Ischaemic Heart disease

Question 1

What is ischaemic heart disease?

Answer 1

When the heart isn’t getting enough blood (and hence oxygen supply)

Question 2

What is IHD caused by?

Answer 2

Atherosclerosis: build-up of fatty deposits on the inner walls of arteries which can lead to coronary artery spasms (sudden narrowing of artery) or coronary thrombosis (clots).

Question 3

What is the proposed mechanism for atherosclerosis?

Answer 3

• damage to the endothelial lining of the artery –> monocytes enter and become macrophages.
• oxidative damage occurs in LDL which makes them targets for phagocytosis.
• the macrophages and SM from damaged vessel takes up this damaged LDL which forms atheroma.
• this atheroma continues to mature from proliferation of SM cells, extracellular matrix proteins and Ca accumulation.
• the release of platelet-derived growth factor (PDGF) causes platelets to attach and hypertrophy (enlargement) of SM leading to thrombosis

Question 4

What’s the difference between stable plaques and unstable plaques?

Answer 4

Stable: regress, remain static or grow slowly over several decades. Can cause stenosis (narrowing of blood vessel) or occlusion (blockage of blood vessel).
Unstable: vulnerable to spontaneous erosion, fissure or rupture. Can lead to thrombosis, occlusion or infarction.

Question 5

What are the three main lipids and their roles?

Answer 5

Cholesterol: synthesis bile acids, steroid hormones cell membranes.
triglyceride: free fatty acids
phospholipids: conversion of carbs from diet (energy conversion)

Question 6

What are the main five types of lipoproteins?

Answer 6

1. Chylomicrons: TG + CH + apo-lipoproteins
2. VLDL: TG + 10-15% CH + lipoproteins
3. IDL: TG + CH
4. LDL: 60-70% CH
5. 20-30% CH + apo-lipoproteins

Question 7

What are the risk factors of high cholesterol?

Answer 7

• diabetes, hypertension and obesity
• smoking, alcohol consumption
• family history of premature CHD, history of vascular disease
• male sex

Question 8

What are the CVD risk guidelines

Answer 8

high: ≥ 10% - doesn’t need reassessment but clinical management
intermediate: 5 % to < 10% - reassess risk every 2 years if not receiving pharmacotherapy to reduce CVD
low: < 5% - reassess every 5 years

Question 9

What are some management tips for reducing calories?

Answer 9

• weight reduction by a reduce fat calorie controlled diet and more exercise
• sub sat fats with poly-unsat and mono-unsat.
• increase in dietary fibres, complex carbs
• reduce alco and stop smoking

Question 10

What is first in line treatment for elevated CH?

Answer 10

• statins: HMG-Coa reductase inhibitors.
  Helps to reduce LDL by increasing hepatocyte LDL receptors –> increase LDL uptake and decrease serum CH synthesis , TG and increase HDL
  e.g. rosuvastatin > atorvastatin > simvastatin > pravastatin > fluvastatin

Question 11

What are ADRs of statins?

Answer 11

• GI effects: constipation, diarrhoea, flatulence
• muscle: aches, soreness, stiffness, weakness, inflammation,
• abnormal liver enzymes or lens opacities (rare)
• long term concerns: increase risk of diabetes and haemorrhagic stroke

Question 12

What are counselling points for statins?

Answer 12

• educate patient about the role of treatment in reducing MI, stroke, blood vessel conditions
• take dose at night for simvastatin and pravastatin
• seek medical advice if muscle pain, tenderness or weakness occur

Question 13

What should be monitored when taking statins?

Answer 13

• lipid levels after 4-8 weeks or 6-12 monthly for maintenance
• creatine kinase for people with muscle symptoms
• liver function tests. e.g. ALT (alanine transferase)

Question 14

When should people not take statins?

Answer 14

• if they can’t tolerate it
• statin alone does not reach targets
• increase in TG
• mix hyperlipidaemia

Question 15

What is second line therapy for elevated CH?

Answer 15

Nicotinic acid: decreases VLDL, LDL by liver and increases HDL levels. The therapy is initiated slowly.
ADRs: flushing, pruritis, gout, hyperglycaemia.

Question 16

What are fibrates and when should they be taken?

Answer 16

Lower CH in the blood by enhanced clearance from plasma and decrease of hepatic production of VLDL PPAR-receptors.
Needs 4 weeks for optimum effect and taken 30 minutes before food.
If TG > 4 mmol/L and high LDL-C: take statins and fibrates
e.g. fenofibrate, gemifibrozil

Question 17

What are ion exchange resins?

Answer 17

Form a non-absorbable complex with bile acids and block entero-hepatic circulation (the movement of bile acid molecules from the liver to the small intestine and back to the liver).
e.g. Cholestyramine (Questran) – and colestipol (Colestid)

Question 18

What are some ADRs and drug interactions with ion exchange resins?

Answer 18

• not well tolerated, constipation, bloating,
  abdominal pain, gas, nausea.
• may interfere with absorption of fat soluble vitamins

d-d interactions: decrease absorption of absorption of digoxin, warfarin, thiazides,
antibiotics, thyroid hormones

Question 19

What is hypertriglyceridaemia and treatments for it?

Answer 19

moderately elevated triglycerides (above 4 mmol/L).
use initial statin and fenofibrate combination therapy
OR
nicotinic acid
OR
Fish oils (2-4g/day): omega-3 fatty acids can reduce VLDL-C synthesis.

Question 20

What is Ezetimibe used for?

Answer 20

selectively inhibits the intestinal absorption of cholesterol and related phytosterols. Reduces LDL-C, TG, CH and increases HDL.
When combined with statins, it enhances LDL lowering effect.

Question 21

What are PCSK9 inhibitors and how do they work?

Answer 21

new class of lipid-lowering medications (monoclonal antibodies) that are administered as monthly or bimonthly subcutaneous injections.
PCSK9 binds with LDL-r in hepatocytes and removes them from circulation. Hence inhibition of PCSK9 increases LDL-r to remove LDL-C from circulation
ADRs: injection site reactions, rash, infections

Question 22

What are plant sterols or stanols?

Answer 22

Reduce serum total and LDL-CH. Available in margarine or spread.