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Statins have been used for over 20 years to lower blood cholesterol, but today you can hear more and more about the dangers of these drugs. What are the short-term and long-term negative effects of statins.

Statins are malicious enemies of excess cholesterol, so it is difficult to imagine the treatment of atherosclerosis without them. But, despite the fact that these drugs have already saved more than one thousand lives, treatment with their help causes a serious blow to the body. What are statins, harm from taking and do they have side effects?

Before considering the harm of drugs, you need to know them better. Statins are drugs that inhibit the synthesis of cholesterol in the liver, in addition, they accelerate the excretion of LDL (low density lipoproteins) from the body, which are harmful to the body, and increase the content of HDL in the blood (high density lipoproteins).

But statins act not only on the organs, they also suppress the absorption of cholesterol from the blood, which came there from food.

Side effects

Intervention in the work of the body of any drugs does not pass without a trace, sometimes the body signals this at the very beginning of treatment. Side effects from taking statins, the patient may notice after 3-4 days:

  • nausea;
  • muscle aches;
  • headache;
  • lack of appetite;
  • indigestion;
  • pain in the liver;
  • rash;
  • flatulence;
  • insomnia.

These side effects appear due to the body's excessive sensitivity to changes in cholesterol metabolism, which increases significantly with prolonged excess of this substance in the blood, because the body gets used to this state.

The risk of the above side effects increases significantly if the patient:

  • taking antibiotics along with statins;
  • uses drugs based on nicotinic acid;
  • do not follow a cholesterol-free diet;
  • consumes alcohol;
  • tolerates colds.

Harm of drugs

If at the beginning of treatment the patient did not notice side effects, this does not mean that the medication was taken without a trace for the body. With their long-term use (the average duration of treatment with these drugs is 3-4 months), the harm "accumulates".

In recent years, many doctors have pointed out that statins do more harm than good. These studies by American experts even claim that more than half of the people who were prescribed these drugs could do without them. What are the negative statements in the direction of statins based on, do they cause real harm?

Damage to muscles

The main damage from taking statins is experienced by the muscles. Often, due to long-term treatment, rhabdomyolysis develops - the process of destruction of striated muscles. This is accompanied by:

  • pain in the muscles;
  • weight loss;
  • reduced pressure;
  • dizziness;
  • discomfort in the heart.

Although statins are used to keep the heart healthy and prevent the effects of atherosclerosis, these drugs also harm it, because it is made up of striated muscle, so its tissues can also be destroyed.

A striking example of the heart-destroying effect of statins is the death of cardiologist Atkins from organ failure due to muscle atrophy. The doctor took drugs to lower his cholesterol, but his body could not bear the accumulated side effects.

Why does rhabdomyolysis occur?

This disease develops while taking statins for a reason, because these drugs for high cholesterol disrupt cellular processes in muscle tissue. This is due to their influence on the synthesis of CoQ10 in myocytes. This substance is responsible for the production of energy in the mitochondria of muscle cells, which is needed for their contraction, “repair”, division and other important processes.

When, due to a lack of CoQ10, energy in the mitochondria of myocytes ceases to be produced, they slowly begin to break down, become dangerous for the body, so their degradation and excretion is accelerated.

Harm to the kidneys

Protein molecules are filtered in the small and narrow vessels of the kidneys so that they are not excreted from the body in the urine. When a person takes statins for a long time, he develops kidney failure, stones appear in paired filter-feeding organs.

This happens due to the fact that during muscle rhabdomyolysis, which was mentioned earlier, a huge amount of protein molecules is released, which clog the narrow lumen of blood vessels in the kidneys.

In addition to the fact that the kidneys are "clogged" with proteins, they accumulate decay products of these substances, for example, ammonia, which are dangerous for the body and harm all organ systems.

Harm to the liver


The long-term side effects of statins also affect liver health. By inhibiting the synthesis of enzymes responsible for the synthesis of cholesterol, these drugs disrupt the functioning of the organ. Often there is an increased activity in the production of other active substances, such as transamylases.

In addition to the direct effect on the liver, there is also an indirect one. The course of treatment with statins lasts at least 3 months, all this time the liver must neutralize the auxiliary components of the drug every day, the load on it increases significantly.

The development of diabetes

If you take statins for a long period, the risk of developing type 1 diabetes increases significantly. Due to the intake of cholesterol-lowering drugs, the load on the pancreas increases, it cannot work normally, producing vital insulin. At the same time, liver resistance to this hormone, which lowers blood sugar, develops.

When insulin resistance occurs, blood glucose levels become unregulated and begin to rise, especially if the person is a sweet tooth or a heavy drinker. Over time, resistance to this hormone will only increase and, without the necessary treatment, insulin-dependent diabetes mellitus will develop.

Resistance (immunity) to insulin increases the duration of inflammatory reactions, so often diabetes is accompanied by gout, nephropathy, and infectious diseases.

Premature cell aging

Cell membranes are responsible for the elasticity and protection of cells. Every day they are “tested for strength” not only by external factors (temperature, pressure, physical impact), but also internal ones, for example, membrane phospholipids can be destroyed by cellular enzymes. But this does not happen due to Q10, which blocks their activity.

Cholesterol molecules are not involved in the synthesis of Q10, how then do statins reduce the amount of this substance? The thing is that from the places of Q10 synthesis, LDL, and mainly triglycerides, move through the blood. When the amount of cholesterol is significantly reduced, the protector of cell membranes simply does not get to the cells. Particularly acute shortage of Q10 is experienced by cells of the immune, lymphatic system and platelets. While cells lack this substance, its molecules circulate freely in the blood, but cannot be delivered to their intended destination.

The consequences of a lack of Q10 are dangerous for the life of cells - their membranes begin to collapse under the action of cellular enzymes, lose elasticity and the ability to quickly regenerate. This is reflected in human health by excessive dryness, lethargy and grayish skin color, the appearance of fine wrinkles, deterioration of blood clotting, and a decrease in immunity. These side effects of statins may appear after 5-6 months of treatment.

Pregnenolone Theft Syndrome

This is not a chronic or genetic disease, but a code name for another long-term side effect of taking statins. The harm from lowering cholesterol lies not only in the lack of Q10, but also in disruption of the endocrine cells.

Cholesterol is used in large quantities by the adrenal glands - endocrine organs that synthesize steroid hormones. When statins sharply block the synthesis of this LDL in the liver, the cells of these organs experience a shock, because they sharply lose the substrate for the synthesis of active substances.

Their answer is dangerous for the body: in the adrenal glands, all the remaining intermediate "raw materials" for the production of various hormones - pregnenolone - are used to create cortisol - the steroid hormone of stress.

Effects of cortisol shock

This “reprioritization” harms several body systems at once. First of all - cardiovascular, because cortisol has a vasoconstrictive effect and speeds up the heartbeat.

The nervous system suffers no less, the neurons of which are constantly in an excited state of stress. At the same time, a person becomes irritable, he has attacks of aggression and panic, insomnia appears, and working capacity decreases.

When considering the harmful effects of statin-induced cortisol shock, we must not forget the endocrine system. The synthesis of the aforementioned hormone stops the production of the most important active substances: sex hormones (estrogen, progesterone, testosterone and others), glucocorticoids, mineralocorticoids, aldosterone and others.

Increased bone fragility

Taking steroids, a person independently harms his own bones. Due to a significant decrease in the level of cholesterol in the blood, the production of vitamin D in the skin, which is produced from LDL under the influence of the sun, decreases. This substance promotes the absorption of the lion's share of calcium entering the body. With prolonged use of statins, especially in winter, there is an increase in bone fragility, muscle aches (their work is impossible without calcium) and other unpleasant symptoms.

This is not the whole list of long-term negative effects of taking statins. Some experts associate their treatment with the development of cataracts, Alzheimer's or Parkinson's disease, memory impairment, decreased thyroid function, chronic fatigue, and others. Such data have not yet been confirmed, but they make one seriously think about whether statins can be used at all.

Unfortunately, statins remain the most effective drugs for lowering cholesterol today. Of course, there are others, but they are more expensive and they are still little known in the CIS countries, so doctors boldly prescribe already proven and inexpensive Simgal, Leskol, Zokor, Vitorin and other medicines.

Treatment with statins is an effective way to lower blood cholesterol, but often their harm far outweighs the benefits. You should not take statins on your own, and if your doctor has prescribed them, you should ask him about a possible drug alternative or a cholesterol-free diet.

For the treatment of lipid metabolism disorders, drugs of different groups are prescribed. But the basic means in the treatment of diseases associated with high cholesterol in the blood are statins. Some of them are also used for liver pathologies. These medications are quite effective, but taking them for a long time can harm the digestive gland and the body as a whole. Therefore, it is important to know how they work and which ones are the safest for the liver.

Statins are a group of drugs that inhibit the synthesis of an enzyme in the liver that is responsible for the formation of cholesterol. The action of the active substances of these funds is also aimed at:

  • reduction of inflammation in blood vessels, the risk of atherosclerosis;
  • normalization of the tone of veins and arteries;
  • prevention of myocardial infarction;
  • reducing the likelihood of ischemic stroke;
  • acceleration of the recovery process during the period of post-infarction rehabilitation.

Depending on the composition, method of manufacture and effect, all statins are divided into 4 groups: first, second, third and fourth generation. Which one to take - the doctor decides individually.

  • hypercholesterolemia (with the ineffectiveness of the diet);
  • cardiac ischemia;
  • obesity;
  • diabetes;
  • angina;
  • previous heart attack, stroke;
  • high risk of developing pathologies of the heart and blood vessels.

Despite the properties, the use of drugs in this group is not always prescribed: there are factors that exclude the possibility of their use in the treatment and prevention of diseases of the cardiovascular system. These include:

  • individual intolerance to the substances that make up statins;
  • the period of breastfeeding;
  • hepatitis;
  • cirrhosis;
  • use of hormonal contraceptives;
  • diseases of the musculoskeletal system;
  • thyroid dysfunction.

Treatment with statins is also contraindicated during pregnancy. Exceptions are possible in cases where the likelihood of improving the well-being of the expectant mother is much higher than the risk of developmental anomalies in the fetus.

Olga: “I have had diabetes since childhood and I almost constantly take statins. During pregnancy, the doctor also said not to stop taking them, that they are not dangerous in my case, but the annotation says that they should not be drunk during pregnancy. I don’t know what to do: if you stop taking it, your health will definitely worsen, and if not, how will it affect the child?

Possible side effects

Statins are powerful drugs. As a rule, they are taken for a long time. Therefore, sometimes side effects appear during therapy with such drugs. Let's consider the main ones.

Muscle, joint pain

Pain in the muscles can be disturbing in the evening, after an active working day. The occurrence of myalgia is directly related to the ability of statins to destroy muscle cells - myocytes. In their place, inflammation appears. This leads to increased production of lactic acid and even more irritation of the nerve endings.

When taking statins, the muscle tissue of the lower extremities is most often affected. But this side effect occurs in only 0.4% of patients and is temporary. After the cessation of drug therapy, the cells are restored, and all pain sensations disappear.

In rare cases, rhabdomyolysis develops - a syndrome characterized by the death of part of the muscle fibers, the occurrence of acute renal failure due to the ingress of decay products into the blood.

Sometimes patients experience complications from the joints. By lowering cholesterol, statins also reduce the amount of intra-articular fluid and change its properties. This results in arthritis and arthrosis. If measures are not taken in time, joint contracture may occur - fusion of its main elements. This threatens with loss of mobility in the limbs.

Malfunctions in the digestive tract

Such consequences occur in 2-3% of patients taking statins. May be concerned:

  • nausea;
  • frequent belching;
  • vomit;
  • discomfort, pain in the stomach, intestines;
  • increased or, conversely, decreased appetite.

The appearance of all these symptoms indicates an increased sensitivity to statins and is a reason for adjusting their dosage or replacing them with other medical agents that have a similar principle of action.

Up to 80% of "bad" cholesterol is produced in this organ. Statins inhibit its synthesis, but some of them destroy liver cells. This leads to a deterioration in the functioning of the organ, the occurrence of complications against the background of existing pathologies.

These side effects are not observed in all patients. To assess the negative effect of drugs on hepatocytes, liver tests are regularly performed, as well as a study of indicators of general and biochemical blood tests.

Disorders of the nervous and vascular systems

Long-term use of statins can cause the following symptoms:


All these side effects do not always appear: according to studies, disturbances in the functioning of the nervous system are observed in only 2% of patients undergoing statin therapy.

Statins help prevent the occurrence of pathologies of the cardiovascular system. But in some cases they cause disturbances in its work. The negative consequences of the use of cholesterol-lowering drugs can be:

  • increased heartbeat;
  • low or high (rarely) blood pressure;
  • migraine;
  • arrhythmia.

In the first week of taking statins, there may be an increase in angina symptoms, but over time, the patient's condition returns to normal.

Other consequences

Skin reactions are rare, but sometimes occur:

  • hives;
  • puffiness;
  • redness.

Long-term treatment with statins can also adversely affect the state of the respiratory system. Against the background of their reception it is possible:

  • decreased immune defense and infectious diseases of the nasopharynx;
  • the appearance of difficulties with breathing;
  • the occurrence of nosebleeds;

There is also a high chance that an existing infection will spread to the lower respiratory tract (lungs). This threatens the development of bronchitis and pneumonia. The consequences of therapy with drugs of this group can also be: anaphylactic shock, Steven-Jones syndrome. But such severe reactions are extremely rare, the likelihood of their occurrence is minimal.

Use in NAFLD

Among lipid-lowering drugs used to correct cholesterol levels in cardiovascular disease, statins are considered the drugs of choice. But for many years the question of the possibility and effectiveness of their use in non-alcoholic fatty liver disease has remained open. To assess the benefits and harms of drugs in this group, more than one study has been conducted.

It turned out that the use of statins for the treatment of liver diseases such as fatty liver and steatohepatitis is not only possible, but necessary and safe.

After their use, there is a decrease in the level of total cholesterol, low density lipoproteins and liver enzymes. But since the destruction of hepatocytes is possible when taking drugs of this group, before prescribing them, doctors must necessarily compare the therapeutic effect and the risk of hepatotoxicity, study the positive effect of statins on the processes occurring in the organ.

Basic drugs

Patients with such a diagnosis can be prescribed drugs of different groups. Of the statins, the safest and most effective are:


How to support the body?

To prevent liver damage, maintain its work during the period of statin use, the following are additionally prescribed:


Hepatoprotectors not only help prevent the destruction of liver tissue, but also accelerate its recovery after the use of statins, enhance the effectiveness of the main treatment.

Should I take medication?

Despite the possible negative effect of statins on the liver, the need for their use and effectiveness in non-alcoholic fatty pathology are justified. Let's take a clinical case.

A 73-year-old patient was admitted to the intensive care unit with complaints of:

  • high blood pressure;
  • headache;
  • asthma attacks at night;
  • feeling of heaviness in the chest;
  • swelling of the lower extremities;
  • fast fatigue.

At the age of 35, the patient began to gain weight, at 65 she underwent laparoscopic cholecystectomy. She didn't go to the doctors anymore. The woman does not smoke, but leads a sedentary lifestyle. Mother and father died at the age of 67 and 69, respectively: the woman suffered from hypertension, and the man from type 2 diabetes.

On admission, the general condition of the patient was severe. After the examination, it turned out that she had coronary heart disease, diabetes, abdominal obesity, atherosclerosis of the aorta and pronounced fatty infiltration of the liver.

The patient was given:

  • diet
  • taking drugs that lower blood pressure;
  • prolonged mononitrates.

In addition, taking into account the presence of dyslipidemia in the patient, signs of non-alcoholic steatohepatitis, combined lipid-lowering therapy (simvastatin and ursodeoxycholic acid - Ursosan) was additionally prescribed.

During the treatment, the patient's well-being improved: chest pain and shortness of breath disappeared, resistance to physical exertion increased, swelling of the legs and feet decreased, and working capacity increased. The woman was discharged from the hospital with recommendations to continue therapy and undergo regular examinations.

The results of the studies after 3 months: no new symptoms, lipid metabolism indicators improved slightly, recurrences of anginal attacks were not observed.

The statin dosage was increased. At the same time, the level of liver enzymes (AST and ALT) was constantly monitored.

After 3 months, the patient was again examined, during which a significant improvement in blood counts was found. In addition, the woman reduced body weight, got rid of peripheral edema and pain in the legs when walking.

This clinical examination confirms the need for statins in the treatment of non-alcoholic fatty liver disease, combined with other pathologies. It is possible to use lipid-lowering agents as part of the complex therapy of metabolic disorders even in old age.

Statins are one of the most effective drugs used in the treatment of non-alcoholic fatty liver disease and cardiovascular diseases. They help reduce the likelihood of developing complications against the background of existing pathologies and improve the quality of life in general.

But in addition to the benefits, their use can harm the body. Therefore, it is impossible to take drugs of this group on your own: only a doctor can choose the correct, safe for the liver, dosage of drugs.

Ivashkin V.T., Drapkina O.M.,

The purpose of the review. To describe the role of hydroxymethylglutaryl-CoA reductase inhibitors in reducing the incidence of cardiovascular morbidity and mortality from the standpoint of evidence-based medicine and the possibility of using statins in patients with non-alcoholic fatty liver disease as part of the metabolic syndrome.

Cardiovascular diseases are the main causes of disability and death worldwide. The pathogenesis of these diseases is based on atherosclerosis, one of the main problems of modern medicine. A fairly large number of studies have shown the possibility of reducing the incidence of cardiovascular morbidity and mortality up to 42% by reducing the level of low density lipoproteins. This became possible thanks to the use of the main class of lipid-lowering drugs - statins. The uniqueness of statins lies not only in the ability to significantly reduce the synthesis of cholesterol, but also in the presence of a number of other properties, united under the name of "pleiotropic effects". Due to the steady increase in patients with metabolic syndrome, a high risk of cardiovascular complications, the appointment of statins is inevitable. It is known that atherogenic dyslipidemia in such patients in most cases is combined with non-alcoholic fatty liver disease. In Russia, adherence to statin therapy is extremely low (in 2001, only 0.6% of patients with acute myocardial infarction were taking statins). Among the many possible reasons for the insufficient use of statins in our country, the issue of the safety of prescribing this class of drugs remains relevant. The results of the studies show that in individuals with an initially elevated level of hepatic transaminases due to various reasons, taking statins does not cause an increased risk of hepatotoxicity (a clinically significant increase in liver enzymes in 0.8% of patients versus 0.6% of cases in the placebo group). There is also evidence that the combination of low doses of statins and ursodeoxycholic acid is more effective than using a double dose of statins. The article deals with the necessity and safety of statins in patients with non-alcoholic fatty liver disease.

Conclusion. Prescribing statins for primary and secondary prevention of cardiovascular diseases could prevent tens of thousands of premature deaths. The results of a large number of studies suggest the efficacy and safety of prescribing simvastatin to patients with non-alcoholic fatty liver disease as part of the complex therapy of metabolic syndrome. The combined use of statins and ursodeoxycholic acid is justified as a pathogenetic therapy for NAFLD, as well as lipid-lowering therapy in patients with metabolic syndrome.

Cardiovascular diseases (CVD) (ischemic heart disease - ischemic heart disease, cerebrovascular disease, peripheral arterial occlusive disease) are the main causes of disability and death worldwide. The pathogenesis of these diseases is based on atherosclerosis, one of the main problems of modern medicine. The history of close study of the essence of the processes underlying atherosclerosis has been going on for more than a century. At present, there is a clear idea of ​​atherosclerosis as a multifactorial disease, a dynamic process that has been progressing in the vascular system for decades and has the possibility of reverse development of changes in the artery wall. Over time, the process progresses inexorably, often appearing suddenly, often fatally (sudden coronary death or myocardial infarction).

As is known, most cases of coronary artery disease occur against the background of long-term coexistence of risk factors, among which lipid metabolism disorders are of particular importance. The statement “without atherogenic lipoproteins there will be no atherosclerosis” is confirmed by the results of the largest epidemiological studies (Framingham, MRFIT, a study of 7 countries), in which a clear direct correlation was shown between the concentration of cholesterol in the blood and the mortality rate from coronary artery disease (Fig. 1) .

Figure 1. Mortality rates from coronary artery disease depending on the level of cholesterol.(Data from the MRFIT study)

Lipid metabolism disorders play one important role in the pathogenesis of diseases associated with atherosclerosis. Clear evidence of this can serve as the results of a recently completed international study INTERHEART, which included 15152 patients with acute myocardial infarction (case) and 14820 people without obvious signs of coronary heart disease (control) from 52 countries. The aim of this study was to investigate the relationship between acute coronary syndrome and 9 risk factors (dyslipidaemia, smoking, arterial hypertension, obesity, diabetes, stress/depression, alcohol consumption, vegetable and fruit consumption, and physical activity). It turned out that regardless of gender, nationality and socio-ethnic conditions in the development of acute myocardial infarction, dyslipidemia ranks first among all risk factors.

In Framingham prospective epidemiological study, which began in the 1950s and continues to this day, optimal levels of high-density lipoprotein (LDL), total cholesterol (TC), triglycerides (TG) and high-density lipoprotein (HDL) were determined as the main lipid risk factors cardiovascular outcomes of atherosclerosis. However, the results of studies of the last decade indicate an unequal contribution of different classes of lipids to the risk of CVD. For example, in an intrapopulation study PROCAM (Prospective Cardiovascular Munster Study) the risk of association of low HDL, hypertriglyceridemia and moderately elevated LDL levels has been proven. In a prospective study AMORIS (Apolipoprotein Mortality Risk Study) it was confirmed that Apo B is a more sensitive marker of CVD risk, and the size and density of LDL particles are stronger predictors of adverse vascular events than total cholesterol and LDL. The ApoB/ApoA-1 ratio has also been proven to be the most powerful predictor of the risk of ischemic stroke.

A fairly large number of studies have shown the possibility of reducing the incidence of CVD and mortality up to 42% by lowering LDL levels. This was made possible by the use of a new class of lipid-lowering drugs - statins.

The discovery and introduction into practice of inhibitors of hydroxymethylglutaryl-CoA reductase (HMG-CoA reductase), the main enzyme that regulates cholesterol biosynthesis in hepatocytes, has become one of the most striking achievements of the second half of the 20th century. Having created the first statin in 1976, Japanese researcher Akira Endo could hardly even imagine that 30 years later he would be called the "discoverer of a" Penicillin "for cholesterol" (discoverer of a "Penicillin for cholesterol"). Completely two different classes of drugs made a revolutionary revolution in medicine: the use of antibiotics prevented the deaths of millions of people from infections, and under the influence of statins, the most common, many-sided dangerous disease, atherosclerosis, became vulnerable.

Numerous large multicenter placebo-controlled studies (4S, CARE, LIPID, WOSCOPS, AF CAPS/TexCAPS, HPS, CARDS, etc.) have proven the high efficacy of statins in atherogenic dyslipidemia in terms of reducing the incidence of cardiovascular complications, including reducing the risk of premature death in patients with clinical manifestations of atherosclerosis.

The Scandinavian research should be considered fundamental among these works. 4S (Scandinavian Simvastatin Survival Study). This was the first long-term (5.4 years) placebo-controlled study using simvastatin (using Zocor) 20-40 mg/day, in which 4444 people with coronary artery disease participated. This study was the first to study the effect of simvastatin treatment on cardiovascular and overall mortality. The study population was patients with coronary artery disease after a history of myocardial infarction, aged 35–70 years, with an initial level of total cholesterol of 213–309 mg/dL. The decrease in LDL levels over 5 years of follow-up was 36%, which led to a decrease in overall mortality by 30% (p=0.0003). The number of major coronary events decreased by 34%, cardiovascular mortality - by 42%, the need for myocardial revascularization operations - by 37%. This study largely dispelled doubts about the need for lipid-lowering therapy in patients with coronary heart disease in order to prevent its complications and answered many questions about the safety of such treatment. The results of this landmark study greatly contributed to the development of statin drugs as a class.

It is necessary to refer to the research HPS (Heart Protection Study)- the largest study of recent times, in which 20,536 patients participated: 50% of patients took simvastatin (the drug Zocor was used), 50% - placebo. Taking into account the design of the study, half of the patients took an antioxidant cocktail: vitamin E (600 mg) + vitamin C (250 mg) and β-carotene (20 mg), half - placebo vitamins. According to the main results of HPS, taking simvastatin at a dose of 40 mg/day for 5 years significantly reduced cardiovascular mortality by 17%, the incidence of any major cardiovascular event by 24% (p

The uniqueness of statins lies not only in the ability to significantly reduce the synthesis of cholesterol, but also in the presence of a number of other properties, united under the name of "pleiotropic effects". The diversity of pleiotropic effects of statins is likely in the near future to allow the use of this class of drugs for the treatment of more than just cardiac patients. Experimental and clinical evidence is increasingly providing evidence for the need to expand the "therapeutic niche" of statins. Of greatest importance are such pleiotropic effects of statins as: improvement of endothelial function (this property of statins is already manifested at low doses and this does not require long periods of treatment), inhibition of proliferation and migration of smooth muscle cells; decrease in platelet aggregation, anti-inflammatory effect, improvement of the fibrinolytic system. There is increasing evidence of the effectiveness of statins in individuals with Alzheimer's disease, multiple sclerosis, chronic heart failure, and renal failure. Korean scientists on experimental mouse models when analyzing the effect of simvastatin on tumor growth obtained results indicating the antitumor potential of simvastatin against colon cancer.

"In the face" of statins, doctors received an effective and safe drug for inpatient and outpatient use, which was included in the pharmacopoeial lists of "mandatory" drugs in many countries of the world. According to a European study EUROASPIRE, which monitors the dynamics of risk factors and CVD, in Europe statin prescription has increased from 32.2% to 88.8% over the past decade, however, achievement of LDL levels remains at 40%. One of the main problems, both in Western and Eastern Europe, is the low adherence of patients to statin therapy. Things are far from rosy in Russia. According to the USA Food and drug administration in 2005, the Russian Federation was among the world leaders in drug consumption (in terms of consumption of finished drugs - 12th in the world and 6th in Europe). But statins are not even among the top ten most used drugs. There are no exact statistics proving the frequency of statin use by Russian patients, however, the available separate data indicate an extremely unfavorable situation that has developed around this class of drugs. Thus, according to a multicenter study VALIANT, in which Russia also took part, by 2001 only 0.6% of our compatriots who had suffered acute myocardial infarction received statins (Fig. 2) .

Figure 2. Frequency of statin use in patients with acute myocardial infarction in different countries.(Data from VALIANT: Nippon Rinsho. 2002 Oct; 60(10):2034-8, Am Heart J 2003 May;145(5):754-7)

Due to the steady increase in patients with metabolic syndrome (MS), a high risk of cardiovascular complications, the appointment of statins is inevitable. It is known that atherogenic dyslipidemia in such patients in most cases is combined with non-alcoholic fatty liver disease (NAFLD). NAFLD is an asymptomatic disease that does not significantly affect the quality of life until the development of terminal forms. At the same time, the main causes of death in patients with NAFLD are related to cardiovascular pathology. A long-term study conducted in Sweden showed that over 15 years of follow-up, out of 129 patients with morphologically proven NAFLD accompanied by "chronic hypertransaminasemia", 12.7% died from cardiovascular diseases, and only 1.6% from hepatic pathology. . Therefore, NAFLD, as one of the manifestations of MS, could become an independent niche for statins in hepatology.

Among the many possible reasons for the insufficient use of statins in our country, the issue of the safety of prescribing this class of drugs remains relevant. The study of Chalasani N. et al. demonstrated that in individuals with initially elevated levels of hepatic transaminases due to various reasons, statin use does not cause an increased risk of hepatotoxicity. The HPS study, conducted with the inclusion of more than 20 thousand people who received simvastatin for a long time, showed the relative safety of their administration - a clinically significant increase in liver enzymes was observed in 0.8% of patients (versus 0.6% of cases in the placebo group).

Is there a risk of statin hepatotoxicity in the treatment of dyslipidemia in patients with MS? It is known that an increase in liver enzymes - the most common side effect of statins - is observed in 0.5-2% of cases and depends on the dose of the drug. Although liver disease is on the list of contraindications for the use of statins, cases of worsening of the course of liver disease while taking this class of drugs have not yet been described. There are a number of studies, the results of which have shown the efficacy and safety of the use of statins in the treatment of atherogenic dyslipidemia in patients with MS.

According to the Report of the US National Lipid Association Committee on the Safety of Statin Treatment, statin therapy may be recommended for patients with chronic liver disease, non-alcoholic steatohepatitis, fatty liver under careful monitoring of the level of liver enzyme activity.

If the patient is shown taking statins, and the level of hepatic transaminases exceeds 2-3 times the norm, then ursodeoxycholic acid (UDCA) can come to the aid of the clinician. The appointment of UDCA is pathogenetically justified in NAFLD. UDCA is a drug of pleiotropic action, which is expressed in the presence of choleretic, cytoprotective, immunomodulatory, anti-apoptotic, hypocholesterolemic and litholytic mechanisms of action. The use of UDCA in NAFLD with elevated levels of transaminases at a dose of 10-15 mg / kg per day, lasting 6 months or more has a positive effect on biochemical parameters, leads to a decrease in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP) , gamma-glutamyl transpeptidase (GGT) and a decrease in the severity of steatosis and inflammation according to the histological examination of the liver. After normalization of the level of AST, ALT while taking UDCA, the patient can be prescribed statins.

There is also evidence in the literature that the combination of low doses of statins and UDCA is more effective than using a double dose of statins. In a Spanish study, combination therapy with simvastatin 20mg/day and UDCA 300mg/day for 4 months, compared with simvastatin 40mg/day alone, achieved a more pronounced reduction in LDL levels (p = 0.0034). A similar result was obtained in the same study in the group of patients treated with atorvastatin 20 mg/day and UDCA 300 mg/day for 4 months, compared with atorvastatin 40 mg/day alone (p=0.0037). .

It should be noted that studies that have studied the combination therapy of statins and UDCA are few, but at the same time, the addition of UDCA to the regimen of lipid-lowering statin therapy in patients with NAFLD is justified.

We present a clinical observation.

Patient D., 73 years old, was admitted to the intensive care unit of the Clinic for Propaedeutics of Internal Diseases, Gastroenterology and Hepatology named after V.Kh. Vasilenko (director of the clinic - Academician of the Russian Academy of Medical Sciences, Professor V.T. Ivashkin) in December 2007 with complaints about:

  • feeling of heaviness in the chest;
  • severe headache in the occipital region against the background of an increase in blood pressure to a maximum of 240 and 110 mm Hg;
  • attacks of nocturnal suffocation;
  • pain in the legs when walking, cold feet;
  • swelling of the legs and feet;
  • general weakness, fatigue.

From the anamnesis it is known that after the second birth at the age of 35, she began to notice a significant weight gain. From the age of 44, headaches began to disturb against the background of an increase in blood pressure to 180 and 90 mm Hg, about which she was observed by a doctor at the place of residence, was treated irregularly, and her blood pressure remained elevated. In 1998, at the age of 63, for the first time, a feeling of heaviness behind the sternum appeared, which occurs with moderate physical exertion and passes at rest. She was not examined, she did not receive regular therapy. In 2000, at the age of 65, the patient underwent laparoscopic cholecystectomy for calculous cholecystitis, at the same time an increase in glucose levels was detected, and an appeal to an endocrinologist was recommended. However, the patient no longer went to the doctors, was not treated. A significant deterioration in well-being over the past 8 months, when the above complaints began to grow. Due to the severity of the condition, the patient was hospitalized in the intensive care unit of the clinic.

The patient does not smoke, leads a sedentary lifestyle, eating behavior is excessive. The family history is burdened with CVD: mother and father suffered from HD and type 2 diabetes, died at the age of 67 and 69 years, respectively.

On admission: general condition of moderate severity. Consciousness is clear. The presence of abdominal obesity drew attention: body weight 123 kg, BMI = 45.2 kg/m2 (morbid obesity), waist circumference (WT) =153cm, hip circumference (OB) =168cm, OT/OB =0.91. The skin is pale pink. Moderate cyanosis of the lips. Xanthelasmas on the upper eyelids. Frank's positive symptom. Swelling of legs and feet. The pulsation of the vessels of the lower extremities is sharply reduced. On percussion of the chest, a clear lung sound with a boxy tone. Weakened vesicular breathing, below the angle of the shoulder blades on both sides, damp, unvoiced fine bubbling rales are heard in moderate amounts. NPV 22 min. On examination, the region of the heart is not changed. The boundaries of the relative dullness of the heart are shifted to the left by 1.5 cm outward from the mid-clavicular line. On auscultation, the 1st tone is weakened, the accent of the 2nd tone over the aorta, systolic murmur on the aorta with conduction to the carotid arteries, short systolic murmur at the apex. The pulse is rhythmic, heart rate is 81 beats. in min., p. durus, BP 230 and 100 mm. rt. Art. The abdomen is significantly enlarged in size due to the excess subcutaneous fat layer, multiple whitish striae are visible, soft, painless on palpation (Fig. 3). On percussion, the liver is 2 cm below the edge of the costal arch along the right mid-clavicular line. The symptom of tapping in the lumbar region is negative on both sides.

Figure 3. Abdominal obesity in patient D., 73 years old.

In the resuscitation and intensive care unit, when studying the level of cardiospecific enzymes and ECG in dynamics, acute focal myocardial damage was excluded. Against the background of the therapy (antiplatelet agents, anticoagulants, nitrates, antihypertensive drugs), heaviness behind the sternum and paroxysmal nocturnal asthma attacks did not recur, shortness of breath decreased, exercise tolerance increased, swelling of the legs and feet decreased. However, arterial hypertension remained at the level of 160-180 and 90 mm Hg. For further examination and selection of therapy, the patient was transferred to the cardiology department.

During the laboratory and instrumental examination in the Department of Cardiology, the following were revealed:

  • in a biochemical blood test, signs of atherogenic dyslipidemia: total cholesterol - 284 mg / dl, TG - 345 mg / dl, HDL - 45 mg / dl, LDL - 172 mg / dl, VLDL - 67 mg / dl; atherogenic index - 5.3, type of dyslipidemia - IIb.
  • elevated levels of ALT (76 units/l), AST (70 units/l), de Ritis index 0.92.
  • In order to non-invasively determine the likelihood of developing fibrosis in a patient with metabolic syndrome suffering from non-alcoholic fatty liver disease, the APRI test was used, the calculation of which was carried out according to the formula: AST? 100 / ((upper limit of AST) ? platelets (10^9/l) = 0.58 (low probability).
  • indicators of insulin metabolism: glucose - 138 mg / dl, IRI - 29 μIU / ml, C-peptide - 1680 pmol / l. A quantitative control index of insulin sensitivity was calculated - QUICKI - test (QUICKI=1/, where I0 is the basal insulin level in the blood, G0 is the basal blood glucose level): 0.278, which confirmed the presence of a high degree of insulin resistance. The patient was diagnosed with type 2 diabetes, moderate severity, in the stage of subcompensation.
  • ECG - sinus rhythm with a heart rate of 84 per minute, signs of LV hypertrophy.
  • Echo-KG - aortic atherosclerosis, left ventricular myocardial hypertrophy (IVS - 1.35 cm, LV LV - 1.2 cm), EF 42%. Stenosis of the mouth of the aorta of atherosclerotic origin.
  • ambulatory blood pressure monitoring: patient type – non-dipper.
  • Ultrasound of the abdominal organs: the liver is not enlarged, the contours are even, the parenchyma is hyperechoic with signs of severe fatty infiltration. The gallbladder has been removed. The pancreas is not enlarged, the contours are fuzzy, the parenchyma has increased echogenicity. The spleen is not enlarged. Kidneys - without features.

Based on complaints, anamnesis, objective examination, data of laboratory and instrumental methods of examination, the following clinical diagnosis was formulated:

Combined diseases:

Ischemic heart disease: exertional angina III F.K.

Diabetes mellitus type 2, moderate severity, subcompensation phase.

Background diseases: Hypertension stage II, very high risk. Atherosclerosis of the aorta, coronary, cerebral arteries. Atherosclerotic heart disease: stenosis of the aortic mouth. Atherosclerotic cardiosclerosis. Abdominal obesity 3 degrees. Dyslipidemia type IIb.

Complications of the underlying disease: NK stage 2B. NYHA III f.cl.

Concomitant diseases: Cholelithiasis: laparoscopic cholecystectomy in 2000.

The patient was given dietary recommendations, the need for dosed physical activity was explained. Combination antihypertensive therapy (indapamide 2.5 mg/day, lisinopril 10 mg/day, amlodipine 5 mg/day), prolonged mononitrates (monomak 40 mg/day), metformin 1000 mg/day, antiplatelet agents (aspirin at a dose of 100 mg/day) days). In addition, given the presence of atherogenic dyslipidemia in the patient, as well as signs of non-alcoholic steatohepatitis, combined lipid-lowering therapy was prescribed (simvastatin 40 mg/day + ursodeoxycholic acid at a dose of 1250 mg/day). In this combination, the drug ursodeoxycholic acid also acted as a pathogenetic treatment of non-alcoholic steatohepatitis.

During the observation period in the clinic against the background of the therapy, there was a positive trend in the patient's condition: anginal pain and shortness of breath did not bother, tolerance to physical activity increased, swelling of the legs and feet significantly decreased, and general weakness decreased. The patient was discharged with recommendations to continue the above treatment and regular follow-up on an outpatient basis.

Outpatient examination after 1 month: no complaints, BP 160 and 90 mm Hg, AST 54 units/l, ALT 61 units/l, CPK 87 units/l.

Outpatient examination after 3 months: no new complaints, blood pressure 150/80 mm Hg, anginal attacks did not recur, lipid metabolism improved slightly. Considering the persistent severe atherogenic dyslipidemia, the dose of simvastatin was increased to 60 mg/day. Under the control of serum transaminases: AST 51 units/l, ALT 55 units/l.

When conducting a re-examination after another 3 months (after 6 months from the start of treatment): anginal attacks do not bother, there are no peripheral edema, pain in the legs decreased when walking, tolerance to physical activity slightly increased. The patient reduced body weight from 123 to 119 kg, WC = 149 cm, WC / OB = 0.89, BMI = 43.7. BP 135 and 80 mm Hg. Improved laboratory parameters: AST 40 units/l, ALT 44 units/l, CPK 74 units/l, APRI index decreased to 0.34. The target values ​​of blood lipids have not yet been achieved, however, lipid metabolism indicators have improved significantly: total cholesterol - 248 mg / dl, TG - 210 mg / dl, HDL - 55 mg / dl, LDL - 157 mg / dl, VLDL - 36 mg / dl; atherogenic index - 3.5. The glucose level normalized (fasting glycemia = 100 mg/dl), the degree of insulin resistance decreased (QUICKI test = 0.296). At the control ultrasound of the abdominal organs, the degree of fatty infiltration of the liver decreased: from severe to moderate. The patient continues to receive the selected therapy on a regular basis and is monitored in our clinic.

This clinical observation demonstrates a patient with multiple comorbidities within MS. The following clinical features associated with the difficulties of selecting therapy attract attention:

  • advanced age of the patient;
  • the presence of morbid obesity;
  • atherogenic dyslipidemia with severe clinical manifestations;
  • severe arterial hypertension;
  • high degree of insulin resistance;
  • the presence of comorbidity, including non-alcoholic fatty liver disease.

However, the improvement in the patient's condition and the positive dynamics of laboratory and instrumental parameters against the background of compliance with non-drug measures and regular use of combination therapy indicate success in the treatment of MS in elderly patients as well. In addition, this observation emphasizes the need (efficacy and safety) of prescribing lipid-lowering therapy (in this situation, a combination of drugs that affect lipid metabolism was used: simvastatin and UDCA) for the treatment of atherogenic dyslipidemia in elderly patients.

Increasing the use of statins for primary and secondary prevention of cardiovascular disease could prevent tens of thousands of premature deaths each year. Currently, there is compelling scientific evidence and clinical data supporting the need to include statins (primarily simvastatin) in the mandatory list of drugs for the active prevention and treatment of atherosclerosis. The results of a large number of studies suggest the efficacy and safety of simvastatin in patients with non-alcoholic fatty liver disease as part of the complex therapy of the metabolic syndrome. I would like to believe that in the near future statins will take their rightful place in the top ten vital drugs in our country.

Literature

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14. Aronov D.M. The triumphal march of statins. Difficult patient. 2007; 5(4): 33-7.
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Oncological diseases of the mammary glands are diagnosed in women quite often. Therefore, diagnostic measures to detect a dangerous tumor do not lose their relevance. Immunohistochemical study in breast cancer is designed to determine the susceptibility of malignant cells to specific substances. Through the study, it is found out whether the treatment being carried out is correct.

IHC - what is this study?

Immunohistochemical research used in oncology makes it possible to detect the relationship between proteins synthesized by malignant cells and antigens. Having identified this connection, specialists establish the type and structure of the neoplasm.

Purpose of the study

IHC in oncological pathologies of the mammary glands is carried out in order to:

  • establish the type of disease susceptible to a particular therapy;
  • , launched by the tumor, and the degree of their spread;
  • find the source of metastases;
  • establish the stage of development of the detected tumor;
  • evaluate the effectiveness of therapy;
  • find out the rate of spread of metastases;
  • identify the sensitivity of blood cells to specific drugs to screen out ineffective drugs.

Indications for IHC

Diagnostic research is used to determine the state of any part of the human body. The procedure is prescribed not only for breast cancer, but also for any neoplasms that are presumably malignant. IHC determines the state of the endometrium at:

  • the appearance of metastases;
  • pathologies of the uterus;
  • infertility;
  • unsuccessful IVF procedures;
  • diseases of the pelvic organs with different etiologies;
  • constant spontaneous abortion.

There are no contraindications to the procedure. They refuse to study only if for some reason it is impossible to take a biomaterial from a patient.

Study preparation

Before the procedure, the patient:

  • should not take hormonal drugs (one week before taking the biomaterial);
  • should not take medication to stop bleeding;
  • should carry out thorough hygiene procedures.

The study is carried out on specific days of the menstrual cycle:

  • on the 5th - 7th day, pathological changes in the endometrium are studied;
  • on days 20-24, secretory and receptor activity is assessed.

Research progress

To conduct an immunohistochemical test, a certain amount of tumor tissue of the breast is taken by biopsy. The fence is carried out at the site where the specialist suspects the accumulation of malignant cells.

Before the procedure, the physician marks the selected point on the patient's chest. Also pieces of the tumor can be taken for analysis cut during surgery.

  1. The collected biomaterial is taken to the laboratory.
  2. Tumor samples are lowered into a container with formalin.
  3. The biomaterial is degreased.
  4. Paraffin liquid is poured in, which makes it possible to determine the structure and type of tumor tissues.
  5. Cut off a piece of the tumor 1 mm thick.
  6. Place on laboratory glass.
  7. Chemical reagents and antibodies are used as dyes.
  8. The results of the test are ready after two weeks.

Different markers are used to detect breast cancer. If the test results revealed the presence of a significant amount of female sex hormones in the tumor tissues, then the tumor is actively developing. It is even possible that metastases have already begun. If the accumulation of hormones is average, then malignant cells multiply inactively. So, with proper and timely treatment, the patient has the opportunity to restore health.

A positive outcome of hormonal treatment is possible if the Ki-67 marker in a malignant breast tumor does not exceed 15-17%. The neoplasm grows rapidly if the marker reaches 35%. In this situation, chemotherapy is immediately carried out, which allows to slow down the reproduction of malignant cells. If the marker is above 85%, then it is too late to treat, death is inevitable.

Deciphering the results

Deciphering the results, look at the progesterone (PR) and estrogen (ER) receptors. IHC also determines the amount of the human epidermal growth factor receptor (HER-2 protein) in the biomaterial taken from the patient. In breast cancer, HER-2 is elevated.

With increased ER and PR in tumor tissues, it can be said that the malignant formation grows under the influence of hormones. If the concentration of ER and PR does not go beyond the norm or goes slightly, then the patient can hope for successful treatment.

The IHC indicators are deciphered according to a special color scale, correlating the colors on the scale with the shades of the biomaterial.

  1. 0 and +1. The protein concentration is normal. Therapeutic measures are not needed.
  2. +2. The protein concentration is average. There is a malignant tumor in the breast. Usually, an additional study is carried out to confirm the correct result of the first test. An additional study called FISH allows you to find out the protein content in each cell. If HER-2 is normal, then the FISH test will give a positive result, if it is elevated, then it will be negative.
  3. +3. The protein concentration is much higher than the normal value. Definitely there is a malignant neoplasm in the breast.

If the test showed a high concentration of protein, then the tumor is of an aggressive type, it grows intensively.

According to the results of IHC, 4 types of breast cancer are distinguished:

  • – ER receptors are positive, protein receptors are negative, Ki-67 is below 14%;
  • B-luminal - ER and HER-2 receptors are negative, Ki-67 is above 15%;
  • overexpressing - ER and PR receptors are negative, protein receptors are positive;
  • basal-like - all receptors are negative.

Prognostic markers

They determine the most likely behavior of the neoplasm at the time of the test. There is no effect of therapy on the study. The test allows you to determine the aggressiveness of the tumor. The prognosis is important for the selection of the most appropriate medications and treatment procedures.

Diagnostic markers

The study shows the effectiveness of the treatment. If the presence of aggressive cancer is detected, then chemotherapy is prescribed.

IHC is a complex test that uses a large number of markers. The more markers are tested, the higher the cost of the study. The test is effective in determining the type of cancer, helps to prescribe optimal therapy.

Immunohistochemical (IHC) study is a method for identifying specific antigenic properties of malignant tumors. are used to detect the localization of a particular cellular or tissue component (antigen) in situ by binding it to labeled antibodies and are an integral part of modern cancer diagnostics, providing the detection of localization in tissues of various cells, hormones and their receptors, enzymes, immunoglobulins, cell components and individual genes.

Goals of the IHC study

IHC studies allow:

1) to carry out histogenetic diagnosis of tumors;

2) determine the nosological variant of the neoplasm;

3) identify the primary tumor by metastasis with an unknown primary focus;

4) determine the prognosis of a tumor disease;

5) determine the malignant transformation of cells;

6) identify opportunities;

7) identify both resistance and sensitivity of tumor cells to chemotherapeutic drugs;

8) determine the sensitivity of tumor cells to radiation therapy.

How is an IHC study performed?

The IHC study begins with the collection of material. To do this, it is carried out, in which a tissue column is taken from the tumor and nearby tissues, or the material comes from the operation. Then the material is fixed. After fixing, the material is sent to the wiring, which allows you to prepare it for work (degrease and additionally fix it). After wiring, all samples are embedded in paraffin, receiving histological blocks. Paraffin blocks are stored forever, so it is possible to conduct an IHC study in the presence of paraffin blocks made earlier.

The next stage of the IHC study is microtomy - the laboratory assistant makes sections from paraffin blocks up to 1.0 microns thick and places them on special histological glasses.

Then sequentially routine staining and immunohistochemical examination are performed, allowing at each stage to more and more differentiate the phenotype and nosology of the tumor.

As you can see, an IHC study is a complex multi-stage process, and therefore, to conduct an IHC study, you should choose the most modern laboratory with highly qualified specialists and a high degree of automation - this way you will negate the risks of receiving poor-quality diagnostics. Such a laboratory today is UNIM.

Separately, it should be said about the timing of this study. On average in Russia, IHC research is carried out in terms of 10 days to several weeks. When contacting UNIM, you can do an IHC test in just 3 days! Also, the advantage of conducting IHC research at UNIM is your materials for research from any city in Russia. If necessary, specify the cost by submitting an application for research, or call the hotline (free of charge in Russia): 8 800 555 92 67.

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