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I. ДИАГНОСТИКА И ЛЕЧЕНИЕ
мрнти 76.29.48 FEATURES OF THE CARDIOVASCULAR SYSTEM OF A WOMAN DURING
ABOUT THE AUTHORS
Gulim Akhmetovna Aldangarova -doctor of medical sciences, gynecologist, National Scientific Surgical Centre named after A.N. Syzganov, head of the department of postgraduate continuous professional education. Course of Obstetrics and Gynecology of the Kazakhstan-Russian Medical University, Almaty, Kazakhstan, tel: +77772221878.
E-mail: [email protected]
Gulbanu Azimkhanovna Zhaymurzaeva -
Master student of the Kazakh National University. E-mail: [email protected]
Zhansaya Bauyrzhanovna Musabekova
- Resident Obstetrician - Gynecologist of theKazakhstan-Russian Medical University.
E-mail:[email protected]
Kuat Bayandyevich Abzaliyev - head of the Department of Cardiovascular Surgery of the Kazakh Medical University of Continuing Education,doctor of Medical Sciences, professor.E-mail: [email protected]
HORMONAL ADJUSTMENT
Keywords
cardiovascular diseases, physiological hypogonadism, surgical hypogonadism, estrogen
Aldangarova G.A.13, Zhaymurzaeva G.A.2, Musabekova Zh.B.3, Abzaliyev K.B.4
1National Scientific Center of Surgery named after A.N. Syzganov, 2Kazakh National University named after Al-Farabi, 3Kazakhstan-Russian Medical University,
"Kazakh Medical University of Continuing Education, Almaty, Kazakhstan
Abstract
In connection with the increase in the life expectancy of women, the issue of improving the quality of life of a woman becomes urgent.One of the most frequent pathologies leading to disability and high mortality of women is cardiovascular disease. Globally, mortality from cardiovascular diseases among older women continues to rise compared with men, but this issue has not been given due attention so far. In recent years, interest in the problem of gender differences in risk factors for CVD has attracted the attention of the medical community. The particular course of cardiovascular diseases in women and the effects of steroid sex hormones on cardiovascular system allowed us to determine the protective effect of estrogen on the cardiovascular system. The success of solving this problem depends largely from continuity in the joint work of gynecologists and cardiologists.
Эйел агзасындагы гормональды кайтакуру кезецшдеп XYpeK-кантамыр жуйесшщ ерекшелiктерi
АВТОРЛАР ТУРАЛЫ
Алдангарова Г.А.-м.г.д., А.Н.
Сьжанов arbiHMaFbi YFXO Fылыми кызметкер!,Казакстан-Ресей Медицина Университету ЖОО-дан кей!нп бл!м беру кафедрасыныц мецгершю!. Тел.: +77772221878.E-mail: [email protected]
Жаймырзаева Г.Э.- Казак, Улттык Университет1ну магистранты.
E-mail: [email protected]
Мусабекова Ж.Б - Казахстан Ресей медицина университету^ резидент акушер -гинекологы.
E-mail:[email protected]
Абзалиев К.Б.- м.Ед., профессор, МВА, Казак Медицинлык узд!кс!з бш!м беру университету кардиохирургия ангио-жэне рентгенэндоваскулярлы хирургия курсымен кафедрасыныу мецгерушю!, E-mail: [email protected]
Туйш сездер
журек-кантамыр аурулары, физиологиялык гипогонадизм, хирургиялык гипогонадизм, эстроген.
Алдангарова Г.А.13, Жаймырзаева Г.Э.2, Мусабекова Ж.Б.3, Абзалиев К.Б.
1 АК, «А.Н. Сьстанов атында?ы Улттык Рылыми Хирургия орталь™»,
2 Эл-Фараби атында?ы Казак ¥лттык Университету 3Казакстан-Ресей Медицина Университету
4Казак Медицинлык Yздiксiз 6miM беру университету Алматы, Казакстан
Ацдатпа
дйeлдeрдiн eMipcYpy узакты^ынын есуне байланысты ейелдн eMip сапасын жаксарту езет месeлeлeрдiн алдыцры катарында.Эйелдер арасында мугедекткке жэне елiмге екелетн жи кездеселн патологиялардын 6ipi журек-кан тамырлары аурулары болып табылады. Еуропа елдернде ересек ейeлдeрдiн арасында журек-кан та-мырлары ауруларынан болатын елiм-жiтiм ерлермен салыстырганда артуда, бiрак бул меселеге бупнп кунге дeйiн назар аударылмаган.
Со^ы жылдары журек-кан тамырлары ауруларынын кауп факторларында€ы гeндeрлiк айырмашылыктары медицина корамдаспрынан езiнe кеп назар аудартуда. Эйелдердеп журек-кантамыр ауруларынын ерекше агымы жене стероидт жыныс гормондардын журек-кан тамырлары ауруларына есeрiн кeшeндi зерттеу эстрогeндeрдiн журек -кантамыр жуйесне протективт есeрiн аныкгауга мумюн^к бeрдi. Онын шeшiмiнiн табысы непзнен гине-кологтар мен кардиологтардын б'рлескен щмысындагы сабактастыкка байланысты.
4
Особенности сердечно-сосудистой системы женщины в период гормональной перестройки
Алдангарова ПА.13, Жаймырзаева Г.А.2, Мусабекова Ж.Б.3, Абзалиев К.Б.4
1АО «Национальный Научный центр хирургии имени А.Н.Сызганова», 2Казахский Национальный Университет имени Аль-Фараби, 3Казахстанско-Российский Медицинский Университет,
"Казахский Медицинский Университет непрерывного образования, Алматы, Казахстан
Аннотация
В связи с увеличением продолжительности жизни женщин актуальным становится вопрос улучшения качества жизни женщины. Одной из наиболее частых патологий приводящих к инвалидизации и высокой смертности женщин является сердечно-сосудистые заболевания (ССЗ). Во всем мире смертность от сердечно-сосудистых заболеваний среди женщин старшего возраста продолжает повышаться по сравнению с мужчинами, однако этому вопросу до настоящего времени не уделяется должного внимания. В последние годы интерес к проблеме гендерных различий в факторах риска ССЗ привлекает внимание медицинской общественности.Особое течение сердечнососудистых заболеваний у женщин и влияния стероидных половых гормонов на на сердечно-сосудистую систему (ССС) позволило определить протективное влияние эстрогенов на сердечно-сосудистую систему.Успех решения данной проблемы во многом зависит от преемственности в совместной работе гинекологов и кардиологов.
ОБ АВТОРАХ
Алдангарова Г.А. - д.м.н.,научный сотрудник ННЦХимени А.Н. Сызганова,зав. кафедрой послевузовской подготовки по акушерству и гинекологии Казахстанско-Российского Медицинского Университета. Тел.: +77772221878 E-mail: [email protected]
Жаймырзаева Г.Э. - магистрант Казахского Национального Университета имени Аль-Фараби
E-mail: [email protected]
Мусабекова Ж.Б - резидент акушер -гинеколог Казахстанско- Российского Медицинского Университета. E-mail:[email protected]
Абзалиев К.Б.-д.м.н, профессор, МВА, заведующий кафедрой кардиохирургии с курсом ангио и рентгенэндоваскуляр-ной хирургии Казахского медицинского университет непрерывного образование. E-mail: [email protected]
Ключевые слова
сердечно-сосудистые заболевания, физиологический гипогонадизм,хирургический гипогонадизм, эстроген
Since the beginning of the XX century, there is a tendency to increase the life expectancy of the population, which has a huge impact on the structure of society. According to the Organization for Economic Co-operation and Development (OECD) average life expectancy in the world for 2016 was 80.6 years, this figure reaches 78.3 years for males and 83.6 years for females.
According to the Ministry of Healthcare of the Republic of Kazakhstan for 2016 average life expectancy was 72 years, 67.5 years for males and 76.5 years for females.
Cardiovascular disease (CVD) is not accidentally called the "epidemic of the XXI century." Despite improvements in the quality of diagnosis and treatment of CVD are still the leading cause of death worldwide, more than 17.5 million people die per year from CVDs according to World Health Organization (WHO).
The most common cause of death for Americans were the CVD, from CVD on average die 168.5 people per 100 thousand people.
According to WHO, due to diseases of the circulatory system the mortality rate in the RK is almost twice as high as in the European countries. Over the past ten years, the incidence rate of CVD in Kazakhstan has increased 1.7 times. There is also evidence of a fourfold increase in hospitalization due to chronic heart failure (CHF) compared to a period of 20 years ago.
According to the UN 52 million women will be aged 55 years and elder in 2020, and in 2050,
women aged 60 years and elder get closer to 1 billion. Due to the increase in life expectancy, a third of the life of a woman spends in menopause. At the beginning of the XXI century, every second woman of the world will be over 45 years old, therefore improving the quality of life expectancy of women of pre-and postmenopausal age have health and socio-economic value [1.3].
In recent years, interest in the problem of gender differences in CVD risk factors has attracted the attention of the medical community. It is known that women of reproductive age are 4-6 times lower than the incidence of CHD and 2 times lower risk of myocardial infarction (MI) in CHD, compared with men of the same age. [4].
CHD is the cause of death for women in 23% of cases, MI -18% and other CVD-in 15% of observations, while in men these rates are 21%, 11% and 11% respectively [1]. Women have the worst prognosis for CVD compared to men. One in four postmenopausal women dies from CHD, compared to one in thirty who die of breast cancer. Within a year after confirmed AMI, 25% of men and 38% of women die. Among women who underwent MI, due to heart failure 46% are disabled, developing within six years after suffering MI [6].
The peak of CVD in women is 65-75 years old [2]. To understand the development of pathological changes in the cardiovascular system (CVS), it is necessary to take into account that women have smaller chambers of the heart, myocardial thickness, size of coronary arteries, smaller diameter
of the aorta, smaller length of the vascular bed in comparison with men. At rest, the heart rate (heart rate) in one minute in women is 3-5 beats longer, the recovery time of the sinus node function is shorter, the corrected QT interval is longer and women are therefore more sensitive to tachycardia caused by some drugs [7].
Clinical manifestations of coronary heart disease in women are linked to the fact that estrogen deficiency status contribute to the development of dysfunction of small vessels and microvascular ischemia [9,30,31]. It was found that "cardiac syndrome X" (CSX) in women is manifested by typical chest pain, positive stress tests, angiographic normal EPI cardiac coronary arteries and the lack of clinical or angiographic evidence of coronary artery spasm. The frequency of this pathology in the period of pre and post menopause is 80-90% of all cases of CSX. This condition often occurs against the background of systemic endothelial dysfunction, which is typical for women in the period of menopause and is eliminated by the introduction of exogenous estrogens [9,30,31]. Data from a metaanalysis of 25,000 patients showed that among patients with proven stable angina pectoris, atypical pain syndrome was significantly more common in women than in men [23]. The prevalence of atypical pain syndrome in women is associated with a higher incidence of vasospastic component and microvascular ischemia [23,17]. Features of the clinical course of coronary heart disease in women are that very often there are difficulties in the interpretation of pain. In women, more often than in men, the pain is atypical, observed not only in the chest, but can be in the neck, arm, shoulder, abdomen; occur at rest or during sleep. In addition, symptoms such as nausea, shortness of breath, and epigastric discomfort predominate in women [23,17]. The type of pain syndrome also allows assessing the prognosis of the disease in female patients. Most studies have shown that the likelihood of serious coronary events is much higher in patients with typical pain syndrome. According to the J.M. Zamanet al. (2008), a typical pain syndrome in women with chronic CHD was associated with a high risk of coronary death or the development of acute coronary syndrome. At the same time, no such connection was found in the male population. In the study by K.A. Milneret al. (2008) there is also a high probability of development of a serious coronary event in patients with typical CHD pain syndrome [23]. Moreover, a long-lasting typical pain syndrome, even in intact coronary arteries, is a high-risk marker [24]. In his article, Bugiardini (2010) summarized these data as follows: "nonspecific chest pain syndrome and normal coronary angiography data are not synonymous
with good prognosis in women." An interesting fact is that, according to Richards H. M., et al. (2002) even when women had complaints typical of stable angina pectoris, they were still less likely than men to be referred for coronary angiography.
Diagnosis of coronary heart disease in women also presents certain difficulties. Even with a typical pain syndrome (angina), a significant part of them with angiography find unchanged (or with hemodynamically insignificant lesions) coronary arteries(VA). According to the authors, in women more often (in 65% of cases) MI occurs without Q wave and slightly higher ejection fraction (EF) in the first 10 days of the disease [2,7]. When analyzing the depth of myocardial damage in women, it was found that small-focal MI was observed in 65%, large - focal - in 21% and transmural-in 14% of patients. A higher percentage of small-focal myocar-dial damage is probably due to two reasons: first, the peculiarities of coronary circulation in women (in particular, a significant "depletion" of oxygen in the subendocardial myocardium) and, secondly, a more frequent lesion of small branches of the coronary arteries. Unstable angina pectoris and AMI without ST - segment elevation are more common in women, while acute coronary syndrome (ACS) in the form of AMI with ST-segment elevation is more common in men [2]. Perhaps this is due to the peculiarities of coronary arteries [17].
An important feature of the course of coronary artery disease in women is a more frequent lesion of small, rather than main coronary arteries. Coronary angiography very often reveals intact coronary arteries even in the presence of typical angina pains and reduction of regional blood flow in the myocardium [7]. Angiographic studies have shown that the left coronary artery (LCA) and its anterior interven-tricular branch in women have a smaller diameter regardless of body size. The collateral network is also less developed, and the diameter of the vessels is smaller. When carrying out coronary ventriculography (CVG) in women, one or two vessels are more often diagnosed, whereas in men, the lesion of the trunk of the LCA or three CA is more often observed [17].
When performing tests with dosed physical activity (DPA) performed on a Bicycle Ergometer or treadmill, their specificity, according to Stangl M., Witzel M., Baumann P., et al. (2008), in women was lower and ranged from 33 to 73%, compared to 7489% in men. The frequency of false-positive results varied from 25% in typical angina to 50% in atypical pain syndrome [17].
Myocardial ischemia is often painless in the form of the diagnosed with Holter ECG monitoring (HM ECG). In General, the sensitivity of HM ECG is
44-81%, and specificity - 61-85%. Daily ECG monitoring is less informative than samples with DPA. This method is of particular value for the detection of vasospastic angina, and can also be used as a screening in patients with risk factors (RF) and a family history of cardiovascular diseases.
Moreover, menopause itself can be considered as a risk factor for the development of cardiovascular diseases, which causes a number of changes in the woman's body, including abdominal obesity, the emergence of insulin resistance, increased sympathoadrenal tone, hypertension, dyslipidemia, Pro-inflammatory and Pro-atherogenic effects, en-dothelial dysfunction through the direct influence of estrogen deficiency on the cardiovascular system.
Experimentally (Nofer JR 2012, Wang et al. 2013, Knowlton AA et al. 2014) established the presence of estrogen receptors (ER) on endothelial, smooth muscle cells of the heart and blood vessels, cardiac fibroblasts, and macrophages (MP), mono-cytes, mast and dendritic cells, components of the renin-angiotensin-aldosterone system (RAAS). The biological effect of estrogen is realized by two main mechanisms: genomic and non-genomic effects through estrogen receptors (ER) -a and-p.
Genomic (slow) effects lead to long-term effects, reducing the response to vessel damage and preventing the development of atherosclerosis. Estrogens, interacting with intracellular ER-a and ER-p, regulating the expression of certain gene complexes, stimulate the synthesis of protein molecules that inhibit the processes of cellular free radical peroxidation. This blocking of tissue oxidative stress protects against endothelial damage. It is proved that ER vessels can be transcriptionally activated without connection with estrogen, and by direct phosphorylation of the receptor by various kinases (ligand-independent activation of the re-ceptor).The non-genomic (fast) effect of estrogens is manifested by dilation of vessels by increasing the synthesis of nitric oxide (NO). In caveola membranes of endothelial cells to estrogen receptors in the process of using proteinkinase phosphorylation cascades activate endothelial NO-synthase [7,8]. Endothelium is the most vulnerable in the CS for various pathogenic effects, being on the border between circulating blood and tissues. One of the main mechanisms of the influence of estrogen on the cardiovascular system and, in particular, on the endothelial cells is the regulation of the synthesis of nitric oxide (NO), which is a potent endogenous vasodilator, causes relaxation of smooth muscles of blood vessels, has anti-inflammatory effect on the endothelium through the inhibition of leukocyte attraction and formation of reactive oxygen species,increases neovascularization through the
increase of migration to the ischemic tissue and proliferation of differentiated endothelial cells of blood vessels [9].
According to Grodstein et al. (2007) estrogens have a direct vasodilative effect on arterial vessels, including coronary arteries. The mechanisms of estrogen vasodilatation action differ depending on their dosage: when using high doses through smooth muscle cells of vessels, direct action is detected, and at low doses, vasodilatation is mediated primarily due to changes in the activity of endothelial factors - increase in the formation of nitric oxide, prostacycline, decrease in the synthesis of endothelin-1 and thromboxane B-2 [16].
Estrogens can reduce the level of active vasoconstrictor peptide endothelin-1 and the number of receptors to it, which affects vascular tone [10]. In recent years, data on the positive effect of estrogen on the components of the vascular wall on such characteristics of vascular tone as compliance have been accumulated - index, quantitatively expressing extensibility, which is mainly used by foreign authors) and resistance: inhibition of the processes of vascular wall fibrosis by reducing the synthesis of collagen and elastin in smooth muscle cells, reducing migration and proliferation of smooth muscle cells, inhibition of endothelial cell apoptosis [16]. Estrogens have an anti-apoptotic effect on various cell types, including endotheliocytes by reducing the release of cytochrome C from mitochondria, thus acting through a receptor-independent pathway, it also inhibits the expression of the Fas ligand, affecting the receptor-mediated pathway [12,13].
Examined the effects of estrogen on the cells-precursors of endothelial cells. It was experimentally established that women with high estrogen levels in the blood have a greater number of circulating endothelial progenitor cells [14]. Estrogens have antiarrhythmic and cardioprotective effects, this is due to the non-genomic mechanisms that block the channels of CA L-type exerting a negative inotropic effect [18].
Estrogens increase HDL by 20-30%. This effect is mediated by increasing the production of apoli-poprotein AI and reducing its clearance rate [11]. The contents of HDL is directly proportional to the estrogen level and inversely proportional to the content of progesterone [7].
Estrogens reduce HDL-C levels by 10-20% by enhancing receptor elimination of HDL by liver cells [11].
In Europe and Russia, the most common scale of risk assessment SCORE (SystematicCoronar-yRiskEvaluation), and the U.S. - Fremingham risk scale (FraminghamRiskScore). It is shown that when using the Fremingham scale, taking into ac-
count age, hypertension, Smoking, diabetes and hyperlipidemia, the majority of middle-aged people are classified as patients with low or moderate risk, and > 3/4 women under 80 years have a 10-year Fremingham risk of CVD < 10%, which does not accurately reflect the situation [9]. Therefore, experts are increasingly stating the need for cardiological studies with a wider inclusion of women, and that it is necessary to take into account the specific risk factors for women in the prognosis of CVD in women.The Reynolds risk assessment algorithm (ReynoldsRiskScore) was developed specifically for the assessment of cardiovascular risk in women in the United States.The main difference between this scale and the fremingham scale Is the inclusion of family history data on CVD and levels of highly sensitive C-reactive protein, as well as accounting for the level of glycated hemoglobin in patients with diabetes mellitus. When using this scale in a study of Women sHealthStudy 15% of women with moderate risk were reclassified in patients with a high risk [31,32].
The list of traditional risk factors in men and women is the same, but some of them are Smoking, type 2 diabetes and hypertension, women are more important than men [5]. An interesting fact is that Smoking more than 5 cigarettes a day helps to reduce the level of estrogen and in this way launches another, specific for women, risk factor - hypoestr-ogenemia. According to Nurse'shealthstudy, when Smoking up to 14 cigarettes a day, the relative risk of coronary heart disease is 2.1, and when Smoking up to 25 cigarettes - increases to 6. It should be noted that menopause is not the only risk factor for coronary heart disease, specific for women. These factors include preeclampsia, diabetes in pregnant women, polycystic ovary syndrome, androgen levels after menopause.
Without a doubt, surgical and early menopause of other Genesis are important, modifiable risk factors. Now the role of such factors as metabolic disorders in pregnancy and childbirth, late pregnancy is considered. Of particular importance in women is the level of C-reactive protein (CRP) and the early appearance of cardiovascular disease in the family (for women - before 65 years). At the moment, risk assessment systems specific to women are proposed. Most famous among them are the system Reynold (ReynoldsRiskScore) and is specific to women scale obtained from the analysis of survey data WHI (WomenHealthInitiative) [23].
The identification and control of risk factors (FR) is essential as a preventive measure to reduce the level of CVD in both women and men. Due to the fact that the prevalence of RF remains quite high in the population, this is the basis for the widespread
introduction of measures for their primary and secondary prevention.
Unmodified RF include: sex, age (older than 45 years in men and older than 55 years in women), burdened hereditary history (early onset of coronary artery disease in close relatives: myocardial infarction or sudden death in men < 55 years, in women < 65 years).
The main modified RF include: dyslipidemia, hypertension, Smoking, impaired glucose tolerance or type 2 diabetes,abdominal obesity, low physical activity.
It is advisable to consider in more detail the most significant CVD risk factors. According to who, three RF plays a significant role in the development of premature mortality from CVD: the first most important RF -arterial hypertension (AH) in menopause is one of the most important but modifiable risk factors (RF) for CVD [25]. According to the data of the S. Wassertheil-Smoller et al., the prevalence of hypertension in postmenopausal women is about 40%, while in women aged 65 years and older its frequency is 3 times higher compared to women 45-54 years. With the exception of the influence of other risk factors (age, violation of fat and carbohydrate metabolism, overweight), the onset of menopause increases the risk of hypertension by almost 2 times. Before menopause, hypertension occurs much less frequently in the female population than in men, which is to some extent explained by the multidirectional effects of testosterone and estrogen on the cardiovascular system [1].
Hypertensive syndrome is observed in 15-30% of pregnant women, which not only causes serious complications during pregnancy and childbirth, but also has an adverse effect on the long-term prognosis in the mother. The development of preeclampsia during pregnancy is a specific risk factor for CVD in women [7].
Deficiency of sex hormones disrupts the function of the vascular endothelium and the balance between different vasoactive substances, the functioning of smooth muscle cells of blood vessels, leading to an increase in peripheral vascular resistance and, as a consequence, the level of blood pressure (BP).The presence of arterial hypertension in a woman at the time of menopause significantly increases the likelihood of developing diastolic dysfunction of the left ventricle. Left ventricular diastolic dysfunction occurs in half of patients with early menopause and in 3/4 patients with late menopause [26].
For hypertension in premenopause characterized by: activation of the sympathoadrenal system, hyperkinetic state of blood circulation, clinical manifestations of autonomic dystonia, the prevalence of
increased systolic blood pressure with a moderate increase in diastolic blood pressure. For hypertension in pre - and postmenopausal characterized by universal mechanisms: the gradual development of menopausal metabolic syndrome, delay in the body of sodium chloride and water.Postmenopausal hypertension is characterized by gradual progressive activation of the components of the renin-angioten-sin-aldosterone system, transformation of the type of blood circulation into hypokinetic, increase in total peripheral resistance, a significant increase in systolic and diastolic blood pressure, and in older age groups - isolated systolic hypertension.
Complications of hypertension occupy the first place in the structure of mortality in the female population. In women older than 45 years, more often than in men, hypertension is detected with a predominance of isolated increase in systolic blood PRESSURE. Another equally important factor is dyslipidemia, a recognized risk factor for CVD in both women and men. It is known that hyperin-sulinemia during menopause affects the activity of lipoprotein lipase, and in the case of RI, the level of non-esterified fatty acids increases, which contributes to enhanced Tg synthesis and a decrease in HDL levels. These and other changes in the spectrum of lipoproteins are well known in perimeno-pausal women: along with hypertriglyceridemia, there was an increase in total cholesterol, HDL and lipoprotein-(a) subfraction (LP(a)), a decrease in HDL, especially in the 2nd subfraction.
In addition, estrogen-deficient "unoccupied" estradiol estrogen receptors located in the endothelium promote the introduction of HDL into the vascular wall [27]. At the same time, low levels of HDL and hypertriglyceridemia are more significant risk factors for CVD, in particular CHD, for postmenopausal women than for men [26]. Jensen J. et al. specify that the levels of total cholesterol, low-density lipoproteins most significantly increased after 6 months after the termination of menstruation, the level of high-density lipoproteins decreases for 2 years before menopause. However, elevated levels of cholesterol and HDL are important risk factors for heart disease in men but not in women, while low HDL levels and high levels of TG, Smoking and hypercholesterolemia are considered to be more important risk factors in women [9].
The third RF is Smoking.The prevalence of tobacco Smoking among modern women is high, while there is an Association of Smoking with an earlier onset of menopause and a decrease in the density of estrogen receptors on the cells of some tissues. The frequency of tides among smokers is directly correlated with the number of cigarettes smoked. It is known that Smoking contributes to
the development of endothelial dysfunction, various hemorheological disorders and dyslipidemia, increases the production of free radicals [26]. It is proved that Smoking contributes to the development of oxidative oxidative stress, which is manifested by the activation of lipid peroxidation processes with an increase in the content of oxidized HDL in the blood, a decrease in the enzyme paraoxonase that protects lipoproteins from oxidative modification. Due to structural damage of endothelium by toxins and free radicals of tobacco smoke, endothelium-dependent vasodilation of peripheral and coronary arteries is disturbed.A study conducted among young women (16-44 years), showed that Smoking 3 to 6 cigarettes a day the risk of death from THEM they doubled. For women and men Smoking 20 cigarettes a day, the risk of CONTRACTING it increased by 6 and 3 times, respectively, compared to non-smokers [22].
Along with dyslipidemia, another risk factor-increased body weight and obesity-is of great im-portance.The tendency of women after menopause to increase the proportion of adipose tissue in the body-a known fact. Abdominal obesity is a recognized independent risk factor for CVD because it is associated with insulin resistance and is closely related to accelerated atherogenesis [26]. The frem-ingham study found a twofold increase in the risk of coronary heart disease in obese women, compared with women without it. The study "Nurseshealth-Study" showed an increase in the risk of coronary heart disease in 2-3 times in women with obesity, compared with those with normal body weight. This risk persists even when other risk factors are controlled [28].Weight gain is observed in 75-80% of women with the beginning of perimenopause, especially expressed in postmenopause. According to Shestakova (2001), in women aged 52.6y5.3 years, the increase in body weight is 5-24kg (9.7y4.2 kg) compared with reproductive age. According to data from M. J. Toth et al.(2000) the character of fat deposition in menopause does not depend on the age and degree of obesity, but depends only on the cessation of ovarian function: already in early postmenopause,the volume of fat in the hips is 36% more, and the volume of intraabdominal fat is increased by 49% compared to women, whose ovarian function is preserved. Obesity in menopause is accompanied by a decrease in weight that does not contain fat,including muscle tissue. Studies using dual-energy x-ray absorptiometry revealed a progressive decrease in the "low-fat" mass in the body and limbs [27]. Women with abdominal obesity (an-dromahi) significantly more often suffer myocardial infarction, strokes and die suddenly than women with obesity of the female type (gynecomasty) or
with normal body weight. The appearance of the first clinical signs of CHD in andromorphic women is noted at a young age [28]. Euroaspire demonstrated that visceral obesity (waist circumference over 80 cm in women and 94 cm in men) is more common among women (70%) than among men (46%) suffering from coronary heart disease [19].
One of the most significant RF is diabetes melli-tus (DM) and glucose metabolism disorders. Menopause is accompanied by a violation of glucose tolerance: every year after the termination of ovarian function, this probability increases by 6%.
Fremingham study showed that the risk of coronary heart disease in men with diabetes is 2.4 times higher than in men without diabetes, while in women with diabetes this risk is 5.4 times higher than in women without diabetes. In the study "Nurse-shealthStudy" it was shown that in women with diabetes the overall risk of cardiovascular mortality is 6.3 times higher than in women without diabetes [28]. Elevated fasting plasma glucose levels, impaired glucose tolerance, and type 2 diabetes are common risk factors for CVD in postmenopausal women [26]. Hyperactivity of the sympathetic nervous system observed in menopause causes stimulation of gluconeogenesis, glycogenolysis in the liver, reduces glucose uptake by skeletal muscles, which leads to the development of hyperglycemia and hyperinsulinemia. Hyperinsulinemia leads to the development of insulin resistance, which in combination with hyperglycemia also contributes to the development of endothelial dysfunction. Hyper-glycemia, in turn, contributes to the accumulation of end products of glycosylation of proteins in the subendothelial space and activation of free radical processes with an increase in the production of superoxide anions. The end products of glycosyl-ation are atherogenic factors due to their ability to increase endothelial permeability and stimulate smooth muscle cell proliferation [10]. Against the background of diabetes in women, the risk of atherosclerosis increases by 3-4 times, and in men by 2 times. A major European epidemiological study, DECODE, assessed the causes of cardiovascular mortality in women and men with normal blood
pressure and hypertension, and in the presence or absence of diabetes. It was demonstrated that the risk of mortality in women was 2 times higher than in men with the combination of hypertension and diabetes mellitus [7].
Pregnancy-a state of physiological insulin resistance, so in itself is a significant risk factor for carbohydrate metabolism. Gestational diabetes mellitus (GDM) is a risk factor for obesity, type 2 diabetes and CVD in mother and offspring in the future. The frequency of gestational diabetes in the General population of different countries varies from 1% to 20%, averaging 7%. These variations are due to differences in the methods of its diagnosis and are directly related to the prevalence of type 2 diabetes in certain ethnic groups. According to the literature, in 20-50% of women who have had GDM, it occurs during subsequent pregnancy, and in 25-75% - 16-20 years after birth develops manifest diabetes [29].
Due to the increase in the life expectancy of women, the increase in the retirement age, as well as the fact that this is the age of realized women who have reached professional heights, are more often in leadership positions and engaged in mental activities, the issue of improving the quality of life of women, as a third of her life falls on postmeno-pause. One of the most frequent pathologies leading to disability and high mortality of women is CVD. Despite advances in the diagnosis, prevention and treatment of CVD, disability and mortality remain high and tend to increase, particularly among women. In recent years, interest in gender differences in CVD risk factors has attracted the attention of the medical community. The study of risk factors for CVD in women showed the most important role in the development of cardiovascular disease plays a decrease in ovarian function. A comprehensive study of the effect of steroid sex hormones on CS allowed to determine the protective effect of estrogen on it. Analysis of available literature on gender cardiology has shown the need for further study of this problem. The success of its solution largely depends on the consistency in the joint work of gynecologists and cardiologists.
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