Cholesterol

Thanks to OverdosedAmerica and Dr Abramson.

The Framingham Heart study began in 1948. They enrolled 5,000 people. The association between high cholesterol and heart disease was found in 1957. HDL and LDL cholesterol and their effects came to light in 1977.

When I started GP work in 1976 Atromid S was the big thing. After many years of use it was discovered that it increased the overall death rate by 47%. Yes fewer people died of heart attacks but cancer and violent deaths more than made up for this drop. Didn't take long for a replacement to be discovered, statins in 1987. It took a while for the fashion to kick in - it's in full swing now! How bad will be this awakening?

Cholesterol is an essential molecule. It plays a major role in the brain, hormones, cell membrane and nerones.

Data from Framingham show higher cholesterol levels significantly correlate with an increased risk of death from coronary heart disease 'through the age of 60'. This does not extend to 70 and beyond. The over all risk of death correlates with high cholesterol till 50 and not beyond.

If the above surprises you what about the following. The risk of death from non coronary artery diseases increases significantly the lower the total cholesterol level for men and women after they reach the age of 50.

The most active third of the Framingham people have a 40% lower death rate than the least active third.

Modern guidelines are based on five major studies. Two terms you need to know - primary and secondary prevention. Secondary is for folk with coronary artery disease or CAD. Primary is for those who haven't got CAD.

Primary prevention in men younger than 65.
Men is this group with very high cholesterol levels may benefit from statins but the benefits are not miraculous. In one study 100 men have to be treated for 2 years to prevent one heart attack. To prevent one death 100 men would have to be treated for 5.5 years. In another study of people with moderate levels of cholesterol treatment with statins did not alter the over all mortality. In order to prevent one death, in those with moderate levels, from heart disease 100 people would have to be treated for 25 years. To prevent an episode of heart disease 100 would have to be treated for two and a half years.

Women under 65
A review article in 1995 in JAMA concluded " there is no evidence in primary prevention trials that statins affect total mortality in healthy women". Studies with these women show that statins may lower risk of recurrent CHD but they do not affect over all death stats.

Over 65
Remember that total cholesterol is not significantly related to mortality from CAD beyond the age of 60. There is no increase in the risk of heart attack with higher cholesterol levels in the elderly. In those 70 and above without heart disease statin therapy does not reduce risk of stroke or heart attack. It does increase their risk of cancer. By the fourth year of taking statins there is one extra cancer for every 100 elderly people taking statins that year and eacah year after.

Men with CAD
166 need to be treated to prevent one heart attack.

Women with CAD
Statins lower the risk of recurrent CAD but do not lower the over all mortality.

Abramson states .... it stretches credulity beyond reasonable limits to recommend statin therapy for primary prevention of heart disease in women, people over 65 and men with only moderately elevated cholesterol.

Few trials of statin therapy last more than five years. We have evidence of cancer with statin therapy in the elderly and in animal studies. If the maxim is first do no harm, then maybe some caution is appropriate here especially when the numbers to treat are pretty high and especially if we are going to treat people for many years. It takes a few years for smoking to produce cancer of the lungs.

There is a very rare condition with statins that leads to break down of muscles and kidney failure. My brother a gp in England knows of a man in his 50s who took statins without any history of CHD and died from this condition.

Statins have a small but statistically significant negative effect on cognitive function.

One study showed about 50% of men on statins have sexual dysfunction.

Statins should be used with caution in those with a history of liver disease or with a high alcohol intake (use should be avoided in active liver disease). Hypothyroidism should be managed adequately before starting treatment with a statin (see Lipid-regulating drugs). Liver-function tests should be carried out before and within 1–3 months of starting treatment and thereafter at intervals of 6 months for 1 year, unless indicated sooner by signs or symptoms suggestive of hepatotoxicity. Treatment should be discontinued if serum transaminase concentration rises to, and persists at, 3 times the upper limit of the reference range. Statins should be used with caution in those with risk factors for myopathy or rhabdomyolysis; patients should be advised to report unexplained muscle pain (see Muscle Effects below). Statins should be avoided in porphyria (section 9.8.2) but rosuvastatin thought to be safe. Interactions:

Contra-indications
Statins are contra-indicated in active liver disease (or persistently abnormal liver function tests), in pregnancy (adequate contraception required during treatment and for 1 month afterwards) and breast-feeding

Side-effects
The statins also cause headache, altered liver-function tests (rarely, hepatitis), paraesthesia, and gastro-intestinal effects including abdominal pain, flatulence, constipation, diarrhoea, nausea and vomiting. Rash and hypersensitivity reactions (including angioedema and anaphylaxis) have been reported rarely.

I have heard people describe lethargy and tiredness too.

The picture isn't quite as rosy as we are led to believe.

Medsafe information sheet on lipex

New Zealand guidelines
These present a more optimistic outlook.

Statins, Asprin and treated hypertension is the way to go, is the message.

The problem is polypharmacy. This was a no no a few years back. It's all go now. Often lowering BP requires 3 drugs. Patient haved other problems too - arthritis, asthma, diabetes, indigestion and so on all needing yet more pills.

Do they do these controlled trials on elderly people taking a zillion pills?? I doubt it.

Do a survey of docs and find out how many would swallow their own medicines.