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Study Analyzes Association Between Obesity and Endothelial Dysfunction in COVID-19 Patients

Publicado em 16 novembro 2021

In COVID-19 patients, obesity is the factor most associated with the development of endothelial dysfunction, a condition in which blood vessels become unable to adequately contract and relax, increasing the risk of events such as heart attacks, thrombosis (blood clotting), and stroke.

Endothelium refers to the thin layer of cells that line the walls of arteries and veins, as well as inside the heart. Endothelial cells release substances that control vascular relaxation and contraction, and enzymes that regulate blood clotting and immune function.

The association between obesity and endothelial dysfunction in COVID-19 patients is analyzed in an article published in the journal Obesity. The authors are researchers from Brazilian universities, with the exception of one affiliated with a Colombian university. The group is supported (17 / 25648-4 and 15 / 26501-1) by the FAPESP.

The study analyzed data from 109 patients hospitalized with acute COVID-19 but not in critical condition. “We characterized patients in general and then sought to identify factors that could modulate or intensify endothelial damage. The results showed that the key factor was BMI. [body mass index], followed by far by the level of creatinine in the blood, a marker of kidney function, ”said Alessandro Domingues Heubel, doctoral student in physiotherapy at the Federal University of São Carlos (UFSCar) in the state of São Paulo, au Brazil, and first author of the article.

Heubel explained that BMI (weight divided by height squared) is one of the main parameters used by medical professionals to measure overweight and obesity. Individuals with a BMI of 30 kg / m2 and more are considered obese.

Patients of both sexes were included in the study. Their average age was 51 and 51% were men. They were undergoing treatment at Bauru State Hospital and Santa Casa de São Carlos in São Paulo State. Their most common comorbidity was obesity (62%), followed by hypertension (47%) and diabetes (17%).

Blood samples were taken shortly after hospital admission, and endothelial function was assessed non-invasively 72 hours later by the flow-mediated dilation (FMD) method, in which the Brachial artery diameter (the main blood vessel in the upper arm) is measured by high-resolution ultrasound before and after circulation is restricted in the forearm for a few minutes.

"Immediately after removal of the occlusion cap, blood flow in the artery increases, and this is a mechanical stimulus for the endothelial cells [which line the inside of blood vessels] produce nitric oxide, a vasodilator. The more the artery dilates, the better the endothelial function. We found that foot-and-mouth disease was very low in these obese patients with COVID-19 during the period of active infection. “

Alessandro Domingues Heubel, PhD student in physiotherapy, Federal University of São Carlos

In addition to foot-and-mouth disease and BMI, the researchers assessed muscle health by measuring grip strength with a dynamometer and analyzed blood levels of hemoglobin, leukocytes, lymphocytes, creatinine and platelets, as well as C reactive protein, ferritin and D-dimers (markers of inflammation and coagulation). Other parameters included time since symptom onset, smoking, co-morbidities, and medications used. No patient was in intensive care at the time of this assessment, but 72% were using supplemental oxygen.

To find the determinants of endothelial dysfunction in the study sample, the researchers used univariate regression (a statistical technique that predicts the values ​​of one variable from the values ​​of another) and multiple regression ( which analyzes several variables simultaneously). Only a high BMI and creatinine level were directly correlated with a decrease in foot-and-mouth disease.

According to Renata Gonçalves Mendes, professor at UFSCar and thesis director at Heubel, each additional unit of BMI corresponded to a 0.19% decrease in foot-and-mouth disease.

“When two COVID-19 patients are compared, one with normal weight [BMI ≈ 20 kg/m2] and the other obese [BMI ≥ 30 kg/m2], the latter tends to have FMD 1.9% lower. Based on prior knowledge, this suggests a 17% higher cardiovascular risk, ”Mendes told Agência FAPESP.

“In clinical practice, we find that obese patients have more cardiovascular events during their hospitalization. Our study may help to understand the mechanisms underlying this problem and why obesity increases the risk of progression to COVID- 19 severe. “

Previous proof

Since the start of the SARS-CoV-2 pandemic, researchers have speculated that the virus could directly infect and damage endothelial cells, and this has been confirmed in studies using samples obtained from autopsies. of patients who died from COVID-19. .

The damage caused to the endothelium by the virus may also be associated with blood clotting disorders leading to the formation of microthrombi and the development of intense systemic endothelial dysfunction, both of which are believed to explain the progression to severe COVID-19. .

“We do not yet know for sure to what extent endothelial dysfunction is directly caused by damage caused by the virus or by the cytokine storm typical of this disease [in which the immune system releases large amounts of inflammatory molecules]”said Heubel.

Previous research has shown that obesity increases the risk of severe COVID-19 regardless of age, gender, ethnicity, and comorbidities such as diabetes, high blood pressure, and heart or lung disease (more on: agencia.fapesp.br/34343). The reasons for this are the mechanical alterations of the respiratory system due to the increase in abdominal mass, which compresses the diaphragm and the lungs. Obese people also often have a weakened immune system.

There is some evidence that SARS-CoV-2 can infect fat cells and that fat tissue can become a reservoir for the pathogen. As a result, viral loads in obese people tend to be higher than in individuals of normal weight (more on: agencia.fapesp.br/33729).

“One possible explanation for our results is that higher viral loads in obese people increase the risk of direct endothelial cell infection,” Heubel said. “It may also be that the process is influenced by inflammation, which is usually exacerbated in overweight people. Limitations associated with the study design prevented us from observing a direct correlation between inflammatory markers and foot-and-mouth disease.”

For the researchers, healthcare workers should become more attentive to vascular complications when treating obese patients with COVID-19. “They are more sensitive to cardiovascular events and therefore need more assistance. Several strategies are available to prevent the development of complications,” Heubel said.

According to Mendes, the results pave the way for new therapeutic approaches focused on the endothelium. “It would be a good idea to research a compound that can block the process that leads to endothelial dysfunction, given the associated risk of serious complications,” she said.

Many study participants progressed to critical condition after being admitted to hospital and required intensive care, according to Emmanuel Gomes Ciolac, professor at São Paulo State University (UNESP) in Bauru and before. -last author of the article.

“This is a large-scale project, in which patients are assessed at three points in time – in hospital, 30 to 45 days after discharge and four months after discharge. Further results will be communicated soon.” , did he declare.

For Ciolac, the data obtained so far underscores the need for society to view obesity as a serious problem. “We urgently need broad and effective public health policies to tackle this disease, which is associated with severe COVID-19 and countless other disorders,” he said.

Source:

São Paulo Research Foundation (FAPESP)

Journal reference:

Heubel, AD, et al. (2021) Determinants of endothelial dysfunction in non-critically ill hospitalized COVID-19 patients: a cross-sectional study. Obesity. doi.org/10.1002/oby.23311.

Sources

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