Hyperlipidaemia and therapeutic approaches

Question 1

hyperlipidaemia

Answer 1

is the term used to denote raised serum levels of one or more of total cholesterol (Tchol), low density lipoprotein cholesterol (LDL-C), Triglycerides (TGs) or both Tchol and TG (combined Hyperlipidaemia)

Question 2

dislipidaemia

Answer 2

is a wider term that also includes low levels of high density lipoprotein cholesterol (HDL-C)

Question 3

chylomicrons

Answer 3

transport TGs/cholesterol from intestine indirectly (via lymph) to the blood.

Question 4

Veyr ow density lipoproteins VLDL

Answer 4

(liver synthesised) have a high TG content. The capillary enzyme lipoprotein lipase converts the VLDLs TGs to free fatty acids, used for either energy [in muscle or liver] or storage [in adipose tissue].

Question 5

low density lipoproteins LDL

Answer 5

contain a high cholesterol content.

Question 6

high density lipoproteins HDL

Answer 6

absorb and transport peripherally-mobilised cholesterol from cell breakdown to the liver (protective).

Question 7

what does the body use lipids for

Answer 7

Energy storage
Intracellular signalling 
Extracellular mediators/signalling
(lipoprotein)
Base for steroid hormone synthesis
Vitamin D synthesis
Cell membranes

Question 8

excess carbs converted to what

Answer 8

triglycerides and transported to fat cells

Question 9

main site of sytnhteis of cholesterol

Answer 9

liver

higher TAG( triglycerides) lower cholesterol

Question 10

choylomicorns sourced where

Answer 10

intestines

Dietary Lipids inc chol and FFA emulsified by bile acids & transported within chylomicrons to the liver
Then circulated as chol and triglycerides to disuse inVLDL
Endothelial lipoprotein lipase (LPL) liberate FFA in adipose and muscle for storage or metabolism
Resulting LDL return to hepatocytes via LDL receptors or taken up by LDL receptors in extrahepatic tissue where they are oxidised and contribute to atherogenesis
HDL pool derived from chylomicrons from action of LPL and reverse cholesterol pathways return HDL to liver vis HDL receptors

Question 11

Hypercholesterolemia

Answer 11

Elevated LDL-C

Question 12

Dyslipidemia

Answer 12

Includes elevated triglycerides and low HDL-C

serum total cholesterol, LDL-C, triglycerides, apolipoprotein B, or lipoprotein(a) concentration >90th percentile

HDL-C or apolipoprotein A-I concentrations <10th percentile

Question 13

why is dyslipidemia important

Answer 13

Promotes atherosclerosis-cholesterol plaques
Ischemic heart disease
Cerebrovascular disease
Peripheral vascular disease

Question 14

LDL-C normal range

Answer 14

1.8-2.6 -3.3

Question 15

total cholesterol desirable range

Answer 15

under 5.2 optimal under 4.4

Question 16

triglycerides desirable range

Answer 16

1.1-1.7

Question 17

HDL-C range

Answer 17

under 1

Question 18

how do we diagnose high cholesterol

Answer 18

rings around eyes

Xanthomas are lesions on the skin containing cholesterol and fats. They are often associated with inherited disorders of lipid metabolism (inherited problems with the way that fats are broken down and used). Xanthomas are raised, waxy-appearing, frequently yellowish-colored skin lesions.

Question 19

primary - eugenics as single gene

Secondary causes of dyslipidemia

Answer 19

Diet
Obesity
Diabetes (T1 and T2)
Hypothyroidism
Alcohol dependency
CKD
Nephrotic syndrome
Drugs (glucocorticoids, anti-retrovirals, oral oestrogens, atypical antipsychotics)
Cushings

Question 20

How do we treat hyperlipidemia?

Answer 20

lifestyle - reduce total and saturated fats , weigh loss, exercise , plant sterols
this all lowers LDL-C and increases HDL-C

also use statins

Question 21

what are statins

Answer 21

HMG-CoA reductase inhibitors (3-hydroxy-3-methylglutaryl coenzyme A)
Important enzyme in cholesterol synthesis

↑ LDL receptors →↑LDL Clearance
Ultimately eliminated in bile (significant re-uptake)

Dose and preparation dependent LDL-C reductions of 20-50%

Question 22

PCSK9 inhibitors

Answer 22

Proprotein convertase subtilisin/kexin type 9 binds LDL receptors for degradation in hepatic cell lysosomes

Key determinant of LDL-c concentration

Blocking PCSK9 with a monoclonal antibody allows the LDL receptor to be recycled back to the cell membrane surface to continue LDL uptake from blood

Examples Evolocumab, Alirocumab (specialist rx only)

Question 23

Ezetimibe

Answer 23

add on to statin therapy

Question 24

Colestyramine and Colesevelam

Answer 24

Bile acid sequestrants

Modest reductions in cholesterol 10-24%

GI side effects limit use (nausea, cramps, bloating, diarrhoea, constipation)

Ineffective in FH

Question 25

fibrates

Answer 25

PPARα agonist
Increased FFA uptake by liver
Increased HDL-C

Still in use, though not commonly

Question 26

nicotinic acid

Answer 26

B vitamin
Effective
Poor SE profile (flushing due to prostaglandin induction, ) limited use
Rarely used

Question 27

what can you eat to protect

Answer 27

omega 3

Question 28

what Is hyperlipidemia?

different types

causes plaques

Answer 28

Hyperlipidemia means your blood has too many lipids (or fats), such as cholesterol and triglycerides

Question 29

Hyperlipidaemia is/are most characteristically caused by

Answer 29

corticosteroids

Question 30

Familial hypertriglyceridaemia
eruptive xanthomas
Familial hypercholesterolaemia
tendon xanthoma

Answer 30

Characteristic xanthomata seen in hyperlipidaemia:

Palmar xanthoma
remnant hyperlipidaemia
may less commonly be seen in familial hypercholesterolaemia

Eruptive xanthoma are due to high triglyceride levels and present as multiple red/yellow vesicles on the extensor surfaces (e.g. elbows, knees)

Causes of eruptive xanthoma
familial hypertriglyceridaemia
lipoprotein lipase deficiency

Tendon xanthoma, tuberous xanthoma, xanthelasma
familial hypercholesterolaemia
remnant hyperlipidaemia

Xanthelasma

Xanthelasma are yellowish papules and plaques caused by localized accumulation of lipid deposits commonly seen on the eyelid. They are also seen in patients without lipid abnormalities.

Management of xanthelasma, options include:
surgical excision
topical trichloroacetic acid
laser therapy
electrodesiccation