Skin lipid barrier and cleansers. Lipid metabolism: symptoms of disorders and methods of treatment

The lipid barrier of the skin is the part of the epidermal barrier that first contacts the environment. This is a unique mechanism that allowed a person in the course of evolution to defend himself from the often aggressive environment.

The stratum corneum of the epidermis consists of 10-25 layers of cells oriented parallel to the skin surface and immersed in the lipid matrix ( lipid barrier skin). It is the cells of the stratum corneum of the epidermis and the lipid matrix that fills the intercellular spaces that provide the barrier functions of the skin, protecting the body from the penetration of bacteria, viruses and other exogenous substances, as well as retaining water and electrolytes.

The lipid matrix of the stratum corneum of the epidermis makes up about 10% of its volume and has a unique structure and chemical composition.

Chemical composition of the lipid barrier of the skin

The lipids of the epidermal barrier of the skin are mainly composed of:

ceramides (50%);
cholesterol and its esters (25%);
saturated fatty acids (10%).

A balanced ratio of these three categories of lipids is essential to ensure the integrity and protective properties of the lipid barrier of the skin.

Ceramides- This is the simplest type of sphingolipids, consisting of sphingosine and a fatty acid (in particular, linoleic). Currently, 342 ceramides have been identified in the stratum corneum of the epidermis, belonging to 12 different types. Their list is constantly updated.

Ceramides perform a huge number of biological functions. One of the most important is structuring (ceramides are able to form bilayers).

Cholesterol is one of the most important lipids that form the lipid barrier of the skin. Basically, it is synthesized directly in the epidermis. A small amount of it can come directly from the bloodstream.

The main function of cholesterol as a component of the epidermal barrier is to impart plasticity to the lipid matrix. Without it, the stratum corneum of the epidermis would be very fragile.

Concerning free fatty acids, then saturated fatty acids dominate in the stratum corneum of the epidermis, and long-chain fatty acids predominate. Most of them are synthesized in the body itself. Some acids (for example, linoleic, gamma-linolenic) enter the body only with food.

Free fatty acids also play a structuring role.

Lipids in the intercellular spaces of the stratum corneum are organized in the form of plates collected from 3 layers (wide - narrow - wide). The wide layer is paired bilayers of ceramides and cholesterol, the narrow one is one unifying layer of ceramides.

The formation of a bilayer of ceramides is due to the fact that they turn their nonpolar part towards each other, and the polar part outward. This is a unique quality of ceramides, which determines the barrier properties of the epidermis.

Placed in this way, ceramides essentially "stitch" the layers. Due to this, in a plane perpendicular to the plates, lipids are organized into a rigid rectangular crystal lattice.

Figuratively, such a system of organization of the lipid barrier of the skin can be described as a quilt 🙂 Lipid layers are stitched with ceramide chains. Similarly, lipid layers are "sewn" to the cells of the stratum corneum of the epidermis, ensuring the integrity of the epidermal barrier of the skin.

For the correct structural organization of the lipid barrier of the skin, the chemical composition of lipids, the ratio of the main components, is very important. If this balance is disturbed, the stratum corneum of the skin becomes unable to perform its protective functions.

Why is the lipid barrier of the skin destroyed?

Many factors can provoke the destruction of the lipid barrier of the skin:

any mechanical damage skin (wounds, burns, frostbite, cuts, scratches);
skin diseases (acne, atopic dermatitis, psoriasis, etc.);
impact ultraviolet radiation(see "Photoaging") and other factors environment(frequent showers, pool visits, dry air from heating systems, cold air);
exposure to aggressive surfactants in cleansers, shower gels, shampoos, etc.;
metabolic diseases with impaired lipid synthesis;
decrease in cholesterol synthesis in the epidermis with age;
constant contact with chemicals(for example, with chemical detergents);
psychological stress (hormones synthesized during stress negatively affect the epidermal barrier);
oxidative stress - damage to the intercellular structures of the stratum corneum of the epidermis by free radicals (see "Lipid peroxidation", "Antioxidants and skin");
unbalanced diet (lack of fatty acids).

Such a number of provoking factors in Everyday life leads to the fact that every day we gradually remove its natural protective barrier from the skin.

The skin is trying to replenish the content of lipids (they are in stock in the "pantries" of the skin - lamellar bodies), but its possibilities are not unlimited. It takes time for the synthesis of new lipids in the skin. If the protective barrier of the skin during this period is affected by other adverse factors, then it is not able to fully restore itself, and as a result, external signs destruction of the lipid barrier of the skin.

How is the destruction of the lipid barrier of the skin manifested?

If this structure is violated, the barrier ceases to partially or completely cope with its task - primarily to preserve water in the body and protect against the penetration of harmful substances and microorganisms.

The first sign of the destruction of the lipid barrier of the skin is dehydration of the skin due to increased evaporation of water. Dehydrated skin ages quickly, loses firmness and elasticity. Dry skin, peeling, fine wrinkles appear.

The skin becomes sensitive, vulnerable to external factors. The destruction of the barrier that protects against the penetration of bacteria and viruses leads to irritation, the development of inflammatory processes in the skin (for example, acne), and skin diseases.

This situation requires urgent measures to restore the lipid layer of the skin:

termination of exposure to factors that provoke the destruction of the epidermal barrier;
the use of creams containing physiological lipids (ceramides, free fatty acids and cholesterol) in a balanced combination.

We will talk more about ways to restore the epidermal barrier in the article “Restoring the lipid barrier of the skin“.

Lipid metabolism - fat metabolism that takes place in the organs digestive tract with the participation of enzymes produced by the pancreas. If this process is disturbed, the symptoms can vary depending on the nature of the failure - an increase or decrease in lipid levels. With this dysfunction, the number of lipoproteins is examined, since they can identify the risk of developing cardiovascular diseases. Treatment is established strictly by the doctor based on the results obtained.

What is lipid metabolism?

When ingested with food, fats undergo primary processing in the stomach. However, in this environment, complete splitting does not occur, since it has a high acidity, but there are no bile acids.

Scheme of lipid metabolism

When it enters the duodenum, which contains bile acids, lipids undergo emulsification. This process can be characterized as partial mixing with water. Since the environment in the intestine is slightly alkaline, the acidic contents of the stomach are loosened under the influence of the released gas bubbles, which are the product of the neutralization reaction.

The pancreas synthesizes a specific enzyme called lipase. It is he who acts on the molecules of fats, splitting them into two components: fatty acids and glycerol. Usually fats are transformed into polyglycerides and monoglycerides.

Subsequently, these substances enter the epithelium of the intestinal wall, where the biosynthesis of lipids necessary for human body. Then they combine with proteins, forming chylomicrons (a class of lipoproteins), after which, together with the flow of lymph and blood, they spread throughout the body.

In the tissues of the body, the reverse process of obtaining fats from blood chylomicrons occurs. The most active biosynthesis is carried out in the fatty layer and the liver.

Symptoms of a disturbed process

If the presented lipid metabolism is disturbed in the human body, then the result is various diseases with characteristic external and internal features. It is possible to identify the problem only after conducting laboratory tests.

Impaired fat metabolism can manifest itself with such symptoms advanced level lipids:

the appearance of fatty deposits in the corners of the eyes;
an increase in the volume of the liver and spleen;
increase in body mass index;
manifestations characteristic of nephrosis, atherosclerosis, endocrine diseases;
increased vascular tone;
the formation of xanthoma and xanthelasma of any localization on the skin and tendons. The former are nodular neoplasms containing cholesterol. They affect the palms, feet, chest, face and shoulders. The second group is also cholesterol neoplasms that have a yellow tint and occur on other areas of the skin.

At reduced level lipids show the following symptoms:

weight loss;
delamination of the nail plates;
hair loss;
nephrosis;
violation menstrual cycle and reproductive functions in women.

Lipidogram

Cholesterol moves in the blood along with proteins. There are several types of lipid complexes:

1. Low density lipoproteins (LDL). They are the most harmful fraction of blood lipids, which have a high ability to form atherosclerotic plaques.
2. High density lipoproteins (HDL). They have the opposite effect, preventing the formation of deposits. They transport free cholesterol to the liver cells, where it is subsequently processed.
3. Very low density lipoproteins (VLDL). They are the same harmful atherogenic compounds as LDL.
4. Triglycerides. They are fatty compounds that are a source of energy for cells. With their redundancy in the blood, the vessels are predisposed to atherosclerosis.

Assessment of the risk of developing cardiovascular diseases by cholesterol level is not effective if a person has a lipid metabolism disorder. With the predominance of atherogenic fractions over conditional harmless (HDL), even with normal cholesterol levels, the likelihood of developing atherosclerosis is seriously increased. Therefore, in case of impaired fat metabolism, a lipid profile should be performed, that is, a biochemistry (analysis) of blood for the amount of lipids should be performed.

Based on the obtained indicators, the coefficient of atherogenicity is calculated. It shows the ratio of atherogenic and non-atherogenic lipoproteins. Defined as follows:

The formula for calculating the coefficient of atherogenicity

Normally, CA should be less than 3. If it is in the range from 3 to 4, then there is high risk development of atherosclerosis. If the value equal to 4 is exceeded, the progression of the disease is observed.

Violation of lipid metabolism is observed in various diseases of the body. Lipids are called fats synthesized in the liver or ingested with food. Their location, biological and Chemical properties differ depending on the class. The fatty origin of lipids causes a high level of hydrophobicity, that is, insolubility in water.

Lipid metabolism is a complex of various processes:

splitting, digestion and absorption by the organs of the PT;
transport of fats from the intestines;
individual species exchanges;
lipogenesis;
lipolysis;
interconversion of fatty acids and ketone bodies;
fatty acid catabolism.

Major groups of lipids

Phospholipids.
Triglycerides.
Cholesterol.
Fatty acid.

These organic compounds are part of the surface membranes of all cells of a living organism, without exception. They are necessary for steroid and bile connections, are needed for the construction of myelin sheaths of nerve pathways, and are required for the production and accumulation of energy.

A complete lipid metabolism is also provided by:

lipoproteins (lipid-protein complexes) of high, medium, low density;
chylomicrons that carry out the transport logistics of lipids throughout the body.

Violations are determined by failures in the synthesis of some lipids, increased production of others, which leads to their overabundance. Further, all kinds of pathological processes appear in the body, some of which turn into acute and chronic forms. In this case severe consequences can't be avoided.

Causes of failure

In which abnormal lipid metabolism is observed, it can occur with a primary or secondary origin of disorders. So the causes of the primary nature are hereditary-genetic factors. Causes of a secondary nature - wrong image life and series pathological processes. More specific reasons are:

single or multiple mutations of the corresponding genes, with a violation of the production and utilization of lipids;
atherosclerosis (including hereditary predisposition);
sedentary lifestyle;
abuse of cholesterol-containing and fatty acid-rich foods;
smoking;
alcoholism;
diabetes;
chronic liver failure;
hyperthyroidism;
primary biliary cirrhosis;
side effect of taking medicines;
thyroid hyperfunction.

chronic insufficiency liver can cause lipid metabolism disorders

Moreover the most important factors influences are called cardiovascular disease and overweight. Disturbed lipid metabolism, causing, is characterized by the formation of cholesterol plaques on the walls of blood vessels, which can result in complete blockage of the vessel -,. Among all cardiovascular diseases, atherosclerosis is largest number cases of early death of the patient.

Risk factors and influences

Fat metabolism disorders are primarily characterized by an increase in the amount of cholesterol and triglycerides in the blood. Lipid metabolism and its state - important aspect diagnosis, treatment and prevention of major diseases of the heart and blood vessels. Preventive treatment blood vessels is required for patients with diabetes mellitus.

There are two main influence factors that cause a violation in lipid metabolism:

Change in the state of low-density lipoprotein (LDL) particles. They are uncontrollably captured by macrophages. At some stage, lipid supersaturation sets in, and macrophages change their structure, turning into foam cells. Lingering in the wall of the vessel, they contribute to the acceleration of the process of cell division, including atherosclerotic proliferation.
Inefficiency of high-density lipoprotein (HDL) particles. Because of this, disturbances occur in the release of cholesterol from the endothelium of the vascular wall.

Risk factors are:

gender: men and women after menopause;
the aging process of the body;
a diet rich in fats;
a diet that excludes the normal consumption of coarse fiber foods;
excessive consumption of cholesterol food;
alcoholism;
smoking;
pregnancy;
obesity;
diabetes;
nephrosis;
uremia;
hypothyroidism;
Cushing's disease;
hypo- and hyperlipidemia (including hereditary).

Dyslipidemia "diabetic"

A pronounced abnormal lipid metabolism is observed with diabetes. Although the basis of the disease is a violation of carbohydrate metabolism (pancreatic dysfunction), lipid metabolism is also unstable. Observed:

increased lipid breakdown;
an increase in the number of ketone bodies;
weakening the synthesis of fatty acids and triacylglycerols.

At healthy person at least half of the incoming glucose normally breaks down into water and carbon dioxide. But diabetes mellitus does not allow the processes to proceed correctly, and instead of 50%, only 5% will get into “processing”. Excess sugar is reflected in the composition of the blood and urine.

In diabetes mellitus, carbohydrate and lipid metabolism is disturbed.

Therefore, in diabetes mellitus is prescribed special diet and special treatment aimed at stimulating the pancreas. The absence of treatment is fraught with an increase in the blood serum of triacylglycerols and chylomicrons. Such plasma is called "lipemic". The process of lipolysis is reduced: insufficient breakdown of fats - their accumulation in the body.

Symptoms

Dyslipidemia has the following manifestations:

External signs:

overweight;
fatty deposits in the inner corners of the eyes;
xanthomas on tendons;
enlarged liver;
enlarged spleen;
kidney damage;
endocrine disease;
high levels of cholesterol and triglycerides in the blood.

With dyslipidemia, there is an enlargement of the spleen

Internal signs (detected during examination):

Symptoms of disorders vary depending on what exactly is observed - an excess or a deficiency. Excess is more often provoked by: diabetes mellitus and other endocrine pathologies, congenital metabolic defects, not proper nutrition. In excess, the following symptoms appear:

deviation from the norm of cholesterol in the blood towards an increase;
a large amount of LDL in the blood;
symptoms of atherosclerosis;
obesity with complications.

Deficiency symptoms are manifested with intentional starvation and non-compliance with the culture of nutrition, with pathological digestive disorders and a number of genetic anomalies.

Lipid deficiency symptoms:

exhaustion;
deficiency of fat-soluble vitamins and essential unsaturated fatty acids;
violation of the menstrual cycle and reproductive functions;
hair loss;
eczema and other inflammations of the skin;
nephrosis.

Diagnostics and therapy

To evaluate the whole complex of lipid metabolism processes and identify violations, laboratory diagnostics are required. Diagnostics includes a detailed lipid profile, where the levels of all the necessary lipid classes are prescribed. In this case, the lipoproteinogram is also standard analysis.

Such diagnostics should become regular in diabetes mellitus, as well as in the prevention of diseases of the cardiovascular system.

Helps to normalize lipid metabolism complex treatment. The main method of non-drug therapy is low calorie diet with limited intake of animal fats and "light" carbohydrates.

Treatment should begin with the elimination of risk factors, including the treatment of the underlying disease. Smoking and consumption of alcoholic beverages are excluded. An excellent means of burning fat (expending energy) is physical activity. Leading a sedentary lifestyle requires daily physical exercise, healthy body shaping. Especially if improper lipid metabolism has led to overweight.

There is also a special drug correction of lipid levels, it is included if non-drug treatment was ineffective. Incorrect lipid metabolism of "acute" forms will help to correct lipid-lowering drugs.

The main drug classes for dyslipidemia are:

Statins.
Nicotinic acid and its derivatives.
fibrates.
Antioxidants.
Bile acid sequestrants.

Nicotinic acid is used to treat dyslipidemia.

The effectiveness of therapy and a favorable prognosis depend on the quality of the patient's condition, as well as on the presence of risk factors for the development of cardiovascular pathologies.

Basically, the level of lipids and their metabolic processes depend on the person. Active lifestyle without bad habits, proper nutrition, regular complex medical examination body has never been the enemy of well-being.

Everyone's skin needs reliable protection from viruses, bacteria, dehydration and a great many other equally unfavorable factors. It's no secret that the protective function in this case designed to fulfill the lipid layer. When it is violated, the skin becomes dull and looks unkempt, moreover, wrinkles appear on it and the person begins to look older than his real age. To avoid such troubles, it is necessary to systematically restore the lipid layer. How to do it?

Lipid layer - what is it and why is it needed?

The horny layer of the skin is the outer layer of the epidermis, which performs a protective function and reliably protects the skin from dehydration and harmful effects external environment. Such an interesting name is due appearance its cells - all cells of this layer are equipped with spikes and very much resemble horns. The nuclei in such cells are absent, but they contain the protein keratin. By the way, such an interesting and informative science as corneotherapy is engaged in the study of the stratum corneum of the skin.

As for the lipid layer, it covers the surface of the stratum corneum (often also called water-lipid) and is a mixture of exfoliating particles of the stratum corneum, sweat and sebum. After reading such an unsightly description, many may think that this is something absolutely unhygienic, but in fact it is completely wrong: the lipid layer is an extremely important component not only for human skin, but for his entire body. It is he who actively prevents the penetration of a wide variety of harmful substances into the skin from the outside, while at the same time perfectly passing vital oxygen into it.

What causes the lipid layer to deteriorate?

There can be several reasons for the violation of the lipid layer:

Washing the face with soap , poor quality cleansers or hot water .
Uncontrolled sunbathing and visits to the solarium.
Abrupt change temperatures (for example, frequent entry from frost into well-heated rooms).
Physical stress (too much rubbing of the skin of the face with a towel at the end of washing can also easily lead to a disruption in the production of lipids).

What to do to restore the lipid layer?

The damaged lipid mantle entails not only dehydration of the skin, but also an increase in its sensitivity to various negative external factors. Some oils do an excellent job of restoring the damaged lipid layer - this is due to the fact that the main components of the lipid layer, as well as many oils, are phospholipids, free fatty acids, cholesterol and ceramides. So if you choose the right oils, the similarity of the composition will contribute to the restoration of both artificial and real lipid layers - natural oils are very rich in phospholipids and natural fatty acids. And phytosterols in the composition of such oils are endowed with the ability to replace the natural cholesterol of the stratum corneum. There are also antioxidants in oils that actively prevent the oxidation of skin lipids.

by the most suitable oils to restore the lipid layer there will be grape seed oil, as well as burdock and linseed oils - all of them are equally well suited even to owners of oily skin. Ideally, the oil is applied to the skin before going to bed, and after ten minutes, the face is thoroughly blotted with a paper towel. If the skin is too oily in the morning, it is quite acceptable to rinse your face with water at room temperature (but by no means hot!). The oil is applied to the skin before going to bed every day for a month, and after this period it will be possible to notice that dryness and dehydration have disappeared without a trace, and they have been replaced by a healthy glow and blush!

In addition, some modern manufacturers produce excellent creams and serums to restore the lipid layer of the skin, and they also deserve the closest attention!

Revitalizing cream-reconstructor for all skin types from Marina Kazarina

Russian cosmetic brand Marina Kazarina boasts a truly revolutionary achievement in the field of corneotherapeutic cosmetics - an excellent regenerating cream-reconstructor for all skin types. This corneotherapy cream helps restore the lipid barrier of the skin and is very effective in combating such symptoms of skin hypersensitivity like redness, tightness and peeling, as well as burning and itching. In just a few days of use, it will return the skin to perfect health and healthy look! best helper to restore the lipid layer of the skin is simply not found!

The composition of the cream-reconstructor contains such valuable components as cholesterol, ceramides, omega acids, mosquito rose oil, borage oil, shea butter, deionized water, d-panthenol, lipid-membrane complex, arabinogalactan, horse chestnut extract and an organic preservative. The cream is sold in bottles of 15 and 30 ml, and its shelf life is nine months without opening in the refrigerator, five months in the refrigerator after the start of use, and only three months after the start of use if the cream is stored at room temperature(by the way, it is not worth storing it in the bathroom).

With Marina Kazarina's regenerating cream-reconstructor, the skin will quickly transform and acquire a radiant look!

Links

Marina Kazarina - reviews on cosmetics, beauty portal MyCharm.ru
Absolutely incomparable shampoo from Marina Kazarina , beauty portal MyCharm.ru
Delicate foam from Marina Kazarina for delicate skin , beauty portal MyCharm.ru

I. A. Libov, Candidate of Medical Sciences
D. A. Itkin
S. V. Cherkesova

RMAPO, Moscow

The need to correct lipid metabolism disorders is now beyond doubt. Numerous studies conducted before the beginning of the 90s proved the possibility of lowering the level of cholesterol (CS), triglycerides (TG) and normalizing lipid metabolism against the background of hypocholesterolemic therapy.

But does a pronounced decrease in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) always improve life prognosis?

The CARE study showed that lowering LDL-C below 3.2 mmol/L did not result in a further reduction in mortality. At the same time, according to the POST-CABGT study, which included patients after coronary artery bypass grafting (CABG), with a decrease in LDL cholesterol to a level of less than 2.6 mmol/l (compared to patients with a level of 3.4-3.5 mmol/l), the need for repeated CABG operations is reduced by 29%. Similar results were obtained in the CARS study, which included patients with coronary artery disease, with respect to normal level OH (from 4.1 to 5.6 mmol/l) and an average level of LDL-C (3.17 mmol/l). Currently, the goal of hypocholesterolemic therapy in secondary prevention of coronary artery disease is considered by European cardiologists to achieve an LDL cholesterol level of less than 3.0 mmol/l, and American cardiologists - less than 2.6 mmol/l.

The effectiveness of both drug and non-drug methods for correcting the level of dyslipidemia has been shown. At the same time, any correction should begin with the elimination of risk factors that contribute to the progression of atherosclerosis, such as smoking, physical inactivity, as well as with the normalization of the body mass index.

In cases of dyslipidemia on the background of diseases such as hypothyroidism, nephrotic syndrome, etc., it is necessary first of all to begin treatment of the underlying disease.

One of the main methods of non-drug treatment is diet with restriction of the intake of animal fats and easily digestible carbohydrates, restriction of caloric intake. In the Veterans Administrations study, patients were prescribed a diet high in polyunsaturated fatty acids and reduced in animal fats (compared to patients on the standard North American diet). Diet therapy for eight years led to a decrease in the level of TC by 12.7% and a decrease in the incidence of myocardial infarction (MI) by 20%. At the same time, there was no decrease in overall mortality in any of the groups of patients. In the Finnish Mental Hospital Study, over a six-year follow-up period, 450 patients of both sexes aged 34–64 years on a low-cholesterol diet showed a 15% reduction in blood cholesterol levels. At the same time, the achievement of an average TC level of 5.8 mmol/l did not cause a significant reduction in overall mortality or mortality from cardiovascular diseases. In the DART study, which included more than 2000 patients, average age who was 56.5 years old, following the diet for two years resulted in an insignificant decrease in the level of total mortality and mortality from coronary artery disease. However, ischemic events (non-fatal MI) were even more common in the dieting group. The largest study, the Minnesota Coronary Survey, which included approximately 5,000 patients of both sexes and all ages with a mean baseline TC level of 5.3 mmol/L, found that following a low-cholesterol diet alone resulted in a 14.5% reduction in TC levels over 4.5 years compared with a control group on a standard diet. This study also did not show a reduction in the development of cardiovascular diseases and a decrease in overall mortality.

In our opinion, the treatment of patients with hypercholesterolemia and hypertriglyceridemia should in all cases begin with the elimination of risk factors and the appointment of a hypocholesterolemic diet. At the same time, if the diet is effective, then it can be considered as monotherapy only if the patient is really able to follow the diet for the rest of his life. However, patients with coronary artery disease during an exacerbation of the disease and in the presence of severe hypercholesterolemia are shown, along with diet, the simultaneous administration of hypocholesterolemic drugs in adequate doses. Normalization of the level of lipid metabolism indicators only against the background of a diet in such patients is not possible, and untimely initiation of treatment can lead to the development of adverse complications.

In the absence of an "acute" situation, the ineffectiveness of non-drug therapy for three months is an indication for the inclusion of drug therapy. It should be noted that the use of lipid-lowering drugs, no matter what class they belong to, in no case means a refusal to follow a diet. On the contrary, any hypocholesterolemic therapy will be effective if the diet is followed.

Five main classes are currently in use medicines applied taking into account the mechanism of their action, effectiveness and availability side effects, as well as contraindications for one or another type of dyslipidemia.

I Statins.
II Nicotinic acid and its derivatives.
III fibrates.
IV Bile acid sequestrants.
V Antioxidants.

To date, the effect on overall mortality, mortality from cardiovascular diseases and the risk of developing cardiovascular complications has been proven only for drugs from the statin group. The action of these drugs is based on the inhibition of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme-A (HMG-co-A) reductase. By inhibiting cholesterol biosynthesis in the liver and intestines, statins reduce intracellular cholesterol stores. It causes education increased amount receptors for LDL and accelerates their removal from plasma.

Other mechanisms of action of statins on the vascular endothelium and platelet aggregation have not been fully studied.

The effect of statins is primarily aimed at lowering LDL cholesterol and total cholesterol. In works recent years it has been shown that the use of high doses of statins can significantly reduce triglyceride levels, and compete with the effect of fibrates.

Currently registered in Russia the following drugs from the statin group:

lovastatin (mevacor, Merck Sharp & Dohme)
simvastatin (Zokor, same company)
pravastatin (lipostat, Bristol Mayer Sweeb)
fluvastatin (leskol, Novartis)
atorvastatin (Liprimar, Pfizer)
cerivastatin (lipobay, Bayer)

According to W. C. Roberts (1997), a 10 mg dose of simvastatin is approximately equivalent to 20 mg of lovastatin or pravastatin and 40 mg of fluvastatin. According to his studies, doubling the dose of statins relative to the initial dose leads to an additional decrease in TC by approximately 5% and LDL-C by 7%. At the same time, an increase in the level of high-density lipoprotein cholesterol (HDL-C) does not depend on an increase in the dose of the drug.

Drugs from the statin group are used for primary and secondary prevention of coronary artery disease. Secondary prevention refers to the use of drugs in patients with proven coronary artery disease.

It seems to us that the greatest effectiveness in prescribing statins should be determined not only by the level of baseline lipid metabolism, but also by the combination of the total risk of developing cardiovascular complications and the clinical course of the disease. Thus, in patients with acute coronary syndrome, the clinical effect of statin use may be more pronounced than in patients with stable angina pectoris, and tactics should be more aggressive. However, these conclusions are based on our practical experience and have not yet been confirmed in multicenter randomized trials.

Statins, as well as aspirin and β-blockers, are among the agents that affect the prognosis of the disease in patients with coronary artery disease.

Statins have also been shown to be effective in primary prevention studies.

The 4S, CARE, LIPID, WOSCOPS, AFCAPS/TEXCAPS and others studies demonstrate the efficacy of statin therapy for secondary and primary prevention of CHD. At the same time, the effect of statins on the "end points" in secondary prevention is more pronounced and more economically justified. Therefore, the use of statins in patients with diagnosed coronary artery disease in combination with dyslipidemia can be recommended for all patients. The effectiveness of statin therapy is higher in the group of patients with more severe lipid metabolism disorders. The development of "coronary events" in a number of patients with coronary artery disease on the background normal values indicators of lipid metabolism indicates the multifactorial nature of the genesis of these complications and emphasizes the importance of not only the level of dyslipidemia, but also the combination of a number of factors, the most important of which are clinical manifestations exacerbation of the disease.

One of the possible reasons for the effectiveness of hypocholesterolemic drugs in the prevention of coronary artery disease is their ability to slow down the progression and even the possibility of regression of the atherosclerotic process, demonstrated in a number of studies. These effects were studied by measuring the diameter of the vessels using arteriography or intravascular ultrasound.

In the MAAS study in patients with coronary artery disease, treatment with simvastatin at a dose of 20 mg for four years revealed a statistically significant reduction in the development of new coronary artery stenosis and regression of existing coronary stenosis; the lumen of the vessels increased from 0.06 to 0.17 mm in the presence of an initial stenosis of more than 50%.

Slowing down the progression or regression of atherosclerosis is achieved through intensive and aggressive hypocholesterolemic therapy with a significant decrease in the level of LDL-C. Simvastatin and atorvastatin have the greatest hypocholesterolemic activity in the same dosage. In the SMAC study, the use of atorvastatin and simvastatin at a dose of 10-20 mg per day allowed almost 50% of patients with coronary artery disease and an initial level of LDL-C from 4.2 to 7.8 mmol / l to reach the target level after 52 weeks of treatment. At the same time, the effect of atorvastatin occurred somewhat faster, and after 16 weeks of treatment, it was achieved in 46% of patients compared with 27% during treatment with simvastatin. By the end of the year, this difference leveled out, amounting to 50% with atorvastatin and 48% with simvastatin, and was not statistically significant. This study showed a pronounced hypocholesterolemic efficacy of both statins and approximately the same effect after a year of treatment with both drugs. At the same time, in most European countries the cost of simvastatin was slightly lower than that of atorvastatin. In this study, no serious side effects were observed that required discontinuation of the drugs.

Another important lipid-lowering agent used to normalize lipid metabolism is nicotinic acid and its derivatives (niacin). According to V. Parson, the advantage of this group of drugs is that "they do everything the way they should." Along with a decrease in the level of OH and LDL-C, drugs in this group reduce the level of triglycerides and more successfully than any other lipid-lowering drugs increase the level of HDL-C. These drugs have a number of other advantages. For example, they reduce the level of lipoprotein "a", which is given great importance as an important independent risk factor for the development of complications such as heart attack and stroke. Preparations of nicotinic acid and its derivatives reduce the level of LDL, affecting mainly their small, most atherogenic particles. These drugs increase the level of HDL-C at the expense of the HDL 2 fraction, which is the most active in terms of removing lipids from plaques, and thus prevent the progression of atherosclerosis.

A number of studies have shown the possibility of reducing cardiovascular complications and overall mortality with the use of niacin.

The US Cardiovascular Drug Program compared a range of cholesterol-lowering drugs. The study was conducted in men aged 30-65 years who had a history of at least one heart attack. The effect of estrogens, thyroxine, clofibrate and niacin has been studied. Each group consisted of approximately 1100 patients, and the placebo group was twice as large. The expected duration of the study was 5 years, but for the first two agents, it was terminated early due to the development a large number heart attacks and other complications. Clofibrate had no beneficial effect on mortality or cardiovascular events. Thus, nicotinic acid was the only drug that was able to reduce the number of non-fatal heart attacks by about 27%, strokes by 24%, the number of hospitalizations for cardiovascular complications by 12%, and the need for surgical treatment of the heart and vessels by 46%.

The downward trend in mortality observed over 5 years of follow-up with niacin was not statistically significant.

An important advantage of this group of drugs is their relatively low cost compared to other lipid-lowering drugs. Currently, slow-release forms of nicotinic acid are most often used. They provide a longer and more gradual release of the active compound and cause a significant reduction in side effects. These drugs include:

connection of nicotinic acid with polygel;
nicotinic acid in capsules with an inert filler;
nicotinic acid in a tropical wax matrix (enduracin, which is most widely used at a dose of 500 mg three times a day.

The effectiveness of these drugs also varies somewhat. According to Figge et al. (1988), the bioavailability of extended-release niacin preparations with a wax matrix is almost two times higher than with dosed release. Therefore, the effectiveness of enduracin at a dose of 1500 mg per day in relation to LDL-C, HDL-C, according to D. Keenan, was even slightly greater than when taking 3000 mg of extended-release niacin.

Large-scale studies comparing the characteristics of efficacy, dosage, side effects of various prolonged forms of nicotinic acid are not yet available.

Maximum daily dose nicotinic acid preparations should not exceed 6 g, and for enduracin - 3 g. Increasing the dose did not lead to improved results, and the number of side effects may increase. General feature of all nicotinic acid preparations is the need for a gradual increase in the dose under the control of the level of lipid metabolism, even if they are well tolerated. Most often, treatment begins with a dose of 500 mg per day for a week, then 500 mg twice a day for another 1-3 weeks, and then the dose is adjusted depending on lipid metabolism. To reduce adverse reactions, drugs are used with meals, limit the use of hot drinks, and when the first signs of hyperemia appear, small doses of aspirin (100-325 mg) are added, which helps to reduce these manifestations in the first 3-4 days until their subsequent complete disappearance.

The most commonly reported side effects with niacin are hot flushes and pruritus, as well as a feeling of hyperesthesia and paresthesia; constipation, diarrhea, dizziness, palpitations, disturbance of accommodation, dryness skin or a violation of its pigmentation. All these side effects account for 2 to 7%

(D. Keenan) and do not significantly differ from side effects in the placebo group. Usually, every four weeks to control for unwanted liver complications, biochemical research. The appearance of nausea, vomiting or other ailments requires a temporary discontinuation of the drug and an additional study of liver tests. At the same time, a slight increase in the level of AST, ALT, LDH, GGTP during treatment with niacin is allowed. In addition to liver tests, during treatment with nicotinic acid preparations, the level of sugar and uric acid should be regularly monitored.

The use of other groups of drugs, such as fibrates, ion exchange resins (bile acid sequestrants) and antioxidants, also makes it possible in a number of cases to improve impaired lipid metabolism. However, data on their impact on overall mortality, mortality from cardiovascular diseases, the development of cardiovascular complications, the need for surgical methods of treatment, the frequency of hospitalizations, etc., have not yet been obtained. Lately large-scale studies on the use of fibrates and antioxidants may make it possible to more accurately determine their role and place in the treatment of dyslipidemia in a wide range of patients.