Statins to lower cholesterol: choose and get acquainted with them. Contraindications, side effects of statins The effect of statins reaches its maximum after

Introduction…………………………………………………………………………………3

1. Mechanism of action of statins……………………………………………………5

2. General principles for the use of statins…………………………………..........6

3. Pharmacological effects of statins…………………………………...6

4. Pharmacokinetics and pharmacodynamics of statins………………………………8

5. Polymorphism of genes…………………………………………………………….13

5.1. Polymorphism of genes responsible for the pharmacokinetics of statins……..13

5.2. Polymorphism of genes responsible for the pharmacodynamics of statins…….18

5.3. Polymorphism of genes involved in the pathogenesis of atherosclerosis…………19

6. Place of statins in therapy…………………………………………………...20

7. Appointment and dosage of statins……………………………………………..23

8. Contraindications………………………………………..23

9. Drug interactions of statins…………………………………..24

Conclusion…………………………………………………………………………….27

References…………………………………………………………………28

Introduction

Statins are inhibitors of HMG-CoA reductase, the most effective and well-studied group of lipid-lowering drugs, which reversibly inhibit the activity of the key enzyme of cholesterol biosynthesis (CS) in humans.

Statins are the main drugs in the treatment of hyperlipoproteinemia IIa, IIb, III types.

The results of controlled clinical trials using statins indicate that these drugs have a lipid-lowering effect, reduce cardiovascular and overall mortality, improve the quality of life and prognosis of patients. ischemic disease heart (IHD) and atherosclerosis.

The drugs of this group have radically changed the approach to primary and secondary prevention of coronary artery disease and other atherosclerotic vascular lesions, pushing into the background traditional lipid-lowering drugs: nicotinic acid, fibrates, anion-exchange resins.

However, not all patients use these drugs is effective. At the same time, there are patients in whom these drugs cause adverse drug reactions (ADRs), primarily from the liver, so their use in this category of patients becomes limited.

In modern conditions, using statins, the possibility of stabilizing and reversing the development of atherosclerotic plaques in the coronary arteries, reducing their tendency to rupture, improving endothelial function, and suppressing cellular inflammatory reactions has been demonstrated. Statins have a positive effect on a number of indicators that determine the tendency to form blood clots - blood viscosity, platelet and erythrocyte aggregation, fibrinogen concentration.

The results of clinical trials of statins in recent years have demonstrated their efficacy and safety in patients with arterial hypertension, type 2 diabetes mellitus, and acute coronary syndrome.

Mechanism of action of statins

Statins are inhibitors of the HMG-CoA reductase enzyme, a key enzyme in cholesterol synthesis. As a result of a decrease in the intracellular content of cholesterol, the liver cell increases the number of membrane receptors for LDL on its surface, which bind and remove LDL from the bloodstream, thus reducing its concentration in the blood.

One of the parts of the statin molecule (the lactone ring) is similar in structure to part of the HMG-CoA reductase enzyme. According to the principle of competitive antagonism, the statin molecule binds to the part of the coenzyme (coenzyme) A receptor to which this enzyme is attached.

Another part of the statin molecule inhibits the conversion of hydromethylglutarate to mevalonate, an intermediate substance in the synthesis of the cholesterol molecule.

Inhibition of the activity of HMG-CoA reductase leads to a series of successive reactions, as a result of which the intracellular content of cholesterol decreases and catabolism of LDL cholesterol is accelerated.

Along with the lipid-lowering effect, statins have pleiotropic (non-lipid) effects, i.e. improve the function of the endothelium, reduce the content of C-reactive protein, inhibit platelet aggregation, proliferative activity of smooth muscle cells and have a number of other properties, the mechanism of which is not well understood. The non-lipid effects of statins are discussed in more detail in Chapter 3.

General principles for the use of statins

Statins reduce LDL cholesterol by 20-60%, triglycerides by 10-40% and increase HDL cholesterol by 5-15%.

Long-term use of statins, at least 5 years, reduces the incidence of deaths in coronary artery disease and other cardiovascular diseases by 25-40%.

The maximum lipid-lowering effect occurs after 2-3 weeks from the start of treatment, however, the results of therapy to reduce cardiovascular complications begin to appear no earlier than 6-9 months from the start of treatment.

The severity of the effect depends on the daily dose of drugs. It is believed that each doubling of the daily dose of statins is accompanied by an additional decrease in LDL cholesterol by 6-7%.

The dose is increased every 4 weeks if the desired cholesterol content is not reached.

The appointment of the maximum daily dose of statins is usually resorted to in cases of high cholesterol levels, mainly in patients with familial hypercholesterolemia, not forgetting that taking a high dose of a statin is dangerous due to the more frequent development of serious side effects(hyperfermentemia, myopathy, rhabdomyolysis).

With a decrease in LDL cholesterol less than 2.6 mmol / l (100 mg / dl), the dose is reduced.

Supportive therapy is carried out for a long time, for years, under the control of lipid metabolism.

Pharmacological effects of statins

Statins have both lipid and non-lipid effects.

The lipid-lowering effect is associated with a decrease in the content of total cholesterol due to LDL cholesterol. Depending on the dose, statins reduce the content to 65% (rosuvastatin at a dose of 80 mg / day). The effect of statins on LDL-C is dose-dependent, but this relationship is not linear, but exponential. Each doubling of the statin dose results in an additional 6% reduction in LDL cholesterol (the “rule of six”).

The effectiveness of different statins in reducing the content of LDL cholesterol is different. When using high doses (up to 80 mg / day), the effects on lowering the content of LDL cholesterol in different statins (atorvastatin and simvastatin, atorvastatin and fluvastatin) become similar.

The effect of statins on triglycerides and high-density lipoprotein (HDL) cholesterol levels depends on their initial values and, apparently, does not depend on the dose.

The use of statins in moderate hypertriglyceridemia is justified if the content of triglycerides (TG) does not exceed 4.4 mmol/L. In this case, it is possible to achieve a decrease in the level of triglycerides by about 1/3 of the initial values. With severe hypertriglyceridemia (triglyceride content of more than 10 mmol / l), treatment with statins is justified only in combination with fibrates or nicotinic acid.

The effect of statins on HDL cholesterol levels is not yet fully understood. When using statins, an increase in the content of HDL cholesterol by 6-10% is possible.

One new statin, a sustained-release form of fluvastatin, is capable of increasing HDL-C by 20%.

HMG-CoA reductase inhibitors have practically no effect on the content of fibrinogen and lipoprotein a (LP-a), which are considered additional risk factors for atherosclerosis.

Non-lipid effects of statins:

Decreased activity of inflammatory mediators and proatherogenic mediators: plasminogen activator inhibitor type 1 (ICAM-1), vascular adhesion molecule type I (VCAM-1), monocyte chemoattractant protein (MCP-1), interleukin-8, CD 40L, tissue factor, reduced migration and proliferation of smooth muscle cells.

Antioxidant properties (decrease in the ability to oxidize phospholipids and LDL).

Improving endothelial function (increasing endothelial-dependent vasodilation and nitric oxide synthesis).

Immunomodulatory properties (increase in the number of T-lymphocytes).

Reduced production of tumor necrosis factor.

Increased bone mineralization.

Reducing the lithogenicity of bile.

· Currently, work is underway to study the effect of statins on blood pressure and anticancer activity.

It is assumed that the pleiotropic effects of statins are not related to their lipid-lowering effect.

The main side effects of statins are muscle pain, fatigue, liver damage, digestive disorders, high blood sugar, and risk of type 2 diabetes. Less well-known but common problems in people taking statins are memory and thinking disorders, similar to dementia. The side effects of cholesterol pills worry people who take them. There are suspicions that pharmaceutical companies are trying to downplay the frequency of problems with their drugs.

Side effects of statins: detailed article

An increased risk of statin side effects is in people who:

taking multiple cholesterol medications at the same time (don't do this!);
over 65 years old;
suffer from kidney or liver disease;
drink a lot of alcohol.

Drinking plenty of alcohol is more than two drinks a day for men under the age of 65. For men over 65 years of age, as well as for all women, no more than one serving of alcohol per day is allowed. One serving of alcohol is 10-15 grams of pure alcohol. One can of beer 0.33 l, one glass of wine or a glass of strong 40-degree liquor. If you drink more alcohol than indicated above, then you should not be treated with statins in order to avoid liver problems. Discuss this with your doctor.

Latest generation statins: rosuvastatin

If you have a high risk of heart attack and stroke, then you should take statins, despite the possible side effects. High-risk patients are patients with hypertension, diabetes mellitus, coronary heart disease, atherosclerosis of the lower extremities, as well as people who have undergone stenting or coronary bypass surgery. They should stop statins only if the side effects become intolerable. Because no other drugs and dietary supplements can significantly reduce the risk of a cardiovascular catastrophe and prolong life.

Pain in muscles and joints	The most common side effect. Muscle problems can be mild discomfort or severe enough to interfere with your daily life. For example, it will become difficult to climb stairs or even walk.
Rhabdomyolysis	The destruction of muscle tissue, as a result of which substances that damage the kidneys enter the bloodstream. The patient feels acute pain and symptoms of kidney failure. A deadly but extremely rare side effect.
Liver damage	Taking statins can cause worse blood test results for ALT, AST, and other liver enzymes. But this does not mean that the liver is broken. Typically, patients do not experience any symptoms. There is no need to stop taking medication. In 2012, the US Department of Health (FDA) reported that the danger of statins to the liver is less than previously thought.
Digestive disorders	Taking statins can cause nausea, bloating, diarrhea, or constipation. In fact, this rarely happens. But statins can exacerbate digestive disorders that the patient already had before starting treatment with cholesterol drugs. Try taking the medicine in the evening with food.
Increase in blood sugar	Statins increase blood sugar and increase insulin resistance. People who are predisposed to type 2 diabetes have an increased risk of developing the disease. It is worth worrying for patients with metabolic syndrome - overweight, hypertension, poor blood tests for cholesterol and triglycerides. However, you can take preventive measures and not stop taking statins.
Thinking and memory disorders	Pharmaceutical companies pretend that these side effects of cholesterol pills do not exist. In fact, they are very common, creating many problems for patients and their relatives. For example, the patient may forget where he was going and who he even is. There may be lapses in memory for recent events.

When selecting and adjusting the dosage of statins, you need to focus less on "bad" and "good" cholesterol, and more on. The main goal of taking medications is not to reduce "bad" cholesterol, but to extinguish chronic sluggish inflammation. Watch the video to find out if you need to take these drugs or not.

Read in detail about the inflammatory nature of cardiovascular diseases in the article "". Watch how the results of blood tests for C-reactive protein change under the influence of statins. You may find that taking the minimum dosage of these drugs is enough for you. And the lower the dosage, the lower the risk of side effects.

Detailed information about medicines:

How to counteract the side effects of statins

If you are concerned about muscle weakness, then another 1-2 grams can be added to coenzyme Q10. The daily dose of this remedy can be divided into 2 doses, always on an empty stomach.

Muscle pain caused by statins cannot be controlled with non-steroidal anti-inflammatory drugs. Try not to take ibuprofen, acetaminophen (paracetamol) and other NSAIDs once again. From the side effects of statins, they will not help, and they will create an additional load on the liver.

Effective Coenzyme Q10 supplements from the USA, optimally priced:

- with hawthorn extract
Japanese Coenzyme Q10 Prepackaged Doctors' Best - Best value for money
- Japanese product, best quality

How to order Q10 and other supplements from the USA on iHerb - or . Instruction in Russian.

It can be difficult to determine what the unpleasant symptoms you are experiencing are. Are these side effects of statins or natural aging disorders? To figure it out, you will have to, in agreement with the doctor, take a break for 10-14 days in taking the medicine. Assess how different you feel when you take statins and when you don't. In fact, problems with muscles and joints in most cases are caused by a sedentary lifestyle, and drugs have nothing to do with it. Unfortunately, instead of getting moving, the sick prefer to complain about the side effects of the pills that the villainous doctor has prescribed for them.

Try switching from one statin to another, strictly on the advice of your doctor. It is possible that atorvastatin and rosuvastatin are less likely to cause side effects than simvastatin. These drugs rarely have negative interactions with other drugs. Do not change the medicine you are taking on your own! Check with your doctor. Some patients who switch to atorvastatin or rosuvastatin do not get better, but worse than they did when they took simvastatin.

Atorvastatin preparations: instructions for use

Carefully read the information about the interaction of the statin you have been prescribed with other medicines. There can be problems with blood pressure pills, heart rhythm disorders, antibiotics, antifungals, antidepressants, immunosuppressants, and many other drugs. Tell your doctor about all medications, supplements, and herbs you are taking before you are prescribed a statin. Rosuvastatin may be less likely to cause drug interaction problems than previous generation statins. Discuss with your doctor.

In addition to statins, there are other pills that lower blood cholesterol. These are bile acid sequestrants, fibrates, cholesterol absorption inhibitors in the intestine (ezetimibe). They do not reduce the risk of heart attack, stroke, and death from all causes, so don't take them even if your doctor tells you to. If you have elevated blood triglycerides, then do not take fibrates, but instead switch to. Triglycerides will return to normal in a few days. Do not take any other cholesterol medication in combination with statins.

Also watch the video "Statins for Cholesterol: Information for Patients".

How to normalize cholesterol without statins

Statins are often prescribed for people who have high cholesterol but no other risk factors for heart disease. For these patients, the side effects of statins will outweigh the possible benefits. To normalize cholesterol without harmful drugs, go on a low-carb diet and follow the other steps indicated in the article "".

Watch yours more closely than your cholesterol. Because C-reactive protein and other markers of inflammation are strong predictors of heart attack and stroke risk, and cholesterol often lies. Half of cardiovascular accidents happen to people who have normal blood cholesterol. Statins not only normalize cholesterol, but also reduce chronic sluggish inflammation. Many experts believe that this is their main therapeutic effect.

The above explains why patients at high cardiovascular risk should take statins. It details how to determine if your risk is high or low. Statins are not considered the main drug, but only complementary to a healthy diet and physical activity. Even if you started taking these pills, no one cancels the need to lead a healthy lifestyle.

Frequently Asked Questions and Answers

Can statins cause anxiety, depression, cloudy thinking?

Yes, all the symptoms you mentioned can be side effects of drugs that normalize cholesterol in the blood. The article above tells how to figure out what happened to you - age-related disorders or drug side effects.

I have been taking cholesterol pills for 7 years after my heart attack. Recently, I have been worried about the deterioration of memory for recent events. What to do?

Study the section of this article "How to normalize cholesterol without statins" and do what it says. At the very least, you can reduce the dosage of drugs, or even completely abandon them. If you've had a heart attack, you're at high risk of having another heart attack. This means that stopping statins should only be done as a last resort.

It worries that I have heaviness in my legs, swelling, shortness of breath, it is difficult to climb stairs. Are these side effects of statins?

Yes, all the symptoms you listed can be side effects of statins. The question makes you suspect that you are developing heart failure. Statins can make it worse because they deplete coenzyme Q10, a substance involved in energy production in the heart. Learn and do what it says. Cancel statins only in consultation with your doctor, who will evaluate the balance of benefits and harms from these pills for you.

Can statins cause leg cramps?

Basically, they can. But rather, the reason is the lack of magnesium in the body. Just in case, get blood and urine tests that check if your kidneys are working well. If everything is fine with the kidneys, then take large doses for leg cramps. You need these pills at the dosages listed on the site, not the low doses that doctors usually prescribe them for.

Can statins cause low testosterone levels in men?

They can because testosterone is made from cholesterol. And you didn't know that? Well, you have to...

Study the section "How to normalize cholesterol without statins" and do what it says. Try to reduce the dosage of statins. Find a smart urologist and discuss with him how to increase testosterone levels. This may turn out to be an effective measure, but only as prescribed by a doctor, without fanaticism, no self-treatment. Try to raise your blood testosterone to the middle of the normal range. This can improve not only your personal life, but also your cholesterol levels and lower your cardiovascular risk. In no case do not use "underground" products that are sold in sex shops.

Statins, specifically designed for lipid-lowering treatment, have gone far beyond their original use due to their large number of pleiotropic effects. The concept of "pleiotropy" implies: the effect of the drug on several targets, triggering various biochemical processes in the body. In addition to lipid-lowering effects, statins have a number of pleiotropic effects, such as an effect on endothelial function through an increase in nitric oxide (NO) production, an anti-inflammatory effect, which is mediated by a decrease in the production of pro-inflammatory cytokines and C-reactive protein by statins, anti-ischemic and antioxidant effects. Statins stabilize atherosclerotic plaque by increasing its collagen content and inhibiting metalloproteinases. Also, statin therapy affects myocardial hypertrophy, fibrosis, and the hemostasis system. The pleiotropic effects of statin therapy include immunosuppressive action, preventing the development of osteoporosis by increasing the production of bone-forming protein growth factor 2 and osteoblast maturation. Thus, the pleiotropic effects of statin therapy offer advantages over other lipid-lowering drugs, since they are available and can be used not only in the treatment of cardiovascular pathology, but also in other diseases.

polymorbidity

pleiotropic effect

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4. Nikitina N.M., Rebrov A.P. The place of statins in the complex therapy of patients with rheumatoid arthritis // Consilium Medicum. - 2009. - No. 4. .- S. 76-86.

5. Kausik K. Ray, Christopher P. Cannon. The Potential Relevance of the Multiple Lipid-Independent (Pleiotropic) Effects of Statins in the Management of Acute Coronary Syndromes. // Journal of the American College of Cardiology. - 2005. - Vol. 46.- P. 1425-1433

6. Ridker P.M., Rifai N., Stampfer M.J., Hennekens C.H. Plasma concentration of Interleukin-6 and the Risk of Future Myocardial Infarction Among Apparently Healthy Men. // Circulation. - 2000. - Vol. 101. - No. 15. - 1767-1772.

7. Sager P.T., Melani L., Lipka L. Effect of coadministration of Ezetimibe and Simvastatin on High-Sensivity C-Reactive Protein // Am J. Cardiol. - 2003. - Vol. 92. - No. 12. - 1414-1418.

8. Schonebeck U., eVaro N., Libby P. Soluble CD40L and cardiovascular risk in women. // Circulation. - 2001.-V. 104.-2266-2268.

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Introduction. The concept of "pleiotropy" implies the effect of the drug on several targets, triggering various biochemical processes in the body; divergence of biochemical and pathophysiological processes emanating from the main (single) target.

The aim of our study was the study of the pleiotropic effects of statin therapy and their role in overcoming the problem of polymorbidity, as well as the development of a classification of the pleiotropic effects of statins.

Material and methods: analysis of periodical literature over the past 5 years, Internet resources.

Results and discussion

Effect of statins on the functional state of the endothelium

In recent years, a positive effect of statins on endothelial function and arterial stiffness has been demonstrated. Statins restore the ability of the endothelium to vasodilate by increasing the production of NO (nitric oxide) by the endothelium through the mechanism of enhancing the expression of NO synthetase. This effect develops as a result of both the lipid-normalizing action of statins and independently of it. Thus, by activating protein kinase B (serine/threonine kinase Act) directly in endothelial cells, phosphorylation of eNOS (endothelial NO synthase) causes an increase in NO production when simvastatin is administered. The result of the inhibition of an excess of one of the main blockers of eNOS activation by the formation of a heterocomplex with this enzyme, caveolin-1, is the stimulation of NO production, which is achieved when using statins at very low concentrations (0.01 nmol), i.e. much smaller than needed for NO production (10 nmol). Thus, this action of atorvastatin can be regarded as lipid-independent, in other words, as a manifestation of a pleiotropic effect.

One of the main vasoconstrictors synthesized directly in the endothelium is the peptide endothelin-1 (ET-1), the content of which is increased not only in severe atherosclerosis, but also in its early stages, as well as in the presence of dysfunction of the coronary arteries.

Effect of statins on inflammatory factors

In patients with atherosclerosis, certain cellular and humoral changes occur. The activity of cytokines, acute phase proteins, growth factors, and adhesion molecules increases. It has been established that the main factor initiating the synthesis of C-reactive protein (CRP) by hepatocytes is cytokines, primarily interleukin-6 (IL-6). Since CRP, interleukins, and adhesion molecules are inflammatory markers, a decrease in their level can be regarded as a positive effect. The mechanism of CRP reduction under the influence of statins is being actively studied at the present time. Statins reduce the expression of the IL-1 family of interleukins, which have a pro-inflammatory action, reduce the level of soluble protein (sCD40L) associated with the tumor necrosis factor TNF-L. A high level of sCD40L is associated with an increased rate of recurrence of cardiovascular events. Anti-inflammatory effects of statins are also known, such as their effect on leukocyte activation and reduction of CRP levels. It has been shown that the pro-inflammatory cytokine tumor necrosis factor, which impairs endothelial function, can be inhibited in macrophages during statin therapy.

Anti-ischemic effect of statins

There is evidence in favor of the anti-ischemic effect of statins. An example of the protective, anti-ischemic effect of statins is the fact that the administration of high doses of atorvastatin (80 mg / day) within a time interval of 24-96 hours after an ACS episode reduced the risk of cardiovascular events (“endpoints”) such as death, non-fatal acute myocardial infarction (AMI), sudden death, the number of recurrent episodes of acute coronary syndrome (ACS), by 16%, which served as the basis for cooperative large-scale projects AZ (Aggrastat-to-zocor), PAEIT (Pravastatin or Atorvastatin Evaluation and Infection Therapy ) and PACST (Pravastatin in Acute Coronary Syndromes Trial).

Moreover, in animal models ( in vivo) in the vast majority of observations, the effects listed above were obtained using such low doses of statins that they cannot affect lipid levels or are not able to cause significant inhibition of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase. Assessing this “disappointing” fact from the position of a practicing cardiologist, it can be noted that it is this fact that indicates the potential ability of statins to cause various pleiotropic effects, the prospect of using which may be extremely important.

Antioxidant effect of statins

The antioxidant effect of statins is associated with a reduction in the synthesis of free oxygen radicals. This leads to a decrease in the formation of oxidized LDL (low density lipoproteins), and therefore slows down the accumulation of cholesterol in macrophages, inhibits the formation of foam cells, reduces their cytotoxicity, reduces the level of activity of inflammatory processes, which also inhibits atherogenesis.

Influence statin therapyon the cellular components of atherosclerotic plaque,macrophage activation, cell proliferation and apoptosis

An unstable plaque, ready for rupture and cracking, is characterized by the fact that its thinned fibrous-altered coating (“cap”) contains many lipoproteins, single SMCs (smooth muscle cells) and an excessive number of macrophages. The latter play a key role in destroying the plaque extracellular matrix by either phagocytosis or the secretion of proteolytic enzymes such as matrix metalloproteinases (MMPs). Statins stabilize atherosclerotic plaque by increasing its collagen content and inhibiting metalloproteinases. Statins can affect the composition of the plaque by blocking the accumulation of macrophages in monocytes or by reducing the content of free cholesterol (CS), as well as by reducing the synthesis of mevalonate and its derivatives responsible for the esterification of cholesterol.

The initial manifestations of atherosclerosis are characterized by proliferation and migration of SMCs. This process is pathogenetic, determining in terms of the progression of vascular damage in patients with postoperative restenosis and occlusion of venous grafts.

It has been established that the maximum decrease in cholesterol synthesis in the cell culture of patients treated with fluvastatin is observed 1 hour after taking the drug, while the maximum effect of inhibition of SMC proliferation is observed after 6 hours, i.e. with a low (not peak) concentration of a statin in the blood. The experiment found that lipophilic (atorvastatin, simvastatin and lovastatin) and hydrophilic statins (pravastatin) have different effects on the proliferation of vascular SMCs and cell apoptosis, which may be due to their different ability to penetrate into the cell. These data are consistent with the results on the final effect of various statins on neointimal thickening of the carotid artery due to SMC proliferation in rabbits. In particular, it has been shown that lovastatin, simvastatin and fluvastatin, in contrast to pravastatin, have an antiproliferative effect, and cerivastatin has the greatest effect on the process of SMC proliferation, while simvastatin, fluvastatin and atorvastatin have a less pronounced effect; pravastatin has the least effect. The described pleiotropic effects of statins in relation to the processes of apoptosis and cell proliferation can only be considered as potentially useful for practicing cardiologists, since there is no clinical confirmation of this action to date.

Effect of statins on myocardial hypertrophy

Many experimental studies have shown that statins can contribute to the regression of cardiac hypertrophy and fibrosis by affecting the mechanisms involved in the onset and progression of cardiac muscle remodeling, for example, by affecting signaling molecules that control the function of contractile proteins and are involved in the process of cardiac remodeling. by influencing collagen I as well as the heavy chain fatal myosin enzymes, or by reducing the effect of intracellular Ca2+ accumulation associated with anoxia. It is possible that in addition to the rapid favorable effect of statins on endothelial dysfunction of the coronary vessels, which is closely related to the prognosis of the course, in acute coronary syndrome, its cardioprotective effect plays an important role in the positive effect of large doses of atorvastatin (MIRACL, 2001).

Statins and hemostasis

In the early stages of treatment with statins, their antithrombogenic activity is manifested: activation of fibrinolysis, suppression of procoagulative activity of the blood. A positive effect of statins on hemostasis and vasoregulatory ability of the vascular wall in patients with unstable angina has been shown. During therapy with atorvastatin, a significant decrease in platelet aggregation was observed after 2 weeks of its use. There was a decrease in the level of fibrinogen by 2-10% during therapy with atorvastatin or the absence of changes in its level.

A number of studies have demonstrated the positive effects of HMG-CoA reductase inhibitors on fibrinolysis parameters. During therapy with pravastatin, a decrease in the level of PAI-1 antigen by 26-56% was noted. Similar effects have been described for lovastatin, atorvastatin, simvastatin, and fluvastatin.

Statins and atherosclerotic plaque vascularization

Angiogenesis is enhanced under conditions of local tissue hypoxia, and this process is likely aimed at restoring blood flow under conditions of ischemia. So, in patients with coronary heart disease (ischemic heart disease), angina attacks stimulate the development of collateral blood supply. On the other hand, angiogenesis is also observed in atherosclerotic plaques, which has a negative effect on the course of the disease. An increase in the content of vascular endothelial growth factor in the blood serum is observed in patients with elevated blood cholesterol levels, regardless of the presence of atherosclerosis. Fluvastatin leads to both a decrease in lipid levels and a decrease in the content of vascular endothelial growth factor. It is a fact that the introduction of vascular endothelial growth factor to animals leads to an accelerated increase in the size of atherosclerotic plaques and an increase in the content of macrophages and endothelial cells in them (Celletti F.L., Waugh J.M., 2001). In this context, the report that simvastatin suppresses the expression of this factor in the coronary arteries and this action is independent of its lipid-lowering effect is of great importance. Another factor in atherogenesis are matrix metalloproteinases responsible for extracellular proteolysis. Fluvastatin, simvastatin and cerivastatin inhibit the secretion of macrophage matrix metalloproteinases. These data indicate that the inhibitory effect of statins on individual components of the angiogenesis process may manifest itself in the antiangiogenic effect.

The immunosuppressive effect of statins

In connection with the rapidly increasing number of patients with coronary artery disease who undergo surgery on the vessels of the heart, the property of statins to prevent the development of atherosclerosis in bypassed vessels, as well as in the arteries of the transplanted heart, is becoming increasingly important. An unusually rapid progression of atherosclerosis of the coronary arteries after heart transplantation to recipients has been established.

With regard to the prevention of fractures of the bones of the lower extremities and pelvis in the elderly, it was found that taking simvastatin and lovastatin reduces the risk of fractures by 45-71%, including in postmenopausal women - by 51%. This is due to the ability of statins to stimulate the production of bone-forming protein factor 2 for the growth of proliferation and maturation of osteoblasts, which not only prevents the development of osteoporosis, but also promotes the formation of bone tissue.

Conclusion

Thus, the most promising is further more in-depth study of the pleiotropic effects of statins and their application in clinical practice, which may lead to a decrease in polymorbidity.

Pleiotropic effects of statins

Influence on the functional state of the endothelium.
Effect of statins on inflammatory factors.
Anti-ischemic action of statins.
Antioxidant effect of statins.
Influence on cellular components of atherosclerotic plaque, macrophage activation, cell proliferation and apoptosis.
Effect of statins on hemostasis.
Effect of statins on angiogenesis.
Effect of statins on myocardial hypertrophy.
Effects not proven in large studies:

antiarrhythmic action;
slowing the progression of Alzheimer's disease and dementia;
immunosuppressive action;
injury prevention.

In the future, the use of this classification will allow more targeted and targeted study of the pleiotropic effects of statins and in the future to apply them in practice.

Reviewers:

Ilnitsky A.N., Doctor of Medical Sciences, Professor of the Department of Medical Rehabilitation of the Polotsk State University, Novopolotsk.
Pavlova T.V., Doctor of Medical Sciences, Professor, Head. Department of Pathology, Belgorod.

Bibliographic link

Fesenko E.V., Proschaev K.I., Polyakov V.I. PLEIOTROPIC EFFECTS OF STATIN THERAPY AND THEIR ROLE IN OVERCOMING THE PROBLEM OF POLYMORBIDITY. // Modern problems of science and education. - 2012. - No. 2.;
URL: http://science-education.ru/ru/article/view?id=5773 (date of access: 01/30/2020). We bring to your attention the journals published by the publishing house "Academy of Natural History"