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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF NATIONAL DEFENCE 108 INSTITUTE OF CLINICAL MEDICAL AND PHARMACEUTICAL SCIENCES LƯƠNG THỊ HƯƠNG LOAN RESEARCH OF INTIMA MEDIA-THICKNESS AND

MINISTRY OF EDUCATION AND TRAINING MINISTRY OF 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

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

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)

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

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

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

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

Women with diabetes and hypertension

Women with peripheral artery disease and varicose veins 2.2 Research Methods

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

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

Parameters

Menopausal women (n = 232)

menopasal women (n = 58) p Trung bình Trung bình

Non-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

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

(mmHg) 127,6 ± 14,9 113,1 ± 16,2 < 0,001 Diastolic blood pressure

(mmHg) 79,0 ± 10,0 71,2 ± 10,4 < 0,001 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

Table 3.11 Morphological characteristics and thickness of IMT, atherosclerosis of menopausal women and non-menopausal women Group

IMT, atheroclerosis

Menopaus

al women (n= 232)

menopausal women (n = 58) p

< 0,05 IMT (>1mm) 70 30,2 10 17,2

Table 3.12 The ratio of IMT and atheroclerosis according to menopause

> 5 years (n =96) p

Atheroclerosis (≥

14,

6 < 0,001 Shallo

Atheroclerosis (≥

Menopausal time

IMT, atheroclerosis

≤ 5 years (n = 136)

> 5 years (n =96) p

Atheroclerosis (≥

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

FMD

Menopausal women