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Saturday 2 April 2011

Cholesterol - to treat or not to treat?

The crux lies in having a better understanding of cholesterol and the drugs prescribed to lower the risk of heart attack and stroke. By Michael Lim


CHOLESTEROL is essential for the function of the body, yet high cholesterol levels may result in blockage of heart and brain arteries. Over the years, doctors have increasingly been prescribing cholesterol drugs known as statins to reduce the risk of heart attack and stroke.

Most people think that cholesterol deposits in the arteries only appear in adulthood, but in reality, they can appear even before birth... Mothers who have high cholesterol levels have foetuses whose arteries have early deposits of cholesterol in the walls of the arteries

Statins block one of the steps in the production of cholesterol in the liver which is the main production source of cholesterol in the body. Commonly used statins include rosuvastatin, atorvastatin, simvastatin, lovastatin and pravastatin. With its widespread use, it is important to have a better understanding of cholesterol and statins.

What is 'Bad' cholesterol and 'Good' cholesterol? 'Bad' cholesterol refers to Low-density lipoprotein (LDL) cholesterol. The LDL is like a delivery truck that goes around the body through the blood vessels and delivers cholesterol to the organs of the body which then use it for making hormones, new cells and other functions. 'Good' cholesterol refers to High-density lipoprotein (HDL) cholesterol. The HDL is like the waste removal truck which removes unused cholesterol from the bloodstream.

Hence, excessive amounts of LDL cholesterol is bad for the arteries as it gets deposited in the walls of the arteries and can cause narrowing of the arteries. On the other hand, a high level of HDL is protective and reduces the likelihood of cholesterol deposits in the walls of the arteries.

What is the earliest age at which cholesterol deposits in the arteries start appearing? Most people think that cholesterol deposits in the arteries only appear in adulthood, but in reality, they can appear even before birth. Cholesterol deposits in arteries start as early as the stage of foetal development. Mothers who have high cholesterol levels have foetuses whose arteries have early deposits of cholesterol in the walls of the arteries.

The sites of these cholesterol deposits are no different from that commonly seen in adolescents and adults, but the deposits are smaller in amount. Fortunately, these cholesterol deposits tend to disappear or are reduced as the cholesterol levels in the baby become low towards the end of the pregnancy or early infancy.

What is the 'normal' cholesterol level? While the question is simple, the answer is not. In a study on newborns, the average total cholesterol (TC) level was almost 160 mg/dl, LDL cholesterol (LDL-C) was about 70 mg/dl and HDL cholesterol (HDL-C) was about 53 mg/dl. Studies of communities in their 'natural' state, such as segregated tribal hunter-gatherer communities in Africa, Canada and Australia, showed a low mean TC of 123 mg/dl.

Unlike the normal cholesterol values in the 'natural' state, the recommendations for desirable cholesterol levels for those in Western populations are much higher. Based on current recommendations, the desirable level of TC level is <200 mg/dl (5.2 mmol/l), LDL-C is <130 mg/dl (3.4 mmol/l) and HDL-C is >50 mg/dl (1.3 mmol/l).

However, if you are at high risk for heart disease (such as having a history of a previous heart attack, previous stroke, narrowing of neck, arm or leg arteries), the LDL-C should be <100 mg/dl (2.6 mmol/l).

Interestingly, for those at very high risk of heart disease or have significant heart disease, the LDL-C should be <70 mg/dl, a level similar to the LDL-C levels in newborns and hunter-gatherer communities.

When will your doctor start recommending cholesterol lowering medication?

Generally, if your LDL-C is >130 mg/dl and you have other risk factors for heart disease such as family history of heart disease, smoking, diabetes, hypertension, narrowing in the neck or limb arteries, your doctor may recommend that you take medication to lower your cholesterol level.

Do statins have additional health benefits? The main mechanism of a heart attack is a tear in the lining of the artery where there is a narrowing of the artery due to an underlying accumulation of cholesterol. The likelihood of a tear in the lining of the artery is higher if there is underlying inflammation of the lining. Statins have anti-inflammatory properties and are able to stabilise the lining of arteries, thereby reducing the likelihood of a heart attack. Research has also shown that statins can potentially reduce the likelihood of some cancers and progression of kidney disease.

Side effects of statins

What are the common potentially serious side effects of statins?

The more common serious potential side effects which doctors often tell you about are liver damage and muscle problems. When starting on statins, the liver enzymes (blood test) should be checked within six weeks, as occasionally, patients may show an increase in liver enzymes without any symptoms after taking statins.

If the liver enzymes are increased by more than three times the upper limit of normal, the statin dosage should be reduced or the statin should be stopped.

Statins may cause muscle ache and tenderness and this is more likely if higher doses of statins are used. If the blood level of muscle enzymes (creatine kinase or CK) is more than 10 times the upper limit of normal, the statin should be stopped.

In serious cases, the muscle cells breakdown and the breakdown products (myoglobin) can damage the kidney. This is potentially life threatening. The CK level should therefore be checked regularly or whenever there is muscle ache.

Can statin usage cause muscle weakness, tiredness and shortness of breath?

Over the last few years, there is increasing evidence of other uncommon but serious side effects. Damage to the nerves of the limbs and body (peripheral neuropathy) is one of the lesser known side effects of statin. Symptoms may include muscle weakness, tiredness, difficulty in getting up from a sitting position, shortness of breath and difficulty in walking.

The incidence rate of neuropathy related to statin consumption is about one in 2,200 persons and may sometimes be permanent even after stopping statin. A study on 465,000 residents in a Danish community showed that statin consumption increased the risk of neuropathy by 16 times.

Can memory be affected by statin usage?

The impact of statin consumption on memory was most vividly seen in a patient of mine who complained of a significant loss of memory within weeks of taking a statin. His memory recovered upon stopping the statin. Pre-market release studies showed that 4.5 in 1,000 who took a statin had memory loss or cognitive difficulties such as impairment in thinking, concentration, mentation, judgement or irrational thinking.

Statins, the current wonder drugs for cholesterol, are not without serious side effects and hence should be taken in consultation with your doctor. Red yeast rice preparations, which can be bought over the counter, contain the statin lovastatin and users are similarly at risk of statin side effects.

The good news is that there will be alternatives - there is a new class of cholesterol lowering medication which can raise the HDL-C by >100 per cent and decrease the LDL-C by 40 per cent and it will be available in the near future.

Dr Lim is the medical director at Singapore Medical Specialists Centre. He is also editor-in-chief, Heart Asia, British Medical Journals Publishing Group chairman, Scientific Advisory Board, Asia Pacific Heart Association honorary professor and senior medical adviser, Peking University Heart Centre

This series is produced on alternate Saturdays in collaboration with Singapore Medical Specialists Centre.

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