Dr.M.G.R. MEDICAL UNIVERSITY

A CROSS SECTIONAL STUDY ON CLINICAL PROFILE AND RISK FACTORS IN FEMALE CORONARY

ARTERY DISEASE PATIENTS ATTENDING CHENGALPATTU MEDICAL COLLEGE

Dissertation submitted to

THE TAMIL NADU

Dr.M.G.R. MEDICAL UNIVERSITY

In partial fulfillment of the regulations for the award of the degree

M.D. GENERAL MEDICINE

BRANCH – I Reg. No. 201711253

GOVT. CHENGALPATTU MEDICAL COLLEGE & HOSPITAL CHENGALPATTU - 603001.

MAY - 2020

CERTIFICATE

This is to certify that the dissertation titled "A CROSS SECTIONAL STUDY ON CLINICAL PROFILE AND RISK FACTORS IN FEMALE CORONARY ARTERY DISEASE PATIENTS ATTENDING CHENGALPATTU MEDICAL COLLEGE” is the Bonafide original work of DR.P.KANNAN, in partial fulfillment of the requirements for M.D., Branch - I, (General Medicine) Examination of the Tamil Nadu Dr.M.G.R. Medical University to be held in May 2020.

Dr.G. HARIHARAN M.S., Mch., DEAN

Govt. Chengalpattu Medical College and Hospital,

Chengalpattu - 600 001.

Dr.R. NARMADHALAKSHMI MD., DCH., Professor and Head Department of Medicine

Govt. Chengalpattu Medical College and Hospital,

Chengalpattu – 600 001.

BONAFIDE CERTIFICATE

This is to certify that dissertation "A CROSS SECTIONAL STUDY ON CLINICAL PROFILE AND RISK FACTORS IN FEMALE CORONARY ARTERY DISEASE PATIENTS ATTENDING CHENGALPATTU MEDICAL COLLEGE” is a Bonafide work performed by DR.P.KANNAN, Postgraduate student of General Medicine, Govt. Chengalpattu Medical College, Chengalpattu under my guidance and supervision in fulfillment of regulations of The Tamil Nadu Dr. M.G.R Medical University for the award of M.D. Degree during the Academic period 2017-2020.

Dr. B. PRABAKAR M.D., Professor, III Unit Chief, Department of Medicine

Govt. Chengalpattu Medical College and Hospital,

Chengalpattu - 600 001.

Dr. R. NARMADHALAKSHMI., MD., DCH., Professor and Head Department of Medicine

Govt. Chengalpattu Medical College and Hospital,

Chengalpattu – 600 001.

DECLARATION

I, Dr.P.KANNAN, solemnly declare that this dissertation "A CROSS SECTIONAL STUDY ON CLINICAL PROFILE AND RISK FACTORS IN FEMALE CORONARY ARTERY DISEASE PATIENTS ATTENDING CHENGALPATTU MEDICAL COLLEGE " is Bonafide record of work done by me in the Department of Medicine, Government Stanley Medical College and Hospital, Chennai under the guidance of Prof. Dr.R. NARMADHA LAKSHMI., M.D., DCH Professor of Medicine, Government Chengalpattu Medical College and Hospital, Chengalpattu – 603001.

This dissertation is submitted to the Tamilnadu Dr.M.G.R. Medical University, Chennai in partial fulfillment of the University regulations for the award of MD Degree (General Medicine) Branch-I, Examination to be held in May 2020.

Place: Chengalpattu

Date: (Dr.P. KANNAN)

ACKNOWLEDGEMENT

I owe my thanks to the Dean, Govt. Chengalpattu Medical College and Hospital, Dr.G.HARIHARAN M.S., Mch. For allowing me to avail the facilities needed for my dissertation work.

I extend my sincere thanks to Dr.R.NARMADHALAKSHMI., MD., DCH., Professor and Head of the Department of Medicine, Govt. Chengalpattu Medical College and Hospital for her guidance during the study.

I express my gratitude to Prof. Dr.B.PRABAKAR., M.D., Professor of Medicine, Chief of Medical Unit III, Government Chengalpattu Medical College and Hospital for his valuable Suggestions and guidance.

I thank my Co-Guide Dr.E.ARULANANDHAN M.D., Assistant Professor, Department of Medicine for his guidance and cooperation in the study.

I am extremely thankful to my Assistant Professors Dr.K.KAMATCHI M.D., and Dr.G.BANUGOPANAR M.D., for their guidance and encouragement.

I owe my sincere thanks to all Professors and Assistant Professors in Cardiology Department for their valuable advice and appropriate suggestions.

I extend my thanks to my parents, my wife S.MuthuLakshmi and my junior and senior postgraduates who stood by me during my times of need. Their help and support have been invaluable to the study.

Finally, I thank all the patients for their extreme patience and cooperation.

PLAGIARISM CERTIFICATE

This is to certify that this dissertation work titled “A CROSS SECTIONAL STUDY ON CLINICAL PROFILE AND RISK FACTORS IN FEMALE CORONARY ARTERY DISEASE PATIENTS ATTENDING CHENGALPATTU MEDICAL COLLEGE” of the candidate DR.P.KANNAN., with registration Number 201711253 for the award of Degree of M.D in the branch of GENERAL MEDICINE-BRANCH-I. I personally verified the urkund.com website for the purpose of plagiarism Check. I found that the uploaded thesis file contains from introduction to conclusion pages and result shows 3% percentage of plagiarism in the dissertation.

Guide & Supervisor sign with Seal DR. R. NARMADHALAKSHMI M.D., D.C.H.

Professor and Head

Department of General Medicine Chengalpattu Medical College

Chengalpattu

CONTENTS

CHAPTER

NO. TITLE PAGE NO.

1. INTRODUCTION 1

2. AIM OF THE STUDY 3

3. REVIEW OF LITERATURE 4

4. MATERIALS & METHODS 51

5. RESULTS & ANALYSIS 58

6. DISCUSSION 87

7. CONCLUSIONS 98

8. LIMITATIONS 99

9. ACRONYMS 100

9. BIBLIOGRAPHY 102

10. ANNEXURES

(A) PROFORMA

(B) INFORMED CONSENT FORM

(C) PATIENT CONSENT FORM (ENGLISH) (D) PATIENT CONSENT FORM (TAMIL) (E) MASTER CHART

(F) KEY TO MASTER CHART

117 120 122 123 124 127

1. INTRODUCTION

Coronary heart disease has been defined as “impairment of heart function due to inadequate blood flow to the heart compared to its needs, caused by obstructive changes in the coronary circulation to the heart”.

Despite the importance of CAD for female, there is persistent perception that CAD is a man’s disease. Contributing to this notion is the observation of differences in incidence rates according to age; the incidence of CAD in women is lower than men, but rises steadily after fifth decade. In addition, women are more likely to have symptoms considered atypical compared with men. There is an urgent need to better understand the presentation of cardiac symptoms in females, in order to facilitate diagnosis and treatment, to initiate aggressive risk factor intervention and to improve the quality of life^{. (1)}

Coronary artery disease is the leading cause of death among women, regardless of race or ethnicity and causing the deaths of 1 in 3 women ⁽²⁾ than from stroke, lung cancer, chronic obstructive lung disease, and breast cancer combined.

Women with coronary artery disease present differently than men, have different pathophysiologies and risks profiles and are often significantly older and thus often have poorer outcomes. Framingham study showed that the risk of heart disease in women increased equally by natural menopause or by surgical menopause. Uterine factors especially regular menstrual blood loss might be

responsible for protection of pre-menopausal women against ischemic heart disease. ^[3,4]

Experts in industrialized societies have long recognized that the first presentation with coronary heart disease occurs approximately 10 years later among women than men, most commonly after menopause ⁽⁵⁾. Despite this delay in onset, mortality from coronary heart disease is increasing more rapidly among women than men from both developed and developing world ^(5).

Epidemiological studies from various parts of India have reported the rising trends and a high burden in the levels of conventional risk factors such as diabetes, hypertension and metabolic syndrome ^(6,7). Hence this study was considered to look for association of various risk factors and to study the clinical profile of coronary artery disease in female patients in Chengalpattu medical college, Chengalpattu.

2. AIM OF THE STUDY

1. To study the clinical profile of coronary artery disease in female patients in Chengalpattu Medical college.

2. To assess the various risk factors associated with coronary artery disease among the study Population.

3. REVIEW OF LITERATURE

DEFINITION

Coronary heart disease has been defined as “impairment of heart function due to inadequate blood flow to the heart compared to its needs, caused by obstructive changes in the coronary circulation to the heart”.

Depending on the rate of development and ultimate severity of the arterial narrowing(S) and the myocardial response, four ischemic syndromes may result.

1. Angina pectoris, of which there are three variants, the most threatening being unstable angina.

2. Myocardial infarction, the most important form, in which there can be substantial myocardial damage.

3. Chronic ischemic heart disease with CHF.

4. Sudden cardiac death.

Many women die every year from cardiovascular disease than from any other cause, yet women worry more about breast cancer than heart disease.

Women with heart disease may present differently than men, have unique underlying patho-physiologies, and have distinctive risk benefit profiles with commonly accepted therapies ^(8).

Heart disease is far more age dependent in women than in men; women with cardiovascular disease are older and have more comorbidities. This fact, in

turn, make diagnostic and treatment procedures more problematic in women. In addition, many effective pharmacological strategies are underutilized, and there is a lack of gender specific date on numerous therapies.

The etiology of atherothrombotic cardiovascular disease is multi-factorial, and several ‘risk factors’ are recognized to predispose an individual to develop the disease. These cardiovascular risk factors, which were initially characterized in the Framingham Heart Study, include: age, family history of premature cardiovascular disease, smoking, hypertension, hyperlipidemia, diabetes, obesity and sedentary lifestyle.⁽⁵⁾ The risk factors of acute MI are broadly divided into modifiable and non-modifiable.⁽⁹⁾ Modifiable risk factors are Hypercholesterolemia, Diabetes mellitus, Hypertension, Obesity, Smoking. Non modifiable risk factors are Age, Family history, Sex.

Although a family history of cardiovascular disease is a recognized risk factor, it is important to emphasize that cardiovascular disease is polygenic and numerous genetic abnormalities have been implicated in the development of the final common disease state.

Incidence and prevalence rates for cardiovascular diseases depend to a large extent on the age profile of the population, socio-economic, food habits and other lifestyle patterns; although other influences, including genetic differences influenced by ethnicity and race are also important.

ATHEROSCLEROSIS AND MI

In most of the cases CAD happens because of the inadequate coronary perfusion relative to myocardial demand. This may result from a combination of pre-existing (“fixed“) atherosclerotic occlusion of coronary arteries and new superimposed thrombosis and/or vasospasm of coronary arteries. Myocardial infarction (MI) occurs because of abrupt plaque change followed by thrombosis.

The initiating event is typically disruption of a plaque due to: Rupture, fissuring, or ulceration of plaques exposing highly thrombogenic plaque constituents or underlying sub endothelial basement membrane. Hemorrhage into the core of plaques with expansion of plaque volume and worsening of the luminal occlusion is a well-known mechanism by which MI occurs. The contemporary view of atherogenesis is expressed by the response to injury hypothesis. This model views atherosclerosis as a chronic inflammatory response of the arterial wall to endothelial injury. Inflammation plays an essential role at all stages of atherosclerosis, from inception to plaque rupture.

A. Adventitia B. Media C. Intima

Figure 3.1 Atheromatous Plaque

Figure 3.2 Complicated Atheromatous Plaque a. Thickened arterial wall b. Intraluminal hemorrhage c. Ulceration

Table 3.1 RISK FACTORS IN CAD FEMALES ^(10,11)

NON-MODIFIABLE RISK FACTORS Age

Women, in comparison with men, tend to have a better risk factor profile at younger ages, whereas the opposite is true at older ages.⁽⁸⁾ Women are about 10 years older than men at first manifestation of CAD, although they have similar plaque burden.⁽¹²⁾ Women will lose this 10-year advantage if they smoke, having diabetes, or had premature menopause. Younger women with ACS have up to 50% higher risk for mortality than their young male counterparts.^(13,14) The higher risk of mortality in these young females may be due in part to the perception that younger females are at very low risk of CAD and therefore diagnostic and therapeutic intervention is minimal.

Family history

Among women, a history of an MI or sudden death before the age of 55 in a sister is more strongly associated with risk of MI than that in a brother or parent. Family history of CAD in a sister is associated with 12-fold higher risk vs. 6-fold for a brother and 3-fold for a parent.⁽¹⁵⁾ Difference in genetic expression leads to difference in pathophysiology of atherosclerosis including plaque composition, endothelial dysfunction and hemostasis ⁽¹⁶⁾ Positive family history is said to be present when the problem occurs in first degree relative at a relatively younger age <55 years for men and < 65 years for women. ⁽¹⁾

MODIFIABLE RISK FACTORS FOR CORONARY HEART DISEASE IN WOMEN AND THEIR MODIFICATION

Diabetes Mellitus and Metabolic Syndrome

Diabetes is associated with a greater incremental risk in women, completely negating the “female advantage.” The American Heart Association awards double weight to diabetes in women ⁽¹⁸⁾ when calculating CHD risk, similar to the weight given a systolic blood pressure of 173 mm Hg or above or cholesterol level of 316mg / dl or above. According to the Nurses’ Health Study, patients with type 2 diabetes have a 3- to 7-fold increased risk of having a cardiovascular event ⁽¹⁹⁾. More than in male, diabetes dramatically increases the mortality of cardio vascular events in female. Diabetic women with myocardial infarction (MI) have twice the risk of another heart attack and a 4-fold likelihood of developing heart failure ⁽¹⁹⁾.

Type 2 diabetes⁽²⁰⁾ is associated with obesity, abdominal body fat distribution, hypertension, atherogenic dyslipidemia, and insulin resistance, all of which have been associated with higher CHD risk. This complex of abnormalities, termed “metabolic syndrome,” alters hepatic metabolism, lipoprotein levels, and circulating insulin levels. More so than in men, obesity and body fat distribution appear to be independent coronary artery disease risk factor in women ⁽²¹⁾. Diabetes is also linked with endothelial dysfunction and a variety of platelet abnormalities ⁽²²⁾. Two out of three people with diabetes die of

some type of CVD. Therefore, aggressive therapy for diabetes and high blood pressure is usually needed and can reduce the risk of heart disease and its associated complications. ^(23,24)

Hypertension

Men have a higher percentage of hypertension than women until the age of 45 years; between 45 and 64 years of age, men and women have similar percentages of hypertension; and after 64 years of age, a higher percentage of women have diagnosed hypertension than men. Women have 15% higher prevalence of hypertension than in men when age increases ⁽²⁵⁾. More than 25 million American women have high blood pressure, and cardiovascular risk related to hypertension ⁽²⁶⁾ rises steeply with age in females. Further, although women have fewer cardiovascular events, the population risk attributable to hypertension is higher for women ⁽²⁷⁾ than men because of the increased incidence with age and the longevity of women. According to the latest JNC-8 Guidelines, ⁽²⁸⁾ lifestyle interventions (e.g., low salt diet, increasing physical activity) are still a vital component in the management of hypertension. weight reduction of 9 kg can lower systolic BP by 6mmHg and diastolic BP by 3mmHg in hypertensive patients. ⁽²⁹⁾ However, compliance with such changes is low (~10 percent) and blood pressure increases again when physical activity decreases or weight is regained.

Most trails have shown equal efficacy of blood pressure lowering to prevent cardiovascular events in men and women. Although it is clear that hypertension in women should be treated as aggressively as in men, it is possible that the optimal choice of antihypertensive agent may differ. Pharmacologic therapy is based on patient’s age, ethnicity, and the presence of diabetes mellitus (DM) or chronic kidney disease (CKD). Blood pressure targets have become more lenient with a target blood pressure goal of <150/90 mm Hg for patients aged >60 years and a target blood pressure goal of <140/90 mm Hg for all other patients including those with DM and CKD. Thiazide type diuretic and calcium channel blockers are still the recommended class of medications for treating hy- pertension in most patients, with a preference for angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blockers (ARB) in patients with DM and with CKD ⁽²⁸⁾. Available evidence no longer supports the use of beta- adrenergic blocking agents (beta blockers) as first-line therapy for primary prevention, because of less benefit than with other drugs, particularly in elderly persons, and increasing evidence that the most frequently used beta blockers at usual doses carry an unacceptable risk of inducing type 2 diabetes ⁽³⁰⁾.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) demonstrated superiority of diuretic therapy in the prospecified female cohort, as in the trial as a whole. The Second Australian National Blood Pressure Study Group found that angiotensin-converting enzyme (ACE) inhibitor therapy decreased cardiovascular endpoints relative to

hydrochlorothiazide in men but not in women. The numbers of women included in trials are often too small to draw conclusions.

Figure 3.3:Prevalence of high blood pressure among adults 20 years of age and older, by age and sex, based on NHANES 2007 to 2010⁽³¹⁾ Smoking

The risk of death from cigarette smoking progressively increasing among women and the increased risks are now nearly identical for men and women.

Tobacco contributes to 17 percent of all female deaths in the United States and results in more deaths from CHD and stroke than any other cause. The combination of accelerated atherosclerosis and propensity to vascular thrombosis induced by cigarette smoking is responsible for a six-to nine-fold increased risk of myocardial infarction among female smokers compared with nonsmokers.

There is a similar increase in stroke risk. The combination of cigarette smoking and oral contraceptive use having synergistic effect at increasing the risk of arterial thrombosis and elevated risks for premature coronary disease and stroke.

Cigarettes have an anti estrogenic effect and induce an unfavorable lipid profile, leading female to lose their “natural” protection against atherosclerotic vascular disease. Smokers who quit reduce their excess risk of a coronary event by 50% within the first 2 years after cessation, with much of this benefit seen even within the first few months ⁽³²⁾. Counseling by physicians and other pro- viders is vital and has a great impact ⁽³³⁾.Cessation medications found to be effective for treating tobacco dependence include nicotine replacement products, either over-the-counter (e.g., nicotine patch, gum, lozenge) or prescription (e.g., nicotine inhaler, nasal spray), and prescription non-nicotine medications such as bupropion SR, varenicline tartrate, or new agents such as cytisine⁽³⁴⁾.Currently available methods to assist with quitting may be less effective in female, perhaps because of a greater behavioral component and less nicotine addiction in women smokers. Environmental exposure to tobacco smoke increases the risk of cardiovascular disease in women, and assessment of environmental exposure is an important part of risk assessment.

Lipids

Figure 3.4:RiskinCAD

The average lipid profile women are affected by hormonal status and changes throughout life. Young women have lower low-density lipoprotein (LDL) ⁽³⁵⁾ cholesterol levels and higher high-density lipoprotein (HDL) ⁽³⁶⁾ cholesterol levels than men of the same age. Many studies observed a rise in triglyceride and LDL cholesterol with menopause ⁽³⁷⁾ and the risk of CHD also increases. Elevated total cholesterol and LDL levels are only weakly associated with CHD in women and only in women 65 years old or younger. Instead cholesterol is closely and inversely associated with CHD ⁽³⁸⁾ risk.

Triglycerides ⁽³⁹⁾ are an independent predictor of CHD, particularly in older women. Indian women worldwide have a high TC/HDL ratio by virtue of low HDL, even when TC level are not elevated ⁽⁴⁰⁾. Optimum TC/HDL ratio is 3 and average ratio is 4. Ratio more than 5 appears to be a strong predictor of CAD and is observed in 25% of industrial and 32% of urban female populations in India.⁽⁴¹⁾ Lp(a) was a powerful predictor of mortality in the 4S study.⁽⁴²⁾Initial modification of a high-risk lipoprotein profile is generally accomplished by the same life-style changes and medications in men and women, although dietary interventions may be less effective in women.

Multiple trials have demonstrated efficacy of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors ⁽⁴³⁾, or statins in both primary and secondary prevention of coronary events and death in women with both elevated and normal cholesterol, supporting the persistent theory that there are benefits of these agents independent of LDL-lowering effects. Hormone replacement therapy reduces Lp(a) by an average of 20% in women with high Lp(a) levels. ⁽⁴⁴⁾

Women have generally not been included in trails of other classes of lipid-lowering agents, such as the bile acid sequestrant cholestyramine and the fibrate gemfibrozil.

In addition, there are no data from large trails on the efficacy of lipid- lowering agents targeted more specifically at altering the HDL and triglyceride

lipid sub fractions, which appear more important in women. It seems reasonable to apply strategies shown to be successful in male, recognizing that optimal care of female with dyslipidemia may eventually be different from that of male ⁽⁴⁵⁾. Estrogen

Due to Estrogen induced coronary vasodilation, Women are twice as likely to have plaque erosion (37% in women vs. 18% in men) while men are more likely to have plaque rupture (82% in men vs. 63% in women).⁽⁴⁶⁾The presence of estrogen in the premenopausal female population, the obvious protection this group enjoys against cardiovascular events, and documentation of estrogen receptors in cardio myocytes and vascular tissues in both men and women led tremendous enthusiasm for use of postmenopausal hormone replacement therapy as a preventive measure against atherosclerotic heart disease. This enthusiasm was bolstered by multiple observational studies suggesting improved longevity and decreased cardiac events in postmenopausal women receiving hormone replacement therapy as well as mechanistic data supporting biological plausibility ⁽⁴⁷⁾

Multiple randomized controlled trails in the past 5 years have refuted this hypothesis and provided strong evidence of an increase in cardiovascular risk particularly in the first year after beginning therapy, combined with increased risk of breast cancer, thromboembolic disease, and stroke exceeded the benefits

on reductions of fracture and colon cancer ⁽⁴⁸⁾resulting in a withdrawal of prior recommendations.

In the Women’s Health Initiative Study, use of estrogen alone, without a progestin, neither caused nor prevented cardiac events, although it did increase the risk of stroke and decrease the risk of hip fracture. Other studies documenting progression of atherosclerosis during hormone replacement therapy have confirmed the lack of benefit. Hormone replacement therapy has no place in prevention of heart disease in women at present. Hormone therapy retains a role in clinical practice only for the treatment of moderate to severe menopausal symptoms. ⁽⁴⁹⁾ Estrogen therapy is associated with impressive changes in so many risk factors, including lower LDL, higher HDL, improved glucose tolerance, and reductions in weight and waist circumference, that an understanding of the mechanism of increased risk is likely to revolutionize yet again our understanding of the atherosclerotic process.

Obesity and Diet

Obesity is a major public health problem in developed countries and an emerging health problem in developing nations, such as India. According to WHO report in 2016, 650 million adults were obese ^(50). India ranks 3 in the top 10 countries with obese people with a count of 40.4 million ⁽⁵¹⁾ Obesity is associated with increased risk of hypertension, diabetes, dyslipidemia and CAD.

Obesity is also said to be one of the most ignored health problems⁽⁵²⁾Body Mass

Index (BMI), is now accepted as the single best measure of obesity.⁽⁵³⁾In the 16- year data from the Nurses’ Health Study (NHS), CAD mortality was 4-fold lower in lean (BMI<21) than in obese women. ⁽⁵⁴⁾ For Asians, the optimum BMI is <23, whereas >23 is considered overweight and >25 obese. The prevalence of obesity is increasing amongst Indian female. Most women did not engage in leisure-time physical activity and 18.5% were smokers. ⁽⁵⁵⁾.

Obesity is associated with elevated-reactive protein (CRP), particularly in women. The combination of obesity and diabetes appears particularly very danger in women, as does the pattern of fat distribution. Abdominal fat accumulation is an important predictor of type 2 diabetes mellitus, hypertriglyceridemia, hypertension, and CHD ⁽⁵⁶⁾. Among women, a waist-to-hip ratio greater than 0.88 is predictive of a substantially increased risk of cardiovascular events, as is a waist circumference of more than 38inches ⁽⁵⁷⁾. Physical Activity

Physical Activity ⁽⁵⁸⁾ is more prevalent among women than men. There is a strong contrary association between physical activity and coronary events in women. Physical activity also has a salutary effect on other cardiovascular risk factors, including hypertension, obesity, and diabetes mellitus.

The effect of regular exercise to increase HDL cholesterol and include weight loss may be less in women than in men. Significant barriers to regular exercise exist for American women, particularly older women. If the goal is to

lose significant weight, the ACSM states that >250 minutes (four hours plus) per week of moderate intensity physical activity is necessary. To prevent regaining any weight that has been lost, the ACSM states that evidence suggests that as much exercise as needed for weight loss - more than four hours a week (more than 250 minutes) is necessary to achieve this goal ⁽⁵⁹⁾

Other factors which help weight loss and management including the simplification of the diet by avoiding processed foods, such as replacing sugary sodas with water and fresh fruit, taking whole grains, nuts and vegetables/ fruit, and not taking foods containing high fructose corn syrup. Patient should also promote to decrease the quantity of their meals while improving the quality of their meals. Additionally, patients should ideally eat their heaviest meal in the morning and their meals should get smaller towards end of the day when their activity level decreases.

Inflammation

Chronic inflammation is triggered by the accumulation of cholesterol crystals and free fatty acids in macrophages and other cells. The resulting inflammation leads to the production of the pro-inflammatory cytokine IL-1 and macrophage and T cell activation ⁽⁶¹⁾. Intimal smooth muscle cell proliferation and extracellular matrix deposition convert a fatty streak into a mature atheroma and contribute to the progressive growth of atherosclerotic lesions. Intimal smooth muscle cells have a proliferative and synthetic phenotype distinct from

the underlying medial smooth muscle cells. Platelet-derived growth factor fibroblast growth factor, and transforming growth factor-α stimulate smooth muscle cells to synthesize extracellular matrix (collagen), which stabilizes atherosclerotic plaques. The key processes in atherosclerosis are intimal thickening and lipid accumulation.

Baseline CRP levels predict future cardiovascular risk in healthy women, particularly those metabolic syndromes. Tionget al. ⁽⁶²⁾ demonstrated that serum and peripheral blood levels of CRP and VWF were significantly higher in ACS reflecting an acute phase response due to endothelial dysfunction in early the phase of ACS. Most importantly, in the JUPITER trial⁽⁶³⁾in apparently healthy men and women with LDL cholesterol levels less than 130 mg/dL who were at increased risk because of hsCRP levels of 2 mg/L or greater, the use of rosuvastatin resulted in a 44% reduction in the trial primary endpoint of all vascular events, a 54% reduction in MI, 48% reduction in stroke a 46%

reduction in need for arterial revascularization, and a 20% reduction in all-cause mortality. The JUPITER trial also provides data demonstrating the efficacy of statin therapy in women ⁽⁶⁴⁾ and elderly persons ⁽⁶⁵⁾ and in the primary prevention of stroke ⁽⁶⁶⁾.

Psychosocial Factors

The interaction of psychosocial and behavioral factors and heart disease is complex and has not been rigorously studied. Psychosocial factors such as depression, chronic stress and anxiety, chronic hostility and anger, social isolation, and perceived lack of social support have consistently been linked with the risk of coronary heart disease. ⁽⁶⁷⁾ Although depression increases cardiac risk in both women and men, a causal relationship is unclear, as is the impact of treatment.

Approximately 20% of patients hospitalized for acute coronary syndromes have major depressive disorder on admission or within a few weeks thereafter; among these patients, the mortality rate is approximately 2.5 times that in patients without depression after adjustment for infarct severity and cardiovascular risk factors, with risk increasing with severity of depression. ⁽⁶⁸⁾

Both physiologic and behavioral mechanisms have been postulated to explain the link between depression and coronary heart disease. These include effects on inflammation, endothelial dysfunction, increased platelet activity, increased whole blood serotonin, enhanced activity of the hypothalamic- pituitary-adrenal axis, alterations in cardiac autonomic tone, and elevated catecholamine levels, as well as worse underlying severity of disease; adverse lifestyle factors including poor diet, smoking, and lack of exercise; and non adherence to medications and inability to change adverse lifestyle risk factors^(68,

69).

Figure:3.5 Conceptual framework linking emotions to cardiovascular disease ⁽⁷⁰⁾

Moderate Alcohol consumption

Alcohol consumption has complex effects on cardiovascular disease, and can be associated with either beneficial or adverse cardiovascular outcomes.

Habitual heavy alcohol consumption increases total mortality, cardiovascular disease mortality, coronary heart disease, and stroke. ⁽⁶⁷⁾ By contrast light to

moderate alcohol consumption, compared with nondrinkers, associates inversely with risk of heart attack, ischemic stroke, peripheral vascular disease, sudden cardiac death, diabetes mellitus, and death from all cardiovascular causes ⁽⁶⁷⁾. Data for both men and women regarding risk of mortality from cardiovascular endpoints such as coronary heart disease, stroke, and sudden cardiac death illustrate a U-shaped relationship of reduced risk with moderate alcohol consumption. ⁽⁷¹⁾ Moderate alcohol consumption is associated with decreased cardiovascular risk for both primary and secondary prevention, in both men and women. Defined as up to one drink per day for women⁽⁷²⁾and up to two drinks per day for men, moderate alcohol consumption consistently corresponds to a reduction in risk of cardiovascular disease of approximately20% to 40%.Any individual or public health recommendation must consider the complexity of alcohol’s metabolic, physiologic, and psychological effects⁽⁷³⁾.Anyway, Guidelines discourage the initiation of moderate alcohol drinking to reduce risk of heart disease. People who already drink alcohol on light to moderate basis can get the information that this pattern of alcohol consumption is associated with a decreased risk of cardiovascular disease.

Early markers of risk due to genetic polymorphism

Genetic polymorphism is explained on as change in DNA sequence due to single nucleotide polymorphism (SNP), sequence repeats, insertion/deletion and recombination. This genetic polymorphism increases the risk of coronary vascular disease and hence needs to be contemplate for cardiovascular risk

prediction. Several SNP have been recognized in genes encoding HDL, LDL, triglycerides CRP and body mass index which lead to an increased risk of MI. ⁽⁷⁴⁾ Homocysteine is an emerging new risk factor for CVD. Polymorphisms of genes encoding homocysteine metabolism-related enzymes (methylenetetrahydrofolate reductase, methionine synthase, methionine synthase reductase, and cystathionine beta-synthase) impact plasma homocysteine concentration and thereby cardiovascular health. A common polymorphism in the gene coding for 5,10-methylene tetrahydrofolate reductase (C677T, Ala --> Val) is associated with decreased activity of the enzyme due to thermolability. Homozygosity for the Val allele leads to a mild-to-moderate hyper homocysteinemia which is recognized as an independent risk factor for atherosclerosis.^[75]

Emerging Risk Factors

Many newer markers of increased cardiovascular risk apply equally to men and women, including abnormal endothelial reactivity, increased pulse pressure (thought to be a surrogate for increased vascular stiffness), factor V Leiden mutation, and elevated fibrinogen, Coronary artery calcification (CAC) has been directly correlated with growing risk of future cardiac events, establishing its prognostic value in CVD risk prediction. The Multi-Ethnic Study of Atherosclerosis reported CAC score as an excellent risk predictor of CAD events.^[76]The first study, St. Francis Heart Study (n = 1005), concluded atorvastatin dose of 20 mg per day when administered to patients with a CAC score >400 caused 42% decrement in relative risk and 6.3% reduction in the

absolute risk of coronary events.^[77]Carotid intima-media thickness (CIMT) is a widely recognized imaging marker of generalized atherosclerosis’s has been characterized as early atherosclerosis and as non atherosclerotic compensatory enlargement; both these characteristics differently influence risk prediction of cardiovascular events in large epidemiological studies.^[78]IMT values above 0.9mm are found as abnormal. Focal thickening of the luminal surface >1.5 mm is called as plaque. Myeloperoxidase (MPO), a leucocyte-derived enzyme belongs to heme-peroxidase superfamily. It generates reactive intermediates leading to oxidative damage of host lipids and proteins.^[79]MPO strongly predicted future coronary events in healthy individuals independent of other traditional risk factors, indicating MPO as a potential clinical useful marker of CHD risk.^[80]

In 2008, Michael et al., reported strong association between low vitamin D status and adverse cardiovascular outcomes, including high blood pressure, diabetes, obesity and hyperthyroidism. In the Framingham Heart Study, participants with vitamin D levels lower than15 ng/mL when enrolled had twice higher risk of cardiovascular events than participants with higher levels of vitamin D. ^[81] Ankle-brachial index (ABI) is the ratio of systolic pressure at the ankle to that in the arm. In 1995, Kuller et al., reported ABI score ≤0.90 as an indicator of subclinical atherosclerosis and led to an increased incidence of cardiovascular mortality, MI, and stroke.^[82]

ACUTE CORONARY SYNDROMES

The term “acute coronary syndrome” is used to narrate a spectrum of conditions associated with clinical symptoms compatible with acute myocardial ischemia and it comprises unstable Angina (UA), non-ST Elevation Myocardial Infarction and ST Elevation Myocardial Infarction.

Myocardial ischemia and infarction can result from various coronary disease processes, including vasospasm, increased myocardial demand in the setting of a fixed coronary lesion, and erosion or rupture of vulnerable atherosclerotic plaque leading to acute thrombus formation and subsequent ischemia. All result in myocardial oxygen supply-demand mismatch and can precipitate ischemic symptoms, and all processes, when severe or prolonged, will lead to myocardial necrosis or infarction. Non thrombotically mediated events (bottom half, left side) typically occur without ST-segment elevations on the ECG but can have elevated levels of cardiac biomarkers if the ischemia is severe and long enough, in which case they are classified as having type II MI.

The atherothrombotic lesion is the hallmark pathobiologic event of an ACS. The reduction in flow may be caused by a completely occlusive thrombus (bottom half, right side) or by a subtotally occlusive thrombus (bottom half, middle). Ischemic discomfort may occur with or without ST-segment elevation on the ECG. Of patients with ST-segment elevation, Q-wave MI ultimately develop in most, whereas non–Q-wave MI develops in a few. Patients without

ST-segment elevation are suffering from either unstable angina or NSTEMI, a distinction that is ultimately made by the presence or absence of a serum cardiac marker such as CK-MB or cardiac troponin detected in blood.

Figure 3.6: Myocardial ischemia and infarction. ⁽⁸³⁾

Non–Q-wave MI ultimately develops in most patients with NSTEMI on the ECG; Q-wave MI may develop in a few. MI that develops as the result of the athero thrombotic lesion of an ACS is classified as type I MI.

Table 3.2 CORONARY ARTERY PATHOLOGY ⁽⁸⁴⁾

Syndrome Pathology

1. Stable Angina >75% stenoses

2. Unstable Angina Plaque rupture with mural thrombus, often thromboembolic

3. Myocardial Infarction Plaque rupture, complete thrombosis 4. Sudden death Severe multi vessel disease, often

Plaque rupture, often thrombus or thromboembolic

Figure 3.7 Acute syndrome

Potential outcomes of reversible and irreversible ischemic injury

Figure 3.8 Potential outcomes of ischemia

Causes of non-athero thrombotic coronary artery disease:

Arteritis

➢ Infection:

Bacterial Fungal Viral Rickettsial Spirochetal

➢ Immunological:

Immune complex-mediated: Lupus vasculitis, hepatitis B microscopic polyarteritis.

Direct antibody attack-mediated: Kawasaki (anti endothelial antibodies) ANCA associated (mediated): Wegener’s granulomatosis.

Cell-medicated: best known is allograft organ rejection.

Hypersensitivity reaction: drugs.

➢ Unknown:

Polyarteritis nodosa (classic) Giant cell arteritis

Takayasu’s arteritis.

Embolism

➢ Infectious endocarditis.

➢ Nonbacterial thrombotic endocarditis (NBTE).

➢ Parasitic disorders.

➢ Vegetations on catheters or fragment of catheter: iatrogenic material.

➢ Tumors:

Myxoma

Paradoxical; embolus.

Foreign bodies, including gas.

Occlusion of the coronary arterial orifice

➢ Thrombus from stalky endocarditic excrescence.

➢ Papillary fibroelastoma: papillary tumor of the leaflet.

➢ Surgical material:

Felt pads, which can also be embolic.

Suture material gripping the coronary artery in relation to arterioplastic operations or bypass

Dissection

➢ Spontaneous

➢ Marfan’s syndrome

➢ Hypertension.

Miscellaneous

➢ Congenital coronary anomalies:

Arterio venous malformation.

Anomalous origin of coronary arteries.

➢ Fibro muscular dysplasia/hyperplasia.

➢ Perivascular/vascular fibrosis in hypertrophic cardiomyopathy

➢ Endocrine and metabolic disorder:

Diabetes, hypothyroidism.

Homocysteinemia, mucopolysaccharidoses CLINICAL FEATURES STEMI ⁽⁸⁵⁾

1) Chest pain

Table 3.3 CHEST PAIN FEATURES

Site Substernal

Nature Pressing, Squeezing, Strangling, Constricting, ‘a band across the chest’, ‘a weight in the Centre of the chest’. The patient cannot pinpoint the site of pain.

Radiation To both the shoulders, epigastrium, back, neck, jaw, teeth. Anginal pain can be radiate in all directions, as mentioned above, but more commonly radiates to the left shoulder and ulnar aspect of the left arm.

Duration 5-15minutes

Aggravating Factors Exertion, emotion, after a heavy meal, or exposure to cold.

Relieving Factors Rest, nitrates.

2) Often accompanied by Weakness, Sweating, Nausea, Vomiting, anxiety and Sense of impending doom.

3) May present as

➢ Sudden onset of breathlessness

➢ With or without pain

➢ Loss of consciousness

➢ A confusional state

➢ A sensation of profound weakness

➢ The appearance of arrhythmia

➢ Evidence of peripheral embolism

➢ Merely an unexplained drop in arterial pressure.

Physical signs include

1. Elevated BP, low because of cardiogenic shock 2. Basal crepitation

3. S3, S4

4. Systolic murmur of MR 5. Soft S1

6. Paradoxic S2 7. Pallor

8. Sweating, restless, in agony due to pain and tossing in the bed in an attempt to get relief

9. Pulse – rapid or slow, regular or irregular a. Tachycardia –AWMI

b. Bradycardia – IWMI 10. Pulmonary edema.

Investigations

• Blood Investigations

1. Leukocytosis with polymorphonuclear reaction 2. High ESR

3. Elevated CRP

• ECG changes may be normal initially, hence serial ECGs must be taken

1. ST Elevation and T wave inversion ⁽⁸⁶⁾ 2. T wave inversion in opposite leads 3. Q wave on the ECG

• Cardiac Markers

1. Cardiac – Specific Troponin T and I ⁽⁸⁷⁾ 2. Creatinine Phosphokinase ⁽⁸⁸⁾

3. LDH1 4. AST

5. Myoglobin.

Enzyme levels in acute MI

Figure 3.9 Enzyme levels according to time Radionuclide imaging techniques

Myocardial perfusion imaging with ²⁰¹T1 or ^99m TC – sestamibi, which are distributed in proportion to myocardial blood flow and concentrated by viable myocardial, reveal a ‘cold spot’ (defect).

Figure 3.10 Block shows in Infarcted area and 18 slice CT angiogram

99m TC- labeled red blood cells frequently demonstrates wall motion disorders and reduction in the ventricular ejection fraction.

Myocardial infarction can be detected accurately with high resolution cardiac MRI using (gadolinium) a technique referred to as late enhancement.

Figure 3.11 Shows in 64 slice computed tomography in coronary angiogram Table 3.4

a) CPK-MB This cardiac isoenzyme starts rising within 4-6 his after development of acute MI, peaks during the 2^nd day (4-fold risk) and disappears in 2-3days

b) LDH1 Starts rising by second day, peaks around 3-4days (3-fold rise) and disappears in 10 days.

c) Troponin T Cardiac Troponin T is a regulatory contractile protein hot normally found in blood. Its detection in the circulation has been shown to be a sensitive and specific marker for myocardial cell damage.

Troponin T and I reach a reliable diagnostic level in plasma by 12-16 hrs, maximal activity by 24-32 hrs, returns to normal in 10-12 days.

Troponin I :0-0.4 ng/ml

Cardiac troponin is detected in the serum by using monoclonal antibodies. These antibodies have negligible cross reactivity to skeletal muscle. Cardiac troponin I and T start to rise within 3-4 hours after myocardial infarction and remain raised for 4-10 days.

Chest X-ray

Signs of heart failure or pulmonary edema.

Cardiac Imaging Echo

Abnormalities of wall motion on two-dimensional echocardiography are almost universally present. LV function estimation is assessed. Echo may also identify the presence of RV infarction, ventricular aneurysm, pericardial effusion, LV thrombus.

Doppler echo detects – Ventricular Septal Defect, Mitral Regurgitation Management

a. Asses the vital signs b. Establish an IV line

c. Connect the patient to a cardiac monitor d. Measure O2 saturation in breathless patients.

1. Start O2 using a nasal canula (4-6L/min)

Especially in pulmonary edema or oxygen saturation <90% continue for 4-6 hrs.

2. Aspirin (325mg) is given to the patient, to be chewed and swallowed continue 150- 325mg / day indefinitely.

3. Inj. Morphine – for Analgesia 5 mg IV stat and 2 mg IV can be repeated every 10 minutes till adequate analgesia is achieved (Maximum dose of16mg)

Caution: In inferior wall MI as it may precipitate heart blocks Inj.Pethidine 50-100 mg IV with Inj. Phenergan 12.5-25 mg IV is an alternative analgesia.

4.a. Sublingual nitroglycerine

➢ 0.4 mg can be repeated every 15 minutes maximum of 3tablets

➢ If the pain is not relieved with adequate sublingual Nitroglycerine tablets and morphine injection, start nitroglycerine drip.

4.b. Nitroglycerine drip Indications

➢ For 24-489 hours in case of persistent angina

➢ Large AMI

➢ MI with CCF or hypertension.

10 µgram/min to increase to 200 µgram/min for pain relief. Titrate dose to pain relief with monitoring of blood pressure.

CI

Hypotension- SBP less than 90mmHZ change over to oral nitrates when pain subsides.

5. Thrombolysis with streptokinase (to decide and start at the earliest, ideally within 30 minutes of chest pain/entry to emergency department)

If there are no contraindications and the BT, CT, PT, APTT and platelet count are normal.

➢ Best response it used within 6 hrs. of onset

➢ Can be used up to 12-24hrs.

Indications

➢ Typical chest pain

➢ ECG/enzyme evidence

➢ <12 hrs from onset of pain

➢ Age less than 75 yrs.

Major contraindication for streptokinase ⁽⁸⁹⁾

➢ Stroke within the previous 12months

➢ Severe hypertension BP>180/110mmHg

➢ Bleeding disorders and patient on anticoagulants.

➢ Active peptic ulcer

➢ Surgery within the previous one month

➢ Recent aggressive cardiac resuscitation

➢ Previous treatment with SK

Use of SK

➢ 1.5 million units dissolved in 100 ml of NS to run in one hour

➢ 750000 units in the first 20 minutes as IV infusion

➢ 750000 units in the next 40 minutes as IV infusion

➢ Give 100 mg of hydrocortisone and 25 mg pheniramine maleate IV before giving SK to present minor allergic reaction

➢ If BP falls, give volume expanders like saline.

6. If pain persists after thrombolysis consider urgent PTCA or CABG.

7. Inj.Heparin

➢ To prevent clot formation and embolization in cases of large MI/AI

➢ LV thrombus – stabilize the clot

➢ Following thrombolysis/PTCA/CABG.

UFH

➢ Gives 6 hrs after the SK to maintain APTT Around 1.5 to 2 times the control for 5-7days

➢ 5000 IU IV stat followed by 1000 U/hour IV alternatively LMWH

➢ Given 5-7 days Enoxaparin 1mg/kg/BD

➢ No need to monitor APTT but it is expensive

8. Beta blockers Indications

1. All patients with 12 hrs of MI with no major contraindication to this drug

2. Patients with recurring or ongoing chest pain 3. Arrhythmias such as AF/VF

➢ Metoprolol 5mg IV stat and repeat every 5 minutes if needed till 15mgs.

➢ Use oral beta-blockers indefinitely

➢ Metoprolol 50mg orally BD.

Use with caution 1. IWMI

2. SBP < 95mm/Hg 3. HR < 55/min 4. Severe LVD 5. Heart blocks

6. Severe COPD/Asthma 9. ACE inhibitors

If cardiac failure / LVD/

➢ Enalapril 5-20mg

➢ Ramipril 2.5-20mg

Avoid in hypotension /renal failure/ hyperkalemia.

10. Calcium channel blockers

➢ Used only when beta-blockers are contraindicated and there is ongoing chest pain.

➢ To control ventricular rate in AF

➢ Avoid in CCF and LVD

➢ Diltiazem – bolus 0.25 mg/kg IV over 2-5 min for arrhythmias

➢ Infusion dose is 5-15mg / hour. 250mg in 250 ml = 1ml. infusion rate 5-15ml/hour or micro drops/min or Diltiazem PO 30-60mg 8^thhourly.

11. Amiodarone

➢ For atrial and ventricular arrhythmia.

➢ Bolus – 150mg in 20ml 5% D over 5-15 minutes.

➢ Infusion – Inj. Amiodarone 1amp = 3ml = 150mg

➢ 6amp in 500ml of 5% D slow loading dose1mg/min.

Supportive Treatment 1. Reassurance

2. Complete Bed rest for 12-24 hrs if no complications 3. Movements of legs in bed and deep breathing exercises

4. Avoid straining or Valsalva for any reason including defecation and passing urine

5. Laxative to be given to avoid straining during defecation 6. Toilet facilities near bedside

7. Sedatives like Diazepam 5-10mg or alprazolam 0.5mg should be given at night and a calm and quiet atmosphere to be maintained

8. Diet – patient should be in stable soft diet; small frequent feeds are started after 6 hrs.’ of MI.

9. Treat Hyperlipidemia a. If LDL >100mg/dl or b. HDL <35mg/dl.

10. Specific treatment of complication

• Severe hypotension

• Pulmonary edema Should be treated

• Arrhythmias

Refer for cardiac pacing if there is 1. Asystole

2. Symptomatic bradycardia

3. BBB or bifascicular blocks or complete heart block.

While waiting for cardiac pacing the following drugs can be tried

➢ Inj. Atropine 1mg IV, total 3doses

➢ Inj. Deriphylline 1 amp

➢ Inj. Isoprenaline 2mg in 500ml NS/5%D.

NSTEM1 AND UNSTABLE ANGINA ARE CLOSELY RELATED IN PATHOGENESIS AND CLINICAL PRESENTATION.

UNSTABLE ANGINA Symptoms

1. Angina at rest

2. Recent onset severe angina 3. Progressing severity of angina 4. Post infarction angina

ECG

1. May show ST depression and 2. T wave inversion

3. NO ST elevation /Q wave 4. Normal cardiac enzymes Treatment

1) Aspirin 325mg oral stat and daily. If not tolerated, ticlopidine 250mg BD monitor for neutropenia.

2) Heparin –unfractionated

1000 IU/hr., as an infusion with monitoring APTT (or)

LMW Heparin – given for 5 days

• Enoxaparin 1mg/kg SCBD

• Dalteparin 100 IU/kg SCBD

• Nandopanin 50 IU/kg SCBD

• Reviparine 3500-6300 U SCBD

• Fondaparinux -OD 3) Beta blockers

➢ Atenolol 50-100mg

➢ Metoprolol50-100mg

➢ Watch for BP fall and bradycardia

Table: 3.5 : CANDIDATES FOR USE OF BETA-BLOCKING AGENTS FOR ANGINA ⁽⁹⁰⁾

Ideal Candidates Poor Candidates Prominent relationship of physical

activity to attacks of angina Coexistent hypertension History of supraventricular or ventricular arrhythmias Previous MI

LV systolic dysfunction Mild to moderate heart failure

symptoms (NYHA functional classes II, III)

Prominent anxiety state

Asthma or reversible airway

component in patients with chronic lung disease

Severe LV dysfunction with severe heart failure symptoms (NYHA functional class IV)

History of severe depression Raynaud phenomenon

Symptomatic peripheral vascular disease

Severe bradycardia or heart block Brittle diabetes

12^thhrly

4) Nitrates

➢ NTG IV starting from 10-30µg/mt up to 200-400 µg/min.

Titrate the dose to relieve pain

➢ Watch for hypotension<90mmHg

➢ In hypertensives do not lower below 120mmHgsystolic

➢ If Patient has mild pain, oral or S/L glyceryl trinitrate 0.5mg every 3 minutes till the pain subsides C maximum 3mg in(hr.) 5) Calcium channel blockers

➢ Used only if beta blockers are contraindicated,

➢ Avoid short acting drugs like nifedipine

➢ Diltiazem 30 to 60 mg TID can be given.

6) Treat Associated Aggravating factors like anemia, stress, fever, tachyarrhythmia

➢ Detect and treat risk factors like DM, SHT, Lipid abnormalities

➢ Advice to stop smoking

➢ If pain subsides, Treadmill test on drugs is indicated, after the patient instable.

➢ Depending upon the outcome revascularization can be planned for high risk patients.

➢ Refractory Angina – Refer for emergency PTCA/CABG ⁽⁸⁹⁾

Complications

Figure 3.12 Complications

A, Anterior myocardial rupture in an acute infarct (arrow). B, Rupture of the ventricular septum (arrow). C, Complete rupture of a necrotic papillary muscle.

D, Fibrinous pericarditis, showing a dark, roughened epicardial surface overlying an acute infarct. E, Early expansion of anteroapical infarct with wall thinning (arrow) and mural thrombus. F, Large apical left ventricular aneurysm.

The left ventricle is on the right in this apical four-chamber view of the heart.

Complications

1. Arrhythmias 2. Heart failure 3. Cardiogenic shock

4. Sudden death

5. Infarction of papillary muscle of mitral value 6. Rupture of Inter ventricular septum leading toVSD 7. Thrombosis in LV causing cerebral embolism

8. Rupture of ventricle into pericardial sac causing cardiac tamponade 9. Deep vein thrombosis is legs causing pulmonary embolism

10. Pericarditis during massive infarction

11. Aneurysm of ventricle with thrombosis and thrombo embolic phenomenon

12. Dressler’s syndrome

Table 3.6: EVALUATION AND INTERVENTIONS IN RELATION TO DIFFERENT COMPONENTS OF A MULTIFACTORIAL

REHABILITATION PROGRAM

Evaluation Intervention

Patient assessment

Medical history Physical examination

Compose patient care program.

Nutritional counseling

Obtain estimate of daily food intake Assess eating habits

Prescribe dietary modifications.

Individualize eating plan.

Educate and counsel patient and family.

Smoking cessation

Document smoking status Determine readiness to change

Provide formal smoking cessation program

Update status at each visit Weight

management

Measure weight, height, Calculate BMI

In patients with BMI>25 establish reasonable short-term and long- term weight goals. Develop a combined diet, exercise and behavioral program.

Exercise training

Obtain an exercise test Develop a documented indivi- dualized exercise prescription for aerobic resistance training.

Psychosocial management

Use interview and/or standardized measurement tools to identify

psychosocial distress

Offer individual education and counseling. Develop supportive rehabilitation environment to enhance social support Cooperate with appropriate mental health specialist.

Discharge therapy

Evaluate relevant long-term therapy with aspirin, beta blockers, and ACE inhibitors.

Monitor dose adjustments and side effects (ECG, kidney function)

Lipid

management

Obtain fasting measures of total cholesterol, HDL, LDL andTG.

Repeat lipid profiles 4-6

weeks after hospitalization and 2 months after changes in therapy.

Provide nutritional counseling and add drug treatment until:

LDL <100 mg/dl (2.8 mmol/l), HDL >35 mg/dl (1.0 mmol/l), TG <200 mg/dl (2.5 mmol/l).

Evaluation Intervention Hypertension

and diabetes management

Measure of resting BP on at least 2 visits. Identify diabetic subjects.

Obtain fasting plasma glucose in all patients and HbA l c in diabetic

patients to monitor therapy.

Continue assessment and optimize treatment until BP<140/90 mmHg [18.7/12 kPa] or BP <130/85 mmHg [17.3/11.3 kPa]

(diabetics).

Continue monitoring and optimize diet, exercise, and oral hypoglycemic agents or insulin until near normalization of glycemic control with HbA l c

<7.0%.

4. MATERIALS AND METHODS

PLACE OF THE STUDY

➢ Chengalpattu (Tertiary Care Centre). The study was conducted at Government Chengalpattu Medical College hospital.

PERIOD OF STUDY

➢ July 2018 to June 2019 DESIGN

➢ Prospective cross-sectional study.

METHODOLOGY

➢ One Hundred and sixty female patients admitted with symptoms and signs and ECG changes suggestive of CAD with Biochemical markers taken as cases.

SAMPLE SIZE: 160

➢ Based on the study done by Bhatt P, et al the proportion 11% is taken for sample size calculation ⁽⁹¹⁾

INCLUSION CRITERIA

1. Patients above 35 years 2. Hypertension

3. Diabetes mellitus 4. Dyslipidemia 5. Obesity

6. Patients willing for study

EXCLUSION CRITERIA

1. Congenital Heart disease.

2. Rheumatic Heart disease.

3. Structural Heart disease.

4. Electrical abnormalities.

5. Connective tissue disorders 6. Thyroid disorders

7. Patients not willing for study

➢ Admitted 160 female patients were examined and detailed history was taken about the patient’s age, menstrual history, sedentary habits, Food habits, h/o Smoking, Alcohol in take history, h/o OCP intake, Family history and systemic hypertension history and h/o Type 2 DM and other risk factors analysis was made.

➢ Baseline investigations like complete blood count, urine R/E, renal function test, ECG, Chest X-ray, Blood pressure monitoring was done in all study subjects. Echo done in all patients. CAG done in 70 patients because in initial part of my study CAG not available in my college.

➢ Hypertension was diagnosed by documented history of hypertension / medication or with BP >140/90 mmHg, during the present visit.

Figure :4.1

➢ Diabetes mellitus was considered by documented history of Fasting blood Sugar and Postprandial Blood Sugar values were evaluated.

1. FBS- 126 &Above

Taken as criteria for Diabetes Mellitus 2. PPBS-160 & Above

➢ Clinical Symptoms like chest pain, Nausea, Vomiting, Dyspnea, Syncope, Radiation of the pain to shoulder or back were all taken into account.

➢ Signs like hypertension, hypotension, raised JVP, S3, S4, Lung Crepitations, where were all looked for.

➢ Total cholesterol, LDL, HDL, Triglycerides levels identified and taken into the study.

➢ Patients were grouped into four categories according to their age as 36- 45yrs., 46-55yrs., 56-65yrs., above 65yrs.

➢ Body mass Index was calculated by using Quetlet’s formula (wt(kg) / ht(m²) in all patients.

➢ Waist/Hip ratio calculated in all patients.

Killip Score was assigned according to the clinical presentation.

Table 4.1 Killip Classification

Class Features

I No heart failures

II Mild to moderate heart failure (S3; rales no more than half way to the back) III Severe heart failure (Pulmonary edema) IV Cardiogenic shock

➢ Electrocardiogram was performed in all study subjects

➢ Echocardiogram was performed in all study subjects

➢ Troponin study was done in NSTEMI and unstable angina patients.

Types of ECG Abnormalities Recorded

➢ ST Elevation MI

➢ Non-ST Elevation MI

➢ Unstable Angina ECG PATTERNS

➢ Extensive anterior Wall MI – L1, avL and Precordial leads.

➢ Antero septal wall MI –V1 toV4.

➢ Anterolateral wall MI –L1, avL, V4, V5, V6.

➢ Apical wall MI –V5, V6.

➢ Inferior wall MI –LII, LIII, avF.

➢ Infero lateral wall MI –LII, LIII, avF, V5, V6.

➢ RVMI –V1 and V4 R

➢ Posterior wall MI –Right V1-V3 and especially V2 – respect the universe charge.

BMI

BMI was calculated by using Quetlet’s formula: weight (kg)/ height (m2).

Figure 4.2

Table 4.2

CLASSIFICATION BMI

Normal 18.5-22.9

Overweight 23.0-24.9

Obese ≥ 25.00

WAIST HIP RATIO

More than 0.8 considered as risk for metabolic complications LIPID PROFILES

Total cholesterol (mg%)

<200 Desirable

200-239 Borderline high

>240 High

LDL cholesterol (mg%)

<100 Optimal

100-129 Near optimal/above

160-180 High

≥ 190 Very high.

HDL (mg%)

<40 Low

≥ 60 Borderline high