In patients with Covid-19, obesity is the factor that is most associated with the development of endothelial dysfunction – a condition in which blood vessels lose the ability to contract and relax properly, increasing the risk of events such as heart attack, thrombosis and stroke brain (stroke).
The finding was made by a group of researchers supported by FAPESP based on data from 109 hospitalized patients with moderate conditions of the disease. The results were published in the magazine obesity.
“We performed the general characterization of these patients and tried to identify which factors could modulate or accentuate the endothelial damage. The results indicate that the most prevalent item was the BMI [índice de massa corporal]. In second place, with much less relevance, we find the level of creatinine in the blood, which is a marker related to renal function”, says Alessandro Domingues Heubel, doctoral candidate in the Postgraduate Program in Physiotherapy at the Federal University of São Carlos (UFSCar) and first author of the article.
Heubel explains that BMI is one of the main tools used by health professionals to measure the degree of overweight and obesity. The index is calculated by dividing weight (in kilograms) by height (in meters) squared. Individuals with a result equal to or greater than 30 kg/m2 are considered obese.
Patients of both genders, with a mean age of 51 years, admitted to the State Hospital of Bauru and Santa Casa de São Carlos were included in the research. Obesity was the most prevalent comorbidity (62%) in this population, followed by hypertension (47%) and diabetes (17%).
Blood samples were collected soon after hospital admission and endothelial function was assessed 72 hours later using a parameter known as flow-mediated dilation (FMD). The non-invasive method consists of measuring the diameter of the brachial artery (in the arm), through a vascular ultrasound exam, before and after a maneuver that obstructs the blood flow of the forearm for a few minutes.
“Immediately after unblocking, there is an increase in blood flow in the artery and this constitutes a mechanical stimulus for the endothelial cells [que formam o revestimento interno dos vasos sanguíneos] produce nitric oxide, a vasodilating substance. The more the artery dilates, the better the endothelial function. And we saw that obese patients, in the period of active infection by Covid-19, had very small flow-mediated dilation”, says the doctoral student.
In addition to FMD and BMI, handgrip strength was measured (measured with a dynamometer and applied to assess physical capacity) and blood levels of hemoglobin, leukocytes, lymphocytes, platelets, C-reactive protein (inflammation marker) were analyzed. , ferritin, D-dimer (thrombosis marker) and creatinine. The analysis also considered age, presence of comorbidities, physical activity, smoking and medications used. At the time they were evaluated, none of the participants were admitted to the Intensive Care Unit (ICU), but 72% were using oxygen supplementation.
To find the determinants of endothelial dysfunction in the sample evaluated, a univariate regression analysis was performed (a statistical technique that allows considering each risk factor separately) and also a multiple regression analysis (which analyzes the factors together). Only high BMI and creatinine level were directly related to the reduction in FMD.
According to UFSCar professor Renata Gonçalves Mendes, a Heubel advisor, each additional unit in the BMI represented a 0.19% reduction in FMD.
“When two patients with Covid-19 are compared, one with normal weight [IMC de 20 kg/m2] and the other one with obesity [IMC de 30 kg/m2], the latter tends to have a 1.9% lower FMD value. Based on prior knowledge, this suggests an increased cardiovascular risk of approximately 17%,” the researchers state in the article.
“In clinical practice, we see that obese people have more cardiovascular events during hospitalization. Our study can help to understand one of the mechanisms by which this happens and why obesity increases the risk of worsening Covid-19”, says Mendes to the FAPESP Agency.
Since the beginning of the pandemic caused by Sars-CoV-2, several studies have hypothesized that the virus could directly infect and damage endothelial cells, which was proven in analyzes performed with autopsy samples carried out on patients who died of Covid- 19.
It is also speculated that the endothelial damage caused by the virus is associated with blood coagulation disorders (microthrombi formation) and the development of intense and systemic endothelial dysfunction, two factors that would lead to aggravation of the condition.
“We still don’t know for sure to what extent endothelial dysfunction is due to direct damage caused by the virus or a consequence of the cytokine storm [liberação de moléculas inflamatórias pelo sistema imune] typical of Covid-19”, ponders Heubel.
Previous studies have shown that obesity increases the risk of worsening Covid-19 regardless of age, gender, ethnicity and the existence of comorbidities such as diabetes, hypertension, heart or lung disease. Among the reasons are mechanical changes in the respiratory system caused by increased abdominal content, which compresses the diaphragm and lung. In addition, obese people often have dysfunctions in the immune system.
There is evidence that Sars-CoV-2 is capable of infecting adipose tissue cells, which end up serving as a reservoir for the pathogen. This contributes to the fact that, in general, the viral load of obese individuals is higher than that of non-overweight individuals.
“One possible explanation for our findings is that the higher viral load of obese individuals increases the risk of direct infection of endothelial cells. It is also possible that inflammation, which is usually more exacerbated in overweight individuals, has an influence on the process. But due to limitations associated with the study design, it was not possible to observe a direct correlation between inflammatory markers and FMD”, says the doctoral student.
For researchers, health professionals should be more aware of vascular complications when treating obese patients with Covid-19. “Because they are more susceptible to cardiovascular events, they need more assistance. And we have several strategies to prevent complications from developing,” says Heubel.
Mendes believes that the findings pave the way for the search for new therapeutic approaches focused on the endothelium. “It would be interesting to look for a compound capable of stopping the process that leads to endothelial dysfunction, as it is a factor that increases the risk of serious complications.”
Emmanuel Gomes Ciolac, professor at the São Paulo State University (Unesp) in Bauru and co-author of the article, says that many study participants evolved into critical cases during hospitalization and needed to be admitted to the ICU.
“This is a large project, in which patients are being evaluated in three stages: hospital, between 30 and 45 days after discharge, and again four months after hospital discharge. More results should be announced soon”, he says.
For Ciolac, the data obtained so far reinforce the need for society to look at obesity as a serious problem. “Broad and efficient public health strategies are urgently needed to combat this disease, which is associated with the greater severity of Covid-19 and countless other diseases.”
The article Determinants of endothelial dysfunction in non-critically ill hospitalized COVID-19 patients: a cross-sectional study can be read at: https://onlinelibrary.wiley.com/doi/10.1002/oby.23311.