Coronary heart disease

Question 1

Occlusive vascular disease

Answer 1

Occlusive vascular disease is most commonly due to atherosclerosis
Affects arteries causing stenosis, leading to distal arterial insufficiency
Ischaemia of subtended tissues

Question 2

Atherosclerosis

Answer 2

Atheroma = fatty plaque/ deposit
Sclerosis = hardening
NB distinct from arteriosclerosis (hardening and loss of elasticity without atheroma)
Atheromatous plaques predominantly in large and medium sized arteries
May be restricted to one site but often occur at multiple sites throughout body

Question 3

Clinical consequences of atherosclerosis

Answer 3

Coronary arteries: ischaemic heart disease, angina, MI
Cerebral arteries and carotid arteries: cerebrovascular disease, stroke, transient ischaemic attack, vascular dementia
Renal arteries: renovascular disease
Aorta: aortic aneurysm
Legs and arms: claudication, peripheral gangrene

Question 4

Endothelial dysfunction

Answer 4

Vascular endothelium is a target of all of the CV risk factors
Endothelial dysfunction/ damage is pivotal in the development of atherosclerosis

Question 5

The fatty streak

Answer 5

Response to injury hypothesis
Lesions begin as a response to injury/ dysfunction of endothelium NB endothelium is intact
Increases permeability to plasma constituents, notably oxidised LDL
Increases monocyte and platelet adherence
Early, reversible development of fatty streaks

Question 6

Fatty streak formation

Answer 6

Subsequent development of atheroma usually slow, but highly variable
Rate of development may vary in coronary arteries, cerebral arteries and peripheral arteries
Rate and extent of formation dependent on the intensity of exposure to risk factors
Extremely complex pathological process: lipid accumulation, fibro-intimal hyperplasia, inflammation, calcification

Question 7

Sites of coronary atheroma

Answer 7

Anywhere in major epicardial coronary arteries
Often at tortuosities and bifurcations where turbulent flow of blood&raquo_space;> endothelial shear stress is greatest
Collateral vessel formation is stimulated by various growth factors, upregulated in response to chronic or repetitive ischaemia
A long term beneficial structural adaptation

Question 8

Myocardial O2 supply-demand balance

Answer 8

O2 supply: coronary blood flow (incl. collaterals), tissue O2 extraction (75-95%)

O2 demand: pressure/volume work, heart rate, wall tension/ wall stress, inotropy, ionic homeostasis

Question 9

Myocardial ischaemia

Answer 9

Develops when blood supply to the myocardium is inadequate to meet the metabolic demand of the tissue
Absolute reduction in blood flow at rest (supply ischaemia) supply < demand
Relative reduction in face of increased muscle work (demand ischaemia) demand > supply
In > 95% of cases, myocardial ischaemia is associated with a critical stenosis of one or more coronary arteries i.e. practically unknown without coronary atherosclerosis

Question 10

Characteristics of myocardial ischaemia

Answer 10

Coronary plaques develop over several For may decades
Disease is asymptomatic in most patients during its development
Typically, symptoms and diagnosis occur when one or more arteries has >70% stenosis
For many patients, first sign is plaque rupture and sudden thrombotic occlusion: acute coronary syndrome, cardiac arrest, sudden death

Question 11

Stable coronary disease

Answer 11

Implies a long period of atheroma development, uncomplicated, fixed stenosis with or without symptoms
Many patients have chronic stable angina
Typically, angina pectoris on exertion (demand ischaemia)
Angina is a symptom; characteristic pattern of pain (often referred pain)

Question 12

Silent ischaemia

Answer 12

Ischaemia may be silent; patient experiences little or no pain
Probably very common (estimated 3-4 million cases in USA)
Occurs especially when poorly controlled diabetes or pre-existing heart muscle disease e.g. MI
Detected by ecg changes on exercise or stress testing, or continuous ambulatory ecg recording

Question 13

Other symptoms of transient ischaemia

Answer 13

Characteristic ecg changes during acute ischaemia
ST segment depression; >1mm diagnostic
Dyspnoea
Rhythm disturbance (palpitations)
Dizziness, mental changes

Question 14

Other forms of angina

Answer 14

Most angina is chronic stable, associated with a fixec coronary stenosis; other forms are:
Prinzmetal’s (variant) angina: occurs at rest, due to coronary spasm/ constriction, rare
Cardiac syndrome X (microvascular angina) angina without epicardial coronary disease, likely to be a microvascular disease, more common in women
Unstable (crescendo) angina: sudden onset, at rest or exercise, an acute coronary syndrome, thrombosis leads to occlusion at site of plaque rupture

Question 15

Ischaemic cardiomyopathy and hibernating myocardium

Answer 15

Chronic coronary disease can lead to ischaemic cardiomyopathy resulting in reduced LV output
When ejection fraction < 35-40% there will be signs of heart failure
Structural changes to myocardium are irreversible if cell death has occurred
Sometimes chronic hypoperfusion leads to reduced output in viable myocardium; this condition is caled hibernating myocardium and is reversible with revascularisation

Question 16

Acute coronary syndromes

Answer 16

Unstable angina and acute myocardial infarction
Sudden rupture of an atherosclerotic plaque precipitates coronary thrombosis (with or without embolism from fragments of plaque)
Rate/ extent of thrombus formation determined by balance of prothrombotic and antithrombotic/ endogenous fibrinolytic factors
Unstable angina is indicative of unstable plaque and prothrombotic state; strongly predictive of acute MI

Question 17

Signs and symptoms of acute coronary syndrome

Answer 17

Crushing chest pain- referral to neck, face, arms
Dyspnoea 
Nausea/ vomiting
Profound sweating (diaphoresis)
Palpitations
Anxiety or sense of impending death
Symptoms steadily worsen, unrelieved by rest or nitrates
Always a medical emergency

Question 18

Diagnosis of acute coronary syndrome

Answer 18

Initially based on symptoms and risk factor profile
ECG changes
Serum markers (troponin)

Question 19

ECG changes

Answer 19

There may or may not be early ST segment elevation

Later development of Q-wave is associated with established myocardial infarction

Question 20

Serum markers

Answer 20

Provide biochemical diagnosis

Appearance in plasma of myocardial proteins are indicative of muscle damage

Question 21

Diagnosis of acute coronary syndrome

Answer 21

myocardial infarction = necrosis of cardiac muscle
pathologically, coagulative necrosis within an ischaemic risk zone
at a cellular level, oncosis with some evidence of apoptosis and autophagy