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:
• Frederickson’s hyperlipoproteinaemia; idiopathic familial hyperlipoproteinaemia; fat-induced hyperlipaemia
• Rare; present at birth
• Due to deficiency or abnormality of lipoprotein lipase
• 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
• Familial broad-beta hyperlipoproteinaemia; xanthoma tuberosum
• Rare; usually occurs after age 20
• Defect of LDL receptor
• Endogenous hypertriglyceridaema
• Common – especially in association with obesity, diabetes and hypertension
• Primary defect is not known
• Mixed hypertriglyceridaema
• Defective clearance if triglycerides
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 .
Musculoskeletal manifestations predated the diagnosis of hyperlipidaemia in 62% – 63% resolved with lipid lowering therapy.
? Australian guidelines
• Diet – reduce energy intake to achieve ideal body weight; moderate alcohol intake; reduce total at intake; reduce saturated fat intake; increase dietary fibre intake
• 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