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MINISTRYOF EDUCATION AND TRAINING

MINISTRYOF NATIONAL DEFENCE

108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES

LƯƠNG THỊ HƯƠNG LOAN

RESEARCH OF INTIMA MEDIA-THICKNESS AND
BRACHIAL ARTERY FLOW MEDIATED DILATION
IN MENOPASAL WOMEN BY DOPPLER
ALTRASOUND
Specialized: Cardiovascular
Code: 62720141

ABSTRACT OF DOCTORAL THESIS

Hanoi, 2020


WORKS ARE COMPLETED IN 108 INSTITUTE OF CLINICAL
MEDICAL AND PHARMACEUTICAL SCIENCES

SCIENCE INSTRUCTOR:
1. Associate professor. Nguyen Van Quynh
2. Associate professor. Nguyen Duc Hai
Reviewer 1: .........................................................................................
Reviewer 2: .........................................................................................
Reviewer 3: .........................................................................................
The dissertation is defended in front of
the institute – level judging counncil


108 institute of clinical medical and pharmaceutical sciences
Vào hồi .…… hour….… minutes, date ….. month …… year 20…..
The thesis can be explored:
1. Việt Nam national library
2. The library of 108 institute of clinical medical and
pharmaceutical sciences
3. The institute of central medical information


1

INTRODUCTION OF THE THESIS
1. Introduction
Atherosclerosis is one of the leading causes of death and
disability. The role of atherosclerosis has been identified in
cardiovascular diseases, brain stroke and peripheral artery disease...
In 2013, worldwide statistics, the number of deaths from myocardial
infarction were 8.56 million, 10.3 million are stroke cases. Mortality
rates vary between men and women, with women having a higher
cardiovascular death rate than men, especially in women after
menopause. The deficiency of estrogen in menopause causes a severe
disorder of lipid metabolism, redistribution of body fat (central fat),
insulin resistance ... so the potential artery damage available at this
stage. Therefore, the investigation of endothelial dysfunction, or
atherosclerosis in the preclinical stage is very interested. In Vietnam,
many authors' studies have mentioned carotid artery intima media
thickness and brachial artery flow mediated dilation in type 2
diabetes patients, hypertension patients, coronary artery ... There
have been no studies investigating menopausal women. We
conducted the study of femoral intima-medial thickness under the

guidance of the European Heart Association and brachial artery flow
mediated dilation in menopausal women with Doppler ultrasound
under the guidance of The American Cardiology Association aims to
help menopausal women limit vascular events with the following
two goals:
1.Investigation of femoral intima-medial thickness (IMT) and
brachial artery flow mediated dilation (FMD) in menopausal women
with Doppler ultrasound.
2.Investigate the association between IMT, FMD and
cardiovascular risk factors in postmenopausal women.
2. The contributions of the thesis:
The study identified: At the same age, menopausal women
was a higher IMT than non menopausal women, responding to FMD
was lower in menopausal women than non menopausal women.
The study noted an association between IMT and FMD with
hypertension, hyperglycemia, dyslipidemia and estradiol depletion.
Thickening of IMT and decreased FMD are most affected by
systolic blood pressure, blood glucose and estradiol in menopausal
women.


2

3. The thesis layout:
The thesis consists of 130 pages, including 2-page problems,
34-page overview of documents, 20-page research objects and
methods, 35-page research results, 36-page discussion, 3-page
conclusions and recommendations. There are 35 tables, 10 pictures, 9
charts and 150 references (27 Vietnamese documents, 123 English
documents).



3

Chapter 1
LITERATURE REVIEW
1.1. Menopause difinition
Natural menopause occurs after 12 consecutive months of
menopause without a clear cause. The onset of menopause is
determined only by retrospective look at least one year after the last
cycle.
1.2. Endocrine disorders in menopause
In women of reproductive age, estradiol is created primarily
from ovary. At menopause, there are very few original follicles in the
ovaries, resulting in a decrease in the concentration and rate of
estradiol production.
Testosterone in women of reproductive age is made from two
sources: by the ovaries and converting androstenedion precursors to
testosterone in peripheral tissues. At menopause, testosterone levels
decrease by about 20% and androstenedion decreases by about 50%.
1.3. Cardiovascular risk factors are common in postmenopausal
women
1.3.1. Lipid disorders
During menopause, a decrease in estradiol levels leads to an
increase in total cholesterol (CT), LDL-Cholesterol (LDL-C),
triglyceride (TG) and decreased HDL-Cholesterol (HDL-C) levels in
the blood. These changes increase the risk of cardiovascular disease.
In menopausal women, CT increases with age, but women over the
age of 50 this increase becomes sudden.
1.3.2. Disorders of fat distribution

In menopausal women due to a decrease in estrogen levels
leads to a change in body fat distribution: increased accumulation of
abdominal and visceral fat, large waist circumference, CT, LDL-C
and apo B, blood pressure and blood glucose is higher than younger
women. In addition, male obesity causes intracellular insulin
resistance leading to increased insulin levels.
1.3.3. Hypertention
Menopausal women with reduced estrogen cause endothelial
dysfunction, in addition to an increase in body weight (BMI),
increased sympathetic nervous system activity, increased renin and


4

angiotensin II and The ultimate consequence causes hypertension in
menopausal women.
1.3.4. Insulin resistance
Pathophysiology of complex insulin resistance. Insulin
resistance increases free fatty acid production from adipose tissue
leads to reduced absorption of glucose, increasing the formation of
glucose in the liver, reducing the effect of insulin in the liver. In
addition, the lipodystrophy caused by a decrease in estrogen in
menopausal women causes insulin resistance. Combining these two
mechanisms leads to menopausal women have a very high rate of
insulin resistance.
1.3.5. Fasting blood glucose disorders
In menopausal women, the risk of type 2 diabetes may be due
to the effects of menopause (the earlier the menopause, the higher the
risk of type 2 diabetes).
1.3.6. Inflammatory factors

CRP is considered as an inflammatory marker associated with
atherosclerosis and cardiovascular diseases. High CRP in
menopausal women may be an indicator of risk for cardiovascular
disease. This means estrogen deficiency, increased central obesity
are associated with increased blood clotting disorders.
1.4. Vascular changes in menopausal women
The vascular system is considered as one of the important
target tissues of estrogen. Estrogen works to develop vascular
endothelial cells but inhibits the renewal of vascular smooth muscle
cells, regulating intracellular calcium. On the other hand, estrogen
acts directly on the vascular wall which increases NO production in a
few minutes and induction of nitric oxide synthase increases
prostacyclin production more slowly. All of the above effects cause
vasodilation.
1.5. Vascular endothelium and some survey methods
Vascular endothelium is a thin, single-celled layer that covers
the inner surface of the entire vascular system.
1.5.1. Function of vascular endothelial cells
Vascular endothelium has an important role in homeostasis of
body. An uncontrolled response of vascular endothelial cells
involves a lot of pathological processes.
1.5.2. Endothelial dysfunction and atherosclerotic process


5

Several factors can disrupt the balance of the endothelium,
causing the endothelium to have atherosclerotic properties such as
changes in vascular permeability, increased adherence and
discontinuation of platelets, leukocytes, and increased stimulation

smooth muscle, characterized by coagulation, inflammation and
oxidation.
1.6. Investigation of vascular endothelium by the arm artery
ultrasound method
Basis of the method: the factor that stimulates NO excretion
are the mechanical opposites of the endothelium, mainly the direct
effects on the vascular wall due to the increase of blood flow. When
we cause anemia in place by garo blocking arm artery for a few
minutes and then remove the garo will have congestion phenomenon
(increased perfusion response). Increased blood flow to increased
pressure on the vascular wall, endothelium will respond to increased
NO production, causing vasodilation to increase arm artery diameter.
The degree of dilatation of the brachial artery with increased blood
flow is called flow-mediated dilation. We can rely on this response to
assess endothelial function of the arm artery.
1.7. Femoral artery Doppler ultrasound:
The IMT thickness is the distance between the two edges on
the lumen line - the endothelium is far from the artery to the edge to
the line between the mediastinum - the periphery.
A consensus on the definition, clinical significance, and
method of determining the IMT thickness of arteries was presented at
the 13th European stroke conference held in Mannheim (Germany)
in 2004 and was added later. It was at the 14th conference in
Brussels (Belgium) in 2006. Accordingly, many standards were set
to distinguish between IMT thickness and atherosclerosis.
Atherosclerosis are determined to be over 1.5mm.
1.8. Situation of studying IMT changes and FMD in contry and
abroad by Doppler ultrasound
Study on "Frequency and risk factors related to femoral
atherosclerosis among older women in the UK" Leng GC et al.

(2000) conducted a survey on 367 menopausal women aged 56-77
noted that two-thirds of the women who participated in the study had
femoral atherosclerosis plaque.


6

The study "The role of flow-mediated vasodilation and
cardiovascular risk factors in postmenopausal women" by Rossi R on
2,264 menopausal women (54 ± 6 years), long follow-up time (45 ±
13 months). As a result, after adjusting for age and traditional risks,
the relative risk of cardiovascular events increased in the low FMD
triad group. In the group with FMD level ≤ 4.5%, the risk of
cardiovascular events is 4 times higher than the group with FMD
level ≥ 8.1%.
The study of brachial artery flow-mediated dilation by
ultrasound in patients with metabolic syndrome of Nguyen Hai Thuy
showed results: hypertension, TG level and blood glucose related to
endothelial dysfunction. The FMD value of the metabolic syndrome
group was lower than the control group (5.00 ± 3.16% compared to
11.89 ± 3.86%), with (p <0.001).
Chapter 2
SUBJECTS AND METHODS OF THE STUDY
2.1. Research subjects
Our study was conducted on women including 232
menopausal women and 58 women who are non menopausal women.
2.1.1. Standard selection
- Criteria for choosing menopausal women
Menopausal women who have stopped menstrual periods ≥ 12
months.

Agree to join the research.
- Criteria for choosing non-menopausal women
Women have regular menstruation.
Agree to join the research.
2.1.2. Exclusion criteria
- Menopausal women
Women undergoing hormone replacement therapy.
Women removed the ovaries, uterus.
Women have a hunched or bent spine.
Severe, malignant women accompanied.
Women receiving immunodeficiency medications ...
- Non menopausal women
Women with acute illnesses being treated.


7

Women with diabetes and hypertension.
Women with peripheral artery disease and varicose veins ...
2.2. Research Methods
2.2.1. Research design
Cross-section research with comparative control.
2.2.2. Sample size
Convenient sampling
2.2.3. Research location
At the on-demand clinic and outpatient's department Thai
Nguyen Central Hospital.
2.2.4. Research time
From April 2014 to May 2015
2.2.5. Steps to conduct research

- To conduct data collection from women participating in the
research.
We directly ask about the medical history, history and physical
examination of all women present (see Appendix 1).
- Clinical examination:
Collect data according to sample medical records, to assess
general condition, vital signs, cardiovascular disease status,
peripheral vascular examination.
- Laboratory testing:
The patient was tested for: fasting blood glucose, blood
insulin, lipid components, estradiol, blood testosterone, and hs-CRP
- Arteries were investigated by Doopler ultrasound
Measure femoral artery IMT thickness and measure arm artery
diameter before and after vasodilation test.
2.2.6. Research indicators
- Clinical criteria
- Subclinical criteria.
2.3. Standards used in research
Diagnostic criteria for femoral endothelial thickening
according to the European Heart Association and measurement of
vasodilatation by the arm artery flow according to the American
Cardiovascular Association.


8

Chapter 3
RESEARCH RESULTS
During the period from April 2014 to May 2015, we recruited
232 menopausal women and 58 non-menopausal women.

3.1. General characteristics of the research group
Table 3.1. Age characteristics, anthropometric indicators and blood
pressure of menopausal women and non-menopausal women
Group
NonMenopausal
menopasal
women
women
(n = 232)
p
Parameters
(n = 58)
Trung bình
Trung bình
Age (year)
54,6 ± 5,8
53,8 ± 3,2
> 0,05
BMI (kg/m2)
23,8 ± 2,1
22,4 ± 1,8
< 0,001
Waist circumference
83,0 ± 6,2
79,7 ± 3,9
< 0,001
(cm)
Hip circumference (cm)
92,6 ± 4,9
90,7 ± 3,9

< 0,01
Waist to hip ratio
0,9 ± 0,06
0,9 ± 0,04
< 0,05
Systolic blood pressure
127,6 ± 14,9 113,1 ± 16,2 < 0,001
(mmHg)
Diastolic blood pressure
79,0 ± 10,0
71,2 ± 10,4
< 0,001
(mmHg)
Survey on mean values of age, BMI, VB, VM, , waist to hip
ratio and blood pressure in menopausal women were all higher than
those of non-menopausal women with (p <0.05), except for age
difference no difference statistical significance p > 0.05.
3.2. Investigation of IMT thickness characteristics FMD in
menopausal women and non-menopausal women
3.2.1. Investigation of thickness characteristics of IMT in
menopausal women and non-menoposal women


9

Table 3.11. Morphological characteristics and thickness of IMT,
atherosclerosis of menopausal women and non-menopausal women
Group
IMT, atheroclerosis
IMT (mm)

Commo
Nomal artery
n
IMT (>1mm)
femoral
artery atheroclerosis
(≥1,5mm)
IMT (mm)
Shallow Nomal artery
femoral IMT (>1mm)
artery atheroclerosis (≥
1,5mm)
IMT (mm)
Nomal artery
Deep
femoral IMT (>1mm)
artery atheroclerosis (≥
1,5mm)

NonMenopaus
menopausal
al women
women
p
(n= 232)
(n = 58)
n
%
n
%

1,0 ± 0,3
0,8 ± 0,2
< 0,001
162 69,8 48 82,8
< 0,05
70 30,2 10 17,2
14

6,0

0,8 ± 0,4
227 97,8
5
2,2
2

0,9

0,7 ± 0,3
223 96,1
9
3,9
3

1,3

0

0,0


> 0,05

0,6 ± 0,1
58 100,0
0
0,0

< 0,01

0

> 0,05

0,0

> 0,05

0,6 ± 0,1
58 100,0
0
0,0

< 0,01

0

> 0,05

0,0


> 0,05

The IMT in menopausal women was higher than nonmenopausal women (p <0.05).
The IMT and atheroclerosis were thicker than menopausal
women compared to non-menopausal women. The diference was
only found in the common femoral artery, (p < 0,05).


10

Table 3.12. The ratio of IMT and atheroclerosis according to
menopause
Age group
40 - < 50
50 - 60
n

%

n

%

p

IMT, atheroclerosis
Nomal artery
72 97,3 90 57,0
<
Common

IMT (>1mm)
2
2,7
68 43,0 0,001
femoral
Atheroclerosis (≥
artery
0
0,0
14
8,9 < 0,01
1,5mm)
Nomal artery
73 98,7 154 97,5
> 0,05
Shallow IMT (> 1mm)
1
1,3
4
2,5
femoral Atheroclerosis (≥
0
0,0
2
1,3 > 0,05
artery
1,5mm)
Nomal artery
73 98,7 150 94,9
> 0,05

Deep
IMT (> 1mm)
1
1,3
8
5,1
femoral
Atheroclerosis (≥
artery
0
0,0
3
1,9 > 0,05
1,5mm)
The IMT and atheroclerosis were mainly found in common
femoral artery (p < 0.001)
Table 3.13. The ratio of IMT and atheroclerosis according to
menopausal time
≤ 5 years > 5 years
Menopausal time
(n = 136)
(n =96)
p
IMT, atheroclerosis
n
%
n
%
90,
40,

Nomal artery
123
39
4
6
Comm
< 0,001
on
59,
IMT (>1mm)
13
9,6 57
femora
4
l artery Atheroclerosis (≥
14,
0
0,0 14
< 0,001
1mm)
6
99,
95,
Nomal artery
135
92
3
8
> 0,05
Shallo

w
IMT (> 1mm)
1
0,7
4
4,2
femora Atheroclerosis (≥
0
0,0
2
2,1
> 0,05
l artery 1,5mm)


11

Menopausal time
IMT, atheroclerosis
Nomal artery

≤ 5 years
(n = 136)
n
%
97,
133
8
3
2,2


> 5 years
(n =96)
n
%
93,
90
8
6
6,2

p

> 0,05
IMT (> 1mm)
Atheroclerosis (≥
1
0,7
2
2,1
> 0,05
1,5mm)
Menopausal women with time > 5 years were at greater risk of
developing IMT and atheroclerosis in femoral arteries than those
with menopause time < 5 years, the deference is statistically
significant only in common femoral artery, (p < 0.001).
3.2.2. Investigation of FMD in menopausal and non-menopausal
women
Table 3.22. FMD reduction rates among menopausal women and
non-menopausal women

Group
Menopausal
Non-menopausal
women
women
p
FMD
n
%
n
%
166
71,6
49
84,5
≥ 7,8%
< 0,05
66
28,4
9
15,5
< 7,8%
Menopausal women had higher FMD reduction rates than nonmenopausal women (28.4% versus 15.5%), (p <0.05).
Table 3.23. FMD reduction rates among menopausal women by age
group
Age group
40 - < 50
50 - 60
p
n

%
n
%
FMD
≥ 7,8 %
61
82,4
105
66,5
< 0,001
< 7,8%
13
17,6
53
33,5
Menopausal women from 50 to 60 years of age had a higher
rate of FMD reduction than women in the 40 to 50 year old age
group (33.5% copares to 17.6%), this difference was statistically
significant. (p <0.001).
Deep
femora
l artery


12

Table 3.24. FMD reduction rates among menopausal women by
manopause time
Menopause
time


≤ 5 years
(n = 135)

> 5 years
(n = 97)

n

n

%

p

%

FMD
≥ 7,8%
113 83,1
53
55,2
< 0,001
< 7,8%
23
16,9
43
44,8
Women with menopause> 5 years had a higher rate of FMD
reduction than women with menopause period ≤ 5 years, (p <0.001).

3.3. Relationship between IMT and FMD in menopausal women
3.3.1. Relationship between cardiovascular risk factors and
menopause status with IMT in menopausal women
Table 3.26. Relationship between common femoral artery IMT and
age, menopause, waist circumference, BMI
Menopausal women (n = 232)
IMT
IMT
Total
(95%CI)
p
Parameters
n
%
< 50 74
2
2,7
1
Age
(year)
≥ 50 158 68 43,0 10,2( 6,4 - 24,8) < 0,001
Menopause
time (year)
BMI (kg/m2)

≤5

136

13


9,6

1

>5

96

57

59,4

< 23

77

15

19,5

1

≥ 23

155

55

35,5


2,3 (1,1 – 4,7)

-

13,8 (6,9 - 27,9) < 0,001
< 0,05

Waist
< 80 96
21 21.9
1
circumference
≥ 80 136 49 36,0
1,7 (0,9 - 3,2) > 0,05
(cm)
Menopausal women aged ≥ 50 and menopause > 5 years have
a higher risk of IMT thickness than the other group (OR = 10.2; 95%
CI: 6.4 - 24.8 and OR = 13.8; 95% CI: 6.9 - 27.9), p <0.001.
For women with waist circumference ≥ 23, the risk of
common femoral artery IMT was 2.3 times higher than for
menopausal women with BMI <23 (OR = 2.3; 95% CI: 1.1 - 4.7),
with (p <0.05).


13

Table 3.27. Relationship between femoral artery IMT and blood
pressure, lipid, glucose, and hs-CRP in menopauusal women
IMT

Parameters
Blood
pressure

Blood
lipids

Blood
glucose

Menopausal women (n = 232)
IMT
Total
(95%CI)
p
n
%

Normal

155

29

18,7

1

Hypertention


77

41

53,3 5,0( 2,6-9,5) < 0,001

Normal

37

5

13,5

Lipid disorders

195

65

33,3 3,2 (1,2-11,0) < 0,05

Normal

97

13

13,4


Prediabetes

135

57

42,2 4,7 (2,3-10,1) < 0,001

Normal

151

41

27,2

hs-CRP increase

81

29

35,8 1,5 (0,8-2,8)

1

1

1


-

-

-

-

Hs-CRP
> 0,05

Menopausal women with hypertension were at higher risk of
common femoral arterial IMT compared with the menopausal
women without hypertension (OR = 5.0; 95% CI: 2.6 - 9.5), p
<0.001.
Blood lipid disorders in menopausal women were 3.2 times
more likely to have IMT thickening than women without lipid
disorders (OR = 3.2; 95% CI: 1,2 - 11,0), p <0, 05.
Menopausal women with type 2 diabetes have a risk of IMT
many times higher than menopausal women with normal blood
glucose (OR = 4.7; 95% CI: 2.3 - 10.1), the difference is significant
statistic (p <0.001).


14

Table 3.28. Relationship between femoral artery IMT and estradiol,
testosterone in menopausal women
IMT
Menopausal women (n = 232)

Estradiol, testosterone

Total

IMT
n

%

(95%CI)

p

1

-

Estradiol
(pg/ml)

Bình thường

38

6

15,8

Giảm


194

64

33,0 22,6(1,0– 7,9 < 0,05

Testosterone
(ng/dl)

Bình thường

7

0

0,0

1

-

Giảm
225 70 31,1
Menopausal women with reduced estradiol levels were 2.6
times more likely to have IMT than menopausal women with normal
estradiol levels (OR = 2.6; 95% CI: 1.0 - 7.9), p <0.05.
3.3.3. Relationship between cardiovascular risk factors and
menopausal status, and the FMD in menopausal women
Table 3.29. Relationship between FMD and age, menopause time,
waist circumference, BMI

FMD
Menopausal women (n = 232)
Reduction
FMD
Total
(95%CI)
p
Parameters
n
%
< 50 74
13
17,6
1
Age
(year)
≥ 50 158
53
33,5 2,4 (1,2 – 5,1) < 0,05
≤ 5 136
23
16,9
1
Menopause
year
>5
96
43
44,8 4,0 (2,1 - 7,6) < 0,001
<

23
77
21
27,3
1
BMI (kg/m2)
≥ 23 155
45
29,0 1,1 (0,6 - 2,0) > 0,05
Waist
< 80 96
24
25,0
1
circumference
≥ 80 136
42
30,9 1,3 (0,7 - 2,4) > 0,05
(cm)
Women with age of menopause ≥ 50 and menopause time > 5
years, the risk of FMD reduction is many times higher than women
aged <50 and menopause time ≥ 5 years, respectively (OR = 2.7;
95% CI: 1.2 - 5.1 and OR = 4.0; 95% CI: 2.1 - 7.6).


15

Table 3.30. The relationship between FMD and blood pressure,
blood lipid, glucose and hs-CRP
FMD

Menopausal women (n = 232)
Reduction
FMD
Total
(95%CI)
p
Parameters
n
%
Blood Normal
pressur
Hypertentio
e
n
Blood
lipids

Blood
glucose

HsCRP

155

22

14,2

1


-

77

44

57,1

8,1 (4,1 –
16,1)

< 0,001

Normal

195

5

13,5

1

-

Lipid
disorders

37


61

31,3

2,9 (1,1 –
10,0)

< 0,05

Normal

97

12

12,4

1

-

Prediabetes

135

54

40,0

4,7 (2,3 –

10,4)

< 0,001

Normal

151

37

24,5

1

-

hs-CRP
81
29 35,8 1,7 (0,9– 3,2) > 0,05
increase
Menopausal women with hypertension were 8.1 times more
likely to reduce FMD than Menopausal women without hypertension
(OR = 8.1; 95% CI: 4.1 - 16.1), p <0.001. Menopausal women with
type 2 prediabetes have a much higher risk of FMD reduction than
menopausal women with normal blood glucose (OR = 4.7; 95% CI:
2.3 - 10.4), p <0.001. In women with lipid disorder, the risk of FMD
was reduced by 2.9 times compared with women without lipid
disorder (OR = 2.9; 95% CI; 1.1 - 10.0), the difference was statistical
significance (p <0.05).



16

Table 3.31. The relationship between FMD and estradiol,
testosterone
FMD

Menopausal women (n = 232)
Reduction
FMD
n
%

Tot
al

Parameters

(95%CI)

p

Norm
38
5
13,2
1
al
Estradiol
(pg/ml)

Reduc
3,0 (1,1 194 61
31,4
< 0,05
tion
10,4)
Norm
7
0
0,0
1
Testosterone al
(ng/dl)
Reduc
225 66
29,3
tion
Menopausal women with decreased estradiol levels were 3.0
times more likely to have decreased FMD than women with normal
estradiol levels (OR = 3.0; 95% CI: 1.1 - 10.4), p <0.05.
3.3.5. Multivariate regression correlation between IMT and FMD
with cardiovascular risk factors
Table 3.34. Multivariate regression correlation between IMT and
cardiovascular risk factors in meopausal women
Characteristics

B

β


t

p

95% CI

Constant

- 1,300

Age (year)

0,013 0,268 2,878 < 0,05 (0,004: 0,022)

Menopause year

0,004 0,092 1,119 > 0,05

Waist circumference - 0,001 - 0,018 - 0,288 > 0,05

(- 0,003:
0,011)
(- 0,007:
0,005)
(- 0,304:
1,096)

Waist to hip ratio

0,396 0,069 1,114 > 0,05


Systolic
pressure

0,004 0,200 2,442 < 0,01 (0,001: 0,008)

blood


17

Characteristics
B
β
t
p
Diastolic
blood
0,005 0,142 2,017 < 0,05
pressure

95% CI
(<
0,001:0,009)
(- 0,041:
0,121)
(- 0,116:
0,053)

CT (mmol/L)


0,040 0,122 0,971 > 0,05

Non - HDL-C

- 0,031 - 0,095 - 0,734 > 0,05

LDL-C (mmol/L)

0,066 0,161 2,719 < 0,01 (0,018: 0,114)

HOMA -IR

- 0,001 - 0,016 - 0,364 > 0,05

Hs-CRP (mg/L)

0,001 0,011 0,243 > 0,05

Estradiol (pg/ml)

- 0,003 - 0,145 - 3,170 < 0,01

Testosterone (ng/ml) <0,001 0,007 0,164 > 0,05
Glucose (mmol/l)

(- 0,006:
0,004)
(- 0,009:
0,012)

(- 0,005:
0,001)
(- 0,002:
0,003)

0,027 0,159 1,787 < 0,05 (0,001: 0,095)

IMT was only statistically correlated with some risk factors:
inversely correlated with estradiol, positively correlated with LDL-C,
systolic blood pressure, diastolic blood pressure, age, and blood
glucose.
Table 3.35. Multivariate regression correlation between FMD and
cardiovascular risk factors in menopausal women
Characteristics
B
Constant
3,030
Age (year)

β

t

p

95% CI

- 0,166 - 0,389 - 4,906 < 0,001 (- 0,066: 0,118)

Menopause

- 0,006 - 0,015 - 0,214 < 0,001 (- 0,150: - 0,010)
year
Waist to hip
0,084 0,002 0,044 > 0,05 (- 8,377: 1,986)
ratio
Systolic BP

- 0,026 - 0,137 - 1,960

< 0,05 (- 0,089: - 0,015)


18

Characteristics

B

β

t

p

95% CI

Diastolic BP

- 0,023 - 0,079 - 1,318


> 0,05 (- 0,059: 0,035)

LDL-C
(mmol/L)

- 0,098 - 0,027 - 0,710

> 0,05 (- 0,700: 0,051)

HOMA -IR

0,053

1,105

> 0,05 (- 0,093: 0,170)

- 0,023 - 1,00 - 1,092

> 0,05 (- 0,071: 0,042)

0,016

0,089

2,278

< 0,05 (- 0,009: 0,029)

0,005


0,020

0,523

> 0,05 (- 0,015: 0,034)

Insulin
(µUI/ml)
Estradiol
(pg/ml)
Testosterone
(ng/ml)
Glucose
(mmol/l)

0,102

- 1,191 - 0,290 - 4,601 < 0,001 (- 3,094: - 1,681)

FMD is only statistically correlated with some risk factors:
inversely correlated with blood glucose, age, menopause year,
systolic blood pressure, positively correlated with estradiol.


19

Chapter 4
DISCUSSIONS
4.1. General characteristics of menopausal women and nonmenopausal women

BMI, waist circumference, hip circumference, Waist to hip
ratio, the blood pressure of menopausal women was higher than that
of non-menopasal women, p <0.05, except age (54, 6 compared to
53,8), p> 0.05.
4.2. Characteristics of IMT and FMD in menopausal women and
non-menopausal women
4.2.1. Characteristics of IMT thickness in women
Our research results show that the ratio of thickness of IMT
and femoral atherosclerotic plaque is mainly found in common
femoral artery IMT (p <0.05). Our conclusion is consistent with
Tran Hong Nghi's study, which is probably a natural phenomenon to
adapt to a larger flow than a branched artery.
IMT thickness and femoral atherosclerotic plaque by age group
We found that among menopausal women aged 50-60 years,
the rate of IMT thickening and femoral atherosclerotic plaque was
higher than that in the 40- < 50 year group and statistically
significant in the common femoral artery, p < 0.01 .Hamilton George
surveyed femoral artery IMT in older women (58.5) and noted:
femoral artery IMT increased by 0.0031mm every year and after 10
years, femoral artery IMT increased significantly from 0.04 to 0.06
mm.
Thickening of IMT and femoral atherosclerotic plaque over time of
menopause
Menopausal women with menopause time ≤ 5 years, the
proportion of IMT thickening and femoral atherosclerotic plaque is
higher than that of postmenopausal women with duration <5 years
and mainly seen in common femoral artery. Al-Nimer and Husein
when studying the incidence of IMT thickness in patients with
femoral artery also concluded that IMT thickness mainly occurs in
large arteries. Tran Dinh Dat's research has similar conclusions when

examining atheroclerosis in postmenopausal women.
4.2.2. Characteristics of FMD in Menopausal women and
nonmenopausal women


20

FMD in menopausal women and non-menopausal women
The average value of FMD among menopausal women (9.6)
and non-menopausal women (10.6). Comparing FMD research
results with Vo Bao Dung, Noveanu, and Naidu, we found that:
FMD in the disease group ranged from (5.00 - 9.42%), in the control
group (9.93 - 21.11%). Thus, studies have shown that in patients
with specific diseases, FMD evaluation shows that vascular
endothelial function has marked damage. The average FMD value in
healthy people ranges from 9% - 21%, it is still within the allowed
range according to the guidelines of the European Heart
Association.Decreased FMD follow by age group, menopause time
Menopausal women aged 40 - <50 reduce the rate of FMD
(17.6%), and age 50 - 60 years reduce FMD (33.5%), (p <0.001). For
women with menopause that is > 5 years, the rate of FMD reduction
(44.8%), and for menopausal women with duration from ≤ 5 years,
the rate of FMD reduction is (16.9%), (p <0.001). A 2010 Virdis
study notes that the greater risk of developing IMT and
cardiovascular diseases.
4.3. Finding the association between common femoral artery
IMT thickness and FMD in Menopausal women
4.3.1. Relationship between femoral artery IMT and cardiovascular
risk factors
Relationship between common femoral artery IMT and BMI

Changes in sex hormones during menopause are believed to
have an important impact on weight gain, the prevalence of obesity
in Menopausal women accounts for 73.86%. Both of these risk
factors combined with the same female IMT tend to change,
particularly among menopausal women with BMI ≥ 23, the risk of
IMT was 2.3 times higher. among menopausal women with BMI
<23.
Relationship between common femoral artery IMT and hypertension
Menopausal women with hypertension were at risk of many
times higher IMT than those without hypertension (OR = 5.0; 95%
CI: 2.6 - 9.5). Ebrahim found an association between systolic blood
pressure and arterial IMT on 375 women with an average age of 66
years. Menopausal women with hypertension was 2.3 times more
likely to develop arterial IMT than non-hypertensive people.


21

Relationship between common femoral artery IMT and lipid
disorders
Menopausal women with lipid disorders were 1.8 times more
likely to develop femoral artery IMT than menopausal women
without lipid disorders (OR = 3.2; 95% CI: 1,2 - 11,0). Jeremias et al
(2018), studying "Femoral endothelial thickening, risk factors and
inflammatory markers in cardiovascular pathology" in women aged
71.08, concluded: relationship between blood CT and femoral artery
IMT.
Relationship between common femoral artery IMT and dysglycemia
In the glucose tolerance disorder group, we found the risk of
IMT was much higher than the group without glucose tolerance

disorder (OR = 4.7; 95% CI: 2.3 - 10.1 ). Kawamoto demonstrated
that patients with glucose tolerance disorders were 1.36 times more
likely to suffer from IMT thickening than those without glucosse
tolerance disorders.
Relationship between common femoral artery IMT and estradiol and
testosterone
Postmenopausal women who decreased estradiol were 2.6
times more likely to develop IMT than women with normal estradiol
group. Naessen T (2012) noted androgen and estradiol related to
IMT.
4.3.2. Relationship between FMD and cardiovascular risk factors
Relationship between FMD and age, year of menopause
We found an association between FMD reduction and age and
women with age of menopause ≥ 50 and menopause time (> 5 years)
respectively (OR = 2.4, 95% CI: 1 , 2 - 5.1) and (OR = 4.0; 95% CI:
2.1 - 7.6). Menopause affects a woman's vascular endothelial
function. According to research by Moreau K (2012), over 132
women were divided into different groups: the group of menopause,
early menopause, late menopause. In the early menopause and late
menopause group, it was observed that: FMD decreases with age.
Relationship between FMD and hypertension
The group with hypertension was 8.1 times more likely to
suffer from FMD reduction. Rossi, when analyzing FMD
measurement results with cardiovascular risk factors at 2,264
menopausal women had an average age (54 ± 6), the author noted


22

that the lower the FMD three-percentile, the hypertension rate was

high.
Relationship between FMD and lipid disorders
Reduced arm artery FMD in PNMK with lipid disorders was
2.9 times higher than in menopausal women without lipid disorders.
Rosi studied 2,264 menopausal women with the aim of finding an
association between FMD and cardiovascular risk factors, and
discovered CT blood increased gradually as FMD got smaller.
Relationship between FMD and fasting blood glucose disorders
Menopausal women had fasting blood glucose disorders, the
risk of FMD decreased by 4.7 times higher than the group without
fasting blood glucose disorders. A study by Skaug E (2014),
investigating the cardiovascular risk impact on endothelial
dysfunction in women noted: decreased FMD in the high blood
glucose.
Relationship between FMD and estradiol, testosterone
Data analysis showed that the risk of FMD reduction in
women with estradiol decreased 3.0 times higher than menopausal
women without hormone reduction. Lee S (2001), investigating the
effect of estrogen on endothelial function in postmenopausal women
noted that supplementation with estrogen increased vasodilator
responses in postmenopausal women.
4.3.3. Correlation between IMT and cardiovascular risk factors
When multivariate analysis between femoral artery IMT and
cardiac risk factors, the analysis showed that the maximum blood
pressure, minimum blood pressure, LDL-C, estradiol and blood
glucose were correlated to a significant degree. mean with femoral
artery IMT, (p <0.05).
4.3.4. Correlation between FMD and cardiovascular risk factors
When multivariate analysis between FMD and risk factors, the
analysis showed that age, menopause, systolic blood pressure,

estradiol and blood glucose were significantly correlated with
decreased FMD.


23

CONCLUSION
1. Characteristics of femoral artery and FMD in menopausal
women and non-menopausal women
IMT thickness was higher in menopausal women than nonmenopausal women, the difference was statistically significant only
in common femaral artery (30.2% versus 17.2%), p <0.05.
The prevalence of IMT and atherosclerotic plaques varies with
menopause, menopausal women have menopause period (≥ 5 years),
and the proportion of IMT and femoral atherosclerotic plaques is
larger than those of menopause time <5 years, mainly found in
common femoral artery, (p <0.001). The prevalence of IMT and
atheroclerosis plaques varies with menopause, while among women
aged 50-60 years, the IMT and atheroclerosis are higher than among
women aged 40 - <50, mainly in common femoral artery. FMD in
menopausal women was lower than that of non-menopausal ươmen
(9.6% compared with 10.6%), p <0.05. The rate of FMD reduction
seen in menopausal women having menopause time (> 5 years) is
higher than that of menopausal women having menopause time ≤ 5
years (44.8% and 16.9%) (p <0.001). FMD among women aged 5060 years is higher than menopausal women aged 40 - <50 (33.5%
and 17.6%), (p <0.001).
2. Relationship between common femoral artery IMT thickness
and FMD and cardiovascular risk factors
An association between femoral artery IMT was found with
age (OR = 10.2), menopause year (OR = 13.8), BMI (OR = 2.3),
blood pressure (OR = 5.0), blood glucose (OR = 4,7), blood lipids

(OR = 3,2) and estradiol (OR = 2,6), with p <0,05.
Menopausal women had age-related FMD reduction (OR =
2,4), menopause (OR = 4.0), blood pressure (OR = 8.1), blood lipids
(OR = 2.9), glucose (OR = 4.7) and estradiol (OR = 3.0), with p
<0.05.
The femoral artery IMT is most affected by systolic blood
pressure (p <0.01), LDL – C (p <0.01), estradiol (p <0.01), blood
glucose (p <0.05), age (p <0.05) and diastolic blood pressure (p
<0.05).
Important risk factors affecting FMD reduction are age and
menopause (p <0.001), blood glucose (p <0.001), followed by
systolic blood pressure (p <0.05) and estradiol (p <0.05).


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