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Updated 17 September 2014

Hypercholesterolaemia: treatment

High cholesterol, or hypercholesterolaemia, is a condition in which the amount of cholesterol in the blood exceeds normal values.

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High cholesterol, or hypercholesterolaemia, is a condition in which the amount of cholesterol in the blood exceeds normal values

  1. The first step is to have your cholesterol checked so you "know your numbers".
  2. Next, your doctor should identify any underlying conditions or risk factors which may contribute to a high cholesterol count.
  3. Based on this, the doctor will choose a target total cholesterol level appropriate to you.
  4. You and your doctor can then decide on a treatment plan.

The point at which treatment becomes necessary will depend on the presence of associated risk factors as explained above.

Treatment plans
The aim of treatment is to lower your cholesterol levels and so minimise your risk of serious CVD and organ damage, which could be permanent (think heart attack, stroke or sudden death). Very high-risk patients (those with genetic disorders, manifest vascular disease or diabetes) will need treatment with medication regardless of other considerations.

Those who have been identified as high risk by calculating their risk from multiple risk factors also need treatment. In most cases, you will be considered high risk if you have a higher than 20% risk of a heart attack, or a higher than 5% risk of death within 10 years.

Non-medical interventions
These include dealing with known risk factors and can consist of:

  • Smoking cessation. Smoking is an independent major risk factor for CHD, cerebrovascular disease and total atherosclerotic cardiovascular disease.
  • Exercising more. This normalises the composition of the TC, raising HDL, lowering triglycerides and possibly lowering LDL; improves body mass and lessens the risk of diabetes.
  • Losing weight. Obesity is associated with a number of risk factors for atherosclerosis, cardiovascular disease and cardiovascular mortality. These include hypertension, insulin resistance and glucose intolerance, hypertriglyceridaemia and reduced HDL-cholesterol.
  • Eating correctly (quantity and quality). Except for the inherited genetic forms of hypercholesterolaemia, cholesterol production is closely linked to fat intake and metabolism. Just by controlling intake, especially of fat, your total cholesterol can be lowered by 10-20%. The prudent diet advised here includes:
    • Eating enough kilojoules to reach and maintain your correct body weight, which is a BMI of 20-25 kg/m2.
    • Eating 55% or more of your total kilojoules (kJ) as complex carbohydrates.
    • Eating 12-15% of your total kilojoules as protein.
    • Eating generous amounts of fresh fruits, vegetables, grains, cereals, poultry, fish, lean meats and low-fat dairy products.
    • Limiting your total daily fat consumption to 30% or less of your total kilojoule intake.
    • Consuming less than 200 mg cholesterol daily.
  • Taking supplements. Omega-3 oils, soy, sterol-enriched margarines, some forms of fibre, garlic, nuts, green tea and calcium have individually been shown to have a small LDL-lowering effect, especially when combined with diet modification and the use of statins.

Medical interventions
These include:

  • Identifying and treating known contributory conditions, such as diabetes, hypertension, thyroid disorders, kidney disease and several others.
  • Medical treatment to lower your total cholesterol or its components.

As cholesterol is derived from two sources, there are two basic approaches to lowering total cholesterol: limiting the amount the body manufactures, and interrupting the recycling of used cholesterol. The best results are obtained when these two approaches are combined.

Drugs that limit the production of cholesterol

1. Statins

The statins are a group of drugs which interfere with the production of cholesterol in the liver, in the process lowering the level of cholesterol in your blood. They are the most commonly used and most potent anti-cholesterol drugs, and can reduce your total cholesterol by 20 to 60%. They work by inhibiting one of the enzymes needed to produce cholesterol.

The effects of statins add to those of a controlled diet. Adverse reactions, such as muscle pain, occur in a minority of patients.

For patients with severe hypercholesterolaemia, statins alone may not be enough – even at high doses, which increase the risk of side effects. For every doubling of the dose of a statin, there is only a further 6% reduction in cholesterol. In such cases, the addition of a different type of medication is advised.

Examples of statins include pravastatin, simvastatin, atorvastatin and rosuvastatin.

2. Fibrates
This group of drugs act mainly to lower triglycerides and may help to raise HDL. They act on several genes to alter the metabolism of lipids in many tissues. This includes lowering the export of triglyceride from the liver and raising the production of HDL.

Examples of fibrates are bezafibrate, gemfibrozil and fenofibrate.

3. Nicotinic acid
This is one of the B group of vitamins. It can help normalise cholesterol levels when given in very large doses. Its use, however, is often limited by its unpleasant side effects, such as severe flushing. Some more recent products claim to be flush-free and although there is anecdotal experience that this is the case, it has not been validated in published studies yet.

Nicotinamide is a different chemical form but is ineffective.

Drugs that interrupt the recycling of cholesterol

1. Bile acid sequestrants

The best known of these is cholestyramine. It binds to bile acids in the gut and so prevents reabsorption. As a result, the liver is stimulated into producing new bile. Because cholesterol is used in the production of bile, the total amount in circulation is gradually reduced.

Side effects are common and include abdominal discomfort and possible vitamin deficiencies, as it interferes with the absorption of fat-soluble vitamins.

2. Ezetimibe
This drug prevents the reabsorption of cholesterol by the small intestine and so the cholesterol recycling process. As a result there’s an increased clearance of cholesterol from the blood and a decrease in total cholesterol, LDL-cholesterol, ApoB (a low-density lipoprotein) and triglycerides.

Side effects are uncommon; most patients tolerate the drug well.

At present, ezetimibe plus a statin is the most effective drug combination to drastically lower LDL cholesterol,

Caution
All of these medications must be used with care and under medical supervision. They can all potentially cause abnormalities in liver function, so liver function should be tested before the drugs are started and should afterwards be regularly monitored if necessary.

There are also known drug interactions which can affect the results and side effects of cholesterol drugs, such as when they’re used with warfarin, certain herbs and other anti-cholesterol medication. Cholesterol drugs should not be used in pregnancy.

Outcome
All patients with hypercholesterolaemia will benefit from lowering their total cholesterol, by whatever means. Regardless of the drugs used, permanent lifestyle changes remain necessary. If old habits are resumed, the risk of CVD will not be fully lowered.

Patients with familial or genetic HC will need individually tailored treatment plans and are best managed at a specialised lipid clinic. Treating these patients may be very difficult, and many of them may suffer heart attacks at an early age despite the best of treatments.

Written by Prof David Marais, head of the Lipid Clinic at Groote Schuur Hospital and head of lipodology at the faculty of health sciences of the University of Cape Town, September 2010.

 
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