The Cholesterol Conundrum -“Know Your Metrics”

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2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 1012. Standard Lipid Test

• Total Cholesterol Concentration• LDL / HDL Cholesterol Concentration• Serum Triglyceride

3. The All-Important Ratios• Total Cholesterol / HDL• Triglyceride / HDL

4. Introduction to some other Critical Metrics• Fasting Insulin, Blood Glucose/HbA1c, 25 Hydroxy Vitamin D

5. Conclusion

Metrics Content:

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Cholesterol and Triglyceride can be measured in mg/dL (e.g. USA) or

mmol/L (e.g. Europe)

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Cholesterol and Triglyceride can be measured in mg/dL (e.g. USA) or

mmol/L (e.g. Europe)

Be careful converting – Cholesterol and Triglyceride both have DIFFERENT conversion factors as you switch from one unit to another

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Cholesterol and Triglyceride can be measured in mg/dL (e.g. USA) or

mmol/L (e.g. Europe)

Be careful converting – Cholesterol and Triglyceride both have DIFFERENT conversion factors as you switch from one unit to another

To convert CHOLESTEROL from mmol/L to mg/dL, multiply by 38.7

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Cholesterol and Triglyceride can be measured in mg/dL (e.g. USA) or

mmol/L (e.g. Europe)

Be careful converting – Cholesterol and Triglyceride both have DIFFERENT conversion factors as you switch from one unit to another

To convert CHOLESTEROL from mmol/L to mg/dL, multiply by 38.7

To convert CHOLESTEROL from mg/dL to mmol/L, divide by 38.7

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Cholesterol and Triglyceride can be measured in mg/dL (e.g. USA) or

mmol/L (e.g. Europe)

Be careful converting – Cholesterol and Triglyceride both have DIFFERENT conversion factors as you switch from one unit to another

To convert CHOLESTEROL from mmol/L to mg/dL, multiply by 38.7

To convert CHOLESTEROL from mg/dL to mmol/L, divide by 38.7

To convert TRIGLYCERIDE from mmol/L to mg/dL, multiply by 88.6

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Cholesterol and Triglyceride can be measured in mg/dL (e.g. USA) or

mmol/L (e.g. Europe)

Be careful converting – Cholesterol and Triglyceride both have DIFFERENT conversion factors as you switch from one unit to another

To convert CHOLESTEROL from mmol/L to mg/dL, multiply by 38.7

To convert CHOLESTEROL from mg/dL to mmol/L, divide by 38.7

To convert TRIGLYCERIDE from mmol/L to mg/dL, multiply by 88.6

To convert TRIGLYCERIDE from mg/dL to mmol/L, divide by 88.6

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Metric Current Desired Action Result

Tot Chol 200 mg/dL mmol/L Divide by 38.7 5.16 mmol/L

LDL 100 mg/dL mmol/L Divide by 38.7 2.58 mmol/L

Tot Chol 6.8 mmol/L mg/dL Multiply by 38.7 263 mg/dL

HDL 1.7 mmol/L mg/dL Multiply by 38.7 66 mg/dL

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Metric Current Desired Action Result

Tot Chol 200 mg/dL mmol/L Divide by 38.7 5.16 mmol/L

LDL 100 mg/dL mmol/L Divide by 38.7 2.58 mmol/L

Tot Chol 6.8 mmol/L mg/dL Multiply by 38.7 263 mg/dL

HDL 1.7 mmol/L mg/dL Multiply by 38.7 66 mg/dL

Triglyceride 150 mg/dL mmol/L Divide by 88.6 1.69 mmol/L

Triglyceride 0.78 mmol/L Multiply by 88.6 69 mg/dL

2013 Ivor Cummins BE(Chem) MIEI

1. Cholesterol Units 101 Metric Current Desired Action Result

Tot Chol 200 mg/dL mmol/L Divide by 38.7 5.16 mmol/L

LDL 100 mg/dL mmol/L Divide by 38.7 2.58 mmol/L

Tot Chol 6.8 mmol/L mg/dL Multiply by 38.7 263 mg/dL

HDL 1.7 mmol/L mg/dL Multiply by 38.7 66 mg/dL

Triglyceride 150 mg/dL mmol/L Divide by 88.6 1.69 mmol/L

Triglyceride 0.78 mmol/L Multiply by 88.6 69 mg/dL

RatioUse mg/dL(!)

Ivor Guide My Target Result

Tot Chol/HDL 263 / 66 <4.5 <4.0 ~3.5

Trig/HDL 69 / 66 <2.0 <1.0 ~1.0

2 Standard Lipid Test

2.1 Total Cholesterol

<200 200-240 240-280 >280

2.1 Total Cholesterol Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants)Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3

Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5

<200 200-240 240-280 >280

2.1 Total Cholesterol Is the use of cholesterol in mortality risk algorithms in clinical guidelines valid? Ten years prospective data from the Norwegian HUNT 2 study (>58,000 Participants)Halfdan Petursson MD,1 Johann A. Sigurdsson MD Dr med,2 Calle Bengtsson MD Dr med,3

Tom I. L. Nilsen Dr Philos4 and Linn Getz MD PhD5

Total Cholesterol:•Hopelessly confounded•Only useful for research•But interesting interaction with w6/w3 ratio…

2.2 LDL & HDL Cholesterol

2.2 LDL & HDL Cholesterol

2.2 LDL & HDL Cholesterol

LDL•Confounded

HDL•Guide >40mg/dL•Generally true…

2.3 Serum Triglyceride

2.3 Serum Triglyceride (< 2.25 mmol/L)(> 2.25 mmol/L)

2.3 Serum Triglyceride (< 2.25 mmol/L)(> 2.25 mmol/L)

Triglyceride:•Guide <150mg/dL•Ideally <100mg/dL

3 All-Important Ratios

3.1 – The Total Chol / HDL Ratio

3.1 – The Total Chol / HDL Ratio

Ratio <5, LDL being low or High is irrelevant

Ratio >5, LDL being low or High is irrelevant

Am J Cardiol. 2001 Oct 1;88(7):737-43.Efficacy of cholesterol levels and ratios in predicting future coronary…..

3.1 – The Total Chol / HDL Ratio

Tot Chol / HDL Ratio:•Guide <4.5 or 5•Ideally <4.0

Ratio <5, LDL being low or High is irrelevant

Ratio >5, LDL being low or High is irrelevant

Am J Cardiol. 2001 Oct 1;88(7):737-43.Efficacy of cholesterol levels and ratios in predicting future coronary…..

3.2 The Trig / HDL Ratio

3.2 The Trig / HDL Ratio Study: “High Ratio of Triglycerides to HDL-Cholesterol Predicts Extensive Coronary Disease”

3.2 The Trig / HDL Ratio

Triglyceride / HDL Ratio:•Guide <2.0•Ideally <1.0

Study: “High Ratio of Triglycerides to HDL-Cholesterol Predicts Extensive Coronary Disease”

4 Other Key Metrics

4.1 Fasting Insulin

4.1 Fasting Insulin

4.1 Fasting Insulin

Fasting Insulin:•Guide: Unclear•Ideally <10uU/mL•Again, watch the units!

4.2 Fasting Glucose

4.2 Fasting Glucose

“The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy – a review of the evidence”. WALLDIUS1,2 & I . JUNGNER3 , 4 From the 1King Gustaf V Research Institute, Karolinska Institute, Stockholm; 2AstraZeneca, So¨derta¨lje; 3Department of Medicine, Karolinska Institute, Epidemiological Unit, Stockholm; and 4CALAB Research, Stockholm; Sweden

Journal of Internal Medicine 2006; 259: 493–519

4.2 Fasting Glucose

Blood Glucose:•Guide <6 mmol/L•Ideally <5 mmol/L

Note 1: watch the units(!) – mmol/L used above, but multiply by 18 to get mg/dL

Note 2: HbA1c is a more stable indication of long-term blood glucose levels

“The apoB/apoA-I ratio: a strong, new risk factor for cardiovascular disease and a target for lipid-lowering therapy – a review of the evidence”. WALLDIUS1,2 & I . JUNGNER3 , 4 From the 1King Gustaf V Research Institute, Karolinska Institute, Stockholm; 2AstraZeneca, So¨derta¨lje; 3Department of Medicine, Karolinska Institute, Epidemiological Unit, Stockholm; and 4CALAB Research, Stockholm; Sweden

Journal of Internal Medicine 2006; 259: 493–519

4.3 25 Hydroxy Vitamin D

4.3 25 Hydroxy Vitamin D Study: “Association of vitamin D deficiency and coronary artery disease with cardiovascular risk factors”

4.3 25 Hydroxy Vitamin D

25 Hydroxy Vit D:•Should be >=75 nmol/LNote: watch the units again(!) – 75nmol/L used above equates to 30ng/ml: so, divide by 2.5 to get from nmol/L to ng/ml, and vice versa)

Study: “Association of vitamin D deficiency and coronary artery disease with cardiovascular risk factors”

5 – Conclusion

5 – Conclusion •Need to understand lipid unit conversion to avoid confusion•Traditional Tot Chol and LDL are outdated predictors•Tot Chol / HDL and Trig / HDL are powerful predictors•Fasting Insulin, HbA1c and other metrics are underused•25 Hydroxy Vitamin D level is critical and underemphasised

5 – Conclusion

Watch “The Cholesterol Conundrum – Root Cause and Solution” for engineering-level explanation of this arena.

•Need to understand lipid unit conversion to avoid confusion•Traditional Tot Chol and LDL are outdated predictors•Tot Chol / HDL and Trig / HDL are powerful predictors•Fasting Insulin, HbA1c and other metrics are underused•25 Hydroxy Vitamin D level is critical and underemphasised