Type II hyperlipidemia. Hyperlipoproteinemia type II. Diseases associated with changes in cholesterol levels

Hyperlipidemia (hyperlipoproteinemia)- abnormally elevated levels of lipids and / or lipoproteins in the blood of a person. Violation of lipid and lipoprotein metabolism is quite common in the general population. Hyperlipidemia is an important risk factor for the development of cardiovascular diseases, mainly due to the significant influence of cholesterol on the development of atherosclerosis. In addition, some hyperlipidemias affect the development of acute pancreatitis.
Classification
Classification of lipid disorders based on changes in the profile of plasma lipoproteins during their electrophoretic separation or ultracentrifugation. However, it does not take into account the level of HDL, which is an important factor in reducing the risk of atherosclerosis, as well as the role of genes that cause lipid disorders. This system remains the most common classification.

Type I hyperlipoproteinemia
A rare type of hyperlipidemia that develops in LPL deficiency or a defect in the LPL activator protein, apoC2. Manifested in an increased level of chylomicrons, a class of lipoproteins that carry lipids from the intestines to the liver. The frequency of occurrence in the general population is 0.1%.

Hyperlipoproteinemia type II
The most common hyperlipidemia. It is characterized by an increase in LDL cholesterol. It is subdivided into types IIa and IIb depending on the absence or presence of high triglycerides.
Type IIa
This hyperlipidemia can be sporadic (due to malnutrition), polygenic, or hereditary. Hereditary hyperlipoproteinemia type IIa develops as a result of a mutation in the LDL receptor gene (0.2% of the population) or the apoB gene (0.2% of the population). The familial or hereditary form is manifested by xanthomas and early development of cardiovascular disease.
Type IIb
This subtype of hyperlipidemia is accompanied by an increased concentration of triglycerides in the blood as part of VLDL. A high level of VLDL occurs due to the increased formation of the main component of VLDL - triglycerides, as well as acetyl-coenzyme A and apoB-100. A more rare cause of this disorder may be delayed clearance (removal) of LDL. The frequency of occurrence of this type in the population is 10%. This subtype also includes hereditary combined hyperlipoproteinemia and secondary combined hyperlipoproteinemia (usually in metabolic syndrome).
Treatment for this hyperlipidemia includes dietary modification as a major component of therapy. Many patients require the appointment of statins to reduce the risk of cardiovascular disease. In the case of a strong rise in triglycerides, fibrates are often prescribed. The combined use of statins and fibrates is highly effective but has side effects such as the risk of myopathy and should be under constant medical supervision. Other drugs (nicotinic acid, etc.) and vegetable fats (ω 3 fatty acids) are also used.

Hyperlipoproteinemia type III
This form of hyperlipidemia is manifested by an increase in chylomicrons and LPP, therefore it is also called dis-beta-lipoproteinenia. The most common cause is homozygosity for one of the apoE isoforms, E2/E2, which is characterized by impaired binding to the LDL receptor. The occurrence in the general population is 0.02%.

Type IV hyperlipoproteinemia
This subtype of hyperlipidemia is characterized by an elevated concentration of triglycerides and is therefore also called hypertriglyceridemia. The frequency of occurrence in the general population is 1%.

Type V hyperlipoproteinemia
This type of hyperlipidemia is in many ways similar to type I, but is manifested not only by high chylomicrons, but also by VLDL

Fundamentals of diagnosis

• Plasma total cholesterol exceeds 200 mg/dl on two samples at least 2 weeks apart;
• Low-density lipoprotein (LDL) cholesterol greater than 100 mg/dL;
• High-density lipoprotein (HDL) cholesterol less than 40 mg/dL;
• Triglyceride levels are greater than 200 mg/dL.

• Hypothyroidism raises LDL cholesterol levels.
• Eating causes an increase in triglyceride levels.
• Diabetes is accompanied by an increase in triglyceride levels, a decrease in HDL cholesterol.
• Alcohol consumption causes an increase in triglyceride levels.
• Taking oral contraceptives causes an increase in triglyceride levels.
• Nephrotic syndrome causing high LDL cholesterol levels
• In kidney failure, LDL cholesterol and triglycerides increase.
• Primary biliary cirrhosis increases LDL cholesterol levels.
• In acute hepatitis, triglyceride levels rise.
• Obesity increases triglyceride levels.

• Exercise, weight loss, high fiber diet.

• Intestinal endothelial blockers: ezetimid.
• Fibric acid derivatives: gemfibrozil, clofibrate, fenofibrate.
• A nicotinic acid.
• Hepatic 3-methylglutaryl reductase inhibitors: atorvastatin, pravastatin, simvastatin.

Hyperlipidemia is a violation of lipid metabolism with an increased content in human blood. This disorder is a risk factor for the development of cardiovascular diseases and pancreatitis.

Causes and symptoms of hyperlipidemia

Hyperlipidemia can provoke the deposition of atherosclerotic plaques and the development of vascular atherosclerosis. An excess amount of lipids affects the active formation of cholesterol and calcium deposits. With a large excess of lipids, blood circulation worsens and the likelihood of developing coronary disease, heart attack, aortic aneurysm and cerebrovascular accidents increases.

The causes of hyperlipidemia can be blood pressure disorders, obesity, diabetes mellitus and old age. The development of the disease is facilitated by a sedentary lifestyle, kidney and thyroid diseases, smoking and drinking alcoholic beverages.

Symptoms of hyperlipidemia are mild, and the disease is detected using a biochemical blood test. Hyperlipidemia can manifest itself as a hereditary disease, and the risk of its occurrence increases after 40 years.

Some medications cause increased accumulation of lipids in the body. These include: estrogens, hormonal and contraceptive drugs, diuretic drugs.

Types of hyperlipidemia

There are five main types of hyperlipidemia, which differ in the factors that lead to the development of the disease and the degree of its progression. The general classification of lipid disorders was formed by the scientist D. Fredrickson in 1965 and adopted as the official version by the World Health Organization.

The first type of hyperlipidemia is the rarest and develops with a deficiency of the LPL protein, and also causes an increase in the content of chylomicron.

Hyperlipidemia type 2 is the most common form of the disease and is associated with high triglycerides.

A lipid disorder of a sporadic or hereditary type is caused by genetic mutations and a family predisposition to develop cardiovascular disease.

A special subtype of hyperlipidemia is a violation of clearance, as well as an increased content of acetyl coenzyme and triglycerides.

The third type of hyperlipidemia is manifested in an increased amount of chylomicron and LDLR caused by disorders of the LDL receptors.

The fourth and fifth types of the disease are the most rare and are accompanied by an increased concentration of triglycerides.

Treatment of hyperlipidemia

Treatment of hyperlipidemia begins with establishing the type of disease and the level of lipids in the body. An important component of treatment is a low-calorie diet, which is aimed at reducing the amount of lipids and maintaining their normal levels in the body.

Also, the attending physician prescribes special physical exercises to reduce the content of cholesterol and triglycerides. Eliminating excess weight, regular exercise and the elimination of bad habits will significantly reduce the amount of fat.

The course of treatment for hyperlipidemia includes the following medications:

• statins that lower blood cholesterol and prevent its deposition in the liver;
• choleretic drugs;
• fibrates;
• vitamin B5.

In patients over 50 years of age, the treatment of hyperlipidemia should be complex, with a combination of drug therapy, a special diet, exercise, and therapeutic cleansing procedures.

Video from YouTube on the topic of the article:

Cholesterol on the vessels - the cause of hyperlipidemia

Hyperlipidaemias are common: nearly 25% of the adult population has plasma cholesterol levels above 5 mmol/l. Since this increases the risk of cardiovascular disease, timely treatment of hyperlipidemia is very important. When examining a patient with hyperlipidemia, first of all, its secondary origin should be excluded, that is, the causes should be established, for example, diseases of the liver and biliary system, obesity, hypothyroidism, diabetes mellitus, malnutrition and alcohol abuse. In most cases, hyperlipidemia is multifactorial, i.e. due to both external causes and genetic predisposition. Some forms of hyperlipidemia are primary, genetically determined. This fact is the basis of their classification. When confirming the diagnosis of hyperlipidemia, all members of the patient's family should be examined.

Risk factors

In most patients, hyperlipidemia can only be corrected by an appropriate diet. Significant efforts in clinics during treatment are aimed at eliminating other risk factors in patients with lipid metabolism disorders, such as hypertension, diabetes mellitus, thyroid disease, smoking, as well as correcting impaired lipid metabolism. The use of lipid-lowering drugs is justified only in a relatively small number of patients with large changes in the lipid profile in order to reduce the risk of coronary heart disease.

Biochemical diagnosis is based on the results of a blood test taken from a patient 14 hours after eating. If there is a question about treatment throughout the life of the patient, the study is repeated 2-3 times with a weekly interval. In patients with recurrent myocardial infarction and other severe diseases, the concentration of triglycerides in plasma is increased, and cholesterol is reduced. Their lipid profile is not stable for 3 months after the acute period of the disease. However, the indicators obtained in the first 24 hours after the development of the pathological process, when significant changes in metabolism have not yet occurred, can be considered quite informative.

Lipoproteins and hyperlipidemia

Dietary triglycerides in the bloodstream are converted into chylomicrons, the number of which progressively decreases during lipolysis. This process is carried out with the participation of the enzyme lipoprotein lipase associated with the capillary endothelium in certain tissues, including adipose, skeletal muscle and myocardium. Fatty acids released during lipolysis are taken up by the tissues, and the remaining chylomicrons are eliminated by the liver. Endogenous triglycerides are synthesized by the liver and circulate bound to very low density lipoproteins (VLDLs). They are eliminated from the bloodstream using the same lipolytic mechanism that is involved in the elimination of exogenous triglycerides. Low-density lipoproteins (LDL) formed during the metabolism of triglycerides are the main delivery system for cholesterol in human tissues. These are rather small molecules that, passing through the vascular endothelium, bind to specific receptors with high affinity for LDL on cell membranes and enter the cells by pinocytosis. Intracellular cholesterol is necessary for the growth and repair of membrane structures, as well as for the formation of steroids.

High-density lipoproteins (HDL) are cholesterol-rich particles that act as transport intermediaries that mobilize peripheral cholesterol, for example from the vascular wall, and transport it to the liver for elimination. Thus, they perform the function of protectors in coronary heart disease.

Types of hyperlipidemia

There are several types of hyperlipidemia. Type 1 (rare) is characterized by high levels of chylomicrons and triglycerides in the blood due to lipoprotein lipase deficiency and is accompanied by abdominal pain, pancreatitis, and xanthomatous rashes.

Type 2a (common) is characterized by high blood levels of both LDL and cholesterol and is associated with a risk of coronary heart disease. These patients make up 0.2% of the population, and their familial hypercholesterolemia is inherited as a heterozygous monogenic type, which leads to the premature development of severe heart disease and xanthomatosis.

Type 2b (common) is characterized by a high concentration of LDL and VLDL, cholesterol and triglycerides in the blood and is associated with the risk of coronary heart disease.

Type 3 (rare) is characterized by a high level of so-called floating 3-lipoproteins, cholesterol and triglycerides in the blood due to a hereditary apo-lipoprotein anomaly, combined with xanthomatosis on the palmar surfaces, coronary heart disease and peripheral vascular disease.

Type 4 (common) is characterized by high levels of VLDL and triglycerides in the blood, may be accompanied by obesity, diabetes and alcoholism, leads to the development of coronary heart disease and peripheral vascular disease.

Type 5 (rare) is characterized by high blood levels of chylomicrons, VLDL, and triglycerides. Some of these metabolic changes may be due to alcohol abuse or diabetes. Patients of this type often develop pancreatitis.

Drugs for the treatment of hyperlipidemia

Cholestyramine (Questran) is available in the form of packages containing 4 g of the drug, and is an ion-exchange resin that binds bile acids in the intestine. Bile acids formed in the liver from cholesterol enter the intestine with bile and are reabsorbed in the upper small intestine. In total, the body contains 3-5 g of bile acids, but due to enterohepatic recirculation, which occurs 5-10 times a day, an average of 20-30 g of bile acids enters the intestine daily. By binding to cholestyramine, they are excreted in the feces and the depletion of their reserves in the depot stimulates the conversion of bile acids into cholesterol, as a result of which the level of the latter, in particular LDL, in plasma decreases by 20-25%. However, in some patients in the liver, cholesterol biosynthesis can be increased compensatory. The daily dose of cholestyramine is 16-24 g, but sometimes up to 36 g / day is required to correct the lipid profile. Such a dose is too large (9 packets of 4 g per day), which is inconvenient for patients. Almost half of those who take cholestyramine develop side effects (constipation, sometimes anorexia, bloating, rarely diarrhea). Since the drug binds anions, when combined with warfarin, digoxin, thiazide diuretics, phenobarbital and thyroid hormones, it should be borne in mind that their absorption is reduced, so these drugs should be taken one hour before taking cholestyramine.

Colestipol (Colestid) is similar to cholestyramine.

Nicotinic acid (available in 100 mg) lowers plasma cholesterol and triglyceride levels. Perhaps its action is due to the anti-lipolytic effect in adipose tissue, resulting in a decrease in the level of non-esterified fatty acids, which are the substrate from which lipoproteins are synthesized in the liver. For the treatment of patients with hyperlipidemia, 1-2 g of nicotinic acid is used 3 times a day (normally, the body's need for it is less than 30 mg / day). In this case, the patient often has reddening of the skin of the face and the function of the digestive tract is disturbed. With a gradual increase in dose over 6 weeks, adverse reactions are less pronounced and tolerance develops.

Nicofuranose (tetranicotinoylfructose, Bradilan), a fructose nicotinic acid ester, may be better tolerated by patients.

Clofibrate (Atromid; available in 500 mg doses) inhibits hepatic lipid synthesis, lowering plasma cholesterol levels by 10-15%. In patients with type 3 hyperlipidemia, the effect may be twice as pronounced. Clofibrate is readily absorbed from the gastrointestinal tract and is largely bound to plasma proteins. Its action is terminated as a result of metabolism in the liver, in addition, it is excreted unchanged in the urine. In the amount of 500 mg, it is taken 2-3 times a day after meals. Side effects are mild, but sometimes acute myalgia develops, especially in hypoproteinemic conditions, such as nephrotic syndrome, when the concentration of free substance is unusually high. The results of a placebo-controlled study in which 15,475 patients participated indicate that when using clofibrate for the purpose of primary prevention of myocardial infarction, the incidence of myocardial infarction was 25% lower in patients who received the active drug. However, an increase in the frequency of deaths from diseases not associated with coronary heart disease was unexpected, which remained without explanation (report of the Committee of Leading Investigators. Br. Heart J., 1978; Lancet, 1984). In patients taking clofibrate, the incidence of calculous cholecystitis, which required surgical treatment, increased. When combined with oral anticoagulants, furosemide and sulfourea derivatives, interactions may occur as a result of their competition with clofibrate for association with plasma albumins. In this regard, the concentration in the blood of pharmacologically active non-protein compounds increases, which leads to an increase in the effects of these drugs when administered in therapeutic doses. In many countries, clofibrate is banned for long-term use as a lipid-lowering agent.

Benzafibrate (Bezalip) is similar in action to clofibrate. It lowers plasma levels of triglycerides and cholesterol.

Probucol (Lurcell) increases the excretion of bile acids and reduces the biosynthesis of cholesterol, resulting in a decrease in the concentration of lipids in plasma, both low and high density, with protective properties. Usually the drug is well tolerated by patients, but some of them develop disorders of the digestive tract and abdominal pain.

Treatment of hyperlipidemia depending on its type

Treatment for hyperlipidemia should be carried out subject to certain general provisions. First, you must first try to influence any pathology that can cause lipid metabolism disorders, such as diabetes mellitus, hypothyroidism.

Secondly, they correct the diet: a) reduce the amount of calories consumed in case of excess body weight until it normalizes (of course, it is necessary to reduce the consumption of alcohol and animal fats); the cessation of alcohol consumption is accompanied by a decrease in the level of triglycerides in the blood; b) patients who do not lose body weight or it already corresponds to the norm should eat less fat, animal fats should be replaced with polyunsaturated fats or oils. Adherence to a special diet, such as the exclusion of egg yolk, sweets, meat, is not necessary, since reducing fat intake is quite effective.

Thirdly, appropriate treatment is recommended for certain types of hyperlipidemias.

Type 1 (sometimes type 5). They reduce the amount of dietary fat to 10% of the total calories consumed, which can be achieved by partial replacement of fats with medium chain triglycerides, which, without entering the general circulation as part of chylomicrons, enter directly into the liver through the portal system.

Type 2a. Usually hyperlipidemia is corrected by diet, but in the hereditary form it is almost always necessary to prescribe ion exchange resins (cholestyramine or colestipol), and often other agents.

Types 2b and 4. As a rule, patients suffer from obesity, diabetes, alcoholism, they have nutritional errors. These disorders can be corrected by diet. In resistant cases, nicotinic acid, clofibrate or bezafibrate are additionally prescribed.

Type 3. Diet is usually sufficient for patients, but sometimes they have to prescribe drugs clofibrate or bezafibrate, which are highly effective in this type of hyperlipidemia. Hereditary hyperlipidemias of type 2a and severe types 3, 4 and 5 are difficult to correct; these patients should be examined by a specialist.

What should you do after reading this article? If you suffer from hyperlipidemia, first of all try to change your lifestyle, and then, according to the doctor's recommendation, select the drug. If you are over 40 and you do not know your cholesterol status, do not be too lazy to take a blood test. It is possible that timely treatment of hypercholesterolemia will become an important method for the prevention of cardiovascular diseases. Be healthy!

Overview of drugs used in the correction of dyslipidemia (hyperlipidemia)

Roza Ismailovna Yagudina, d.f. n., prof., head. Department of Organization of Drug Supply and Pharmacoeconomics and Head. Laboratory of Pharmacoeconomic Research of the First Moscow State Medical University named after A.I. I. M. Sechenov.

Evgenia Evgenievna Arinina, Candidate of Medical Sciences, Leading Researcher, Laboratory of Pharmacoeconomic Research, First Moscow State Medical University. I. M. Sechenova

Cardiovascular disease (CVD) is the leading cause of death worldwide. WHO estimates that 17.3 million people died of CVD in 2008, accounting for 30% of all deaths worldwide. 7.3 million of this number died from coronary heart disease. According to WHO forecasts, by 2030, about 23.3 million people will die from CVD every year.

The group of cardiovascular diseases combines several nosological units:

• coronary heart disease - a disease of the blood vessels that supply blood to the heart muscle;
• disease of the cerebral vessels that supply it with blood;
• disease of the peripheral arteries supplying blood to the arms and legs;
• rheumatic heart disease - damage to the heart muscle and heart valves as a result of a rheumatic attack caused by streptococcal bacteria;
• congenital heart disease - deformations of the structure of the heart that have existed since birth;
• deep vein thrombosis and pulmonary embolism - the formation of blood clots in the leg veins that can displace and travel to the heart and lungs.

One of the most common pathologies in the structure of CVD is coronary heart disease (CHD), which we will devote a number of articles to. IHD, according to WHO, is an acute or chronic dysfunction of the heart resulting from an absolute or relative decrease in arterial blood supply to the myocardium.

In more than 90% of cases, the anatomical basis for the development of IHD is damage to the coronary arteries of the heart, leading to a decrease in coronary blood flow and an imbalance between the need for oxygen and nutrients in the heart muscle and the possibilities of blood supply to the heart. Often this effect is caused by dyslipidemia, leading to the development of atherosclerosis, therefore, in the first article on the problem of pharmacotherapy of coronary artery disease, we will dwell on dyslipidemia (hyperlipidemia) in detail.

Currently, the following forms of IHD are distinguished:

• Sudden cardiac arrest
• angina pectoris
• Painless cardiac ischemia
• Syndrome X (microvascular angina)
• myocardial infarction
• Cardiosclerosis (atherosclerosis)
• Heart failure
• Heart rhythm disorders

Types of dyslipidemia

What is it and how to treat? Dyslipidemia (hyperlipidemia) is an increase in lipid and lipoprotein levels relative to optimal values ​​and / or a possible decrease in high-density lipoprotein or alpha-lipoprotein levels. In the group of dyslipidemias, the focus is on hypercholesterolemia, since elevated levels of cholesterol (low-density lipoprotein) are directly associated with an increased risk of coronary artery disease.

In plasma, the two major lipid fractions are cholesterol and triglycerides. Cholesterol (Cholesterol) is the most important component of cell membranes; it forms the "skeleton" of steroid hormones (cortisol, aldosterone, estrogens and androgens) and bile acids. Cholesterol synthesized in the liver enters the organs and tissues and is utilized by the liver itself. Most of the cholesterol in the composition of bile acids is in the small intestine, from the distal parts of which approximately 97% of the acids are absorbed with subsequent return to the liver (the so-called enterohepatic circulation of cholesterol). Triglycerides (TG) play an important role in the process of energy transfer of nutrients into cells. Cholesterol and TG are transported in plasma only as part of protein-lipid complexes - lipoproteins (complexes include a simple protein - protein).

Currently, there are several classifications of dyslipidemia. One of them divides dyslipidemia into types according to the factors of occurrence into primary and secondary.

Primary dyslipidemias are disorders of lipid metabolism, most often associated with genetic abnormalities. These include: conventional (polygenic) and familial (monogenic) dyslipidemia, familial hypercholesterolemia, familial endogenous hypertriglyceridemia, familial chylomicronemia, familial combined dyslipidemia.

Lipoproteins differ in size, density, amount of cholesterol and triglyceride and composition of apoproteins (proteins localized on the surface of lipoproteins - lipoprotein receptor ligand, enzyme cofactors):

• chylomicrons(HM) - saturated TG and poor cholesterol, are formed in the wall of the small intestine from alimentary fats;
• very low density lipoproteins (VLDL) - synthesized in the liver from endogenous sources and contain a lot of TG and little cholesterol. An increase in VLDL levels is associated with an increased risk of atherogenesis;
• low density lipoproteins(LDL) - cholesterol-containing class. Synthesized in the liver, transferring cholesterol to its "consumers" - the adrenal glands, liver, etc. Today, LDL is considered the main atherogenic fraction of lipoproteins and the main "target" for lipid-lowering drugs;
• high density lipoproteins(HDL) is an anti-atherogenic class of lipoproteins that ensures the elimination of excess cholesterol from the walls of arteries and tissues. HDL have a positive effect on the state of the endothelium and prevent the oxidation of LDL.

The classification of primary lipid disorders was developed back in 1965 by the American researcher Donald Fredrickson. It has been adopted by the WHO as the international standard nomenclature for dyslipidemias/hyperlipidemias and remains the most common classification (see Table 1).

Secondary dyslipidemias are lipid metabolism disorders that develop against the background of the following diseases:

• obesity (increased TG levels, decreased HDL-C);
• sedentary lifestyle (decreased levels of HDL-C);
• diabetes mellitus (increased levels of TG, total cholesterol);
• alcohol consumption (increased levels of TG, HDL-C);
• hypothyroidism (increased levels of total cholesterol);
• hyperthyroidism (decrease in the level of total cholesterol);
• nephrotic syndrome (increased levels of total cholesterol);
• chronic renal failure (increased levels of total cholesterol, TG, decreased HDL);
• cirrhosis of the liver (decrease in the level of total cholesterol);
• obstructive liver disease (increased levels of total cholesterol);
• malignant neoplasms (decrease in the level of total cholesterol);
• Cushing's syndrome (increased levels of total cholesterol);
• iatrogenic lesions while taking: oral contraceptives (increased TG levels, total cholesterol), thiazide diuretics (increased levels of total cholesterol, TG), b-blockers (increased levels of total cholesterol, decreased HDL), corticosteroids (increased TG levels, increased total cholesterol ). See table 2 for cholesterol levels.

Treatment of dyslipidemias (hyperlipidemias)

If the patient suffers from coronary artery disease and has dyslipidemia, it is advisable to avoid smoking, control blood pressure, take aspirin, and, if possible, conduct hormone replacement therapy in postmenopausal women. The decision on the need for drug therapy is made based on the level of LDL-C and an assessment of other risk factors for developing coronary artery disease (including HDL values). For people with low HDL levels without an increase in LDL levels, pharmacotherapy is not indicated.

The key to successful correction of secondary hyperlipoproteinemia is the detection and treatment of the underlying disease. For example, rational hormone replacement therapy often normalizes lipid levels in patients with diabetes mellitus and hypothyroidism. With ethanol-induced hypertriglyceridemia, a similar result is achieved by avoiding alcohol.

Currently, several groups of drugs are used to treat lipid profile disorders. Their hypolipidemic effect is based on the ability to reduce the content of atherogenic lipoproteins (LP) in the blood plasma: VLDL, LDL and their lipids - cholesterol and TG. Classes of lipid-lowering drugs and the main indications for their use, see table 3.

Statins

At the present stage of development of medicine, the main class of lipid-lowering drugs used in the treatment of coronary heart disease are statins, which have the largest evidence base. Statins are structural inhibitors of the enzyme hydroxy-methylglutaryl-coenzyme-A-reductase (HMG-CoA), which regulates cholesterol biosynthesis in hepatocytes. As a result of a decrease in the intracellular content of cholesterol, the hepatocyte increases the number of membrane receptors for LDL on its surface. Receptors bind and remove atherogenic LDL particles from the bloodstream and, thus, reduce the concentration of cholesterol in the blood.

Statins also have vascular and pleiotropic effects. At the level of the vascular wall, by reducing the formation of cholesterol and LDL, they increase the ratio of HDL / LDL, reduce the inclusion of cholesterol in the subintima of the vessels, help stabilize existing atherosclerotic plaques by reducing the lipid core, and therefore reduce the risk of plaque rupture and thrombosis.

The classification of HMG-CoA reductase inhibitors is based on differences in statins both in chemical structure (drugs obtained by fermentation of mushrooms and synthetic statins) and in terms of the time they started to be used in clinical practice (statins of the I-IV generation). The first statins (simvastatin, pravastatin and lovastatin) were isolated from a culture of penicillin fungi and Aspergillus terrens fungi; fluvastatin (II generation), atorvastatin (III generation) and rosuvastatin (IV generation) are synthetic drugs. Statins also differ in their physicochemical and pharmacological properties: simvastatin and lovastatin are more lipophilic; atorvastatin, rosuvastatin and pravastatin are more hydrophilic; fluvastatin is relatively lipophilic. These properties provide different permeability of drugs through cell membranes, in particular liver cells. The half-life of statins does not exceed 2-3 hours, with the exception of atorvastatin and rosuvastatin, the half-life of which exceeds 12 hours, which probably explains their higher efficiency in lowering cholesterol and LDL-C.

Side effects: increased levels of liver enzymes, less often - hepatitis, myopathy and myositis, extremely rarely - rhabdomyolysis. These substances can cause headache, abdominal pain, flatulence, constipation, diarrhoea, nausea and vomiting. Methods for monitoring the safety of treatment is the assessment of the activity of transaminases and creatine phosphokinase, which must be carried out before treatment, repeated after 2-3 weeks, 2-3 months. and then every 6-12 months. or more often. Statins should be discontinued if there is a persistent increase in alanine aminotransferase and / or aspartate aminotransferase more than 3 times, with creatine phosphokinase activity more than 5 times normal, or with severe symptoms of muscle damage.

Fibrates

Fibrates are derivatives of fibric acid. Fibrates are lipid-lowering drugs that mainly affect the metabolism of triglyceride-rich lipoprotein particles (HM, VLDL, and DILI). They also moderately lower LDL-C levels by decreasing small, dense LDL particles and increasing large, less dense LDL, which increases their recognition by liver receptors and improves catabolism. Fibric acid derivatives are able to increase the synthesis of "good cholesterol" apoproteins - apo A-I, apo A-II. These drugs improve the lipolysis of TG-rich lipoproteins by activating lipoprotein and hepatic lipases. The pleiotropic and hypolipidemic effects of fibrates are realized through the activation of nuclear α-receptors that activate peroxisome proliferation (PPARα). The use of fibrates leads to a decrease in the level of TG by 20-50 % from the initial level and an increase in the level of HDL-C by 10-20%.

Side effects: digestive disorders, headache, dizziness, skin rashes, sometimes atrial fibrillation, rarely - hematopoietic depression, myositis, visual impairment.

NB! The combined administration of statins and fibrates is highly effective, but has side effects (for example, the risk of myopathy) and should be under constant medical supervision.

ezetimibe

Ezetimibe is a selective inhibitor of cholesterol absorption in the small intestine by inhibiting the activity of the corresponding NPC1L1 transporter. It is a prodrug. After absorption, it is metabolized to the pharmacologically active ezetimibe-glucuronide. In plasma, most (90%) of the drug and its metabolite bind to proteins. Excretion occurs mainly through the intestines.

Side effects: dyspepsia, headache, weakness, myalgia, depression. Less often - hypersensitivity reactions, toxic hepatitis, toxic pancreatitis. Thrombocytopenia, myopathy, and rhabdomyolysis are very rare.

Bile acid sequestrants

The mechanism of action of these drugs (water-insoluble anion-exchange resins that are not absorbed in the intestine) is to bind bile acids in the intestine, which prevents their enterohepatic circulation, as a result of which the liver increases the production of bile acids using cholesterol from its own reserves. The activity of hepatic receptors for LDL increases, and the level of total cholesterol and LDL-C in plasma decreases (by 6-9 and 15-25%, respectively) with a slight increase in HDL. In some patients, the concentration of TG (compensatory synthesis of VLDL) sometimes increases, which requires caution in the use of these drugs in the presence of initial hypertriglyceridemia. At TG levels above 400-500 mg/dL, sequestrants should be discarded.

Side effects: can cause constipation, less often diarrhea, also nausea, vomiting. Sometimes hypertriglyceridemia and a lack of vitamins A, D and K are noted.

A nicotinic acid

When used in a full therapeutic dose (3.5-4 g per day), nicotinic acid reduces the production of VLDL with a secondary decrease in LDL levels (by 15-25 %) and an increase in HDL (by 25-35 %). Nicotinic acid also nearly halved TG and lipoprotein levels. Unfortunately, 50-60% of patients cannot tolerate the full dose. Prostaglandin-mediated flushing of the skin is described by patients as a feeling of "rush", heat, often with itching. This problem is partially solved by prescribing 81-325 g of aspirin per day (or another antiprostaglandin agent) and starting therapy in small doses (50-100 mg at dinner), which are doubled every week to 1.5 g per day. After re-evaluation of the lipid spectrum, the dose is divided into parts and brought up to 3-4.5 g per day.

It is recommended to use short-acting nicotinic acid preparations. Long-acting forms (enduracin) are expensive and reduce LDL-C to a lesser extent. Nicotinic acid can enhance the effect of antihypertensive drugs with a sudden sharp drop in blood pressure.

Side effects: often - redness of the face, dizziness, increased transaminases, dry skin, itching, dyspeptic disorders (loss of appetite, diarrhea, nausea, vomiting, abdominal pain, flatulence). Rarely - insomnia, tachycardia, peripheral edema, increased uric acid levels and the development of exacerbation of gout, gynecomastia and severe liver damage. Very rarely - prolongation of prothrombin time and a decrease in the number of platelets.

Omega-3-polyunsaturated fatty acids

The relevance of the use of omega-3-polyunsaturated fatty acids (omega-3-PUFAs) is associated with the identification of an association between an extremely low level of cardiovascular diseases (atherosclerosis, coronary heart disease, hypertension) in the inhabitants of Greenland and their consumption of a large amount of seafood with a high content omega-3‑PUFA. In the blood plasma of the inhabitants of Greenland, high concentrations of eicosapentaenoic and docosahexaenoic acids were noted, with a low content of linoleic and arachidonic acids. The lipid-lowering effect of fish oil is to suppress the synthesis of VLDL and LDL, to improve their clearance and increase bile excretion.

When using drugs containing eicosapentaenoic and docosahexaenoic acids, the most significant positive effect is observed in patients with dyslipidemia types IIb and V: the content of TG, VLDL and LDL decreases, the level of HDL increases. Metabolites of eicosapentaenoic acid also have antispasmodic and platelet aggregation inhibiting properties. Omega-3-PUFAs have a profibrinolytic effect, reducing the activity of an inhibitor of tissue plasminogen activator, and also reduce the content of fibrinogen.

Side effects: most often - digestive disorders, less often - taste perversion, dizziness, headache, liver damage, hypersensitivity reactions, hyperglycemia, very rarely - arterial hypotension, leukocytosis.