Abstract 14725: Association of Adipokines With Subclinical Myocardial Dysfunction - The Multi-Ethnic Study of Atherosclerosis (MESA)

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Mohammad R Ostovaneh ◽  
Bharath Ambale Venkatesh ◽  
Kihei Yoneyama ◽  
Shishir Sharma ◽  
Matthew A Allison ◽  
...  

Background: Adipokines such as adiponectin, leptin and resistin have been associated with heart failure. We explore the association of adipokines and myocardial fibrosis as MRI-derived measure of subclinical myocardial dysfunction. Methods: For the current analysis, we studied MESA subjects who had adiponectin, leptin, resistin and TNF-α measured at second/third follow-up exams (2003-2005) and underwent post gadolinium MRI T1 mapping at 25 minutes for assessment of myocardial fibrosis at the fifth follow-up exam (2010 -2012). Linear regression analysis was used to evaluate the association of log-transformed adipokine levels with T1 time. BMI-stratified analysis was performed when the interaction term of BMI and adipokines was significant. Lower T1 time reflects greater myocardial fibrosis. Results: Four hundred and twenty three subjects (mean age: 61.4(8.1), 187 females) were included in the analysis. Median values of adiponectin, leptin, resistin and TNF-α were 16.9 μg/ml (IQR: 11-25), 11.1 ng/ml (IQR:5-25), 14 ng/ml(IQR:11-17) and 4.5 pg/ml(IQR:3.5-5.9). Higher adiponectin was associated with lower degree of myocardial fibrosis in subjects with BMI<25 (p = 0.005). Higher leptin in individuals with BMI≥30 (p<0.001) and higher resistin in those with BMI<25 (p=0.02) was associated with greater myocardial fibrosis. Conclusion: Higher adiponectin is associated with lower degree of myocardial fibrosis in normal weight subjects. Leptin in obese individuals and resistin in those with normal BMI are positively associated with myocardial fibrosis.

2021 ◽  
Vol 22 (Supplement_2) ◽  
Author(s):  
M Karolyi ◽  
M Kolossvary ◽  
L Weber ◽  
I Matziris ◽  
J Sokolska ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Both ST elevation (STE) on ECG and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) are related to poor outcome in myocarditis. Purpose We evaluated if there is an association between regional STE and LGE pattern in patients with suspected myocarditis. Methods 51 patients (42 male, 32 ± 13 years old) underwent 12-lead ECG and CMR with LGE due to suspected myocarditis. &gt;1mm STE was assessed in the antero-septal (V1-V4, aVR), inferior (II, III, aVF) and lateral (I, aVL, V5-V6) localizations. LGE was quantified as visual presence score (VPS) (1-17) and visual transmurality score (VTS) (1-68) on CMR, according to the 17-segment AHA model. STE and LGE were correlated using linear regression analysis.  Results 31% of the patients had STE on admission ECG and a median VPS of 3 (IQR: 1-5) and VTS of 6 (IQR: 3-11) on CMR. STE showed an association with VPS and VTS in univariate and multivariate analysis (p &lt; 0.001 all). STE was most frequent in the lateral and inferior leads (48% and 31%) which correlated with regional VPS and VTS in univariate model (p &lt; 0.05 all), and remained significant in multivariate analysis for VPS (p &lt; 0.05 both). STE was less frequent in the antero-septal region (21%, where no association between LGE and STE could be revealed (p &gt; 0.05 all). Conclusions  Inferior and lateral STE in myocarditis is associated with regional LGE on CMR, which is an indicator of myocardial fibrosis and possible poor outcome. Our results need not be validated on larger cohorts with follow-up.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Tamar S Polonsky ◽  
Dongxue Zhang ◽  
Lydia A Bazzanno ◽  
Michael H Criqui ◽  
Luigi Ferrucci ◽  
...  

Background: Overweight or obese adults with PAD have greater functional decline than normal-weight adults with PAD. Walking exercise is first-line therapy for PAD. It is unknown whether weight loss+exercise is associated with less functional decline than exercise alone. Weight loss could worsen functional decline by decreasing muscle mass. Methods: Adults with PAD (ABI <0.90) and BMI ≥25 kg/m 2 underwent baseline testing 2002-2004. Mean follow-up was 3.4 years. Weight, six minute walk distance (6MWD) and self-reported exercise were measured annually. Weight loss was defined as ≥5 lb decrease compared to the prior year. Exercise was defined as walking ≥3 times/week for ≥30 min. To compare annual changes in 6MWD between groups (no exercise, exercise only, or exercise+weight loss) a mixed-effects linear regression analysis was used with a subject-specific random intercept, to account for the chance that a person’s annual change in 6MWD correlated with the prior annual change. Person-years for each group were summed from successive annual changes; adults could contribute person-years to ≥1 group. Analyses were adjusted for age, race, sex, ABI, smoking, comorbidities, lower extremity revascularization or hip/knee replacement during follow-up. Results: Among 271 adults (41% women, 15% black), mean age was 74±7.6 and ABI was 0.64±0.15. Mean baseline BMI was similar across groups (no exercise 30.7±4.6 kg/m 2 ; exercise only 28.8±3.5 kg/m 2 ; exercise+weight loss 30.1±4.3 kg/m 2 ). PAD participants who walked for exercise and lost weight had less decline in 6MWD than those who walked without weight loss, or who neither exercised nor lost weight (p trend = 0.004) (Table). Conclusions: Overweight and obese adults with PAD who exercised and lost ≥5 lbs experienced less annual decline in the 6MWD than adults with only exercise or no exercise. A randomized trial is needed to determine whether weight loss+exercise improves functional outcomes for overweight or obese adults with PAD.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1099.2-1099
Author(s):  
E. Chatelus ◽  
V. Poindron ◽  
M. Canuet ◽  
A. S. Korganow ◽  
P. Germain ◽  
...  

Background:All patients included in the study fulfilled the ACR/EULAR classification criteria for SSc. We prospectively included patients who underwent at least two CMR at 1.5T, including native T1 and T2 mapping (which give account for myocardial fibrosis and myocardial edema respectively), left and right ventricles morphology and functional assessment, and Late Gadolinium Enhancement (LGE) as a part of routine follow-up between 2015 and 2019.Objectives:To evaluate the prognostic value of initial abnormal T1 mapping.Methods:All patients included in the study fulfilled the ACR/EULAR classification criteria for SSc. We prospectively included patients who underwent at least two CMR at 1.5T, including native T1 and T2 mapping (which give account for myocardial fibrosis and myocardial edema respectively), left and right ventricles morphology and functional assessment, and Late Gadolinium Enhancement (LGE) as a part of routine follow-up between 2015 and 2019.Results:Sixty-three patients underwent at list two CMR during the study period. Forty-three patients were women. Mean age was 52.5±15.5 years old. Follow-up duration between the initial and the follow-up CMR was 14.5±11.5 months. Forty-one had diffuse SSc. The mean native T1 was 1066.8 ±44.6 ms. Twenty-one patients suffered from cardiac clinical manifestations. Nine patients died during the follow-up. Thirty patients (47.6%) had elevated T1 (ET1) with mean T1 1105.4±36.7 ms at the time of initial CMR. Initial ET1 was clearly correlated with: 1/ alteration of Left Ventricle (LV) Ejection fraction (EF) (r=0.5, p<0.0001) during the study period, 2/LV dilatation at initial screening and follow up (r=0.22, p=0.03 and r=0.3, p=0.02). Regarding Right ventricle, initial ET1 was correlated with initial Right Ventricle (RV) dilatation (r=0.3, p=0.02) but neither with RV volume nor RVEF at follow-up. Interestingly, initial ET1 correlated with pericardial effusion (r=0.3, p=0.003) which is known to be a pejorative prognostic factor. Seventeen patients (28%) had LGE but the ET1 at initial screening and follow-up was not correlated with LGE.Six patients had elevated T2 (ET2) which correlated with initial and follow up LV dilatation (r=0,32, p=0.002 and r=0.5, p<0.0001 respectively) but not with LVEF during the period study. Among other parameters, initial increased BNP was correlated with follow up ET1 LVEF and RVEF (r=0.4, p=0.01; r=0.35, p=0.007; r=0,37, p=0.005 respectively). In the same way, initial Pulmonary Arterial Hypertension (PAH) was correlated with follow up ET1 (r=0.3, p=0.02). Initial ET1 did not correlate with age, sex, cardiovascular risk factors, cardiac manifestations or death.Conclusion:Assessment of diffuse myocardial fibrosis by native T1 is predictive of the occurrence of cardiac dysfunction at the follow-up as initial ET1 was associated with decreased left ventricular function and LV and RV dilatations). These data highlights the potential role of CMR with T1mapping in initial screening and at the follow-up and provides new insights in the cardiac SSc follow up strategy.References:[1]Poindron V, Chatelus E, Canuet M, Gottenberg JE, Arnaud L, Gangi A, Gavand PE, Guffroy A, Korganow AS, Germain P, Sibilia J, El Ghannudi S, Martin T.T1 mapping cardiac magnetic resonance imaging frequently detects subclinical diffuse myocardial fibrosis in systemic sclerosis patients.Semin Arthritis Rheum. 2019 Jun 19.Disclosure of Interests:None declared


2021 ◽  
Vol 15 ◽  
Author(s):  
Tuomas Karhu ◽  
Sami Myllymaa ◽  
Sami Nikkonen ◽  
Diego R. Mazzotti ◽  
Juha Töyräs ◽  
...  

Study ObjectivesObesity, older age, and male sex are recognized risk factors for sleep apnea. However, it is unclear whether the severity of hypoxic burden, an essential feature of sleep apnea, is associated with the risk of sleep apnea worsening. Thus, we investigated our hypothesis that the worsening of sleep apnea is expedited in individuals with more severe desaturations.MethodsThe blood oxygen saturation (SpO2) signals of 805 Sleep Heart Health Study participants with mild sleep apnea [5 ≤ oxygen desaturation index (ODI) &lt; 15] were analyzed at baseline and after a mean follow-up time of 5.2 years. Linear regression analysis, adjusted for relevant covariates, was utilized to study the association between baseline SpO2-derived parameters and change in sleep apnea severity, determined by a change in ODI. SpO2-derived parameters, consisting of ODI, desaturation severity (DesSev), desaturation duration (DesDur), average desaturation area (avg. DesArea), and average desaturation duration (avg. DesDur), were standardized to enable comparisons between the parameters.ResultsIn the group consisting of both men and women, avg. DesDur (β = 1.594, p = 0.001), avg. DesArea (β = 1.316, p = 0.004), DesDur (β = 0.998, p = 0.028), and DesSev (β = 0.928, p = 0.040) were significantly associated with sleep apnea worsening, whereas ODI was not (β = −0.029, p = 0.950). In sex-stratified analysis, avg. DesDur (β = 1.987, p = 0.003), avg. DesArea (β = 1.502, p = 0.024), and DesDur (β = 1.374, p = 0.033) were significantly associated with sleep apnea worsening in men.ConclusionLonger and deeper desaturations are more likely to expose a patient to the worsening of sleep apnea. This information could be useful in the planning of follow-up monitoring or lifestyle counseling in the early stage of the disease.


Author(s):  
Reza Afrisham ◽  
Sahar Sadegh-Nejadi ◽  
Reza Meshkani ◽  
Solaleh Emamgholipour ◽  
Molood Bagherieh ◽  
...  

Introduction: Obesity is a disorder with low-grade chronic inflammation that plays a key role in the hepatic inflammation and steatosis. Moreover, there are studies to support the role of exosomes in the cellular communications, the regulation of metabolic homeostasis and immunomodulatory activity. Accordingly, we aimed to evaluate the influence of plasma circulating exosomes derived from females with normal-weight and obesity on the secretion of inflammatory cytokines in human liver cells. Methods: Plasma circulating exosomes were isolated from four normal (N-Exo) and four obese (O-Exo) women. The exosomes were characterized and approved for CD63 expression (common exosomal protein marker) and morphology/size using the western blot and TEM methods, respectively. The exosomes were used for stimulation of HepG2 cells in vitro. After 24 h incubation, the protein levels of TNF-α,IL-6, and IL-1β were measured in the culture supernatant of HepG2 cells using the ELISA kit. Results: The protein levels of IL-6 and TNF-α in the cells treated with O-Exo and N-Exo reduced significantly in comparison with control group (P=0.039 and P<0.001 respectively), while significance differences were not found between normal and obese groups (P=0.808, and P=0.978 respectively). However, no significant differences were found between three groups in term of IL-1β levels (P=0.069). Based on the correlation analysis, the protein levels of IL-6 were positively correlated with TNF-α (r 0.978, P<0.001). Conclusion: These findings suggest that plasma circulating exosomes have probably anti-inflammatory properties independently from body mass index and may decrease the secretion of inflammatory cytokines in liver. However, further investigations in vitro and in vivo are needed to address the anti-inflammatory function of N-Exo and O-Exo in human liver cells and/or other cells.


2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 318.1-318
Author(s):  
D. Santos Oliveira ◽  
A. Martins ◽  
F. R. Martins ◽  
F. Oliveira Pinheiro ◽  
M. Rato ◽  
...  

Background:Anti-tumour necrosis factor alpha (anti-TNF-α) therapy is commonly used to treat inflammatory conditions such as rheumatoid arthritis (RA). Autoantibodies namely antinuclear antibodies (ANA) induced by these treatments are well established. However, anti-TNF-α-induced systemic lupus erythematosus (SLE) is rarely described and its incidence is yet unknown.Objectives:This study aimed to determine the prevalence of ANA seroconversion and to characterize the development of SLE induced by anti-TNF-α therapy in patients with RA over time.Methods:An observational retrospective cohort study was conducted with at least one year of follow-up. Patients with diagnosis of RA, according to American College of Rheumatology criteria (ACR), and registered on Rheumatic Diseases Portuguese Register (Reuma.pt) who started their first anti-TNFα between 2003 and 2019 were included. Patients with positive ANA (titer ≥100) and/or positive double-strand DNA (dsDNA) antibodies and/or with a diagnosis of SLE at their first visit were excluded. Demographic, clinical and laboratory data were obtained by consulting Reuma.pt. As there are no recognized criteria for drug-induced SLE, the diagnosis of SLE induced by anti-TNF-α was considered if there is a temporal relationship between clinical manifestations and anti-TNF-α-therapy, the presence of at least 1 serologic ACR criteria (ANA or anti-dsDNA) and at least 1 nonserologic ACR criteria (arthritis, serositis, hematologic disorder or malar rash) [1]. Continuous variables are presented with mean, standard deviation, median, quartile 1 and quartile 3. Categorical variables are presented with absolute and relative frequencies.Results:A total of 211 patients (mean age of 49.9±10.9 years old; 84.4% female) were included with a median follow-up time of 6 [3-14] years. We found a seroconversion rate for ANA of 75.4% (n=159) with median treatment duration of 31 [8.5-70.5] months. The most common titre was 1/100 with diffuse and speckled patterns. ANA seroconversion was higher for etanercept (47.8%, n=76) than with adalimumab (23.9%, n=38), infliximab (13.8%, n=22), golimumab (12.6%, n=20) or certolizumab (1.9%, n=3). SLE induced by anti-TNF-α occurred in two patients (0.9%) with erosive and seropositive (rheumatoid factor and anti-citrullinated protein antibodies) RA previously treated with two conventional synthetic disease-modifying antirheumatic drugs, including methotrexate. The first patient, a female with 66 years old and 17 years of disease duration, developed SLE after 16 months of infliximab, with constitutional symptoms, abrupt worsening of polyarthritis, ANA titer of 1/320 diffuse pattern and positive dsDNA (248 UI/mL) antibodies. The second patient, a woman with 43 years old and 11 years of disease duration, developed SLE after 41 months of adalimumab with malar rash and ANA titer of 1/320 diffuse pattern, positive dsDNA (285 UI/mL), positive anti-histone antibodies and hypocomplementemia. In these two cases, anti-TNF-α therapy was stopped and recovery was spontaneous without treatment. The first patient switched to adalimumab and the second switched to golimumab without recurrence of SLE for more than ten years.Conclusion:We found a high rate of ANA seroconversion induced by anti-TNFα therapy in patients with RA. However, similar to previous literature, only 0.9% of patients developed SLE with mild manifestations without major organ involvement. Although the drug with the highest ANA seroconversion rate was etanercept, those responsible for induced SLE were infliximab and adalimumab. Patients improved after discontinuation of therapy and tolerated an alternative anti-TNF-α drug without recurrence of induced SLE over time. Therefore, ANA and SLE induced by anti-TNF-α should be considered and reported in the follow-up of RA patients. Further research is needed to explore the impact of this adverse event on the outcomes of treatment over time.References:[1]Hochberg MC. Arthritis Rheum. 1997;40(9):1725.Disclosure of Interests:None declared


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ang Wei ◽  
Honghao Ma ◽  
Liping Zhang ◽  
Zhigang Li ◽  
Yitong Guan ◽  
...  

Abstract Objective To investigate the clinical characteristics, treatment, prognosis and risk factors for chronic active Epstein–Barr Virus infection (CAEBV) associated with coronary artery dilatation (CAD) in children. Methods Children with CAEBV associated with CAD hospitalized at Beijing Children’s Hospital, Capital Medical University from March 2016 to December 2019 were analyzed. Children with CAEBV without CAD were selected as the control group and matched by sex, age, treatment and admission time. The clinical manifestations, laboratory and ultrasound examinations, treatment and prognosis of the children were collected in both groups. Results There were 10 children with CAEBV combined with CAD, including 6 males and 4 females, accounting for 8.9% (10/112) of CAEBV patients in the same period, with an onset age of 6.05 (2.8–14.3) years. The median follow-up time was 20 (6–48) months. All the patients had high copies of EBV-DNA in whole blood [1.18 × 107 (1.90 × 105–3.96 × 107) copies/mL] and plasma [1.81 × 104 (1.54 × 103–1.76 × 106) copies/mL], and all biopsy samples (bone marrow, lymph nodes or liver) were all positive for Epstein–Barr virus-encoded small RNA. Among the 10 children, 8 had bilateral CAD, and 2 patients had unilateral CAD. After diagnosis, 7 children were treated with L-DEP chemotherapy in our hospital. After chemotherapy, four patients underwent allogeneic hematopoietic stem cell transplantation (HSCT). The others were waiting for HSCT. At the time of the last patients follow up record, the CAD had returned to normal in 3 patients, and the time from the diagnosis of CAD to recovery was 21 (18–68) days. LDH, serum ferritin, TNF-α and IL-10 levels were statistically significantly different between the two groups (P = 0.009, 0.008, 0.026 and 0.030). There were no significant differences in survival rate between the two groups (P = 0.416). Conclusion The incidence of CAEBV with CAD was low. CAEBV with CAD did not influence the prognosis. Patients who had high LDH, serum ferritin, TNF-α, and IL-10 levels early in their illness were more likely to develop CAD.


Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.


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