Lecture 2: atherosclerosis Flashcards
What are the risk factors for CVD?
- Dyslipidaemia
- HTN
- Cigarette smoking
- Type 2 diabetes
- Obesity
What is the most important risk factor for developing CVD?
Hypertension
High blood pressure damages the endothelium of conduit arteries (aorta, coronary, carotid, renal) promoting the development of atherosclerosis.
Hypertension increases afterload (the force the left ventricle needs to generate to expel blood into the aorta), and this causes left ventricular hypertrophy and cardiac ischaemia.
How does cigarette smoking relate to increased CVD risk?
- Endothelial dysfunction
- Inflammation
- ↑ plaque vulnerability
- ↑ thrombosis and ↓ fibrinolysis
- ↑ activation of the sympathetic nervous system
- ↑ risk of insulin resistance and type 2 diabetes
How does diabetes relate to increased CVD risk?
- ↑oxidative stress
- ↑ endothelial cell adhesion molecule expression
- inflammation
- effects on macrophages which promote the expansion of the necrotic core of plaque.
How would you reduce CVD risk?
Exercise !!
What does a lipoprotein consist of?
- A phospholipid outer layer
- A core off triglycerides and cholesterol esthers
- Lipoproteins on the cell surface
Describe a chylomicron
- Transporting exogenous triglycerides from intestines to liver
- B-48
Describe VLDL
- Synthesised in the liver
- Transporting endogenous triglycerides
- B-100
- VLDL can turn into IDL by gaining more cholesterol and donating triglycerides to HDL
How does LDL arise?
VLDL is made by the liver (Apo B100), which donates TGs to form IDL
IDL gets converted into LDL by lipoprotein hepatic lipase, which can then cause oxidation
What is the pathology in familial hypercholesterolaemia?
LDL receptor pathway defect
What are the characteristics of familial hypercholesterolaemia?
Autosomal dominant
Often present with TC > 7.5 mmol per L and LDL-C over 4.7 mmol per L
CVD at 55
Tendon xanthomata and arcus
What are the characteristics of homozygous familial hypercholesterolaemia?
- TC over 16 mmol per L
- Cardiovascular disease in 20s and death in untreated patients at 34
How does sitostanol work?
Prevents uptake of cholesterol and blocks cholesterol from going into the vessel
What is the first lipid-modifying drug you’d prescribe?
Atorvastin (after lifestyle modifications)
What is mean arterial pressure influenced by?
- Blood volume
- Cardiac output
- Resistance of the system to blood flow
What cardiac changes occur with age?
S-BP goes up
Pulse pressure increases
What effect does arterial stiffness have on systolic and diastolic BP?
Systolic pressure increases with stiffness
Diastolic pressure falls with stiffness
! The main determinant of pulse pressure is arterial stiffness: Coronary arteries are mainly perfused during diastole, if diastolic pressure falls due to stiffness, there is less perfusion
How does NICE define HTN?
140/90
Patients with HTN often present asymptomatically
How does blood pressure relate to CVD?
No matter how low your blood pressure is, the risk of stroke or CHD will continuously go down
There is no lower threshold at which there is no more benefit
What is stage 1 HTN?
Clinic BP: 140/90 - 159/99
ABPM: 135/85 - 149/94
What is stage 2 HTN?
Clinic BP: 160/100 - 180/120
ABPM: 150/95
What is stage 3 HTN?
Clinic BP > 180 systolic or 120 diastolic
What are the Korotkoff sound?
- Is a loud tapping sound → mark of systolic BP
- A soft swishing murmur-like sound → Can feature as ausculatory gap
- Crisp thumping → similar to sound 1
- Muffling
- Silence
What is QRISK3?
The QRISK3 algorithm calculates a person’s risk of developing a heart attack or stroke over the next 10 years.
What is the purpose of QRISK3?
- 10 year risk >20%, treatment will benefit
- Accept a 10% risk, anything over 10% you treat
Remember 2ndary prevention = Atorvastatin 80mg
