Lipid Metabolism and Cardiac Test Markers: Importance of ...

Lipid Metabolism and Cardiac Test 

Markers: 

Importance of Standardization 

Barbara M. Goldsmith, Ph.D., FACB 

Vice President, Marketing, Membership 

and Education 

Clinical and Laboratory Standards 

Institute (CLSI)

Outline of Presentation 

• CLSI Background Information 

• Standards and Guidelines 

• Lipid Standardization and Traceability 

• Cardiac Markers and Risk Assessment 

• Summary 

2

Our Common Goal: Quality Healthcare

CLSI Background 

• Established in 1968 

• Nonprofit organization based in the United States 

• American National Standards Institute (ANSI)– 

accredited standards-development organization 

• Volunteer driven through our governance structure 

and technical operations 

• An organization of organizations 

• More than 200 standards and guidelines

CLSI Name 

Name change in 2005 to reflect global constituencies

CLSI’s Vision 

To be the leader in clinical and 

laboratory standards to improve 

the quality of medical care.

CLSI’s Mission 

To develop best practices in clinical and laboratory 

testing and promote their use throughout the world, 

using a consensus-driven process that balances 

the viewpoints of industry, government, and the 

health care professions.

CLSI Today 

• $7M annual budget 

• 45 employees 

• 2,000 member organizations 

• nearly 2,000 active volunteers (>600 

Non-North American memberships, >70 

countries) 

• consensus standards and guidelines 

• >75,000 documents each year distributed

CLSI Consensus Process 

Government 

Balance 

Industry 

Professions 

9

CLSI consensus process 

• Meetings are open to everyone 

• Meeting materials are fully available 

• Balanced interests 

• Conflicts of interest are fully disclosed 

• Appeals process 

• All comments addressed

CLSI products 

• Standards 

• Guidelines 

• Collections 

• Videos 

• Toolkits 

• Reports 

• ISO documents

‣ New method evaluation software 

• Developed in conjunction with Analyse-it ® 

Benefits 

Software 

• Only software to faithfully implement the 

eight most popular CLSI method evaluation 

guidelines 

• Evaluates and verifies performance 

characteristics of laboratory methods 

• Provides clear step-by-step advice on 

performing a study 

• Delivers tools for accreditation 

preparedness 

• Easy-to-use workflow 

• Provides timely, accurate statistical results 

• Professional reports, customizable graphs 

and charts 

• Large hospital laboratories 

• Small hospital laboratories 

• Physician office laboratories 

• Reference laboratories 

• In vitro diagnostic customer 

support departments

Use of CLSI Documents 

• Regulatory Compliance 

- Compliance with recognized CLSI consensus documents 

to facilitate regulatory review of IVD devices. 

• Professional Practice 

- Implementation of CLSI best practices for accreditation 

preparedness 

• Education in Clinical Laboratory Sciences 

• Translations include: 

- Japanese -Spanish 

- Korean (In progress) -Turkish 

- Portuguese -Chinese (In progress) 

- Russian - German

Adoption of Documents into Accreditation 

Process – Example of Crosswalk 

14

CLSI Members & Volunteers 

Diverse representation from three constituencies 

Industry Government Professions 

IVD Manufacturers Public Health Agencies Hospitals and Laboratories 

LIS Vendors Regulatory Bodies Healthcare Delivery Systems 

Startup Companies Accrediting Organizations Educational Institutions 

Suppliers Others Professional Societies 

Trade Organizations 

15

CLSI Area Committees 

• Automation and 

Informatics 

• Clinical Chemistry and 

Toxicology 

• Evaluation Protocols 

• Hematology 

• Immunology and 

Ligand Assay 

• Microbiology 

• Molecular Methods 

• Point-of-Care Testing 

• Quality Systems and 

Laboratory Practices

Global Health Partnerships 

• Grant funding from U.S. 

government 

• 10 staff members 

• More than 60 volunteers 

qualified as trainers 

17


CLSI Lab Strengthening Program Services: 

• Assessment/Gap Analysis 

• Training and Education 

• Mentoring 

• Laboratory Self-assessment 

• Continuous Quality Improvement


Current programs planned 

or underway in 

- Côte d’Ivoire Mali 

- Tanzania Azerbaijan 

- Ethiopia Georgia 

- Namibia Uzbekistan 

- Vietnam Kazakhstan 

- Nigeria Ghana

Preparing laboratories for 

WHO-Afro accreditation 

Cote 

d'Ivoire 

Nigeria 

Senegal 

Ethiopia 

Rwanda 

Botswana

CLSI’s Key Global Activities 

International Organization for Standardization (ISO) 

• CLSI is Secretariat for ISO Technical Committee 212 

“Clinical Laboratory Testing and in vitro Diagnostic Test 

Systems” and its working groups: 

WG 1: Quality and competence in the 

medical laboratory. 

WG 2: Reference Systems 

WG 3: In vitro diagnostic products 

WG 4: Antimicrobial susceptibility testing 

• CLSI is administrator of the ANSI-Accredited US 

Technical Advisory Group (TAG) to ISO/TC 212.

Relationship of CLSI and ISO Standards 

broad, standard 

requirements 

detailed help and 

practical guidance 

Complimentary, not conflicting, roles

Standards and Guidelines 

23

Standards & the Lab 

• Most medical lab errors 

are caused by systems 

and process issues, not 

people. 

• They are the areas 

where standards can 

help the most.

Why do Standards Matter? 

• Raise levels of quality, safety, reliability, efficiency, 

and interchangeability 

• Lower trade barriers 

• Act as a base for legislation 

(or avoid the need for legislation) 

• Aid in technology transfer 

• Provide easy access to best-in-class practices 

• Deliver improved outcomes at an economical cost 

25

Standards Development Consensus Process 

A consensus standard or guideline is a 

document developed to promote uniform 

products, materials, methods, or practices. 

Levels of the consensus process: 

• Proposed Level 

• Approved Level 

26

Standard or Guideline? 

• A standard must be followed exactly as written. 

- Written using verbs such as will, must, and shall 

• A guideline may be modified by the user. 

- Written using verbs such as should, could, may, 

or might 

27

Standardization and Traceability 

28

Reasons for testing 

• To identify individuals at increased risk of 

disease and/or monitor disease management 

• To develop epidemiologic data from which to 

establish public health strategies for disease 

management 

G. Myers, CDC, with permission

Requirements to meet testing goals 

• Precise and accurate assays 

• Results must be comparable, independent of 

where and when test performed and assay used 

• Specific measurement standards of higher order 

– Reference measurement procedure(s) (RMP) 

– Reference laboratories that provide RMPs 

– Reference material(s) 

• Process or program to establish and maintain 

traceability to established standards 

G. Myers, CDC, with Permission

Standardization of Laboratory Results 

In the context of laboratory medicine we really 

mean Metrological Traceability 


Traceability: ISO Definition 

• Traceability - property of the result of a 

measurement or the value of a standard whereby it 

can be related to stated references, usually national 

or international standards, through an unbroken 

chain of comparisons all having stated uncertainties. 


Traceability in Laboratory Medicine 

‣Tools Needed for Traceability 

• Reference measurement procedure(s) 

• Gold Standard 

• Reference MP Laboratories 

• Reference materials (commutable) 


Metrological Traceability 

Traceability in Laboratory Medicine 

RMP 

Patient Sample Result 

process that ensures 

patient sample results by a routine 

measurement procedure are 

equivalent to RMP results 

Reference Materials 

(commutable) 

Routine MP 

Patient Sample Result 


Standardization vs. Proficiency Testing 

• Standardization is NOT the same as proficiency 

testing (PT) 

– Most PT programs in the US are NOT accuracybased 

programs 

– PT programs use peer-group grading where 

laboratories are evaluated using the group mean for a 

particular instrument/method 

– Standardization programs must be accuracy-based 

and provide an analytical anchor for traceability 

purposes 


To establish traceability and be standardized, a 

laboratory must be: Precise and Accurate 

Accurate, not precise 

Neither accurate nor precise 

RMP 

Precise, not accurate 

Precise and accurate 


When and Why Is Traceability Most 

Important? 

• To insure the reliability and comparability of 

research findings across studies 

• When patients are seen in a variety of health care 

settings, each using different clinical labs 

• When patient’s clinical test results are being 

compared to guidelines from the medical literature 

and/or large national or international research 

studies (e.g., estimated GFR for CKD, HbA1c for 

diabetes, cholesterol for CVD, etc.). 


Three Separate Measurement Components that 

Require Traceability to Reference Standards 

• Research Laboratories that support 

investigational studies 

• Manufacturers that develop and provide routine 

clinical assays 

• Clinical laboratories that provide test results for 

assessing risk and monitoring therapy 


Calibration Traceability Scheme 

Primary 

Calibrator 

Reference procedure 

(GC-IDMS or LC-IDMS) 

Reference Laboratories 

2 

1 3 

Calibration 

Patient Sample 

Correlation 

Calibration 

SRM 

Proficiency Testing 

Commutable Samples 

Manufacturer 

Clinical Lab. 

G. Meyers

Calibration Hierarchy 

Traceability Chain for Cholesterol Measurement 

NIST IDMS 

SRM 1951b 1º reference material 

SRM 911 (pure cholesterol standard) 

CDC 2º reference materials 

Fresh sample comparison 

Mfr working calibrator 

CDC AK 

CRMLN AK 

Manufacturer 

Clinical Laboratory 

Metrological Traceability 

QC and GLP 

Patient 


Reference Measurement Procedure, HDL & LDL 

Beta-quantification 

1. Ultracentrifuge 

serum 

Rem. 

IDL 

Lp(a) 

Apo E 

Chylo 

VLDL 

LDL 

HDL 

2. Hep/Mn ++ precipitate 

HDL 

LDL 

3. Abell-Kendall Chol. 

(LDL + HDL) – HDL = LDL 


Lipoproteins include a range of particles 

UC density cut 

Hep-Mn ppt 

Hep-Mn soluble 

Used with permission

Beta-quantification limitations 

• A range of lipoprotein particles are included in 

HDL, LDL and VLDL fractions 

• Consequently, the measurand is poorly defined 

• Lipoproteins may be distributed differently in 

diseased vs. normal serum 

• A particular lipoprotein may be present in unusually 

high proportion 

• A lipoprotein that is normally a minor component may 

be present in relatively high concentration 


NCEP performance criteria 

Total Error Bias* CV* 

TC 9% 3% 3% 

HDL-C 13% 5% 4% a 

LDL-C 12% 4% 4% 

TG 15% 5% 5% 

*Suggested limits to meet TE requirement 

a CV 4% at 42 mg/dL; SD 1.7 at 42 mg/dL 

Clinical Chemistry 1988;34:193-201 (TC), and 1995;41:1414-1433 (HDL,LDL, TG) 

NCEP = National Cholesterol Education Project

Routine Method 

SIGNAL 

Trueness (accuracy) Traceability 

Manufacturer comparison with a CDC Network Reference Lab 

Patient Specimens 

Traceability to the reference system is through the 

manufacturer’s method specific calibrators 

Reference Method 

Routine Method 

Calibration 

Calibrator value 

Reportable 

patients’ 

results are 

traceable 

to 

Cannot mix calibrators and reagents from different manufacturers 


Lipids: method evaluation 

• Precision 

– CLSI EP5 

• Bias vs. RMP using patient specimens 

– CLSI EP9 

• Interferences 



• Interferences: 

– Metabolites, drugs (e.g. Hb, bilirubin, ascorbate) that 

cause a measurement interference 

• CLSI EP7 

– Distinguish between a measurement interference and a 

physiologic effect 

• E.g. bilirubin can cause spectrophotometric effect, 

react with H 2 O 2 , and correlates with liver disease that 

may produce an abnormal lipoprotein (e.g. LpX) 



• Interferences: 

– Method non-specificity is important 

– Influence on physicochemical separation of lipoprotein 

molecular forms 

• To normal lipoproteins in abnormal concentrations 

• To abnormal lipoproteins 

• To other proteins 

• CLSI EP21 total error 


Homogeneous HDL-C: approach 1 

Step 1: prevent reaction of non-HDL-C 

Y 

+ - 

Chylo VLDL LDL 

+ - 

Y 

Y 

+ - 

+ - 

Y 

+ - + - 

+ - 

+ - 

Step 2: convert HDL-C to a measurable substance 

Y 

Y 

HDL 

Chol esterase 

Chol oxidase 

Dye 

Peroxidase 

COLOR 


Homogeneous HDL-C: approach 2 

1. Protect HDL-C from reaction and convert non-HDL- 

C to non-measurable substances 

- 

+ 

+ 

HDL 

- 

Chylo 

VLDL LDL 

Chol esterase 

Chol oxidase 

Catalase 

NO COLOR 

2. Un-protect HDL-C and convert to a measurable substance 

+ 

- 

HDL + 

- 

HDL 

Dye 

Peroxidase 

COLOR 


Homogeneous LDL-C: analogous to HDL-C 

1. Protect 

+ 

non-LDL 

- 

+ - 

+ - 

+ - 

Chylo VLDL HDL 

+ - + - 

+ - 

+ - 

2. Convert LDL-C 

Chol esterase 

Chol oxidase 

Dye 

Peroxidase 

LDL 

COLOR 

1. Protect LDL and convert non-LDL-C 

LDL 

Chol esterase 

Chol oxidase 

Catalase 

Chylo VLDL HDL 

NO COLOR 

2. Unprotect and convert LDL-C 

Dye 

LDL 

LDL 

Peroxidase 

COLOR 

G. Meyers, CDC, with permission

Homogeneous measurement challenges 

• Measure the same lipoprotein fractions that are 

measured by beta-quant 

• Not measure anything else 

• Do it for a wide range of clinical conditions with 

abnormal lipoproteins and other proteins 

• Do it with acceptable total error for individual 

samples (not just trueness and imprecision) and cost 


Why is standardization important 

clinically?

Comparison of HDL and LDL Cholesterol Methods 

to Reference Measurement Procedures 

Background: 

• Current guidelines on use of LDL-C and HDL-C 

for cardiovascular risk assessment based on early 

epidemiologic studies that established link 

between lipoproteins and cardiovascular disease 

• Based on older methods that depended on 

physical separation of different lipoprotein classes 

and not direct methods 

• Direct measurements prompted by NCEP panel 

that stated LDL-C should be measured directly 

Miller WG et al Clin Chem 56:6 977-986 (2010) 

54



• Methods from 7 manufacturers and 1 distributer for direct 

measurement of HDL-C and LDL-C were evaluated for 

imprecision, trueness, total error, and specificity in 

nonfrozen serum samples 

• 6 of 8 HDL-C and 5 of 8 LDL-C direct methods met NCEP 

total error goals for non-diseased individuals 

• Patients included individuals with and without disease and 

patients with various types of lipoprotein disorders (unlike 

previous studies) 

• All methods failed to meet NCEP goals for diseased 

individuals due to lack of specificity toward abnormal 

lipoproteins 

Miller WG et al Clin Chem 56:6 977-986 (2010) 

55



Authors’ Conclusions: 

• NCEP accuracy goals based on laboratory testing when 

guidelines were developed (e.g. precipitation-based 

methods for HDL-C, Friedewald equations for LDL-C) and 

clinical need to classify CHD risk and monitor lipid 

treatment (drugs) 

• Composition of lipoproteins in various dyslipidemias affect 

direct methods in specifically measuring cholesterol 

content of one lipoprotein class in presence of other 

lipoproteins; challenging for manufacturers of direct 

methods 

Miller WG et al Clin Chem 56:6 977-986 (2010 

56



Authors’ Conclusions (Con’t) 

• Cannot rule out interferences (drugs, comorbidities, 

triglycerides, nutrition, nonfasting 

specimens) 

• Differences between direct methods and RMPs 

could affect diagnosis and clinical management of 

patients 

• 30-45% test results outside of NCEP total error 

goals for some methods; could reduce overall 

effectiveness of screening for CV risk assessment 

Miller WG et al Clin Chem 56:6 977-986 (2010 

57

Cardiac Markers and Guidelines

National Academy of Clinical Biochemistry (NACB) 

Laboratory Medicine Practice Guidelines (LMPG)

Published NACB LMPGs 

• Therapeutic Drug Monitoring 1999 

• Cardiac Markers 1999 

• Hepatic Injury 2000 

• Diabetes Mellitus 2002 

• Thyroid Disease (2nd edition) 2002 

• Tumor Markers in the Clinic 2003 

• Emergency Toxicology 2005 

• Maternal-fetal Risk Assessment 2006 

• Biomarkers of ACS 2007 * 

• Point of Care Testing 2007 

• Tumor Marker Quality Requirements 2009 

• Expanded Newborn Screening 2009 

• Emerging Biomarkers for CV Risk Factors 2009 * 

• Major Tumor Markers 2009 

• Pharmacogenetics 2010 

• Liver Tumor Markers 2010

NACB LMPG: 

Biomarkers of Acute Coronary 

Syndrome (ACS) 

(Published 2007) 

61

Steps to consider in evaluating 

Biomarkers 

• Is concentration different in persons affected by 

disease in comparison to those not affected 

• Is there a body of evidence from case-control and 

prospective studies that have evaluated the test 

• Does measurement improve ability to assess risk 

above and beyond current approaches 

• Are there reliable analytical methods available for 

measurement 

NACB LMPG, ACS, 2007 

62

Risk Stratification of Acute Coronary 

Syndromes (ACS) 

• Tools: 

– History and physical 

– Standard ECG and non-standard ECG leads 

– Cardiac biomarkers (Troponin I or T, CK-MB, 

Myoglobin, others) 

– Predictive indices/schemes (better as research 

tools than for real-time decision-making) 

– Non-invasive imaging studies (echo, stress 

test) 

NACB LMPG, ACS, 2007

NACB Guideline Recommendations (selected 

recommendations for ACS) 

• Biomarkers of myocardial necrosis should be 

measured in all patients who present with 

symptoms consistent with ACS 

• Cardiac troponin is the preferred marker for the 

diagnosis of MI. CK-MB by mass assay is an 

acceptable alternative when cardiac troponin is 

not available 

• Blood should be obtained for testing at hospital 

presentation followed by serial sampling with 

timing of sampling based on clinical 

circumstances. For most patients, blood should 

be obtained at presentation, 6-9 hrs, and 12-24 

hrs if earlier sample negative 

Note – Recommendation Classes omitted

NACB Recommendations (Con’t) 

• For patients who present within 6 hrs of onset of 

symptoms, an early marker may be considered in 

addition to troponin. Myoglobin is the most 

extensively studied marker for this purpose 

• Total CK, AST, beta-hydroxybutyric 

dehydrogenase, and/or LD should NOT be used 

as biomarkers for the diagnosis of MI 


NACB Recommendations (Con’t) 

• A cardiac troponin is the preferred marker for 

risk stratification and, if available, should be 

measured in all patients with suspected ACS. In 

patients with a clinical syndrome consistent with 

ACS, a maximal concentration exceeding the 99 th 

percentile of values for a reference control group 

(with acceptable precision) should be considered 

indicative of increased risk of death and recurrent 

ischemic events 


Death or MI 

Troponin as a Marker of Increased Risk in 

ACS 

40% 

30% 

30% 

34% 

Troponin + 

Troponin - 

22% 

23% 

20% 

19% 19% 

12% 

11% 

12% 

10% 

0% 

2% 

Hamm 

(1992) 

FRISC 

(1996) 

4% 4% 

TRIM 

(1999) 

Pettijohn 

(1997) 

1% 

Hamm 

(1997) 

0% 

Hamm 

(1997) 

6% 

Polanczyk 

(1998) 

6% 

Galvanni 

(1997)

Strengths of Troponin as biomarker: 

• Almost 100% sensitivity for acute MI with 

serial draws 

• Cardio-specific 

• Remains elevated in circulation up to 7 

days 

• Excellent for retrospective diagnosis of 

acute MI 

• Best prognostic indicator for ACS 


Limitations of Troponin 

• Not an early marker 

• No standardization of methods across 

troponin I assays from different 

manufacturers 

• Sporadic elevations from minor myocardial 

damage may confuse interpretation 

NACB LMPG ACS, 2007

Not all Troponins are Alike 

• Analytical recommendations (NACB 

Guidelines): 99 th percentile with a CV 

FDA Approved Cardiac Troponin Assays

Myoglobin 

• Early rising necrosis marker 

• Rises within 1-3 hours of onset of ACS 

• Doubles in concentration over a two hour 

period 

• Specificity of >95-98% for acute MI 

• 2 negative results 2 hours apart rules out 

acute MI in 97-99% patients 


Limitations of Myoglobin 

• Can be cleared in 6 hrs 

• Present in cardiac and skeletal muscle 

(non-specific) 

• Elevated in muscle trauma and renal 

dysfunction 


Optimal TAT for Cardiac Biomarkers 

for ACS 

• NACB Recommendations: 

– Laboratory should perform cardiac marker testing with 

TAT of 1 hour, optimally 30 minutes or less. 

• TAT defined as time from blood collection to the reporting of 

results 

– Institutions that cannot consistently deliver cardiac 

marker TAT of 1 hour should implement POC platform 

– Acceptable harmonization to central lab results should 

be < 20% 


NACB Recommendations-BNP 

• Plasma BNP or NT-proBNP testing should be 

performed to confirm the diagnosis of HF in 

patients with suspected diagnosis, but with 

presenting signs and symptoms that are 

ambiguous with confounding disease (COPD) 

• In diagnosis of patients with HF, routine plasma 

BNP or NT-proBNP with obvious clinical diagnosis 

is not necessary 


BNP and NT-proBNP - NACB 

Recommendations 

• No primary reference materials are validated for 

calibration of BNP or NT-proBNP. Harmonization 

around the current presumed optimal diagnostic 

medical decision cutoff of 100 pg/mL for BNP 

should be validated. There is only one source of 

antibodies and calibrators for NT-proBNP so 

harmonization of NT-proBNP assays should not 

be a problem 


BNP and NT-proBNP – NACB 

Recommendations 

• Normal reference limits (95 th or 97.5 th percentile) 

should be independently established for both BNP 

and NT-proBNP based on age (by decade) and 

by gender. Each commercial assay should be 

validated separately. The effect of ethnicity needs 

to be evaluated as a possible independent 

variable 


National Academy of Clinical 

Biochemistry (NACB) Laboratory 

Medicine Practice Guidelines 

(LMPG): 

Emerging Biomarkers for Primary 

Prevention of Cardiovascular 

Disease and Stroke 

(Published 2009) 

78

Emerging Risk Factors for 

Cardiovascular Disease 

• C-Reactive Protein 

• Serum amyloid A 

• Soluble CD-40 ligand 

• Fibrinogen 

• D-dimer 

• Factovs V,VII,VIII 

• Lipoprotein(a) 

• LDL and HDL subtypes 

• Homocysteine 

• Microalbuminuria 

• Cystatin C 

• Apo E genotype 

• Remnant lipoproteins 

• Interleukins (eg, IL-6) 

• Vascular and cellular adhesion 

molecules 

• Leukocyte count 

• Plasminogen activator inhib 1 

• Tissue-plasminogen activator 

• Small dense LDL 

• Apoliproproteins A1 and B 

• Oxidized LDL 

• Lipoprot-assoc phopholipaseA2 

• Creatinine (GFR) 

• Infectious agenst 

• Fibrinopeptide A 

• Von Willebrand factor antigen 

NACB LMPG Emerging Biomarkers for CVD 2009 

79

Biomarkers and Cardiovascular Disease 

Risk – NACB Guidelines 

• Inflammation Biomarkers * 

• Lipoprotein Subclasses and Particle 

Concentration 

• Lipoprotein (a) 

• Apolipoproteins A-I and B * 

• Markers of Renal Function 

• Homocysteine * 

• Natriuretic Peptides (BNP and NT-proBNP)

Inflammation Biomarkers and 

Cardiovascular Disease Risk - hsCRP 

High-sensivity C-Reactive Protein (hsCRP) 

• Recommendation 1: After standard global risk 

assessment, if the 10-year predicted risk is

Inflammation Biomarkers and 

Cardiovascular Disease Risk (Cont) 

• Recommendation 3 – There are insufficient data 

that therapeutic monitoring using hsCRP over 

time is useful to evaluate effects of treatments in 

primary prevention 

• Recommendation 4 – The utility of hsCRP 

concentrations to motivate patients to improve 

lifestyle behaviors has not been demonstrated 

• Recommendation 5 – Evidence is inadequate to 

support concurrent measurement of other 

inflammatory markers in addition to hsCRP for 

coronary risk assessment 

NACB LMPG, CVD, 2009 

82

Apolipoproteins A-I and B and 

Cardiovascular Disease Risk 

• Recommendation 1 – The first step to monitor 

efficacy of lipid lowering therapies is to measure 

LDL-C (and non-HDL-C) in patients with elevated 

triglycerides 

• Recommendation 2 – Although apoB measures 

atherogenic lipoproteins and is a good predictor of 

CVD risk (equal at least to LDL-C and non-HDL- 

C), it is only a marginally better predictor than the 

current lipid profile and should not be routinely 

measured at this time for use in global risk 

assessment 


83

Apolipoproteins A-I and B and 

Cardiovascular Disease Risk 

• Recommendation 3 – Measurement of apo-B can 

be used to monitor efficacy of lipid-lowering 

therapies as an alternative to non-HDL-C 

• Recommendation 4 – The apo B/apo A-I ratio can 

be used as an alternative to the usual total 

cholesterol/HDL-C ratio to determine lipoproteinrelated 

risk for CVD 

• Recommendation 5 – Manufacturers of apo-B and 

apo-A I assays should establish traceability to 

accepted standards to assure reliable and 

comparable results 


84

Homocysteine (Hcy) and Cardiovascular 

Disease Risk 

• Recommendation 1 – Hcy concentrations (umol/L) 

derived from standardized assays categorize 

patients as follows: 

– Desirable < 10 

– Intermediate (low to high) >10 to 15 - 30 


85

Homocysteine and Cardiovascular 

Disease Risk 

• Recommendation 2 – The analytical performance 

goal for clinical usefulness for measurement of 

Hcy should be

NACB LMPG 

Point of Care Testing 

(Published 2007)

Point of Care Cardiac Markers 

• Benefits of cardiac marker POCT: 

– Reduced bottleneck in the ED 

– Identification of cardiac patients more quickly 

– Reduce inappropriate treatment pathways 

– Allow for more rapid rule-out of a cardiac event 

– Reduction in LOS for chest pain, CHF, and MI

NACB Guideline Recommendations-”Evidence- 

Based Practice for Point of Care Testing”: POC 

Cardiac testing 

• The laboratory should perform cardiac marker 

testing (for the ED) with a TAT of 1 hour, optimally 

30 minutes or less. TAT is defined as the time 

from blood collection to the reporting of results 

• Comments: timeframe required to determine need 

for thrombolytic therapy. Rule out of MI requiring 

serial samples diminishes the need for a very 

rapid TAT on any single sample 

NACB LMPG, POC, 2007

NACB POC Cardiac Marker 

Recommendations (Con’t) 

• Institutions that cannot consistently deliver cardiac 

marker TAT of approximately 1 hour should 

implement POC testing devices 

• Performance characteristics should not be 

different between central laboratory and POC 

platforms 

• While it is recognized that qualitative systems do 

provide useful information, it is recommended that 

POC systems provide quantitative results 

NACB LMPG, POC, 2007

Summary 

• CLSI is an internationally recognized, consensus-based 

standards organization producing a large number of 

documents and related materials 

• Standards and Guidelines are essential in establishing 

uniform good laboratory practices 

• Standardization and traceability of methods allow 

commutability of results and improve quality and clinical 

care 

• Although work has been done in areas of lipid and cardiac 

marker standardization/harmonization, further work is 

needed 

91

Contact Information – Speaker 

• Barbara M. Goldsmith, Ph.D., FACB 

• Email: Bgoldsmith@clsi.org 

• Phone: 610-688-0100 Ext 112 

• Address: 940 West Valley Road 

Suite 1400 

Wayne, Pennsylvania 19087 USA 

92

THANK YOU FOR YOUR 

ATTENTION 

93

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