Statins Health Dictionary

A LIPID that is an important constituent of body cells and so widely distributed throughout the body. It is especially abundant in the brain, nervous tissue, adrenal glands and skin. It is also found in egg yolk and gall-stones (see GALLBLADDER, DISEASES OF). Cholesterol plays an important role in the body, being essential for the production of the sex hormones as well as for the repair of membranes. It is also the source from which BILE acids are manufactured. The total amount in the body of a man weighing 70 kilograms (10 stones) is around 140 grams, and the amount present in the blood is 3·6–7·8 mmol per litre or 150–250 milligrams per 100 millilitres.

A high blood-cholesterol level – that is, one over 6 mmol per litre or 238 mg per 100 ml – is undesirable as there appears to be a correlation between a high blood cholesterol and ATHEROMA, the form of arterial degenerative disease associated with coronary thrombosis and high blood pressure. This is well exempli?ed in DIABETES MELLITUS and HYPOTHYROIDISM, two diseases in which there is a high blood cholesterol, sometimes going as high as 20 mmol per litre; patients with these diseases are known to be particularly prone to arterial disease. There is also a familial disease known as hypercholesterolaemia, in which members of affected families have a blood cholesterol of around 18 mmol per litre or more, and are particularly liable to premature degenerative disease of the arteries. Many experts believe that there is no ‘safe level’ and that everybody should attempt to keep their cholesterol level as low as possible.

Cholesterol exists in three forms in the blood: high-density lipoproteins (HDLs) which are believed to protect against arterial disease, and a low-density version (LDLs) and very low-density type (VLDLs), these latter two being risk factors.

The rising incidence of arterial disease in western countries in recent years has drawn attention to this relationship between high levels of cholesterol in the blood and arterial disease. The available evidence indicates that there is a relationship between blood-cholesterol levels and the amount of fat consumed; however, the blood-cholesterol level bears little relationship to the amount of cholesterol consumed, most of the cholesterol in the body being produced by the body itself.

On the other hand, diets high in saturated fatty acids – chie?y animal fats such as red meat, butter and dripping – tend to raise the blood-cholesterol level; while foods high in unsaturated fatty acids – chie?y vegetable products such as olive and sun?ower oils, and oily ?sh such as mackerel and herring – tend to lower it. There is a tendency in western society to eat too much animal fat, and current health recommendations are for everyone to decrease saturated-fat intake, increase unsaturated-fat intake, increase daily exercise, and avoid obesity. This advice is particulary important for people with high blood-cholesterol levels, with diabetes mellitus, or with a history of coronary thrombosis (see HEART, DISEASES OF). As well as a low-cholesterol diet, people with high cholesterol values or arterial disease may be given cholesterol-reducing drugs such as STATINS, but this treatment requires full clinical assessment and ongoing medical monitoring. Recent research involving the world’s largest trial into the effects of treatment to lower concentrations of cholesterol in the blood showed that routine use of drugs such as statins reduced the incidence of heart attacks and strokes by one-third, even in people with normal levels of cholesterol. The research also showed that statins bene?ted women and the over-70s.... cholesterol

A drug of value in the treatment of the PRURITUS, or itching, which occurs in association with JAUNDICE. It does this by ‘binding’ the bile salts in the gut and so preventing their being reabsorbed into the bloodstream, where their excess in jaundice is responsible for the itching. It reduces the level of cholesterol and triglycerides in the blood and thereby, like clo?brate and STATINS, helping to reduce the incidence of coronary artery heart disease. (See HEART, DISEASES OF; HYPERLIPIDAEMIA.)... cholestyramine

One of the STATINS group of drugs used to reduce the levels of LDL-CHOLESTEROL in the blood and thus help to prevent coronary heart disease, which is more prevalent in people with raised blood cholesterol levels (see HEART, DISEASES OF).... fluvastatin

An excess of fat in the blood, characterising a group of metabolic disorders. The two most important fats circulating in the blood are CHOLESTEROL and TRIGLYCERIDE. Raised blood levels of cholesterol predispose to ATHEROMA and coronary artery disease (see HEART, DISEASES OF); raised triglycerides predispose to pancreatitis (see PANCREAS, DISORDERS OF). Six types of hyperlipidaemia have been identi?ed, and diagnosis of the di?erent types depends upon blood tests to discover lipid levels. Some of the hyperlipidaemias are familial, and some are secondary to other diseases such as hypothyroidism (see THYROID GLAND, DISEASES OF), DIABETES MELLITUS, nephrotic syndrome and alcoholism.

Treatment There is evidence that therapy which lowers the lipid concentration reduces the progression of premature atheroma, particularly in those who suffer from the familial disorder. Treatment should include appropriate diets, usually food that is low in cholesterol and saturated fats. There are a number of drugs available for lowering the lipid content of the plasma, but these should be reserved for patients in whom severe hyperlipidaemia is inadequately controlled by weight reduction. Anion-exchange resins – clo?brate, beza?brate and gem?brozil, for example – and statins such as atorvastatin and simvastatin, as well as nicotinic acid, all lower plasma cholesterol and plasma triglyceride concentration through their e?ect on reducing the hepatic production of lipoproteins. Cholestyramine and colestipol, both of which are anion-exchange resins, bind bile salts in the gut and so decrease the absorption of the cholesterol that these bile salts contain – hence lowering plasma cholesterol concentrations. Probucol lowers plasma cholesterol concentrations by increasing the metabolism of low-density lipoproteins.

The statins (atorvastatin, cerivastatin, ?uvastatin, pravastatin and simvastatin) inhibit an enzyme involved in synthesising cholesterol, especially in the liver. They are more e?ective than anion-exchange resins in lowering LDL (low-density lipoprotein) cholesterol – a form of low-density cholesterol carried in the bloodstream, high levels of which are believed to be the main cause of atheroma. Statins are, however, less e?ective than the clo?brate group in reducing triglycerides and raising HDL (highdensity lipoprotein) cholesterol (high-density cholesterol).... hyperlipidaemia

These drugs reduce the amount of low-density LIPOPROTEINS, which transport CHOLESTEROL and triglycerides (see TRIGLYCERIDE) in the blood, or raise the concentration of high-density lipoproteins. The aim is to reduce the progression of ATHEROSCLEROSIS and therefore help prevent coronary heart disease (see HEART, DISEASES OF). These drugs should be combined with reducing other risk factors for raised lipid concentrations, such as a high-fat diet, smoking and obesity. Lipid-regulating drugs include STATINS, ?brates, anion-exchange resins, and NICOTINIC ACID, which may be used singly or in combination under careful medical supervision (see HYPERLIPIDAEMIA).... lipid-regulating drugs

Also called pharmacogenetics – the use of human genetic variations to optimise the discovery and development of drugs and the treatment of patients. The human race varies much more in its genetic make-up than has previously been realised; these variations in GENES and their PROTEIN products could be utilised to provide safer and more e?ective drugs. Genes affect drug absorption, distribution, METABOLISM and excretion. Drugs are designed and prescribed on the basis of a population’s needs, but patients comprise a diverse range of individuals. For example, nearly one-third of patients fail to respond to the cholesterol-reducing group of drugs, the STATINS. Around half do not respond to the tricyclic ANTIDEPRESSANT DRUGS. Over 80 per cent of patients’ responses to drugs depends on their genetics: this genetic variation needs to be identi?ed so as to make the prescription of drugs more e?ective, and technology for analysing genetic variants is progressing. Assessing drug e?ectiveness, however, is not simple because the health and diets of individuals are di?erent and this can affect the response to a drug. Even so, the genetic identi?cation of people who would or would not respond to a particular drug should bene?t patients by ensuring a more accurately targeted drug and by reducing the risks to a person of side-effects from taking a drug that would not work. There would also be substantial economic savings.... pharmacogenomics

One of the STATINS – a group of LIPID-lowering drugs which are e?ective – in combination with a low CHOLESTEROL diet – in reducing the incidence of heart attacks (see HEART, DISEASES OF – Coronary thrombosis).... simvastatin

A group of drugs used to treat hyperlipidaemia.

These drugs help to prevent, or slow the progression of, severe atherosclerosis and coronary artery disease.

The most commonly used types are statins and fibrates.... lipid-lowering drugs

(LDL) a *lipoprotein that is the principal form in which *cholesterol is transported in the bloodstream: it accounts for approximately 70% of the circulating cholesterol in an individual. LDL is derived from *very low-density lipoprotein and is eventually cleared from the circulation by the liver. LDL may be deposited within the lining of arteries, thus causing *atheroma; the higher the circulating concentration of LDL, the higher the likelihood of atheroma developing (see also hypercholesterolaemia). *Statins are effective in lowering circulating LDL levels.... low-density lipoprotein

n. the rapid breakdown of skeletal muscle cells, with the release of myoglobin and other potentially toxic cell components. Blood levels of *creatine kinase are raised. It can result in *hyperkalaemia, *hypovolaemia, *myoglobinuric acute renal failure, and *disseminated intravascular coagulation. Causes include muscle trauma and crush injury, alcohol abuse, seizures, and medications (notably statins).... rhabdomyolysis

n. any one of a class of drugs that inhibit the action of an enzyme involved in the liver’s production of cholesterol (see HMG CoA reductase). Statins can lower the levels of *low-density lipoproteins (LDLs) by 25–45% and are used mainly to treat hypercholesterolaemia but also to reduce the risk of coronary heart disease in susceptible patients. Muscle inflammation and breakdown (see rhabdomyolysis) is a rare but serious side-effect of statins. The class includes *atorvastatin, fluvastatin, *pravastatin, rosuvastatin, and *simvastatin.... statin