ANSWER 97
The obvious abnormal investigation is a very high serum cholesterol with high LDL and
low HDL levels. He has many clinical features to go with the high cholesterol and prema-
ture vascular disease. This man has familial hypercholesterolaemia. He has presented
with premature coronary artery disease. His absent pedal pulses suggest peripheral vascular
disease. Familial hypercholesterolaemia is an autosomal dominant condition. The homo-
zygous condition is rare and affected individuals usually die before the age of 20 years due
to premature atherosclerosis. The heterozygous form affects about 1 in 400 individuals in
the UK, and 50 per cent of males will develop ischaemic heart disease before the age of 50
years. Corneal arcus, xanthelasmata and xanthomata on Achilles tendons and the exten-
sor tendons on the dorsum of the hands develop in early adult life. The metabolic defect
is a result of a reduced number of high-affinity cell-surface LDL receptors. This leads to
increased LDL levels. Increased uptake of LDL by macrophage scavenger receptors leads to
increased oxidized LDL, which is particularly atherogenic. Triglyceride and VLDL levels
are normal or mildly elevated. HDL levels are low. The other major causes of hypercho-
lesterolaemia are familial combined hyperlipidaemia and polygenic hypercholesterol-
aemia. Familial combined hyperlipidaemia differs from familial hypercholesterolaemia by
patients having raised triglycerides. Patients with polygenic hypercholesterolaemia have a
similar lipid profile to familial hypercholesterolaemia but they do not develop xanthomata.
Hypercholesterolaemia may commonly occur in hypothyroidism, diabetes mellitus, nephrotic
syndrome and hepatic cholestasis.
This patient is at extremely high risk for further vascular events and especially occlusion
of his coronary artery bypass grafts. His risk depends on the combination of his risk fac-
tors, and all of these need attention. He should be advised to stop smoking, reduce his
alcohol intake (which is also affecting his liver as judged from the raised gamma-glutamyl
transpeptidase), take more exercise and eat a strict low-cholesterol diet. Diet alone will not
control this level of cholesterol. He should have pharmacological treatment with a statin
but may need combined treatment for this level of hyperlipidaemia. His children should
have their lipid profile measured so that they can be treated to prevent premature cor-
onary artery disease. There is clear evidence from clinical trials that primary prevention
of coronary artery disease can be achieved by lowering serum cholesterol. The West of
Scotland Coronary Prevention Study (WOSCOPS) showed cholesterol lowering with
pravastatin reduced both the number of coronary events and coronary mortality in middle-
aged men with a serum LDL level of greater than 4 mmol/L. In patients who have evidence
of cardiovascular disease secondary prevention is even more important, aiming for a cho-
lesterol level as low as possible. Statins are well tolerated although myositis is a rare but
serious complication.
- The commonest causes for hypercholesterolaemia are polygenic hypercholesterolaemia,
familial hypercholesterolaemia and familial combined hyperlipidaemia. - Effective drugs are now available to treat hypercholesterolaemia and should be used
aggressively to reduce coronary artery disease. - In secondary prevention the aim is the lowest possible cholesterol level.