IMED1004 - Cardiovascular Disease (L25, 26)

Recall: Anatomy and Phsyiology of the Heart 1

DIAGRAM ON SLIDE 5

Recall: Anatomy and Physiology of the Heart 2

DIAGRAM ON SLIDE 6

Recall: Anatomy and Physiology Of the Heart 3

DIAGRAM ON SLIDE 7

Recall: Anatomy and Phsyiology of the Heart 4

DIAGRAM ON SLIDE 8

"Cardiovascular disease" describes a diverse range of conditions

Clinical Manifestations of Pathology: molecular, functional or morphologic abnormalities

- Failure of the pump

- Obstruction to flow

- Regurgitant flow

- Shunted flow

- Disorders of cardiac contraction

- Rupture of heart or major vessel

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AETIOLOGIES: Causes of disease

- ischemia

- infection

- maternal disease

- genetics

- nutritional deficiencies

- alcohol, smoking, drug use and other modifiable risk factors

- environment

Congenital Heart Disease

- gross structural abnormality of the heart or intrathoracic great vessels

- Colloquially: "hole in the heart"

- shunt permits flow of blood between two sides of heart

- Symptoms, prognosis will vary with the type and severity of the defect

Congenital Heart Disease Causes

- 90% of cases - cause not known

- chromosomal disorders

- genetic (family history)

- prematurity

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IN UTERO:

- infectious disease; Syphilis, rubella, toxoplasmosis

- diabetes mellitus

- micronutrient deficiencies

- teratogens

- tobacco, alcohol and illicit drug exposure

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- Incidence: around 1% of live births

- Leading cause of birth defects

- Treatment of neonates improving; newly-diagnosed adults increasing proportion of cases

Cardiomyopathies (Myocardial Diseases)

INTRINSIC CARDIOVASCULAR MUSCLE DISEASE:

- Some aetiologies: idiopathic, genetic, infection/immune response, toxic exposures

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DIASTOLIC DYSFUNCTION:

- mutations affecting cytoskeletal proteins - hypertrophy

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SYSTOLIC DYSFUNCTION:

- genetic

- toxic exposures (e.g alcohol)

- pregnancy

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NONCOMPLIANT MYOCARDIUM:

- endomyocardial scarring

- depositions (e.g amyloid)

Valvular Heart Disease: Rheumatic Heart Disease (RHD)

CAUSE: Streptococcal infection of tonsils and pharynx

Rheumatic Fever:

- anti-streptococcal antibodies are cross-reactive with cardiac tissue

- Fibrosis, stenosis (narrowing) of mitral valve

- pressure buildup in left atrium

- Dilation of left atrium; hypertrophy

- atrial fibrillation; congestive heart failure

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- Common in poor socioeconomic conditions

- 15.6 million people

- Poor access to healthcare, nutrition

Myocarditis: Chagas disease (American trypanosomiasis)

- Parasitic infection - Trypanosoma cruzi

- Transmitted by insects (triatomine), live in cracks of poorly constructed homes

- 10 million people are infected worldwide

- some control achieved through vector control, screening

- further control could be achieved by improving living conditions

- Causes destruction of heart muscle: inflammatory response; necrosis

- Acute attack: 10% die

- Chronic, immune-mediate: congestive heart failure, arrhythmia

Ischaemic Heart Disease, coronary heart disease and stroke are major causes of death

DIAGRAM ON SLIDE 15

Pathophysiology of Atherosclerosis

- Atherosclerosis results in narrowing of blood vessels

- this is a major cause of heart attack and stroke

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- when we have imbalance between the LDL and HDL, HDL cant remove sufficient amounts of these LDL, resulting in increased concentration of these LDL in circulation

- these can stick or aggregate to extracellular matrix and they can oxidise

- this attracts monocytes which differentiate into macrophages and they will ingest these lipoproteins and become foam cells

- endothelium becomes more permeable to the lymphocytes and monocytes and so these cells migrate into the vessel wall

- this will attract more LDL which migrates into the cholesterol wall (which accumulates which we call a plaque)

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- anothrer serious thing that can happen is that the macrophages at the centre of the plaque can die and we have formation of necrotic core and fibrous cap

- hence this fibrous cap can cause thrombosis

Pathogenesis of myrocardial infarction, stroke

- fibrous cap ruptures -> lipid fragments, cellular debris released into vessel lumen

- thrombogenic agents -> formation of thrombus

- thrombus: accumulation of RBCs, platelets (commonly called a clot)

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larger thrombus in:

- coronary blood vessel --> heart attack

- cerebral blood vessel --> stroke

Coronary Artery Disease (CAD)/Ischaemic Heart Disease (IHD)

- damage to heart: gradual decrease in blood flow to the heart. Decrease in supply of oxygen and nutrients

- acute damage to heart: suden increase in blood flow to the heart

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- diagram important to understand

Ischeamic Heart Disease: Myocardial Infarction (Heart Attack)

MECHANISMS OF DAMAGE:

Ischaemia:

- waste not removed

- mitochondrial damage

- leaking of proteolytic enzymes

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Ischaemia reperfusion injury:

Oxygen restoration:

- more free radicals, reactive oxygen species -> damage

- Calcium overloading -> arrhythmias, apoptosis

- Exaggerates inflammation

Ischaemic Stroke

ISCHAEMIC STROKE: blood supply to brain affected

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Embolisms block blood flow:

- Thrombus formation in atherosclerotic cerebral blood vessels

- small vessel disease in brain (very small atherosclerotic plaques)

- thrombi which form in other organs (e.g heart) travel to brain through blood vessels

Haemorrhagic Stroke

HAEMORRHAGIC STROKE: due to blood vessel rupture

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- Aneurysm (swelling in vessel wall)

- can be cauesd by uncontrolled high blood pressure

- Atherosclerosis can increase blood pressure

Cardiac Arrhythmia

- Heartbeat originates as an electrical impulse, causes synchronised contraction of the ventricles of the heart

- Abnormal electrical activity causes cardiac arrhythmia (too fast, too slow, regular, irregular)

- can lead to deterioration in the mechanical function of the heart

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AETIOLOGIES: genetic (rare) or ischemic injury (common)

Sudden Cardiac Death

- Cessation of normal cardiac electrical activity, heart stops pumping blood

CAUSES:

5-10% are due to arrhythmias

- note - not all arrhythmias will be rectified by defibrillation

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10% are due to structural heart disease

- congenital coronary artery abnormalities

- myocarditis (inflammatory cardiomyopathy)

- hypertensive heart disease

- myocardial hypertrophy

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15-20% are non-cardiac causes

- e.g trauma, aortic rupture, poison

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65-70% - coronary heart disease (age 35+)

Congestive Heart Failure (CHF)

HEART CANNOT PROVIDE ADEQUATE PERFUSION TO MEET METABOLIC REQUIREMENTS OF PERIPHERAL TISSUES

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- "Congestive" - congestion of venous circulation

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Decrease in cardiac output is more common

- gradual, progressive onset (age, chronic work overload)

- acute (myocardial infarction, acute valve dysfunction)

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- imbalance between output and requirement (anaemia, hyperthyroidism)

Congestive Heart Failure (CHF) Mechanisms

- ventricle cannot relax, fill with blood (diastolic failure)

- ventricle cannot contract, eject blood (systolic failure)

Congestive Heart Failure (CHF): Secondary to other conditions

LEFT-SIDED FAILURE:

- Secondary to: Primary myocardial disease, mitral or aortic valve disease, ischaemic heart disease

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RIGHT-SIDED FAILURE:

- Secondary to: left sided heart failure, Primary pulmonary disorders (rare)

Congestive Heart Failure: Compensation

- Sympathetic nervous system activation e(e.g adrenaline increases heart rate, contractility)

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FRANK-STARLING MECHANISM:

- larger volume pumped, dilates heart

- increased contractility, stroke volume

- actin-myosin cross-bridges at optimal length generate greater force

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STRUCTURAL CHANGES:

- hypertrophy

CVD is the leading cause of death in the world

DIAGRAM ON SLIDE 28

Major cause of morbidity and mortality globally

- 75% in low and middle income countries

Mortality due to CVD increases with age

DIAGRAM ON SLIDE 30

Cardiovascular disease in australoa

DIAGRAM ON SLIDE 31

About 90% of CVD is preventable

THE RISK FACTORS CAN BE AVOIDED:

- high blood pressure

- smoking

- type 2 diabetes

- lack of exercise

- obesity

- hyperlipidaemia

- high blood cholesterol

- excessive alcohol consumption

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ALL SHARED CAUSATIVE FACTORS WITH:

- heart disease

- stroke

- cancer

- diabetes

- respiratory disease

CVD and public health

- Target population at as whole, and high risk populations with appropriate strategies

- overall aim is to shift population out of the high risk category

Prevention of CVD through reducing modifiable risk factors

- the rates of ischemic heart disease have been decreasing dramatically since the 1980s

EXAMPLE: in the UK:

- 42% decrease is due to treatment (11% secondary prevntion (catching it early), 13% heart failure treatment, 8% initial treatment of acute myocardial infarction and 3% ypertension treatment)

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- 58% is due to population-wide risk factor reductions

Risk factors for CVD

DIAGRAM ON SLIDE 35

Tobacco use is an avoidable risk factor

CONTRIBUTES TO:

- myocardial infarction

- stroke

- sudden death

- heart failure

- aortic aneurism

- peripheral vascular disease

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AIMS:

- reduce smoking and reduce second-hand smopke

Alcohol and CVD

- 14% of alcohol attributable deaths are due to CVD and diabetes mellitus

- direct casual relationship between level, patterns of alcohol consumption and CVD

- binge (episodic) drinking associated with increased risk of CVD

- damage heart msucle - risk of stroke, cardiac arrhythmia

Physical Inactivity and CVD

- insufficient physical activity is the 4th leading risk factor for mortality

- 3.2 million deaths each year attributed to insufficient physical activity

- 20-30% increase risk of all-cause mortality vs those who engage in 30 min of moderate activity

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MECHANISM: improves endothelial function

- enhances vasodilation, vasomotor function in blood vessls

- effect on CVD partially through intermediate risk factors (glycaemic control, improved BP, lipid profile, insulin sensitivity)

CVD, atherosclerosis and modifiable risk factors (SUMMARY)

DIAGRAM ON SLIDE 40