Myocardial Ischaemia: Causes and Results

Hypertension

• Definition: A diastolic pressure consistently at or above 90 mmHg and/or a systolic pressure at or above 140 mmHg.

• Statistical Considerations:

  • Approximately 1/3rd of Australian adults are hypertensive.

  • Hypertension increases the risk of cardiovascular disease 2- to 4-fold.

  • Hypertension treatment/management costs around $1 billion annually.

  • Indigenous Australians are 79 times more likely to die from hypertension.

Hypertension Classification

• Context is essential when classifying hypertension.

• A blood pressure of 120/80 is the population average.

• It's important to consider a patient's previous blood pressure readings for accurate assessment.

Primary Hypertension

• Also known as essential or idiopathic hypertension.

• Underlying cause is unknown.

• Represents approximately 90% of cases.

• Family history is a common factor, suggesting a possible genetic contribution.

• Contributing factors include obesity, stress, smoking, and dietary habits.

Secondary Hypertension

• Represents approximately 10% of cases.

• Due to an underlying identifiable condition, including:

  • Renal parenchymal disease

  • Renovascular disease

  • Alcoholism

  • Overactive renin-angiotensin-aldosterone system (RAAS)

  • Metabolic disturbances and overactive sympathetic nervous system (SNS)

Pre-eclampsia

• Elevated blood pressure and proteinuria associated with pregnancy.

• Affects approximately 1/4 of women.

• Symptoms of severe pre-eclampsia include:

  • ≥ 160/110 mmHg in more than one reading per 6 hours with proteinuria.

  • Or 140/90 mmHg with headaches, altered vision, nausea, abdominal pain, and difficulty breathing.

  • Signs of HELLP syndrome (haemolysis, elevated liver enzymes, and low platelets).

• Eclampsia can also occur.

Underlying Causes of Hypertension

• Four primary theories for underlying disease development:

  • Excess sympathetic nervous system activity

  • Overactive RAAS

  • Altered neurohormonal control

  • Metabolic disturbances, such as insulin resistance

• Pathophysiology involves vessel wall inflammation and vascular smooth muscle hypertrophy.

Effects and Complications of Hypertension

• Three key effects:

  • Increased afterload pressure on the heart.

  • Increased vasoconstriction, leading to increased total peripheral resistance (e.g., myocardial infarction, heart failure).

  • Pressure damage to blood vessel walls, causing microtears that contribute to spontaneous haemorrhage, atherosclerosis, aneurysms, and strokes.

  • Pressure damage to organs, increasing afferent blood vessel pressure.

Heart and Hypertension

• Hypertrophy, initially meant to compensate, becomes excessive.

• Limited space in the chest leads to hypertrophy growing inward, which compromises the capacity (volume) of the ventricle.

Atherosclerosis

• "Athero" = Gk = "gruel" or "porridge"

• "Sclerosis" = Gk = "hardness"

• Stationary blockage of an artery or arteriole.

• Composed of smooth muscle cells, macrophages, fatty deposits, cell debris, and cholesterol crystals.

Lipoproteins

• Density is determined by the amount of protein in the structure.

• Represent metabolically interconverted structures.

• Low-density lipoprotein (LDL) is colloquially known as "cholesterol" because 55% of its structure is molecular cholesterol.

Molecular Cholesterol

• Cholesterol is an essential compound with multiple roles, including:

  • Membrane repair

  • Synthesis of steroid hormones (e.g., oestrogen)

  • Regulation of receptor function

Atherosclerosis Key

• RLP = remnant-like particle = cholesterol found in triglyceride-rich lipoproteins

• LDL = low-density lipoprotein

• Ox-LDL = oxidised LDL

• CRP = C-reactive protein

• Pentraxin-3 regulates immune responses, tissue remodelling, and angiogenesis

Inappropriate Thrombosis

• Creation of an abnormal intravascular thrombus attached to the blood vessel wall.

• Embolus: Detached structure that travels through blood vessels and can become lodged in smaller blood vessels; may be a thrombus, fat, air bubble, or other material.

• Virchow’s triad:

Types of Thrombi

• Structures of thrombi and emboli have different compositions influenced by local conditions and time since formation.

Thrombosis & Thromboembolism

Aneurysms

• May occur due to:

  • Excess pressure against the wall (e.g., hypertension).

  • Tear in the wall (e.g., at the edge of an atherosclerotic plaque).

  • Pre-existing (e.g., inherited) structural weakness of the wall.

• Two primary types:

  • True aneurysm: All three tunics (layers) involved.

  • Dissecting aneurysm: Tear between two tunics.

True Aneurysm

• Two subgroups:

  • Saccular: Only one side is weakened.

  • Fusiform: Both sides are weakened.

• In early stages, there is no pooling of blood.

• As the aneurysm grows, blood may begin to pool at the bottom of the out-pouching, creating an embolus risk.

• Size and location determine symptoms.

• AAA (abdominal aortic aneurysm) often has no initial symptoms; possible pain in the abdomen, groin, or back.

Dissecting Aneurysm

• Tear between any two layers of the vessel wall.

• Commonly a consequence of trauma.

• Usually, a thrombus forms to plug the leak (false aneurysm).

• If no thrombus forms, blood pools between the layers.

• The thrombus forms between layers and can close the vessel due to pressure/size of the thrombus.

Ischaemic Heart Disease

• Most common cause of death in Australia.

• Incidence-based lifetime CVD cost = 72 billion (2020).

• “Ischaemia” = Gk iskhein “to hold” & haima “blood” = “to hold back blood”.

• Therefore, a lack of O_2 and nutrients.

• Also prevents the removal of waste.

• Manifests as angina, acute coronary syndrome, and myocardial infarction (MI).

Ischaemia vs. Hypoxia

• Ischaemia is NOT the same as hypoxia.

• Focus on oxygen deficit is insufficient to explain the impact.

• Ischaemia = lack of blood flow, meaning: lack of oxygen AND lack of nutrients AND decreased waste removal; all factors combine to create the condition.

• Hypoxia = lack of oxygen; MANY reasons for which O_2 is diminished AND does not require reduced blood flow.

Ischaemic Heart Disease

• Core problem = imbalance between the supply of blood to the heart and the demand for that blood by the heart.

• Focus = atherosclerosis and/or inappropriate vasoconstriction (= reduced supply) & increased work (=demand).

• Cause of imbalance will differ between patients.

Influences on Supply/Demand Imbalance

• Supply:

  • Diastolic perfusion pressure (e.g., hypertension, atherosclerosis).

  • Coronary vascular resistance (e.g., age-related vascular stiffness, endothelial cell dysfunction, increased sympathetic tone (nicotine use)).

  • O_2-carrying capacity of blood (e.g., nicotine use, anaemia).

• Demand:

  • Wall tension (infiltration of ventricular muscle by scar tissue (previous MIs), fibrosis, amyloid, iron, etc.; unbalanced hypertrophy).

  • Heart rate (increased sympathetic tone (nicotine), insensitivity to regulatory factors).

  • Contractility (unbalanced hypertrophy, calcium regulation).

Types of Angina

• Stable Angina: presence of atherosclerotic plaque key.

• Unstable Angina: presence of atherosclerotic plaque key.

• Variant (Prinzmetal) Angina: Intense vasospasms, usually no plaque; due to vasospasm.

Variant (Prinzmetal) Angina

• Unrelated to exertion.

• Vasospasms occur primarily between midnight and early morning, with a peak at 5 am.

• The first symptom may be MI and can lead to fatal tachycardias/fibrillations, both of which can result in cardiac arrest.

Acute Coronary Syndrome

• Comprises unstable angina, myocardial infarction, and sudden cardiac death.

• Note: the latter can be due to other causes such as congenital hypertrophic cardiomyopathy, long QT syndrome (congenital, drug-related, acquired), untreated or poorly managed hypothyroidism, etc.

Myocardial Infarction

• Tissue necrosis due to ischaemia.

• Mostly due to obstruction of artery/arteries.

• NOTE: ~10% of MI cases are independent of atherosclerosis; may be due to vasospasm, emboli, vasculitis, haemoglobinopathies, amyloid deposition, or vascular dissection.

• Permanent loss of tissue.

• The zone of injured cells around/near the infarct heals partially or completely by repair.

• Dead cells within the infarct are replaced by scar tissue.

MI Risk Factors

• Male individuals ≥ 45 years.

• Female individuals ≥ 55 years.

• Risk factors for atherosclerosis include (but are not limited to):

  • Lifestyle: cigarette smoking, lack of physical activity, illegal drug use, stress.

  • Physiological: hypertension, diabetes mellitus, hypercholesterolaemia, obesity.

Myocardial Infarctions

• Transmural: ischaemic necrosis spans the full thickness of the ventricular wall; due to full occlusion of one or more arteries (e.g., LAD).

• Subendocardial: ischaemic necrosis is limited to the inner 1/3rd of the ventricular wall; due to partial or complete occlusion of one or more epicardial arteries.

• ECG abnormalities reflect the extent to which something happened.

Morphology Following MI

• Required to know macro & micro features at 1 day, 2 days, 1 week, 2 weeks & 2 months

Timeline of MI Complications

• Arrhythmia:

  • Immediate leading to sudden death

  • Early

  • Ongoing i.e. bundle branch block

• Contractile dysfunction

  • Immediate, within 60 seconds

  • Cardiogenic shock

  • Chronic left ventricular failure

• Pericarditis

  • 2-3 days usual

  • May appear weeks after MI = Dressler's syndrome

• Myocardial rupture

  • 3-7 days when necrotic myocardium at its weakness

• Mural thrombosis with risk of embolism

  • Highest risk at 10 days, lasting for 3 months

• Aneurysm - late complication

Necrosis vs Apoptosis

• Necrosis:

  • Pathologic process.

  • Immune system-dependent.

  • Inflammation-associated.

• Apoptosis:

  • Normally = physiological process.

  • Active, energy-dependent process.

  • Inflammation-independent.

Summary

• Primary hypertension – cause unknown (90%)

• Secondary hypertension – identifiable underlying conditions

• Pre-eclampsia – elevation of BP & proteinuria associated with pregnancy

• Effects of hypertension – heart failure, stroke, MI, haemorrhage, renal failure, retinal damage, aneurysm

• IHD: angina (stable, unstable, variant (Prinzmetal)), MI, sudden cardiac death

• Acute coronary syndrome (ACS): unstable angina, MI, sudden cardiac death

• MI risk factors: include hypertension, smoking, diabetes mellitus, atherosclerosis, obesity, family history

• MI: transmural & subendocardial

• Complications of MI: include arrhythmia (dysrhythmia), contractile dysfunction