Friends, Romans, Cardiac Practitioners, lend me your ears; I come here to bury LDL, not to praise him
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- Cornelius Fleming
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1 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
2 An Alternative Viewpoint A Biomedical Approach to Tackling CVD Prevention Ivor Cummins, BE(Chem) CEng MIEI Jeffry N. Gerber, MD FAAFP
3 Disclosure 1. My work is supported by David Bobbett and the Irish Heart Disease Awareness ( 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 (!)
4 Content 1. Engineering Problem Solving for Primary Prevention? 2. Beyond Cholesterol Primary Markers for CVD Risk 3. CVD Prevention the Root Cause Solution-Space
5 PART 1 Engineering Problem Solving for Primary Prevention?
6 Ivor the Engineer, c2013
7 Ivor the Engineer, c GGT Ferritin Cholesterol
8 Ivor the Engineer, c GGT Ferritin Cholesterol
9 Ivor the Engineer, c PRIMARY 5.0 ROOT CAUSE(S) GGT Ferritin Cholesterol
10 Ivor the Engineer, c Doctor 1: Haemochromatosis? Reduce wine intake? More healthy wholegrains? Doctor 2: Haemochromatosis? Reduce wine intake? Reduce Fat? Doctor 3: Haemochromatosis? (note*) Reduce wine intake? Reduce Fat? GGT Ferritin Cholesterol
11 When the experts don t know: RESEARCH!
12 Cholesterol A Weapon of Mass Distraction Cholesterol
13 Cholesterol A Weapon of Mass Distraction 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 Feb; 18(1):
14 GGT Subjected to Research GGT
15 GGT Subjected to Research GGT Coronary Artery Disease
16 GGT Subjected to Research GGT Type 2 Diabetes
17 Ferritin Subjected to Research GGT Ferritin
18 Ferritin Subjected to Research GGT Ferritin Incident Atherosclerosis
19 Ferritin Subjected to Research Adjusted Risk Low LDL <5mmol/L High LDL > 5mmol/L 35 GGT Ferritin Heart Attacks
20 Ferritin Subjected to Research Adjusted Risk Low LDL <5mmol/L High LDL > 5mmol/L 35 GGT Ferritin Heart Attacks
21 More Research Revelations Another month, and hundreds of papers: July Singapore
22 More Research Revelations Hypothesised that GGT & Ferritin MUST be SERIOUS markers of the Metabolic (Insulin Resistance) Syndrome July Singapore
23 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):
24 Applying Root-Cause Solution Intervention: Nutritional Only
25
26 Belly Crazy GGT Crazy Ferritin Insulin Resistant Root Cause Solutions July Singapore
27 Root Cause Solution applied for 8 Weeks: Ivor the Laboratory Rat GGT Ferritin
28 Root Cause Solution applied for 8 Weeks: Ivor the Laboratory Rat GGT Ferritin
29 Root Cause Solution applied for 8 Weeks: Ivor the Laboratory Rat < 1.0 mmol /L 0.92 < >1.20 mmol /L GGT Ferritin HDL Trig Trig/HDL
30 Root Cause Solution applied for 8 Weeks: Ivor the Laboratory Rat >1.20 mmol /L < 1.0 mmol /L < GGT Ferritin HDL Trig Trig/HDL
31 Root Cause Solution applied for 8 Weeks: Continued <135 mmhg 95 <80 mmhg Ideal ~80 Ideal 32 Systolic BP Diastolic BP Weight (Kg) Waist (inches)
32 Root Cause Solution applied for 8 Weeks: Continued <135 mmhg 130 <80 mmhg 80 Ideal ~80 82 Ideal Systolic BP Diastolic BP Average of 20+ readings from same Equipment Weight (Kg) Waist (inches)
33 Root Cause Solution applied for 8 Weeks: Continued <135 mmhg 130 <80 mmhg 80 Ideal ~82Kg 82.5 Ideal Systolic BP Diastolic BP Average of 20+ readings from same Equipment Weight (Kg) Waist (inches)
34
35 Fat Chol Fat Chol Fat Fat Chol Chol Fat Chol Fat Chol Chol Chol Chol
36 PART 2 Beyond Cholesterol To The Primary Metrics and Drivers of Heart Disease
37 Google Cholesterol Conundrum
38 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 )
39 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
40 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
41 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
42 (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
43 Risk of Insulin Resistance (Lower) 4 3 ( Trig/HDL) 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,
44 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: ?????? Total/HDL < 5.0 LOW LDL GROUP (average 2.76 mmol/l) Total/HDL < 5.0 HIGH LDL GROUP (average 4.53 mmol/l)
45 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: ?????? 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)
46 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: ?????? 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)
47 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
48 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
49 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
50 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
51 Insulin Resistance as a Predictor of Age-Related Diseases The Journal of Clinical Endocrinology & Metabolism 86(8): 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?
52 Insulin Resistance as a Predictor of Age-Related Diseases The Journal of Clinical Endocrinology & Metabolism 86(8): 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?
53 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):
54 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):
55 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):
56 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 )
57 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
58 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 / kcj
59 2015 Euroaspire - CHD and Diabetes Status Those with cardiovascular disease not identified with diabetes are simply undiagnosed - Dr. Joseph R. Kraft
60 2015 Euroaspire - CHD and Diabetes Status
61 2015 Euroaspire - CHD and Diabetes Status Known Diabetics! Non-Diabetic CAD Victims ~7,000 CAD Victims Across All of Europe
62 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
63 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
64 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
65 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
66 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.
67 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.
68 Very Latest Data Feb 15 th Medscape
69 Very Latest Data Feb 15 th Medscape IF YOU DOn t MEASURE It, It DOn t GEt FIXED.
70 PART 3 CVD Prevention The Root Cause Solution-Space
71 CAC: THE MASTER MEASURE Google Budoff Ivor
72 CAC: THE MASTER MEASURE Google Budoff Ivor
73 CAC: THE MASTER MEASURE Calcium Score Risk Equivalent 10-Year Event Rate, % 0 Very low Low Intermediate >400 High >1000 Very high 37 Reproducible and quantifiable Based on 100 s of thousands of subjects J Am Coll Cardiol Img. 2015;8(5):
74 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:
75 And what about CAC Score progression??
76 And what about CAC Score progression?? Starting CAC Score 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
77 And what about CAC Score progression?? Starting CAC Score Progression 15% per year Starting CAC Score 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
78
79 The Human Chronic Disease Spectrum
80 The Human Chronic Disease Spectrum Truly NON Diabetic
81 The Human Chronic Disease Spectrum Full Blown Diabetes Truly NON Diabetic
82 The Human Chronic Disease Spectrum Full Blown Diabetes Hyperinsulinemic Very Unhealthy Very Diabetic Truly NON Diabetic Euinsulinemic Healthy Non-Diabetic Hyperinsulinemic Unhealthy Pre-Diabetic
83 The Human Chronic Disease Spectrum Full Blown Diabetes Hyperinsulinemic Very Unhealthy Very Diabetic Truly NON Diabetic Euinsulinemic Healthy Non-Diabetic Hyperinsulinemic Unhealthy Pre-Diabetic
84 The Human Chronic Disease Spectrum Full Blown Diabetes Hyperinsulinemic Very Unhealthy Very Diabetic Truly NON Diabetic Euinsulinemic Healthy Non-Diabetic Hyperinsulinemic Unhealthy Pre-Diabetic
85 The Human Chronic Disease Spectrum Full Blown Diabetes Hyperinsulinemic Very Unhealthy Very Diabetic Truly NON Diabetic Euinsulinemic Healthy Non-Diabetic Hyperinsulinemic Unhealthy Pre-Diabetic
86 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
87 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 Calcium Scan PP Glucose Insulin
88 The Human Chronic Disease Spectrum Full Blown Diabetes YOU? Truly NON Diabetic
89 The Human Chronic Disease Spectrum Calcium Score Risk Equivalent 10-Year CVD Event Rate, % Full Blown Diabetes 0 Very low Low Intermediate >400 High >1000 Very high 37 All-Cause MORTALITY! Truly NON Diabetic
90 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
91 The Human Chronic Disease Spectrum Full Blown Diabetes FIX? Truly NON Diabetic
92 The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes? Truly NON Diabetic
93 The Human Chronic Disease Spectrum Fixing it with the 10 levers. Full Blown Diabetes Ref Carb / Sugar Proc Food Truly NON Diabetic Veg Oil
94 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
95 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
96 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
97 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
98 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
99 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
100 But in the end, Truth will out The Merchant of Venice (2:2)
101 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 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 years old High HDL People LDL being relevant - depends entirely on your HDL status
102 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
Guidelines on cardiovascular risk assessment and management
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