Cardiovascular Disease

Coronary blood flow to a region of the myocardium may be reduced by a mechanical obstruction that is due to:
- Atheroma
- Thrombosis
- Spasm
- Embolus
- Coronary ostial stenosis
- Coronary arteritis (e.g. SLE)
There can be a decrease in the flow of oxygenated blood to the myocardium that is due to:
- Anemia
- Carboxyhaemoglobulinaemia
- Hypotension causing decreased coronary perfusion pressure
An increased demand for oxygen may occur owing to an increase in cardiac output or myocardial hypertrophy.

Process of coronary atherosclerosis
The development of atherosclerosis follows the endothelial dysfunction, with increased permeability to and accumulation of oxidized lipoproteins, which are taken up by macrophages at focal sites within the endothelium to produce lipid-laden  foam cells. Release of cytokines by monocytes, macrophages or the damaged endothelium promotes further accumulation of macrophages as well as smooth muscle cell migration and proliferation. The layer of smooth muscle cells that separates plaque core thickens over time. Collagen is produced in larger and larger quantities by the smooth muscle and the whole sequence of events cumulates as an 'advanced or raised fibrolipid plaque'. Two different mechanisms are responsible for thrombosis on the plaques:

• First process is superficial endothelial injury, which involves denudation of the endothelial covering over the plaque. Subendocardial connective tissue matrix is then exposed and platelet adhesion occurs because of reaction with collagen.
• Second process is deep endothelial fissuring, which involves an advanced plaque with a lipid core. The plaque cap tears (ulcerates, fissures or ruptures) allowing blood from the lumen to enter the inside of the plaque itself. Thrombus forms within the plaque. Thrombosis may then extend into the lumen.

Haemodynamically significant stenosis (50% reduction of luminal diameter) causes dilation of smaller distal arteries and arterioles and any increase in myocardial oxygen demand provokes ischemia.

Cardiovascular disease door mednotez
Angina
Classical or exertional angina pectoris is characterized by:
- Constricting discomfort in the front of the chest, arms, neck, jaw
- Provoked by physical exertion especially after meals and in cold, windy weather or by angel or excitement
- Relieved with rest or glyceryltrinitrate.
Types
Unstable angina = recent onset or deterioration in previous stable angina with symptoms frequently occurring at rest
Refractory angina = patients with severe coronary disease in whom revascularization is not possible and angina is not controlled by medical therapy
Variant (Prinzmetal's) angina = angina that occurs without provocation usually at rest as result of coronary artery spasm. ST elevation.
Cardiac syndrome X = patients with a good history of angina, a positive exercise test and angiographically normal coronary arteries
Examination
There are usually no abnormal findings in angina.
Signs; anaemia, throtoxicosis, hyperlipidaemia, fourth heart sound maybe heard.
Diagnosis and investigation
The diagnosis of stable angina can be made on clinical assessment alone OR by clinical assessment combined with anatomical (cardiac catherization or CT coronaru angiography) or functional imaging (SPECT, stress-echography, stress-magnetic resonance imaging)
! Patients presenting with chest pain should have a 12-lead ECG performed to exclude and acute coronary syndrome.
Management
Underlying problems such as anaemia or hyperthyroidism should be treated. Management of coexistent condtitions such as DM and hypertension, should be optimized. Risk factors should be evaluated and steps made to correct them when possible e.g. smoking stopped.
Low-dose aspirin is indicated. Prophylaxis should be started with either beta-blocker or calcium channel blocker. If patient remain symptomatic then a beta-blocker can be combined with a dihydropyridine. Patients intolerant of beta-blocker or calcium channel blockers are treated with long-acting nitrates, ivarbradine, nicorandil and ranolazine. Revascularization should be used in patients who remain symptomatic despite two-antianginals.
Revascularization
Percutaneous coronary intervention (PCI) is the procress of dilating a coronary artery stenosis using an inflatable balloon and metallic stent introduced into the arterial circulation via the femoral radical or brachial artery
Coronary artery bypass grafting (CABG); with CABG autologous veins or arteries are anastomosed to the ascending aorta and to the native coronary arteries distal to the area of stenosis.

Coronary Artery Bypass Graft (CABG)

Acute coronary syndromes
Acute coronary syndromes (ACS) include:
- ST-elevation myocardial infarction (STEMI)
- Non-ST-elevation myocardial infarction (NSTEMI)
- Unstable angina (UA)
The difference between UA and NSTEMI is that in the latter there is occluding thrombus, which leads to myocardial necrosis and rise in serum troponins or CK-MB.

• Type 1 - spontaneous MI with ischemia due to a primary coronary event e.g. plaque erosion/rupture, fissuring or dissection
• Type 2 - MI secondary to ischemia due to increased oxygen demand or decreased supply, such as coronary spasm, coronary embolism, anaemia, arrhythmias, hypertension or hypotension.
• Type 3,4,5 - diagnosis of MI in sudden cardiac death, after percutaneous coronary intervention (PCI) and after coronary artery bypass graft (CABG) respectively.

Pathophysiology

The common mechanism to all ACS is rupture or erosion of the fibrous cap of a coronary artery plaque. This leads to platelet aggregation and adhesion, localized thrombosis, vasoconstriction and distal thrombus embolization. Thrombus formation and the vasoconstriction produced by platelet release of serotonin and thromboxane A2, results in myocardial ischaemia due to reduction of coronary blood flow.
Diagnosis
Patients with an ACS may complain of a new onset of chest pain, chest pain at rest or a deterioration of pre-existing angina. However some patients present with atypical features including indigestion, pleuritic chest pain or peptic ulceration.
12-lead ECG; ST depression and T wave inversion are highly suggestive for an ACS.
Biochemical markers:
- Cardiac troponin
- Creaktine-kinase-MB
- Myoglobin
Treatment
High risk patients should have early coronary angiography and interventions.
Low-risk patients can be managed with oral aspirin, clopidrogel, beta-blockers and nitrates.
Antiplatelet agents

Rupture of the atheromatous plaque exposes the circulating platelets to ADP (adenosine diphosphate). thromboxane A2 (TxA2), epinephrine, thrombin and collagen tissue factor. Platelet activation stimulates the expression of glycoprotein (GP) IIb/IIIa on the platelet surface. These receptors bridge fibrinogen between adjacent platelets, causing platelet aggregates.
Aspirin blocks the formation of thromboxane A2 and so prevents platelets aggregation.
Clopidrogen inhibits ADP dependent activation of the GPIIb/IIIa complex.

PERIPHERAL VASCULAR DISEASE
Peripheral vascular disease (PVD)  is commonly caused by atherosclerosis and usually affects the aorta-iliac or infrainguinal arteries.
Chronic lower limb ischaemia
Peripheral arterial disease can be described using the Fontaine classification:
- Stage I - asymptomatic
- Stage II - intermitted claudication (excertional discomfort commonly in the calf or in aorta-ilac disease in the buttock, hip or thigh and erectile dysfunction)
- Stage III - rest pain/ nocturnal pain (severe unremitting pain in the foot which stops patient from sleeping)
- Stage IV - necrosis/gangrene

Signs. The lower limbs are cold with dry skin and lack of hair. Pulses may be diminished or absent.

Premature atherosclerosis in patients aged <45 years may be associated with thrombophilia and hyperhomocyteinaemia.

Differential diagnosis
- Spinal canal claudication
- Osteoarthritis hip/knee
- Peripheral neuropathy
- Fibromuscular dysplasia
- Venous claudication
- Popliteal artery entrapment

Investigations
- Digital subtraction angiography (DSA)
- Duplex ultrasound
- 3D contrast enhanced magnetic resonance angiography
- CT angiography

Acute lower limb ischaemia

Patients complain of pain, that looks white (pallor), parathesia, paralysis and that it feels cold. The pain is unbearable and normally requires opioids for relief.

Signs. The limb is cold with mottling or marbling of the skin. Pulses are diminished or absent. The sensation and movement of the leg are reduced in severe ischaemia. Patients may develop compartment syndrome.

Causes. Acute limb ischaemia (ALI) may occur because of embolic or thrombotic disease. 

Abdominal aortic aneurysm

Abdominal aortic aneurysms (AAA) occur most commonly below the renal arteries. Aneurysm may occur secondary to atherosclerosis, infection, trauma or maybe genetic (Marfan, Ehlers-Danlos)

Symptoms. Most aneurysms are asymptomatic. rapid expansion or rupture of an AAA may cause severe pain. A ruptured AAA causes hypotension, tachycradia, profound anaemia and sudden death