Association between sleep patterns and galectin-3 in a Chinese community population.

BACKGROUND: Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population. METHODS: A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml. RESULTS: Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized ß [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3. CONCLUSIONS: Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease.

Serum Mac-2 binding protein glycosylation isomer and galectin-3 levels in adult-onset Still's disease and their association with cytokines.

Background: Autoinflammation with cytokine dysregulation may be implicated in the pathophysiology of adult-onset Still's disease (AOSD); however, the relationship between galectins and cytokines in patients with active AOSD remains unknown. We aimed to examine the relationship between circulating cytokines/chemokines and galectin-3 (Gal-3) or its ligand, Mac-2 binding protein glycosylation isomer (M2BPGi), in Japanese patients with AOSD. Methods: We recruited 44 consecutive patients diagnosed with AOSD according to the Yamaguchi criteria, 50 patients with rheumatoid arthritis (RA) as disease controls, and 27 healthy participants. Serum M2BPGi levels were directly measured using a HISCL M2BPGi reagent kit and an automatic immunoanalyzer (HISCL-5000). Serum Gal-3 concentrations were measured by enzyme-linked immunosorbent assay. The serum levels of 69 cytokines were analyzed in patients with AOSD using a multi-suspension cytokine array. We performed a cluster analysis of each cytokine expressed in patients with AOSD to identify specific molecular networks. Results: Significant increases in the serum concentrations of Gal-3 and M2BPGi were found in the serum of patients with AOSD compared with patients with RA and healthy participants (both p <0.001). There were significant positive correlations between serum Gal-3 levels and AOSD disease activity score (Pouchot score, r=0.66, p <0.001) and serum ferritin levels. However, no significant correlations were observed between serum M2BPGi levels and AOSD disease activity scores (Pouchot score, r = 0.32, p = 0.06) or serum ferritin levels. Furthermore, significant correlations were observed between the serum levels of Gal-3 and various inflammatory cytokines, including interleukin-18, in patients with AOSD. Immunosuppressive treatment in patients with AOSD significantly reduced serum Gal-3 and M2BPGi levels (p = 0.03 and 0.004, respectively). Conclusions: Although both Gal-3 and M2BPGi were elevated in patients with AOSD, only Gal-3 was a useful biomarker for predicting disease activity in AOSD. Our findings suggest that circulating Gal-3 reflects the inflammatory component of AOSD, which corresponds to proinflammatory cytokine induction through inflammasome activation cascades.

Galectin-3 in chronic kidney disease.

BACKGROUND AND AIMS: High serum galectin-3 has been associated with adverse outcomes among dialysis patients, although its prognostic role remains unclear among individuals with earlier-stage chronic kidney disease. The present systematic review aims to evaluate the association of serum galectin-3 with survival, cardiovascular disease and kidney disease progression among non-dialysis chronic kidney disease patients. METHODS: PubMed, Scopus, Web of Science, CENTRAL and Google Scholar were systematically searched till November 10, 2023. All observational studies assessing the prognostic role of serum galectin-3 in patients with non-dialysis chronic kidney disease were included. RESULTS: Overall, 12 studies (10 cohort, 2 cross-sectional) were included, comprising 9,349 patients. The endpoint of survival was assessed in 5 studies, indicating a significant association between increasing serum galectin-3 levels and higher all-cause mortality risk (Hazard ratio per unit: 1.22, 95 % confidence intervals-CI: 1.05-1.41, ≥6 ng/mL: 2.66, 95 % CI: 1.68-4.23). Current evidence coming from 4 studies was inconclusive regarding the potential link of galectin-3 and kidney function decline, yielding conflicting results. No significant associations between serum galectin-3 and heart failure, cardiovascular events or death were consistently reported. CONCLUSIONS: This systematic review supports the prognostic role of galectin-3 in chronic kidney disease, as its increased serum values may be associated with higher all-cause mortality risk. No clear role could be supported for serum galectin-3 regarding the prediction of cardiovascular disease or kidney disease progression.

Serum Galectin-3 as a Non-Invasive Marker for Primary Sclerosing Cholangitis.

Primary sclerosing cholangitis (PSC) is a serious liver disease associated with inflammatory bowel disease (IBD). Galectin-3, an inflammatory and fibrotic molecule, has elevated circulating levels in patients with chronic liver disease and inflammatory bowel disease (IBD). This study aims to clarify whether galectin-3 can differentiate between patients with IBD, PSC, and PSC-IBD. Our study measured serum galectin-3 levels in 38 healthy controls, 55 patients with IBD, and 22 patients with PSC (11 patients had underlying IBD and 11 patients did not), alongside the urinary galectin-3 of these patients and 18 controls. Serum and urinary galectin-3 levels in IBD patients were comparable to those in controls. Among IBD patients, those with high fecal calprotectin, indicating severe disease, exhibited lower serum and elevated urinary galectin-3 levels compared to those with low calprotectin levels. Serum galectin-3 levels were inversely correlated with C-reactive protein levels. PSC patients displayed higher serum and urinary galectin-3 levels than IBD patients, with the highest serum levels observed in PSC patients with coexisting IBD. There was no correlation between serum and urinary galectin-3 levels and laboratory indicators of liver injury in both IBD and PSC patients. In conclusion, this study demonstrates that serum and urinary galectin-3 levels can distinguish IBD from PSC patients, and also reveals higher serum galectin-3 levels in PSC-IBD patients compared to those with isolated PSC.

The role of Matrix Metalloproteinase-2 and Galectin-3 as predictive biomarkers for all-cause mortality in patients undergoing transfemoral transcatheter aortic valve implantation.

BACKGROUND: Currently available risk scores fail to accurately predict morbidity and mortality in patients with severe symptomatic aortic stenosis who undergo transcatheter aortic valve implantation (TAVI). In this context, biomarkers like matrix metalloproteinase-2 (MMP-2) and Galectin-3 (Gal-3) may provide additional prognostic information. METHODS: Patients with severe aortic stenosis undergoing consecutive, elective, transfemoral TAVI were included. Baseline demographic data, functional status, echocardiographic findings, clinical outcomes and biomarker levels were collected and analysed. RESULTS: The study cohort consisted of 89 patients (age 80.4 ± 5.1 years, EuroScore II 7.1 ± 5.8%). During a median follow-up period of 526 d, 28 patients (31.4%) died. Among those who died, median baseline MMP-2 (alive: 221.6 [170.4; 263] pg/mL vs. deceased: 272.1 [225; 308.8] pg/mL, p < 0.001) and Gal-3 levels (alive: 19.1 [13.5; 24.6] pg/mL vs. deceased: 25 [17.6; 29.5] pg/mL, p = 0.006) were higher than in survivors. In ROC analysis, MMP-2 reached an acceptable level of discrimination to predict mortality (AUC 0.733, 95% CI [0.62; 0.83], p < 0.001), but the predictive value of Gal-3 was poor (AUC 0.677, 95% CI [0.56; 0.79], p = 0.002). Kaplan-Meier and Cox regression analyses showed that patients with MMP-2 and Gal-3 concentrations above the median at baseline had significantly impaired long-term survival (p = 0.004 and p = 0.02, respectively). CONCLUSIONS: In patients with severe aortic stenosis undergoing transfemoral TAVI, MMP-2 and to a lesser extent Gal-3, seem to have additive value in optimizing risk prediction and streamlining decision-making.

Prognosis value of galectin-3 in patients with dilated cardiomyopathy: a meta-analysis.

Background: Accurate prediction and assessment of myocardial fibrosis (MF) and adverse cardiovascular events (MACEs) are crucial in patients with dilated cardiomyopathy (DCM). Several studies indicate that galectin-3 (gal-3) as a promising prognostic predictor in patients with DCM. Methods: A comprehensive search was conducted in PubMed, EMBASE, the Cochrane Library, and Web of Science for relevant studies up to August 2023. The hazard ratios (HRs) of gal-3 for MACEs in DCM patients, and for MACEs in LGE(+) versus LGE(-) groups, were evaluated. Statistical analysis was performed using STATA SE 14.0 software. Results: Seven studies, encompassing 945 patients, met the eligibility criteria. In DCM patients, abnormally elevated gal-3 levels were indicative of an increased MACEs risk (HR = 1.10, 95% CI [1.00-1.21], I2 = 65.7%, p = 0.008). Compared with the LGE(-) group, the level of gal-3 in LGE(+) group was higher (HR = 1.12, 95% CI [1.05-1.19], I2 = 31.4%, p = 0.233), and the combination of gal-3 and LGE significantly improved the prediction of MACEs. Sensitivity analysis confirmed the robustness of all results. Conclusions: This study's findings suggest that elevated gal-3 levels significantly correlate with increased MACE risk in DCM, highlighting its potential as a biomarker. However, significant heterogeneity among studies necessitates further research to ascertain gal-3's predictive and diagnostic value in DCM prognosis, particularly in conjunction with LGE. PROSPERO ID: CRD42023471199.

Diagnostic Value of Galectin-3 in Exacerbations of Chronic Obstructive Pulmonary Disease.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease characterized by acute exacerbations. Systemic inflammation and oxidative stress play an important role in the pathogenesis of COPD. Exacerbations in COPD reduce the quality of life and are associated with rapid disease progression. Galectin-3 is a beta-galactoside-binding lectin of approximately 30 kDa with pro-inflammatory and pro-fibrotic properties. This study aims to analyze the efficacy of serum galectin-3 in predicting exacerbations in COPD patients. Materials and Methods: Baseline demographic and clinical characteristics of all patients were recorded and blood samples were collected. A total of 58 consecutive COPD patients, including 28 patients (19 male and 9 female) with stable COPD and 30 patients (23 male and 7 female) with acute exacerbation of COPD (AECOPD), were included in the study. Results: Serum galectin-3 levels were significantly higher in the AECOPD group compared to the stable COPD group. A logistic regression analysis revealed that increased galectin-3 levels and disease duration were independent predictors of COPD exacerbation (OR = 5.322, 95% CI: 1.178-24.052, p = 0.03; and OR = 1.297, 95% CI: 1.028-1.635, p = 0.028; respectively). Conclusions: The results of our study demonstrated that Galectin-3 was a strong and independent predictor of exacerbations in COPD patients.

Can Galectin-3 be a reliable predictive biomarker for post-COVID syndrome development?

BACKGROUND AND OBJECTIVES: Reliable biomarkers able to predict post-COVID syndrome development are still lacking. The aim of the study was to evaluate the relationship between Galectin-3 blood concentrations and the development of post-COVID syndrome. METHODS: We performed a single-center, prospective, observational study, enrolling 437 consecutive patients attending our outpatient clinic for the post-COVID assessment. For each patient, we recorded the main clinical, functional and radiological findings. We also dosed several blood biomarkers which have been related to COVID-19 disease, including Galectin-3. We performed Receiver Operating Characteristic (ROC) and multivariate regression analysis to evaluate the predictive performance of Galectin-3 for post-COVID syndrome development. RESULTS: Among the blood biomarkers tested, Galectin-3 resulted the only one correlated with the outcome, although the insufficient performance of the Cox regression model from a statistical standpoint. Correlation coefficients and ROC curves analysis revealed the close relationship between Galectin-3 levels and the time passed from the acute phase of COVID-19 disease, suggesting a possible predictive role for this biomarker when dosed from 60 to 120 days after the infection. CONCLUSIONS: Galectin-3 could play an important role as predictive biomarker for COVID-19 sequelae, but its evaluation must be carefully planned along the follow up to avoid misinterpretations.

Galectin-3 levels in children with cystic fibrosis.

Cystic fibrosis (CF) is a multisystemic disease in which airway obstruction, infection, and inflammation play a critical role in the pathogenesis and progression of CF lung disease. The carbohydrate-binding protein Galectin-3 is increased in several inflammatory and fibrotic diseases and has recently been forwarded as a biomarker in these diseases. We aimed to define the role of serum Galectin-3 in children with CF by comparison with healthy subjects. This is a cross-sectional, case-control study. 143 CF and 30 healthy subjects were enrolled in the study. Peripheral blood and sputum concentrations of Galectins-3, interleukin (IL)-17A, IL-8, and neutrophil elastase (NE) were determined with commercial ELISA kits. There was no significant difference between the groups in age and gender (p = 0.592, p = 0.613, respectively). Serum Galectin-3 and NE concentrations were higher in the patient group than in healthy controls (p = 0.002, p < 0.001, respectively). There were no significant differences between groups according to IL-17A and IL-8 concentrations. Serum Galectin-3 was correlated with age (r = 0.289, p < 0.001) and body mass index (BMI) (r = 0.493, p < 0.001) in children with CF. Sputum Galectin-3 levels are negatively correlated with percent predictive forced expiratory volume in 1 s (FEV1) (r = - 0.297, p = 0.029), FEV1 z-score, (r = - 0.316, p = 0.020), percent predictive forced vital capacity (FVC) (r = - 0.347, p = 0.010), and FVC z-score (r = - 0.373, p = 0.006).   Conclusion: The study shows that serum Galectin-3 levels increased in clinically stable CF patients, and serum Galectin-3 response may depend on age, gender, and BMI. The sputum Galectin-3 was found to be negatively correlated with patients' lung functions. What is known: • Galectin-3 is a key regulator of chronic inflammation in the lung, liver, kidney, and tumor microenvironment. What is new: • Children with cystic fibrosis (CF) have higher serum Galectin-3 concentrations than healthy children. • Serum Galectin-3 expression influenced by age, BMI, and gender in children with CF.

MicroRNAs are associated with cardiac biomarkers, cardiac structure and function and incident outcomes in heart failure.

AIMS: The association between microRNAs (miRNAs) and established cardiac biomarkers is largely unknown. We aimed to measure the association between plasma miRNAs and N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin I, soluble urokinase-type plasminogen activator receptor (suPAR), and galectin-3 with cardiac structure and function and clinical outcomes. METHODS AND RESULTS: We quantified 32 plasma miRNAs using the FirePlex miRNA assay and measured biomarkers in 139 individuals with symptomatic heart failure (HF). We used principal component (PC) analysis and linear regression to evaluate the association between miRNAs and biomarkers with ventricular size and function by echocardiography and Cox modelling for the incidence of a first composite event of HF hospitalization, heart transplant, left ventricular assist device implant, or death. The mean (standard deviation) age at baseline was 64.3 (12.4) years, 33 (24%) were female, and 122 (88%) were White. A total of 45 events occurred over a median follow-up of 368 (interquartile range 234, 494) days. Baseline NT-proBNP (ß = -2.0; P = 0.001) and miRNA PC2 (ß = 2.6; P = 0.002) were associated with baseline left ventricular ejection fraction. NT-proBNP (ß = 20.6; P = 0.0004), suPAR (ß = -39.6; P = 0.005), and PC4 (ß = 21.1; P = 0.02) were associated with baseline left ventricular end-diastolic volumes. NT-proBNP [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.28-2.18, P = 0.0002], galectin-3 (HR 2.02, 95% CI 1.05-3.91, P = 0.036), PC3 (HR 1.75, 95% CI 1.23-2.49, P = 0.002), and PC4 (HR 1.67, 95% CI 1.1-2.52, P = 0.016) were independently associated with incident events. CONCLUSIONS: Biomarkers and miRNA PCs are associated with cardiac structure and function and incident cardiovascular outcomes. Combining information from miRNAs provides prognostic information beyond biomarkers in HF.

Galectin-3 and Myeloperoxidase May Monitor Cancer-Therapy-Related Cardiotoxicity? A Systematic Review and Meta-Analysis.

Galectin-3 and myeloperoxidase (MPO) are novel biomarkers in the field of cardio-oncology, but conflicting results have been reported. Hence, a meta-analysis was performed to assess the monitoring value of galectin-3 and MPO in cancer-therapy-related cardiotoxicity. PubMed, Cochrane, Web of Science, Embase, CNKI databases and ClinicalTrials.gov were queried. According to the predefined inclusion and exclusion criteria, eight studies with 1979 patients were included in this meta-analysis. The examination of the study's heterogeneity (I2), quality assessment and statistical analysis were performed by two reviewers. No significant differences in galectin-3 levels were noted before and after treatment (WMD = -0.10, 90% CI -6.06-5.85, I2: 99%), and a weaker relationship was observed between galectin-3 evaluations and cancer-therapy-related cardiotoxicity (HR = 1.39, 90% CI 0.97-1.98, I2: 0%). However, MPO levels were increased in patients post-treatment (SMD = 0.58, 90% CI 0.35-0.80, I2: 56%), and an increased risk of cardiotoxicity was associated with early pre-post MPO assessments (HR = 1.16, 90% CI 1.02-1.32, I2: 21%). Surprisingly, the MPO levels were a more effective indicator of the response to tumor treatment compared with the TnI (SMD = 2.46, 90% CI -0.26-5.19, I2: 96%) and NT-proBNP levels (SMD = 1.08, 90% CI -0.82-2.98, I2: 96%). In conclusion, our meta-analysis suggests that MPO may rep-resent a potential biomarker for the early detection of cardiotoxicity in current cardio-oncology practice, but the monitoring value of galectin-3 requires further study.

Serum Galectin-3 in Hepatitis C Virus Infection Declines after Successful Virus Eradication by Direct-Acting Antiviral Therapy.

BACKGROUND AND AIMS: Serum galectin-3 is regarded as an inflammatory marker in patients with chronic liver diseases. Hepatitis C virus (HCV) infection is associated with higher levels of inflammatory molecules which ameliorate by efficient treatment with direct-acting antivirals (DAAs). The aim of this study was to compare serum galectin-3 levels between HCV patients before treatment with DAAs and at the time of sustained virologic response at 12 weeks post-treatment (SVR12). METHODS: Hepatitis B and human immunodeficiency virus-negative HCV infected patients not treated with HCV therapies before were recruited at the University Hospital of Regensburg. Galectin-3 was measured by enzyme-linked immunosorbent assay in the serum of patients with chronic HCV infection, before treatment initializing, at four and twelve weeks after the start of DAA therapy and at SVR12. Associations of serum galectin-3 with C-reactive protein (CRP), leukocyte count and measures of liver disease severity were analyzed. Liver fibrosis was assessed by acoustic radiation force impulse, the aspartate aminotransferase/platelet ratio index, and the fibrosis-4 score. RESULTS: In the serum of 81 HCV patients, galectin-3 did not correlate with viral load, viral genotype, CRP, leukocyte count, or the model for end stage liver disease score. Therapy with DAAs effectively diminished viral load within four weeks in all patients. The median value of the serum galectin-3 was 3.0 (Q1:2.0, Q3:4.0) ng/ml before therapy and declined to 2.4 (Q1: 1.7, Q3: 3.4) ng/ml at SVR12 (p<0.001; paired samples of 67 patients). At SVR12, serum galectin-3 was not correlated with CRP (r=0.057, p=0.646) or leu-kocyte count (r=0.222, p=0.071) and did not change with increasing fibrosis stage. The associations between serum galectin-3 and body mass index, liver steatosis or diabetes could not be observed. CONCLUSIONS: Elimination of HCV by DAA treatment lowered serum galectin-3 compared to the pre-treatment levels suggesting that HCV infection causes an increase of this immune-regulatory protein.

Galectin-3 is an independent predictor of postoperative atrial fibrillation and survival after elective cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery and is associated with thromboembolic events, prolonged hospital stay, and adverse outcomes. Inflammation and fibrosis are involved in the pathogenesis of atrial fibrillation. OBJECTIVE: The purpose of this study was to assess whether galectin-3, which reflects preexisting atrial fibrosis, has the potential to predict POAF and mortality after cardiac surgery. METHODS: Four hundred seventy-five consecutive patients (mean age 67.4 ± 11.8 years; 336 (70.7%) male) undergoing elective heart surgery at the Medical University of Vienna were included in this prospective single-center cohort study. Galectin-3 plasma levels were assessed on the day before surgery. RESULTS: The 200 patients (42.1%) who developed POAF had significantly higher galectin-3 levels (9.60 ± 6.83 ng/mL vs 7.10 ± 3.54 ng/mL; P < .001). Galectin-3 significantly predicted POAF in multivariable logistic regression analysis (adjusted odds ratio per 1-SD increase 1.44; 95% confidence interval 1.15-1.81; P = .002). During a median follow-up of 4.3 years (interquartile range 3.4-5.4 years), 72 patients (15.2%) died. Galectin-3 predicted all-cause mortality in multivariable Cox regression analysis (adjusted hazard ratio per 1-SD increase 1.56; 95% confidence interval 1.16-2.09; P = .003). Patients with the highest-risk galectin-3 levels according to classification and regression tree analysis (>11.70 ng/mL) had a 3.3-fold higher risk of developing POAF and a 4.4-fold higher risk of dying than did patients with the lowest-risk levels (≤5.82 ng/mL). CONCLUSION: The profibrotic biomarker galectin-3 is an independent predictor of POAF and mortality after cardiac surgery. This finding highlights the role of the underlying arrhythmogenic substrate in the genesis of POAF. Galectin-3 may help to identify patients at risk of POAF and adverse outcome after cardiac surgery.

Obesity, Galectin-3, and Incident Heart Failure: The ARIC Study.

Background Laboratory data suggest obesity is linked to myocardial inflammation and fibrosis, but clinical data are limited. We aimed to examine the association of obesity with galectin-3, a biomarker of cardiac inflammation and fibrosis, and the related implications for heart failure (HF) risk. Methods and Results We evaluated 8687 participants (mean age 63 years; 21% Black) at ARIC (Atherosclerosis Risk in Communities) Visit 4 (1996-1998) who were free of heart disease. We used adjusted logistic regression to estimate the association of body mass index (BMI) categories with elevated galectin-3 (≥75th sex-specific percentile) overall and across demographic subgroups, with tests for interaction. We used Cox proportional hazards models to assess the combined associations of galectin-3 and BMI with incident HF (through December 31, 2019). Higher BMI was associated with higher odds of elevated galectin-3 (odds ratio [OR], 2.32; 95% CI, 1.88-2.86) for severe obesity ([BMI ≥35 kg/m2] versus normal weight [BMI 18.5-<25 kg/m2]). There were stronger associations of BMI with elevated galectin-3 among women versus men and White versus Black participants (both P-for-interaction <0.05). Elevated galectin-3 was similarly associated with incident HF among people with and without obesity (HR, 1.49; 95% CI, 1.18-1.88; and HR, 1.71; 95% CI, 1.38-2.11, respectively). People with severe obesity and elevated galectin-3 had >4-fold higher risk of HF (HR, 4.19; 95% CI, 2.98-5.88) than those with normal weight and galectin-3 <25th percentile. Conclusions Obesity is strongly associated with elevated galectin-3. Additionally, the combination of obesity and elevated galectin-3 is associated with marked HF risk, underscoring the importance of elucidating pathways linking obesity with cardiac inflammation and fibrosis.

Dynamic personalized risk prediction in chronic heart failure patients: a longitudinal, clinical investigation of 92 biomarkers (Bio-SHiFT study).

The aim of our observational study was to derive a small set out of 92 repeatedly measured biomarkers with optimal predictive capacity for adverse clinical events in heart failure, which could be used for dynamic, individual risk assessment in clinical practice. In 250 chronic HFrEF (CHF) patients, we collected trimonthly blood samples during a median of 2.2 years. We selected 537 samples for repeated measurement of 92 biomarkers with the Cardiovascular Panel III (Olink Proteomics AB). We applied Least Absolute Shrinkage and Selection Operator (LASSO) penalization to select the optimal set of predictors of the primary endpoint (PE). The association between repeatedly measured levels of selected biomarkers and the PE was evaluated by multivariable joint models (mvJM) with stratified fivefold cross validation of the area under the curve (cvAUC). The PE occurred in 66(27%) patients. The optimal set of biomarkers selected by LASSO included 9 proteins: NT-proBNP, ST2, vWF, FABP4, IGFBP-1, PAI-1, PON-3, transferrin receptor protein-1, and chitotriosidase-1, that yielded a cvAUC of 0.88, outperforming the discriminative ability of models consisting of standard biomarkers (NT-proBNP, hs-TnT, eGFR clinically adjusted) - 0.82 and performing equally well as an extended literature-based set of acknowledged biomarkers (NT-proBNP, hs-TnT, hs-CRP, GDF-15, ST2, PAI-1, Galectin 3) - 0.88. Nine out of 92 serially measured circulating proteins provided a multivariable model for adverse clinical events in CHF patients with high discriminative ability. These proteins reflect wall stress, remodelling, endothelial dysfunction, iron deficiency, haemostasis/fibrinolysis and innate immunity activation. A panel containing these proteins could contribute to dynamic, personalized risk assessment.Clinical Trial Registration: 10/05/2013 https://clinicaltrials.gov/ct2/show/NCT01851538?term=nCT01851538&draw=2&rank=1 .

Serum Galectin-3 levels and all-cause and cardiovascular mortality in maintenance hemodialysis patients: a prospective cohort study.

BACKGROUND: Higher serum galectin-3 levels are related to adverse outcomes in different disease states. However, the association of galectin-3 with mortality in the maintenance hemodialysis (HD) population has not been fully described. Thus, we aimed to assess the predictive significance of galectin-3 for all-cause and cardiovascular (CV) mortality through a Chinese maintenance HD population. METHODS: A prospective cohort study was conducted in five hundred and six patients with end-stage renal disease who underwent hemodialysis at Dalian Central Hospital before December 31, 2014. Serum galectin-3 levels were measured at baseline and classified as high (> 8.65 ng/ml) or low (≤ 8.65 ng/ml) according to the "X-tile" program. Primary and secondary outcomes were all-cause and CV mortality, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated by the Cox proportional hazards regression models. RESULTS: During the median follow-up of 60 months, there were 188 all-cause deaths and 125 CV deaths. Compared with maintenance HD population with galectin-3 ≤ 8.65 ng/ml, the adjusted HR for all-cause mortality among those with galectin-3 >  8.65 ng/ml was 1.59 (CI: 0.96-2.65, p = 0.07). Furthermore, multivariable analysis showed that maintenance HD patients with galectin-3 >  8.65 ng/ml had a 2.13-fold higher risk of CV death than those with galectin-3 ≤ 8.65 ng/ml (HR = 2.13, 95% CI 1.07-4.26). CONCLUSION: Galectin-3 is an independent predictor of CV mortality in maintenance HD patients.

Therapeutic implications of galectin-3 in patients with atrial fibrillation.

Atrial fibrosis can present as an arrhythmogenic substrate that is correlated with higher recurrence after catheter ablation for atrial fibrillation. Galectin-3, a beta-galactoside-binding lectin, is highly expressed and secreted from macrophages and is important in inflammation and fibrosis. We assessed the clinical implications of serum galectin-3 in patients with atrial fibrillation. This was a prospective cohort study of consecutive patients who underwent radiofrequency catheter ablation in a tertiary referral center from February 2017 to September 2017. Intracardiac blood sampling, echocardiographic measurements, magnetic resonance imaging with late gadolinium enhancement, electrophysiologic testing, and endocardial voltage mapping were consistently implemented in 75 patients before the ablation. Serum galectin-3 level was higher in patients with diabetes mellitus and was correlated with values that indicated the left atrial size. During a median 14 months of follow-up, atrial tachyarrhythmia recurred in 27% of patients. In multivariable Cox regression analysis, non-paroxysmal atrial fibrillation (hazard ratio 6.8; 95% confidence interval 1.6-28.9) and higher galectin-3 levels (hazard ratio 1.3; 95% confidence interval 1.0-1.7) were associated with increased risk of recurrence. Serum galectin-3 may be a prognostic biomarker for risk stratification in patients with atrial fibrillation planned catheter ablation.

Establishment of Galectin-3 Time-resolved Fluoroimmunoassay and its Application in Idiopathic Membranous Nephropathy.

The aim of this study was to establish a time-resolved fluorescent immunoassay (TRFIA) for the detection of serum Galectin-3 (Gal-3) and apply this method to evaluate the clinical significance of serum Gal-3 in predicting Idiopathic Membranous Nephropathy (IMN) progression. The Gal-3-TRFIA was established using the double antibody sandwich method, with the capture antibodies coated on a 96-well microplate and the detection antibodies chelated with Europium (III) (Eu3+). Serum Gal-3 was detected in 81 patients with IMN and 123 healthy controls to further evaluate the value of the Gal-3 in staging of IMN. The sensitivity of the Gal-3-TRFIA assay was 0.85 ng/mL, and the detection range was 0.85-1000 ng/mL. The Gal-3 intra-batch and inter-batch coefficients of variation were 3.45% and 5.12%, respectively. The correlation coefficient (R) between the Gal-3-TRFIA assay and commercially available enzyme-linked immunosorbent assay kits was 0.83. The serum Gal-3 concentration was higher in patients with IMN (65.57 ± 55.90 ng/mL) compared to healthy controls (16.29 ± 9.91 ng/mL, P < 0.0001). In this study, a wide detection range Gal-3-TRFIA assay was developed using lanthanide (Eu3+) chelates for the detection of Gal-3 concentrations in serum. Gal-3 concentration is elevated in patients with IMN.

Galectin-3: a new biomarker for differentiating periodic fever, adenitis, pharyngitis, aphthous stomatitis (PFAPA) syndrome from familial Mediterranean fever?

Differentiating PFAPA (periodic fever, aphthosis, pharyngitis, and adenitis) syndrome from familial Mediterranean fever (FMF) could be challenging in some cases. Galectin-3 is a lectin with regulatory functions in apoptosis and inflammation. We aimed to test whether galectin-3 could be a biomarker for differentiating PFAPA syndrome from FMF. Patients with PFAPA syndrome, FMF, cryopyrin-associated periodic syndrome (CAPS), and streptococcal pharyngitis, and healthy controls were included in this study. Serum galectin-3 levels were measured using enzyme-linked immunosorbent assay. Eighty-seven patients (36 with PFAPA, 39 with FMF, 8 with CAPS, 4 with streptococcal pharyngitis), and 17 healthy controls were included. Blood samples were drawn during attacks from 20 PFAPA and 7 FMF patients and attack-free periods from 22 PFAPA, 35 FMF, and 8 CAPS patients. The median serum galectin-3 level in the PFAPA-attack group (1.025 ng/ml) was significantly lower than the levels in healthy control (2.367 ng/ml), streptococcal pharyngitis (3.021 ng/ml), FMF attack (2.402 ng/ml), and FMF-attack-free groups (2.797 ng/ml) (p = 0.006, 0.03, 0.01, and < 0.001, respectively). PFAPA-attack-free group had lower galectin-3 levels than the FMF-attack-free group (1.794 vs. 2.797 ng/ml, respectively; p = 0.01). Galectin-3 levels did not differ significantly between CAPS and attack-free PFAPA patients (1.439 ng/ml vs. 1.794 ng/ml, respectively; p = 0.63). In our study, for the first time, we defined galectin-3 as a promising biomarker that differs between PFAPA and FMF patients during both disease flares and attack-free periods. Further studies with high number of patients could validate its role as a biomarker.

The association of galectin-3 level with ventricular arrhythmias and left ventricular strain in heart failure patients with implantable cardioverter defibrillator.

BACKGROUND: Ventricular arrhythmias are life-threatening complications of heart failure (HF). Galectin-3, an indicator of fibrosis, is associated with incident HF and was found to be related to poor prognosis in these patients. We aimed to investigate the association of galectin-3 level with left ventricular (LV) arrhythmias in HF. METHODS: A total of 92 non-ischaemic HF patients who had implantable cardioverter-defibrillator were included in this study. Patients were divided into two groups based on the galectin-3 level. Ventricular arrhythmic events and LV strain indices were compared between the two groups. Negative binomial regression was used to detect the independent predictors of total arrhythmic events in HF patients. RESULTS: The median age was 65 (54-71) in the high galectin-3 group (HGAL) and 62 (52-68) in the low galectin-3 group (LGAL). Ventricular arrhythmic events were more frequent in HGAL than in LGAL, including non-sustained ventricular tachycardia (VTnon), sustained-VT (VTs), and ventricular fibrillation (VF) (p < 0.0001, p = 0.002, and p = 0.026, respectively). There were no statistically significant differences between HGAL and LGAL in terms of LV strain measurements. Galectin-3 level was positively significantly correlated with total arrhythmic events (r = 0.58, p < 0.001), but no correlation was found between galectin-3 and LV global longitudinal strain (r = 0.15, p = 0.16). Galectin-3 was an independent predictor of total ventricular arrhythmic events in HF patients (p < 0.0001). CONCLUSION: VTnon, VTs, and VF events were higher in HGAL compared to LGAL. Galectin-3 was an independent predictor of total ventricular arrhythmic events in HF patients and might be used to detect high-risk HF patients for arrhythmic events.