Most patients with hyperlipidaemia are asymptomatic and have no clinical signs. Many are discovered whilst screening high-risk individuals.

Whose lipids should be measured?

There are great doubts as to whether blanket screening of plasma lipids is warranted. Selective screening of people at high risk of cardiovascular disease should be undertaken including those with:
• Family history of coronary hear  disease (especially below 50 years of age)
• Family history of lipid disorders
• Presence of a xanthoma
• Presence of xanthelasma or corneal arcus before the age of 40 years
• Obesity
• Diabetes mellitus
• Hypertension
• Acute pancreatitis
• Those undergoing renal replacement therapy
Where one family member is known to have a monogenic disorder such as familial hypercholesterolaemia (1 in 500 of the population), siblings and children must have their plasma lipid concentrations measured. It is also worth screening the prospective partners of any patients with  this heterozygous monogenic lipid disorder because of the small risk of producing children homozygous for the condition.
Acute severe illnesses such as myocardial infarction can derange plasma lipid concentrations for up to 3 months. Plasma lipid concentrations should be measured either within 48 hours of an acute myocardial infarction (before derangement has had time to occur) or 3 months later.  Serum cholesterol concentration does not change significantly after a meal and as a screening test a random blood sample is sufficient. If the total cholesterol concentration is raised above 6.5 mmol litre “, HDL cholesterol, triglyceride, and LDL cholesterol concentrations should be quantitated on a fasting sample. If a test for hypertriglyceridaemia is needed, a fasting blood sample is mandatory.


If a lipid disorder has been detected it is vital to carry out a clinical history, examination and simple special investigations to detect causes of secondary hyperlipidaemia , which may need treatment in their own right. The biochemical tests needed are for thyroid stimulating hormone, fasting blood glucose concentration, urea and electrolyte concentrations and liver biochemistry.


As the genetic basis of lipid disorders becomes clearer the genetic classification of Goldstein and colleagues is proving of greater clinical relevance than the Fredrickson (WHO) classification (based on the pattern of lipoproteins found in plasma). The lack of direct correspondence between these two systems of classification can be confusing. For clarity we have used the genetic classification and not the Fredrickson classification. This has the advantage that the genetic disorders may be grouped by the results of simple lipid biochemistry into causes of hypertriglyceridaemia alone, hypercholesterolaemia alone or of combined hyperlipidaemia.

Hypertriglyceridaemia alone (without hypercholesterolaemia)

The majority of cases will be due to multiple genes acting together to produce a modest excess circulating concentration of VLOL particles, such cases being termed polygenic hypertriglyceridaemia. In a proportion of cases there will be a family history of a lipid disorder or its effects (pancreatitis). Such cases are often classified as familial hypertriglyceridaemia. The defect underlying the vast majority of such cases is not understood. The only clinical feature is a history of attacks of pancreatitis or retinal vein thrombosis in some individuals.
LIPOPROTEIN LIPASE DEFICIENCY AND APOPROTEIN C-II DEFICIENCY are rare diseases which produce greatly elevated triglyceride concentrations due to the persistence of chylomicrons (and not VLOL particles) in the circulation. The chylomicrons persist because the triglyceride within cannot be metabolized if the enzyme lipoprotein lipase is defective or because they cannot gain access to the normal enzyme due to deficiency of the apoprotein C-II on the surface of the chylomicron particles. The disorder is unlikely to be confused clinically with cases of polygenic or familial hypertriglyceridaemia as the patients present in childhood with eruptive xanthomas, lipaemia retinalis and retinal vein thrombosis, pancreatitis  and hepatosplenomegaly. If the disorder is not identified in childhood it can present in adults with gross  hypertriglyceridaemia resistant to simple measures. The most important test is to confirm the presence of chylomicrons in fasting plasma stored overnight (chylomicrons float like cream). This is confirmed by plasma electrophoresis or ultracentrifugation. An abnormality of apoprotein C can be deduced if the hypertriglyceridaemia improves temporarily after infusing fresh frozen plasma, and lipoprotein lipase deficiency is likely if it does not.


Diabetes mellitus (when poorly controlled)
Renal impairment
Nephrotic syndrome
Hepatic dysfunction
Drugs: oral contraceptives in susceptible individuals, retinoids, thiazide diuretics, corticosteroids, opDDD (used in the treatment of Cushing’s syndrome) Hypercholesterolaemia (without hypertrig Iyceridaem ia).

The monogenic disorder of heterozygous familial hypercholesterolaemia is present in 1 in 500 of the normal population. The average general practitioner would therefore be expected to have four such patients on his or her list, but because of clustering within families the prevalence is lower in some general practice lists and much higher in others. Surprisingly, most individuals with this disorder remain undetected. Patients may have no physical signs, in which case the diagnosis is made on the presence of very high plasma cholesterol concentrations which are unresponsive to dietary modification and are associated with a typical family history. Diagnosis can be more easily made if typical clinical features are present. These include xanthomatous thickening of the Achilles tendons and xanthomas over the extensor tendons of the fingers. Xanthelasma may be present, but is not diagnostic  of familial hypercholesterolaemia. The genetic defect of this disorder is the underproduction or malproduction of the LOL cholesterol receptor in the liver. Many different monogenic lesions producing various abnormalities of the receptor have been described in different families.  Homozygous familial hypercholesterolaemia is very rare indeed. Affected children have no LOL receptors in the liver. They have a hugely elevated LOL cholesterol concentration, and massive deposition of lipid in arterial walls, the aorta and the skin. The natural history is for death from ischaemic heart disease in late childhood or adolescence. Plasmapheresis has been used to regularly remove LOL cholesterol with some success in these patients. Liver transplantation offers the possibility of cure, but the numbers of patients having undergone this procedure is small. The possibility of gene therapy offers a glimmer of hope on the horizon for affected individuals. Patients who have raised serum cholesterol concentrations, but do not have familial hypercholesterolaemia exist in the right  hand tail of the normal distribution of cholesterol concentration, and are deemed to have polygenic hypercholesterolaemia. The precise nature of the polygenic variation in plasma cholesterol concentration remains unknown.

Combined hyperlipidaemia (hypercholesterolaemia and hypertrig Iyceridaem ia) The most common patient group IS a polygenic combined hyperlipidaemia.
FAMILIAL COMBINED HYPERLIPIDAEMIA is relatively common affecting 1 in 200 of the general population. The genetic basis for the disorder has not yet been characterized. It is diagnosed by finding raised cholesterol and triglyceride concentrations in association with a typical family history.
REM ANT HYPERLIPIDAEMIA is a rare cause of combined hyperlipidaemia. It is due to accumulation of LDL remnant particles and is associated with an extremely high risk of cardiovascular disease. It may be suspected in a patient with raised total cholesterol and triglyceride concentrations by finding xanthomas in the palmar creases (diagnostic) and the presence of tuberous xanthomas typically over the knees and elbows. Remnant hyperlipidaemia is almost always due to the inheritance of a variant of the apoprotein E allele (apoprotein E2) together with an aggravating factor such as another primary hyperlipidaemia. When suspected clinically the diagnosis can be confirmed using ultracentrifugation of plasma, or phenotyping apoprotein E.

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