CoChat
Sign Up
Cited by 240Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCancer, Lipids, and Metabolism

Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM

Open access
Nordestgaard, Børge G., Langlois, Michel R., Langsted, Anne, Chapman, M. John, Aakre, Kristin M., Baum, Hannsjörg, Borén, Jan, Bruckert, Eric +21 more·2020·Atherosclerosis
DOI 10.1016/j.atherosclerosis.2019.12.005
Open this paper in CoChat — free accountOpen PDF

Abstract

The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.

Integrity signals

Registry

Crossref · 10.1016/j.atherosclerosis.2019.12.005

Cites

110 of 110 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

100 of 160 cited sources checked · 50 supported · 1 flagged · accuracy not yet measured

  • Interpretationcitation

    Replacing LDLC by apoB would identify more individuals with increased risk of ASCVD.

    “suggesting that replacing LDLC by apoB would identify more individuals with increased risk of ASCVD [74]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [74] Welsh, 2019, Comparison of conventional lipoprotein tests and apolipoproteins in the prediction of cardiovascular disease. Data from UK biobank, Circulation source

      The Discussion (page unavailable) concludes that replacing standard cholesterol measures with apolipoproteins does not improve CVD risk prediction. The Results likewise report no improvement in risk classification from adding an apolipoprotein measure to a model containing total cholesterol and HDL-C. The paper therefore does not support the claim that substituting apoB for LDL-C would identify more people at increased risk. (LLM, conf=0.88)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    All LDL particles are atherogenic, regardless of size.

    “While earlier studies emphasized the atherogenicity of small LDL particles, it is now recognized that all LDL particles are atherogenic, regardless of size [10].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [10] Mora, 2009, Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use, Circulation source
  • Interpretationcitation

    Nonfasting lipid profiles can potentially be more relevant to the estimation of an individual's cardiovascular risk than fasting lipids since in real life the postprandial state predominates most of the 24-h cycle.

    “Nonfasting lipid profiles, therefore, can potentially be more relevant to the estimation of an individual's cardiovascular risk than fasting lipids since in real life the postprandial state predominates most of our 24-h cycle [15,16].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [15] Mora, 2008, Fasting compared with nonfasting lipids and apolipoproteins for predicting incident cardiovascular events, Circulation source

      The Discussion (page unavailable) reports that several lipids predict cardiovascular events when measured nonfasting, supporting the possibility that nonfasting measurements are useful. It also says total, LDL, and non-HDL cholesterol may provide less useful risk information when measured nonfasting. The paper does not establish that nonfasting lipid profiles are generally more relevant because the postprandial state predominates over a 24-hour cycle. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [16] Nordestgaard, 2017, A test in context: lipid profile, fasting versus non-fasting, J. Am. Coll. Cardiol. source
  • Premisecitation

    In patients with mild-to-moderate hypertriglyceridemia, defined as 2-10 mmol/L, elevated baseline and on-treatment apoB helps identify the atherogenic dyslipidemia related to remnant lipoproteins combined with small dense LDL particles that is not reflected by LDLC and non-HDLC.

    “In patients with mild-to-moderate hypertriglyceridemia, defined as 2-10 mmol/L [33], elevated baseline and on-treatment apoB helps identify the atherogenic dyslipidemia related to remnant lipoproteins combined with small dense LDL particles that is not reflected by LDLC and non-HDLC.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [33] Hegele, 2014, European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management, Lancet Diabetes Endocrinol. source
  • Premisecitation

    Monogenic disorders such as familial hypercholesterolemia (FH) can be easily recognized from the standard lipid panel without the need to measure apoB.

    “Monogenic disorders such as familial hypercholesterolemia (FH) can be easily recognized from the standard lipid panel without the need to measure apoB [31,32].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [31] Nordestgaard, 2013, Eur. Heart J. source

      The Diagnosis section (page not provided) identifies very high LDL cholesterol on repeated measurements as a criterion for FH, and its diagnostic criteria do not require an apoB measurement. But it also calls for considering family and clinical history, physical findings, genetic testing, and secondary causes; it does not say FH can generally be easily recognized from a standard lipid panel alone. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [32] Wiegman, 2015, European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment, Eur. Heart J. source

      The Diagnosis section and Table 2 support using LDL-C from cholesterol testing to identify probable paediatric FH without listing apoB measurement as a requirement. But they also call for family history, repeat LDL-C testing and evaluation of secondary causes; genetic testing establishes the diagnosis. The paper therefore does not support the broader claim that FH is easily recognized from a standard lipid panel alone. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
  • May combine two claims. 41
  • Classified as probably not a substantial claim. 18
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Measurement of apolipoprotein B (apoB) or advanced measurement of LDLP can be used to assess the number of LDL particles.

    “Measurement of apolipoprotein B (apoB), the major protein component of LDL, or advanced measurement of LDLP (not yet widely available) can also be used to assess the number of LDL particles [10,12].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [10] Mora, 2009, Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use, Circulation source
    • cites [12] Contois, 2009, Apolipoprotein B and cardiovascular disease risk: position statement from the AACC lipoproteins and vascular disease working group on best practices, Clin. Chem. source

  • May combine two claims.

    Premisecitation

    Cholesterol-enriched remnant particles may enter the arterial intima and contribute to atherosclerosis, whereas nascent chylomicrons and very large VLDL particles do not cross the endothelial layer.

    “These cholesterol-enriched remnant particles may enter the arterial intima and contribute to atherosclerosis, whereas nascent chylomicrons and very large VLDL particles do not cross the endothelial layer [17].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [17] Nordestgaard, 2016, Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology, Circ. Res. source

      The Biology section (page unavailable) says medium-sized triglyceride-rich lipoproteins can enter the arterial intima and become trapped, while large chylomicrons are too large to cross the endothelial barrier. It does not establish the same exclusion for very large VLDL particles, so that part of the claim is unsupported. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Recent studies with PCSK9 inhibitors revealed that patients with higher baseline Lp(a) concentration experienced greater absolute reductions in Lp(a) and tended to derive greater clinical benefit from PCSK9 inhibition.

    “Although recent studies with PCSK9 inhibitors were not designed to target patients with high Lp(a) concentrations, they nevertheless revealed that patients with higher baseline Lp(a) concentration experienced greater absolute reductions in Lp(a) and tended to derive greater clinical benefit from PCSK9 inhibition [27,28].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [27] O'Donoghue, 2019, Lipoprotein(a), PCSK9 inhibition and cardiovascular risk: insights from the FOURIER Trial, Circulation source
    • cites [28] Ray, 2019, Lipoprotein(a) reductions from PCSK9 inhibition and major adverse cardiovascular events: pooled analysis of alirocumab phase 3 trials, Atherosclerosis source

      Section 3.3 reports a stronger association between Lp(a) reduction and fewer major adverse cardiovascular events among patients with baseline Lp(a) ≥50 mg/dL; the Discussion describes greater benefit as a possibility, consistent with the claim’s 'tended to' wording. The Discussion says higher initial Lp(a) levels are likely to offer greater absolute reductions, but the cited text does not establish as an observed subgroup result that these patients experienced greater absolute reductions with PCSK9 inhibition. Page numbers were not available in our copy. (LLM, conf=0.78)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Circulating LDL particles are highly atherogenic and there is a direct, graded relationship between LDLC concentration and the incidence of ASCVD observed in randomized controlled trials, prospective epidemiological cohort studies, and Mendelian randomization studies.

    “Circulating LDL particles are highly atherogenic and there is a direct, graded relationship between LDLC concentration and the incidence of ASCVD observed in randomized controlled trials, prospective epidemiological cohort studies, and Mendelian randomization studies [7,8].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [7] Ference, 2017, Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel, Eur. Heart J. source
    • cites [8] Baigent, 2010, Cholesterol Treatment Trialists' (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials, Lancet source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    When Friedewald-calculated LDLC is used, calculated RemnantC simply equals TG/2.2 (in mmol/L) and does not add clinical information beyond TG concentration.

    “Direct LDLC measurement should preferably be used in the calculation of RemnantC; otherwise RemnantC simply equals TG/2.2 (in mmol/L) when Friedewald-calculated LDLC is used, i.e.TC -HDLC -(TC -HDLC -TG/2.2),and it does not add clinical information beyond TG concentration [1]”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

  • May combine two claims.

    Premisecitation

    RemnantC, measured or calculated, differs from non-HDLC in that non-HDLC contains RemnantC plus LDLC and does not differentiate between these two causal risk factors.

    “RemnantC, measured or calculated, differs from non-HDLC in that non-HDLC contains RemnantC plus LDLC and does not differentiate between these two causal risk factors [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

  • May combine two claims.

    Premisecitation

    All LDL particles are atherogenic, but their concentration is not always reflected by LDLC measurement because the cholesterol content in the particles can vary widely between individuals according to the continuous remodeling of lipoproteins in blood.

    “All LDL particles are atherogenic, but their concentration is not always reflected by LDLC measurement because the cholesterol content in the particles can vary widely between individuals according to the continuous remodeling of lipoproteins in blood [10].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [10] Mora, 2009, Advanced lipoprotein testing and subfractionation are not (yet) ready for routine clinical use, Circulation source

      In §1.B (page not supplied), the paper says small and large LDL particles are similarly atherogenic and illustrates that two people can have the same LDL cholesterol level but different LDL particle concentrations because smaller particles contain less cholesterol. The passage does not attribute this variation to continuous remodeling of lipoproteins in blood, so that causal explanation is unsupported. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Non-HDLC represents the cholesterol in all particles causing cardiovascular disease, that is, LDL, VLDL, IDL, and Lp(a); in the nonfasting state this additionally includes the cholesterol in chylomicrons and their remnant particles.

    “Calculated by subtracting HDLC from TC, non-HDLC represents the cholesterol in all particles causing cardiovascular disease, that is, LDL, VLDL, IDL, and Lp(a); in the nonfasting state this additionally includes the cholesterol in chylomicrons and their remnant particles [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

      The CALCULATED NON-HDLC section (p. 12) defines non-HDLC as total cholesterol minus HDL cholesterol and lists LDL, VLDL, IDL, chylomicron remnants, and Lp(a) among the particles it covers. The LDL PARTICLES section (p. 5) specifies that chylomicron remnants contribute in the nonfasting state. The REMNANT PARTICLES section (p. 5) distinguishes these atherogenic remnants from nascent chylomicrons, which it says are initially too large to enter the arterial wall; the claim does not preserve that distinction when describing chylomicrons as particles causing cardiovascular disease. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingcitation

    Changes in a patient's LDLC test result over time are within the range of uncertainty of laboratory method variation and may not be due to therapeutic intervention.

    “Not uncommonly, changes in a patient's LDLC test result over time are within the range of uncertainty of laboratory method variation and may not be due to therapeutic intervention [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

  • May combine two claims.

    Findingcitation

    Direct measurements of dLDLC and dHDLC in normolipidemic samples usually meet the NCEP total error goals of ≤12% and ≤13%, respectively, but total error ranged from -26% to +32% for dLDLC and -20% to +36% for dHDLC in a comprehensive study of different assays in dyslipidemic samples.

    “Direct measurements of dLDLC and dHDLC in normolipidemic samples usually meet the National Cholesterol Education Program (NCEP) total error goals of ≤12% and ≤13%, respectively, but total error ranged from -26% to +32% for dLDLC and -20% to +36% for dHDLC in a comprehensive study of different assays in dyslipidemic samples [42].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [42] Miller, 2010, Seven direct methods for measuring HDL and LDL cholesterol compared with ultracentrifugation reference measurement procedures, Clin. Chem. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Non-HDLC yields more accurate cardiovascular risk classification than either Friedewald cLDLC or dLDLC, and also more consistent risk scores using different manufacturers' assays for dHDLC in the calculation.

    “Despite this limitation, non-HDLC yields more accurate cardiovascular risk classification than either Friedewald cLDLC or dLDLC, and also more consistent risk scores using different manufacturers' assays for dHDLC in the calculation [58].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [58] van Deventer, 2011, Non-HDL-cholesterol shows improved accuracy for cardiovascular risk score classification compared to direct or calculated LDL cholesterol in a dyslipidemic population, Clin. Chem. source

  • May combine two claims.

    Premisecitation

    Guideline-recommended therapeutic goals for non-HDLC are arbitrarily set typically at 0.8 mmol/L (30 mg/dL) higher than LDLC goals; this value is based on the assumption that the optimal VLDLC concentration associated with the fasting TG threshold 1.7 mmol/L is 0.8 mmol/L, as estimated by the Friedewald formula (TG/2.2).

    “Guideline-recommended therapeutic goals for non-HDLC are arbitrarily set typically at 0.8 mmol/L (30 mg/dL) higher than LDLC goals (Table 6); this value is based on the assumption that the”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source
    • cites [2] Nordestgaard, 2016, Eur. Heart J. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • The authors state this as an assumption: The optimal VLDLC concentration associated with the fasting TG threshold 1.7 mmol/L is 0.8 mmol/L.

  • May combine two claims.

    Premisecitation

    ApoB is the structural protein for all non-HDL lipoproteins and exists as 2 isoforms: apoB100, the major isoform in VLDL, IDL, LDL, and Lp(a), and apoB48 in chylomicrons and chylomicron remnants.

    “It is the structural protein for all non-HDL lipoproteins and exists as 2 isoforms: apoB100, the major isoform in VLDL, IDL, LDL, and Lp(a), and apoB48 in chylomicrons and chylomicron remnants [12].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] Contois, 2009, Apolipoprotein B and cardiovascular disease risk: position statement from the AACC lipoproteins and vascular disease working group on best practices, Clin. Chem. source

      The ‘apo B STRUCTURE AND FUNCTION’ section (p. 2) identifies two isoforms and calls apo B-48 the structural protein of chylomicrons. The ‘apo B-CONTAINING LIPOPROTEINS AND CVD RISK’ section (p. 2) lists VLDL, IDL, LDL, and Lp(a) as apo B-containing particles. Our copy does not explicitly assign apo B-100 to each of those particles or mention apo B-48 in chylomicron remnants. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Lowering LDLC to concentrations below a target of 1.8 mmol/L in patients at high cardiovascular risk or 1.4 mmol/L in patients at very high risk (or by ≥ 50% if these targets cannot be attained) is of critical importance.

    “Lowering LDLC to concentrations below a target of 1.8 mmol/L in patients at high cardiovascular risk or 1.4 mmol/L in patients at very high risk (or by ≥ 50% if these targets cannot be attained) is of critical importance [4].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Mach, 2019, 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. The Task force for the management of dyslipidaemias of the European society of cardiology (ESC) and European atherosclerosis society (EAS), Eur. Heart J. source

      The treatment-goals passage recommends LDL-C below 1.8 mmol/L for high-risk patients and below 1.4 mmol/L for very-high-risk patients. It recommends a ≥50% reduction from baseline alongside each absolute goal, not only as an alternative if the goal cannot be attained. (LLM, conf=0.91)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Even at peak postprandial concentrations, the number of chylomicron-apoB48 particles in healthy individuals is usually < 1% and the number of VLDL-apoB100 particles is < 10% of the number of LDL-apoB100 particles.

    “ApoB can be measured in the nonfasting state because even at peak postprandial concentrations, the number of chylomicron-apoB48 particles in healthy individuals is usually < 1% and the number of VLDL-apoB100 particles is < 10% of the number of LDL-apoB100 particles [12].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [12] Contois, 2009, Apolipoprotein B and cardiovascular disease risk: position statement from the AACC lipoproteins and vascular disease working group on best practices, Clin. Chem. source

      The MEASUREMENT ISSUES section (p. 9) says fasting is not required for apo B measurement, and the apo B-CONTAINING LIPOPROTEINS AND CVD RISK section (p. 2) says most plasma apo B is associated with LDL. Neither passage gives the claimed <1% chylomicron-apoB48 or <10% VLDL-apoB100 particle ratios at peak postprandial concentrations in healthy individuals. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    A major impediment to LDLP testing is its limited availability in the clinical laboratories, higher cost, and lack of standardization.

    “A major impediment to LDLP testing is its limited availability in the clinical laboratories, higher cost, and lack of standardization [63], although it does provide additional information on other lipoproteins VLDL and HDL, beyond LDLP.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [63] Clouet-Foraison, 2017, Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling, Clin. Chem. Lab. Med. source

  • Classified as probably not a substantial claim.

    Interpretationcitation

    ApoB may be preferred over non-HDLC, if available, in persons with mild-to-moderate hypertriglyceridemia (2-10 mmol/L), diabetes, obesity or metabolic syndrome, or very low LDLC < 1.8 mmol/L.

    “ApoB is recommended for risk assessment and may be preferred over non-HDLC, if available, in persons with mild-to-moderate hypertriglyceridemia (2-10 mmol/L), diabetes, obesity or metabolic syndrome, or very low LDLC < 1.8 mmol/L [4].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [4] Mach, 2019, 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. The Task force for the management of dyslipidaemias of the European society of cardiology (ESC) and European atherosclerosis society (EAS), Eur. Heart J. source

      The “Changes in recommendations” section recommends ApoB for risk assessment in people with high triglycerides, diabetes, obesity or metabolic syndrome, or very low LDL-C, and says it may be preferred over non-HDL-C in several of those groups. It does not give the claimed triglyceride range of 2–10 mmol/L or define very low LDL-C as <1.8 mmol/L; its preference-over-non-HDL-C statement also does not explicitly include metabolic syndrome. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    LC-MSMS enables the simultaneous (multiplexed) measurement of multiple apolipoproteins in addition to apoB100 in a single run of the assay, thus making it possible to achieve a complete apolipoprotein profile in the patient.

    “Another advantage of LC-MSMS is that it enables the simultaneous (multiplexed) measurement of multiple apolipoproteins in addition to apoB100 in a single run of the assay, thus making it possible to achieve a complete apolipoprotein profile in the patient, including HDL-and VLDL-associated apolipoproteins for comprehensive characterization of dyslipidemias [68].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [68] van den Broek, 2016, Automated multiplex LC-MS/MS assay for quantifying serum apolipoproteins A-I, B, C-I, C-II, C-III, and E with qualitative apolipoprotein E phenotyping, Clin. Chem. source

      The Discussion (page unavailable) says the assay expands the panel to six apolipoprotein quantities in one workflow, supporting multiplexed measurement alongside apoB-100. The paper does not establish that those six measurements constitute a complete patient apolipoprotein profile; it presents their clinical value for dyslipidemia as a potential benefit. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    ApoB cannot substitute for NMR or ion mobility-based particle size measurements and does not differentiate between LDL and VLDL particle numbers.

    “However, apoB cannot substitute for NMRor ion mobility-based particle size measurements and does not differentiate between LDL and VLDL particle numbers [61,62].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [61] Cole, 2013, Association of apolipoprotein B and nuclear magnetic resonance spectroscopy-derived LDL particle number with outcomes in 25 clinical studies: assessment by the AACC Lipoprotein and Vascular Diseases Division Working Group on Best Practices, Clin. Chem. source
    • cites [62] Mora, 2015, Circulation source

  • May combine two claims.

    Premisecitation

    Addition of PCSK9 inhibition to statin therapy allows more patients to achieve non-HDLC and apoB goals and lower risk of ASCVD, with no attenuation of benefit at lower concentrations.

    “Addition of PCSK9 inhibition to statin therapy allows more patients to achieve non-HDLC and apoB goals and lower risk of ASCVD, with no attenuation of benefit at lower concentrations [88].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [88] Ray, 2016, Reductions in atherogenic lipids and major cardiovascular events: a pooled analysis of 10 ODYSSEY trials comparing alirocumab with control, Circulation source

      The Results (Lipid Levels During Treatment; page unavailable) report that more alirocumab-treated patients achieved very low non–HDL-C and apoB levels, but do not establish that more patients met specified goals. The Discussion (page unavailable) finds lower non–HDL-C and apoB associated with lower MACE rates without discernible attenuation at lower levels. The Conclusions say outcomes trials were still assessing whether PCSK9 inhibition added to statins reduces MACE, so the claim overstates a demonstrated reduction in ASCVD risk. (LLM, conf=0.87)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Although apoB demonstrates competitive clinical performance compared with non-HDLC, there is no evidence yet of significant population health-economic benefit of intensifying pharmacological intervention aiming to further reduce apoB at very low concentrations of LDLC.

    “Although apoB demonstrates competitive clinical performance compared with non-HDLC, there is no evidence yet of significant population healtheconomic benefit of intensifying pharmacological intervention aiming to further reduce apoB at very low concentrations of LDLC [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Guideline-based non-HDLC thresholds have been arbitrarily defined by consensus of expert groups, based on the assumption that a normal VLDLC concentration exists when TG are < 1.7 mmol/L, which is < 0.8 mmol/L as estimated by the Friedewald formula.

    “Guideline-based non-HDLC thresholds have been arbitrarily defined by consensus of expert groups, based on the assumption that a normal VLDLC concentration exists when TG are < 1.7 mmol/L, which is < 0.8 mmol/L as estimated by the Friedewald formula [1,2].”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source
    • cites [2] Nordestgaard, 2016, Eur. Heart J. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Diabetes and abdominal obesity, disorders that underlie the clinical expression of complex dyslipidemias without elevated LDLC, are attaining epidemic proportions.

    “Diabetes and abdominal obesity, disorders that underlie the clinical expression of complex dyslipidemias without elevated LDLC, are attaining epidemic proportions [11].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [11] Miller, 2011, Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association, Circulation source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In patients with mixed hyperlipidemias, routine genetic testing is not warranted.

    “In patients with mixed hyperlipidemias, routine genetic testing is not warranted [33].”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [33] Hegele, 2014, European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management, Lancet Diabetes Endocrinol. source

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Novel technologies provide complementary diagnostic information regarding the complex molecular basis of dyslipidemias and can be used to explore and evaluate precision medicine approaches for identifying better and individualized treatment options for patients at high risk of ASCVD.

    “These novel technologies provide complementary diagnostic information regarding the complex molecular basis of dyslipidemias and, as such, can be used to explore and evaluate precision medicine approaches for identifying better and individualized treatment options for patients at high risk of ASCVD [99].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [99] Ruhaak, 2019, Apolipoprotein profiling as a personalized approach to the diagnosis and treatment of dyslipidaemia, Ann. Clin. Biochem. source

  • May combine two claims.

    Interpretationcitation

    This may compensate for the under- or overestimation of LDLC in terms of clinical decision making, given the uncertainty of dLDLC measurements or the Friedewald calculation in dyslipidemic samples when LDLC lowering approaches 1.4 mmol/L, and non-HDLC can be used at high TG ≥ 4.5 mmol/l.

    “This may compensate for the under-or overestimation of LDLC in terms of clinical decision making, given the uncertainty of dLDLC measurements or the Friedewald calculation in dyslipidemic samples when LDLC lowering approaches 1.4 mmol/L, and non-HDLC can be used at high TG ≥ 4.5 mmol/l.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    There are practical advantages of adding non-HDLC to every lipid profile report for follow-up without the need to fast.

    “To improve patient comfort and compliance, there are practical advantages of this approach for follow-up without the need to fast [2].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [2] Nordestgaard, 2016, Eur. Heart J. source

  • Classified as probably not a substantial claim.

    Premisecitation

    In a pediatric setting, reporting age- and gender-specific reference intervals is relevant for early identification of children with hyperlipidemia associated with premature atherosclerosis, especially FH.

    “In a pediatric setting, reporting age-and gender-specific reference intervals is relevant for early identification of children with hyperlipidemia associated with premature atherosclerosis, especially FH [32].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [32] Wiegman, 2015, European Atherosclerosis Society Consensus Panel. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment, Eur. Heart J. source

      The Screening section recommends using country-, age- and gender-specific LDL-C levels to screen children for FH when DNA testing is unavailable. The Conclusions link early FH identification to preventing atherosclerosis. The paper does not specifically recommend reporting laboratory reference intervals or extend that recommendation to pediatric hyperlipidemia generally. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    For nonfasting samples, the threshold for abnormal TG concentrations is ≥2 mmol/L according to the Women's Health Study, which found that this threshold was optimal for ASCVD prediction.

    “For nonfasting samples, laboratories should flag abnormal TG concentrations as ≥2 mmol/L according to the Women's Health Study, which found that this threshold was optimal for ASCVD prediction [91].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [91] White, 2015, Identifying an optimal cutpoint for the diagnosis of hypertriglyceridemia in the nonfasting state, Clin. Chem. source

      The Results and Discussion identify 175 mg/dL (1.98 mmol/L, approximately 2 mmol/L) as the optimal nonfasting triglyceride cutpoint for predicting incident CVD in the Women’s Health Study. The paper proposes a diagnostic cutpoint, but does not specifically direct laboratories to flag results at that level; its measured outcome is a composite of CVD events rather than an outcome expressly defined as ASCVD. (LLM, conf=0.82)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Interpretationcitation

    This necessarily results in on-treatment LDL and VLDL particle numbers that are higher than would be anticipated from the concurrent LDLC follow-up measurement and may explain part of residual risk among statin-treated patients.

    “This necessarily results in on-treatment LDL and VLDL particle numbers that are higher than would be anticipated from the concurrent LDLC follow-up measurement and may explain part of residual risk among statin-treated patients [62,90].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [62] Mora, 2015, Circulation source

      The Results report that rosuvastatin lowered LDL particle numbers less than LDL-c (27.8% versus 48.5%), and the Discussion links on-treatment atherogenic particles, including VLDL subfractions, to residual risk. The paper does not establish that LDL and VLDL particle numbers are necessarily higher than a concurrent LDL-c measurement would predict for every statin-treated patient. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
    • cites [90] Lawler, 2017, Atherogenic lipoprotein determinants of cardiovascular disease and residual risk among individuals with low low-density lipoprotein cholesterol, J. Am. Heart Assoc. source

      The Results sections ‘Lipoprotein Subclass Response to Statin Therapy’ and ‘Residual Risk of CVD’ (page unavailable) report that LDL-c fell more than some LDL particle subclasses, VLDL particle responses were variable, and small VLDL particle levels were associated with residual risk. They do not establish that both LDL and VLDL particle numbers are necessarily higher than a concurrent LDL-c measurement would predict for every statin-treated patient. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Guidelines propose using non-HDLC or apoB as a secondary treatment target in the management of patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L), including patients with diabetes.

    “Guidelines propose using non-HDLC or apoB as a secondary treatment target in the management of patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L), including patients with diabetes [4,5].”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [4] Mach, 2019, 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. The Task force for the management of dyslipidaemias of the European society of cardiology (ESC) and European atherosclerosis society (EAS), Eur. Heart J. source

      Section 9.4.2.2 calls non-HDL-C or ApoB a secondary objective of therapy and discusses atherogenic dyslipidaemia in people with type 2 diabetes. The secondary-goals passage likewise recommends risk-based non-HDL-C and ApoB targets. Neither passage ties those targets specifically to the claimed triglyceride range of 2–10 mmol/L, so that qualifier is not supported by our copy. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [5] Anderson, 2016, Canadian cardiovascular society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult, Can. J. Cardiol. source

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationcitation

    The combination of non-HDLC with Martin-Hopkins cLDLC may be considered as an appropriate strategy to guide therapy and they can be calculated from the standard lipid profile.

    “For the present purposes, the combination of non-HDLC with Martin-Hopkins cLDLC may be considered as an appropriate strategy to guide therapy and they can be calculated from the standard lipid profile [1].”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [1] Langlois, 2018, Clin. Chem. source

      The LDLC VS NON-HDLC section (p. 18) says combining non-HDLC with calculated LDL-C is an appropriate strategy to guide therapy, and ON-TREATMENT DISCORDANCES (p. 21) says these measures can be calculated from a standard lipid profile. The paper does not specifically recommend Martin-Hopkins calculated LDL-C for that combination; the VLDLC section (p. 9) says the clinical value of alternative LDL-C calculations remains to be determined. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Apolipoprotein B concentrations < 0.1 g/L (10 mg/dL) indicate genetic abetalipoproteinemia.

    “< 0.1 g/L (10 mg/dL): genetic abetalipoproteinemia”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] Nordestgaard, 2016, Eur. Heart J. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Apolipoprotein A-I concentrations < 0.1 g/L (10 mg/dL) indicate genetic hypoalphalipoproteinemia.

    “< 0.1 g/L (10 mg/dL): genetic hypoalphalipoproteinemia”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [2] Nordestgaard, 2016, Eur. Heart J. source

  • May combine two claims. The quote only partly states this claim.

    Findingcitation

    For conversion of Lp(a) concentrations in mg/dL to nmol/L, 13930 individuals from the Copenhagen General Population Study had measurements in both mg/dL and nmol/L by Denka Seiken assays; the correlation was done by linear regression with an R2 value of 0.996, and the conversion equation is Lp(a), nmol/L = 2.18*Lp(a), mg/dL-3.83.

    “for conversion of Lp(a) concentrations in mg/dL to nmol/L, 13930 individuals from the Copenhagen General Population Study had measurements in both mg/dL and nmol/L by Denka Seiken assays distributed by Roche Diagnostics (Rotkreuz, Switzerland).The correlation was done by linear regression with an R 2 value of 0.996, and the conversion was done by the following equation: Lp(a), nmol/L = 2.18*Lp(a),”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [3] Langsted, 2019, High lipoprotein(a) and high risk of mortality, Eur. Heart J. source

  • May combine two claims.

    Premisecitation

    LDLs are effectively lowered by statins, whereas Lp(a) is typically resistant to this treatment.

    “One of the major differences between Lp(a) and LDL particles is that LDLs are effectively lowered by statins, whereas Lp(a) is typically resistant to this treatment [24].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [24] Willeit, 2018, Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials, Lancet source

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing). May combine two claims.

    Premisecitation

    Direct homogeneous assays have been developed to specifically measure cholesterol in remnant particles (RemnantC) and some have revealed significant associations of RemnantC with ASCVD.

    “Direct”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Varbo, 2017, Remnant lipoproteins, Curr. Opin. Lipidol. source
    • cites [20] Varbo, 2018, Remnant cholesterol and myocardial infarction in normal weight, overweight, and obese individuals from the copenhagen general population study, Clin. Chem. source

  • May combine two claims.

    Premisecitation

    Lp(a) concentrations do not change in response to normal food intake and are minimally increased in inflammation.

    “Lp(a) concentrations do not change in response to normal food intake and are minimally increased in inflammation, although the influence of acute illness or acute phase reactions on Lp(a) concentration is discussed controversially [34].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Langsted, 2014, Lipoprotein(a): fasting and nonfasting levels, inflammation, and cardiovascular risk, Atherosclerosis source

  • May combine two claims.

    Premisecitation

    The Friedewald equation uses a fixed TG:cholesterol ratio (TG/2.2 in mmol/L or TG/5 in mg/dL) to estimate VLDLC and assumes lack of chylomicrons which are more TG-rich than VLDL.

    “The equation uses a fixed TG:cholesterol ratio (TG/2.2 in mmol/L or TG/5 in mg/dL) to estimate VLDLC and assumes lack of chylomicrons which are more TGrich than VLDL [44].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Nauck, 2002, Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation, Clin. Chem. source

  • May combine two claims.

    Premisecitation

    The cLDLC equations and also most dLDLC assays include the cholesterol content of Lp(a).

    “The cLDLC equations and also most dLDLC assays include the cholesterol content of Lp(a) [52].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Yeang, 2015, ‘LDLC’ = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering, Curr. Opin. Lipidol. source

  • May combine two claims.

    Premisecitation

    An Lp(a) particle is composed of about 30-45% of cholesterol by weight, and a significant overestimation of LDLC concentration occurs in subjects with high and very high Lp(a) concentrations.

    “Considering that an Lp(a) particle is composed of about 30-45% of cholesterol by weight, a significant overestimation of LDLC concentration occurs in subjects with high and very high Lp(a) concentrations [52]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Yeang, 2015, ‘LDLC’ = LDL-C + Lp(a)-C: implications of achieved ultra-low LDL-C levels in the proprotein convertase subtilisin/kexin type 9 era of potent LDL-C lowering, Curr. Opin. Lipidol. source

  • May combine two claims.

    Interpretationcitation

    The biases noted in dLDLC and dHDLC assays when analyzing dyslipidemic samples suggest that non-specific cross-reaction takes place, reflecting difficulties in selectively measuring the cholesterol in LDL or HDL fractions when atypical lipoproteins are present.

    “The biases noted in dLDLC and dHDLC assays when analyzing dyslipidemic samples suggest that non-specific cross-reaction takes place, reflecting difficulties in selectively measuring the cholesterol in LDL or HDL fractions when atypical lipoproteins are present.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [40] Ramasamy, 2018, Update on the laboratory investigation of dyslipidemias, Clin. Chim. Acta source
    • cites [41] Contois, 2011, Reliability of low-density lipoprotein cholesterol, non-high density lipoprotein cholesterol, and apolipoprotein B measurement, J. Clin. Lipidol. source

  • May combine two claims.

    Premisecitation

    Non-HDLC can be obtained in the nonfasting state and does not require TG to be less than 4.5 mmol/L, which is the limitation for calculation of cLDLC.

    “Non-HDLC can be obtained in the nonfasting state and does not require TG to be less than 4.5 mmol/L, which is the limitation for calculation of cLDLC [44].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [44] Nauck, 2002, Methods for measurement of LDL-cholesterol: a critical assessment of direct measurement by homogeneous assays versus calculation, Clin. Chem. source

  • May combine two claims.

    Interpretationcitation

    Some individuals with high RemnantC have low LDLC and thus will have relatively low non-HDLC if Lp(a) is also low, and if interpreting non-HDLC instead of RemnantC, the high RemnantC will be masked in these individuals.

    “Some individuals with high RemnantC have low LDLC and thus will have relatively low non-HDLC if Lp(a) is also low, and if interpreting non-HDLC instead of RemnantC, the high RemnantC will be masked in these individuals [30].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Langlois, 2018, Which lipids should be analyzed for diagnostic workup and follow-up of patients with hyperlipidemias?, Curr. Cardiol. Rep. source

  • May combine two claims.

    Premisecitation

    Discordance of Martin-Hopkins cLDLC and, as a consequence, risk underestimation is still common (80-90%) in patients with TG ≥ 4.5 mmol/L.

    “When compared to Martin-Hopkins cLDLC, non-HDLC translates to only modest improvement for risk classification that could change clinical management (in ~2% of individuals in a general population), although discordance of Martin-Hopkins cLDLC and, as a consequence, risk underestimation is still common (80-90%) in patients with TG ≥ 4.5 mmol/L [60].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [60] Sathiyakumar, 2018, Impact of novel low-density lipoprotein-cholesterol assessment on the utility of secondary non-high-density lipoprotein-cholesterol and apolipoprotein B targets in selected worldwide dyslipidemia guidelines, Circulation source

  • Classified as probably not a substantial claim.

    Interpretationnone given

    At this point of time, there is insufficient evidence of benefit from outcome studies to support the option to replace the standard lipid profile by single follow-up measurement of apoB to guide lipid-lowering therapies.

    “At this point of time, there is insufficient evidence of benefit from outcome studies to support the option to replace the standard lipid profile (with calculation of cLDLC and non-HDLC) by single followup measurement of apoB to guide lipid-lowering therapies.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationreasoning

    The suggested use of apoB would be cost-effective if these tests guide therapy to reduce the healthcare costs of ASCVD to a greater extent than standard therapy guided by LDLC.

    “The suggested use of apoB would be cost-effective if these tests guide therapy to reduce the healthcare costs of ASCVD to a greater extent than standard therapy guided by LDLC, yet the evidence base of this approach is still incomplete (Table 7).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Like non-HDLC, apoB can always be measured in the nonfasting state and is not affected by biological TG variability.

    “Like non-HDLC, apoB can always be measured in the nonfasting state and is not affected by biological TG variability.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Lowering non-HDLC thresholds leads to upward reclassification of patients (if the goal is to reduce undertreatment), higher thresholds lead to downward reclassification (if the goal is to reduce overtreatment).

    “Lowering non-HDLC thresholds leads to upward reclassification of patients (if the goal is to reduce undertreatment), higher thresholds lead to downward reclassification (if the goal is to reduce overtreatment).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    If ≤ 2 of 20 values (≤10%) fall outside the reference interval then the interval can be adopted.

    “If ≤ 2 of 20 values (≤10%) fall outside the reference interval then the interval can be adopted [96,97].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [96] Ceriotti, 2009, Reference intervals: the way forward, Ann. Clin. Biochem. source
    • cites [97] Henny, 2016, Working Group Accreditation and ISO/CEN standards (WG-A/ISO) of the EFLM. Recommendation for the review of biological reference intervals in medical laboratories, Clin. Chem. Lab. Med. source

  • May combine two claims.

    Premisecitation

    Calculation of non-HDLC is at least equally good at predicting ASCVD compared with measurement or calculation of LDLC in the overall population and statin-treated patients; it may also be superior to LDLC if discordantly high, especially at normal or low LDLC concentrations and in individuals with hypertriglyceridemia because it includes RemnantC.

    “Data from concordance/discordance analyses suggest that calculation of non-HDLC is at least equally good at predicting ASCVD compared with measurement or calculation of LDLC in the overall population and statin-treated patients; it may also be superior to LDLC if discordantly high, especially at normal or low LDLC concentrations and in individuals with hypertriglyceridemia because it includes Rem”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [81][82][83]

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    At TG concentration ≥4.5 mmol/L, use of Friedewald cLDLC or Martin-Hopkins cLDLC is not recommended and dLDLC is likely to be inaccurate.

    “At TG concentration ≥4.5 mmol/L, a condition wherein use of Friedewald cLDLC or Martin-Hopkins cLDLC is not recommended and also dLDLC is likely to be inaccurate, use of non-HDLC calculation may be considered instead of dLDLC measurement to evaluate therapeutic response.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    This situation is challenging for new generation assays to meet regulations for in vitro diagnostic medical devices, requiring evidence of clinical performance of the assays.

    “This situation is challenging for new generation assays to meet regulations for in vitro diagnostic medical devices, requiring evidence of clinical performance of the assays [70].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Horvath, 2014, From biomarkers to medical tests: the changing landscape of test evaluation, Clin. Chim. Acta source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    For decision thresholds it is unnecessary to validate them in the laboratory.

    “For decision thresholds it is unnecessary to validate them in the laboratory [97].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [97] Henny, 2016, Working Group Accreditation and ISO/CEN standards (WG-A/ISO) of the EFLM. Recommendation for the review of biological reference intervals in medical laboratories, Clin. Chem. Lab. Med. source
54 of 54

  • The paper relies on this without support.

    ApoB assays currently provide the most accurate measurement of overall burden of atherogenic particles in the fasting and nonfasting state.

    “ApoB assays currently provide the most accurate measurement of overall burden of atherogenic particles in the fasting and nonfasting state.”

  • The authors state this as an assumption.

    The optimal VLDLC concentration associated with the fasting TG threshold 1.7 mmol/L is 0.8 mmol/L.

    “this value is based on the assumption that the”

  • The paper relies on this without support.

    dHDLC measurement errors in hypertriglyceridemic samples affect the calculation of non-HDLC.

    “However, dHDLC measurement errors in hypertriglyceridemic samples still affect the calculation of non-HDLC and most assays limit the measurement of dHDLC to TG < 10 mmol/L.”

  • The paper relies on this without support.

    Most dHDLC assays limit the measurement of dHDLC to TG < 10 mmol/L.

    “However, dHDLC measurement errors in hypertriglyceridemic samples still affect the calculation of non-HDLC and most assays limit the measurement of dHDLC to TG < 10 mmol/L.”

  • The paper relies on this without support.

    ApoB is a clearly defined measurand in contrast to the heterogeneous LDLC fraction.

    “In contrast to the heterogeneous LDLC fraction, apoB is a clearly defined measurand.”

  • The paper relies on this without support.

    ApoB quantification by automated immunoassays such as immunonephelometry and immunoturbidimetry can be easily implemented in clinical laboratories.

    “ApoB quantification by automated immunoassays such as immunonephelometry and immunoturbidimetry can be easily implemented in the clinical laboratories.”

  • The paper relies on this without support.

    Most nephelometric and turbidimetric apoB measurements are limited to TG < 10 mmol/L due to interference of light scattering or absorption caused by chylomicrons and large VLDLs.

    “Far higher than the maximum allowed TG concentration of 4.5 mmol/L for cLDLC, most nephelometric and turbidimetric apoB measurements are limited to TG < 10 mmol/L due to interference of light scattering or absorption caused by chylomicrons and large VLDLs;”

  • The paper relies on this without support.

    Implementation of apoB assays in follow-up of lipid-lowering therapies would impose healthcare systems and patients with yearly extra cost.

    “Implementation of apoB assays in follow-up of lipid-lowering therapies would impose healthcare systems and patients with yearly extra cost, although one might consider replacing the standard lipid profile (needed for calculation of LDLC and non-HDLC) by single follow-up measurement of apoB in order to attenuate the rise of expenses.”

  • The paper relies on this without support.

    Guideline-recommended LDLC thresholds are based on observations with Friedewald cLDLC using older HDLC precipitation methods which differ from dHDLC assays used nowadays.

    “Guideline-recommended LDLC thresholds are based on observations with Friedewald cLDLC using the older HDLC precipitation methods which differ from dHDLC assays used nowadays.”

  • The paper relies on this without support.

    Increased baseline glycerol concentrations can be found in patients with diabetes and chronic kidney disease and during intravenous lipid infusion, and TG may be wrongly flagged in these patients unless a glycerol-corrected TG assay is used.

    “Increased baseline glycerol concentrations can be found in patients with diabetes and chronic kidney disease and during intravenous lipid infusion, and TG may be wrongly flagged in these patients unless glycerol-corrected TG assay is used.”

  • The paper relies on this without support.

    There is no consensus on which threshold value in mmol/L to be used for Lp(a).

    “There is no consensus on which threshold value in mmol/L to be used for Lp(a); however, for conversion of Lp(a) concentrations in mg/dL to nmol/L, 13930 individuals from the Copenhagen General Population Study had measurements in both mg/dL and nmol/L by Denka Seiken assays distributed by Roche Diagnostics (Rotkreuz, Switzerland).”
11 of 11

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • HDL cholesterol conversion is wrong for men aged 20-39

    Minor

    The median HDL cholesterol value of 1.2 mmol/L corresponds to about 46 mg/dL, not 85 mg/dL. The reported 85 mg/dL also exceeds the 75th-percentile value of 56 mg/dL in the same row.

    Reported 85 · recomputed 46.32

1 of 1

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Nordestgaard, B. G., Langlois, M. R., Langsted, A., Chapman, M. J., Aakre, K. M., Baum, H., Borén, J., Bruckert, E., Catapano, A., Cobbaert, C., Collinson, P., Descamps, O. S., Duff, C. J., von Eckardstein, A., Hammerer-Lercher, A., Kamstrup, P. R., Kolovou, G., Kronenberg, F., Mora, S., Pulkki, K., Remaley, A. T., Rifai, N., Ros, E., Stankovic, S., Stavljenic-Rukavina, A., Sypniewska, G., Watts, G. F., Wiklund, O., & Laitinen, P.
Affiliations
  • University of Copenhagen (DK)
  • Ghent University (BE)
  • Inserm (FR)
  • Haukeland University Hospital (NO)
  • Klinikum Ludwigsburg (DE)
  • Sahlgrenska University Hospital (SE)
  • University of Milan (IT)
  • Leiden University Medical Center (NL)
  • St George's, University of London (GB)
  • Cliniques Universitaires Saint-Luc (BE)
  • University Hospitals of North Midlands NHS Trust (GB)
  • Onassis Cardiac Surgery Center (GR)
  • Innsbruck Medical University (AT)
  • Brigham and Women's Hospital (US)
  • University of Turku (FI)
  • National Institutes of Health (US)
  • Boston Children's Hospital (US)
  • Instituto de Salud Carlos III (ES)
  • Univerzitetski Klinički Centar Srbije (RS)
Corresponding author
  • Nordestgaard, Børge G.
  • Langlois, Michel R.
ORCID
Venue
Atherosclerosis
Publisher
Elsevier BV
Published
2020-02
Volume
294
Pages
46-61
ISSN
0021-9150 (ISSN-L)
DOI
10.1016/j.atherosclerosis.2019.12.005
OpenAlex
W2996456596
Semantic Scholar
440b3e0b67ecf979049e435e66f4f3e2ecb15ca5
Cited by
240
References
107
Citations by year
2026: 11 · 2025: 17 · 2024: 31 · 2023: 58 · 2022: 30 · 2021: 45 · 2020: 43
FWCI
35.50
Type
journal article
Language
en
Open access
Licence
Locations
  • Atherosclerosis (publishedVersion)
  • PubMed (publishedVersion)
  • Ghent University Academic Bibliography (Ghent University) (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
  • UWA Profiles and Research Repository (University of Western Australia) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
  • HAL (Le Centre pour la Communication Scientifique Directe) (submittedVersion)
  • DIAL (Catholic University of Leuven) (submittedVersion, other-oa)
  • Työväentutkimus Vuosikirja (submittedVersion, other-oa)
  • St George's Online Research Archive (St George's University of London) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich)
Funders
Merck
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
atherogenic lipoproteins, lipid-lowering therapy, LDL cholesterol, non-HDL cholesterol, HDL cholesterol, triglycerides, lipoprotein(a), apolipoprotein B
MeSH terms
Hypolipidemic Agents, Humans, Hyperlipidemias, Lipoproteins, Atherosclerosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review