INTRODUCTION

Coronary heart disease (CHD) has reached enormous proportions striking

more and more at younger subjects. It will result in coming years the greatest

epidemic mankind has faced; unless we are able to reverse the trend by

concentrating on research into its cause and prevention1.Coronary Heart disease

and its major manifestations were a medical rarity prior to first world war.2

The prevalence of coronary heart disease is on the raise in our country, more

so in South India cutting across all class and age distinctions, imposing severe

burden on the health care system. Hence the present study aims to address the

reasons for high prevalence of CAD and the risk factors involved, namely the

Metabolic Syndrome3. Metabolic syndrome refers to constellation of inter-related

cardiac risk factors that appear to directly promote development of atherosclerotic

cardiovascular disease4. A recent review of insulin resistance syndrome revealed a

rapid escalation of this syndrome among Indians and the prevalence of predominant

component of METS varies from region to region.5

Studies have revealed the pathophysiology of this syndrome, with close to a

six fold increase in cardiovascular mortality in those possessing this disorders.6 The

increased risk of morbidity and mortality associated with the METS makes it

essential that there be a clear understanding of the dimensions of this syndrome for

the allocation of health care and research resources and for other purposes.8 Data

regarding the prevalence of metabolic syndrome in coronary artery disease from this

part of the country is scanty and conclusions are drawn based on the studies done in

northern India. Indian population is non-homogeneous and data specific to this

region is a dire necessity which this study aims to address.

1

Only very few studies have reported on the prevalence of IRS as a whole in

the native Indian population based on epidemiological studies. This is particularly

relevant as India has the maximum number of diabetes patients in any given country

in the world.10

This study was conducted in a large teaching hospital with a medical college

fully equipped with a cardiology department with cath lab facility and located in the

heart of Andhra Pradesh, thereby attracting representative population from all areas

and especially the lower strata of society. Results of this study are therefore relevant

to the general public in this part of the country. By examining the prevalence of

metabolic syndrome in established CAD, this study aims to create awareness

regarding the syndrome so that by early intervention, this menace could be tackled

effectively.

2

OBJECTIVES

1. To assess the prevalence of metabolic syndrome in angiogram

proven coronary artery disease.

2. To assess the extent of coronary artery disease in patients with

metabolic syndrome.

3

REVIEW OF LITERATURE

The concept of METS has existed for at least 80 years. This constellation of

metabolic disturbances, all risk factors for CVD, was first described in the 1920s by

Kylin, a Swedish physician, as the clustering of hypertension, hyperglycemia, and

gout.11

Abnormalities of glucose metabolism and diabetes were added to this risk

factor conglomerate later. IR in diabetes was reported by Himsworth in 1939 in a

series of Goulstonian lecturer to the Royal College of Physicians in London.12

Later in 1947, Vague drew attention to upper body adiposity (android or male-

type obesity) as the obesity phenotype that was commonly associated with metabolic

abnormalities associated with type 2 diabetes and CVD.13

The Reaven Banting lecture from the year 1988 introduced the concept of

syndrome X as a fundamental factor in the pathogenesis and clinical course of what

are often referred to as the diseases of western civilization – type 2 diabetes,

hypertension(HT), and atherosclerotic CVD – received much attention.14

Reaven’s syndrome X originally consisted of resistance to insulin stimulated

glucose uptake, hyperinsulinemia, hyperglycemia, an increased concentration of

very-low-density lipoprotein triglycerides, a decreasedconcentration of high-density

lipoprotein cholesterol (HDL-C), and high BP.14

Reaven did not offer specific criteria for having syndrome X, and he did not

include obesity or visceral obesity as a criterion. Later, others, including leading

organizations and associations working in primary and secondary prevention of

4

CVD, added measures of visceral obesity and offered specific criteria to define this

syndrome.15

The causes of the METS remain obscure. Reaven proposed that IR was the

most important abnormality, while Lemieux proposed that visceral obesity and

hyperglyceridemic waist was important.14,16,17

Despite the ongoing arguments among various groups, the ultimate

importance of this condition is that it helps to identify individuals at high risk of

CVD.16

Table.1 Various terminologies used to describe the METS18

• Athero-thrombogenic syndrome• Beer-belly syndrome• Cardiovascular syndrome• Chronic cardiovascular risk factor clustering syndrome• Deadly quartet• DysMETS• IR syndrome• Metabolic cardiovascular syndrome• METS• Multiple syndrome• Multiple METS• PluriMETS• Reaven’s syndrome• Syndrome X• New world syndrome

Epidemiologic research has identified risk factors that increase the likelihood

of coronary heart disease events. Basic and clinical studies have revealed plausible

biological links between many of the risk factors and atherosclerosis and have

demonstrated that management of risk factors can improve coronary endothelial

function, stop the progression of atherosclerosis, prevent disruption and thrombosis

5

of vulnerable atherosclerotic plaque, and reduce CHD morbidity and mortality. When

risk factors coexist, they multiply the risk of CHD several fold7. Identification and

management of risk factors are essential in preventing CHD in high – risk

asymptomatic individuals (primary prevention). A recent Bethesda conference

proposed a classification scheme according to the strength of evidence that risk

factor intervention favorably affects outcome9.

DEFINITION AND CONSTITUENTS OF METABOLIC

6

SYNDROME

The contemporary definition of METS “refers to a cluster of metabolic

abnormalities related to a state of IR which is often associated with a high-risk

overweight/obesity phenotype. The major characteristics of METS include IR,

abdominal obesity, elevated BP, and lipid abnormalities [i.e., elevated levels of

triglycerides (TGs) and low levels of HDL-C].

METS is associated with a proinflammatory / prothrombotic state that may

include elevated levels of C-reactive protein(CRP), endothelial dysfunction,

hyperfibrinogenemia, increased platelet aggregation, increased levels of

plasminogen activator inhibitor 1, elevated uric acid levels, microalbuminuria, and a

shift toward small, dense particles of low-density lipoprotein (LDL-C) cholesterol”9.

Several groups have attempted to develop diagnostic criteria for diagnosis of

METS.

The World Health Organisation19(WHO) proposal was designed as a first

attempt to define the syndrome in 1999 includes Diabetes or impaired fasting

glycemia or impaired glucose tolerance or IR (under hyperinsulinemic and

euglycemic conditions, glucose uptake in lowest 25%) plus two or more of the

following:

1. Obesity: body mass index >30 kg/m2 or waist: hip ratio >0.9 (male) or

>0.85 (female).

2. Dyslipidemia: TGs ≥ 1.7 mmol/L or HDL-C <0.9 (male) or <1.0 (female)

mmol/L.

3. Hypertension: BP ≥ 140/90 mmHg.

7

4. Microalbuminuria: albumin excretion ≥ 20 μg/min.

The European group for the study (EGIR)20 of IR also defined the METS in

1999 includes – IR (defined as hyperinsulinemia, top 25% of fasting insulin valves

among the non-diabetic population) plus two or more of the following:

1. Central obesity: waist circumference ≥ 94 cm (male) or ≥ 80 cm

(female).

2. Dyslipidemia: TGs >2.0 mmol/L or HDL-C <1.0 mmol/L.

3. Hypertension: BP ≥140/90 mmHg and/or medication.

4. Fasting plasma glucose >6.1 mol/L.

The National cholesterol Education Program(NCEP) Export Panel on

detection, evaluation and treatment of high blood cholesterol in adults – otherwise

known as the Adult Treatment Panel III (ATP III) definition of METS presented in

200121 includes –

Three or more of the following :

1. Central obesity : waist circumference > 102 cm(male) or > 88 cm (female).

2. Hypertriglyceridemia : TGs ≥ 1.7 mmol/L

3. HDL cholesterol : <1.0 mmol/L (male) or <1.3 mmol/L (female)

4. Hypertension: BP ≥130 /85 mmHg or medication.

5. Fasting plasma glucose ≥ 6.1 mmol/L.

In retrospect, it is apparent that the WHO definition more suited as a research

tool whereas the NCEP: ATP III definition was more useful for clinical practice22.

8

The criteria for defining METS in adult Asian Indians needs revision. Inclusion

of modified cutoffs of waist circumference (>90 cm for men, > 80 cm women) and

BMI (>23 kg/cm2) and measures of truncal subcutaneous fat in the NCEP ATP III

definition requires further validation.23

Yet another attempt at definition came from the American Association of

Endocrinology and American Association of clinical endocrinologist.24

There were problems associated with all these definitions in terms of

applicability, uniformity and positive predictive value. A major problem was

applicability to different ethnic groups, especially among East Asians and South

Asians.22

The International Diabetes Federation (IDF)25 has recently revised the

guidelines to remedy the ethic group based disparities in the original classification.

According to the new IDF, for a person to be defined as having the METS,

they must have: Central obesity (defined as waist circumference ≥ 94 cm for

European men and ≥ 80 cm for European women, with ethnicity specific values for

other groups).

In addition, any 2 of the following 4 factors:

Raised TGs level: ≥150 mg/dl (1.7 mmol/L), or specific treatment for this lipid

abnormality.

Reduced HDL – cholesterol: <40 mg/dl (1.03 mmol/L) in men and <50 mg/dl

(1.29 mmol/L) in women, or specific treatment for these lipid abnormalities.

9

Raised Blood pressure: systolic BP ≥130 or diastolic BP ≥85 mmHg, or

treatment of previously diagnosed HT.

Raised fasting plasma glucose: fasting plasma glucose ≥100 mg/dl

(5.6mmol/L), or previously diagnosed type 2 diabetes.

If above 5.6 mmol/L or 100mg/dl, an OGTT is stronglyrecommended, but is

not necessary to define the presence of the syndrome.

American Heart Association/Updated NCEP

There is confusion as to whether AHA/NHLBI intended to create another set

of guidelines or simply update the NCEP ATP III definition.

According to Scott Grundy, University of Texas Southwestern Medical School,

Dallas, Texas, the intent was just to update the NCEP ATP III definition and not

create a new definition.26,27

Elevated waist circumference:

Men — Equal to or greater than 40 inches (102 cm)

Women — Equal to or greater than 35 inches (88 cm)

Elevated triglycerides: Equal to or greater than 150 mg/dL

Reduced HDL (“good”) cholesterol:

Men — Less than 40 mg/dL

Women — Less than 50 mg/dL

Elevated blood pressure: Equal to or greater than 130/85 mm Hg or use of

medication for hypertension

10

Elevated fasting glucose: Equal to or greater than 100 mg/dL (5.6mmol/L) or

use of medication for hyperglycemia

Other

High-sensitivity C-reactive protein (hs-CRP) has been developed and used as

a marker to predict coronary vascular diseases in metabolic syndrome, and it was

recently used predictor for non-alcoholic fatty liver disease in correlation with serum

markers that indicated lipid and glucose metabolism.28

There is a need for standardized definition of METS. Furthermore, a definition

tailored for children and adolescents is essential.

Prospective long-term studies are needed to validate the prognosticpower of

these definitions. As new information becomes available, the definition of METS

might be further modified.29

METS is estimated to affect more than one in five adults, and itsprevalence is

growing in the adults and pediatric population.30

Coronary angiography :

First performed by Sones31 in 1959, coronary arteriography hassubsequently

become one of the most widely used invasive procedures in cardiovascular

medicine. Methods used to perform coronary arteirography have evolved

substantially since 1959.

Coronary arteriography remains the standard by which all methods of

diagnosing coronary artery disease are measured. It is the primary method of

11

defining coronary artery disease are measured. It is the primary method of defining

coronary anatomy in living patients.

Coronary arteriography remains the “Gold standard”32 for identifying the

presence or absence of arterial narrowing related to a atherosclerotic coronary artery

disease and provides the most reliable anatomical information for determining the

appropriateness of medical therapy, percutaneous coronary intervention or coronary

artery bypass surgery in patients with ischemic coronary artery disease.

Coronary arteriography can establish the presence or absence of coronary

stenoses, define therapeutic options, and determine the prognosis of patients with

acute myocardial infarction at young age.

A recent study33 also showed that young patients with acute myocardial

infarction had more often single vessel disease followed by normal coronary arteries

angiographically.

A finding in which older patients had extensive atherosclerosis with more

number of diseased and diffusely involved coronary vessels than the young patients

have led to the conclusion that younger patients having less extensive coronary

artery atherosclerosis with better prognostic probability should be evaluated

angiographically for further definitive management in the form of revascularization34.

PREVALENCE OF METS:

12

Metabolic syndrome is a strong marker indicating the likelihood of CAD, while

strongest association of CAD were found with obesity and microalbuminuria. This

seems strongly significant than traditional risk factors like elevated LDL cholesterol,

hypertension and triglyderides.35

A higher prevalence of metabolic syndrome in young females compared with

young males with premature coronary artery disease was found. The overall

prevalence of metabolic syndrome was 37%. Women with premature CAD were

found to have a higher premature of metabolic syndrome than man.36

Metabolic syndrome but not BMI predicts future cardiovascular risk in women.

Although it remains prudent to recommend weight loss in overweight and obese

women, control of all modifiable risk factors in both normal and overweight. Persons

to prevent transition to metabolic syndrome should be considered the ultimate goal.37

A very consistent finding is that the prevalence of METS is highly age –

dependent, in USA (National health and Nutrition examination surgery [NHANES III])

prevalence of METS increased from 7% in participants aged 20-29 years to 44% and

42% for those aged 60-69 years and at least 70 years respectively.38

Data from 12-19 years age group is the NHANES III study, with NCEP: ATP

III criteria modified for adolescents, reported that the prevalence of the METS in

adolescents was 4.2%.39

Of particular interest are the two Indian studies, which differed in their

definition of obesity; one study used obesity criteria that were suitable for Indians,

while the others used the standard ATP III definition of obesity. Both studies used

13

population-based samples writing the same age range but reported prevalence of

13% in Jaipur and 41% in Chennai.40,41

Interestingly, a third Indian study42 also from Chennai, reported a METS

prevalence of 11.2% (using EGIR criteria), which was much closer to the prevalence

reported for Jaipur than the other Chennai study. Therefore, even within the same

ethnic population group it appears that there can be significant differences in the

prevalence of both the individual factors that constitute the METS and the METS

itself.43

A low education level links cardiovascular disease with risk factors such as

smoking, HT, impaired glucose tolerance, diabetes mellitus, physical inactivity and

overweight associated with other metabolic abnormalities.

The prevalence of METS was found to be elevated in women who abstained

from alcohol. Slight and moderate alcohol consumption has been found to be

associated with low coronary heart disease risk possibly through beneficial

alterations in HDL cholesterol and BP.44

High prevalence of obesity and IR in urban Indian population is wellknown. A

study from Chennai report 18.7% prevalence of IRS in upper socio-economic strata

in south India, while it was 6.5% in the low socioeconomic strata.39\

14

Fig.1:Prevalence of the metabolic syndrom from ATP III definition.47

Fig.2:Age-specifi prevalence rates of metabolic syndrome

(Jaipur Heart Watch-2)43

15

The I164T mutation in adiponectin gene was a common genetic background

associated with metabolic syndrome and CAD in Japanese population.4

Higher prevalence of METS in women as compared with men is seen in urban

south Indian population.40

Approximately 20-25 percent of urban souths Asians have evidence of the

METS. Furthermore, IR was reported, to be present in nearly 30 percent of children

and adolescents in India, more so in girls.45

According to a recent study on south Indians, the prevalence of the METS (%)

was estimated to be 23.2, 18.3 and 25.8 according to WHO, ATP III and IDF

definitions respectively.46

High prevalence of cardiovascular risk factors and the METS (~12%) have

been shown by our group in intra-country rural-to-urban migrant population

belonging to low socio-economic stratum residing in urban shins. Further, certain

communities in India (eg. Punjabi, Bhatia community) have inordinately high

tendency to develop obesity, type 2 diabetes mellitus, and METS.45

The METS was present in 31.6% of Indian urban population, prevalence was

22.9% in men and 39.9% in women, the age-adjusted prevalence was 24.9%, 18.4%

in men and 30.9% in women there was a significant age-related increase in its

prevalence.47

CARDIOMETABOLIC RISK: is defined as a cluster of modifiable risk factors

and markers that identify individuals at increased risk for CVD (myocardial

infarction, stroke, peripheral artery disease) and Type 2 diabetes mellitus.

16

Cardiometabolic risk factors21 :

Elevated BP

Abdominal adiposity

Low HDL-C

Elevated TGs

Elevated blood glucose

Smoking

Elevated LDL-C

Inflammatory markers

IR

The risk of cardiovascular events conferred by the presence of the METS was

greater than the risk associated with any of the individual components, emphasizing

the predictive value of this clinical entity in terms of cardiovascular complications.48

Renin-angiotensin system is known to be present in human adipose tissue,

thereby offering a potential link between obesity and HT, as well as the

prothrombotic properties of CVD49.

In asymptomatic middle-aged adults, METS also is associated with

accelerated atherosclerosis.50

INTERHEART study found that nine potentially independent risk factors, such

as smoking, history of HT and diabetes, alcohol consumption, psychosocial factors,

waist/hip ratio, dietary habits, physical activity, apolipoproteins, and alcohol

consumption, were all related to myocardialinfarction.51

17

Applying the ATP III criteria to 10537 NHANES III participants resulted in a

significant association between the METS with prevalent myocardial infarction and

stroke.52

Cardiovascular disease rate over 7.6 year was 79% or 1% per year, but of

even greater significance was the fact that 22% of group with METS developed

cardiovascular disease during 7-8 years follow up.53

In patients who had myocardial infarction with in previous 3 months, 30% of

patients had METS.54

It is not known if the METS has a greater association with women versus

men, but the presence of coronary disease in middle-aged women is highly

associated with METS.55

People with the METS have atleast a 2 fold increase in the risk of CVD

events, and a much poorer prognosis following the event. The METS more strongly

predicts congestive heart failure and CVD mortality than its individual components.56

The presence of METS is a strong marker indicating the likelihood of CAD,

while the strongest association of CAD were found with obesity and

microalbuminuria. This seems more strongly significant than traditional risk factors

like elevated LDL-C, HT, and TGs.57

18

Fig.3: Risk factors Cardiometabolic syndrome9

Fig.4: Progression and outcome of metabolic syndrome

METHODOLOGY

19

This study is based on analysis of 100 patients admitted to the CCU of

Government General hospital attached to the Medical College, Guntur during a

period from March 2013 to March 2014.

Criteria:

The proforma was used for the selection of patients with definitive evidence of

myocardial infarction.

Inclusion criteria:

Patients with evidence of coronary artery disease proven by coronary

angiogram.

Age > 30 years independent of sex.

Exclusion criteria:

Patients with evidence of coronary artery disease who has not undergone

coronary angiogram.

Patients having coexisting valvular heart disease.

Age < 30 years.

All patients of CAD including both STEMI, and NSTEMI were included.

A final diagnosis of CAD was made in the presence of serial increases in

serum biochemical markers of cardiac necrosis, has associated with typical

electrocardiographic changes and by coronary angiography and/or typical symptoms

as defined by the joint committee of the European society of cardiology and the

American college of cardiology.109

20

Patients with ST segment elevation or new or suspected new left bundle

branch block on admission electrocardiogram were defined as having ST segment

elevation MI (STEMI). The remaining patients were categorized as having non-

STEMI.

Criteria of diagnosis of METS:

The NCEP-ATP III22 definition was used for the diagnosis of METS includes

any three of the following

Central obesity : waist circumference > 102 cm (male) or > 88 cm (female).

Hypertriglyceridemia : triglycerides ≥ 150 mg/dl ♠ HDL cholesterol : <40 mg/dl

(male) or <50 mg/dl (female)

Hypertension: blood pressure ≥ 130 /85 mmHg or medication.

Fasting plasma glucose ≥ 110mg/dl.

A detailed case history was taken including the symptoms, past history of

diabetes mellitus, HT, smoking and alcohol consumption.

A careful physical examination was done with special reference to resting BP

before discharge, WC, Height and weight. The BMI was calculated using the formula

BMI = Weight in kg/Height in m2.

WC was recorded according to the national health and nutrition survey.110

“The subject stand and the examiner, positioned at the right of the subject, palpates

the upper bone to locate the iliac crest. Just above the uppermost lateral border of

right iliac crest, a horizontal mark is drawn, and then crossed with vertical mark on

the midaxillary line. The measuring tape

21

is placed in a horizontal plane around the abdomen at the level of this marked

point on the right side of the trunk. The plane of the tape is parallel to the floor and

the tape is snug, but does not compress the skin. The measurement is made normal

minimal inspiration.”

Investigations:

The following investigations were done in all the patients. The blood samples

were drawn at the admission, the following morning (lipid profile) and day 5 for

FBS.111

Electrocardiogram

Cardiac enzymes creatinine kinase, lactate dehydrogenase, aspartate

transaminse.

Fasting blood sugar, fasting lipid profile including serum cholesterol,serum

triglycerides, HDL-C, LDL-C.

Coronary angiogram.

All the coronary artery disease patients were followed up over a period of one

week for the development of complications like Heart failure, arrhythmias (ventricular

tachycardia/fibrillation), Recurrent MI. Heart failure was defined according to Killip`s

classification112

Statistical analysis:

Results were expressed as mean± SD and median for continuous data and

were compared by unpaired t test/Mann-whitney test between two groups.

Categorical data are presented as numbers and percentages, were analysed by chi-

square test. Odds ratios were calculated wherever required. A p value of 0.05 or less

was considered for statistical significance.

22

RESULTS

TABLE -2: TOTAL ADMITTED CASES IN CCU OF ACUTE MI

No. Of cases admitted

Total No. Of coronary artery disease 100

METS with CAD 44 (44%)

A total of 100 cases of acute CAD admitted during the 1year study period, out

of which 44 cases had METS which showed an overal percentage of 44% in the

present study.

TABLE -3: AGE GROUPING

With METS ( n = 44 ) Without METS ( n =

56 )

Total

Age

( years )

No. % No. % No. %

31-40 8 18 9 16 17 17

41-50 14 32 20 36 34 34

51-60 13 30 14 25 27 27

61-70 6 14 12 21 18 18

71-80 3 7 1 2 4 4

Total 44 56 100

The age incidence was more between the age group 41-50 years followed by

51-60 years in both the groups. There was no statistical difference in Age between

the 2 groups. (p value 0.48)NS

23

24

Table -4: SEX DISTRIBUTION

Sex CAD with METS CAD without METS Total

N = 44 % N = 56 % N = 100 %

Males 33 75 44 79 77 77

Females 11 25 12 21 33 33

Chi-square test. X2=1.33, p value = 0.25 NS

It was observed that 77 case among the 100 studied cases were male. The males

perdominated in both the grounps. The METS was more in females with MI but it

was not statistically significant. (p value 0.25)NS

TABLE-5 : SYMPTOMATOLOGY AT PRESENTATION

25

With METS ( n =

44 )

Without METS (n =

56 )

Total

Symptoms No. % No. % No. %

Chest pain 42 95 56 100 98 98

Breathlessnes

s

14 32 11 20 25 25

Cough/ sputum 8 18 10 18 18 18

Palpitation 7 16 8 14 15 15

Syncope 2 4.5 1 2 3 3

Sweating 25 56 20 36 45 45

Vomiting 2 4.5 5 9 7 7

The most common mode of presentation in both groups was chest pain

followed by sweating. Breathlessness (32% vs. 20%) & sweating (56% vs. 36%)

were more common in METS compared to those without METS.

TABLE- 6: RISK FACTORS

26

With METS ( n = 44 )

Without MET (n = 56 )

Total

Risk factors No. % No. % No. % P* value,

sig.Diabetes Mellitus

25 57 16 29 41 41 0.004 S

Hypertension 24 56 16 29 35 35 0.01 SFamily History

12 27 12 21 24 24 0.49 NS

Current Smoker

13 29.5 14 25 27 27 0.61 NS

Alcohol Consumption

19 43 14 25 33 33 0.055 NS

Chi- square test. S=Significant, NS=Not Significant

The past history of DM and HT were more common in the METS group compared to

those without METS which were statistically significant. There was no significant

difference in the current history of smoking, alcohol consumption and family history

of CAD in both the groups

27

TABLE – 7 : COMPONENTS OF METS

Components of METS

With METS ( n = 44 )

Without MET (n = 56 )

Total P* value,

sig.No. % No. % No. %FBS =

110mg/dl36 82 21 38 57 57 P <

0.001HS

HTN or BP = 130/85 mm Hg

37 84 12 21 49 49 P < 0.001

HSTGS = 150

mg/dl42 95 18 32 60 60 P <

0.001HS

HDL< 40

mg/dl(males)<50

mg/dl(females)

42 95 32 57 74 74 P < 0.001

HS

Waist circumference

>102 cm(males)

> 88 cm(females)

17 39 8 14 25 25 0.01 S

28

TABLE -8 : MEAN VALUES OF PARAMETERS

MI with METS MI without METS P value

FBS (mg/dl) 174.2 ± 66 133.3 ± 54.2 0.001 HS

TC (mg/dl) 186.5 ± 46.7 191.2 ± 49.8 0.63 NS

TGS (mg/dl) 246.1 ± 109.8 157.9 ± 46.3 < 0.001 HS

HDL-C (mg/dl) 35.8 ± 5.6 39.1 ± 3.9 < 0.001 HS

LDL-C (mg/dl) 137.3 ± 40.4 129.1 ± 41.2 0.31 NS

SBP mm of Hg 139.6 ± 29.4 128.8 ±23.1 0.04 S

DBP mm of Hg 88.2 ± 19.6 81.6 ± 10.1 0.03 S

Unpaired t test. HS= Highly significant, NS : Not significant, S=Significant

It was observed that, the all the components were more common in the METS

group than patients without METS and were highly significant. Low HDL-C was the

major component in both the groups. High TGS is the next major component in

METS group followed by the DM or FBS ≥110mg/dl, HT or BP ≥ 130/85 and high

WC. HT or BP ≥ 130/85 was the next major component in patients without METS

followed by high TGS, DM or FBS ≥110mg/dl and high WC.

29

TABLE -9 : OTHER FACTORS

Other factors

CAD with METS CAD without METS

Total P value

N = 44 % N = 56 % N = 100 %

Obesity ( BMI ≥ 30kg/m2

17 38.6 3 5.3 20 20 0.01 S

Serum cholesterol (≥240mg/d

l

9 20.45 6 10.7 15 15 0.63 NS

LDL-C > 160mg/dl)

12 27.2 9 16.7 21 21 0.31 NS

S= Significant, NS: Not significant

The obesity with BMI> 30Kg/m2 was present in 38.6 (Mean 27.2± 3.3) of patients

with METS compared to 5.3% (25.7±2.4) of those without METS, which was

statiscally significant (p Value)

30

TABLE – 10 : ANGIOGRAM

Angiogram With METS ( n =

44 )

Without METS( n

= 56)

Total P*

value,

sig.No. % No. % No. %

LAD 28 64 40 71 68 68 0.4 NS

RCA 8 18 14 25 22 22 0.4 NS

LCX 8 18 10 18 18 18 0.9 NS

It was observed that LAD was the most common vessel involved of the 100

studied cases 70 case 71 case were LAD and there was no much significance

related to METS.

31

TABLE -11: IN HOSPITAL PROGNOSIS OF CAD IN 1 WEEK

Prognosis in 1

week of

hospital stay

CAD with METS CAD without

METS

Total P value

N = 44 % N = 56 % N = 100 %

Heart failure 23 52 10 18 33 33 < 0.001

HS

Arrhythmias

VT/VF

4 9 4 7 8 8 0.98

NS

Recurrent MI 3 7 1 2 4 4 0.74

NS

HS= Highly Significant, NS: Not significant

All the complication were more common in the METS group compared to

those without METS group. Heart failure was present in 52% of METS patents

compared to the 18% in those without METS which was statistically highly significant

(p value <0.001). There was no significant difference in the development of other

complications like arrhythmias (ventricular tachycardia/fibrillation), recurrent MI.

32

DISCUSSION

In the present study, which included 100 cases of CAD, METS was present in 44

cases (44%).

TABLE-12: INCIDENCE OF METS

Study % of METS in CAD

Zeller M113 et al (2005) 46%

Schwartz G114 et al (2005) 38%

Levatasi G54 et al (2005) 29%

Ninomiya52 et al (2004) 41.5%

Milani R6 et al (2003) 58%

Present study 44%

These findings suggest the METS, as defined by the NCEP ATP III criteria, is

very common among patients with CAD, because almost 1 in 2 patients had METS

and that is associated with advanced coronary artery vascular damage.

This high incidence may be related to the vascular damage in METS by

oxidative stress, endothelial dysfunction and pro-inflammatory state.108

AGE INCIDENCE:

In the present study age incidence was more between the age group 41-50

years (32% in METS group and 36% in without METS group). There was no

difference in mean age of presentation between the two groups. (p- value 0.04 NS).

33

TABLE -13: AGE OF PEAK INCIDENCE OF METS

Study Age in years

Schwartz G114 et al (2005) 65 ± 11

Levatasi G54 et al (2005) 68.2

Zeller M113 et al (2005) 70 (57-67)

Ninomiya52 et al (2004) 58.6 ± 10.3

Milani R6 et al (2003) 65.7 ± 10.3

Jeppesen et al (2007) 61 (41-71)

Present study 44

There is early incidence of METS in CAD patients in the present study

compared to the other studies. About 25% CAD in India occurs under the age of 40

and 50% under 50119. In general MI develops 5-10 years earlier in Asian Indian than

in other population.120-121

SEX INCIDENCE:

In the present study the males predominated in both the groups (75 in METS group

and 79 in without METS group).

34

TABLE -14: SEX INCIDENCE

Study Males Females

Zeller M113 et al (2005) 63% 37%

Schwartz G114 et al (2005) 55% 45%

Levatasi G54 et al (2005) 85% 15%

Ninomiya52 et al (2004) 64% 32%

Milani R6 et al (2003) 55% 45%

Present study 75% 25%

Comparison between the two groups indicates that patients with METS were

more likely to be a female, which was consistent with the other studies. In the

present study, confounding factors like pre or post menopausal status and presence

or absence of anemia have not yielded statistically significant results. Higher waist

circumference and BMI appeared to play a more significant role in female subjects

than in males.

35

SYMPTOMATOLOGY:

There was no difference in the 2 groups in presenting symptoms except that more

number of patients with METS had sweating, breathlessness (56% and 32% as

compared 36% and 20% without METS).

RISK FACTORS:

In the present study past history of diabetes mellitus (57%) and hypertension

(56%) more in METS patients compared with no METS, which were statistically

significant. However, there was no statistically significant difference in the current

smoking, alcohol consumption and family history of CAD

TABLE -15: RISK FACTORS.

Zeller M113 et al

(2005)

Schwartz G114

et al (2005)

Jeppesen et al

(2007)

Present study

Past history of

DM

48% 48% 8.1% 57.0%

Past history of

HT

79% - 17.1% 56.0%

Current smoker 23% 25% 44% 29.5%

Family history

of CAD

32% - - 27.0%

36

All the risk factors were comparable to other studies but there was wide variation for

the past history of HT.

BODY MASS INDEX:

The BMI of ≥30kg/m2 as obesity was present in 38.6% of METS group as

compared to 5.3% of without METS group. The mean values were 27.2± 3.3 and

25.7± 2.6 kg/m2 respectively, which was comparable to other studies. It was

statistically significant with p value of 0.04 (<0.01).

TABLE -16: BODY MASS INDEX

Study BMI kg/m2

Zeller M113 et al (2005) 25(23-37)

Schwartz G114 et al (2005) 46%

Milani R6 et al (2003) 38%

Present study 38.6%

COMPONENTS OF METS:

All the components were more common in METS group compared to those

without METS and were statistically highly significant. METS scoring was given to

each patient depending on the number of risk factors present in the individual

patient. METS score of 3 and above was associated with a significant increase in

CAD risk.

37

TABLE -17: COMPONENTS OF METS

FBS mg/dl BP mm of

Hg

TGS mg/dl HDL-C

mg/dl

WC in cms

Schwartz

G114 et al

(2005)

- 90% - 88% 76%

Ninomiya52

et al (2004)

- 48.2% 43.2% 45% 51%

Present

study

82.0% 84.0% 95.0% 95.0% 39.0%

TABLE -18: MEAN VALUES OF COMPONENTS OF METS

Milani R6 et

al (2003)

111 ± 26 140 ± 18/

76 ± 13

176 ± 101 37.7 ± 11 102 ± 12

Zeller M113

et al (2005)

123 - 160 37 106

Present

study

174 ± 67 139.6 ±

29.4/

88.2 ± 19.6

246.1 ±

109.8

35.8 ± 5.6 96.8 ± 6.7

Low HDL-C was the most prevalent individual component in both the groups

(95% and 57%) with mean values lower in the METS group (35.8±5.6 vs. 39.1±3.9).

High TGS was the next major component prevalent in the METS group (95%) and

HT (84%) in the without METS group. The very high prevalence of dyslipidemia in

38

the present study compared to other studies can be explained by the fact that most

patients in the present study were either not on statin therapy or were inadequately

treated. Known diabetic and hypertensive patients on prolonged duration of therapy

for above ailments were inadequately tested for serum lipids.

This highlights the need for making the Lipid Profile testing more affordable to

the common public, spreading the awareness regarding the need for periodical lipid

profile testing and early counselling regarding life style management in all diabetic

and hypertensive patients. Government initiative in this direction should include

making generic drugs available and advocacy regarding the menace of non-

communicable diseases. This should also serve as a reminder to the health care

providers to search for other risk factors when the patient presents with one risk

factor i.e., to screen for the full spectrum of METS at the beginning of therapy and

periodically thereafter.

The mean FBS was 174.2 ± 67 in METS group and 133.3 ± 54.2 in the

without METS group. Both these values were more than the cut off value for the

inclusion of FBS in the NCEP ATP III criteria for the diagnosis of METS. In the

present study, glycemic control measured by FBS was associated with high

prevalence of CAD. The degree of severity of lesions was directly related to the FBS,

though the number of vessels involved did not correlate with the presence or

absence of METS. Thus the pivotal role of glycemic control in the onset and

progression of CAD has been re-established in this study.

Even in non-diabetic individuals, impaired glucose tolerance could be

associated with CAD and its severity. But this correlation could not be adequately

established from this study due to limitations of sample size. However, this data is

39

sufficient to reinforce the fact that intensive glycemic control is an important

component of CAD prevention. Another significant observation from the present

study is that the duration of diabetes is directly related to the prevalence of CAD.

However, the scope of this study does not include collection of data regarding the

history of metabolic control of our subjects particularly in the early years of their

diabetes, this period being probably important in the metabolic memory of these

individuals.

This factor limits the more in-depth analysis of metabolic control in the

evolution of CAD. The proportion of denovo diabetes detected after admission with

symptoms of angina is similar in both the arms ie, those with and without METS in

this study. In the present study the METS patients had high FBS (174±67mg/dl)

compared to other studies. This may be due to poor control of blood sugar in our

study patients and also irregularities in the treatment by the patients.

WC was the minor component in both the groups but was also found to be

statistically significant. Visceral fat plays an important role in the pathogenesis of

CAD. Adeponectin is the biomarker for visceral fat. It has direct prognostic

significance in non-diabetic subjects but its significance in diabetic patients in

prediction of CAD is debatable.

This test could not be incorporated in our study. Patients of Indian origin often

fit into the model of normal weight but metabolically obese individuals. Though the

mean weight in our study is 69.2 +/- 2.34 Kg, the waist circumference was 97.57 +/-

9.14 cm and the mean BMI was 26.8 +/- 2.9, demonstrating that they all fall into the

metabolically obese group. The fact that METS can develop in Indian patients with

40

apparently normal BMI was also confirmed in our study, with METS being present in

14% of patients with BMI less than 25 Kg/sq.mt.

Most of the patients in this study were more close to attaining BP targets than

glycemic targets. Most were already on adequate dosage of antihypertensive

medication.

The HT or BP ≥130/80 was comparable to some studies, and there was also

a variation in the incidence of HT in between the studies.

The serum TGS was found to be very high in the present study

(246.1±109.8mg/dl) compared to the other studies which may be related to the south

Indians have high percentage of body fat and low muscle mass.45

Additionally insulin resistance also reduces the concentration of lipoprotein

lipase in the peripheral tissues.22

The predominant component in the present study HDL-C (35.8±5.6) was

found to be same as compared to other studies. This low HDL-C may be due to high

TGs which leads to decreased production and also increased clearance HDL-C from

the circulation.22, 75 Data from this study showed dyslipidemia pattern of high

triglycerides and low HDL which is typical of South-Indian CAD patients.

This pattern of dyslipidemia is commonly associated with high insulin

resistance. However, the role of each component of deranged lipid profile i.e.,

elevated triglycerides / high LDL / low HDL in causing and aggravating CAD could

not be independently ascertained in this study.

Whether elevated triglycerides play a direct role in the causation of CAD or

they are surrogate markers for metabolic disturbances needs to be assessed by

41

further studies. Considering that LDL targets in diabetic patients could be even lower

than 100 mg/dL, the present data shows more correlation with worse HDL levels with

CAD in diabetic patients.

In our study LAD was the most common vessel involving 68% and RCA

(22%), LCX (18%).

Badui E. et al115 also made the similar observation with left anterior

descending artery involvement in 41% of patients.

Similar observation were made by Shat A. et al116 with left anterior

descending artery involvement in 84% of young patients with acute MI. Though the

number of vessels involved was not determined by the presence or absence of

METS, the severity of lesions (tightness of stenosis) was more in patients with METS

The WC was less in the present study (median 95) compared to the other

studies. This may be related to the adult Asian Indians, along with the other ethnic

groups, have different anthropometric characteristics compared with others.

Metabolic abnormalities contributing to cardiovascular risk factors are detectable at a

lower WC in Asians comparison with Caucasians, suggesting that NCEP ATP III

criteria might under estimate the prevalence of METS in Asians.

Obesity, criteria for the diagnosis of METS need to be revised in Asian Indians

and other Asian ethnic groups. Inclusion of modified WC, BMI cut offs and

subscapular skin fold thickness may be considered as defining variables of METS in

the future studies on Asian Indians and other Asian ethnic groups. Interpretation of

BMI as an individual risk factor in the causation of CAD is confounded by the fact

that mortality due to CAD increases at both the ends of spectrum of BMI i.e., very

42

low and very high BMI. Keeping in view the fact that weight loss could also occur due

to poor glycemic control in our subset of patients hailing from the poorer sections of

the society.

Other biochemical parameters serum cholesterol (mg/dl) and LDL-C (mg/dl)

(186.5±46.7 and 137.3±40.4) in the present study, which is comparable to Milani6 et

al (172± 38 and 104± 49), and there was no significant difference.

IN HOSPITAL PROGNOSIS OF CAD (1WEEK):

The heart failure (52%) was the predominant complication in the present

study and was statistically highly significant. Other complications were less common

and were not significant.

TABLE -19: IN HOSPITAL PROGNOSIS OF MI (1WEEK)

Complications Zeller M113 et al (2005) Present study

Heart failure 41.7% 52%

Ventricular

tachycardia/fibrillation

11.7% 9%

Recurrent MI 9.37% 3%

In the CAD patients presence of METS was associated with about 4 times

(odds ratio 3.8, p value <0.001 HS) more chances of complications.

This may be related to the more advanced vascular damage associated with

the presence of METS in patients with manifest vascular disease like CAD, which

43

may worsen the prognosis.113 METS also represent a cluster of several risk factors,

each of which may be involved in this poor outcome.

One of the main result of our study is that the increased risk of development

of heart failure in patients with METS appears to be related to primarily to fasting

hyperglycemia, measured several days after the index event which was very high in

the present study compared to other studies.

The presence of DM and HT were also associated with diastolic/systolic heart

dysfunction, abnormal myocardial substrate metabolism resulting in increased free

fatty acid metabolism, and impaired. blood flow to the non-infarcted myocardium117

are the potential factors explaining the higher incidence of heart failure.

Both METS and DM were associated with unfavorable in terms of all cause

mortality.54 A recent study in India has shown the importance of insulin resistance

as a risk factor for carotid artery intima/media thickness and indirect marker of

atherosclerosis.64

People with METS have at least 2-fold increase in cardiovascular events and

a much poorer prognosis following the event. The METS more strongly predicts the

coronary heart disease and cardiovascular disease mortality than its components.56

Size of the infarct as inferred from the creatinine kinase levels, troponin levels

and regional wall motion abnormality and lower EF in the post-MI echo was

significantly more in the present study in diabetic patients with poor glycemic control

(higher Hb A1c) compared to those with good control or non-diabetic patients.

Scope For Further Improvements Of This Study And Shortcomings

44

1. This study is an attempt to find a clinically relevant relationship between the

concept of METS and its utility in prevention of CAD. As of now, METS may

be considered useful as an educational concept, but has limited practical

utility as a diagnostic or management tool. In this context, future research

should focus on: (a) further elucidation of common metabolic pathways

underlying the development of diabetes and CVD, including those clustering

within the metabolic syndrome; (b) early-life determinants of metabolic risk;

(c) developing and evaluating context-specific strategies for identifying and

reducing CVD and diabetes risk, based on available resources; and (d)

developing and evaluating population-based prevention strategies.

2. The study could have been more objective by including measurable markers

of systemic inflammation said to be associated with METS like highly sensitive

CRP, adeponectin and IL-6 and ‘Insulin Resistance’ derived from Homeostatic

Model assessment (HOMA). However, it could not be done in this study due

to financial constraints involved.

3. The METS score (number of risk factors in each patient) could not be

evaluated vis-a-vis the severity of lesions on coronary angiogram

4. All the patients included in the study belong to the same (lower)

socioeconomic stratum in view of the setting of the study in a Government

General Hospital. Inclusion of patients from higher socio-economic strata

where METS is much more common could possibly alter the figures attained.

5. The relevance of each of the components of METS in the the localization of

lesions (LAD / LCX / RCA / OM etc) could not be independently assessed in

this study

45

6. Asian Indians have a tendency to develop metabolic abnormalities at a lower

BMI and waist circumference than other population groups. Conventional

criteria may therefore underestimate the prevalence of METS. Criteria used

(NCEP - ATP III) may not be entirely appropriate for South Indian patients

who have a different genetic makeup with regards to lipid metabolism.

However, the above criteria were adapted in this study as they are universally

accepted and are convenient for comparisons purpose.

7. In the present study, low HDL, followed by high triglycerides was identified as

the important factor determining the severity of CAD. However, other Indian

studies have arrived at varying conclusions like FBS, BP or waist

circumference being the most important determinant. Larger studies are

required to identify appropriate factors determining the severity of CAD in

local populations.

8. Further studies are required to establish the incidence and the causative

relationship between conditions like cancer, liver disease, hyperuricemia and

sleep apnoea which are said to be associated with METS.

9. METS only offers a Relative Risk of cardiovascular disease. Studies have to

be done to compare them with other widely accepted algorithms like

Framingham score to assess whether this scoring improves the prediction of

cardiovascular mortality and morbidity.

10. Other important factors like smoking, stress, poor treatment adherence, low

BMI (<18 Kg/Sq.mt) and poor life style management have not been included

in the scoring though they have a significant impact in the causation of CVD.

46

CONCLUSION

This is one of the prospective study carried out to describe the prevalence of

metabolic syndrome in coronary artery disease and to assessits impact on hospital

outcome.

The metabolic syndrome is a highly prevalent condition among the patients

with coronary artery disease and has detrimental impact on shortterm outcome.

Metabolic syndrome is a clustering of risk factors of metabolic originthat are

together associated with higher risk of cardiovascular disease and the need to

develop strategies for controlling this syndrome and itscomponent conditions.

In the industrialized countries there is a continuing decline of CAD during the

last three decades. Between 1965-1990, CAD mortality had decreased by 60% in

Japan and Finland and by 50% in USA, Canada, France, and Australia. This has

been possible by focusing on public education programmes for modifying the known

risk factors and by targeting high risk individuals. This achievement of the

industrialized nations must become an inspiration for the physicians and the policy

makers in India.

Early investigations diagnosis, treatment including lifestyle modification and

prevention of the metabolic syndrome will reduce the development of cardiovascular

diseases like myocardial infarction including its complications and it present a major

challenge for health care professionals facing an epidemic of overweight and

sedentary lifestyle.

To conclude, Cardiovascular disease patients with METS must beidentified

and managed aggressively to reduce both morbidity and mortalitysince it is a

preventable condition.

47

SUMMARY

In the present study, 100 cases of acute myocardial infarction were studied

over a period of one year for metabolic syndrome using the NCEPATP III criteria and

metabolic syndrome was present in 44 cases (44%).

The age of the patients ranged from 31 to 80 years, with a median age of 50.5

years. Maximum number of cases was in the 41-50 years (34%).

Male cases predominated in both the groups with and without metabolic

syndrome (75% and 79% respectively). Females were more likely to have

metabolic syndrome.

Chest pain was the most common symptom in both the groups. (95% and

100%). Breathlessness (32%) and sweating (56%) was also more common in

metabolic syndrome patients.

57% and 56% of metabolic syndrome patients had past history of diabetes

mellitus and hypertension respectively. 29.5% of metabolic syndrome cases

were smokers and 43% were alcoholic and 27% had family history of

coronary artery disease.

The body mass index of ≥30 kg/m2 was present in 38.6% of metabolic

syndrome cases with mean value of 27.2±3.3 kg/m2.

Among the components of metabolic syndrome low HDL-cholesterol was the

most prevalent component in both the groups. (95% in metabolic syndrome

and 57% in without metabolic syndrome cases).

High triglycerides (95%) was the next most prevalent component in metabolic

syndrome cases followed by the diabetes or fasting blood sugar ≥110mg/dl

(82%), hypertension or blood pressure of ≥130/85 mm of Hg (84%) and high

waist circumference (39%).

48

During one week in hospital prognosis of myocardial infarction 52% of patients

had heart failure, 8% had ventricular tachycardia/fibrillation, 3% patients had

recurrent myocardial infarction in METS.

Development of complications in coronary artery disease patients was around 4

times higher in metabolic syndrome patients compared to without metabolic

syndrome cases.

RECOMMENDATIONS:

Detection of one component of metabolic syndrome should prompt the

health care provider to look for all the other risk factors so that the

progression to CVD from METS could be slowed.

Government and NGOs should focus on the menace of non-

communicable diseases in the society and spread awareness in the

public.

Low cost screening programmes should be made available and

publicized in the community.

Generic drugs should be made widely available and their usage

encouraged by health care providers.

More focus should be set on the management of post-infarct patients

with METS with strategies such as intensive glycemic control by insulin

infusion in view of significantly increased complication rate as can be

seen from this study.

Steps should be taken to reverse the alarming trend of younger

patients being detected with METS progressing to CVD and more

number of women with METS developing complications by specifically

addressing those particular groups from an early age.

49

REFERENCES

1. Feinlib M, Harlik RJ, and Thom TJ. The changing pattern of ischaemic heart

disease. J Cardiovascualr Med 1982;7:139.

2. Allison RB, Rodriguez FL, and Higgins EA. Clinicopathological correlation in

coronary atherosclerosis. Four hundred thirty patient studies with postmortem

oronary angiography. Circulation1963;27:170.

3. Grundy JM, Cleemanji, Daniels SR, et al. American Heart Association.

National Heart Lung, and Blood Institute. Diagnosis and management of

metabolic syndrome : An American heart association / National Heart Lung

and Blood Institute scientific statement. Circulation 2005;112(17):2735-52.

4. Third report of the National Cholesterol Education Program (NCEP)Expert

panel on Detection, Evaluation, and Treatment of high bloodcholesterol in

adults (Adult Treatment Panel III) Final report. Circulation 2002; 106: 3146-

3421.

5. Yajnik CS. The insulin resistance epidemic in India: fetal origins, later lifestyle

or both? Nutr Rev 2001; 59: 1-9.

6. Milani RV, Lavie CJ. Prevalence and profile of metabolic syndromein patients

following acute coronary events and effects of therapeutic life style change

with cardiac rehabilitation. Am J Cardiol 2003; 92(1): 50-54.

7. Haffner SM. The metabolic syndrome: Inflammation, Diabetes mellitus, and

Cardiovascular disease. Am J Cardiol 2006; 97(suppl): 3A-11A.

8. Ford EA, Giles WH. A comparison of the prevalence of the metabolic

syndrome using Two Proposed Definitions. Diabetes Care 2003; 26: 575-581.

50

9. Munjal YP, Sarena A. Metabolic syndrome: Assessing Cardiometabolic risk,

Chapter 50: In YP Munjal, Post-graduate medicine (Recent Advances in

Medicine): JP Publishers: 2007; XXI: 461.

10.King H, Aubert RE, Herman WH. Global burden of diabetes, 1995- 2005, -

prevalence, numerical estimates, and projections. Diabetes Care 1998; 21:

1414-31.

11.Kylin E. Studien uber das hypertonic – hyperglykamie – hyperurikamie

syndrome. Zentralblatt fur Innere Medizin 1923; 44:105-27.

12.Himsworth HP. The mechanism of diabetes mellitus. Lancet 1939; ii: 1-6.

13.Vague J. La differenciation sexuelle, facteur determinant des forms

del’obesite. Press Med 1947; 30: 339-40.

14.Raven G. Role of insulin resistance in human disease. Diabetes 1988;37:

1595-1607.

15. Jeppesen J, Hansen TW, Rasmussen S, Ibsen H, Pederson CT,Madsbad S.

Insulin resistance, the metabolic syndrome, and risk of Incident

Cardiovascular Disease. J Am Coll Cardiol 2007; 49: 2112-9.

16.Deedwania PC, Gupta R. Management issues in the metabolic syndrome. J

Assoc Physicians India 2006; 54: 797-810

17. Lemieux I, Pascot A, Couillard C, et al. Hypertriglyceridemic waist: a marker

of atherogenic metabolic triad in men? Circulation 2000; 102: 179-84.

18. Ford ES. Prevalence of the metabolic syndrome in US population. Endocrinol

Metab Clin N Am 2004; 33: 333-350.

19.Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes

mellitus and its complications. Part 1: Diagnosis and classification of diabetes

mellitus provisional report of WHO consultation. Diabet Med 1998; 15: 539-53.

51

20. Balkau B, Charles MA. Comment on the provisional report from the WHO

consultation. European group for the study of Insulin resistance (EGIR).

Diabet Med 1999; 16: 442-43. 21.

21. Executive summary of the third report of the National Cholesterol Education

Program (NCEP) Expert panel on Detection, Evaluation, and Treatment of

high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285:

2486-97.

22.Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;

365: 1415-28. 23.

23.Misra A, Wasir JS, Pandey RM. An evaluation of candidate definitions of the

metabolic syndrome in Adult Asian Indians.Diabetes Care 2005; 28: 398-403.

24. Einhorn D, Reaven GM, Cobin RH. American college of endocrinology

position statement on insulin resistance syndrome. Endocr Pract 2002; 9:

236-52.

25. American Diabetes Association. Frequently asked questions aboutpre-

diabetes. Available at http:/www.diabetes.org/pre-diabetes/ faq.jsp.

26.Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant D, for the Conference

Participants. Definition of metabolic syndrome: report of the National, Heart,

Lung, and Blood Institute/American Heart Association conference on scientific

issues related to definition. Circulation. 2004;109:433-438.

27. American Heart Association's description of Syndrome X.

28. Kogiso T, Moriyoshi Y, Shimizu S, Nagahara H, Shiratori K (March 2009).

"High-sensitivity C-reactive protein as a serum predictor of nonalcoholic fatty

liver disease based on the Akaike Information Criterion scoring system in the

general Japanese population". J. Gastroenterol. 44 (4): 313.

52

29. Daskalopoulou SS. Athyros VG, Kolovou GD, Anagnostopoulou KK,

Mikhailidis DP. Definitions of metabolic syndrome: Where are we now? Curr

Vasc Pharmacol 2006; 4(3): 185-97.

30.Joshi Sr. Metabolic syndrome – Emerging clusters of the Indian Phenotype. J

Assoc Physicians India 2003; 51: 445-6.

31. Robert H Franch, John S. Douglas J, Spencer B King III, Morton J Kern.

Cardiac catheterization, coronary arteriography and coronary blood flow and

pressure measures. Chapter 15, In: Valentine Fuster, R Wayne Alexander

Robert A O’Rourke, Robert Roberts, Spencer B. King III, Hein J.J. Wellens

(eds). Hurst’s the heart. 10th Edn., Vol.I, 2001 .p.479-517.

32.Jeffery J Popma. Coronary angiography and intravascular ultrasound imaging.

Chapter 18, In: Douglas P. Zipes, Peter Libby, Robert O, Bonow, Eugene

Braunwald (eds), Braunwald’s heart disease. A text book of Cardiovascular

Medicine. 7th Edn., 2005 .p.423-455.

33. Kanitz MG, Giovannucci SJ and Jones JS, Mott M. Myocardial infarction in

young adults, risk factors and clinical features. J Emerge Med 1996 Mar-Apr;

14(2): 139-145.

34. Osula S, Bell GM, Hornung RS. Acute myocardial infarction in young adults :

Causes and management. Postgrad Med J 2002 Jan; 78(915):27-30.

35.Vijay Achari, Thakur, Arun K Sinha. The metabolic syndrome, its prevalence

and association with coronary artery disease in type 2 diabetes mellitus.

JICAM 2006;7(1):32-8.

36. Turhan, Hansen Ayse, SActi, Basar, Nurcan, Bicer, Asuman. High

prevalence of metabolic syndrome among young women with premature

coronary artery disease. 2005 Feb; 16(1):37-40.

53

37. Kevin E. Kp, Oscar C. Moraquin, David E. Kelly, Steven E. Reis HD, William

J Rojers. WISE Study. Circulation 2004;109:706-713.

38. Ford ES, Giles WH, Dietz WH. Prevalence of the metabolic syndrome among

US adults: findings from the third National Health and Nutrition Examination

Survey. JAMA 2002; 287: 356-59.

39. Mohan V, Shanthirani S, Deepa R, Premalatha G, Sastry NG, Saroja R. Intra-

urban differences in the prevalence of the metabolic syndrome in southern

India – the Chennai urban population study (CUPS No.4). Diabet Med 2001;

18: 280-7.

40. Ramachandran A, Snehalatha C, Satyavani K, Sivasankari S, Vijay V.

Metabolic syndrome in urban Asian Indian adults – a population study using

modified ATP III criteria. Diab Res Clin Pract 2003; 60: 199-204.

41. Gupta A, Gupta R, Sarma M, Rastogi S, Gupta VP, Kothari K.Prevalence of

diabetes impaired fasting glucose and insulin resistance syndrome in an

urban Indian population. Diab Res Clin Pract 2003;61: 69-76.

42. Deepa R, Shanthirani S, Premalatha G, Sastry NG, Mohan V. Prevalence of

insulin resistance syndrome in a selected south Indian population. The

Chennai urban population study-7 (CUPS-7). Indian J Med Res 2002; 115-

118-127.

43.Cameron AJ, Shaw JE, Zimmet PZ. The metabolic syndrome: prevalence in

worldwide population. Endocrinol Metab Clin North Am 2004; 33: 351-75.

44. . Atul G, Agarwal PK. Metabolic syndrome. Indian J Med Sci 2006; 60: 72-81.

45. . Misra A, Misra R, Wijesuriya M, Banerjee D. The metabolic syndrome in

South Asians: Continuing escalation and possible solutions. Indian J Med Res

2007; 125: 345-54.

54

46.Deepa M, Farooq S, Datta M, Deepa R, Mohan V. Prevalence of metabolic

syndrome using WHO, ATP III and IDF definitions in Asian Indians: the

Chennai Urban Rural Epidemiology study. (CURES-34). Diabetes Metab Res

Rev 2007; 23: 127-34.

47. Gupta R, Deedwania PC, Gupta A, Rostagi S, Panwar RB, Kothari K.

Prevalence of metabolic syndrome in an Indian urban population. Int J Cardiol

2004; 97(2): 257-61.

48. Isomaa B, Almgreen P, Tuomi T, et al. Cardiovascular morbidity and mortality

associated with the metabolic syndrome. Diabetes Care 2001; 24: 683-9.

49.Harte A, Meternan P, Chetty R, et al. Insulin mediated upregulation of the

rennin angiotensin system in human subcutaneous adipocyte is reduced by

rosiglitazone. Circulation 2005; 111: 1954-61.

50. Hulthe J, Bokemark L, Wikstrand J, Fagerberg B. The metabolic syndrome,

LDL particle size, and atherosclerosis: the Atherosclerosis and Insulin

resistance (AIR) study. Arterioscler Thromb Vasc Biol 2000; 20: 2140-7.

51. Yusuf S, Hawken S, Onpuu S. On behalf of the INTERHEART study

investigators. Effect of potentially modifiable risk factors associated with

myocardial infarction in 52 countries (the INTERHEART study): Case –

control study. Lancet 2004; 364: 937-52.

52. Ninomiya JK, L’Italien G, Criqui MH, Whyte JL, Gamst A, Chen RS.

Association of the metabolic syndrome with history of myocardial infarction

and stroke in the third national health and nutrition examination survey.

Circulation 2004; 109: 42-46.

55

53.Ridker PM, Burning JE, Cook NR, Rifai N. CRP, The metabolic syndrome,

and risk of incident. Cardiovascular events. Circula ion 2003; 107: 391-97.54.

Levantesi G,

54.Macchia A, Marfici RM, Franzosi MG, Maggloni AP,Z Nicolosi GL, et al.

Metabolic syndrome and risk of cardiovascular events after myocardial

infarction. J Am Coll Cardiol 2005; 46(2):277-83.

55. Knopp RH. Estrogen, female gender and heart disease. Chapter 8 In:Eric J

Topol, Textbook of cardiovascular medicine: Lippincott-Raven Publishers,

1998; 2002.

56. Munja YP. Metabolic syndrome – A useful concept. Chapter-32 in: RK Singal.

Medicine update: Jaypee Publishers 2007; 17: 185-9.

57. Achari V, Thakur AK, Sinha AK. The metabolic syndrome – Its prevalence

and association with coronary artery disease in type 2 diabetes. JIACM 2006;

7(1): 32-8.

58. Lillioja S, Mott DM. In vivo insulin action is familial characteristic in non

diabetic PIMA Indians. Diabetes 1986; 36: 1329-35.

59. Ecker RH. Lipoprotein lipase. A multifunctional enzyme relevant to common

metabolic diseases. N Eng J Med 1989; 320: 1060-68.

60. . Misra A. Insulin resistance syndrome current prospective and its relevance in

Indians. Indian Heart J 1998; 50: 385-95.

61. Mathews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC.

Homeostasis model assessment: insulin resistance and beta-cell function

from fasting plasma glucose and insulin concentrations in man. Diabetologia

1985; 28: 412-19.

56

62.Mishra A, Shukla P, Reddy KS, Lall SB, Panday RM. Serum insulin levels in

non-obese diabetic Asian Indians with acute coronaryevents. Indian Heart J

2000;52:280-4.

63. Schneider JG, Tompkins C, Blumenthal RS, Mora S. The metabolic

syndrome in women. Cardiol Rev 2006; 14(6): 286-91.

64. Rajat J. Gaiha M, Chakravarti AL, Daga MK. Insulin

resistance/Hyperinsulinemia as a risk factor for common carotid artery

intima/media thickness in Essential hypertension. JIACM 2005; 6(2):122-8.

65. Guettier JM, Georgopoulos A, Tsai MY, Radha V, Shanthirani S, Deepa R, et

al. Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III

genes are associated with the metabolic syndrome and dyslipidemia in a

south Asian population. J Endocrinol Metab 2005; 90: 1705-11.

66. Lee S, Janssen I, Ross R. Inter individual variation in abdominal

subcutaneous and visceral adipose tissue: influence of measurement site. J

Appl Physiol 2004; 97: 948-54.

67. . Aubert H, Frere C, Aillaud MF, Morange PE, Vague IJ, Abessi MC. Weak

and non-independent association between plasma TAFI antigenlevels and the

insulin resistances. J Thromb Haemost 2003; 1: 791-97.

68. Lee YH, Pralley RE. The evolving role of inflammation in obesity and the

metabolic syndrome. Curr Diabetes Rep 2005; 5: 70-5.

69. Grundy SM. What is the contribution of obesity to the metabolic syndrome?

Endocrinol Metab Clin N Am 2004; 33: 267-82.

70. Misra A, Wasir JS, Vikram NK. Waist circumference criteria for thediagnosis

of abdominal obesity are not applicable uniformly to all population and ethnic

groups. Nutrition 2005; 21: 969-76.

57

71. . Sivashankaran S, Thankappan KR. Beta cell protection and

metabolicsyndrome. Indian J Med Res 2007; 125: 184-5.

72. Sharma P, Misra S. Metabolic syndrome: Early identification prevents type 2

diabetes and cardiovascular disease. Indian J Clinical Biochemistry 2007;

22(1): 1-3.

73. Das UN. Metabolic syndrome X is common in Indians: but, why and how? J

Assoc Physicians India 2003; 51: 987-98.

74. Lewis GF, Steiner G. Acute effects of insulin in the control of VLDL

production in humans. Implications for the insulin-resistant state.Diabetes

Care 1996; 19: 390-93.

75.Murakami T, Michelagnoli S, Loughi R, et al. Triglycerides are major

determinants of cholesterol esterification/ transfer and HDL remodeling in

human plasma. Arterioscler Thromb Vas Biol 1995; 15: 1819-28.

76. Joseph JW, Koshkin V, Saleh MC. Free fatty acid induced beta-cell defects

are dependent on uncoupling protein 2 expression. J Biol Chem 2004; 279:

15049-56.

77. Porte D. Jr, Kahn SE. β-cell dysfunction and failure in type 2 diabetes–

potential mechanisms. Diabetes 2001; 50: 5160-3.

78.Tripathy D, Mohanty P, Dhindsa S. Elevation of free fatty acids induces

inflammation and impairs vascular reactivity in healthy ubjects. Diabetes

2003; 52: 2882-87.

79.Egan BM. Insulin resistance and the sympathetic nervous system. Curr

Hypertens Rep 2003; 5: 247-54.

58

80. Hanley AJ, Karter AJ, Festa. Factor analysis of metabolic syndrome using

directly measured insulin sensitivity: The insulin resistance atherosclerosis

study. Diabetes 2002; 51: 2642-47.

81.Schillaci G, Pirro M, Vaudo G, Gemelli F, marchesis, Porcellatic et al.

Prognostic value of the metabolic syndrome in essential hypertension. J Am

Coll Cardiol 2004; 43(10): 1817-22.

82. Esler MD. Metabolic syndrome and hypertension: What are the outstanding

problems? Dialogues cardiovasc Med 2004; 9: 167-72.

83. Xingwang YE, Zhijie Y, Li H, Franco OH. Distribution of C-reactive protein

and its association with metabolic syndrome in middle-aged and older

Chinese people. J Am Coll Cardiol 2007; 49(17): 1798-05.

84. . Diamond J. The double puzzle of diabetes. Nature 2003; 423: 599-602.

85. Das UN. Aberrant expression of perilipins and 11-β-HSD-1 as molecular

signatures of metabolic syndrome X in South East Asians. J Assoc Physicians

India 2006; 54: 637-49.

86. Unger RH. Lipid overload and overflow: Metabolic trauma and the metabolic

syndrome. Trends Endocrinol Metab 2003; 14: 398-403.

87. Kesu PA, Di Geogorio GB, Lu T, Rassouli N, Ranganathan G. Adiponectin

expression from human adipose tissue. Relation to obesity, insulin resistance,

and tumour necrosis factor-α expression. Diabetes 2003; 5: 1779-85.

88. Spencer King B. Anatomy of coronary tree. In : Coronary arteriography and

angioplasty, 3rd Edn., 1985 .p.368-369.

89. Donald S. Baim and William Grossman. Coronary angiography. Chapter 11,

In : Donald S. Bain, William Grossman (eds), The textbook of Gossman’s

59

cardiac catheterization, Aniography and intervention, 6th Edn., 2000 .p.211-

256.

90.Deedwania PC, Gutpa R. East Asians, south Asians; and Asian and Pacific

Islander Americans. In: Wong ND, Black HR, Gardin JM. Preventive

cardiology: a practical approach. 2nd Ed. New York: McGraw Hill. 2005; 456-

72.

91. Grundy SM, Cleeman JI, Daniels SR, et al. Diagnosis and management of

the metabolic syndrome : An American Heart Association / National Heart

Lung and Blood Institute scientific statement. Circulation 2005; 112: 2735-52.

92. . Damodaran A, Malathi A, Patil N, et al. Therapeutic potential of yoga

practices in modifying cardiovascular risk profile. J Assoc Physicians India

2002; 50: 633-40.

93. Krejs GJ. Metabolic benefits associated with sibutramine therapy. IntJ

Obesity 2002; 26 (Suppl 4): S34-S37.

94. Pagotto U, Pasquali R. Fighting obesity and associated risk factors by

antagonizing cannabinoid type 1 receptors. Lancet 2005; 365: 1363-64.

95. . Van Gaal LF, Rissanen AM, Scheen AJ, Zigler O, Rossner S, for the RIO-

Europe study group. Effects of cannabinoid – 1 receptor blocker rimonabant

on weight reduction and cardiovascular risk factors in overweight patients: 1 –

year experience from the RIO-Europe study. Lancet 2005; 365: 1389-97.

96. Despres JP, Golay A, Sjostrom L, rimonabant in Obesity lipids (RIOLipids)

study group. Effects of rimonabant on metabolic risk factors in overweight

patients with dyslipidemia. N Engl J Med 2005; 353: 2121-34.

97.Kelley De. Thermodynamics, liposuction and obesity. N Engl J Med2004; 350:

2542-44.

60

98. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on

insulin action and risk factors for coronary heart disease. N Engl J Med 2004;

350: 2449-557.

99. Sjostrom L, Lindroos AK, Peltonen M, et al. Lifestyle, diabetes and

cardiovascular risks factors 10 years after bariatric surgery. N Engl J Med

2004; 351: 2683-93.

100. Deedwania PC. TNT study and metabolic syndrome. Circulation 2005; 112

(Suppl A):88-9.

101. Cottrell DA, Marshall BJ, Falko JM. Therapeutic approaches to dyslipidemia

in diabetes mellitus and metabolic syndrome. Curr Opin Cardiol 2003; 18: 301-

08.

102. Han SH, Quon MJ, Koh KK. Beneficial vascular and metabolic effects of

peroxisome proliferators activated receptor-alpha activators. Hypertension 2005;

46: 1086-92.

103. Sharma M, Sharma DR, Singh V, et al. Evaluation of efficacy and safety of

fixed dose lovastatin-niacin combination in hyperlipidemic patients: a multicentric

study. Vasc Health Risk Management 2006; 2: 87-93.

104. Libby P. The forgotten majority: unfinished business in cardiovascular risk

reduction. J Am Coll Cardiol 2005; 46: 1225-28.

105. Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint

national committee on prevention, detection, evaluation and treatment of high

blood pressure : the JNC-7 report. JAMA 2003;289:2560-72.

106. Diabetes prevention program research group. Impact of intensive lifestyle

and metformin therapy on cardiovascular disease risk factors in the diabetes

prevention program. Diabetes Care 2005;28:888-94.

61

107. Rajagopalan R, Iyer S, Khan M. Effect of pioglitazone on metabolic syndrome

risk factors: results of double blind, multi-center, randomized clinical trials. Curr

Med Res Opin 2005; 21: 163-72.

108. Deedwania PC, Fonesca VA. Diabetes, prediabetes, and cardiovascular risk:

Shifting the paradigm. Am J Med 2005; 118: 939- 47.

109. Wald N, Law MR. A strategy to reduce cardiovascular disease by more than

80%. BMJ 2003; 326: 1149-55.

110. Reaven G. The metabolic syndrome or the insulin resistance syndrome?

Different names, different concepts, and different goals. Endocrinal Metab Clin N-

Am 2004;33:283-303.

111. Alpert JS, Thygesan K, Antman E, Bassand JP. Myocardial infarction

redefined: a consensus document of the Joint European society of

Cardiology/American college of cardiology committee for the redefinition of

myocardial infarction. J Am Coll Cardiol 2000;36:959-69.

112. Norhammar A, Tenerz A, Nilsson G. Glucose metabolism in patients with

acute myocardial infarction and no previous diagnosis of diabetes mellitus: a

prospective study. Lancet 2002; 359:2140-44.

113. . Zeller M, Gabriel P, Ravisy J, Laurent Y, Manifican LJ, Hullier et

al.Prevalence and impact of metabolic syndrome on hospital outcomes in acute

myocardial infarction.

114. Schwartz, Szarek M. Olsson A, Sasiela W, Relation of characteristics of

metabolic syndrome to short-term prognosis and effects of intensive statin

therapy after acute coronary syndrome. Diabetes Care 2005;28:2508-13

62

115. Badui E, Rangel A, Valdespino A, Gracf A, Plaza A, Chavez E, et al. Acute

myocardial infarct in young adults. A report of 142 cases. Arch Inst Cardial Mex

1993 Nov-Dec; 63(6):529-37.

116. Shah A, Sreenivasan S, Shah H, Lanjewar C, Nabas A and Nyayadhish P, et

al. Clincial, biochemical and angiographic profile of young (≤ 40 years) patients

with acute mycardial infarction. Indian Heart Journal 2005;57:423.

117. Aronson D, Ray field EJ, Chesebro JH. Mechanisms determiningcourse and

outcome of diabetes patients who have had myocardial infarction. Ann ntern Med

1997; 126:296-306.

118. Deedwania PC. Metabolic syndrome and vascular disease. Its nature or

nurture leading the new epidemic of cardiovascular disease? Circulation 2004;

109:2-4

119. Jha P, Enas EA, Yusuf S. Coronary artery disease in Asian Indians :

Prevalence and risk factors. Asian Am & Pac Islander J Health 1993;1:161-175.

120. Bahulyan CG Hospital data on CHD from North Kerala. In : Vijaragahavan G,

ed. Cardiovascular disease prevention. MC5459(S).

121. Hughes LD, Raual U, Raftery E. Myocardial infarction in Asian andwhite men.

Br Med J 1989;298:1345-1350.

63

ANNEXURE – I

PROFORMA

Case NO :

D.O.A :

Name : D.O.D :

Age : Sex: IP. NO. :

Occupation :

1) CHIEF COMPLAINTS :

II) HISTORY OF PRESENT ILLNESS :

1) Chest pain : onset

Site

Nature

Duration

Radiation

Aggravating/ Relieving factors.

2) Breathlessness: onset

Duration

Degree

Orthopnoea/PND

3) Cough : Sputum

Mucoid/ Serous

Colour

Blood stained – Y/N

Postural variation

4) Palpitations : Onset

Regular/Irregular

Continuous/intermittent

Relieving factors

At rest – Y/N

5) Sweating : Y/N

6) Syncope : Y/N

64

7) Vomiting : Y/N

8) Miscellaneous :

III) PAST HISTORY: Diabetes mellitus – Duration

Treatment

Hypertension – Duration

Treatment

IHD

IV) FAMILY HISTORY: Coronary Artery Disease

Diabetes mellitus

Hypertension

V) PERSONAL HISTORY: Current smoking – Y/N

Alcohol consumption – Y/N

Diet

Sleep

VI) GENERAL PHYSICAL EXAMINATION:

1) Appearance

2) Built and nourishment

3) Pallor/ Icterus/ Cyanosis/ Clubbing/ Pedal oedema

4) Xanthoma/ Xanthelesma/ Arcus senalis/ juvenalis

5) Vital signs : pulse : BP: SBP Temperature:

JVP: DBP RR:

6) Waist circumference

7) Body-Mass index

8) Waist/ Hip ratio

VII) CARDIOVASCULAR SYSTEM:

INSPECTION: 1)Precordium

2) Apical impulse

3) Other pulsations

65

PALPATION: 1) Apical impulse

2) Para sternal heave

3) Thrills

4) Palpable sounds

5) Other pulsations

PERCUSSION:

AUSCULTATION: 1) Heart sounds

2) Murmurs

3) Extra sounds

4) Others

VIII) RESPIRATORY SYSTEM: 1) INSPECTION

2) PALPATION

3) PERCUSSION

4) AUSCULTATION – Basal Rales Y/N

IX) PER ABDOMAN: 1) INSPECTION

2) PALPATION

3) PERCUSSION

4) AUSCULTATION

X) CENTRAL NERVOUS SYSTEM: 1) HIGHER MENTAL FUNCTIONS

2) CRANIAL NERVES

3) MOTOR SYSTEM

4) SENSORY SYSTEM

5) MENINGEAL SIGNS

6) OTHERS

XI) CLINICAL DIAGNOSIS:

66

XII) INVESTIGATIONS:

1) BLOOD : FBS - PPBS -

BLOOD UREA - S.CREATININE –

LIPID PROFILE: T. CHOLESTEROL -

S. TRIGLYCERIDES -

HDL – C -

LDL – C –

CARDIAC ENZYMES A: CPK - AST - LDH -

2) ECG :

3) ECHO :

4) CORONARY ANGIOGRAM :

a. LAD

b. RCA

c. LCX

XIII) COMMENTS

XIV) FOLLOW – UP: Basal Rales

ECG

CARDIAC ENZYMES – CPK

67

ANNEXURE - II

INFORMED CONSENT FORM(ICF)

Title “Prevalence of Metabolic Syndrome In Coronary Artery Disease

Proven By Coronary Angiogram”.

Name of P.G/U.G. Student/Faculty member : Dr. VASUDHA KAVURU

Name of Guide : Prof Dr. G.Chakradhar Rao M.D

I ______________________________(Name) ______, aged about ______ years, a

resident of _________________ village of ________________ District, have been detailed

about the procedure in this study. I understood that my identity will not be disclosed and I

can withdrawn from the study at any point of the time with out assigning any reason. In fully

aware that my withdrawal from the study will not affect my ongoing treatment.

_________________________ ___________________________

Signature of the witness Signature of the patient/ Gaurdian

68

GUNTUR MEDICAL COLLEE & GOVT. GENERAL HOSPITALGUNTUR-522019(AP)

INSTITUTIONAL ETHICS COMMITTEE(IEC)

ETHICS CLEARANCE CERTIFICATE

The Institutional Ethics Committee of Guntur Medical College & Government General

Hospital, Guntur met on ___________ at _________________ to scrutinize the

Synopsis / Research projects of Post graduate students/Under graduate students/

Faculty members of this College from Ethics point of view. After scrutiny, the

following version of Synopsis of Dissertation/Research project has been accorded

Ethics Clearance.

Title “Prevalence of Metabolic Syndrome In Coronary Artery Disease

Proven By Coronary Angiogram”

69

Name of P.G/U.G. Student/Faculty member : : Dr. VASUDHA KAVURU

Name of Guide : Prof Prof Dr. G.Chakradhar Rao M.D

Date:

Guntur

Member Secretary, IEC Chairman, IEC

Principal

70