scholarly journals Analytical Performance Specifications for Lipoprotein(a), Apolipoprotein B-100, and Apolipoprotein A-I Using the Biological Variation Model in the EuBIVAS Population

2020 ◽  
Vol 66 (5) ◽  
pp. 727-736 ◽  
Author(s):  
Noemie Clouet-Foraison ◽  
Santica M Marcovina ◽  
Elena Guerra ◽  
Aasne K Aarsand ◽  
Abdurrahman Coşkun ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Clinical Chemistry ◽  
Biological Variation ◽  
Analytical Performance ◽  
European Federation ◽  
Published Data ◽  
Cvd Risk ◽  
Lipoprotein A ◽  
Apolipoprotein A ◽  
Performance Specifications

Abstract Background With increased interest in lipoprotein(a) (Lp[a]) concentration as a target for risk reduction and growing clinical evidence of its impact on cardiovascular disease (CVD) risk, rigorous analytical performance specifications (APS) and accuracy targets for Lp(a) are required. We investigated the biological variation (BV) of Lp(a), and 2 other major biomarkers of CVD, apolipoprotein A-I (apoA-I) and apolipoprotein B-100 (apoB), in the European Biological Variation Study population. Method Serum samples were drawn from 91 healthy individuals for 10 consecutive weeks at 6 European laboratories and analyzed in duplicate on a Roche Cobas 8000 c702. Outlier, homogeneity, and trend analysis were performed, followed by CV-ANOVA to determine BV estimates and their 95% CIs. These estimates were used to calculate APS and reference change values. For Lp(a), BV estimates were determined on normalized concentration quintiles. Results Within-subject BV estimates were significantly different between sexes for Lp(a) and between women aged <50 and >50 years for apoA-I and apoB. Lp(a) APS was constant across concentration quintiles and, overall, lower than APS based on currently published data, whereas results were similar for apoA-I and apoB. Conclusion Using a fully Biological Variation Data Critical Appraisal Checklist (BIVAC)–compliant protocol, our study data confirm BV estimates of Lp(a) listed in the European Federation of Clinical Chemistry and Laboratory Medicine database and reinforce concerns expressed in recent articles regarding the suitability of older APS recommendations for Lp(a) measurements. Given the heterogeneity of Lp(a), more BIVAC-compliant studies on large numbers of individuals of different ethnic groups would be desirable.

scholarly journals The EuBIVAS Project: Within- and Between-Subject Biological Variation Data for Serum Creatinine Using Enzymatic and Alkaline Picrate Methods and Implications for Monitoring

2017 ◽  
Vol 63 (9) ◽  
pp. 1527-1536 ◽  
Author(s):  
Anna Carobene ◽  
Irene Marino ◽  
Abdurrahman Coşkun ◽  
Mustafa Serteser ◽  
Ibrahim Unsal ◽  
...  
Keyword(s):  
Serum Creatinine ◽  
Clinical Chemistry ◽  
Biological Variation ◽  
European Federation ◽  
Healthy Individuals ◽  
Homogeneity Analysis ◽  
Variation Data ◽  
Performance Specifications ◽  
Age Range ◽  
Analytical Variation

Abstract BACKGROUND The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) European Biological Variation Study (EuBIVAS) has been established to deliver rigorously determined biological variation (BV) indices. EuBIVAS determined BV for serum creatinine using the enzymatic and alkaline picrate measurement methods. METHOD In total, 91 healthy individuals (38 males, 53 females; age range, 21–69 years) were bled for 10 consecutive weeks at 6 European laboratories. An equivalent protocol was followed at each center. Sera were stored at −80 °C before analysis. Analyses for each patient were performed in duplicate within a single run on an ADVIA 2400 system (San Raffaele Hospital, Milan). The data were subjected to outlier and homogeneity analysis before performing CV-ANOVA to determine BV and analytical variation (CVA) estimates with confidence intervals (CI). RESULTS The within-subject BV estimates [CVI (95% CI)] were similar for enzymatic [4.4% (4.2–4.7)] and alkaline picrate [4.7% (4.4–4.9)] methods and lower than the estimate presently available online (CVI = 5.9%). No significant male/female BV differences were found. Significant differences were observed in mean creatinine values between men and women and between Turkish individuals and those of other nationalities. Between-subject BV (CVG) estimates, stratified accordingly, produced CVG values similar to historical BV data. CVA was 1.1% for the enzymatic and 4.4% for alkaline picrate methods, indicating that alkaline picrate methods fail to fulfill analytical performance specifications for imprecision (CVAPS). CONCLUSIONS The serum creatinine CVI obtained by EuBIVAS specifies a more stringent CVAPS than previously identified. The alkaline picrate method failed to meet this CVAPS, raising questions regarding its future use.

Setting analytical performance specifications based on outcome studies – is it possible?

2015 ◽  
Vol 53 (6) ◽  
Author(s):  
Andrea Rita Horvath ◽  
Patrick M.M. Bossuyt ◽  
Sverre Sandberg ◽  
Andrew St John ◽  
Phillip J. Monaghan ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Clinical Chemistry ◽  
Health Benefit ◽  
Outcome Data ◽  
Outcome Studies ◽  
Analytical Performance ◽  
Performance Criteria ◽  
European Federation ◽  
Performance Specifications ◽  
The Impact

AbstractThe 1st Strategic Conference of the European Federation of Clinical Chemistry and Laboratory Medicine proposed a simplified hierarchy for setting analytical performance specifications (APS). The top two levels of the 1999 Stockholm hierarchy, i.e., evaluation of the effect of analytical performance on clinical outcomes and clinical decisions have been proposed to be replaced by one outcome-based model. This model can be supported by: (1a) direct outcome studies; and (1b) indirect outcome studies investigating the impact of analytical performance of the test on clinical classifications or decisions and thereby on the probability of patient relevant clinical outcomes.This paper reviews the need for outcome-based specifications, the most relevant types of outcomes to be considered, and the challenges and limitations faced when setting outcome-based APS. The methods of Model 1a and b are discussed and examples are provided for how outcome data can be translated to APS using the linked evidence and simulation or decision analytic techniques.Outcome-based APS should primarily reflect the clinical needs of patients; should be tailored to the purpose, role and significance of the test in a well defined clinical pathway; and should be defined at a level that achieves net health benefit for patients at reasonable costs. Whilst it is acknowledged that direct evaluations are difficult and may not be possible for all measurands, all other forms of setting APS should be weighed against that standard, and regarded as approximations. Better definition of the relationship between the analytical performance of tests and health outcomes can be used to set analytical performance criteria that aim to improve the clinical and cost-effectiveness of laboratory tests.

scholarly journals Fasting Is Not Routinely Required for Determination of a Lipid Profile: Clinical and Laboratory Implications Including Flagging at Desirable Concentration Cutpoints—A Joint Consensus Statement from the European Atherosclerosis Society and European Federation of Clinical Chemistry and Laboratory Medicine

2016 ◽  
Vol 62 (7) ◽  
pp. 930-946 ◽  
Author(s):  
Børge G Nordestgaard ◽  
Anne Langsted ◽  
Samia Mora ◽  
Genovefa Kolovou ◽  
Hannsjörg Baum ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Familial Hypercholesterolemia ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Clinical Chemistry ◽  
Hdl Cholesterol ◽  
Lipid Profiles ◽  
Apolipoprotein A1 ◽  
Lipoprotein A ◽  
Remnant Cholesterol

Abstract AIMS To critically evaluate the clinical implications of the use of non-fasting rather than fasting lipid profiles and to provide guidance for the laboratory reporting of abnormal non-fasting or fasting lipid profiles. METHODS AND RESULTS Extensive observational data, in which random non-fasting lipid profiles have been compared with those determined under fasting conditions, indicate that the maximal mean changes at 1–6 h after habitual meals are not clinically significant [+0.3 mmol/L (26 mg/dL) for triglycerides; −0.2 mmol/L (8 mg/dL) for total cholesterol; −0.2 mmol/L (8 mg/dL) for LDL cholesterol; +0.2 mmol/L (8 mg/dL) for calculated remnant cholesterol; −0.2 mmol/L (8 mg/dL) for calculated non-HDL cholesterol]; concentrations of HDL cholesterol, apolipoprotein A1, apolipoprotein B, and lipoprotein(a) are not affected by fasting/non-fasting status. In addition, non-fasting and fasting concentrations vary similarly over time and are comparable in the prediction of cardiovascular disease. To improve patient compliance with lipid testing, we therefore recommend the routine use of non-fasting lipid profiles, whereas fasting sampling may be considered when non-fasting triglycerides are >5 mmol/L (440 mg/dL). For non-fasting samples, laboratory reports should flag abnormal concentrations as triglycerides ≥2 mmol/L (175 mg/dL), total cholesterol ≥5 mmol/L (190 mg/dL), LDL cholesterol ≥3 mmol/L (115 mg/dL), calculated remnant cholesterol ≥0.9 mmol/L (35 mg/dL), calculated non-HDL cholesterol ≥3.9 mmol/L (150 mg/dL), HDL cholesterol ≤1 mmol/L (40 mg/dL), apolipoprotein A1 ≤1.25 g/L (125 mg/dL), apolipoprotein B ≥1.0 g/L (100 mg/dL), and lipoprotein(a) ≥50 mg/dL (80th percentile); for fasting samples, abnormal concentrations correspond to triglycerides ≥1.7 mmol/L (150 mg/dL). Life-threatening concentrations require separate referral for the risk of pancreatitis when triglycerides are >10 mmol/L (880 mg/dL), for homozygous familial hypercholesterolemia when LDL cholesterol is >13 mmol/L (500 mg/dL), for heterozygous familial hypercholesterolemia when LDL cholesterol is >5 mmol/L (190 mg/dL), and for very high cardiovascular risk when lipoprotein(a) >150 mg/dL (99th percentile). CONCLUSIONS We recommend that non-fasting blood samples be routinely used for the assessment of plasma lipid profiles. Laboratory reports should flag abnormal values on the basis of desirable concentration cutpoints. Non-fasting and fasting measurements should be complementary but not mutually exclusive.

scholarly journals An overview of EFLM harmonization activities in Europe

2018 ◽  
Vol 56 (10) ◽  
pp. 1591-1597 ◽  
Author(s):  
Eric S. Kilpatrick ◽  
Sverre Sandberg
Keyword(s):  
Best Practice ◽  
Clinical Chemistry ◽  
Laboratory Medicine ◽  
Biological Variation ◽  
European Federation ◽  
Eu Countries ◽  
European Guidelines ◽  
Common Basis ◽  
Evaluation Procedures ◽  
E Learning

Abstract The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has initiated many harmonization activities in all phases of the examination process. The EFLM is dealing with both the scientific and the educational aspects of harmonization, with the intention of disseminating best practice in laboratory medicine throughout Europe. Priorities have been given (1) to establish a standard for conducting and assessing biological variation studies and to construct an evidence based EFLM webpage on biological variation data, (2) to harmonize preanalytical procedures by producing European guidelines, (3) to improve test ordering and interpretation, (4) to produce other common European guidelines for laboratory medicine and play an active part in development of clinical guidelines, (5) to establish a common basis for communicating laboratory results to patients, (6) to harmonize units of measurement throughout Europe, (7) to harmonize preanalytical procedures in molecular diagnostics and (8) to harmonize and optimize test evaluation procedures. The EFLM is also now launching the 5th version of the European Syllabus to help the education of European Specialists in Laboratory Medicine (EuSpLM), which is being supported by the development of e-learning courses. A register of EuSpLM is already established for members of National Societies in EU countries, and a similar register will be established for specialists in non-EU countries.

scholarly journals Potent lipoprotein(a) lowering following apolipoprotein(a) antisense treatment reduces the pro-inflammatory activation of circulating monocytes in patients with elevated lipoprotein(a)

2020 ◽  
Vol 41 (24) ◽  
pp. 2262-2271 ◽  
Author(s):  
Lotte C A Stiekema ◽  
Koen H M Prange ◽  
Renate M Hoogeveen ◽  
Simone L Verweij ◽  
Jeffrey Kroon ◽  
...  
Keyword(s):  
Gene Expression ◽  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cvd Risk ◽  
Inflammatory Gene Expression ◽  
Lipoprotein A ◽  
Inflammatory Gene ◽  
Apolipoprotein A ◽  
Inflammatory Activation

Abstract Aims Elevated lipoprotein(a) [Lp(a)] is strongly associated with an increased cardiovascular disease (CVD) risk. We previously reported that pro-inflammatory activation of circulating monocytes is a potential mechanism by which Lp(a) mediates CVD. Since potent Lp(a)-lowering therapies are emerging, it is of interest whether patients with elevated Lp(a) experience beneficial anti-inflammatory effects following large reductions in Lp(a). Methods and results Using transcriptome analysis, we show that circulating monocytes of healthy individuals with elevated Lp(a), as well as CVD patients with increased Lp(a) levels, both have a pro-inflammatory gene expression profile. The effect of Lp(a)-lowering on gene expression and function of monocytes was addressed in two local sub-studies, including 14 CVD patients with elevated Lp(a) who received apolipoprotein(a) [apo(a)] antisense (AKCEA-APO(a)-LRx) (NCT03070782), as well as 18 patients with elevated Lp(a) who received proprotein convertase subtilisin/kexin type 9 antibody (PCSK9ab) treatment (NCT02729025). AKCEA-APO(a)-LRx lowered Lp(a) by 47% and reduced the pro-inflammatory gene expression in monocytes of CVD patients with elevated Lp(a), which coincided with a functional reduction in transendothelial migration capacity of monocytes ex vivo (−17%, P < 0.001). In contrast, PCSK9ab treatment lowered Lp(a) by 16% and did not alter transcriptome nor functional properties of monocytes, despite an additional reduction of 65% in low-density lipoprotein cholesterol (LDL-C). Conclusion Potent Lp(a)-lowering following AKCEA-APO(a)-LRx, but not modest Lp(a)-lowering combined with LDL-C reduction following PCSK9ab treatment, reduced the pro-inflammatory state of circulating monocytes in patients with elevated Lp(a). These ex vivo data support a beneficial effect of large Lp(a) reductions in patients with elevated Lp(a).

scholarly journals Evaluation of the clinical chemistry tests analytical performance by using different models and specifications

2019 ◽  
Vol 45 (1) ◽  
pp. 11-18
Author(s):  
Murat Keleş
Keyword(s):  
Quality Management ◽  
Measurement Uncertainty ◽  
Goal Setting ◽  
Clinical Chemistry ◽  
Biological Variation ◽  
Analytical Performance ◽  
Analytical Quality ◽  
Analytical Error ◽  
Circular Letter ◽  
Clinical Chemistry Tests

Abstract Background The importance of managing analytical quality in clinical laboratories is known. Goal-setting models are critical for analytical quality management, along with correctly implemented error models. However, the methods used to determine analytical performance and more importantly, the relevant analytical quality goals are open to discussion. Our aim was to compare the analytical performance characteristics of routine clinical chemistry tests with different goal-setting models which was proposed by various establishments. In addition, to provide a perspective to Turkish total analytical error (TAE) circular letter that compulsory to calculate from 2016. Materials and methods This study was performed by the data obtained from the internal and external quality control of clinical chemistry tests which were measured by Roche Cobas c501 biochemistry analyzer. TAE calculated with TAE% = 1.65 ×(CV%) + Bias% formula. Nordtest uncertainty model was used in the calculation of measurement uncertainty (MU). In this context, total analytical error was evaluated with biological variation (BV), RCPA, CLIA and Turkish allowable total error (ATE) goals. Measurement uncertainty was evaluated with only permissible measurement uncertainty (pU%) goal. Results In our study, RCPA goals are the most stringent, followed by the BVEuBIVAS, BVRicos, pU%, CLIA and finally the ATETurkey goals coming in last. In cumulatively, BVEuBIVAS goals were 18.3% lower than BVRicos for evaluated parameters. Conclusion The balance between applicability and analytical assurance of goals should be well ensured when determining goal-setting models. Circular letter (2016/18) creates awareness to the analytical quality management but still open to development. Biological variation dependent total allowable error model never designed to be used as benchmarks for measurement uncertainty and it is not methodologically appropriate for assessing measurement uncertainty which was estimated by the Nordtest method. Also considered that, the use of “permissible MU” is more methodologically appropriate in the evaluation of measurement uncertainty.

Mo-P4:282 Apolipoprotein A-1, apolipoprotein B and lipoprotein (A) levels at patients with ischemic stroke

2006 ◽  
Vol 7 (3) ◽  
pp. 108
Author(s):  
D. Agapakis ◽  
G. Ntaios ◽  
E. Massa ◽  
C. Savopoulos ◽  
G. Kaiafa ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Apolipoprotein B ◽  
Lipoprotein A ◽  
Apolipoprotein A
Sign in / Sign up

Export Citation Format

Share Document