Introduction
• Atherosclerosis is a progressive inflammatory disorder of the arterial wall that is characterised by focal lipid-rich deposits of atheroma that remain clinically silent until they become large enough to impair tissue perfusion, or until ulceration and disruption of the lesion result in thrombotic occlusion or distal embolization of the vessel.
• Atherosclerosis begins early in life with deposits of lipids in the vessel wall, which tend to occur at sites of altered arterial shear stress, such as bifurcations, and are associated with abnormalities of endothelial function at that site.
• Abnormalities of arterial function have been detected among high-risk children and adolescents, such as cigarette smokers and those with familial hyperlipidaemia or hypertension.
• Early lesions have been found in the arteries of victims of accidental death in the second and third decades of life, but clinical manifestations often do not appear until the sixth, seventh or eighth decade.
• Subsequently, they migrate into the intima, and take up oxidised low-density lipoprotein particles by phagocytosis to become lipid-laden macrophages or foam cells. Extracellular lipid pools appear in the intimal space when foam cells die and release their contents. In response to cytokines and growth factors produced by activated macrophages, smooth muscle cells migrate from the media of the arterial wall into the intima, and change from a contractile to a fibroblastic phenotype, which can stabilise the atherosclerotic lesion.
• If this is successful, the lipid core will be covered by smooth muscle cells and matrix, producing a stable atherosclerotic plaque that will remain asymptomatic until it becomes large enough to obstruct arterial flow. In an established atherosclerotic plaque, macrophages mediate inflammation and smooth muscle cells promote repair.
• If inflammation predominates, the plaque becomes active or unstable and may be complicated by ulceration and thrombosis.
• Cytokines, such as interleukin-1, tumour necrosis factor-alpha, interferon-gamma, platelet-derived growth factors and matrix metalloproteinases, are released by activated macrophages. They cause the intimal smooth muscle cells overlying the plaque to become senescent and the collagen cross-links within the plaque to degrade. This results in thinning of the protective fibrous cap, making the lesion vulnerable to mechanical stress that ultimately causes erosion, fissuring or rupture of the plaque surface.
Atherosclerosis
Definition: Atherosclerosis is multi-focal, multi-factorial smoldering inflammatory disease that affects the intima of medium sized and large arteries, resulting in intimal thickening that may lead to luminal narrowing and inadequate blood supply.
Atherosclerosis derives its name from the Greek word ‘adhere’—means gruel or porridge, and ‘sclerosis’ means hardening, i.e., hardening of gruel-like material inside the blood vessels.
Functional Anatomy And Physiology
The cardiovascular system contributes to homeostasis of other body systems by transporting and distributing blood throughout the body to deliver materials (such as oxygen, nutrients, and hormones) and carry away wastes. The structures involved in these important tasks are the blood vessels, which form a closed system of tubes that carries blood away from the heart, transports it to the tissues of the body, and then returns it to the heart.
Basic Structure of a Blood Vessel
The wall of a blood vessel consists of three layers, or tunics, of different tissues: an epithelial inner lining, a middle layer consisting of smooth muscle and elastic connective tissue, and a connective tissue outer covering. The three structural layers of a generalized blood vessel from innermost to outermost are the tunica interna (intima), tunica media, and tunica externa (adventitia). Modifications of this basic design account for the five types of blood vessels and the structural and functional differences among the various vessel types. Always remember that structural variations correlate to the differences in function that occur throughout the cardiovascular system.
Tunica Interna: The tunica interna (intima) forms the inner lining of a blood vessel and is in direct contact with the blood as it flows through the lumen or interior opening of the vessel. Although this layer has multiple parts, these tissue components contribute minimally to the thickness of the vessel wall. Its innermost layer is called endothelium, which is continuous with the endocardial lining of the heart. Endothelial cells are active participants in a variety of vessel-related activities, including physical influences on blood flow, secretion of locally acting chemical mediators that influence the contractile state of the vessel’s overlying smooth muscle, and assistance with capillary permeability.
The second component of the tunica interna is a basement membrane deep to the endothelium. It provides a physical support base for the epithelial layer. The outermost part of the tunica interna, which forms the boundary between the tunica interna and tunica media, is the internal elastic lamina.
Tunica Media: The tunica media (media = middle) is a muscular and connective tissue layer that displays the greatest variation among the different vessel types. In most vessels, it is a relatively thick layer comprising mainly smooth muscle cells and substantial amounts of elastic fibres. The primary role of the smooth muscle cells, which extend circularly around the lumen like a ring encircling your finger, is to regulate the diameter of the lumen. An increase in sympathetic stimulation typically stimulates the smooth muscle to contract, squeezing the vessel wall and narrowing the lumen. Separating the tunica media from the tunica externa is a network of elastic fibres, the external elastic lamina, which is part of the tunica media.
Tunica Externa: The outer covering of a blood vessel, the tunica externa consists of elastic and collagen fibres. The tunica externa contains numerous nerves and, especially in larger vessels, tiny blood vessels that supply the tissue of the vessel wall.
Epidemiology And Global Trends
Atherosclerotic disease causes more deaths and disability and incurs greater economic costs than any other illness in the developed world.
Atherosclerotic disease is the most common, serious, chronic, life-threatening illness in the United States, where 15.5 million persons have Atherosclerotic disease, and 3.4 million people aged ≥40 years have angina pectoris. Although there is regional variation, about 4% of the population has sustained a myocardial infarction.
Genetic factors, a high-fat and energy-rich diet, smoking, and a sedentary lifestyle are associated with the emergence of atherosclerosis. In the United States and Western Europe, atherosclerosis is growing among low-income groups, but primary prevention has delayed the disease to later in life across socioeconomic groups.
These trends are occurring in the general context of population growth and as a result of the increase in the average age of the world’s population. With urbanization in countries with emerging economies and a growing middle class, elements of the energy-rich Western diet are being adopted. As a result, the prevalence of risk factors for atherosclerosis and the prevalence of IHD itself are both increasing rapidly, so that in analyses of the global burden of disease, there is a shift from communicable to non-communicable diseases.
Pathophysiology
Early Atherosclerotic Lesions
The earliest lesions of atherosclerosis, i.e. fatty streaks, are present in the aorta from early childhood and may even begin to develop early in foetal life. They are highly cellular inflammatory lesions consisting of macrophage foam cells (intracellular lipid) and T-lymphocytes (immune reaction). Fatty streaks do not protrude into the lumen and hence are not symptomatic. Fatty streaks develop under an intact but activated, dysfunctioning endothelium particularly atherosclerosis prone areas with preexisting intimal thickening. Hypercholesterolaemia is associated with increased endothelial permeability, increased transcytosis and intimal retention of lipoproteins and endothelial activation with focal expression of vascular cell adhesion molecule 1 (VCAM-1) leading to monocyte and T-lymphocyte adhesion. It is thought that inflammatory cells are recruited by adhesion molecules and chemokines such as monocyte chemoattractant protein-1 (M-CSF) and activated in the intima by factors such as oxidised lipids and cytokines. Within the intima, the monocyte-derived macrophages engulf the blood derived low-density lipoprotein (LDL), possibly through their scavenger receptors after oxidative modification and become lipid-filled foam cells. These inflammatory cells constitute the major part of the early fatty streak lesions.
Etiological And Risk Factors
I.Major Risk Factors Modifiable By Lifestyle And
1. Dyslipidaemia (High LDL, low HDL cholesterol)
2. Hypertension
3. Diabetes mellitus
4.Smoking
5. Lifestyle risk factors (atherogenic diet, obesity, physical
II. Constitutional Non-Modifiable Risk Factors
1. Age
2. Sex
3. Genetic factors
4. Familial and racial factors
III. Non-Traditional Emerging Risk Factors
1. Environmental influences
2. Oestrogen hormone
3. Stressful behavioural pattern
4. Hyperhomocysteinaemia
5. Homocystinuria
Types
1. Stable Angina Pectoris
Angina is said to be stable when there has been no change in the frequency, duration, precipitating factors, or relief of angina attacks during the last 60 days (provided the patient’s activity level has not decreased during that period).
Symptoms
1. Typical Anginal Pain Or Distress:
(a) Site – Most often over middle or lower sternum or over left precordium, at times in epigastrium. Sometimes discomfort is located only in the left shoulder or left upper arm, occasionally in the lower jaw, rarely in the interscapular area.
(b) Radiation – May spread to the right or left arm or both, neck or jaw. Occasionally pain starts in the wrists, upper arms or face and then spreads to the chest.
(c) Character – Vice-like constriction or choking. Sometimes only pressure or burning pain, rarely mere weakness of one or both arms. An important characteristic is its constancy, the pain being steady while it lasts.
(d) Duration – most commonly 1 to 4 minutes. May force patients to stop walking.
(e) Provocation – by effort specially like walking against the wind or up a climb, hurrying after meals, or unaccustomed exercise. At times due to excitement, anger, fear. In advanced cases, pain is provoked by lying down (angina decubitus) or stooping.
(f) Relief – with sublingual nitroglycerine.
2. Non-St Elevation Myocardial Infarction (Nstemi)
It is often characterised by ST depression and T inversion along with elevation in cardiac enzymes. In some cases, however, ECG may be normal and only abnormality is elevated cardiac enzymes
Clinical Criteria
Angina on effort of recent onset (one month).
• Angina of effort with increasing frequency and duration and provoked by less than usual stimuli (accelerated or crescendo angina).
• Prolonged (>20 min) anginal pain at rest
• Angina in early (<1 month) post-infarction period.
• New onset (de novo) severe angina,
• Recent destabilization of previously stable angina with crescendo angina
• Post MI angina
3. St Elevation Myocardial Infarction (Stemi)
Clinical Presentation
• In up to one-half of cases, a precipitating factor appears to be present before STEMI, such as vigorous physical exercise, emotional stress, or a medical or surgical illness. Although STEMI may commence at any time of the day or night, circadian variations have been reported such that clusters are seen in the morning within a few hours of awakening.
• Pain is the most common presenting complaint in patients with STEMI. The pain is deep and visceral; heavy, squeezing, and crushing; although, occasionally, it is stabbing or burning type.
• It is similar in character to the discomfort of angina pectoris but commonly occurs at rest, is usually more severe, and lasts longer.
• Typically, the pain involves the central portion of the chest and/or the epigastrium, and, on occasion, it radiates to the arms. Less common sites of radiation include the abdomen, back, lower jaw, and neck.
• The frequent location of the pain beneath the xiphoid and epigastrium and the patients’ denial that they may be suffering a heart attack are chiefly responsible for the common mistaken impression of indigestion.
Differential Diagnosis
I. Ischaemic Cardiac Pain
1. Angina pectoris
2. Cardiac arrhythmias – Sudden onset of arrhythmia with tachycardia may be associated with oppressive substernal pain which may be prolonged, and with sweating and dyspnoea.
3. Mitral valve prolapse – Chest pain not related to exertion, usually sharp over precordium, commoner in those with anxiety or nervous temperament. Mid-systolic click with late systolic murmur.
II. Affection Of Aorta
1. Aortitis – Uncomplicated syphilitic aortitis may be accompanied by substernal pain. The pain is localised and not influenced by exertion.
2. Aortic dissection
III .Pericarditis
IV. Pulmonary Disease
1. Massive pulmonary embolism
2. Spontaneous pneumothorax on left side – Pain is usually sharper and more localised to side of chest than to sternal region. Initial spontaneous pain more transient with subsequent pain intensified with deep inspiration or change of posture. Dyspnoea only with effort, hyper-resonance diminished or absent breath sounds over affected part and sometimes shift of mediastinum. Chest radiograph diagnostic.
3. Acute pleurisy – Pain aggravated by deep inspiration and usually in axillary region. Pleural rub.
4. Pneumonia – If in a case of coronary occlusion there is little pain but prominent dyspnoea, fever and rales over circumscribed area of lung, pneumonia may be diagnosed. In pneumonia, pain inside the chest is aggravated by deep breathing. High fever and leucocytosis.
V. Mediastinal Conditions
Diagnostic Test :
- ECG at rest – may be normal or show ST-T changes suggestive of ischaemia, or AV or intraventricular conduction defects.
- Coronary angiography – remains the ‘gold standard’ technique for diagnosis and planning treatment of AETHROSCLEROTIC DISEASE
Investigation
1.Echocardiography – 2D and M-mode echocardiography are valuable in assessment of resting ventricular function and can identify areas of segmentally reduced contraction corresponding to previous MI.
2.Stress echocardiography – Continuous 2D-echocardiography is performed at rest and during and after stress and image comparison is used to determine the extent and distribution of wall motion abnormalities. Stress can be provoked by exercise or by pharmacological stimulation which can be used to predict the location and severity of underlying coronary artery disease.
3.Intravascular ultrasonography (IVUS) – Defines completely the vessel wall, plaque burden, morphology of the plaque, presence of calcification in the lesion, and luminal dimensions.
4.Intracoronary Doppler – Clinical applications include assessment of functional significance of intermediate lesions by coronary arteriography. With use of Doppler wire the velocities and coronary flow reserve across the lesion can be estimated.
Complication
1.Mechanical
1. Lv Failure And Cardiogenic Shock
• Haemodynamic monitoring with an arterial line and pulmonary artery catheter is helpful.
• 2D-Echo determines the extent of myocardial involvement and other complications of AMI which contribute to cardiogenic shock.
• In patients with cardiogenic shock an intra-aortic balloon pump (IABP) insertion reduces the afterload, improves cardiac output, and decreases myocardial O2 requirement.
• Temporary Left Ventricular Assist Device (LVAD), Inotropic and vasopressor agents may be given at lowest doses. Survival improvement is associated only with PCI or CABG.
2. Mitral Regurgition
• Severe or acute MR caused by papillary muscle dysfunction is a life-threatening complication.
• Vasodilator therapy is useful as it reduces SVR and increases CO.
• Surgical therapy: CABG + mitral valve replacement should be considered immediately. Patients with moderate MR may do well with mitral valve repair.
2. Arrythmic Complication
Supraventricular Tachyarrythmia
A. Sinus tachycardia occurs due to anxiety, persistent pain, LV failure, pericarditis, hypovolaemia and cardioaccelerators drugs such as atropine, epinephrine or dopamine.
• It results in augmentation of myocardial O2 consumption and reduction in duration of coronary perfusion. Persistent sinus tachycardia can signify persistent heart failure and suggests poor prognosis.
• Treatment – Analgesics for pain, diuresis for heart failure, beta-blockers and nitroglycerine for ischaemia and aspirin for fever and pericarditis.
B. AF and AFL are usually transient and due to augmented sympathetic stimulation in the atria, LV failure, pericarditis and ischaemic injury to the atria and RVMI
• Tr. Rate control with IV Diltiazem or esmolol. If patient is haemodynamically unstable, immediate intrathoracic cardioversion.
• If patient is haemodynamically stable, cardioversion can be done pharmacologically (amiodarone, ibutilide and procainamide) or with electrical cardioversion. Anticoagulation is necessary for 3 or more weeks, before and for another 4 weeks after cardioversion to prevent thromboembolic complications, if duration of AF is > 48 hrs, if less cardioversion without anticoagulation.
3. Ischaemic Complication
• Recurrent post infarction angina may be due to either an infarct extension or reinfarction in a separate area or reocclusion of infarct related artery.
• If the ECG reveals ST segment re-elevation or presence of new Q waves or there is re-elevation of cardiac markers, PCI is advisable.
• If unavailable repeated fibrinolysis can be considered. Haemodynamically stable symptomatic patients are treated with nitroglycerine and beta-blockers.
• When hypotension, heart failure or ventricular arrhythmias develop during recurrent ischaemia, urgent catheterization and revascularization are indicated. With increasing use if PCI, stent thrombosis may be a cause of ischaemia.
4.Inflammatory
• Pericarditis after MI is classified as early or late. Early pericarditis usually develops 24 to 96 hrs after MI.
• Pain is postural, worse when supine and relieved when sitting up and leaning forward. Radiation of pain to the trapezius ridge is almost pathognomic.
• Treatment – Aspirin. If > 4 weeks have elapsed since AMI, NSAIDs and even steroids may be used for severe symptoms.
5. Embolic Complication
• Systemic embolism most often results in stroke, although there may be limb ischaemia, renal infarction or mesenteric ischaemia.
• Treatment – Heparin IV for 3 to 4 days followed by oral anticoagulation for 3 to 6 months in patients with mural thrombus and those with large akinetic areas detected by 2D-echo.
Homoeopathic Approch
1. Digitalis Purpura
• Sudden flushes of heat, followed by great nervous weakness and irregular intermitting pulse, occurring at the climacteric; < by least motion
• Weak heart without valvular complications
• Sensation as if heart would stop beating if she moved (Cocaine-fears that unless constantly on the move heart will cease beating, Gels.)
• Pulse full, irregular, very slow and weak; intermitting every third, fifth or seventh beat
• Blueness of skin, eyelids, lips, tongue; cyanosis
• Distended veins on lids, ears, lips and tongue
• Fatal syncope may occur when being raised to upright position.
MODALITIES:
Aggravation: When sitting, especially when sitting erect; motion.
2. Adonis Vernalis (Pheasant’s Eye)
• A heart medicine, after rheumatism or influenza, or Bright’s disease, where the muscles of the heart are in stage of fatty degeneration, regulating the pulse and increasing the power of contractions of heart, with increased urinary secretions
• Most valuable in cardiac dropsy
• Heart – Mitral and aortic regurgitation. – Chronic aortitis, Fatty heart pericarditis Rheumatic Endocarditis
• Precordial pain, palpitation, and dyspnoea.
• Marked venous engorgement, Cardiac asthma, Fatty heart, Myocarditis
• irregular cardiac action, constriction, and vertigo Pulse rapid, irregular
3.Cactus Grandiflorus (Night-Blooming Cereus)
MENTAL GENERAL: Fear of death; believes the disease incurable
• Whole body feels as if caged, each wire being twisted tighter and tighter
• Constriction: Of throat, chest, heart, bladder, rectum, uterus, vagina; often caused or brought on by the slightest contact
• Pains everywhere; darting, springing like chain lightning, and ending with a sharp, vice-like grip, only to be again renewed
• Heart feels as if clasped and unclasped rapidly by an iron hand; as if bound, “had no room to beat.’’
• Palpitation: Day and night; worse when walking and lying on left side (Lach.); at approach of menses
4 Convallaria Majalis (Lily Of The Valley)
• Increases energy of hearts’ action, renders it more regular Of use when the ventricles are overdistended and dilatation begins, and when there is an absence of compensatory hypertrophy, and when venous stasis is marked
• Dyspnoea, dropsy, anuric tendency, Anasarca
• Heart – Feeling as if heart beat throughout the chest
• Endocarditis, with extreme orthopnoea
• Sensation as if heart ceased beating, then starting very suddenly
• Palpitation from the least exertion
• Tobacco heart, especially when due to cigarettes
Bibliography
I. Davidson’s Principles & Practice of Medicine 23rd edition.
II. Harrison’s Principles of Internal Medicine 21st edition.
III. Medicine Prep Manual for undergraduates 6th edition by K.George Mathew & Praveen Aggarwal.
IV. Textbook of Pathology by Harsh mohan 6th Edition
V. P.J. Mehta’s practical medicine
VI. Tortora’s Principles of Anatomy & Physiology Book by Bryan H. Derrickson and Gerard J. Tortora
VII. Boericke’s New Manual of Homeopathic Materia Medica with Repertory.
VIII. Allen’s Keynotes with leading remedies of the Materia Medica & Bowel Nosodes.
XI. Golwalla’s Medicine for Students: A Reference Book for The Family Physician
Textbook by Aspi F Golwalla, Milind Y Nadkar, and Sharukh A Golwalla 25th edition.
