Bambang Irawan SpPD [K], SpJP [K],

FIHA, FASCC, FINASIM

Internist [SpPD] 1981

Cardiovascular Consultant [KKV] 1996
Cardiologist [SpJP] 2004
Fellow of Indonsian Heart Association[FIHA] 2004
Cardiologist Consultant [K] 2005
Professor in Cardiology [ Prof ] 2006
Fellow of Asean College Cardiology[FASCC] 2008
Fellow of Ind Society of Internal Medicine 2009
 VBWG
CARDIOMETABOLIC SYNDROME : PROFILING
THE RISK FACTOR FOR ATHEROSKLEROSIS

PROF DR BAMBANG IRAWAN MD FIHA FASCC FINASIM

DEPARTMENT OF CARDIOLOGY , FACULTY OF MEDICINE,
GADJAHMADA UNIVERSITY
 Coronary Heart Disease
a global burden disease

CVDs are the no. 1 cause of death globally

In 2005 An estimate 17.5 million people died from CVDs, representing
30% of all global deaths. Of these deaths, an estimated 7.6 million were
due to coronary heart disease and 5.7 million were due to stroke.
Over 80% of CVD deaths take place in low- and middle-income
countries
By 2015 Almost 20 million people will die from CVDs, mainly from heart
disease and stroke. These are projected to remain the single leading
cause of death.

Source :
WHO Cardiovascular Fact Sheer. February 2007
CRE027/Jul07-Jul08/TEP | RTD Master Slide 2nd Semester
 Atherosclerosis and its clinical impact
Cerebrovascular disease
Transient ischaemic attack (TIA)
Stroke

Cardiovascular disease
Angina
Heart attack
Heart failure

Others
Claudicatio intermiten
Gangren
I
CRE027/Jul07-Jul08/TEP | RTD Master Slide 2nd Semester
Inflammation Promotes Progression of
Atherosclerosis
Vessel lumen
Monocyte
LDL

Endothelium
Adhesion
molecules
(VCAM-1, ICAM-1) LDL

Inflammatory mediators
(CRP, CD40/CD40L, Ox-LDL
TNF-, IL-1, IL-6)
Foam Intima
cell
Macrophage
CD40L=CD40 ligand; TNF-=tumor necrosis factor-alpha; IL=interleukin; VCAM=vascular cell adhesion molecule;
ICAM=intercellular adhesion molecule.
Cockerill GW et al. Arterioscler Thromb Vasc Biol. 1995;15:1987-1994; Andre P et al. Circulation. 2002;106:896-899; Libby
P. Circulation. 2001;104:365-372; Libby P et al. Circulation. 2002;105:1135-1143; Ross R. N Engl J Med. 1999;340:115-126.
 Atherosclerosis Timeline
Foam Fatty Intermediate Atheroma Fibrous Complicated
Cells Streak Lesion Plaque Lesion/
Rupture

Endothelial Dysfunction
From First From Third From Fourth
Decade Decade Decade

Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 10A):23S-27S.

CRE027/Jul07-Jul08/TEP | RTD Master Slide 2nd Semester
Cardiometabolic Risk
 Criteria for Clinical Identification of the
Metabolic Syndrome According to ATP III

1. waist circumference >40

inches for men or 35 inches
for women
2. triglycerides 1.7 mmol/L
3. HDL-C <1.0 mmol/L for men
or <1.3 mmol/L for women
4. BP 130/ 85 mm Hg
5. fasting glucose 110 mg/dl

3 of 5 required for diagnosis

Standard Criteria for Body Mass Index (kg/m2)

<18.5 - underweight
18.5 to <25.0 - healthy weight
25.0 to <30.0 - overweight
30.0 to <40.0 - obesity
>=40.0 - morbid obesity

Sowers JR 2001 Clin Cornerstone 4[2]:17-23

Abnormal Lipid Metabolism

Increased Decreased
Triglycerides HDL

VLDL Apo-I

LDL and small dense LDL

Apo-B

American Diabetes Association. Diabetes Care 2007;30:S4-41.

Clinical Management of the Metabolic Syndrome

The underlying risk factors that promote

development of the metabolic syndrome are
overweight and obesity, physical inactivity, and an
atherogenic diet. All current guidelines on the
management of the individual components of the
metabolic syndrome emphasize that lifestyle
modification (weight loss and physical activity) is
first-line therapy.

Grundy et al, Circulation 2004;109:551

 Relationship between atherosclerosis
and diabetes
Prevalence of death in diabetes

45
40
35
30
25
20
% of deaths

15
10
5
0
Ischemic Diabetes Cancer Stroke Infection Other
Other
heart
heart
disease
disease

Complications of atherosclerosis cause most mortality in patients

with diabetes mellitus
Geiss LS et al. In: Diabetes in America, 2nd ed. Bethesda, MD NIH;1995.
Complications of Hypertension
in Patients with Diabetes

Microvascular Macrovascular
Renal disease Cardiac disease

Autonomic neuropathy Cerebrovascular disease

Eye disease (glaucoma, retinopathy Reduced survival and recovery rates

with potential blindness) from stroke

Peripheral vascular disease

American Diabetes Association. Diabetes Care 2007;30:S4-41.

Type 2 Diabetes and
Coronary Heart Disease
7-Year Incidence of Fatal/Nonfatal MI From the East-West Study
Myocardial Infarction (%)

50
7-year Incidence Rate of

45
45 Nondiabetic (n=1373)
40 Diabetic (n=1059)
35
30
25 20.2
20 18.8*

15
10
5 3.5
0
No DM, no MI No DM, MI DM, no MI DM, MI

* p<0.001 vs. nondiabetic, no MI

p<0.001 vs. diabetic, no MI

Haffner SM et al. N Engl J Med 1998;339:229-34.

Does improved glycemic control
reduce CVD risk?

Studies show that treating lipid disorders and hypertension

reduces CVD risk, and yet 65% of primary care physicians
believe that glycemic control is more effective in
preventing CVD
Improved glycemic control can prevent onset or
progression of microvascular complications
BUT:
We need to aggressively treat all of the commonly
associated features of diabetes in order to effectively
reduce patient CVD risk

Marks J. Clin Diab 2003;21:99-100.

Targets for Common CVD
Risk Factors in Patients with Diabetes
Recommendations for glycemic, blood pressure,
and lipid control for adults with diabetes

A1C <7.0%
Blood pressure 130/80 mmHg
Lipids
LDL-C <100 mg/dL (2.6 mmol/L)*

* In patients with overt CVD, treatment with a statin to lower LDL-C to <70 mg/dL
(<1.8 mmol/L) is an option.

American Diabetes Association. Diabetes Care 2008;31(1):S12-S54.

Treatment Goals for Adults with CMR
and Lipoprotein Abnormalities
Goals
LDL HDL Apo-B
Cholesterol Cholesterol (mg/dL)
(mg/dL) (mg/dL) (mmol/L)
(mmol/L) (mmol/L)
Highest-risk patients,
including those with known CVD <70 <100 <80
or diabetes, plus 1 or more (<1.8) (<2.6) (<2.1)
additional major CVD risk factors.
High-risk patients, including those
with no diabetes or known clinical
CVD, but 2 or more additional <100 <130 <90
major CVD risk factors OR (<2.6) (<3.4) (<2.3)
diabetes but no other major CVD
risk factors.

Brunzell JD et al. J Am Coll Cardiol 2008;51:1512-24.

Reducing CVD in Diabetes

New treatment targets may include:

Specific treatment of dyslipidemia
Active anti-inflammatory treatments
Reduction of inflammatory activity in adipose tissue
Reduced volume of adipose tissue
Antioxidants

Wiklund O et al. J Intern Med 2007;262(2):199-207.

 Risk factors for vascular disease in metabolic syndrome [2]

Hypertension

Vascular complication Risk reduction Significance

Heart failure 56% P=0.0043

Myocardial infarction 21% Not significant
Stroke 44% P=0.013
Combined macrovascular complications 34% P=0.019
Retinal photocoagulation 35% P=0.023
Microalbuminuria 29% P=0.009
Combined microvascular complications 37% P=0.009

An agressive approach to the control of blood pressure considerably

reduces the risk of both microvascular and macrovascular disease

1. UK prospective diabetes study group. BMJ. 1998;317:705-713.

Blood Pressure Target
(WHO-ISH, 1999)

140/90
130/85 (Diabetes Mellitus, young adult)
130/80 (Proteinuria)
125/75 (Proteinuria > 1 gr / day)
Hypertension: Evaluation and Screening

Persons Without Diabetes Persons with Diabetes

BP should be measured at each BP should be measured at each
regular visit or at least once every regular visit
2 years if BP <120/80 mmHg

BP measured seated after 5-min rest BP measured seated after 5-min rest
in office in office

Patients with 130 or 80 mmHg should

have BP confirmed on a separate day

American Cancer Society, American Diabetes Association, American Heart Association.

Circulation 2004;109:3244-55. Diabetes Care 2007;30:S4-41.
Management of Hypertension

Non-pharmacologic Pharmacologic
DASH diet If BP 140 / 90 mmHg, drug therapy
Dietary Approaches to Stop is indicated
Hypertension
High in whole grains, fruits,
vegetables, and low-fat dairy
Low in saturated and trans fat,
cholesterol
Physical activity Combination therapy often necessary

Weight loss, if applicable Treatment should include ACE or ARB

Thiazide diuretic may be added to
reach goals
Monitor renal function and serum potassium

American Diabetes Association. Diabetes Care 2007;30:S4-41.

Adopt DASH eating plan
Lifestyle Modifications

Modification Approximate SBP reduction

(range)

Weight reduction 520 mmHg/10 kg weight loss

Adopt DASH eating plan 814 mmHg

Dietary sodium reduction 28 mmHg

Physical activity 49 mmHg

Moderation of alcohol 24 mmHg

consumption
 Risk factors for vascular disease in metabolic syndrome
[3]

Dyslipidemia

Risk LDL-cholesterol HDL-cholesterol Triglyceride

Higher 3.35 ( 130) <0.90 (<35) 4.50 ( 400)

Borderline 2.60-3.34 (100-129) 0.90-1.15 (35-45) 2.30-4.49 (200-399)

Lower <2.60 (<100) >1.15 (>45) <2.30 (200)

> High levels of LDL-cholesterol and low levels of HDL-cholesterol

are both significant risk factors1

1. American Diabetes Association.Diabetes care. 1998;21(suppl 1): S36-S39.

Risk factors for vascular disease in diabetes [4]

Microalbuminuria

Microalbuminuria (defined as a urinary albumin excretion rate

of 30 to 300 mg/24 hours) is a major independent risk factor
for early mortality in patients with type 2 diabetes,
greatly increasing the risk of both microvascular
(particularly nephropathy) and macrovascular complications

Smoking

Smoking is a significant risk factor for coronary heart disease

in patients with type 2 diabetes
 Risk factors for vascular disease in diabetes (5)

Prothrombotic state

In patients with diabetes, the coagulation system is switched

to a prothrombotic state that enhances the risk of vascular complications,
particularly macrovascular events

Obesity

Moderate weight loss of 5 to 9 kg, irrespective of starting weight, has

been shown to reduce hyperglycemia, dyslipidemia,
and hypertension1

1. American Diabetes Association. Diabetes Care. 1998; 21 (suppl 1): S23-S31.

 Prevention of cardiovascular disease (CVD)

Lifestyle intervention
Diet
Physical exercise

Glycemic control

Treatment of high blood pressure and lipid levels

Antithrombotic therapy

Rosano MCG, ed. Diabetes and Cardiovascular Disease. Abingdon, UK: Wolters Kluwer Health; 2005.
Total risk management
Lifestyle and risk factor goals
Healthy food choices
Be physically active
Achieve ideal weight
Reduce blood pressure to < 140/90 mmHg
Reduce total cholesterol to < 5.0 mmol/l (190 mg/dl)
Reduce LDL cholesterol to <3.0 mmol/l (115 mg/dl)
Achieve optimal glycaemic and blood pressure control
in patients with diabetes mellitus (HbA level between
6.2 and 7.5%) and a blood pressure <130/85 mmHg
.