Syndrome X (High Risk for CHD)

Consists of:
Insulin Resistance
Decreased HDL Cholesterol
Hypertriglyseridemia
Hypertension

The Metabolic Syndrome:

Reduced glucose tolerance

Hyperinsulinemia
Hypertension
Visceral obesity
Hemostatic disorders
Lipid disorders:
o Triglycerides elevated
o LDL-cholesterol normal or moderately elevated
o HDL-C diminished

ATP-III has established a practical definition of the

Metabolic Syndrome

The Metabolic Syndrome consists of highly concordant risk factors

linked to an increased risk of CHD:
1. Abdominal obesity as defined by
Waist circumference > 102 cm in men WHO Western
Pacific 90cm
Waist circumference > 88 cm in women WHO Western
Pacific 80cm
2. TG 150 mg/dl
3. HDL-C in men < 40 mg/dl, in women < 50 mg/dl
4. Blood pressure 130/85 mm Hg
5. Fasting plasma glucose 110 mg/dl
The presence of 3 or more of the above identify the Metabolic
Syndrome in an individual patient

The WHO has developed criteria of the Metabolic

Syndrome strongly focused on impaired glucose
regulation

At least one of the following criteria of insulin resistance and

impaired glucose regulation
- impaired fasting glucose (FPG 110 mg/dl)
- impaired glucose tolerance (2h PG 140 mg/dl)
- elevated insulin levels (4th quartile of reference)
- Diabetes Mellitus (DM)
Plus two or more of the following:

Systolic blood pressure 140 mm Hg and/or diastolic

blood pressure 90 mm Hg
TG 150 mg/dl and/or HDL-C < 35 mg/dl for men and
40 mg/dl for women
Central obesity: waist/hip ratio > 0.90 for men and 0.85
for women and/or BMI > 30 kg/m2
Microalbuminuria: urinary albumin excretion rate 20
mg/ml or albumin/creatinine ratio 30 mg/g

Comparison of ATP III Criteria and WHO criteria for the

Diagnosis of Metabolic Syndrome
Risk Factor
Obesity

ATP III defining level

WCF > 102 cm for men
or >88 cm for women

WHO defining level

BMI 30kg/m2 and/or
WHR>0.9 men, >0.85
women
Blood pressure
130 / 85 mmHg
140 / 90 mmHg
Fasting Glucose
110 mg/dl
IGT for diabetes
Microalbuminuria
Not used for diagnosis
AER 20 g/dl
Triglycerides
150 mg/dL
150 mg/dL
HDL cholesterol
< 40 mg/dL for men
<35 mg/dL for men
< 50 mg/dL for women <40 mg/dL for women
More interest was devoted to earlier detection of insulin resistance to be
able to prevent the unexpected outcome as early as possible.

Causes of Metabolic Syndrome:

Physical inactivity
Overweight and/or obesity
Atherogenic diet

Impacts of metabolic syndrome that can lead to

coronary heart disease:

Atherogenic dyslipidemia
Proinflamatory state
Prothrombotic state
Type 2 diabetes

Insulin Resistance Increases The Risk of Atherosclerosis

Causes of Coronary Artery:

Increase in :
o MMPs
o CRP
o CD 40(L)
o Platelet Aggregation
o Fibrinogen
o vWF

o
o
o
o
o
o

F VII
F VIII
Tissue Factor
Plague Formation
Sympathetic Tone
PAI-1

Decrease in :
o TPA
o PG1

Visceral obesity is associated with a cluster of

metabolic abnormalities
Type 2 diabetes, hypertension, and cardiovascular
disease can be seen through features such as:

Hypertriglyceridemia
Low HDL-cholesterol
Elevated apolipoprotein B
Small, dense LDL particles
Inflammatory profile
Insuline resistance
Hyperinsulinemia
Glucose intolerance
Impaired fibrinolysis
Endothelial dysfunction

Features of Atherogenic Dyslipidemia in Metabolic

Syndrome (The Atherogenic triad):

Low HDL-cholesterol
Small, dense LDL particles
Elevated TG rich particles

Relationship Between Changes in LDL-C and HDL-C

levels and CHD Risk

1% decrease in LDL-C reduces CHD risk by 1%

1% increase in HDL-C reduces CHD risk by 3%

Principles in the Management of Metabolic Syndrome

Management of underlying risk factors

Lifestyle modifications
Overweight and obesity : reduce energy diets (500-1000
cal/day reduction)
Physical inactivity : daily minimum of 30 minutes of
moderate-intensity physical activity

Dietary modification
Management of metabolic risk factor
Atherogenic dyslipidemia : fibrate, nicotinic acid, statin
Elevated blood pressure : anti hypertension
Insulin resistance and hyperglycemia
Prothrombotic state : aspirin
Proinflammatory state

International Expert Panel recommends an HDL-C target

of 40 mg/dl

Raising HDL-C should be considered as important as lowering LDL-C

HDL-C of 40 mg/dl ( 1.0mmol/l) should be the goal for patients
with CVD and at high risk for CVD:
o Type 2 diabetes
o Features of metabolic syndrome
o Abdominal obesity
Therapeutic lifestyle changes should be encouraged to reach this
HDL-C goal
Consideration should be given to fibrate therapy for patients at risk
with low HDL-C and low-risk LDL-C. Niacin may also be considered in
appopriate patients
These recommendations apply to patients who do not require statin
therapy and to those being treated with statins

Summary

Metabolic syndrome is CAD Risk factor, with specific atherogenic

dyslipidemia
Low HDL-C is mainly found in metabolic syndrome, as serious risk of
CHD
The first line treatment in metabolic syndrome is lifestyle
modification
Treatment target on low HDL is to protect patients from CHD
Fibrate (particularly Fenofibrate) is the appropriate treatment for
atherogenic dyslipidemia in metabolic syndrome