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CARDIOVASCULAR CONSEQUENCES OF INSULIN RESISTANCE: AN
OVERVIEW OF CURRENT EVIDENCE
Badritdinova M.N.
Bukhara State Medical Institute
email: matluba_badritdinova@bsmi.uz
https://orcid.org/0000-0002-7814-4106
Annotation.
However, the literature on the role of NTG as RF CHD differs significantly.
Meanwhile, in some cases, NTG can precede the development of DM and, in a certain sense,
it can be considered as a state of "pre-disease" in relation to DM. Hyperglycemia, including
latent hyperglycemia, often proceeds with hyperinsulinemia, which is considered one of the
components of the "metabolic" syndrome. which plays an important role in the formation of
cardiovascular diseases, including coronary artery disease.
Key words:
Blood pressure, hyperlipidemia, obesity, diabetes mellitus.
Topicality.
The epidemiological situation with regard to coronary heart disease (CHD) in
different regions of the world and in individual populations is very ambiguous. More than 1
million Americans had new cases of CHD or exacerbations of this disease (qualified as
myocardial infarction or fatal CHD). Moreover, 650,000 of them had newly diagnosed CHD,
and 350,000 had an exacerbation of chronic CHD. About 250,000 patients died before the
hospital stage. ventricular fibrillation was observed. The value of the standardized indicator
of CHD prevalence in different cities differed significantly. Thus, the highest value of this
indicator was noted in Baku, Kiev and Moscow (19.5%, 16.4% and 14.5%), and the lowest
it was in Nalchik (6.9%). In Tashkent, the prevalence of CHD was 9.3%. Exertional angina
pectoris is most common among the examined contingents (4.5%), somewhat less often
(3.8%) there are "possible" ischemic changes on the ECG. Past myocardial infarction and
painless forms of CHD are even less common (in 1.3% and 1.5%, respectively), and a
possible history of myocardial infarction (not confirmed by ECG changes) was determined
in 1.0%. Factors contributing to an increase in sudden death, along with such generally
recognized risk factors as high blood pressure, hyperlipidemia, obesity, diabetes mellitus,
etc., also include non-painful myocardial ischemia [9] and untimely establishment (or non-
establishment) of diagnosis [16]. In France, a 20-year study of the causes of death of the
population was carried out, which showed a decrease in mortality from cardiovascular
diseases (CVD) by more than 30% [8]. In this regard, the issue of determining the range of
risk factors for mortality from CHD and the development of adequate methods for the
prevention of this disease is of particular importance. Summary data from studies conducted
in three regions of France, two regions of Italy, two regions of Sweden, Barcelona, Belfast
and Glasgow covered the population aged 35-64 years [10]. The authors concluded that the
mortality rate of the population is influenced by both geographical location and lifestyle, diet
and other factors. At the same time, it has been shown that one of the most important factors
in the increase in mortality from CHD is a very low coverage of treatment of both patients
suffering from CHD and those with high blood pressure.
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Objective:
To study the relationship between insulin resistance and increased cardiovascular
risk.
Introduction:
Large population-based studies conducted by the Center of Cardiology of the
Ministry of Health of the Republic of Uzbekistan indicate the importance and fairly high
effectiveness of preventive measures against cardiovascular diseases [3,2,15]. Preventive
programs implemented in production teams made it possible to increase the effectiveness of
drug control of hypertension by 7 times, reduce the incidence of hypertension by 10%, and
quit smoking up to 25% of men [2]. Multifactorial prevention in general was effective in
both men and women [3]. However, it should be noted that the effectiveness of AH and
smoking prevention was more pronounced among men than among women. Among men
aged 30-59 years in Samarkand, the incidence of coronary artery disease was 3.4% in
normal BP, 7.5% in borderline hypertension, and 16.7% in hypertension, respectively [3,4].
Studies in Tomsk were conducted among 647 patients with CHD, whose average age was
53.1
and 2.36 years, and it was shown that HDL-C has a stabilizing effect on
atherosclerotic plaque and has a positive effect on the course of CHD, as well as to a certain
extent prevents the development of MI [9]. Dyslipoproteinemia in some cases can be a
manifestation of a general hereditary syndrome. In patients with a hereditary burden of
cardiovascular diseases, hypertension was significantly more common among patients with
dyslipoproteinemia than in patients with normolipidemia (20.2% and 12.5%, respectively).
At the same time, the authors support the opinion that excess fat consumption contributes to
an increase in blood cholesterol, and this, in turn, leads to an increase in the risk of
developing CHD.
A certain importance in the development of CHD is given to excess div weight (BMI).
Most researchers note that the frequency of BMI among people engaged in mental work is
higher than among people engaged in physical labor. According to an epidemiological study
in Finland [6], BMI is more common among people with low physical activity than with
normal physical activity. At the same time, the risk of death from CHD among people with
BMI and low physical activity is much higher than the risk of death from CHD among
people with normal div weight and sufficient physical activity. Patients with CHD
suffering from BMI are significantly more likely to have increased anxiety, psychosocial
maladaptation, a higher frequency of cardialgias, and less tolerance to isometric load.
Among people with BMI suffering from CHD, the correlation coefficient between div fat
mass and anxiety level is 0.53
0.09 (p <0.001).
60.6% of angina patients have a BMI [4].
CHD patients with BMI have a low tolerance to physical activity and less efficiency of the
cardiovascular system [6]. It should be noted that impaired central and peripheral
hemodynamics is considered one of the important risk factors for death from cardiovascular
diseases [1]. The importance of tobacco smoking in the development of CHD is so great that
many researchers attach great influence to passive smoking. Although the relationship
between secondhand smoke and CHD has not yet been fully understood, there are reports
that secondhand smoke contributes to the development of CHD [8]. It should be noted that it
is possible to objectively assess the importance of alcohol in the formation of CHD only on
the basis of a multivariate analysis. However, alcohol plays an important role in mortality
from other, non-cardiovascular diseases. Studies conducted in various scientific centers
indicate that the same RF, as well as their combinations, have different prognostic
significance in relation to the development of CHD and the prognosis in this disease.
Therefore, the need for further, in-depth research in the field of RF studies becomes obvious.
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The high importance of DM in the formation of CHD and mortality from it is indicated by
the results of many population studies [13, 15]. A 20-year prospective study conducted in
the UK included 2779 people [2]. Overall, 31.1% of those under observation developed
coronary artery disease. Among patients with diabetes, the frequency of new cases of CHD
was significantly higher and amounted to 57%. In Finland, the prevalence of CHD among
patients with newly diagnosed type II diabetes was studied [2]. It turned out that among
patients in whom DM was detected for the first time, the incidence of CHD was 3 times
higher than in the control group, i.e. among patients without DM. The Oxford study was
conducted over a period of 10 years and included 3055 men suffering from type II diabetes,
whose average age was 52 years [13]. During this period, 335 people developed coronary
artery disease. The significance of such indicators as high- and low-density lipoprotein
cholesterol, triglycerides, SBP, smoking and fasting glucose levels was analyzed. A
pronounced relationship between RF CHD and DM has been established. The greatest
association was established with SBP and low-density lipoprotein cholesterol, i.e. with those
RFs that play an important role in the development of CHD. At the same time, it should be
noted that there are indications in the literature that there is no direct relationship between
DM and CHD [15]. Such a view of this problem is explained by the fact that the
etiopathogenetic aspects of DM and CHD have much in common. The authors believe that
in some cases patients with CHD develop DM, and in other cases, patients with DM develop
CHD. A 9-year prospective follow-up of DM patients showed that DM is a very important
RF of death from CHD [9]. This study found that the mortality rate from CHD per 1000
person-years of observation was 28.4 among patients with DM, and 10.2 among people
without DM. At the same time, the total mortality from cardiovascular diseases in patients
with DM was 39.6 per 1000 person-years of follow-up, and among people without DM –
15.5. It should be noted that mortality from other, non-cardiovascular diseases was 16.6 and
13.5, respectively. The course of MI in patients with diabetes is characterized by a large
number of complications and high mortality. The severity of MI is to a certain extent related
to the severity of DM, and the mortality rate in MI patients in DM patients reaches 54% [9].
In patients with DM, the risk of recurrent MI is significantly higher, and the survival rate is
significantly lower than in patients without DM [3]. The presence of DM increases the
likelihood of rupture of the left ventricular wall in MI [2]. Along with a higher incidence of
chronic pain-free CHD in patients with diabetes, pain-free cases of MI are also more often
observed [13]. It should be noted that not all authors share the opinion about a higher
incidence of CHD without pain forms among patients with diabetes. As a result of a study
based on a retrospective analysis of the prognostic significance of the appearance of pain-
free myocardial ischemia during exercise on treadmills, the authors concluded that the
incidence of pain-free myocardial ischaemia does not depend on the presence of diabetes
[15]. Higher mortality from CHD in patients with diabetes is to a certain extent associated
with such a factor as ethnicity [14]. A comparative analysis of mortality from acute MI in
South Asia showed that out of 149 Asians and 313 whites admitted to the clinic with acute
MI, there were significantly more whites alive than Asians [13]. It should be noted that
among Asians admitted to the hospital, the incidence of diabetes was 38%, and among
whites - 11%. At the same time, a study conducted among 150 Europeans and 77 Africans
suffering from insulin-independent diabetes showed that Africans have a lower risk of
developing cardiovascular diseases than whites [7]. Various RF CHDs are significantly
more common among patients with diabetes than among people without diabetes [5].
Patients with CHD [6] with DM have a higher concentration of blood triglycerides and
lower high-density lipoprotein cholesterol than CHD patients without DM (2.51 and 2.07
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mmol/L, 0.93 and 1.19 mmol/L, respectively). At the same time, the atherogenicity
coefficient in CHD patients with DM was 1.4 times higher than among patients without DM
(6.43 and 4.60, respectively). A prospective follow-up of 1342 men in Trinidad revealed
178 deaths, of which 38% were CVD, with 12% having cerebrovascular disease. With an
increase in the level of systolic BP, the risk of all-cause mortality from CVD and cerebral
stroke increased. With a SBP level above 180 mmHg. mortality from CVD increased by 4
times [16]. A 7-year study of mortality among men aged 50-59 years in Moscow revealed
that hypertension is an important risk factor for death from CHD [10]. When comparing RFs
such as hypertension, overweight, smoking, and impaired carbohydrate tolerance, it turned
out that hypertension was the most unfavorable factor, since mortality from coronary artery
disease among people with elevated blood pressure was 7 times higher than in normal blood
pressure, which was significantly higher than in other RFs.
In the presence of hypertension caused by SBP, the risk of death from CVD increases by 5
times, and in the presence of DBP due to DBP, the risk of death increases by 3 times. This
study showed that the risk of myocardial infarction and cerebral stroke increases with an
increase in blood pressure levels, and the risk of cerebral stroke increases more intensively
[104]. It should be noted that it is growing not only among the urban, but also among the
rural population. A study of the mortality structure in Tashkent showed that CVD is the
cause of death in men aged 20-59 years in 33.1% of cases (CHD - 23.87%, HA - 7.16%,
other CVD - 2.06%) [11].
The increase in total mortality rates from 9.6 to 24.1 cases per 1000 people/year as diastolic
BP increases is shown by the data of B.Kh. Makhmudov [8]. According to his data,
mortality from CVD in the group of examined hypertensions was 5 times higher, in the
group of borderline hypertensions - 1.8 times higher than in the group with normal BP.
Prospective observations of the male population of Bishkek have shown that the overall
mortality from CVD and other causes increases significantly with SBP [11].
In 1995, for the first time since 1986, a decrease in mortality was registered in Russia, and
its decrease was noted in 70 regions of the country [9], which was the result of a significant
reduction in mortality from diseases of the circulatory system and unnatural causes of death
- accidents, poisoning and injuries. However, it is noted that the maternal mortality rate
remains high and is not decreasing. The maternal mortality rate in Russia is 5-10 times
higher than in developed Western European countries.
According to the data, cardiovascular diseases are one of the main causes of mortality in the
population of Moscow, accounting for 57% of the total mortality, which exceeds the same
indicators in Russia as a whole. A study of the mortality structure in Tashkent revealed that
CVDs are the cause of death in 37.5% of cases [9,10]. According to data [11], the female
population has an increase in mortality from CVD in all age groups starting from 30-39
years old. Cardiovascular diseases also occupy the first place in the structure of extragenital
pathology, which is one of the main causes of death in pregnant women [10].
Based on the data presented in this section, it can be concluded that hypertension is of great
importance in the formation of coronary artery disease, cerebral stroke and mortality from
them. Timely detection, treatment and prevention of hypertension significantly reduces the
risk of death from CVD. At present, a lot of work is being done in Uzbekistan to improve
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the health of women of childbearing age, which is crucial in the formation of a healthy
generation.
From the information given in the previous chapter, it follows that according to the data of
most studies, the importance of DM as a risk factor for CHD can be considered proven. At
the same time, there is no consensus in the literature regarding the importance of NTG as a
RF for the development of CHD and mortality from it.
According to a number of studies, the risk of developing arterial sclerosis significantly
increases in NTG [15, 16]. A long-term prospective follow-up of 26 years in Framingham
(USA) included 1672 men and 2264 women [16]. After 26 years, 210 men and 199 women
developed coronary artery disease. Among individuals with NTG, along with coronary
vessel involvement, peripheral vascular lesions (primarily the femoral artery) were also
affected. The authors concluded that in conditions of hyperglycemia among persons with
peripheral vascular lesions, there is a high risk of developing coronary artery disease.
Apparently, the combination of lesions of the coronary and peripheral arteries causes
hemodynamic disorders and the formation of a hypokinetic type of blood circulation [11].
There are reports in the literature that NTG significantly affects the severity and clinical
course of CHD [12]. Among people with NTG suffering from CHD, repeated, frequent
hospitalizations, tachycardias, and ischemic changes in the ECG are much more common
[15]. Over time, the glycemia level can change both in the direction of increasing the
glycemic curve and decreasing, and in other cases, the glycemia level stabilizes. prevalence
of coronary artery disease and basal insulinemia levels among individuals with different
dynamics of NTG [14]. It turned out that the development and severity of CHD are closely
related not only to the presence of NTG, but also to the dynamics of hyperglycemic states.
Thus, among individuals with initial IGT, with normalization of glycemia level, the
incidence of CHD is 25%, and with stabilization of NTG, the incidence of CHD reaches
76.5%. At the same time, the level of basal insulinemia increases in accordance with the
progression of hyperglycemia. Among patients in whom hyperglycemia normalized, the
level of basal insulinemia was 18.27
0.92 μU/ml, when NTG turned into overt DM, the
insulin content was more than 2 times higher (39.08
2.1 μU/ml), and when NTG stabilized,
basal insulinemia was the highest – 44.56
3.32 μU/ml. During the entire follow-up period,
864 people developed CHD and 384 people died from this disease.
Along with the works showing the important role of NTG in the formation of CHD and
mortality from it, there is evidence in the literature that denies the role of NTG as RF CHD.
A multivariate analysis that takes into account age, sex, education, hypertension, height-
weight index, and smoking allowed the authors to conclude that, in contrast to DM, NTG is
not CHD RF. One of the largest works devoted to the study of the importance of NTG in the
formation of CHD and deaths in this disease is a cooperative study conducted by The
International Collaborative Group in 14 scientific centers in 11 countries [15]. Studies were
conducted in Australia, England, Denmark (2 populations: males 40 and 50 years old),
Ireland, the USA (2 populations: employees of the gas company and the Western Electric
Company), Italy, Switzerland, Scotland, Finland (2 populations: policemen and unorganized
population), France, and Japan [16]. Such indicators as the prevalence of CHD, the presence
of ischemic changes in the ECG, MI cases and mortality from CHD among individuals with
NTG and different blood glucose levels were taken into account. The results were very
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mixed. Studies among policemen in Finland, employees in Italy, and workers in Japan have
shown that CHD is significantly more common among people with NTG than among people
with normal glucose tolerance. A positive relationship between ischemic changes on ECG
and the presence of NTG in the populations of Australia, Italy, and the unorganized
population of Finland and France was revealed. A higher mortality from CHD was found
among people with NTG in the population of the Gas Company of the USA, France and
policemen in Finland. At the same time, among those surveyed in England, Denmark,
Switzerland and Scotland, no relationship was found between the presence of NTG and the
prevalence of CHD. As follows from these data, the results of studies of different centers
differ significantly. These discrepancies can be explained by the fact that different methods
of population selection were used in the studies, age groups and follow-up periods differed
significantly, not in all studies the study of glucose tolerance covered the state of glycemia at
1 and 2 hours after glucose loading. For example, in Denmark, the population of policemen
is represented by people aged 40 years, and in Italy, the population aged 35-59 years was
surveyed. A prospective study in Finland among an unorganized population lasted 4 years,
in the same country the study of mortality among policemen was carried out for 10 years,
and in the United States among employees of the Western Electric Company the duration of
observation was 15 years. The significance of hyperglycemia for the formation of CHD was
judged by the level of glucose: in Italy - on an empty stomach, in Australia - 1 hour after
glucose loading, in the USA - 2 hours after glucose loading. Thus, the discrepancies in the
results of the cooperative study conducted by The International Collaborative Group in 14
scientific centers in 11 countries and in a number of other population-based studies on the
relationship between the prevalence of CHD and mortality from it with NTG, are largely due
to differences in methodological approaches to both sampling and methods for detecting
NTG, as well as different follow-up periods. At the same time, the results of studies on the
significance of NTG as RF CHD can also be influenced by other factors, as well as their
combinations [14, 15, 16]. The results of a number of population studies indicate that when
several RFs are combined, the prevalence of CHD increases. At the same time, it has been
shown that some RFs can contribute to the formation of other risk factors. In this regard, the
question of the relationship between NTG and other RF CHDs is of some interest. A
prospective study conducted in Italy and followed for 11.5 years involved 1376 people aged
40-59 years. During this follow-up period, systolic BP increased by 7.6 mmHg among
people with NTG. higher than among people with normoglycemia, and diastolic blood
pressure is 3.3 mm Hg. The existence of a relationship between the frequency of
hypertension and the presence of NTG is also indicated by a study in Philadelphia conducted
among black Americans [15]. A study of 437 people over 15 years of age in Central
Australia found a direct correlation between glucose levels on the one hand and the
prevalence of hypercholesterolemia, hypertriglyceridemia, hypertension, and BMI on the
other [16]. Another study conducted in Western Australia among men and women aged 25-
64 years examined the association between the presence of NTG and RF levels of CHD. It is
shown that individual RFs are related to NTG in different ways. For example,
hyperglycemia was associated with BMI in both men and women. Systolic BP was
significantly higher in NTG than in normoglycemia in both men and women. Elevated
triglyceride levels were observed in NTG only among women. However, there were no
differences between the concentrations of total cholesterol and high-density lipoproteins
among men and women depending on the presence of NTG. In general, it was found that in
both men and women with hyperglycemia, RF CHD was more pronounced than in
normoglycemia. Studies in the United States have shown that among obese individuals,
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there is an increased release of insulin in response to glucose load [12]. However, the
authors do not specify what comes first in this regard: whether the presence of obesity leads
to an increased release of insulin or hyperinsulinemia contributes to the development of
obesity. According to the Fremmingham study, the role of DM and NTG as RF CHD
increases significantly when they are combined with other RFs [14]. Observation of the
population of 3595 people for 16 years allowed the authors to establish that DM and NTG
lead to a significant increase in fibrinogen and triglycerides in the blood, as well as an
increase in blood pressure and div weight. The combination of these factors contributes to
an increase in the risk of CHD formation.
In Uzbekistan, as early as 1985-1990, a study of the prevalence of DM in the regions of the
republic was carried out [6]. At the same time, 5000 people were examined in each region.
The prevalence of DM was 1.9% and NTG was 3.6% to 4.0%. This study shows that the true
incidence of DM significantly exceeds the official statistics. The results of another
population study conducted in Tashkent [4] indicate a significant increase in the incidence of
DM and NTG. Between 1980 and 1988, the prevalence of DM among men aged 40-59
increased from 3.9% to 6.92%, and NTG from 29.3% to 38.93%. According to the American
Heart Association, more than 10 million Americans suffer from diagnosed diabetes [5]. The
number of new cases of DM is 798,000 per year. The prevalence of DM among black men is
higher than among white men.
Thus, summarizing the literature data, it can be concluded that CHD is one of the most
significant problems of modern medicine. This is determined by the wide prevalence of
CHD and the high mortality associated with this disease. In most countries of the world,
including Uzbekistan, the number of patients with CHD continues to grow. The formation of
CHD, its course and outcomes are influenced by various risk factors for this disease.
The role of a number of RFs in the development of CHD (such as hypertension, obesity, age,
etc.) is beyond doubt. One of the most significant RFs of CHD is DM. However, the
literature on the role of NTG as RF CHD differs significantly. Meanwhile, in some cases,
NTG can precede the development of DM and, in a certain sense, it can be considered as a
state of "pre-disease" in relation to DM. Hyperglycemia, including latent hyperglycemia,
often proceeds with hyperinsulinemia, which is considered one of the components of the
"metabolic" syndrome that plays an important role in the formation of cardiovascular
diseases, including coronary artery disease. Differences in the literature, often contradictory,
on the role of NTG in the formation of CHD may be associated with rather significant
differences in the methodology of research. Along with a fairly large number of one-time
and long-term prospective studies, there is a lack of work on the dynamics of CHD
development among patients with NTG in "end-to-end" populations. Based on the above,
further study of the role of NTG in the formation of CHD and the outcomes in this disease is
of particular interest.
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