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Multicenter Study
. 2023 Oct;43(7):1496-1505.
doi: 10.1007/s10875-023-01523-6. Epub 2023 Jun 9.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19

Renata Moll-Bernardes  1 , Juliana R Ferreira  1   2 , Eduardo B Schaustz  1 , Andréa S Sousa  1   3 , João D Mattos  1 , Mariana B Tortelly  1   2 , Adriana L Pimentel  1   2 , Ana Cristina B S Figueiredo  1   2 , Marcia M Noya-Rabelo  1   2   4 , Sergio Fortier  1 , Flavia A Matos E Silva  1 , Narendra Vera  5 , Luciana Conde  5 , Mauro Jorge Cabral-Castro  6   7 , Denilson C Albuquerque  1   8 , Paulo Henrique Rosado-de-Castro  1 , Gabriel C Camargo  1 , Martha V T Pinheiro  1 , Daniele O L Freitas  1 , Ana M Pittella  1 , José Afonso M Araújo  1   2 , André C Marques  1   2 , Elias P Gouvêa  1   2 , Flavia V O Terzi  1   2 , Cleverson N Zukowski  1   2 , Ronaldo A O C Gismondi  1   2 , Bruno S Bandeira  1   2 , Renée S Oliveira  1   2   9 , Barbara E J Abufaiad  1   2 , Jacqueline S S Miranda  1   2 , Luiz Guilherme Miranda  1   2 , Olga F Souza  1   2 , Fernando A Bozza  1   3 , Ronir R Luiz  1   10 , Emiliano Medei  11   12   13
Affiliations
Multicenter Study

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19

Renata Moll-Bernardes et al. J Clin Immunol. 2023 Oct.

Abstract

Purpose: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated.

Methods: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury.

Results: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury.

Conclusion: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Keywords: COVID-19; Troponin; hypertension; immune system; myocardial injury.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Log transformed and standardized mean cytokine values in hypertensive patients with Covid-19 with and without myocardial injury. Color scale bar shows a range of log transformed and standardized mean cytokine values. The orange-yellow colors represent higher levels, and dark colors represent lower levels
Fig. 2
Fig. 2
Log transformed and standardized mean immune cell subsets values in hypertensive patients with Covid-19 with and without myocardial injury. Color scale bar shows a range of log transformed and standardized mean cytokine values. The orange-yellow colors represent higher levels, and dark colors represent lower levels
Fig. 3
Fig. 3
Heat map of correlations among log transformed and standardized immune cell subsets and cytokines in hypertensive patients with Covid-19 with and without myocardial injury. Color scale bar shows a range of correlation coefficients (r). The orange color represents a positive correlation, decreasing to dark colors bar, which represents a negative correlation
Fig. 4
Fig. 4
Receiver operating characteristic curves for immune markers associated with myocardial injury in hypertensive patients with COVID-19. A, Total lymphocytes; B, CD8+ HLA-DR+ MFI; C, CD8+ CD38+ MFI; D, EGF. COVID-19, 2019 coronavirus disease; AUC, area under the curve; HLA-DR, human leukocyte antigen DR isotope; MFI, mean fluorescence intensity; EGF, epidermal growth factor
Fig. 5
Fig. 5
Schematic illustration of the main findings: immune biomarkers associated with myocardial injury in hypertensive patients hospitalized with COVID-19
See this image and copyright information in PMC

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