid assessment and clinical decision-making. The proposed harmonized lipid reporting recommendations were critically reviewed by a broad range of laboratory and clinical experts across Canada. Feedback from approximately 30 expert reviewers was reviewed by the Working Group on Reference Interval Harmonization lipid subcommittee, and consensus decisions were incorporated into the 2021 harmonized lipid reporting recommendations. In this position statement, we provide 6 recommendations for laboratory reporting of lipid parameters. These recommendations include implementing the new National Institutes of Health equation to replace the Friedewald equation for calculating low-density lipoprotein cholesterol, offering lipoprotein (a), either as an in-house or send-out test, and using assays that report lipoprotein (a) in molar units (nmol/L). We also developed a harmonized lipid reporting format with interpretive comments that includes flagging results based on screening patients using treatment decision thresholds in a primary prevention setting. Overall, harmonized lipid reporting will help bridge the gap between clinical guideline recommendations and clinical laboratory reporting and interpretation, and will improve cardiovascular risk assessment across Canada.

      Résumé

      Il existe peu de recommandations visant les pratiques des laboratoires en matière de présentation et d’interprétation des résultats du dosage des lipides et des lipoprotéines servant à la stratification du risque cardiovasculaire. Cette situation se traduit par des divergences dans la façon dont les laboratoires cliniques présentent le bilan lipidique. La Société canadienne de cardiologie a publié récemment ses lignes directrices de 2021 sur la prise en charge de la dyslipidémie pour la prévention des maladies cardiovasculaires chez les adultes (en anglais seulement). Un sous-comité du groupe de travail de la Société canadienne des clinico-chimistes sur l’harmonisation des intervalles de référence a formulé des recommandations en matière de présentation harmonisée du bilan lipidique. Ces recommandations ont été établies en concordance avec les lignes directrices de 2021 de la SCC afin d’améliorer la normalisation du bilan lipidique et la prise de décisions cliniques. Les recommandations proposées sur la présentation harmonisée du bilan lipidique ont été l’objet d’un examen critique de la part d’un large éventail de laboratoires et d’experts cliniques partout au Canada. Le sous-comité du groupe de travail sur l’harmonisation des intervalles de référence a passé en revue les commentaires d’environ 30 évaluateurs experts, et les décisions consensuelles ont été intégrées aux recommandations de 2021 sur la présentation harmonisée du bilan lipidique. Dans cet énoncé de position, nous formulons six recommandations visant les paramètres de présentation du bilan lipidique par les laboratoires. Ces recommandations préconisent notamment le dosage du cholestérol à lipoprotéines de faible densité au moyen de la nouvelle équation des National Institutes of Health en remplacement de l’équation de Friedewald, le dosage facultatif de la lipoprotéine (a) à l’interne ou à l’externe et l’expression du taux de lipoprotéine (a) en unités molaires (nmol/l). Nous avons également mis au point une présentation harmonisée du bilan lipidique assortie de commentaires interprétatifs où les résultats signalés sont basés sur le dépistage des patients à l'aide des seuils thérapeutiques décisionnels sélectifs dans un contexte de prévention primaire. Globalement, la présentation harmonisée du bilan lipidique contribuera à combler l’écart entre les recommandations des lignes directrices cliniques et les pratiques des laboratoires cliniques en matière de présentation et d’interprétation des résultats d’analyses. Elle améliorera de ce fait l’évaluation du risque cardiovasculaire à l’échelle du Canada.
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      References

        • Pearson G.J.
        • Thanassoulis G.
        • Anderson T.J.
        • et al.
        2021 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
        Can J Cardiol. 2021; 37: 1129-1150
        • Higgins V.
        • Habeeb N.W.A.
        • Venner A.A.
        • et al.
        A snapshot of lipid reporting practices in Canadian clinical laboratories: an urgent need for harmonization.
        Can J Cardiol. 2021; 37: 933-937
        • Adeli K.
        • Higgins V.
        • Seccombe D.
        • et al.
        National survey of adult and pediatric reference intervals in clinical laboratories across Canada: a report of the CSCC Working Group on Reference Interval Harmonization.
        Clin Biochem. 2017; 50: 925-935
        • Arnett D.K.
        • Blumenthal R.S.
        • Albert M.A.
        • et al.
        2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        Circulation. 2019; 140: e563-e595
        • Anderson T.J.
        • Grégoire J.
        • Pearson G.J.
        • et al.
        2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult.
        Can J Cardiol. 2016; 32: 1263-1282
        • Doran B.
        • Guo Y.
        • Xu J.
        • et al.
        Prognostic value of fasting versus nonfasting low-density lipoprotein cholesterol levels on long-term mortality: insight from the National Health and Nutrition Examination Survey III (NHANES-III).
        Circulation. 2014; 130: 546-553
        • Langsted A.
        • Freiberg J.J.
        • Nordestgaard B.G.
        Fasting and nonfasting lipid levels: influence of normal food intake on lipids, lipoproteins, apolipoproteins, and cardiovascular risk prediction.
        Circulation. 2008; 118: 2047-2056
        • Sidhu D.
        • Naugler C.
        Fasting time and lipid levels in a community-based population: a cross-sectional study.
        Arch Intern Med. 2012; 172: 1707-1710
        • Miller W.G.
        • Myers G.L.
        • Sakurabayashi I.
        • et al.
        Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures.
        Clin Chem. 2010; 56: 977-986
        • Langsted A.
        • Kamstrup P.R.
        • Nordestgaard B.G.
        Lipoprotein(a): fasting and nonfasting levels, inflammation, and cardiovascular risk.
        Atherosclerosis. 2014; 234: 95-101
        • Clarke R.
        • Peden J.F.
        • Hopewell J.C.
        • et al.
        Genetic variants associated with Lp(a) lipoprotein level and coronary disease.
        N Engl J Med. 2009; 361: 2518-2528
        • Kamstrup P.R.
        • Tybjaerg-Hansen A.
        • Steffensen R.
        • Nordestgaard B.G.
        Genetically elevated lipoprotein(a) and increased risk of myocardial infarction.
        JAMA. 2009; 301: 2331-2339
        • Valdivielso P.
        • Ramírez-Bueno A.
        • Ewald N.
        Current knowledge of hypertriglyceridemic pancreatitis.
        Eur J Intern Med. 2014; 25: 689-694
        • Marcovina S.M.
        • Albers J.J.
        • Kennedy H.
        • Mei J.V.
        • Henderson L.O.
        • Hannon W.H.
        International Federation of Clinical Chemistry standardization project for measurements of apolipoproteins A-I and B. IV. Comparability of apolipoprotein B values by use of International Reference Material.
        Clin Chem. 1994; 40: 586-592
        • Cao J.
        • Steffen B.T.
        • Guan W.
        • et al.
        A comparison of three apolipoprotein B methods and their associations with incident coronary heart disease risk over a 12-year follow-up period: the Multi-Ethnic Study of Atherosclerosis.
        J Clin Lipidol. 2018; 12: 300-304
        • International Federation for Clinical Chemistry (IFCC)
        Apolipoproteins by mass spectrometry (WG-APO MS).
        (Available at:) (Accessed Accessed June 15, 2022)
        • Cobbaert C.M.
        • Althaus H.
        • Begcevic Brkovic I.
        • et al.
        Towards an SI-traceable reference measurement system for seven serum apolipoproteins using bottom-up quantitative proteomics: conceptual approach enabled by cross-disciplinary/cross-sector collaboration.
        Clin Chem. 2021; 67: 478-489
        • Steffen B.T.
        • Thanassoulis G.
        • Duprez D.
        • et al.
        Race-based differences in lipoprotein(a)-associated risk of carotid atherosclerosis.
        Arterioscler Thromb Vasc Biol. 2019; 39: 523-529
        • Steffen B.T.
        • Duprez D.
        • Bertoni A.G.
        • Guan W.
        • Tsai M.Y.
        Lp(a) [lipoprotein(a)]-related risk of heart failure is evident in whites but not in other racial/ethnic groups.
        Arterioscler Thromb Vasc Biol. 2018; 38: 2498-2504
        • Lloyd-Jones D.M.
        • Wilson P.W.F.
        • Larson M.G.
        • et al.
        Lifetime risk of coronary heart disease by cholesterol levels at selected ages.
        Arch Intern Med. 2003; 163: 1966-1972
        • Alberti K.G.M.M.
        • Eckel R.H.
        • Grundy S.M.
        • et al.
        Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.
        Circulation. 2009; 120: 1640-1645
        • Nordestgaard B.G.
        • Langsted A.
        • Mora S.
        • et al.
        Fasting is not routinely required for determination of a lipid profile: clinical and laboratory implications including flagging at desirable concentration cut-points-a joint consensus statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine.
        Eur Heart J. 2016; 37: 1944-1958
        • Kathiresan S.
        • Otvos J.D.
        • Sullivan L.M.
        • et al.
        Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study.
        Circulation. 2006; 113: 20-29
        • Nordestgaard B.G.
        • Langsted A.
        Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology.
        J Lipid Res. 2016; 57: 1953-1975
        • Trinder M.
        • Uddin M.M.
        • Finneran P.
        • Aragam K.G.
        • Natarajan P.
        Clinical utility of lipoprotein(a) and LPA Genetic Risk Score in risk prediction of incident atherosclerotic cardiovascular disease.
        JAMA Cardiol. 2020; 6: 1-9
        • Ruhaak L.R.
        • Cobbaert C.M.
        Quantifying apolipoprotein(a) in the era of proteoforms and precision medicine.
        Clin Chim Acta. 2020; 511: 260-268
        • Cegla J.
        • France M.
        • Marcovina S.M.
        • Neely R.D.G.
        Lp(a): when and how to measure it.
        Ann Clin Biochem. 2021; 58: 16-21
        • Gudbjartsson D.F.
        • Thorgeirsson G.
        • Sulem P.
        • et al.
        Lipoprotein(a) concentration and risks of cardiovascular disease and diabetes.
        J Am Coll Cardiol. 2019; 74: 2982-2994
        • Tate J.R.
        • Berg K.
        • Couderc R.
        • et al.
        International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) standardization project for the measurement of lipoprotein(a). Phase 2: selection and properties of a proposed secondary reference material for lipoprotein(a).
        Clin Chem Lab Med. 1999; 37: 949-958
        • Kostner G.M.
        • Ibovnik A.
        • Holzer H.
        • Grillhofer H.
        Preparation of a stable fresh frozen primary lipoprotein[a] (Lp[a]) standard.
        J Lipid Res. 1999; 40: 2255-2263
        • Marcovina S.M.
        • Koschinsky M.L.
        • Albers J.J.
        • Skarlatos S.
        Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: recent advances and future directions.
        Clin Chem. 2003; 49: 1785-1796
        • Sampson M.
        • Ling C.
        • Sun Q.
        • et al.
        A new equation for calculation of low-density lipoprotein cholesterol in patients with normolipidemia and/or hypertriglyceridemia.
        JAMA Cardiol. 2020; 5: 540-548
        • Higgins V.
        • Leiter L.A.
        • Delaney S.R.
        • Beriault D.R.
        Validating the NIH LDL-C equation in a specialized lipid cohort: does it add up?.
        Clin Biochem. 2022; 99: 60-68
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin Chem. 1972; 18: 499-502
        • Martin S.S.
        • Blaha M.J.
        • Elshazly M.B.
        • et al.
        Friedewald-estimated versus directly measured low-density lipoprotein cholesterol and treatment implications.
        J Am Coll Cardiol. 2013; 62: 732-739
        • Grundy S.M.
        • Stone N.J.
        • Bailey A.L.
        • et al.
        2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
        J Am Coll Cardiol. 2019; 73: 3168-3209
        • Mach F.
        • Baigent C.
        • Catapano A.L.
        • et al.
        2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk.
        Eur Heart J. 2020; 41: 111-188
        • Cicero A.F.G.
        • Fogacci F.
        • Patrono D.
        • et al.
        Application of the Sampson equation to estimate LDL-C in children: comparison with LDL direct measurement and Friedewald equation in the BLIP study.
        Nutr Metab Cardiovasc Dis. 2021; 31: 1911-1915
        • Naugler C.
        • Cook C.
        • Morrin L.
        • et al.
        Statin prescriptions for high-risk patients are increased by laboratory-initiated Framingham Risk Scores: a quality-improvement initiative.
        Can J Cardiol. 2017; 33: 682-684

      Linked Article

      • Calculated LDL-C: Time to Move On?
        Canadian Journal of Cardiology
        • Preview
          Despite its shortcomings, the Friedewald equation is still being used today in most clinical laboratories to calculate low-density lipoprotein-cholesterol (LDL-C). Updated equations have been proposed to circumvent some of the problems of LDL-C calculation. A recent article by White-Al Habeeb et al.1 in this journal recommended implementation of the new National Institutes of Health (NIH) equation2 rather than the Friedewald calculation. The authors stated that the new NIH equation “allows for calculation of LDL-C up to triglyceride 9.04 mmol/L.”
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