statins

Question 1

Define statins

Answer 1

Statins are a group of compounds which inhibit hepatic synthesis of cholesterol
Act as competitive inhibitors of 3-hydroxyl-3-methylglutaryl coenzyme A (HMG CoA) reductase

Question 2

briefely describe cholestrols course through the body.

Answer 2

1. dietary intake
2. heptatic synthesis
   leads to:
3. lipoproteins and other cells
4. by product of hepatic process (?) Bile synthesis/ bile salt catabolism

Question 3

what are the positive effects of cholestrol?

Answer 3

Membrane structure and function – membrane fluidity
• Hormone production – steroids
• Vitamin D production
• Bile synthesis

Question 4

what are lipoproteins?

Answer 4

-complex of lipid and protein which allows lipids and -Superficial coating of proteins and phospholipids makes them soluble
in plasma
-Exposed proteins can bind to specific membrane receptors thereby defining which cells absorb the associated lipids
-Differ in the ratio of protein:lipid and also the particular lipids and apoproteins they contain (apoprotein = surface protein)

Question 5

what are the 3 types of fat in the body

Answer 5

lipoproteins
tryglycerides
phospholipids

Question 6

what is an atheroma?

Answer 6

accumulation of intracellular and extracellular lipids in

the intima of large and medium sized arteries

Question 7

what is atherosclerosis?

Answer 7

thickening and hardening of the arterial wall as a

consequence of atheroma

Question 8

what is the role of LDLs in atheroma formation?

Answer 8

-Endothelial damage – smoking, hypertension
- Endothelium becomes permeable to lipoproteins – expression of vascular
adhesion molecules (VCAM1)
- LDL undergoes oxidation, migration of monocytes which transform into
macrophages
- Oxidized LDL taken into macrophage via scavenger receptor – production of foam cells
- Foam cells may secrete cytokines – further inflammatory involvement, the foam cells rupture
- Release of lipids which become the centre of plaque formation – plaque is very thrombogenic (causes thickening of blood)

Question 9

Why is HDL considered ‘good’ cholesterol?

Answer 9

HDL delivers cholesterol to the liver

Including transport from plaques – reverse cholesterol transport

Question 10

what are the target levels for the various lipid classifications?

Answer 10

Total Cholesterol 1mM
TC:HDL >6 is a risk
TGs <1.7

Question 11

What are step forwards statins? How do they work?

Answer 11

• Reduce LDL-C levels , may lead to plaque stabalization and possibly atheroma regression
• Work by blocking the enzyme HMG-CoA-Reductase and reduce
• hepatic synthesis of cholesterol

-May have a whole range of other beneficial effects (pleiotropic effects) anti-inflammatory effects, reduced endothelial dysfunction and reduced platelet activity?

Question 12

give two examples of step forward statins

Answer 12

Artoravastatin and simivastatin very commonly prescribed

Question 13

how effective are statins?

Answer 13

-meta analysis of 27 studies showed a reduction of LDL-C with a statin
-reduced the risk of major vascular
events
-irrespective of age, gender, baseline LDL, previous vascular disease and of vascular and all cause mortality

Question 14

what are the proposed NICE guidelines for CVD treatment?

Answer 14

-Threshold for starting therapy for preventative treatment should be reduced from a 10 year risk factor of developing CVD of 20% to 10% -using QRISK2 assessment tool
-~4.5 million people would be eligible under this change
- could prevent up to 28 000 heart attacks and 16 000 strokes each
year
-Life style measures tried first, followed by 20mg atorvastatin –primary prevention

Question 15

what are the adverse effects of statins?

Answer 15

-some patients experience some harm from these drugs. (eg. myopathy and diabetes)-some of the adverse effects are beneficial – reduced
incidence of nephropathy and pancreatitis
Patients with chronic kidney disease excluded from statin trials, they generally have a higher incidence of adverse effects

Statins, associated with modest risk in muscle inflammation and rhabdomylitis but not myalgia – generally high dose statins (however this is debated)

Question 16

what is the relationship between statins and diabetes?

Answer 16

Reduced insulin secretion via a direct or indirect effect on Ca channels
in pancreatic β cells
• Reduced activity in GLUT4 – glucose transporter responsible for
peripheral glucose uptake stimulated by insulin
• Reduced insulin signalling – inhibiting intracellular phosphorylation
and redistributed G proteins

further: several studies (i.e. jupiter report) suggest increased incidence of diabetes and statin therapy. this is controversial (confounding variables etc…)