Friends, Romans, Cardiac Practitioners, lend me your ears; I come here to bury LDL, not to praise him

Friends, Romans, Cardiac Practitioners, lend me your ears; I come here to bury LDL, not to praise him Adapted from Julius Caesar: Act 3, Scene 2, Page 4

An Alternative Viewpoint A Biomedical Approach to Tackling CVD Prevention Ivor Cummins, BE(Chem) CEng MIEI Jeffry N. Gerber, MD FAAFP

Disclosure 1. My work is supported by David Bobbett and the Irish Heart Disease Awareness (http://www.ihda.ie/) 2. David Bobbett and the IHDA are supporting my efforts to share a better understanding of CVD root causes, prevention strategies and the power of the Calcium Scan. 3. We have no financial ties to the heart imaging industry (!)

Content 1. Engineering Problem Solving for Primary Prevention? 2. Beyond Cholesterol Primary Markers for CVD Risk 3. CVD Prevention the Root Cause Solution-Space

PART 1 Engineering Problem Solving for Primary Prevention?

Ivor the Engineer, c2013

Ivor the Engineer, c2013 200 200 35 GGT Ferritin Cholesterol

Ivor the Engineer, c2013 112 530 260 200 200 35 GGT Ferritin Cholesterol

Ivor the Engineer, c2013 112 530 260 35 200 PRIMARY 5.0 ROOT CAUSE(S) GGT Ferritin Cholesterol

Ivor the Engineer, c2013 112 530 Doctor 1: Haemochromatosis? Reduce wine intake? More healthy wholegrains? 35 200 200 260 Doctor 2: Haemochromatosis? Reduce wine intake? Reduce Fat? Doctor 3: Haemochromatosis? (note*) Reduce wine intake? Reduce Fat? GGT Ferritin Cholesterol

When the experts don t know: RESEARCH!

Cholesterol A Weapon of Mass Distraction 260 200 Cholesterol

Cholesterol A Weapon of Mass Distraction 260 200 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) J Eval Clin Pract. 2012 Feb; 18(1): 159 168.

GGT Subjected to Research 112 35 GGT

GGT Subjected to Research 112 35 GGT Coronary Artery Disease

GGT Subjected to Research 112 35 GGT Type 2 Diabetes

Ferritin Subjected to Research 112 530 200 35 GGT Ferritin

Ferritin Subjected to Research 112 530 200 35 GGT Ferritin Incident Atherosclerosis

Ferritin Subjected to Research Adjusted Risk 112 530 200 Low LDL <5mmol/L High LDL > 5mmol/L 35 GGT Ferritin Heart Attacks

More Research Revelations Another month, and hundreds of papers: July 2013 - Singapore

More Research Revelations Hypothesised that GGT & Ferritin MUST be SERIOUS markers of the Metabolic (Insulin Resistance) Syndrome July 2013 - Singapore

Ferritin pg/ml And then Targeted research: THEY WERE. Serum ferritin and risk of the metabolic syndrome Asia Pac J Clin Nutr 2013;22 (3):400-407

Applying Root-Cause Solution Intervention: Nutritional Only

Belly Crazy GGT Crazy Ferritin Insulin Resistant Root Cause Solutions July 2013 - Singapore

Root Cause Solution applied for 8 Weeks: 112 530 Ivor the Laboratory Rat 200 35 GGT Ferritin

Root Cause Solution applied for 8 Weeks: 112 530 Ivor the Laboratory Rat 200 230 35 35 GGT Ferritin

Root Cause Solution applied for 8 Weeks: 112 530 Ivor the Laboratory Rat 1.47 0.63 200 230 < 1.0 mmol /L 0.92 < 0.5 35 35 >1.20 mmol /L GGT Ferritin HDL Trig Trig/HDL

Root Cause Solution applied for 8 Weeks: 112 530 Ivor the Laboratory Rat 1.73 1.47 0.63 35 35 200 230 >1.20 mmol /L < 1.0 mmol /L 0.92 0.78 < 0.5 0.45 GGT Ferritin HDL Trig Trig/HDL

Root Cause Solution applied for 8 Weeks: Continued. 35 96 145 <135 mmhg 95 <80 mmhg Ideal ~80 Ideal 32 Systolic BP Diastolic BP Weight (Kg) Waist (inches)

Root Cause Solution applied for 8 Weeks: Continued. 96 35 145 95 <135 mmhg 130 <80 mmhg 80 Ideal ~80 82 Ideal 32 32 Systolic BP Diastolic BP Average of 20+ readings from same Equipment Weight (Kg) Waist (inches)

Root Cause Solution applied for 8 Weeks: Continued. 220 35 145 95 <135 mmhg 130 <80 mmhg 80 Ideal ~82Kg 82.5 Ideal 32 32 Systolic BP Diastolic BP Average of 20+ readings from same Equipment Weight (Kg) Waist (inches)

Fat Chol Fat Chol Fat Fat Chol Chol Fat Chol Fat Chol Chol Chol Chol

PART 2 Beyond Cholesterol To The Primary Metrics and Drivers of Heart Disease

Google Cholesterol Conundrum

What do Leading-Edge Experts Say? Cholesterol and Disease Experts are called Lipidologists One of the USA s foremost is Thomas Dayspring, MD, FACP, FNLA, NCMP Clinical Assistant Professor of Medicine, Director of Cardiovascular Education 1) The majority of Heart Attacks are due to INSULIN RESISTANCE 2) LDLc is a near-worthless predictor for cardiovascular issues* *(people with LDLc above 200mg/dL, or 5.3mmol/L are rare )

What do Leading-Edge Experts Say? Cholesterol and Disease Experts are called Lipidologists One of the USA s foremost is Thomas Dayspring, MD, FACP, FNLA, NCMP Clinical Assistant Professor of Medicine, Director of Cardiovascular Education unless LDL levels are very high (7.8 mmol/l or higher), they have no value, in isolation, in predicting those individuals at risk of CHD - William P. Castelli (Framingham Director) Lipids, risk factors and Ischaemic heart disease Atherosclerosis 124 Suppl. (1996) S1-$9

What do Leading-Edge Experts Say? Cholesterol and Disease Experts are called Lipidologists One of the USA s foremost is Thomas Dayspring, MD, FACP, FNLA, NCMP Clinical Assistant Professor of Medicine, Director of Cardiovascular Education The [Total/HDL] RATIO was found to be a better predictor of CHD than TC, LDL, HDL and triglyceride -- not only in the Framingham Study, but also in the Physician's Health Study and many other studies. 2) LDLc is a near-worthless predictor for cardiovascular issues* - William P. Castelli (Framingham Director) Lipids, risk factors and Ischaemic heart disease Atherosclerosis 124 Suppl. (1996) S1-$9

(Lower) ( Trig/HDL) Risk of Heart Disease Non HDL Cholesterol, Apolipoproteins A-I and B100, Standard Lipid Measures, Lipid Ratios, and CRP as Risk Factors for Cardiovascular Disease in Women JAMA, July 20, 2005 Vol 294, No. 3

Risk of Insulin Resistance 6 5 5.15 (Lower) 4 3 ( Trig/HDL) 2 1 1.1 1.9 Risk of Heart Disease Increasing ApoB/ApoA1 Ratio Non HDL Cholesterol, Apolipoproteins A-I and B100, Standard Lipid Measures, Lipid Ratios, and CRP as Risk Factors for Cardiovascular Disease in Women JAMA, July 20, 2005 Vol 294, No. 3 ApoB/apoA-I ratio: an independent predictor of insulin resistance in US non-diabetic subjects European Heart Journal (2007) 28, 2637 2643

Hazard Ratio for CHD Efficacy of Cholesterol Levels and Ratios in Predicting Future Coronary Heart Disease in a Chinese American Journal of Cardiology 2001;88:737 743 3.0 2.0?????? 1.0 1.0 0.97 Total/HDL < 5.0 LOW LDL GROUP (average 2.76 mmol/l) Total/HDL < 5.0 HIGH LDL GROUP (average 4.53 mmol/l)

Hazard Ratio for CHD Efficacy of Cholesterol Levels and Ratios in Predicting Future Coronary Heart Disease in a Chinese American Journal of Cardiology 2001;88:737 743 3.0 2.49 2.0?????? 2.15 1.0 1.0 0.97 Total/HDL < 5.0 Total/HDL > 5.0 LOW LDL GROUP (average 2.76 mmol/l) Total/HDL < 5.0 Total/HDL > 5.0 HIGH LDL GROUP (average 4.53 mmol/l)

Hazard Ratio for CHD Efficacy of Cholesterol Levels and Ratios in Predicting Future Coronary Heart Disease in a Chinese American Journal of Cardiology 2001;88:737 743 3.0 2.49 2.0?????? 2.15 1.0 1.0 0.97 Total/HDL < 5.0 More Insulin Resistant Total/HDL > 5.0 LOW LDL GROUP (average 2.76 mmol/l) Total/HDL < 5.0 More Insulin Resistant Total/HDL > 5.0 HIGH LDL GROUP (average 4.53 mmol/l)

Rate of Heart Disease (IHD) at 8 Years 20% Note: LDL >142 bar was 14.2% - But bar corrected for insulin-elevation effect on LDL estimated from study data 15% 10% 13.1 %??? ~13.8 % 5% LDL 3.67 mmol/l LDL > 3.67 mmol/l We followed 103,646 men and women aged 50 to 75 for 8 years... Study of the Use of Lipid Panels as a Marker of Insulin Resistance to Determine Cardiovascular Perm J 2015 Fall;19(4):4-10

Rate of Heart Disease (IHD) at 8 Years 20% Note: LDL >142 bar was 14.2% - But bar corrected for insulin-elevation effect on LDL estimated from study data 18.5 % 15% 13.1 %??? ~13.8 % 10% 9.2 % 5% LDL 3.67 mmol/l LDL > 3.67 mmol/l Low Trig/HDL RATIO High Trig/HDL RATIO We followed 103,646 men and women aged 50 to 75 for 8 years... Study of the Use of Lipid Panels as a Marker of Insulin Resistance to Determine Cardiovascular Perm J 2015 Fall;19(4):4-10

Rate of Heart Disease (IHD) at 8 Years 20% Note: LDL >142 bar was 14.2% - But bar corrected for insulin-elevation effect on LDL estimated from study data 18.5 % 15% 13.1 %??? ~13.8 % 10% 9.2 % 5% Less Insulin Resistant More Insulin Resistant LDL 3.67 mmol/l LDL > 3.67 mmol/l Low Trig/HDL RATIO High Trig/HDL RATIO We followed 103,646 men and women aged 50 to 75 for 8 years... Study of the Use of Lipid Panels as a Marker of Insulin Resistance to Determine Cardiovascular Perm J 2015 Fall;19(4):4-10

Insulin Resistance as a Predictor of Age-Related Diseases The Journal of Clinical Endocrinology & Metabolism 86(8):3574 3578 Prospective Predictions Based on IR Level Apparently healthy, non-obese individuals aged ~65 Split into tertiles of Insulin Resistance using SSPG (Kraft-Type) Test What happened ~6.5 years later?

Prospective Predictions Based on IR Level Apparently healthy, non-obese individuals aged ~65 Split into tertiles of Insulin Resistance using SSPG (Kraft-Type) Test What happened ~6.5 years later? Insulin Resistance as a Predictor of Age-Related Diseases The Journal of Clinical Endocrinology & Metabolism 86(8):3574 3578

Prospective Predictions Based on IR Level Apparently healthy, non-obese individuals aged ~65 Risk Multiplier: Split into tertiles of Insulin Resistance using SSPG (Kraft-Type) Test What happened ~6.5 years later? High SSPG = 40x! ( CI = 35 to 45 ) Note: LDL was 1.001x, non-significant children between the ages of 6 and 19 years with metabolic syndrome showed a ~15x children increased between risk of the CVD ages at of 256 year and follow-up 19 years with insulin resistance syndrome showed a 15x increased risk of CVD at 25 year follow-up Atherosclerotic Cardiovascular Disease Beginning in Childhood DOI 10.4070 / kcj.2010.40.1.1

2015 Euroaspire - CHD and Diabetes Status Those with cardiovascular disease not identified with diabetes are simply undiagnosed - Dr. Joseph R. Kraft

2015 Euroaspire - CHD and Diabetes Status

2015 Euroaspire - CHD and Diabetes Status Known Diabetics! Non-Diabetic CAD Victims ~7,000 CAD Victims Across All of Europe

2015 Euroaspire - CHD and Diabetes Status Non-Diabetic CAD Victims Known Diabetics! 4,004 Non-Diabetic CAD Victims (supposedly) ~7,000 CAD Victims Across All of Europe 4,004 NON-DIABETIC CAD Victims Ages 18-80, across 24 countries

2015 Euroaspire - CHD and Diabetes Status Non-Diabetic CAD Victims Known Diabetics! More 4,004Diabetics Non-Diabetic! CAD Victims (supposedly) ~7,000 CAD Victims Across All of Europe 4,004 NON-DIABETIC CAD Victims Ages 18-80, across 24 countries

2015 Euroaspire - CHD and Diabetes Status Non-Diabetic CAD Victims Known Diabetics! More 4,004Diabetics Non-Diabetic! CAD Victims (supposedly) Yet More Diabetics! ~7,000 CAD Victims Across All of Europe 4,004 NON-DIABETIC CAD Victims Ages 18-80, across 24 countries

2015 Euroaspire - CHD and Diabetes Status Non-Diabetic CAD Victims Known Diabetics! If INSULIN Tested??? Yet More Diabetics! More Diabetics! ~7,000 CAD Victims Across All of Europe 4,004 NON-DIABETIC CAD Victims Ages 18-80, across 24 countries

2015 Euroaspire - CHD and Diabetes Status Non-Diabetic CAD Victims Known Diabetics! If KRAFT Tested??? Yet More Diabetics! More Diabetics! If INSULIN Tested??? YET MORE Diabetics! KNOWN Diabetics! MORE Diabetics! ~7,000 CAD Victims Across All of Europe 4,004 NON-DIABETIC CAD Victims Ages 18-80, across 24 countries All CAD Patients: Reality Bites.

2015 Euroaspire - CHD and Diabetes Status Those with cardiovascular disease not identified with diabetes are simply undiagnosed - Dr. Joseph R. Kraft Non-Diabetic CAD Victims (supposedly ) Known Diabetics! If KRAFT Tested? Yet More Diabetics! More Diabetics! If KRAFT Tested??? YET MORE Diabetics! KNOWN Diabetics! MORE Diabetics! CAD Victims All of Europe 4,004 NON-DIABETIC CAD Victims Ages 18-80, across 24 countries All CAD Patients: Reality Bites.

Very Latest Data Feb 15 th 2017 - Medscape

Very Latest Data Feb 15 th 2017 - Medscape IF YOU DOn t MEASURE It, It DOn t GEt FIXED.

PART 3 CVD Prevention The Root Cause Solution-Space

CAC: THE MASTER MEASURE Google Budoff Ivor

CAC: THE MASTER MEASURE Calcium Score Risk Equivalent 10-Year Event Rate, % 0 Very low 1.1-1.7 1-100 Low 2.3-5.9 101-400 Intermediate 12.8-16.4 >400 High 22.5-28.6 >1000 Very high 37 Reproducible and quantifiable Based on 100 s of thousands of subjects J Am Coll Cardiol Img. 2015;8(5):579-596

CAC: THE MASTER MEASURE All-Cause MORTALITY! Interplay of Coronary Artery Calcification and Traditional Risk Factors for the Prediction of All-Cause Mortality in Asymptomatic Individuals Circ Cardiovasc Imaging. 2012; 5:467-473

And what about CAC Score progression??

And what about CAC Score progression?? Starting CAC Score 100-1000 Progression 15% per year Progression of Coronary Artery Calcium and Risk of First Myocardial Infarction in Patients Receiving Cholesterol-Lowering Therapy Paolo Raggi, Tracy Q. Callister, Leslee J. Shaw. Arterioscler Thromb Vasc Biol, 2004

And what about CAC Score progression?? Starting CAC Score 100-1000 Progression 15% per year Starting CAC Score 100-1000 Progression <15% per year Progression of Coronary Artery Calcium and Risk of First Myocardial Infarction in Patients Receiving Cholesterol-Lowering Therapy Paolo Raggi, Tracy Q. Callister, Leslee J. Shaw. Arterioscler Thromb Vasc Biol, 2004

The Human Chronic Disease Spectrum

The Human Chronic Disease Spectrum Truly NON Diabetic

The Human Chronic Disease Spectrum Full Blown Diabetes Truly NON Diabetic

The Human Chronic Disease Spectrum Full Blown Diabetes Hyperinsulinemic Very Unhealthy Very Diabetic Truly NON Diabetic Euinsulinemic Healthy Non-Diabetic Hyperinsulinemic Unhealthy Pre-Diabetic

The Human Chronic Disease Spectrum Serum GGT Serum Ferritin Calcium Scan Full Blown Diabetes Hyperinsulinemic Very Unhealthy Very Diabetic Truly NON Diabetic Euinsulinemic Healthy Non-Diabetic Hyperinsulinemic Unhealthy Pre-Diabetic

The Human Chronic Disease Spectrum Full Blown Diabetes YOU? Truly NON Diabetic

The Human Chronic Disease Spectrum Calcium Score Risk Equivalent 10-Year CVD Event Rate, % Full Blown Diabetes 0 Very low 1.1-1.7 1-100 Low 2.3-5.9 101-400 Intermediate 12.8-16.4 >400 High 22.5-28.6 >1000 Very high 37 All-Cause MORTALITY! Truly NON Diabetic

The Human Chronic Disease Spectrum Post-prandial Insulin Post-prandial Glucose Triglyceride/HDL ratio or Total Chol/HDL ratio GGT / Ferritin / BP / CRP Full Blown Diabetes Truly NON Diabetic

The Human Chronic Disease Spectrum Full Blown Diabetes FIX? Truly NON Diabetic

The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes? Truly NON Diabetic

The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes Ref Carb / Sugar Proc Food Truly NON Diabetic Veg Oil

The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes Ref Carb / Sugar Proc Food Truly NON Diabetic Low Carb Healthy Fat HQ Protein Veg Oil

The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes Ref Carb / Sugar Proc Food Truly NON Diabetic Fasting Low Carb Healthy Fat HQ Protein Veg Oil

The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes Ref Carb / Sugar Proc Food Truly NON Diabetic Supp Exercise Sun Stress Sleep Fasting Low Carb Healthy Fat HQ Protein Veg Oil

The Human Chronic Disease Spectrum Full Blown Diabetes Ref Carb / Sugar Proc Food ANCESTRAL Truly Non- Diabetic HEALTH Supp Exercise Sun Stress Sleep Fasting Low Carb Healthy Fat HQ Protein Veg Oil

The Human Chronic Disease Spectrum METABOLIC MAYHEM Ref Carb / Sugar Proc Food ANCESTRAL Truly Non- Diabetic HEALTH Supp Exercise Sun Stress Sleep Fasting Low Carb Healthy Fat HQ Protein Veg Oil

Meeting the Challenges of Current Practice Key Messages: LDL is a weak and misleading risk factor Hyperinsulinemia / Insulin Resistance underpins CVD Root Cause If we don t measure it it don t get fixed It can be addressed effectively with the ten levers We can turn the tide in the CVD war by leveraging root cause science But in the end, Truth will out The Merchant of Venice (2:2) #bacpr2017

But in the end, Truth will out The Merchant of Venice (2:2)

LDL A Weapon of Mass Misleading Risk of Heart Disease after 4 Years Heart Disease Risk Vs LDL & HDL VERY HIGH ~10X HDL= 25 HDL = 45 Decreasing HDL (the Good Cholesterol ) VERY LOW 100 160 220 Increasing LDL (the Bad Cholesterol ) Diagram adapted from article in Journal of Cardiovascular Medicine 2011 HDL = 65 HDL = 85 Data from the Framingham Heart Study showing incidence of CAD over 4 years in men 50-70 years old High HDL People LDL being relevant - depends entirely on your HDL status

HIGHISH FRUCTOSE LOW FRUCTOSE MEDIUM FAT/PROTEIN HIGH HEALTHY FAT / MODERATE PROTEIN EXCESSIVE CARBOHYDRATE Root Cause Solutions LOTS OF NON-STARCHY VEG! BUT LOW STARCHY CARBOHYDRATES