Dataset Information

Prognostic biomarker soluble ST2 exhibits diurnal variation in chronic heart failure patients.

ABSTRACT:

Aim

Soluble suppression of tumorigenicity-2 (sST2) is a strong prognostic biomarker in heart failure. The emerging understanding of circadian biology in cardiovascular disease may lead to novel applications in prognosis and diagnosis and may provide insight into mechanistic aspects of the disease-biomarker interaction. So far, it is unknown whether sST2 exhibits a diurnal rhythm. Repeated measurements of sST2 may aid in clinical decision making. The goal of this study was to investigate whether sST2 exhibits diurnal variation in patients with heart failure with reduced ejection fraction (HFrEF) and in control subjects, thereby enhancing its diagnostic and prognostic values.

Methods and results

The study comprised 32 subjects: 16 HFrEF patients and 16 controls. Blood was collected at seven subsequent time points during a 24 h time period. sST2, N-terminal pro-B-type natriuretic peptide (NT-proBNP), melatonin, and cortisol were measured from serum. Peak values of sST2 clustered at daytime (modal value: 5 p.m.) in 87.6% of all subjects (81.3% of patients, P = 0.021; 93.8% of controls, P = 0.001), and minimum concentrations at night-time (modal value: 5 a.m.) in 84.4% (87.5% of patients, P = 0.004 81.3% of controls, P = 0.021). A cosinor analysis of mean normalized sST2 values revealed significant cosine shaped 24 h oscillations of patients (P = 0.026) and controls (P = 0.037). NT-proBNP in contrast did not show a diurnal rhythm, while melatonin and cortisol patterns were intact in all subjects.

Conclusions

sST2 exhibits a diurnal rhythm with lower values in the morning than in the late afternoon. This new insight could lead to refinement of its diagnostic and prognostic values through specified and consistent sampling times with repeated measurements. For example, by measuring sST2 during the afternoon, when levels are at their highest, false negatives on prognosis prediction could be avoided.

SUBMITTER: Crnko S

PROVIDER: S-EPMC7261542 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Prognostic biomarker soluble ST2 exhibits diurnal variation in chronic heart failure patients.

Crnko Sandra S Printezi Markella I MI Jansen Tijn P J TPJ Leiteris Laurynas L van der Meer Manon G MG Schutte Hilde H van Faassen Martijn M du Pré Bastiaan C BC de Jonge Nicolaas N Asselbergs Folkert W FW Gaillard Carlo A J M CAJM Kemperman Hans H Doevendans Pieter A PA Sluijter Joost P G JPG van Laake Linda W LW

ESC heart failure 20200331 3

<h4>Aim</h4>Soluble suppression of tumorigenicity-2 (sST2) is a strong prognostic biomarker in heart failure. The emerging understanding of circadian biology in cardiovascular disease may lead to novel applications in prognosis and diagnosis and may provide insight into mechanistic aspects of the disease-biomarker interaction. So far, it is unknown whether sST2 exhibits a diurnal rhythm. Repeated measurements of sST2 may aid in clinical decision making. The goal of this study was to investigate ...[more]

PMID: 32233077

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Project description:Objective: The diagnostic performance of soluble suppression of tumorigenicity (sST2) in heart failure (HF) had been investigated in multiple studies, but the results were inconsistent. This meta-analysis evaluated the diagnostic value of sST2 in HF. Methods: Pubmed, Web of Science, Embase, and Cochrane Library databases were searched until March 2021. Cohort studies or case-control studies relevant to the diagnostic value of sST2 in HF were screened, and true positive (TP), false positive (FP), false negative (FN), and true negative (TN) data were extracted for calculating sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC). The quality of the included studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS), the threshold effect was determined by calculating Spearman correlation coefficients and summary receiver operating characteristic (SROC) curve patterns, the heterogeneity was evaluated using the I 2 statistic and the Galbraith radial plot, and sensitivity analysis was also performed. Deeks' test was used to assess publication bias. Results: A total of 11 studies from 10 articles were included in this meta-analysis. The Spearman correlation coefficient was 0.114, p = 0.739, and the SROC curve did not show a "shoulder-arm" shape, which suggests that there was no threshold effect, but study heterogeneity existed because of non-threshold effects. The combined sensitivity was 0.72 [95% confidence interval (CI): 0.65-0.78], specificity was 0.65 (95% CI: 0.45-0.81), PLR was 1.75 (95% CI: 1.33-2.31), NLR was 0.48 (95% CI: 0.37-0.63), DOR was 3.63 (95% CI: 2.29-5.74), and AUC was 0.75. The Deeks' test suggested no significant publication bias in the included studies (P = 0.94). Conclusion: sST has some diagnostic value in HF, but this should be further evaluated in additional studies with rigorous design and high homogeneity.

Project description:BackgroundHeart failure (HF) is the terminal stage of all cardiovascular events. Although implantable cardioverter defibrillator (ICD) therapies have reduced mortality among the high-risk HF population, it is necessary to determine whether certain factors can predict mortality even after cardiac device implantation. Growth stimulation expressed gene 2 (ST2) is an emerging biomarker for HF patient stratification in different clinical settings.AimsThis study aimed to investigate the relationship between baseline soluble ST2 (sST2) levels in serum and the clinical outcomes of high-risk HF patients with device implantation.MethodsBetween January 2017 and August 2018, we prospectively recruited consecutive patients implanted with an ICD for heart failure, with LVEF ≤35% as recommended, and analyzed the basic characteristics, baseline serum sST2, and NT-proBNP levels, with at least 1-year follow-up. All-cause mortality was the primary endpoint.ResultsDuring a 643-day follow-up, all-cause mortality occurred in 16 of 150 patients (10.67%). Incidence of all-cause mortality increased significantly in patients with sST2 levels above 34.98846 ng/ml (16.00% vs. 5.33%, P = 0.034). After adjusting the model (age, gender, device implantation, prevention of sudden death, LVEDD, LVEF, WBC and CLBBB, hsTNT, etiology, and eGFR) and the model combined with NT-proBNP, the risk of all-cause death was increased by 2.5% and 1.9%, respectively, per ng/ml of sST2. The best sST2 cutoff for predicting all-cause death was 43.42671 ng/ml (area under the curve: 0.72, sensitive: 0.69, and specificity: 0.69). Compared to patients with sST2 levels below 43.42671 ng/ml, the risk of all-cause mortality was higher in those with values above the threshold (5.1% vs. 21.2%, P = 0.002). ST2 level ≥43.42671 ng/ml was an independent predictor of all-cause mortality (HR: 3.30 [95% CI 1.02-10.67]). Age (HR: 1.06 [95% CI: 1.01-1.12]) and increased NT-proBNP per 100 (HR: 1.02 [95% CI: 1.01-1.03]) were also associated with all-cause mortality in ICD patients.ConclusionssST2 level was associated with risk of all-cause mortality, and a threshold of 43.43 ng/ml showed good distinguishing performance to predict all-cause mortality in patients with severe heart failure, recommended for ICD implantation. Patients with sST2 levels more than 43.42671 ng/ml even after ICD implantation should therefore be monitored carefully.

Dataset Information

Prognostic biomarker soluble ST2 exhibits diurnal variation in chronic heart failure patients.

Aim

Methods and results

Conclusions

Publications

Prognostic biomarker soluble ST2 exhibits diurnal variation in chronic heart failure patients.

Similar Datasets

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