Dyslipidemia

Hyperlipidaemia/Dyslipidaemia

Primary or secondary elevation of plasma levels of lipoproteins

Types and function of lipoproteins:
Cholesterol and triglyceride are essential components for structure and function of cells as well as being components of some hormones. They are hydrophobic  encapsulated in phospholipid and apoliproprotein for transport in plasma.
Plasma lipoproteins carry cholesterol and triglycerides in the blood as they are not water soluble.

• chylomicron – main transporter of dietary triglyceride
• very low density lipoprotein (VLDL) – main carrier of endogenous triglyceride from liver to adipose tissue and muscle
• low density lipoprotein (LDL) – main cholesterol carrier in blood – transport cholesterol to non-hepatic tissues
• high density lipoprotein (HDL) – transport cholesterol from peripheral tissue to the liver for excretion  cardioprotective function

Classification of hyperlipoproteinaemia:
Type I:
• Frederickson’s hyperlipoproteinaemia; idiopathic familial hyperlipoproteinaemia; fat-induced hyperlipaemia
• Rare; present at birth
• Due to deficiency or abnormality of lipoprotein lipase

Type II:
• Familial hyperbetalipoproteinaemia; essential familial hypercholesterolaemia
• Onset in 2nd and 3rd decades
• Deficiency of cell surface receptor that regulates LDL degradation and synthesis  increased levels of LDL over joints and pressure areas

Type III:
• Familial broad-beta hyperlipoproteinaemia; xanthoma tuberosum
• Rare; usually occurs after age 20
• Defect of LDL receptor

Type IV:
• Endogenous hypertriglyceridaema
• Common – especially in association with obesity, diabetes and hypertension
• Primary defect is not known

Type V:
• Mixed hypertriglyceridaema
• Defective clearance if triglycerides
• uncommon

Consequences of dyslipidaemia:
• major risk factor for ischaemic vascular disease – LDL’s initiate and facilitate the progress of atherosclerosis

Effect on foot:
Peripheral vascular disease risk
? Endothelial dysfunction
Xanthomas in achilles tendon.
Achilles tendonitis has been reported as being the initial presenting compliant in 14 patients and in children with type two lipidaemia .
Oligoarthritis
Musculoskeletal manifestations predated the diagnosis of hyperlipidaemia in 62% – 63% resolved with lipid lowering therapy.

Cholesterol testing/screening:
? Australian guidelines

Management:
• Diet – reduce energy intake to achieve ideal body weight; moderate alcohol intake; reduce total at intake; reduce saturated fat intake; increase dietary fibre intake
• exercise
• drugs are not a first line approach
• pharmacological should be seen as an adjunct to diet and lifestyle changes – HMG CoA reductase inhibitors (eg Simvastatin, pravastatin – inhibit cholesterol synthesis in liver, increase catabolism of LDL’s, lower plasma levels of LDL’s); bile acid sequestrant resins (eg colestipol – blocks intestinal reabsorption of acids); fibrates (eg bezafibrate, fenofibrate – activate LPL, increases VLDL lipolysis, lowers plasma triglycerides and raises HDL); nicotinic acid (inhibits lipolysis, reduces plasma free fatty acids, lowers VLDL synthesis, increases HDL).

Scandinavian Simvastatin Survival Study (4S) (1994):
• multinational randomised study involving 4444 patients aged 35 to 70 years with coronary heart disease and elevated serum cholesterol levels  randomised to simvastatin or placebo
• median follow up of 5.4 years  decrease of 25% in total cholesterol; 35% decrease in LDL’s; and an 8% increase in HDL
• outcomes in event - ?

Cholesterol and Recurrent Events (CARE) Trial :
• multicentre trial of 4159 subjects with myocardial infarction and raised total cholesterol
• randomised to placebo or pravastatin for 5 years