What you need to know about atherosclerosis

School of Pharmacologist: what you need to know about atherosclerosis
L.K.Ovchinnikova, R.I.Yagudina, E.A.Ovchinnikova
FSU "NCESMP" of Roszdravnadzor, I.M.Sechenov MMA
Magazine "Russian pharmacies" No. 14-2007.Diseases of the cardiovascular system occupy a leading place among the causes of mortality and disability in Russia and abroad.

One of the factors of the development of severe lesions of the heart and blood vessels is a violation of lipid (fat) metabolism in the body, leading to the occurrence of atherosclerosis. Atherosclerosis is a systemic disease; with its development, there may be a predominant lesion of one or more departments, but all the vessels of the body suffer to one degree or another.

EpidemiologyAtherosclerosis has been recognized as one of the most urgent diseases of the past twentieth century.

It is in the top four most common diseases and causes of death. This was the basis for calling atherosclerosis the "plague" of the twentieth century.

Cardiovascular diseases, the main cause of which are atherosclerotic vascular lesions, occupy a leading place as a cause of mortality in most economically developed countries of the world. Mortality in cardiovascular pathologies is twice as high as from cancer, and 10 times higher than from accidents. According to data for 2005, mortality from heart and vascular diseases among the male population of Russia was 1,810 per 100,000 people. Such a high indicator cannot but affect the life expectancy, which in Russia is extremely short and, according to the same data, is 58.9 years (for men). For comparison: in Japan, the average life expectancy of men is 87 years, in the European Union – 80, in the USA – 75. It should be noted that for 20 years in the USA and Finland, the state program for the prevention and treatment of atherosclerosis and its complications has been successfully carried out, as a result of which mortality from coronary heart disease and other cardiovascular pathologies decreased by 2-3% annually. As a result, over 20 years it was possible to reduce mortality by more than 50%. The decrease in the frequency of deaths from major cardiovascular diseases in these countries was parallel to the decrease in the average level of cholesterol in the blood of the adult population. Thus, one of the approaches that contribute to increasing the duration and improving the quality of life of patients with cardiovascular diseases is the fight against atherosclerosis or dyslipidemia.

Etiology and pathogenesisSo, what is the essence of atherosclerosis?

In this disease, the inner surface of the arteries is affected due to the deposition of cholesterol in the form of plaques having an uneven surface protruding into the vessel. As a consequence, this leads to narrowing of the vascular lumen and obstruction of blood flow. There can be a lot of such plaques, they literally line the inner surface of the vessels. In places where endothelial cells cease to function, platelets settle, their aggregation process occurs with the formation of a blood clot in the future. Sometimes formed blood clots or parts of them come off and are transferred with the blood flow to smaller vessels, causing their blockage. Similar injuries occur in all vessels, but the coronary vessels and vessels of the brain are most often affected. But peripheral circulatory disorders based on arteriosclerotic damage are primarily manifested by pathology of the vessels of the lower extremities.

One of the main causes of atherosclerosis is a violation of cholesterol metabolism in the body. Cholesterol is a complex chemical compound belonging to the class of lipids. Lipids (including cholesterol) in the human body are localized in cells, intercellular fluid and in the blood. In the blood, i.e. in an aqueous medium, the molecules of hydrophobic lipids cannot be in a free state, and therefore they exist only in a protein–bound form - in the form of lipoproteins (LP). It is lipoproteins that are actively involved in the formation of cholesterol plaques. But they also participate in the reverse process – the process of regression of atherosclerosis. Such a contradictory effect of lipoproteins is due to their heterogeneity.

There are 5 classes of lipoproteins, of which three classes are of the greatest importance – alpha-lipoproteins, or high-density lipoproteins (HDL), beta-lipoproteins, or low-density lipoproteins (LDL) and pre-beta-lipoproteins, or very low-density lipoproteins (VLDL). At the same time, LDL and VLDL have an atherogenic effect, while HDL have the opposite, anti-atherogenic effect. Thus, cholesterol metabolism is regulated in the body, and it is in violation of this regulation that atherosclerosis (or, more precisely, dyslipidemia) can develop.

The main risk factors and predisposing factors for the development of atherosclerosis (dyslipidemia) are:

• hypertension;
• an increase in the level of LDL and VLDL against the background of a decrease in the content of HDL;
• diabetes mellitus;
• physical inactivity;
• fatness;
• belonging to the male sex (men usually get sick 10 years earlier and much more often);
• age (usually older than 35-45 years);
• genetic factors - the presence in the family history of cases of early atherosclerosis;
• psychological features – impulsive people are more often affected by atherosclerosis.

The provoking factors ("catalysts") of atherosclerosis include stressful effects and smoking abuse.

Concerning some pathogenetic nuances of the disease, we add that hyperglyceridemia is usually combined with obesity. In postmenopausal women, the prevalence of clinical manifestations of atherosclerosis increases and approaches the indicator characteristic of men of the corresponding age group.

Prevention of atherosclerosisSince the main risk factor for the development of atherosclerosis is a violation of the ratio of LDL and VLDL in the blood on the one hand and HDL on the other, the main preventive approach is to optimize the diet and fight obesity.

Smoking increases the risk of developing peripheral artery lesions, so you should give up cigarettes, especially for people burdened with other risk factors for cardiovascular diseases or genetic predisposition.

In patients suffering from arterial hypertension, it is necessary to monitor the daily profile of blood pressure. It has been shown that drug pressure control in hypertensive patients reduces the risk of strokes by 40%, myocardial infarction – by 8%, and overall mortality from cardiovascular diseases - by 10%. There are reports that regular physical activity reduces the incidence of myocardial infarction and overall mortality from cardiovascular diseases and contributes to an increase in HDL levels in the blood.

Treatment of dyslipidemiaTreatment of dyslipidemia (atherosclerosis) is a complex process, including diet, exercise and the use of medications.

Diet is a very important factor contributing to the regression of atherosclerosis. It is necessary to limit the consumption of animal fats, fatty meats and dairy products and, conversely, include vegetable oils, products from coarse flour and sea products, as well as food components containing large amounts of vitamin B6, soy products, vegetables in the diet.

As for the drug therapy of atherosclerosis (hyperlipoproteinemia, dyslipidemia), representatives of the following groups of medicines are used in our country today:

• statins;
• nicotinic acid;
• derivatives of clofibric acid (fibrates);
• cholesterol absorption inhibitors;
• hypocholesterolemic drugs of the second row (auxiliary drugs).

We should add that more recently, drugs from the group of anion–exchange resins (sorbents of bile acids) - colestyramine and colestipol were used for the treatment of dyslipidemia. However, today no drug based on these compounds has a valid registration in Russia.

You can read about the properties and the procedure for the use of individual representatives of these categories of drugs in the heading "Algorithm for choosing and offering drugs". Within the framework of this article, we would like to focus in more detail on statins, since they are the most effective hypocholesterolemic drugs (first-line therapies) and at the same time the safest.

The first representative of the statin group was obtained in 1976 by a group of Japanese researchers, but did not find clinical use. In 1980 Merck scientists discovered a second drug, which 7 years later was introduced into clinical practice under the name lovastatin and is still the reference agent of this group of compounds.

The mechanism of action of statins is associated with their ability to block HMG-CoA reductase, an enzyme involved in the synthesis of cholesterol, and mainly in the liver. As a result, the concentration of cholesterol in hepatocytes decreases. As a result, the expression of LDL receptors increases, so liver cells begin to capture cholesterol from the blood, as a result of which its need for cholesterol is satisfied. This contributes to a further drop in its concentration in the blood, while lowering the level of cholesterol, which is absorbed into the blood from food. Statins are active agents that reduce LDL, but they are inferior to fibrates in their ability to reduce plasma triglycerides and increase HDL. Since the maximum synthesis of cholesterol occurs at night, it is rational to take drugs of this series in the evening.

During the first passage through the liver, all HMG-CoA reductase inhibitors undergo intensive metabolism, only 5-20% of the administered dose remains in the blood. Most primary drugs and their metabolites (β-hydroxy acids) are 95% bound to plasma proteins; the exception is pravastatin. After oral administration , the maximum serum concentrations of statins are reached after 1-4 hours . Approximately 70% of the metabolites are excreted with bile. About 30% of lovastatin and up to 85% of simvastatin are absorbed in the intestine; then they are activated in the liver. The main way of excretion is with bile.

In general, the choice and combination of medications for the treatment of dyslipidemia depends on the qualitative and quantitative indicators of various fractions of lipoproteins and cholesterol in the blood, as well as on the safety spectrum of a particular drug and the presence of relative and absolute contraindications for its administration to a particular patient. In addition to the medications described above, in the clinic of hyperlipidemia and atherosclerosis, various phytopreparations and some dietary supplements can be used as additional therapy (for more information about these drugs, see RA No. 7, 2007).