Recommendations for reporting of harmonised, non-fasting lipid cut-offs. David Sullivan and Graham Jones 12 Sept 2016

Transcription

1 Recommendations for reporting of harmonised, non-fasting lipid cut-offs David Sullivan and Graham Jones 12 Sept 2016

2 Lipid Testing The Questions: Harmonised Reporting? (Y/N) What tests / calculations to report? What references and comments? General cardiovascular risk Familial Hypercholesterolaemia (FH) Treatment targets Fasting samples?

3 Harmonisation Y/N? For this we need labs to have: Comparable results Similar populations Same Resources (guidelines, references) (> 3 years)

4 Same results: Total Cholesterol Liquid Serum Chemistry

5 GP Red Book Same Guidelines, resources

6 Harmonisation Y/N? For this we need labs to have: Comparable results Similar populations Same Resources (guidelines, references) Same Customers (ie same understanding of issues) Need for education!

7 What tests / calculations?

8 What s in a lipid panel LDL/HDL 4% CR Index 4% Ratio 4% Non HDL Cholesterol 26% Total/HDL Ratio 48% LDL Cholesterol (Calculated) 13% LDL Cholesterol 87% HDL Cholesterol 91% Triglycerides 96% Cholesterol 91% 0% 20% 40% 60% 80% 100% 120%

9 Lipid test Variation Chol, Trig, HDL Chol, Chol/HDL, Non HDL-Chol, LDL Chol 4% Chol, Trig, HDLC, LDL Chol, TC/HDLC, LDL/HDL 4% Chol, Trig, HDL, Chol/HDL Ratio, LDL, Non HDLC 4% T Chol, LDL Chol, HDL Chol, Trig 4% Chol HDL, Chol LDL, Trig 4% LDL Chol, Non HDL Chol, Trig 4% Chol, Trig, HDL Chol, LDL Chol (calc), Non-HDL Chol, Chol/HDL Ratio 4% HDL Chol, Chol, Trig, LDL Chol, Non-HDL Chol 4% Chol, Trig, HDL Chol, LDL (calc) 4% Chol, HDL, Trig, LDL, Chol/HDL Ratio, CR Index 4% Chol, Trig, LDL Chol (calc), HDL Chol 4% LDL, Chol/HDL 4% Chol, Trig, HDL-C, LDL-C, Ratio, 13% Chol, Trig, LDL Chol, HDL Chol, Chol/HDL Ratio 13% Chol, Trig, HDL Chol, LDL Chol 13% Chol, Trig, HDL Chol, nonhdl chol, LDL Chol, Cholesterol/HDL Ratio 4% Chol, Trig, LDL-Chol, HDL-Chol, Total/HDL Ratio 4% 0% 2% 4% 6% 8% 10% 12% 14%

10 Why Test Lipids? Cardiovascular risk assessment (primary prevention) Treatment assessment Other Pancreatitis, inherited disorders

11 Cardiovascular risk assessment Who not to test for risk assessment? These patients risk is already known

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13 Familial Hypercholesterolaemia Red Book 2012

14 Risk Assessment / FH General Risk Assessment: Age, sex, smoking, BP, diabetes, LVH Total cholesterol / HDL ratio Identification of Familial Hypercholesterolaemia Total Cholesterol > 7.5 mmol/l, LDL >4.9* Dutch Lipid Clinic Score * Red Book 2012

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18 Proposal 1 Laboratories should add comments to elevated LDL or total cholesterol to advise about risk of FH Information should be available about what to do next Yes No Other LDL >5 mmol/l nonhdl>6 mmol/l

19 Proposal 2 Laboratories should report the following (for risk assessment*): Total cholesterol HDL cholesterol Triglycerides LDL (measured or calculated) Total cholesterol to HDL ratio * Reason for request usually unknown, see following

20 Lipids: Treatment assessment High risk patients prior to treatment: Is lipid lowering therapy needed? (i.e. are lipids already at target) Patients on Lipid lowering therapy Is treatment meeting targets?

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22 Red Book 2012

23 Proposal 3 Laboratories should report the following (for treatment monitoring*): Total cholesterol HDL cholesterol Triglycerides LDL (measured or calculated) Non-HDL cholesterol * Reason for request usually unknown, see following

24 Lipids: Reason unknown In practice we rarely know what the reason for the testing is.

25 Proposal 4 Laboratories should report the following for all lipid requests: Total cholesterol HDL cholesterol Triglycerides LDL (measured or calculated) Total Cholesterol / HDL ratio Non-HDL cholesterol

26 Example Report Test Fasting status Cholesterol Triglycerides HDL Chol LDL Chol TC/HDL Non-HDLC 1-Apr-16 fasting 5.0 H Units Reference mmol/l mmol/l mmol/l mmol/l (<5.0) (<2.0) (>1.0) (<3.0) mmol/l (<3.9) Targets for lipid lowering therapy TC: <4.0 mmol/l HDL: 1.0 mmol/l LDLC: <2.0 mmol/l non-hdlc: <2.5 mmol/l Targets from NVDA guidelines 2013

27 Example Report What about fasting? 1-Apr-16 Test Fasting status fasting Cholesterol 5.0 H Triglycerides 1.5 HDL Chol 1.5 LDL Chol 2.8 TC/HDL 3.3 Non-HDLC 3.5 Units Reference What references? mmol/l mmol/l mmol/l mmol/l (<5.0) (<2.0) (>1.0) (<3.0) mmol/l (<3.9) Targets for lipid lowering therapy TC: <4.0 mmol/l HDL: 1.0 mmol/l LDLC: <2.0 mmol/l non-hdlc: <2.5 mmol/l Targets from NVDA guidelines 2013 Treatment Targets

28 To Fast or Not to Fast? April 2016

29 Effect of food on lipid results Fasting standardises the measurement of Triglycerides, but has little effect on other lipids / lipoproteins. Little effect on total cholesterol or HDL-C, hence little effect on Non-HDL cholesterol Some effect on calculated LDL?

30 To Fast or Not to Fast?

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32 Proposal 5 Non fasting samples are acceptable (not compulsory) for Lipid testing in most patients The same decision points should be used for TC, HDLC, non-hdlc, LDLC Different points for triglycerides? The fasting status should be stated on the report Education should be available on the effects of fasting

33 Example Report (reason unknown) Test Fasting status Cholesterol Triglycerides HDL Chol LDL Chol TC/HDL Non-HDLC 1-Apr-16 fasting 5.0 H Units Reference What references? mmol/l mmol/l mmol/l mmol/l (<5.0) (<2.0) (>1.0) (<3.0) mmol/l (<3.9) Targets for lipid lowering therapy TC: <4.0 mmol/l HDL: 1.0 mmol/l LDLC: <2.0 mmol/l non-hdlc: <2.5 mmol/l Targets from NVDA guidelines 2013

34 Reference Limits

35 Desirable Concentrations

36 Prevalence of non-ideal lipids and lipoproteins

37 RCPAQAP RI Scheme: Cholesterol <5.0

38 RCPAQAP RI Scheme: Triglycerides <0.7 <1.0

39 RCPAQAP RI Scheme: HDLC >1.0

40 RCPAQAP RI Scheme: LDLC <2.0

41 Non-HDL Cholesterol Is this a useful marker of cardiovascular risk? Less influenced by fasting (no trigs in calculation) Includes effects of VLDL and remnants But does it predict risk as well as LDL cholesterol?

42 Non-HDL-C out-performs LDL-C as an indicator of CVD risk. Pischon et al. Circulation 2005;112: CHD RR, 95% CI P-Trend LDL-C 2.07 ( ) < Non-HDL-C 2.75 ( ) < Apo B 2.98 ( ) < Biomarker Quintile 5 vs. Quintile 1 P-Trend is a test for a rise or fall in RR from Q1 to Q5

43 Critical Alerts Alert for FH risk discussed What about other risks identified from lipids?

44 Risk flags

45 Proposals A) Adopt EAS/ESFM recommendations as typified by Tables 5, 6 and 8 (in SI units) Favours harmonisation and referencing of source Covers issues of non-hdlc and FH Re-establishes ideal level Appropriate inclusion of Apo(a) (MBS implications) B) Modify EAS/ESFM recommendations. See following slide Delete remnant cholesterol, fasting and non-fasting (TY) Higher HDL in females (TY) Equalise fasting and nonfasting Non-HDLC (DS) Equalise fasting and nonfasting TG (males only) (DS) Aids memory at expense of internal consistency

46 Suggested references CHOL TRIG Fasting* Non Fasting* < 5.0 < 5.0 < 1.7 (Consider < 2.0, or Males < 2.0, Females < 1.7, suggested by DS) < 2.0 > 1.0 > 1.0 HDL-C (Consider Females > 1.2, suggested by Sonic) (Consider Females > 1.2, suggested by Sonic) LDL-C < 3.0 < 3.0 Non HDLC** < 3.8 < 3.9 (Consider < 3.9, suggested by DS)

47 Next Steps Finalise position following meeting Prepare supporting material Website content Flyer Put into action

48 Example Report (reason unknown) Test Fasting status Cholesterol Triglycerides HDL Chol LDL Chol TC/HDL Non-HDLC 1-Apr-16 fasting 5.0 H Units Reference mmol/l mmol/l mmol/l mmol/l (<5.0) (<2.0) (>1.0) (<3.0) mmol/l (<3.9) Targets for lipid lowering therapy TC: <4.0 mmol/l HDL: 1.0 mmol/l LDLC: <2.0 mmol/l non-hdlc: <2.5 mmol/l Targets from NVDA guidelines 2013

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50 Spare Slides

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52 Non-fasting TG a more sensitive indicator of CVD risk. Copenhagen Heart Study

53 New levels of alert: EAS, EFLM Consensus Statement Nordestgaard et al, EHJ 26/4/16

54 A new risk factor: Lipoprotein (a) Mainly genetic (2030% at risk of CVD). Genetic variability (eg > 80th %ile) Antogonises plasminogen Binds artery wall proteoglycans Transports oxidised phospholipids Resistant to diet and lipid-lowering therapy, but may respond to aspirin. Also a risk for aortic stenosis Responds to new Rx, Anti-PCSK9 and Antisense. Apo(a) Metabolic environment Lipid core ApoB Alteration in Lp(a) risk factor properties CVD Risk Inflammation

55 Figure. Levels of lipoprotein(a) and risk of myocardial infarction by KIV-2 genotype. Mendelian Randomisation evidence for Lipoprotein (a) as a CVD risk factor Lipoprotein(a) (mg/dl) Lipoprotein (a) (mg/dl) Kamstrup et al, JAMA 2009;301: KIV-2 quartile Multifactorially adjusted hazard Hazard ratio(95% for MIconfidence (95% CI) interval) KIV-2 quartile 1st 1st 2nd 2nd 3rd 3rd Trend p<0.001 Trend: p< th 4th Trend Trend p<0.001 p<0.001 Trend: p<0.00

56 Lipoprotein (a) affects the progression of Aortic Stenosis & valve calcification.

57 Same Results: HDL Cholesterol Liquid Serum Chemistry

58 Same Results: Triglycerides Liquid Serum Chemistry