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Prognostic value of soluble ST2 and soluble LR11 on mortality and cardiovascular events in peritoneal dialysis patients.

ABSTRACT: BACKGROUND:Although the soluble form of suppression of tumorigenicity 2 (sST2) and soluble low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11) have emerged as novel cardiovascular biomarkers in patients with cardiovascular disease, their prognostic value has not been fully investigated in peritoneal dialysis (PD) patients. METHODS:We included 74 prevalent PD patients from a prospective cohort and measured serum sST2 and sLR11 concentrations by an enzyme-linked immunosorbent assay. The association of these biomarkers and all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs) was evaluated. RESULTS:During a follow-up of 38.5?months, all-cause deaths and MACCEs were observed in 13 (17.6%) patients and 23 (31.3%) patients. Multivariable Cox analyses demonstrated that greater sST2 was independently associated with higher risk of all-cause mortality (?75.8?ng/mL; hazard ratio [HR]?=?5.551; 95% confidence interval [CI]?=?1.360-22.660) and MACCEs (?72.5?ng/mL; HR?=?4.609; 95% CI?=?1.608-13.208). Furthermore, sST2 showed additive predictive value for mortality to the base model including traditional risk factors (net reclassification index?=?0.598, P?=?0.04). sLR11 was not significantly associated with all-cause mortality or MACCE. CONCLUSIONS:sST2, but not sLR11, indicated a significant prognostic value for all-cause mortality and cardiovascular events in PD patients. Further research is needed to validate emerging biomarkers in these populations.

SUBMITTER: Choi YB

PROVIDER: S-EPMC7296670 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Prognostic value of soluble ST2 and soluble LR11 on mortality and cardiovascular events in peritoneal dialysis patients.

Choi Yu Bum YB Lee Mi Jung MJ Park Jung Tak JT Han Seung Hyeok SH Kang Shin-Wook SW Yoo Tae-Hyun TH Kim Hyung Jong HJ

BMC nephrology 20200615 1

<h4>Background</h4>Although the soluble form of suppression of tumorigenicity 2 (sST2) and soluble low-density lipoprotein receptor relative with 11 ligand-binding repeats (sLR11) have emerged as novel cardiovascular biomarkers in patients with cardiovascular disease, their prognostic value has not been fully investigated in peritoneal dialysis (PD) patients.<h4>Methods</h4>We included 74 prevalent PD patients from a prospective cohort and measured serum sST2 and sLR11 concentrations by an enzym ...[more]

PMID: 32539731

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Project description:RATIONALE & OBJECTIVE:Inflammation, cardiac remodeling, and fibrosis may explain in part the excess risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Growth differentiation factor 15 (GDF-15), galectin 3 (Gal-3), and soluble ST2 (sST2) are possible biomarkers of these pathways in patients with CKD. STUDY DESIGN:Observational cohort study. SETTING & PARTICIPANTS:Individuals with CKD enrolled in either of 2 multicenter CKD cohort studies: the Seattle Kidney Study or C-PROBE (Clinical Phenotyping and Resource Biobank Study). EXPOSURES:Circulating GDF-15, Gal-3, and sST2 measured at baseline. OUTCOMES:Primary outcome was all-cause mortality. Secondary outcomes included hospitalization for physician-adjudicated heart failure and the atherosclerotic CVD events of myocardial infarction and cerebrovascular accident. ANALYTIC APPROACH:Cox proportional hazards models used to test the association of each biomarker with each outcome, adjusting for demographics, CVD risk factors, and kidney function. RESULTS:Among 883 participants, mean estimated glomerular filtration rate was 49±19mL/min/1.73m2. Higher GDF-15 (adjusted HR [aHR] per 1-SD higher, 1.87; 95% CI, 1.53-2.29), Gal-3 (aHR per 1-SD higher, 1.51; 95% CI, 1.36-1.78), and sST2 (aHR per 1-SD higher, 1.36; 95% CI, 1.17-1.58) concentrations were significantly associated with mortality. Only GDF-15 level was also associated with heart failure events (HR per 1-SD higher, 1.56; 95% CI, 1.12-2.16). There were no detectable associations between GDF-15, Gal-3, or sST2 concentrations and atherosclerotic CVD events. LIMITATIONS:Event rates for heart failure and atherosclerotic CVD were low. CONCLUSIONS:Adults with CKD and higher circulating GDF-15, Gal-3, and sST2 concentrations experienced greater mortality. Elevated GDF-15 concentration was also associated with an increased rate of heart failure. Further work is needed to elucidate the mechanisms linking these circulating biomarkers with CVD in patients with CKD.

Project description:Objectives:The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods:In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results:Of 1753 patients, the mean age was 51.1 ± 14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29 ± 1.75. During the follow-up period of 31.2 ± 18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log?rank = 22.41, P < 0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, P = 0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR = 1.39, 95% CI 1.10-2.47, P = 0.021). Conclusions:Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients.

Project description:Background Both light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis are types of cardiac amyloidosis (CA) that require accurate prognostic stratification to plan therapeutic strategies and follow-ups. Cardiac biomarkers, e.g., N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (Hs-cTnT), remain the cornerstone of the prognostic assessment. An increased level of soluble suppression of tumorigenesis-2 (sST2) is predictive of adverse events [all-cause death and heart failure (HF) hospitalizations] in patients with HF. This study aimed to evaluate the prognostic value of circulating sST2 levels in AL-CA and ATTR-CA. Methods We carried out a multicenter study including 133 patients with AL-CA and 152 patients with ATTR-CA. During an elective outpatient visit for the diagnosis of CA, Mayo Clinic staging [NT-proBNP, Hs-cTnT, differential of free light chains (DFLCs)] and sST2 were assessed for all AL patients. Gillmore staging [including estimated glomerular filtration rate (eGFR), NT-proBNP] and Grogan staging (including NT-proBNP and Hs-cTnT) were assessed for TTR-CA patients. Results The median age was 73 years [interquartile range (IQR) 61–81], and 53% were men. The endpoint was the composite of all-cause death or first HF-related hospitalization. The median follow-up was 20 months (IQR 3–34) in AL amyloidosis and 33 months (6–45) in TTR amyloidosis. The primary outcome occurred in 70 (53%) and 99 (65%) of AL and TTR patients, respectively. sST2 levels were higher in patients with AL-CA than in patients with ATTR-CA: 39 ng/L (26–80) vs. 32 ng/L (21–46), p < 0.001. In AL-CA, sST2 levels predicted the outcome regardless of the Mayo Clinic score (HR: 2.16, 95% CI: 1.17–3.99, p < 0.001). In TTR-CA, sST2 was not predictive of the outcome in multivariate models, including Gillmore staging and Grogan staging (HR: 1.17, CI: 95% 0.77–1.89, p = 0.55). Conclusion sST2 level is a relevant predictor of death and HF hospitalization in AL cardiac amyloidosis and adds prognostic stratification on top of NT-proBNP, Hs cTnT, and DFLC.

Dataset Information

Prognostic value of soluble ST2 and soluble LR11 on mortality and cardiovascular events in peritoneal dialysis patients.

Publications

Prognostic value of soluble ST2 and soluble LR11 on mortality and cardiovascular events in peritoneal dialysis patients.

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