Correlation between

Coronary Heart Disease

and
Diabetes
(The ABC control for preventing CVD in diabetic patients)

Pugud Samodro
Lab/SMF Ilmu Penyakit Dalam FK Unsoed/RSUD Prof.Margono
Soekarjo
Purwokerto
Diabetes characteristic in
Indonesia
2007 - 2013

Source : Source :
Riskesdas 2007 Riskesdas 2013
 The Cardiovascular Continuum of Events
ACS
Coronary
Secondary Arrhythmia and
prevention
Thrombosis Stroke
Loss of Muscle

Myocardial Remodeling
Ischemia

Ventricular
CAD Dilatation

Atherosclerosis Congestive
Heart Failure
Primary
prevention Risk Factors End-stage
Heart Disease
( Dyslipidemia, BP, DM,
Insulin Resistance, Platelets,
Adapted from
Fibrinogen, etc)
Dzau et al. Am Heart J. 1991;121:1244-1263
Atherothrombosis: A Generalized
and Progressive Process
Unstable
angina ACS
MI
Ischemic
stroke/TIA
Critical leg
ischemia
Cardiovascularde
ath

Atherosclerosis Atherothrombosis

Stable angina
Intermittent claudication

Adapted from Stary HC et al. Circulation. 1995; 92: 135574, and Fuster V et al. Vasc Med.
1998; 3: 2319.
 What are the CHD risk
Factors?
Gender
Smoking
Age
BP control
Race
Lipid management
Family history
Physical activity
Weight
Diabetes
 CV Risk Factors in
Diabetes
12
10.0
10

8
Odds Ratio

6.5
6
3.2
4
2.3
2

0
Microalbuminuria Smoking Diastolic BP Cholesterol

Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.

9
Causes of death in Diabetes
Diabetes = Coronary Artery
Disease

11
DM Strongest RF for CVD

DM = CHD
12
ACS and Diabetes Up to 1 Year
25
P<0.0001
No Diabetes
20 21.3
% of patients

N = 3429
Diabetes P<0.0001
15 N = 1149
14.4 14.1
P=0.035
10
8.9 7.
P<0.0001 7.
5 1
9
3.9
1.8
0
In-Hospital Non-fatal MI 1-y All-Cause 1-y
Mortality Mortality Mortality/MI

Yan R, et al. Can J Cardiol 2003;19(suppl A):260A.

Duration of T2DM and CVD
48%

29%
24%
21%
15%

2 3-5 6-9 10-14 15+

Years after DM Diagnosis

Harris,Setal.;Type2DiabetesandAssociatedComplicationsinPrimaryCarein
Canada:TheImpactofDurationofDiseaseonMorbidityLoad.CDA2003.
Duration of DM - CV Mortality

4 p for trend <0.001

3.5
Relative Risk

3
2.5
2
1.5
1
0.5
0
<5 6 to 10 11 to 15 16 to 25 26 +

Duration of Diabetes (years)

Cho, et al. J Am Coll Card 2002:40:954.
 Life Expectancy with Diabetes

Years
DM
90 No DM 1600
80 1400
70 1200
60 Diabetes
1000 No Diabetes
50
800
40
600
30
400
20
10 200
0 0
Men Women Mortality rate/100,000

Hux JE, et al. Diabetes in Ontario, an ICES Practice Atlas 2003.

Clinical Outcome for Diabetes
4-year Follow-up

14
12
10
8
%
6
4
2
0
CV Death MI Stroke Dialysis

HOPE/MICROHOPE.Lancet2000;355:253.
 OASIS Study: Total
0.25
Mortality
Diabetes/CVD +, (n = 1148)
RR = 2.88 (2.37-3.49)
Diabetes/CVD -, (n = 569)
0.20 No Diabetes/CVD +, (n = 3503)
No Diabetes/CVD -, (n = 2796)
Event rate

0.15 RR=1.99 (1.52-2.60)

0.10 RR=1.71 (1.44-2.04)

0.05
RR=1.00

0.0

Months 3 6 9 12 15 18 21 24

Malmberg K, et al. Circulation 2000;102:10141019.

19
2013 ESC and EASD Guidelines on
Diabetes, Pre-diabetes and
Cardiovascular Disease
A, B, C Key targets* for Prevention of CV
Disease in DM

A: HbA1c <7%
B: BP <140/85 mmHg
C: LDL Cholesterol <70 mg/dL
*These targets should be applied with individual needs taken into account

http:www.escardio.org/GUIDELINES-SURVEYS/ESC-GUIDELINES/Pages/diabetes.aspx
 WHAT IS ABC
CONTROL ???
A = A1C = Glycemic control
B = Blood pressure control
C = Cholesterol-LDL control

These ABC,
major and modifiable risk factor
the primary target goals for the
prevention of
CVD
MANAGING HIDDEN CARDIOVASCULAR
RISK IN DIABETES MELLITUS

Three major risk factors:

Hyperglycemia, focus on A1C (A)
Blood pressure (B)
Cholesterol-LDL (C)
These 3 components, the primary
target goals, namely the ABC
goals
 A1C (GLYCAEMIC)
CONTROL AND CVD

Glucose control remains a major focus in the

management
of patients with type 2 diabetes mellitus
Studies (UKPDS, Kumamoto): reducing
hyperglycemia
decreases onset/progression of microvascular
compli-
cations BUT for CVD complications remains
uncertain
(ACCORD, ADVANCE, VADT)
In older patients, suggested that aggressive
The con-
glycemic new ADA-EASD statement
trol may present some risk
 GLYCEMIC RECOMMENDATION
FOR ADULTS (NON-PREGNANT)
Summary of glycemic recommendations for
nonpregnant adults with diabetes
A1C 7.0%*
Preprandial capillary
plasma glucose 80 - 130 mg/dL* (4.4 7.2
mmol/L)
Peak postprandial capillary
plasma glucose
180 mg/dL* (10.0 mmol/L)
*More or less stringent glycemic goals may be appropriate for individual patients.
Goals should be
individualized based on duration of diabetes, age/life expectancy, comorbid
conditions, known CVD
or advanced microvascular complications, hypoglycemia unawareness, and individual
patient
considerations.
Postprandial glucose may be targeted if A1C goals are not met despite reaching
preprandial
glucose goals. Postprandial glucose measurements should be made 12 h after the
beginning of the
 ANTIDIABETIC AGENTS

OLD agents:
Metfromin, Sulfonilurea, a-glucosidase
inhibi-tor, TZDs/Piogtazone

NEW agents:
DPP-4 inhibitors, SGLT2 inhibitors, GLP-
1recep-
tor agonist, insulin analog
The implementation strategies: ADA-
EASD 2015
A Patient-Centered Approach
 ADA EASD
PATIENT CENTERED
 HEALTHY, EATING, WEIGHT CONTROL, INCREASED PHYSICAL ACTIVITY
Initial drug
monotherapy Metfomin
If needed to reach individualized HbA1c target after 3 months, proceed to two-drug combination (order not
meant to denote any specific preference)

Two-drug Metfomin Metfomin Metfomin Metfomin Metfomin

combinations + + + + +
SUb TZD DPP-4 I Insulin basal GLP-1 RA
If needed to reach individualized HbA1c target after 3 months, proceed to three-drug combination
(order not meant to denote any specific preference)
Three-drug Metfomin Metfomin Metfomin Metfomin Metfomin
combinations + + + + +
SUb TZD DPP-4 I Insulin basal GLP-1 RA
+ + + + +
TZD SUb SUb TZD SUb
or or or or or
DPP-4 I DPP-4 I TZD DPP-4 I TZD
or or or or or
Insulind Insulind Insulind GLP-1 RA Insulind
or or
GLP-1 RA GLP-1 RA
If combination therapy that includes basal insulin has failed to achieve HbA1c target after 3-6 months,
proceed to more complex insulin strategy, usually in combination with one or two non-insulin agents

More complex Insuline (multiple daily doses)

insulin strategies
Inzucchi SE, et al. ADA and EASD. Diabetes Care 2012; 19 April
BLOOD PRESSURE (B)
CONTROL AND CVD IN
DIABETIC PATIENTS
 PREVALENCE OF
HYPERTENSION
IN TYPE 2 DIABETES
Normoalbuminuria (UAE 30 Macroalbuminuria (UAE 300
mg/day) mg/day)
Microalbuminuria (UAE 30-300 All patients
mg/day) 100 93
90
80
71

Prevalence
of
hypertensio 50
n
(%)

0 n=3 n=15 n=7 n=5

23 1 5 4
Hypertension defined as 140/90
mm Hg. Tarnow L et al. Diabetes Care
 250

225
Without
CV mortality rate/ 10.000

diabetes
200
With
diabetes
175
person-years

150

125

100

7
5
5
0
2
5
0
< 120- 140- 160- 180- >
120 139 159 179 199 200
Systolic blood pressure
(mmHg)
Association of systolic blood pressure and CV death
in type 2 diabetes The Lancet 2000; 36: 1955 -
 BLOOD PRESSURE (B) CONTROL ADA
2015
BP should be measured at EVERY
routine visit
The target goals:
Systolic BP < 140 mmHg
Diastolic BP < 130 mmHg
Lower BP, systolic < 130 mmHg,
diastolic < 80 mmHg
for younger patients
Pharmacologic therapy:
either ACE inhibitors or ARB
multiple drug combination is generally
required
 BLOOD PRESSURE (B) CONTROL ADA
2015
Intensive BP target (upper limit of Syst < 130
and Diast < 80 mmHg) vs Standard BP target
(upper limit Syst 140-160, Diast 85-100
mmHg:
- no significant reduction in mortality or
non-fatal MI
BUT statistically reduction in stroke
ACCORD study, SBP < 120 mmHg compared to
SBP 130-140 mmHg, no benefit
ADVANCE study, BP 136/73, 6 yr follow up,
significant reduction of death any cause, and
CVD
 CHOLESTEROL LDL (C)
CONTROL AND CVD IN
DIABETIC PATIENTS
Paradigm shift from:
Treat - to -Target
to
Intensive Statin Therapy
(Gupta A: Endocrinol Metab Clin N Am 2014;43:869-892)
NCEP ATP III LIPID GUIDELINE LDL-C GOALS FOR
DIFFERENT RISK CATEGORIES : TREAT TO TARGET
Risk category LDL goal LDL level at LDL level
at which
(mg/dL) which to initiate to consider
drug
therapeutic life therapy (mg/dL)
style changes
(mg/dL)
0-1 risk factor < 160 > 160 > 190 (160-
189: LDL-lowering
drug optional)

2+ risk factors < 130 > 130 10-y risk

(10-y risk < 20%) 10%-20%: 130
10-y risk
< 10%: 160

CHD or CHD risk < 100 > 100 > 100 (100-
129:
Gupta A, et al. Endocrinology and drug
equivalents metabolism clinics of North America
optional)
2014; 869-912
(10-y risk > 20%)
 The ACC/AHA Guidelines,
November 2013

ACC, American College of Cardiology

AHA, American Heart Association
36
ACC/AHA GUIDELINES, THE 4 STATIN BENEFIT
GROUPS

Group 1 Group 2

Clinical ASCVD LDL-C 190

CHD, stroke, and
mg/dL
peripheral arterial (~5 mmol/L)
disease, all of
presumed
atherosclerotic
origin

Group 3 Group 4

Diabetes ASCVD risk

mellitus 7.5%

+ age of 4075 No diabetes

years + age of 4075
+ LDL-C 70189 years
mg/dL (1.84.9 + LDL-C 70189
mmol/L) mg/dL (1.84.9
ASCVD, atherosclerotic cardiovascular disease mmol/L)
CHD, coronary heart disease
LDL-C, low-density lipoprotein-cholesterol Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print
 WHO TO TREAT: NEW US GUIDELINES
WHICH TRIALS SUPPORT WHICH
GROUPS?
Trials:
Group 1 Group 2
ALLIANCE-
Clinical Trials:
Atorva
LDL-C 190 mg/dL None
PROVE-IT-Atorva ASCVD
SPARCL-Atorva CHD, stroke, and
peripheral arterial
disease, all of presumed
atherosclerotic origin

Group 3 Group 4
Trials: Trials:
CARDS-Atorva ASCOT LLA-
Diabetes ASCVD risk 7.5%
TNT*-Atorva Atorva
HPS*-Simva mellitus No diabetes HPS-Simva
+ age of 4075 years JUPITER-Rosuva
+ age of 4075 years + LDL-C 70189 mg/dL
+ LDL-C 70189 mg/dL

* Subgroup analysis
Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub
 AMERICAN COLLEGE OF CARDIOLOGY
AND AMERICAN HEART ASSOCIATION
(ACC-AHA), 13 November 2013
The guideline focuses on: Treatment of blood
cholesterol
to reduce atherosclerotic cardiovascular disease
(ASCVD)
What is new in the ACC-AHA:
1. Identification of 4 Statin Benefit Groups
- Individuals with clinical ASCVD
- Individuals with primary elevation of LDL-C
> 190
mg/dL
- Individuals 40-75 years of age with diabetes
with
LDL-C 70-189 mg/dL
- Individuals without clinical ASCVD or
 AMERICAN COLLEGE OF CARDIOLOGY
AND AMERICAN HEART ASSOCIATION
(ACC-AHA), 13 November 2013

What is new in the ACC-AHC

2. New ASCVD risk score
3. Different class of LDL-C target:
High- intensity statin therapy
Moderate- intensity statin therapy
Low- intensity statin therapy (next table)
4. Statin use:
High intensity statin therapy lowering LDL-C
> 50%
Moderate intensity statin therapy lowering
LDL-C 30% - < 50%
 Group 3. Diabetes, age 4075 years, LDL-C 70189 mg/dL
High- or moderate-intensity statin recommended

Type 1 or 2 diabetes

No Consider statin
Age 4075 years
individually
Yes

Estimate 10-year ASCVD risk

with Pooled Cohort Equations

ASCVD risk ASCVD risk

7.5% <7.5%

High-intensity Moderate-intensity
statin* statin

*Expected to reduce LDL-C by 50%

Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print

Expected to reduce LDL-C by 30 to <50%

41
ttp://www.tools.cardiosource.org/ascvd-risk-estimator
 Group 3. Diabetes, age 4075 years, LDL-C 70189 mg/dL
High- or moderate-intensity statin recommended

ACC/AHA guidelines for statin therapy

High-intensity
therapy*
Atorvastatin 4080 mg
Rosuvastatin 2040 mg
Moderate-intensity
Low-intensity therapy
therapy
Atorvastatin 1020 mg Simvastatin 10 mg
Rosuvastatin 510 mg Pravastatin 1020 mg

Simvastatin 2040 mg Lovastatin 20 mg

Pravastatin 4080 mg Fluvastatin 2040 mg

Lovastatin 40 mg Pitavastatin 1 mg

Fluvastatin XL 80 mg

Fluvastatin 40 mg BID

Pitavastatin 24 mg

*LDL-C reduced by 50%; Reprinted from J Am Coll Cardiol, ePub ahead of print, Stone NJ, Robinson J, Lichtenstein AH,

LDL-C reduced 3050%; Bairey Merz CN, et al., 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce
Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of

LDL-C reduced <30% Cardiology/American Heart Association Task Force on Practice Guidelines. Copyright (2013), with
BID, 43
twice daily dosing permission
Adapted from Stone NJ, et al. J Am Coll Cardiol 2013 Nov from Elsevier
7. Epub ahead
of print
Recommendations for Nonstatin Drugs

The panel could find no data

supporting the routine use of
nonstatin drugs added to statin
therapy to further reduce ASCVD
events
In addition, identification of any RCTs
that assessed ASCVD outcomes in
statin-intolerant patients was not
found
2013 ACC/AHA Guideline on the Treatment of Blood
 American Diabetes Association Standards of
Care 2015

Recommendations for statin treatment and lipid monitoring were revised after consideration of 2013
ACC/AHA guidelines on the treatment of blood cholesterol
In light of this fact, the 2015 ADA Standards of Care have been revised to recommend when to initiate
and intensify statin therapy (high versus moderate) based on risk profile
Treatment initiation (and initial statin dose) is now driven primarily by risk status rather than LDL
cholesterol level

American Diabetes Association. Diabetes Care 2015;38(Suppl. 1):S49S57

 SUMMARY
CVD is the most common cause of death among
diabetic patients
For the prevention, focus on Glycemic (A1C),
Blood pressure (B), and Cholesterol LDL (C) control

A1C, intensive, ADA combination

Blood pressure, ACE, ARB, mostly combination
Cholesterol LDL, statin first line, high dose in high
risk

From the ABC target goals, A1C is the most

difficult target
THANK YOU