La insuficiencia venosa crónica en el periodo gestacional
Authors
Chen, ChaowenDate
2022Affiliation
Universidad de Alcalá. Departamento de Medicina y Especialidades Médicas; Universidad de Alcalá. Programa de Doctorado en Epidemiología y Salud PúblicaKeywords
Insuficiencia venosa crónica
Gestación
Document type
info:eu-repo/semantics/doctoralThesis
Version
info:eu-repo/semantics/acceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Access rights
info:eu-repo/semantics/openAccess
Abstract
La enfermedad venosa crónica es una condición persistente, progresiva y frecuentemente subestimada; ampliamente representada en la población general, que tiene un enorme impacto socioeconómico, físico y psicológico asociado. Las mujeres tienen un mayor riesgo de aparición de insuficiencia venosa debido a diferentes factores hormonales y fisiológicos, especialmente durante el período gestacional.
El objetivo de la tesis es evaluar el impacto de la insuficiencia venosa crónica en mueres durante la gestación. Para ello, se han realizado diferentes trabajos, presentándose esta tesis por compendio de artículos.
El artículo I es una revisión bibliográfica actualizada de la Enfermedad Venosa Crónica, incluyendo su epidemiología, etiología y factores de riesgo, la fisiopatología y semiología de estos pacientes, incluidas las manifestaciones clínicas, el diagnóstico y los tratamientos¿encontrándose que prácticamente no existen estudios del efecto de la aparición de enfermedad venosa en las mujeres durante la gestación.
El artículo II, es un estudio transversal en el que se analiza y demuestra la asociación entre la aparición de varices infradiafragmáticas durante la gestación y alteraciones fetoplacentarias observadas por los clínicos y reflejadas en sus informes de alta, secundarias a hipoxia por compromiso fetal intraparto.
El artículo III es un estudio longitudinal en el que se hace analiza si existe alteración en la estructura y función celular de la placenta que sea el sustrato de los resultados gestacionales. En concreto, la implicación de la ILK y un conjunto de cadherinas (e-adherina, cadherina-6, y cadherina 7) en la placenta de mujeres con enfermedad venosa. Aims: Chronic venous disease is a persistent, progressive and frequently
underestimated condition, despite being widely represented in the general population
in the World. It has been demonstrated that women has a higher risk of suffer venous
insufficiency problems due to the different hormonal and physiological factors they
present during the perinatal period. The general objective of this dissertation is to
evaluate the specific impact of venous insufficiency in perinatal women.
Methods: To achieve the objective stated above, we conducted 3 specific scientific
studies. In the study I,we carried out a cross-sectional descriptive bibliographic review
of all the research published on chronic venous disease since 1988. From this review,
we compiled the most relevant evidence published on the topic of chronic venous
disease, with special emphasis on the pathophysiology and medical cognition of disease.
Secondly, the article II includes a cross-sectional study, in which we use accurate and
updated data from the administrative medical records (CMBD) corresponding to the
care registered in 2015, both in the public and private health systems of the different
Autonomous Communities of Spain. We used these data to study the association
between the prevalence of LEPVI and different risk factors, such as smoking, obesity,
asthma, hypothyroidism, and intrapartum fetal distress. We performed a conditional
logistic regression to estimate the adjusted odds ratios and the 95% Confidence
Intervalto assess the associations between LEPVI and the risk factors, as well as their
relationship with intrapartum fetal distress.
Finally, in Article III we developed an observational, analytical and prospective study
which included a sample of 114 women in the third trimester of pregnancy. A cohort
study was conducted by gathering information from a database from the Carlos III
Health Institute in 2017. Of these, 62 women were diagnosed with CVD according to
the CEAP classification. The rest of women (n= 52) did not presented CVD diseases in
their Electronic Health Record, and were included in the control group. Those women
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with CVD during pregnancy were identified to investigate its relationship with ILK
expression in placental villi associated with E-cadherin. The relationship between the
expression level of Cadherin 17 and Cadherin 6 with CVD was also explored. For this
purpose, we conducted a conditional logistic regression model to obtain 95%
confidence intervals (95% CI) during pregnancy.
Results:Each study included in this dissertation provided several results which jointly
contributed to achieving the objective of this thesis.
In article I, we find that CVD is a progressive and disabling condition widely
represented in the world population. We compiled some of the most relevant data on
such a complex topic, with special emphasis on the pathophysiological and medical
perceptions of the disease. In particular for the most vulnerable groups, such as the
elderly people, individuals with additional comorbidities and pregnant women.
In article II, we observed that, women with LEPVI were older and presented higher
prevalence of smoking, obesity, asthma, and hypothyroidism, in comparision with
those without LEPVI in the group control. In addition, women with LEPVI were more
likely to have conditions associated with intrapartum fetal distress (9.35%) than women
without this disease (7.41%). Women with LEPVI are 30% (OR = 1.30, 99.5% CI:
1.08-1.54) more likely to have an IFC outcome during the pregnancy, and to have
placental dysfunction (OR = 1.74, 99.5% CI: 1.00-3-05), as well. After adjusting for
age, smoking, obesity, asthma, hypothyroidism, coagulopathy disorders, and anemia,
this association remained significant but slightly attenuated for IFC (OR=1.25, 99.5%
CI, 1.05-1 .50) and placental dysfunction (OR = 1.23, 99.5% CI: 1.01-1.49). However,
there was no association between LEPVI and fetal distress (OR = 1.01, 99.5% CI: 0.46-
2.21).
In article III, women with CVeD during pregnancy show an increase in ILK expression
in the placental villi associated with a decrease in E-cadherin. Histological analysis of
protein expression by immunohistochemical techniques showed a significant increase
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in ILK expression in placental villi of women with CVD during pregnancy compared
to HC, ***p < 0.001 [CVeD = 2.379 ± 0.084 vs HC = 0.976 ± 0.082]. In contrast, we
observed a significant decrease in E-Cad gene expression in the placental villi of
women with CVeD during pregnancy compared to HC, **p = 0.0084 [CVeD = 10.726
± 0.359 vs HC = 11.893 ± 0.461]. In addition, protein expression showed a significant
decrease in E-Cad expression in the placental villi of women with CVeD during
pregnancy compared to HC, ***p = 0.002 [CVeD = 0.903 ± 0.062 vs HC = 1.240 ±
0.058]. The expression level of Cadherin 17 and Cadherin 6 increases in the placental
villi of women with CVD during pregnancy. Cad-17 gene expression showed a
significant increase in placental villi of women with CVD during pregnancy compared
to HC, *p = 0.0228 [CVeD = 7.804 ± 0.325 vs HC = 6.780 ± 0.263]. In this sense,
protein expression showed a significant elevation by immunohistochemical techniques
in the placental villi of women with CVD during pregnancy compared to HC, ** p =
0.0026 [CVeD = 1.403 ± 0.067 vs HC = 1.159 ± 0.085 ]. Similarly, our results have
shown an increase in Cad-6 gene expression in the placental villi of women with CVD
during pregnancy compared to HC, ** p = 0.0016 [CVeD = 7.083 ± 0.251 vs HC =
5.807 ± 0.247]. Furthermore, protein expression showed a significant increase in the
placental villi of women with CVeD during pregnancy compared to HC, **p = 0.0033
[CVeD = 1.202 ± 0.065 vs HC = 0.923 ± 0.066].
Conclusions: CVD is a progressive and disabling disease with high impact in the world
population health. Therefore, the management of pathophysiology and therapeutics is
fundamental and was one of the objectives of our study. An increasing number of
studies, focused on CVD, show the relevance of this vascular pathology, especially in
the most advanced stages (CVI). In this dissertation, we collect some of the most
relevant data on this important topic, with a special emphasis on pathophysiological
and medical insights into the disease. An integrative perspective of this condition would
bring immediate benefits for the clinical management of these patients, particularly for
the most vulnerable groups, such as the elderly people, individuals with additional
comorbidities and pregnant women.
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The second study aimed to determine the association between varicose veins in
pregnancy and placental insufficiency. This study represented a nationwide crosssectional
analysis in Spain to explore the association between the presence of varicose
veins and the existence of alterations in the ischemic placental function. An extensive
database gathered from hospital administrations was used for that purpose.
In the third study, the relationship between chronic venous disease in pregnant women
was observed, causing an increase in ILK in the placental villi associated with a
decrease in E-Cadherin, demonstrating a significant increase in the expression of ILK
proteins and genes, cadherin-6 and cadherin-17 and a reduction in e-cadherin,
associated with the development of CVD during pregnancy.
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