Cardiovascular Disease

Question 1

Pathophysiology of atherosclerosis?

Answer 1

Atherosclerosis
Athero - atheroma formation
Sclerosis - stiffening of the blood vessel walls

• Endothelial dysfunction (triggered by a number of factors such as smoking, hypertension and hyperglycaemia) resulting in a number of changes to the endothelium e.g. development of a proinflammatory, pro-oxidative and proliferate state ; reduced citric oxide availability.
• LDLs infiltrate the subendothelial space.
• Monocytes migrate from the blood stream into these sxbendothelial spaces.
• Monocytes differentiate into macrophages forming large ‘foam cells’. As these macrophages die, they further contribute to the inflammatory process.
• Smooth muscle cells proliferate from the tunica media and migrate to the tunica intimate to form a fibrous capsule that covers the fatty plaque. An atheromatous plaque is formed.

These atheromatous plaques

• stiffen the blood vessel walls –> cause hypertension and increased after load on the heart, placing the heart under strain.
• reduce lumen size of the blood vessel for which blood can pass through –> resulting in ischaemia e.g. in the case of angina.
• may break off leading to thrombus formation and Ischaemia of the distal vessel e.g. acute coronary syndrome.

Question 2

What risk factors increase the risk of developing an atheromatous plaque?

Answer 2

Non-modifiable risk factors
> Male
> Older age
> Family history of cardiovascular disease

Modifiable risk factors 
> Smoking 
> Alcohol consumption 
> Poor diet (high in sugars and transfats, low in fibre (fruits and vegetables) and omega 3). 
> Lack of exercise
> Obesity 
> Poor sleep 
> Stress

Medical co-morbidities that increases the risk of atherosclerosis that needs to be carefully managed to minimise its risk.
> Diabetes (type 1 and type 2)
> Hypertension (high blood pressure)
> Chronic kidney disease –> CKD causes quantitative and qualitative changes in the levels of lipids within our circulation, in favour of atherogenic process.
> Inflammatory conditions such as rheumatoid arthritis –> this is because atherosclerosis is an inflammatory condition.
>Atypical psychotic medications

Question 3

What are potential end-results of atherosclerosis?

Answer 3

• Angina
• MI
• TIA
• Stroke
• Mesenteric Ischaemia
• Peripheral vascular disease

Question 4

Prevention of cardiovascular disease falls under which two categories?

Answer 4

1) Primary prevention

2) Secondary prevention

Question 5

What is primary prevention?

What do you do for primary prevention?

When starting this primary prevention, what must you keep in mind?

Who are also given this primary prevention method?

Answer 5

Preventing the development of a cardiovascular event in patients who have never experienced a cardiovascular event.

Primary prevention includes:

• performing a QRISK3 score to calculate the patient’s risk of developing an MI/stroke within the next 10 years.
• If their risk is more than 10%, then you offer the patient 20mg Atorvastatin to be taken once daily at night. The dose should be titrated up until the patient’s non-HDL cholesterol level has reduced by more than 40%.

Make sure to check the patient’s lipid levels every 3 months to see if their lipid levels have improved. Prior to changing the dose, its also very important to check the patient’s adherence to treatment.

NICE also recommends to check the patient’s LFTs within 3 months of starting a statin and again at 12 months. If their LFTs are normal, then they should be checked again. LFTs are checked because statins can cause a mild increase in ALT (alanine transaminase enzyme) and AST (aspartate transaminase) enzymes in the first few weeks of starting the medication. But they don’t need to be stopped if ALT and AST levels are up to 3x the normal limit. Higher than this, then the drug needs to be stopped.

Note that patients with chronic kidney disease or type 1 diabetes (for more than 10 years) are also given 20mg Atorvastatin at night as well.

Question 6

What is secondary prevention?

What does secondary prevention of cardiovascular disease consist of?

Answer 6

Secondary prevention is when you try and prevent a cardiovascular event from happening in patients that have previously experienced a cardiovascular event.

Secondary prevention consists of the 4As.

• Aspirin (plus a second anti-platelet such as clopidogrel for 12 months).
• Atorvastatin (80mg)
• Atenolol (or other betablockers e.g. bisoprolol titrated to maximum tolerated dose).
• ACE inhibitor (e.g. ramipril titrated to maximum tolerated dose).

Question 7

What are some side-effects of statins?

Answer 7

• Myopathy –> the patient will experience muscle pain and muscle weakness. To check for myopathy, check the patient’s creatinine kinase levels.
• Type 2 diabetes
• Haemorrhagic strokes (occur very rarely).

Despite these side effects, the benefits of statins heavily outweigh the risks of statins. Newer statins e.g. atorvastatin are usually very well tolerated.