International Task Force for Prevention of
Coronary Heart Disease

CORONARY HEART DISEASE: REDUCING THE RISK

2.7 Classification and causes of hyperlipidaemia

Classification of hyperlipidaemias serves several purposes

Prognosis: Is there increased cardiovascular risk, or risk of other complication, or is the finding benign, as when an elevated plasma cholesterol level is due to an increase in plasma HDL-cholesterol alone?
Diagnosis: Underlying causes of hyperlipidaemia such as hypothyroidism may be identified.
Treatment: The appropriate choice of dietary and drug treatment often depends on the type of lipid disorder.
The commonest forms of primary hyperlipidaemia result from the interaction of multiple genes with diet, body weight, exercise habits and endocrine factors, and are often termed multifactorial hyperlipidaemias. Other than corneal arcus and xanthelasmas, which suggest the long-standing presence of a hyperlipidaemia, physical signs are absent. Plasma lipid levels are most often elevated to a moderate extent. Less often the clinician deals with more severe hyperlipidaemia, often caused by a single mutant gene of large effect (monogenic hyperlipidaemias) in which a family history of hyperlipidaemia may be obtained, and in which characteristic xanthomas may be present in tendons or in the skin. These two groups are primary hyperlipidaemias; a clinical classification of which appears in Table 5. A third, quite common, category is secondary hvperlipidaemia (Table 6), in which an underlying cause is the sole basis for- or a substantial contributor to mildly or grossly elevated plasma lipid levels: in this case initial treatment is directed to the underlying cause.

Table 5: Classification of the primary dyslipidaemias (CHD = coronary heart disease, HDL = high density lipoprotein, IDL = intermediate density lipoprotein, PVD = peripheral vascular disease, VLDL = very low density lipoprotein)

Disorder	Lipid abnormality16		Lipoprotein class	Clinical manifestations	Risk conferred	Prevalence (approx)17
	cholesterol	triglyceride
Common (polygenic) hypercholesterolaemia	+		LDL		CHD	depends on definition, but very common
familial hypercholesterolaemia	+++		LDL	tendon xanthomas xanthelasmas	CHD +++	1/500
familial defective apoB	+++		LDL	tendon xanthomas xanthelasmas	CHD +++	1/1000
familial combined hyperlipidaemia	++	++	LDL and/or VLDL		CHD ++	approx.1/100
remnant hyperlipidaemia	+++	+++	IDL (remnant particles)	skin xanthomas (elbows, palms)	CHD/PVD +++ CVD +	approx. 1/1000
familial hypertriglyceridaemia	+	+++	VLDL (± chylomicrons)	skin xanthomas (back, elbows, palms, hepatosplenomegaly, retinal lipaemia)	pancreatitis	approx. 1/1000
chylomicronaemia syndrome	+	+++	chylomicrons	skin xanthomas (back, elbows, palms, hepatosplenomegaly, retinal lipaemia)	pancreatitis	approx. 1/10,000
low HDL syndromes			HDL	Depends on cause. Tangier disease, a rare familial form of HDL deficiency, is associated with enlarged, orange coloured tonsils, hepatosplenomegaly, neuropathy and lymphadenopathy.	CHD risk may be ­ in some forms of HDL deficiency.	very rare in Caucasians, may be higher in other ethnic groups.
HDL hyperlipidaemia	+		HDL	none	CHD risk may be low	not uncommon in women but seen also in older men

In patients with substantial hyperlipidaemia, it is good practice to obtain measurements of cholesterol, triglyceride, LDL and HDL-cholesterol twice, and also a biochemical profile and a thyroid function test. The minimum investigations to exclude causes of secondary hyperlipidaemia are shown in Table 6.

Table 6: Causes of secondary hyperlipidaemia

Cause	Lipid abnormality		Investigation
	cholesterol	triglyceride
overweight and obesity	+	+	physical examination
medications (adrenal and anabolic steroids, oral contraceptives, diuretics, retinoids)	+® +++	+® +++	history
diabetes mellitus		+++	fasting glucose, glucose tolerance test
alcoholism	+	+++	history, carbohydrate deficient transferrin levels
hypothyroidism	++	+	TSH
biliary obstruction	+++		liver function, liver ultrasound
chronic renal failure		+++	creatinine
mild nephrotic syndrome	++		plasma albumin, urine protein
severe nephrotic syndrome	+++		plasma albumin, urine protein
bulimia		+++	history
anorexia nervosa	++		history
polycystic ovarian syndrome		++	physical examination, testosterone, LH, FSH, DHEAS measurement, ovarin ultrasound
Turner's syndrome	+		physical examination, karyotyping