Circulating cytokines predict severity of rheumatic heart disease

Soares, Adriana C.; Passos, Lívia Silva Araújo; Sable, Craig; Beaton, Andrea; Ribeiro, Victor Teatini; Gollob, Kenneth J.; Dutra, Walderez Ornelas; Nunes, Maria Carmo P.

doi:10.1016/j.ijcard.2019.04.063

Cited by 28 publications

(15 citation statements)

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“…There are an estimated 33 million individuals currently living with RHD, accounting for over a million premature deaths annually (1). We have demonstrated that patients with RHD have higher serum levels of inflammatory mediators than healthy controls, which is a clear evidence of ongoing inflammation (2)(3)(4). It is also known that expression of inflammatory cytokines increases in patients with significant pressure or volume overload due to valvular heart disease or chronic heart failure (5)(6)(7).…”

Section: Introductionmentioning

confidence: 77%

Decreased Cytokine Plasma Levels and Changes in T-Cell Activation Are Associated With Hemodynamic Improvement and Clinical Outcomes After Percutaneous Mitral Commissurotomy in Patients With Rheumatic Mitral Stenosis

Silva

Neves

Passos

et al. 2021

Front. Cardiovasc. Med.

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Mitral stenosis (MS) is a consequence of rheumatic heart disease that leads to heart failure requiring mechanical intervention. Percutaneous mitral commissurotomy (PMC) is the treatment of choice for the intervention, and currently there are no soluble markers associated with hemodynamic improvement after PMC. This study aims to determine the changes in cytokine/chemokine plasma levels, as well as T cell activation after PMC, and to investigate their association with immediate hemodynamic improvement and clinical outcomes. Plasma samples from eighteen patients with well-defined MS who underwent PMC and 12 healthy controls were analyzed using BioPlex immunoassay. We observed that 16 out of the 27 (60%) molecules assessed were altered in patients' plasma pre-PMC as compared to control group. Of those, IL-1β, IL-12, IL-6, IL-4, PDGF, and CCL11 showed significant decrease after PMC. Stratifying the patients according to adverse outcome after a 28-month median follow up, we detected a significant reduction of IL-1β, IL-12, IL-6, IL-4, IFN-γ, CXCL-10, VEGF, FGF and PDGF post-PMC in patients without events, but not in those who presented adverse events during the follow-up. Patients with adverse outcomes had lower IL-10 pre-PMC, as compared to the ones without adverse events. In addition, the frequency of CD8+ activated memory cells was increased after PMC, while the frequency of CD4+ activated memory cells did not change. Our results show an association between the decrease of specific cytokines and changes in T cell activation with hemodynamic improvement post-PMC, as well as with long-term outcomes, suggesting their possible use as soluble markers for hemodynamic recovery after MS intervention.

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Section: Introductionmentioning

confidence: 77%

Decreased Cytokine Plasma Levels and Changes in T-Cell Activation Are Associated With Hemodynamic Improvement and Clinical Outcomes After Percutaneous Mitral Commissurotomy in Patients With Rheumatic Mitral Stenosis

Silva

Neves

Passos

et al. 2021

Front. Cardiovasc. Med.

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“…In particular, the pro-inflammatory cytokines TNF-α, interleukin-6, and interleukin-17A are involved in the pathogenesis of both SA and VHD ( 33 , 34 ). These considerations are probably true not only for rheumatic VHD, but also for non-rheumatic ones ( 34 , 35 ). Because we herein show that the association frequency of SA and VHD increases in parallel with AHI increment, it can be reasonably argued that intensification of oxidative stress and inflammation favors the concomitance of upper airway obstruction and cardiac valve dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Association Between Sleep Apnea and Valvular Heart Diseases

et al. 2021

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Background: Although sleep respiratory disorders are known as a relevant source of cardiovascular risk, there is a substantial lack of trials aimed to evaluate the eventual occurrence of associations between sleep apnea (SA) and valvular heart diseases (VHD).Methods: We recruited 411 patients referring to our sleep disorder unit, among which 371 had SA. Ninety-three subjects with SA also suffered from VHD. Physical examination, echocardiography, nocturnal cardio-respiratory monitoring, and laboratory tests were performed in each patient. Patient subgroups were comparatively evaluated through cross-sectional analysis.Results: A statistically significant increase in the prevalence of VHD was detected in relation to high apnea hypopnea index (AHI) values (p = 0.011). Obstructive sleep apnea occurrence was higher in SA patients without VHD (p < 0.0001). Conversely, central and mixed sleep apneas were more frequent among SA patients with VHD (p = 0.0003 and p = 0.002, respectively). We observed a direct correlation between AHI and BMI values (p < 0.0001), as well as between AHI and serum uric acid levels (p < 0.0001), high sensitivity C-reactive protein (p < 0.0001), and indexed left ventricular end-diastolic volume (p < 0.015), respectively. BMI and VHD resulted to be the main predictors of AHI values (p < 0.0001).Conclusions: Our study suggests that a significant association can occur between SA and VHD. It is clinically relevant that when compared to SA patients without VHD, higher frequencies of central and mixed apneas were found in subjects with SA and VHD. Moreover, after elevated BMI, VHD represented the second predictor of AHI values.

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“…Numerous studies on the plasma, PBMC and inflammatory lesions of patients with ARF and RHD have implicated cytokine imbalance and cytokine dysregulation in the pathogenesis of these diseases [104,115,116]. Variations in genes encoding several cytokines, including TNFα, IL-10 and IL-6, have been implicated in increased host susceptibility to ARF and RHD.…”

Section: Genes Encoding Cytokinesmentioning

confidence: 99%

“…While IL-10 diminishes T-cell stimulation and inhibits secretion of pro-inflammatory cytokines, it enhances B-cell survival and proliferation and production of antibodies, including autoantibodies. Several studies have shown that IL-10 production is increased in patients with ARF and RHD [88,116,123] and two different studies of RHD patients in…”

Section: Genes Encoding Cytokinesmentioning

confidence: 99%