Title: Familial Hypercholesterolaemia

Key words: Case history, coronary heart disease, raised LDL, drug treatment, lifestyle intervention, screening

Date: Dec 1999

Category: 13. Specific Conditions

Type: Article

Author: Dr van Rhijn



Familial Hypercholesterolaemia

A Typical Case History and Analysis

A 34 year old marathon runner, George, visits his doctor complaining of a painful Achilles tendon. George’s brother has just been admitted to hospital with a heart attack. His doctor sends George to the well-man clinic and the resulting lipid profile is as follows:

Cholesterol: 8.7 mmol/l, Triglycerides: 1.8 mmol/l,

HDL cholesterol: 1.1mmol/l, LDL cholesterol: 7.24 mmol/l


Management by drug and lifestyle intervention

George has Familial Hypercholesterolaemia (FH), an autosomal dominant disorder of chromosome 19 (heterozygous form) [Type IIa hyperlipidaemia – WHO classification]. The incidence is 1:500 , accounting for 50% of male deaths and 5% of heart attack survivors (before age 60) due to an increased incidence of early coronary heart disease (CHD). It is clinically diagnosed either by total plasma cholesterol > 7.5 mmol/l, or low-density lipoprotein (LDL) > 5.0 mmol/l, with tendon xanthomas. Raised LDL is due to reduced clearance by defective LDL receptors (apo-B100). A wealth of evidence links the increased formation of LDL1 and reduced cardio protective high density lipoproteins (HDL) levels with a subsequent increased risk of CHD2.

The treatment includes drugs, with a choice of:

• Hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors (simvastin or pravastatin).

• Cholestyramine (Questran) or a combination of the two types of therapy.

• Nicotinic acid - optional.

The actions of these drugs include a reduction of plasma cholesterol and LDL3 (rate limiting step in cholesterol synthesis), an increase in LDL receptors, a small reduction in plasma triglyceride and VLDL and an increase in HDL (mechanism unknown). These changes reduce the relative risks4 in the treatment groups for coronary events, non-fatal myocardial infarction and death from definite coronary artery disease5,6.

• Low fat (cholesterol) diet, with sources from polyunsaturated fatty acids (PUFA’s) rather than saturated fatty acids which raise cholesterol levels7. Reduce intake of fried foods as trans fatty acids8 increase serum LDL and decrease HDL, cream, cakes and rich cheeses and biscuits.

• Use lean meats or meat substitutes (soya)9, 10 and oily fish products (n-3 PUFA’s)11, 12, 13. Consumption of oily fish reduced mortality by 50% in CVD (Zutphen study14) and by 29% in post myocardial infarct patients (Dart trial 15). • Encourage stress-reducing techniques and relaxation, which will also help to prevent potential hypertension.




(George is a fit runner, non-smoker and is not overweight)

George is already helping himself by reducing risk factors:

keeping his BMI normal by exercise

being a non-smoker.

Further advice would include moderation of alcohol intake (preferably to red wine only16), a low salt diet and a diet rich in starch rather than fast sugars to minimize his risk of insulin resistance. Encourage fruit and vegetable intake (5 servings a day) to provide antioxidants, flavonoids17, 18 and fibre to protect against CHD. Use carbohydrates with a lower glycaemic index such as beans, peas & spaghetti to raise plasma HDL19.

Other useful advice

Individuals like this should be encouraged to become a member of the support network of the Family Heart Association, to visit their web site and read their magazine for lifestyle and dietary advice.

As FH is a genetic disorder, screening (capillary apolipoproteins A-1 and B20 or cholesterol21) is important to identify family members in childhood. This would help reduce risk factors. Instigating treatment improves the prognosis22. This can be done at general practice surgeries24, 25 for cardiovascular risk indicators such as hypercholesterolaemia, diabetes or hypertension as well as specific tendon xanthomata23 or premature corneal arcus.


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