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Post-Acute COVID-19 Syndrome: Prevalence of Peripheral Microvascular Endothelial Dysfunction and Associations with NT-ProBNP Dynamics - 18/11/24

Doi : 10.1016/j.amjmed.2024.10.012 
Marcus Ståhlberg, MD, PhD a, b, Katarina Fischer, MSc a, b, Maged Tahhan, BSc a, b, Allan Zhao, MD c, Artur Fedorowski, MD, PhD a, b, Michael Runold, MD, PhD a, d, Malin Nygren-Bonnier, PhD e, f, Mikael Björnson, MD a, g, Lars H. Lund, MD, PhD a, b, Judith Bruchfeld, MD, PhD a, g, Liyew Desta, MD, PhD a, b, Frieder Braunschweig, MD, PhD a, b, Ali Mahdi, MD, PhD a, b,
a Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden 
b Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden 
c Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden 
d Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden 
e Division of Physiotherapy, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden 
f Women's Health and Allied Health Professionals Theme, Medical Unit Allied Health Professionals 
g Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden 

Requests for reprints should be addressed to Ali Mahdi, MD, PhD, Department of Medicine, Solna, Karolinska Institutet, SE-171 77 Stockholm, Sweden.Department of MedicineSolnaKarolinska InstitutetStockholmSE-171 77Sweden

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Abstract

Background

Post-acute COVID-19 syndrome (PACS) has been linked to microvascular endothelial dysfunction as a potential underlying pathomechanism and can manifest even following a mild course of the initial infection. Prevalence of microvascular endothelial dysfunction and circulating natriuretic peptides in such PACS patients remains unknown.

Methods

This prospective, cross-sectional cohort study enrolled 92 patients (82% females, median age 48 years) with PACS. Reactive hyperemia index (RHI) was evaluated with peripheral arterial tonometry, where <1.67 was defined as microvascular endothelial dysfunction, 1.67-2.0 as impaired function, and >2 normal endothelial function, on average 31 months after the acute infection. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected at 2 different time points within over a 1-year span.

Results

In total, 41% of PACS subjects had microvascular endothelial dysfunction and 20% had impaired RHI. No major differences in clinical characteristics, routine chemistry laboratory testing, or symptom burden were observed across the groups. Only subjects with microvascular endothelial dysfunction and impaired endothelial function had a significant increase in NT-proBNP levels over time, and those with larger increase in NT-proBNP had significantly lower RHI. There was a significant correlation between relative or absolute increase in NT-proBNP and RHI, which remained significant in a multivariable adjusted linear regression.

Conclusions

Peripheral microvascular endothelial dysfunction was prevalent in a symptomatic PACS population long after recovery from a mild acute infection. Increases in NT-proBNP levels were associated with microvascular endothelial dysfunction, suggesting a link between, and providing a foundation for, future studies on post viral microvascular endothelial dysfunction in PACS.

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Graphical abstract

Ninety-two subjects with post-acute COVID-19 were enrolled in this prospective cohort study. Subjects contracted acute COVID-19 during the first wave. N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1 and symptom evaluation were performed around 10 months after the acute infection. Around 2-3 years after the acute infection, an additional NT-proBNP was collected and evaluation of microvascular endothelial function with reactive hyperemia index (RHI) as readout was performed. Forty-one percent of the subjects had microvascular endothelial dysfunction microvascular endothelial dysfunction (MVD) and 20% had impaired RHI. These 2 groups had increase in NT-proBNP levels, whereas no change in NT-proBNP levels was observed in the group with normal RHI. A significant correlation between microvascular function in all patients and delta or relative change in NT-proBNP levels was observed. No major differences were observered in clinical characteristics.



Image, graphical abstract

El texto completo de este artículo está disponible en PDF.

Keywords : Microvascular endothelial dysfunction, Natriuretic peptides, Post-acute COVID-19 syndrome


Esquema


 Funding: This work was supported by the Swedish Heart and Lung Foundation (20210062 and 20210543), the Swedish Research Council (2021-06531), the Stockholm County Council (988725 and 964100), Dysautonomia International, and Insamlingsstiftelsen Kvinnor och Hälsa.
 Conflicts of Interest: AF: Consulting fees for ArgenX BV. JB: Payment to personal company for Lectures on post-COVID for dermatologists, arranged by Novartis. LHL: Grants, consulting, honoraria to author's institution: Alleviant, Amgen, AstraZeneca, Bayer, Biopeutics, Boehringer Ingelheim, Edwards, Novartis, Novo Nordisk, Owkin, Pharmacosmos, Vifor Pharma; Stock ownership: AnaCardio. FB: consulting fees, all to employer for: AstraZeneca, Pfizer, Novartis, Orion, Boehringer Ingelheim, Biosense Webster, Boston Scientific. All unrelated to the current study. The rest of the authors declare no competing interests.
 Authorship: All authors had access to the data and a role in writing the manuscript. MS, MR, JB, and AM contributed to the study design. MS, KF, MT, MB, and AM acquired the data. AZ and AM conducted the analyses. AM drafted the manuscript. All authors were involved in data interpretation and critically reviewed and approved the manuscript.


© 2024  The Authors. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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