Hyperlipidaemia
D E FI N I T ION
Elevation of one or more plasma lipid fractions.
AE T IOLOGY
Primary: Some have molecular genetic basis, but most are unknown.
. Familial hypercholesterolaemia: # Functional hepatic LDL receptors.
. Familial hypertriglyceridaemia: Unknown. Autosomal dominant.
. Hypertriglyceridaemia: Lipoprotein lipase or apo-CII deficiency.
. Familial combined hyperlipidaemia: Unknown.
. Remnant hyperlipidaemia: Apo-E2 genotype inheritance, accumulation of LDL remnants.
Secondary: Subdivided depending on the predominant abnormality.
. " Cholesterol: Hypothyroidism, nephrotic syndrome, cholestatic liver disease, anorexia
nervosa.
. " Triglycerides: Diabetes mellitus, drugs (b-blockers, thiazides, oestrogens), alcohol,
obesity, chronic renal disease, hepatocellular diseases.
Physiology: LDL accumulates in intima of systemic arteries, and is taken up by LDL receptor
on macrophage. This forms a foam cell, part of atheromatous plaque. HDL acts as shuttle
in periphery for transport of cholesterol esters back to the liver and is therefore
cardioprotective.
E P IDEMIOLOGY
50 % of the UK population have a cholesterol level high enough to be
a risk for CHD.
H ISTORY
Asymptomatic.
Symptoms of CVS complications.
Enquire about other CVS risk factors:
. Diabetes
. Family history
. Smoking
. Hypertension
EXAMINA T I ON
Usually normal. Examine for secondary causes.
Signs of lipid deposits: Around the eyes (xanthelasmas), cornea (arcus), tendons xanthomas
(e.g. extensor tendons of the hands, Achilles tendon, patella tendon), tuberous
xanthomas on knees and elbows, xanthomas in palmar creases (in remnant hyperlipidaemia),
eruptive xanthomas and lipidaemia retinalis (pale retinal vessels) in severe
hypertriglyceridaemia.
Signs of complications: E.g. # peripheral pulses, carotid bruit, other cardiovascular risks –
associated high BP.
INVE S T I G A T IONS
Blood: Fasting lipid profile, exclude secondary causes: glucose, TFT, LFT, U&E.
Cardiovascular risk assessment: Assess using various algorithms, e.g. Framingham risk
equation, QRISK or ASSIGN.1
MANAGEMENT
Treat secondary causes.
Advice: Exercise, lose weight, stop smoking, control BP, control diabetes, # alcohol, dietary
modification.
1 Framingham risk score is well validated for estimating 10-year cardiovascular risk (http://hp2010.nhlbihin.
net/atpiii/calculator.asp), but it is derived from a North American population. The QRisk and ASSIGN
calculators have been developed for an English or Scottish population and can be assessed online at: http://
www.qrisk.org.uk and http://assign-score.com.
Hyperlipidaemia (continued)
Lipid-lowering drugs: Indicated for:
1) Primary prevention: Patients with multiple risk factors and no atherosclerosis (primary
prevention) when risk for coronary heart disease > 20% in 10 years; and
2) Secondary prevention: Patients with established atherosclerosis, e.g. coronary heart
disease, carotid artery disease and aortic aneurysms (secondary prevention).
. Target: total cholesterol < 4 mmol/L, LDL2 mmol/L
For " total cholesterol or " LDL:
. HMG-CoA reductase inhibitors (‘statins’): Potently lowers mortality and CVS morbidity is
demonstrated in numerous trials. High dose is recommended as first line (e.g. 40 mg
simvastatin).
. Ezetimibe: Inhibits cholesterol absorption in the gut. Can be used if a statin is not tolerated,
or as an adjunctive agent.
For " tyriglycerides:
. Fibrates (e.g. bezafibrate): Stimulates lipoprotein lipase activity via specific transcription
factors.
. Fish oil: Rich in omega-3 marine trigylcerides, but this is not a recommended method of
treating hyperlipidaemia (it can aggravate hypercholesterolaemia.)
Other drugs:
. Anion-exchange resins (e.g. colestyramine, colestipol): Binds bile acids and # reabsorption,
" hepatic cholesterol conversion to bile acids and " LDL receptor expression on
hepatocytes.
. Nicotinic acid: # Hepatic VLDL release, # triglycerides, # cholesterol and " HDL. Use is
limited by side effects (prostaglandin-mediated vasodilation, flushing, dizziness, palpitations).
" Glucose and urate.
COMPL I C A T IONS
Coronary artery disease, MI, peripheral vascular disease, strokes.
In hypertriglyceridaemia: Pancreatitis and retinal vein thrombosis.
Complication of treatment: Statins are associated with myositis.
P ROGNOS I S
Depends on early diagnosis, treatment of hyperlipidaemia and control of
other CVS risk factors. There is some evidence that lipid-lowering agents prevent cerebrovascular
accidents.
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