Vascular harmony
Cardiovascular disease and diabetes 2018
Robert Chilton
Professor of Medicine
University of Texas Health Science Center
Director of Cardiac Catheterization labs
Director of clinical proteomics
Very high
risk
INTERHEART trial: 9 modifiable risk factors account for 90%
of myocardial infarctions
Smoking
Diabetes
HT
ApoB/apoA1
ALL 4
All 4 & obesity
010
2030
4050
6070
Odds ratio (99% CI)
All significant
Diabetes phenotype
Lancet 2004; 364: 937–52
Overview of the largest world
Pandemic……Obesity / diabetes
Smoking
Diabetes
Diabetes
Blood pressureDiabetes
Blood pressure
Heart
Peripheral vascular disease
KidneyEyes
Blood vessel lining
Inside look at your
blood vessel
Healthy lifestyle: healthy endothelial cells
(1.6 trillion cells) lining 60,000
miles of blood vessels
Biological biomarkers
Mechanical biomarkers
Metabolic biomarkers
Genetics
Age
Blood pressure
Pulse wave velocity
Central aortic pressure
Inflammation
Lipids
BNP
Troponin
Glucose
Insulin resistance
Oscillatory blood pressure
(hypertension)
IntroductionOscillatory blood pressure (hypertension)
Vascular wall cell signaling
Healthy endothelial cells“endothelial cells dysfunction years ahead of
risk factors”
Antioxidants
Nitric oxide
tPA
Others
Human glycocalyx
Aging
Genetics
Metabolics
Inflammation
LIPIDS
Insulin resistance
Epigenetics
Others
1-3 horsepower on average
Sustain about 0.25 hp
World class 0.54 hp
Most common fuel
Sugar
Free fatty acids
Ketones
Fuel plant
38 lbs/ATP per day
Damaged by free radicals (ROS)
Never rests….at least not for longDiabetes and heart disease
Significantly related to BMI
….nothing beats
healthy weight
loss and lifestyle
0
10
20
30
40
Drugs Normal
weight/exercise
Absolute risk reduction
Rough estimates
Percentage
95% failure rate
Diabetes (≈80% HT / bad lipids)
Longer you have disease
more free radial damage
•
•
•
Healthy lifestyle
Control BP, Lipids, Glucose
Intensively target
Controlvs
N Engl J Med 2008;358:580-91
N Engl J Med 2008;358:580-91
N Engl J Med 2008;358:580-91
N Engl J Med 2008;358:580-91
Steno-2
Picture review of diabetes and vascular disease
…….adjusted for current proven outcome results
Lifestyle still wins
There is no primary and secondary prevention…..its all atherosclerosis
The eye of diabetes
Protecting your kidney with diabetes
N Engl J Med 2016;375:323-34
SGLT 2 inhibitors
RISK CATEGORIES AND LDL-C TREATMENT GOALS
Risk category Risk factors/10-year risk
Treatment goals
LDL-C
(mg/dL)
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
≤2 risk factors and 10-year risk <10%
<100 <130 <90
Low risk0 risk factors
<130 <160 NR
Endocr Practice. 2017;23(4):479-497
Anterior / apex
Am J Physiol Heart Circ Physiol 298: H158–H162
NIRS-IVUS
8 months before
30 y/o/ Hispanic
type 2 DM male
A1c 8.5
Obese
HDL low
High triglycerides
Biopsy proven
NASH
Radial case
Glucosecentric approach: failed to reduce CV events
Glucose-centered approach EVENT drive endpoint after EMPA-REG / LEADER
Treatment for diabetes patients 7.5% risk in 10 years
2015Decreased CV death
Decreased CV events
Reduced progression of kidney disease
Reduced hospital readmission for HF
Target glucose number
N Engl J Med 2012;367:2375-84
Low risk<22
High risk>33
0
5
10
15
20
25
30
35
PCI CABG
19.7
14.1
30.4
20
Non insulin
Low risk<22 High risk>33
Low risk<22
High risk>33
23
24
25
26
27
28
29
PCI CABG
29
26
28
25
Insulin
Low risk<22 High risk>33
5 year % rate of Death/MI/Stroke
%
J Am Coll Cardiol 2014;64:1189–97
5-Year Event Rates (overall): 26.6% PCI vs. 18.7% CABG
New cardiovascular agents for diabetes patients
CV death
Peripheral artery disease
Heart failure
Renal vascular protection
Reduced weight
Reduced BP
CV death
EMPA reg
FDA June 16, 2016
CANADIAN DIABETIC ASSOCIATION
GUIDELINE UPDATE 2016
--In people with clinical cardiovascular disease in whom glycemictargets are not met, an SGLT2 inhibitor with demonstratedcardiovascular outcome benefit should be added toantihyperglycemic therapy to reduce the risk for cardiovascularand all-cause mortality (Grade A, Level 1A for empagliflozin)
Pharmacological Management of Type 2 Diabetes
Canadian Journal of Diabetes 2016 http://dx.doi.org/10.1016/j.jcjd.2016.02.006
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
Metabolic treatment
New era- cardiorenal
agents for T2DM
