Hyperlipidaemia and Lipid Metabolism (RISK)

Question 1

Properties of Chylomicrons

Answer 1

Largest in size 
Lowest in density 
Non-atherogenic 
Synthesised after fatty meal
Transport dietary triglycerides from gut for use and storage
Cleared rapidly from bloodstream

Question 2

Properties of VLDL

Answer 2

Similar but smaller in structure to chylomicrons
Produced in the liver
Carriers of endogenous triglycerides and cholesterol
Involved in synthesis of LDL and HDL
atherogenic (smaller in particular)

Question 3

Properties of IDL

Answer 3

Formed during the breakdown of VLDL and chylomicrons
Atherogenic
Less triglyceride, more cholesterol than VLDL
Use in cholesterol recycling (liver) and LDL formation (blood)

Question 4

Properties of LDL

Answer 4

Generated from IDL in circulation
Atherogenic (oxidised most atherogenic)
Main carriers of cholesterol (60-70% plasma cholesterol)
Four main subtypes (III most atherogenic)

Question 5

Properties of HDL

Answer 5

Smallest but most abundant
Return 20-20% cholesterol to liver
Protective against atherosclerosis
Two main subtypes (HDL2, HDL3)

Question 6

10% LDL Cholesterol raises risk of CVD by…

Risk Factors modifying this relationship?

Answer 6

approx. 20%

Smoking
Hypertension
Diabetes
Low HDL cholesterol.

Question 7

Dyslipidaemia

Answer 7

elevation of plasma cholesterol, triglycerides (TGs), or both, or a low HDL level that contributes to the development of atherosclerosis.
Causes may be primary (genetic) or secondary.

Question 8

How may triglycerides increase risk of atherosclerosis?

Answer 8

Complex relationship, weakened by other risk factors.
Low HDL levels and high atherogenic LDL cholesterol.
VLDL = triglyceride carrier, production produces atherogenic remnants.

Question 9

Triglycerides

Answer 9

In fasting plasma, triglycerides are transported in VLDL synthesised in the liver, and after meals are also found in chylomicrons.
(link to atherosclerosis- production of these molecules produces atherogenic remnants)

Question 10

Low to Very High Triglyceride levels

Answer 10

Normal Triglyceride levels = <200 mg/dl = 2.3mmol/l
Borderline high = 200-400 mg/dl = 2.3- 4.5 mmol/l
High = 400-1000 mg/dl = 4.5- 11.3 mmol/l
Very high = >1000 mg/dl = >11.3 mmol/l

Question 11

Non-atherogenic Hypertriglyceridaemia

Answer 11

Chylomicrons and large forms of VLDL
Increase the risk of pancreatitis
Not CHD (chylomicrons and VLDL are too large to enter the arterial wall)

Question 12

Relationship between Triglycerides and HDL

Answer 12

HDL are usually low where triglycerides are high.

Question 13

Reasons for low HDL

Answer 13

High triglycerides 
Smoking 
Obesity 
Physical Inactivity 
(atherogenic lifestyle)

Question 14

Low HDL value

Answer 14

<1 mmol/l

Question 15

The endogenous pathway of lipid metabolism

Answer 15

VLDL undergo delipidation with the enzyme lipoprotein lipase (chylomicrons similar).
Triglyceride removed from centre, exchanged with cholesterol ester (from HDL)

Question 16

Which enzyme converts large VLDL to IDL?

Answer 16

lipoprotein lipase

Question 17

Which enzyme works upon smaller VLDL and IDL particles?

Answer 17

Hepatic Lipase

Question 18

The enterohepatic circulation

Answer 18

route for excretion of cholesterol and bile acids

Question 19

The Endogenous Pathway

Answer 19

Delipidation of VLDL with the enzyme lipoprotein lipase to release triglyceride centre
VLDL then undergoes further change

Question 20

The Exogenous Pathway

Answer 20

Lipids that are absorbed from diet
Deplipidation of Chlyomicrons by lipoprotein lipase
Remnants uptaken by liver for use or excretion

Question 21

10% reduction in total cholesterol results in…

Answer 21

15% reduction in CHD mortality

11% reduction in total mortality

Question 22

Primary target to prevent CHD

Answer 22

LDL-C

Question 23

Absolute risk vs Relative risk

Answer 23

Absolute- likelihood of developing disease/event happening
Relative- proportional risk between different patient groups

Cholesterol reduction reduces both types of risk

Question 24

Primary Prevention

Answer 24

Reduce the risk to prevent disease before it occurs. The younger a patient treated for risk, the more they benefit in the long term).
40 y/o - 50% risk reduction
70 y/o - 20% risk reduction for the same 10% reduction in cholesterol.

Question 25

Outline of process of atherosclerosis

Answer 25

1. Endothelium damage e.g. smoking 2. protective response - cellular adhesion molecules + monocytes + T lymphocytes 'stick'. 3. Migration to subendothelial space 4. macrophages take up oxidised LDL = FOAM CELLS 5. Fatty streak. Fibrous -> atherosclerotic plaque. Plaque rupture -> thrombosis -> stroke, MI, ischaemic leg, CV death.

Question 26

What is the value for target cholesterol?

Answer 26

< 5 mmol/l

Question 27

How to Statins reduce CHD endpoints?

Answer 27

reduce the total cholesterol and the LDL cholesterol.

Question 28

What are the pleotropic effects of statins?

Answer 28

``` Improvement of endothelial dysfunction Increased Nitric Oxide bioavailability Antioxidant properties Inhibition of inflammatory responses Stabilisation of atherosclerotic plaques ```

Question 29

Where do statins act in the cholesterol synthesis pathway?

Answer 29

Inhibitors of HMG-CoA reductase- the enzyme involved in the rate limiting step of cholesterol formation.

Question 30

Why can statins be seen as "beneficial to all"?

Answer 30

Treatment has been shown to provide morbidity benefits in a wide range of patients- benefit was seen even at patients at low risk with average/baseline cholesterol levels.

Question 31

What are Xanthomas?

Answer 31

Xanthomas are fatty growths which develop underneath the skin. These growths can appear anywhere on the body, but they typically form on the joints, especially the knees and elbows.

Question 32

What are Xanthelasmas?

Answer 32

Xanthelasmas are xanthomas of the eyelids that may or may not be associated with hyperlipidaemia.

Question 33

What are Tendon Xanthomas?

Answer 33

Tendon xanthomas occur at the extensor tendons of the finger, patella, elbows, Achilles tendon (one of the most common sites) etc. Lipid diffuse infiltrates the tendon. This can occur with hypercholesterolemia (types II and III), or from normal lipids such as cerebrotendinous xanthomatosis/plant sterols.

Question 34

What are Tuberous Xanthomas?

Answer 34

Tuberous Xanthomas occur when lipid deposits in the dermis and subcutis. They are papular, nodular or plaques. They grow on extensor surfaces or large joints, hands, buttocks, heels and flexures. Familial or acquired hypertriglyceridemia - biliary cirrhosis.

Question 35

What are Eruptive Xanthomas?

Answer 35

Eruptive Xanthomas are small reddish-yellow papules that form on the buttocks, posterior thighs and body folds. This usually occurs with abrupt increase in serum triglyceride levels.

Question 36

List of diseases attributable to hypertension

Answer 36

``` > Aortic Aneurysm >LV hypertrophy >Heart failure >MI >CHD >Gangrene of the lower limbs >Stroke >Encephalopathy >Cerebral Haemorrhage >Preeclampsia/eclampsia >Chronic Kidney failure >Blindness ```

Question 37

Two subtypes of hypertension (+def.)

Answer 37

Essential- no underlying cause in 90% of cases. | Secondary- underlying cause.

Question 38

Lifestyle modifications recommended in hypertensive patients

Answer 38

``` Weight loss (if overweight) Limit alcohol intake Increase physical activity Reduce salt intake Stop smoking Limit intake of foods rich in fat and cholesterol ```

Question 39

Only 1.5% of hypertensive patients have no other risk factors- what are the commonly associated risk factors of hypertension?

Answer 39

``` Dyslipidaemia Diabetes Age Male gender Smoking FH ```

Question 40

What is more efficient in treating hypertension in terms of solo or combination therapies?

Answer 40

Greater efficiency of combination therapy- reduction of stroke/IHD events increases depending on how many drugs are used. Half doses in combination therapy are more effective than a single drug alone (calcium channel blocker).

Question 41

Why is diabetes a huge risk factor of CVD?

Answer 41

T2DM associated with hypertension, abnormalities in lipoprotein metabolism and increased propensity to oxidative stress and endothelial dysfunction. Hyperglycaemia may accelerate vascular damage. T2DM is a hypercoagulable state with enhanced coagulation, decreased fibrinolysis, and platelet hyperaggregability.

Question 42

Diabetes without prior MI imposes same risk as...

Answer 42

Non-diabetic WITH prior MI

Question 43

What is the ticking clock hypothesis?

Answer 43

Microvascular complications - at onset of hyperglycaemia | Macrovascular complications- before the diagnosis of hyperglycaemia.

Question 44

What is Metabolic Syndrome?

Answer 44

``` Combination of diabetes, high blood pressure and obesity- 3 or more of the risk factors below; Abdominal obesity Triglycerides > 1.7 mmol/l HDL-C <1 (men ) or <1.3 (women) BP > 130/85 mmHg Fasting glucose > 5.6 mmol/l ```

Question 45

How are inflammatory markers measured as a calculation of risk?

Answer 45

hs-CRP and cholesterol.

Question 46

How do ethnic differences effect CVD risk?

Answer 46

South Asians living in the UK have a higher death rate for CHD. This rate is 46% higher in men, and 51% higher in women. Again, the difference in rates is falling. Black Caribbean and black Africans have much lower CHD death rates than average- 50% less in men and 66% less in women. However they have a much higher stroke risk.

Question 47

What value on ASSIGN score is considered high risk?

Answer 47

20 + | Note- this is not a % it is a score.

Question 48

How does having multiple risk factors significantly increase risk?

Answer 48

When risk factors co-exist the sum of their combined effect is often much greater than the sum of their individual effects. Thus, the patient with severe hypercholesterolaemia may be at lower risk than the patient with moderate hypertension, moderately elevated lipid levels and who smokes.

Question 49

Changing the therapeutic Target for Atherothrombotic | Vascular Disease

Answer 49

Ischaemia as the target - antianinals (BBC, Nitrates and BB), Revascularisation (angioplasty and CABG) and risk factor modification. Atherothrombosis as the target- aspirin, statin, BB, ACII, Exercise, smoking cessation and symptom management