Clinical Significance of B-Type Natriuretic Peptide Levels at 3 Months after Atrial Fibrillation Ablation

The role of B-type natriuretic peptide (BNP) levels as a predictor of arrhythmia recurrence (AR) after atrial fibrillation (AF) ablation remains unclear. In this study, we investigated the association of BNP levels before and 3 months after ablation with the risk of AR. A total of 234 patients undergoing their first session of AF ablation were included (68% male, mean age of 69 years). The cut-off value for discriminating AR was determined based on the maximum value of the area under the receiver operating characteristic (ROC) curve. The impact of BNP levels on AR was evaluated using Cox regression analysis. ROC curve analysis showed that the area under the curve for BNP at 3 months after the procedure was larger (0.714) compared to BNP levels before ablation (0.593). Elevated levels of BNP 3 months after the procedure (>40.5 pg/mL, n = 96) was associated with a higher risk of AR compared to those without elevated levels (34.4% vs. 10.9%, p < 0.01). Multivariate Cox regression analysis revealed that elevated BNP levels were associated with an increased risk of AR (hazard ratio 2.43; p = 0.014). Elevated BNP levels 3 months after AF ablation were a significant prognostic factor in AR, while baseline BNP levels were not.

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684 Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: a report from the ESC-EHRA EORP atrial fibrillation general long-term registry

European Heart Journal Supplements ◽

10.1093/eurheartj/suab127.052 ◽

2021 ◽

Vol 23 (Supplement_G) ◽

Author(s):

Marrco Vitolo ◽

Vincenzo Livio Malavasi ◽

Marco Proietti ◽

Igor Diemberger ◽

Laurent Fauchier ◽

...

Keyword(s):

Atrial Fibrillation ◽

Regression Analysis ◽

Cox Regression ◽

Adverse Outcomes ◽

Cox Regression Analysis ◽

Coronary Syndrome ◽

Increased Risk ◽

History Of ◽

Cardiac Troponins

Abstract Aims Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear. To assess the factors associated with cTn testing in routine clinical practice and to evaluate the association of elevated levels of cTn with adverse outcomes in a large contemporary cohort of European AF patients. Methods and results Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into three groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), and (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism/any acute coronary syndrome (ACS)/cardiovascular (CV) death, defined as major adverse cardiovascular events (MACE) and all-cause death were the main endpoints. 10 445 (94.1%) AF patients were included in this analysis [median age 71 years, interquartile range (IQR): 63–77; males 59.7%]. cTn were tested in 2834 (27.1%). Overall, cTn was elevated in 904 (8.7%) and in-range in 1930 (18.5%) patients. Patients in whom cTn was tested tended to be younger (P < 0.001) and more frequently presenting with first detected AF and atypical AF-related symptoms (i.e. chest pain, dyspnoea, or syncope) (P < 0.001). On multivariable logistic regression analysis, female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease (CAD), and atypical AF symptoms were independently associated with cTn testing. After a median follow-up of 730 days (IQR: 692–749), 957 (9.7%) composite endpoints occurred while all-cause death was 9.5%. Kaplan–Meier analysis showed a higher cumulative risk for both outcomes in patients with elevated cTn levels (Figure) (Log Rank tests, P < 0.001). On adjusted Cox regression analysis, elevated levels of cTn were independently associated with a higher risk for MACE [hazard ratio (HR): 1.74, 95% confidence interval (CI): 1.40–2.16] and all-cause death (HR 1.45, 95% CI: 1.21–1.74). Elevated levels of cTn were independently associated with a higher occurrence of MACE, all-cause death, any ACS, CV death and hospital readmission even after the exclusion of patients with history of CAD, diagnosis of ACS at discharge, those who underwent coronary revascularization during the admission and/or who were treated with oral anticoagulants plus antiplatelet therapy. Conclusions Elevated cTn levels were independently associated with an increased risk of all-cause mortality and adverse CV events, even after exclusion of CAD patients. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

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Combination of CHARGE AF score and index of 24-hour electrocardiogram to predict incident atrial fibrillation and cardiovascular events

European Heart Journal ◽

10.1093/eurheartj/ehab724.0487 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

T Nishimura ◽

K Senoo ◽

I Hibiki ◽

T Okura ◽

T Miki ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Regression Analysis ◽

Roc Curve ◽

Cardiovascular Events ◽

Cox Regression ◽

Cox Regression Analysis ◽

Holter Ecg ◽

New Onset

Abstract Background Atrial fibrillation (AF) is associated with increased risks of stroke and heart failure. AF risk prediction can facilitate the efficient deployment of diagnosis or interventions to prevent AF. Purpose We sought to assess the combination prediction value of Holter electrocardiogram (Holter ECG) and the CHARGE-AF score (Cohorts for Aging and Research in Genomic Epidemiology-AF) for the new-onset of AF in a single center study. We also investigated the association between clinical findings and the new-onset of cerebral cardiovascular events. Methods From January 2008 and May 2014, 1246 patients with aged≥20 undergoing Holter ECG for palpitations, dizziness, or syncope were recruited. Among them, 350 patients were enrolled in this study after exclusion of 1) AF history at the time of inspection or before, 2) post cardiac device implantation, 3) follow-up duration <1 year, and 4) no 12-lead ECG records within 6 months around Holter ECG. Results During the 5.9-year follow-up, 40 patients (11.4%) developed AF incidence. Multivariate cox regression analysis revealed that CHARGE-AF score (hazard ratio [HR]: 1.59, 95% confidence interval (95% CI): 1.13–2.26, P<0.01), BMI (HR: 0.91, 95% CI: 0.83–0.99, P=0.03), frequent supraventricular extrasystoles (SVEs) ≥1000 beats/day (HR: 4.87, 95% CI: 2.59–9.13, P<0.001) and first-degree AV block (HR: 3.52, 95% CI: 1.63–7.61, P<0.01) were significant independent predictors for newly AF. The area under the ROC curve (AUC) of the combination of the CHARGE-AF score and frequent SVEs (≥1000) was greater than the CHARGE-AF score alone (0.73, 95% CI: 0.64–0.82 vs 0.66, 95% CI: 0.56–0.75, respectively). On the ROC curve, the CHARGE-AF score of 12.9 was optimum cut-off value for newly AF. Patients with both the CHARGE-AF score≥12.9 and SVEs≥1000 developed AF at 129.0/1000 person-years, compared with those with the CHARGE-AF score<12.9 and SVEs≥1000 (48.9), the CHARGE-AF score≥12.9 and SVEs<1000 (40.0) and the CHARGE-AF score<12.9 and SVEs<1000 (7.4), respectively. In multivariate cox regression analysis, age, past history of congestive heart failure and myocardial infarction, and antihypertensive medication were significant predictors of cerebral cardiovascular events (n=43), all of which signifying the components of the CHARGE-AF score. The AUC of the combination of the CHARGE-AF score and frequent SVEs (≥1000) was not different from the CHARGE-AF score alone (0.73, 95% CI: 0.64–0.81 vs 0.73, 95% CI: 0.64–0.82, respectively). Conclusion CHARGE-AF score has higher predictive power of both the new incident AF and cerebral cardiovascular events. The combination of CHARGE-AF score and SVEs≥1000 beats/day in Holter ECG can demonstrate the additional effect of prediction ability for the new incident AF, but not for cerebral cardiovascular events. FUNDunding Acknowledgement Type of funding sources: None.

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Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Age and Ageing ◽

10.1093/ageing/afab026 ◽

2021 ◽

Cited By ~ 1

Author(s):

◽

Mustafa Alsahab ◽

Lucy Beishon ◽

Bryony Brown ◽

Elinor Burn ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Adverse Outcomes ◽

Care Needs ◽

Multi Centre Study ◽

Cox Regression Analysis ◽

Risk Of Death ◽

Increased Risk ◽

Ordinal Logistic Regression Analysis ◽

The Impact

Abstract Introduction Increased mortality has been demonstrated in older adults with COVID-19, but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty, and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation, and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS), and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, IQR 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 vs 18–49: HR 3.57, CI 2.54–5.02), frailty (CFS 8 vs 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease, and cancer, but not delirium. Age, frailty (CFS 7 vs 1–3: OR 7.00, CI 5.27–9.32), delirium, dementia, and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusions Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age.

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NLRP3 is a Novel Prognostic Biomarker and Correlates With Immune Infiltrates in Lung Adenocarcinoma and Skin Cutaneous Melanoma

10.21203/rs.3.rs-880002/v1 ◽

2021 ◽

Author(s):

Chenxi Yuan ◽

Qingwei Wang ◽

Xueting Dai ◽

Yipeng Song ◽

Jinming Yu

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Lung Adenocarcinoma ◽

Immune Cells ◽

Cutaneous Melanoma ◽

Cox Regression ◽

Cox Regression Analysis ◽

Potential Biomarker ◽

The Impact ◽

Nlrp3 Expression

Abstract Background: Lung adenocarcinoma (LUAD) and skin cutaneous melanoma (SKCM) are common tumors around the world. However, the prognosis in advanced patients is poor. Because NLRP3 was not extensively studied in cancers, so that we aimed to identify the impact of NLRP3 on LUAD and SKCM through bioinformatics analyses. Methods: TCGA and TIMER database were utilized in this study. We compared the expression of NLRP3 in different cancers and evaluated its influence on survival of LUAD and SKCM patients. The correlations between clinical information and NLRP3 expression were analyzed using logistic regression. Clinicopathologic characteristics associated with overall survival in were analyzed by Cox regression. In addition, we explored the correlation between NLRP3 and immune infiltrates. GSEA and co-expressed gene with NLRP3 were also done in this study. Results: NLRP3 expressed disparately in tumor tissues and normal tissues. Cox regression analysis indicated that up-regulated NLRP3 was an independent prognostic factor for good prognosis in LUAD and SKCM. Logistic regression analysis showed increased NLRP3 expression was significantly correlated with favorable clinicopathologic parameters such as no lymph node invasion and no distant metastasis. Specifically, a positive correlation between increased NLRP3 expression and immune infiltrating level of various immune cells was observed. Conclusion: Together with all these findings, increased NLRP3 expression correlates with favorable prognosis and increased proportion of immune cells in LUAD and SKCM. These conclusions indicate that NLRP3 can serve as a potential biomarker for evaluating prognosis and immune infiltration level.

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Abstract P254: Daytime Napping is Associated With Incident Stroke in Community

Circulation ◽

10.1161/circ.141.suppl_1.p254 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Xuting Jin ◽

Bin Yan ◽

Ruohan Li ◽

Ya Gao ◽

Jingjing Zhang ◽

...

Keyword(s):

Regression Analysis ◽

Cox Regression ◽

Life Quality ◽

Health Study ◽

Sleep Habits ◽

Community Based ◽

Cox Regression Analysis ◽

Increased Risk ◽

Registration Number ◽

The Relationship

Introduction: There are conflicting reports regarding whether daytime napping is a risk factor for cardiovascular events. The purpose of this study was to investigate the relationship between daytime napping and incident stroke within a community-based cohort study. Hypothesis: We assessed the hypothesis that the duration and the frequency of daytime napping may be associated with incident stroke. Methods: Participants without previous stroke were enrolled in the present prospective study from the Sleep Heart Health Study (registration number, NCT00005275). Daytime napping were assessed with a self-reported Sleep Habits Questionnaire. Duration of daytime napping was divided into the following categories: no naps, 0-30 min, 31-60 min, or >60 min. Frequency of naps were categorised as: no naps, 1-2 times/week, 3-4 times/week, 5-6 times/week, or daily. After combining nap duration and frequency, participants were further divided into groups with regular long naps (≥5 times per week and >30 min), regular short naps (≥5 times per week and ≤30 min), irregular naps or no naps. Subsequently, participants were followed up until the first stroke occurred between the date of the completed questionnaire and the final censoring date. Cox regression analysis was used to estimate the relationship between daytime napping and incident stroke. Results: The present study enrolled 4757 participants, of which 220 participants (4.6%) experienced incident stroke during an average follow-up of 10.6 years. There was a higher rate of stroke among participants taking longer and more frequent naps than others. Multivariate Cox regression analysis indicated that, when compared with participants with no naps, those with a nap duration of ≥60 min or of 31-60 min had a higher risk of stroke (HR, 2.182; 95% CI, 1.443-3.301; HR, 1.594; 95% CI, 1.003-2.531, respectively). Moreover, there was an increased risk of stroke among participants taking daily daytime naps (HR, 1.563; 95% CI, 1.059-2.307) or napping 5-6 times per week (HR, 1.548; 95% CI, 1.026-2.335) than those with no naps. And after combining nap duration and frequency, regular long naps and regular short naps were also associated with higher risk of incident stroke (HR, 1.903; 95% CI, 1.182-3.065; HR, 1.451; 95% CI, 1.010-2.084, respectively). Conclusions: In conclusion, daytime napping of long duration and high frequency may increase the risk of incident stroke in community. Modification of sleep habits may improve the life quality among those elderly community-based population.

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P1885Cha2ds-2vasc score lacks of ability to predict mortality in patients attending the emergency department with atrial fibrillation in the presence of troponin i

European Heart Journal ◽

10.1093/eurheartj/ehz748.0633 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M I Gonzalez Del Hoyo ◽

G Cediel ◽

A Carrasquer ◽

G Bonet ◽

K Vasquez-Nunez ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Emergency Department ◽

Regression Analysis ◽

Troponin I ◽

Cox Regression ◽

Cox Regression Analysis ◽

All Cause Mortality

Abstract Background CHA2DS2-VASc score has been used as a surrogate marker for predicting outcomes beyond thromboembolic risk in patients with atrial fibrillation (AF). Likewise, cardiac troponin I (cTnI) is a predictor of mortality in AF. Purpose This study aimed to investigate the association of cTnI and CHA2DS2-VASc score with long-term prognosis in patients admitted to the emergency department with AF. Methods A retrospective cohort study conducted between January 2012 and December 2013, enrolling patients admitted to the emergency department with AF and having documented cTnI measurements. CHA2DS2-VASc score was estimated. Primary endpoint was 5-year all-cause mortality, readmission for heart failure (HF), readmission for myocardial infarction (MI) and the composite end point of major adverse cardiac events defined as death, readmission for HF or readmission for MI (MACE). Results A total of 578 patients with AF were studied, of whom 252 patients had elevated levels of cTnI (43.6%) and 334 patients had CHA2DS2-VASc score >3 (57.8%). Patients with elevated cTnI tended to be oldercompared with those who did not have cTnI elevation and were more frequently comorbid and of higher ischemic risk, including hypertension, prior MI, prior HF, chronic renal failure and peripheral artery disease. The overall median CHA2DS2-VASc score was higher in those with cTnI elevation compared to those patients elevated cTnI levels (4.2 vs 3.3 points, p<0.001). Main diagnoses at hospital discharge were tachyarrhythmia 30.3%, followed by heart failure 17.7%, respiratory infections 9.5% and acute coronary syndrome 7.3%. At 5-year follow-up, all-cause death was significantly higher for patients with cTnI elevation compared with those who did not have cTnI elevation (56.4% vs. 27%; logrank test p<0.001). Specifically, for readmissions for HF and readmissions for MI there were no differences in between patients with or without cTnI elevation. In addition, MACE was reached in 165 patients (65.5%) with cTnI elevation, compare to 126 patients (38.7%) without cTnI elevation (p<0.001). On multivariable Cox regression analysis, cTnI elevation was an independent predictor of all-cause death (hazard ratio, 1.67, 95% confidence interval [CI]: 1.24–2.26, p=0.001) and of MACE (hazard ratio 1.47, 95% confidence interval 1.15–1.88; P=0.002), but it did not reach statistical significance for readmissions for MI and readmissions for HF. CHA2DS2-VASc score was a predictor on univariate Cox regression analysis for each endpoint, but it did not reach significance on multivariable Cox regression analysis for any endpoint. Conclusions cTnI is independently associated with long-term all-cause mortality in patients attending the emergency department with AF. cTnI compared to CHA2DS2-VASc score is thus a biomarker with predictive capacity for mortality in late follow-up, conferring utility in the risk stratification of patients with atrial fibrillation.

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P0211GLOMERULAR HYPERFILTRATION AND CANCER: A NATIONWIDE POPULATION-BASED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0211 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Yaerim Kim ◽

Jeongsoo Yoon ◽

Jin Hyuk Paek ◽

Woo Yeong Park ◽

Kyubok Jin ◽

...

Keyword(s):

National Health ◽

Malignant Disease ◽

Cox Regression ◽

Asian Population ◽

Population Based ◽

Glomerular Hyperfiltration ◽

Outcome Variable ◽

Cox Regression Analysis ◽

Increased Risk ◽

The Impact

Abstract Background and Aims Glomerular hyperfiltration is associated with all-cause mortality. Herein, we evaluated the association between glomerular hyperfiltration and the development of malignant disease, the most common cause of death, in an Asian population. Method We retrospectively reviewed the National Health Insurance Service database of Korea for people who received national health screenings from 2012 to 2013. Glomerular hyperfiltration was defined as the 95th percentile and greater after adjusting for age and sex. We performed a multivariate Cox regression analysis using glomerular hyperfiltration at the first health screening as the exposure variable and cancer development as the outcome variable to evaluate the impact of glomerular hyperfiltration on the development of malignant disease. Results A total of 1,953,123 examinations who followed-up for 4.9 years were included in this study. Among the 8 different site-specific malignant disease categories, digestive organs and female genital organs showed a significant associations between glomerular hyperfiltration and malignancy. The population with glomerular hyperfiltration showed an increased risk for stomach cancer (adjusted hazard ratio [aHR], 1.27), colorectal cancer (aHR, 1.23), and liver or intrahepatic malignancy (aHR, 1.40). In addition, the risk for uterine and ovarian cancer was significantly increased in the population with glomerular hyperfiltration (aHR, 1.36). Conclusion Glomerular hyperfiltration was associated with an increased risk for the development of malignant diseases in specific organs, such as the stomach, colorectum, uterus, and ovary. Glomerular hyperfiltration needs to be considered a significant sign of the need to evaluate the possibility of hidden adverse health conditions, including malignancies.

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Impact of Early C-Reactive Protein/Albumin Ratio on Intra-Hospital Mortality Among Patients with Spontaneous Intracerebral Hemorrhage

Journal of Clinical Medicine ◽

10.3390/jcm9041236 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1236 ◽

Cited By ~ 2

Author(s):

Michael Bender ◽

Kristin Haferkorn ◽

Michaela Friedrich ◽

Eberhard Uhl ◽

Marco Stein

Keyword(s):

Regression Analysis ◽

Intracerebral Hemorrhage ◽

Hospital Mortality ◽

Cox Regression ◽

Spontaneous Intracerebral Hemorrhage ◽

C Reactive Protein ◽

Albumin Ratio ◽

Cox Regression Analysis ◽

Reactive Protein ◽

The Impact

Objective: The impact of increased C-reactive protein (CRP)/albumin ratio on intra-hospital mortality has been investigated among patients admitted to general intensive care units (ICU). However, it was not investigated among patients with spontaneous intracerebral hemorrhage (ICH). This study aimed to investigate the impact of CRP/albumin ratio on intra-hospital mortality in patients with ICH. Patients and Methods: This retrospective study was conducted on 379 ICH patients admitted between 02/2008 and 12/2017. Blood samples were drawn upon admission and the patients’ demographic, medical, and radiological data were collected. The identification of the independent prognostic factors for intra-hospital mortality was calculated using binary logistic regression and COX regression analysis. Results: Multivariate regression analysis shows that higher CRP/albumin ratio (odds ratio (OR) = 1.66, 95% confidence interval (CI) = 1.193–2.317, p = 0.003) upon admission is an independent predictor of intra-hospital mortality. Multivariate Cox regression analysis indicated that an increase of 1 in the CRP/albumin ratio was associated with a 15.3% increase in the risk of intra-hospital mortality (hazard ratio = 1.153, 95% CI = 1.005–1.322, p = 0.42). Furthermore, a CRP/albumin ratio cut-off value greater than 1.22 was associated with increased intra-hospital mortality (Youden’s Index = 0.19, sensitivity = 28.8, specificity = 89.9, p = 0.007). Conclusions: A CRP/albumin ratio greater than 1.22 upon admission was significantly associated with intra-hospital mortality in the ICH patients.

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P3759Comparison of equations for renal function assessment and major adverse outcomes in atrial fibrillation: an analysis from the EORP-AF long-term general registry

European Heart Journal ◽

10.1093/eurheartj/ehz745.0611 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

G Boriani ◽

M Proietti ◽

C Laroche ◽

E Fantecchi ◽

M Popescu ◽

...

Keyword(s):

Atrial Fibrillation ◽

Renal Function ◽

Regression Analysis ◽

Creatinine Clearance ◽

Cox Regression ◽

Weighted Kappa ◽

Adverse Outcomes ◽

The Other ◽

Cox Regression Analysis

Abstract Background Several equations exist to estimate creatinine clearance according to serum creatinine values and baseline characteristics. The CKD-EPI equation is usually recommended in general population, while the Cockroft-Gault (CG) equation has been used in atrial fibrillation (AF) clinical trials. Purpose To perform a comparison between 6 different equations for evaluation of renal function in AF patients. Methods We calculated CKD-EPI, CG, body surface area adjusted CG (CG BSA), MDRD, BIS1 and FAS equations in AF patients enrolled in the EORP-AF Long-Term General Registry. Outcomes at 1-year follow-up were considered. Results Renal equations were calculated in 7725 patients. According to CKD-EPI mean (SD) creatinine clearance was 69.14 (21.06) mL/min/1.73 m2. Taking CKD-EPI as reference, the MDRD equation showed the highest agreement (weighted kappa [95% CI]: 0.843 [0.833–0.852]), while CK showed the lowest agreement (weighted kappa [95% CI]: 0.593 [0.580–0.606]. The remaining equations showed moderate agreement. Cox regression analysis showed that all equations were inversely associated with all major adverse outcomes [Figure]. The CKD-EPI equation showed modest predictive ability for the three outcomes (c-statistics: any TE/ACS/CV Death: 0.63379; CV Death: 0.68512; All-Cause Death: 0.67183), with all other equations reporting higher c-statistics (delta-c statistic ranging from +0.01497 for FAS equation for any TE/ACS/CV Death to +0.04547 for CG BSA for all-cause death) for all outcomes (all p<0.0001, for any equation for any outcome). Compared to CKD-EPI, all the other equations showed an improvement in prediction of outcomes, according to IDI and NRI, with the exception of FAS equation for any TE/ACS/CV Death. CG BSA equation showed the greatest improvement in prediction of outcomes compared to CKD-EPI (relative IDI: 21.9% for any TE/ACS/CV Death, 28.8% for CV Death, 34.4% for All-Cause Death). Cox Regression Analysis Conclusions Compared to CKD-EPI equation, all the other equations for creatine clearance has stronger associations with adverse outcomes, with the CG BSA reporting the higher yield for all the outcomes considered.

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Increased Colonic Expression of ACE2 Associates with Poor Prognosis in Crohn’s Disease

10.21203/rs.3.rs-150844/v1 ◽

2021 ◽

Author(s):

Takahiko Toyonaga ◽

Kenza Araba ◽

Meaghan Kennedy ◽

Benjamin Keith ◽

Elisabeth Wolber ◽

...

Keyword(s):

Regression Analysis ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Protein Expression ◽

Cox Regression ◽

Multivariate Regression Analysis ◽

Rna Seq ◽

Cox Regression Analysis ◽

Molecular Stratification ◽

The Impact

Abstract Background and Aims: The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. Methods: We examined the expression of colon ACE2 using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort we validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Results: Colonic ACE2 expression was significantly higher in a subset of adult CD patients (ACE2-high CD). IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of diagnosis, with a Cox regression analysis finding that high ACE2 levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037). Conclusion: Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.

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