Cardiovascular disease and diabetes Vascular harmony

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1 Cardiovascular disease and diabetes 2018 Vascular harmony Robert Chilton Professor of Medicine University of Texas Health Science Center Director of Cardiac Catheterization labs Director of clinical proteomics

Diabetes phenotype HT Diabetes Smoking 0 Odds ratio (99% CI)

2 INTERHEART trial: 9 modifiable risk factors account for 90% of myocardial infarctions All 4 & obesity ALL 4 ApoB/apoA1 Diabetes phenotype HT Diabetes Smoking 0 Odds ratio (99% CI) All significant Very high risk Lancet 2004; 364:

3 Overview of the largest world Pandemic Obesity / diabetes Heart Blood vessel lining Peripheral vascular disease Smoking Diabetes Diabetes Blood pressure Eyes Kidney Diabetes Blood pressure

Healthy lifestyle: healthy endothelial cells (1.

Biological biomarkers Genetics Age Inside look at your blood

Glucose Insulin resistance Oscillatory blood pressure

4 Healthy lifestyle: healthy endothelial cells (1.6 trillion cells) lining 60,000 miles of blood vessels Biological biomarkers Genetics Age Inside look at your blood vessel Metabolic biomarkers Inflammation Lipids BNP Troponin Glucose Insulin resistance Oscillatory blood pressure (hypertension) Mechanical biomarkers Blood pressure Pulse wave velocity Central aortic pressure

Healthy endothelial cells endothelial cells dysfunction years ahead of risk factors Vascular wall cell signaling Antioxidants Nitric oxide tpa Others

5 Healthy endothelial cells endothelial cells dysfunction years ahead of risk factors Vascular wall cell signaling Antioxidants Nitric oxide tpa Others Human glycocalyx Aging Genetics Metabolics Inflammation LIPIDS Insulin resistance Epigenetics Others Introduction Oscillatory blood pressure (hypertension)

Significantly related to BMI Sustain about 0.

6 Damaged by free radicals (ROS) 1-3 horsepower on average Fuel plant Most common fuel Sugar Free fatty acids Ketones 38 lbs/atp per day Diabetes and heart disease Significantly related to BMI Sustain about 0.25 hp World class 0.54 hp Never rests.at least not for long

7 .nothing beats healthy weight loss and lifestyle Absolute risk reduction 95% failure rate Rough estimates Percentage Drugs Normal weight/exercise

8 Diabetes ( 80% HT / bad lipids) Longer you have disease more free radial damage

9 Intensively target Healthy lifestyle Control BP, Lipids, Glucose vs Control N Engl J Med 2008;358:580-91

10 N Engl J Med 2008;358:580-91

11 N Engl J Med 2008;358:580-91

12 Steno-2 N Engl J Med 2008;358:580-91

13 Picture review of diabetes and vascular disease.adjusted for current proven outcome results There is no primary and secondary prevention..its all atherosclerosis Lifestyle still wins

15 The eye of diabetes

16 Protecting your kidney with diabetes N Engl J Med 2016;375:323-34

17 SGLT 2 inhibitors

18 RISK CATEGORIES AND LDL-C TREATMENT GOALS Risk category Risk factors/10-year risk LDL-C (mg/dl) Treatment goals Non-HDL-C (mg/dl) Apo B (mg/dl) Extreme risk Progressive ASCVD including unstable angina in individuals after achieving an LDL-C <70 mg/dl Established clinical cardiovascular disease in individuals with DM, stage 3 or 4 CKD, or HeFH History of premature ASCVD (<55 male, <65 female) <55 <80 <70 Very high risk Established or recent hospitalization for ACS, coronary, carotid or peripheral vascular disease, 10-year risk >20% DM or stage 3 or 4 CKD with 1 or more risk factor(s) HeFH <70 <100 <80 High risk 2 risk factors and 10-year risk 10%-20% DM or stage 3 or 4 CKD with no other risk factors <100 <130 <90 Moderate risk Low risk 2 risk factors and 10-year risk <10% 0 risk factors <100 <130 <90 <130 <160 NR Endocr Practice. 2017;23(4):

19 Am J Physiol Heart Circ Physiol 298: H158 H162 Anterior / apex

20 8 months before NIRS-IVUS 30 y/o/ Hispanic type 2 DM male A1c 8.5 Obese HDL low High triglycerides Biopsy proven NASH

21 Radial case

22 Glucosecentric approach: failed to reduce CV events Treatment for diabetes patients 7.5% risk in 10 years Glucose-centered approach EVENT drive endpoint after EMPA-REG / LEADER 2015 Decreased CV death Decreased CV events Reduced progression of kidney disease Reduced hospital readmission for HF Target glucose number

23 N Engl J Med 2012;367:

Insulin Non insulin 29 28 29 28 35 30 25 20 15 19.7 30.4 14.

24 Insulin Non insulin % PCI 26 CABG 25 High risk>33 Low risk< PCI CABG Low risk<22 High risk>33 High risk>33 Low risk<22 Low risk<22 High risk>33 5 year % rate of Death/MI/Stroke 5-Year Event Rates (overall): 26.6% PCI vs. 18.7% CABG J Am Coll Cardiol 2014;64:

25 CV death Reduced weight Reduced BP Renal vascular protection Heart failure New cardiovascular agents for diabetes patients Peripheral artery disease

26 CV death

27 EMPA reg

28 FDA June 16, 2016

29 CANADIAN DIABETIC ASSOCIATION GUIDELINE UPDATE 2016 Pharmacological Management of Type 2 Diabetes --In people with clinical cardiovascular disease in whom glycemic targets are not met, an SGLT2 inhibitor with demonstrated cardiovascular outcome benefit should be added to antihyperglycemic therapy to reduce the risk for cardiovascular and all-cause mortality (Grade A, Level 1A for empagliflozin) Canadian Journal of Diabetes

30 Metabolic treatment 2 treatments known to extend life expectancy/cv death in diabetes Trial CV events CV death Kidney protection EMPA-SGLT2I Yes Yes Yes CANA Yes No YES LIRA-GLP-1 Yes Yes YES SEMA Yes No YES Statins Yes No NO PCSK9 Yes No NO New era- cardiorenal agents for T2DM

Fasting or non fasting?

Fasting or non fasting? Vascular harmony Robert Chilton Professor of Medicine University of Texas Health Science Center Director of Cardiac Catheterization labs Director of clinical proteomics Which is best to measure Lower continues