Levels of Growth Differentiation Factor 15 and Early Mortality Risk Stratification in Cardiogenic Shock

Hongisto, Mari; Kataja, Anu; Tarvasmäki, Tuukka; Holopainen, Anu; Javanainen, Tuija; Jurkko, Raija; Jäntti, Toni; Kimmoun, Antoine; Lévy, Bruno; Mebazaa, Alexandre; Pulkki, Kari; Sionís, Alessandro; Tolppanen, Heli; Wollert, Kai C.; Harjola, Veli‐Pekka; Lassus, Johan; Investigators, CardShock Study

doi:10.1016/j.cardfail.2019.07.003

Cited by 6 publications

(10 citation statements)

References 26 publications

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“…Other studies have also reported elevated upon-admission GDF15 concentrations in selected, relatively small cohorts of ICU patients, which correlated with poor outcome [ 5 – 8 ]. However, the time course beyond the acute phase and during recovery was not investigated.…”

Section: Discussionmentioning

confidence: 99%

“…Inferentially, elevated GDF15 could function as signal to withhold nutrition in an individual critically ill patient at a time when it cannot be used for anabolism, or vice versa, low GDF15 could identify a good time to start refeeding. Hitherto, the time course of serum GDF15 levels during critical illness and recovery has not been well documented, with only one study reporting values the first three days after cardiogenic shock [8]. Also, the relation between GDF15 and nutrition during critical illness has not been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…GDF15 is a stress response cytokine that is induced by injury and inflammation [ 3 , 4 ]. Hence, it is not surprising that in critically ill patients, very high circulating GDF15 levels have been observed, which were associated with risk of death in a few small studies [ 5 – 8 ]. Also mitochondrial dysfunction, high-fat feeding, and unbalanced protein underfeeding have been shown to increase circulating GDF15 levels [ 3 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

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The clinical potential of GDF15 as a “ready-to-feed indicator” for critically ill adults

et al. 2020

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Background Circulating growth-differentiation factor-15 (GDF15), a cellular stress marker, abruptly increases during critical illness, but its later time course remains unclear. GDF15 physiologically controls oral intake by driving aversive responses to nutrition. Early parenteral nutrition (PN) in ICU patients has overall been shown not beneficial. We hypothesized that low GDF15 can identify patients who benefit from early PN, tolerate enteral nutrition (EN), and resume spontaneous oral intake. Methods In secondary analyses of the EPaNIC-RCT on timing of PN initiation (early PN versus late PN) and the prospective observational DAS study, we documented the time course of circulating GDF15 in ICU (N = 1128) and 1 week post-ICU (N = 72), compared with healthy subjects (N = 65), and the impact hereon of randomization to early PN versus late PN in propensity score-matched groups (N = 564/group). Interaction between upon-admission GDF15 and randomization for its outcome effects was investigated (N = 4393). Finally, association between GDF15 and EN tolerance in ICU (N = 1383) and oral intake beyond ICU discharge (N = 72) was studied. Results GDF15 was elevated throughout ICU stay, similarly in early PN and late PN patients, and remained high beyond ICU discharge (p < 0.0001). Upon-admission GDF15 did not interact with randomization to early PN versus late PN for its outcome effects, but higher GDF15 independently related to worse outcomes (p ≤ 0.002). Lower GDF15 was only weakly related to gastrointestinal tolerance (p < 0.0001) and a steeper drop in GDF15 with more oral intake after ICU discharge (p = 0.05). Conclusion In critically ill patients, high GDF15 reflected poor prognosis and may contribute to aversive responses to nutrition. However, the potential of GDF15 as “ready-to-feed indicator” appears limited. Trial registration ClinicalTrials.gov, NCT00512122, registered 31 July 2007, https://www.clinicaltrials.gov/ct2/show/NCT00512122 (EPaNIC trial) and ISRCTN, ISRCTN 98806770, registered 11 November 2014, http://www.isrctn.com/ISRCTN98806770 (DAS trial)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The clinical potential of GDF15 as a “ready-to-feed indicator” for critically ill adults

et al. 2020

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“…To assess the ability of the CardShock risk score and IABP‐SHOCK II score to predict in‐hospital mortality in the elderly, and to evaluate the additional value of GDF‐15 and sST2 on the risk prediction models, receiver operating characteristic curve analysis was performed. We used previously defined cut‐off values of the biomarkers (GDF‐15 > 7000 ng/L and sST2 > 500 ng/mL) for this analysis 7,8 . The distribution of the elderly patients and observed mortality within risk categories of both risk prediction models were calculated.…”

Section: Methodsmentioning

confidence: 99%

“…Biomarkers have become significant prognostic tools in many cardiovascular diseases. 5,6 Most recently, growth differentiation factor-15 (GDF-15) and soluble ST2 (sST2) have been found to be valuable in risk stratification in heart failure and CS, [7][8][9][10] but data on elderly patients with CS in the contemporary era remain scarce.…”

Section: Introductionmentioning

confidence: 99%

Mortality risk prediction in elderly patients with cardiogenic shock: results from the CardShock study

et al. 2021

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Aims This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor-15 (GDF-15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock. Methods and results Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP-SHOCK II score to predict in-hospital mortality and the additional value of GDF-15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P < 0.05) and more co-morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in-hospital mortality (46% vs. 33%; P = 0.08), but 1 year post-discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP-SHOCK II score. Incorporating GDF-15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84. Conclusions Elderly patients with cardiogenic shock have higher in-hospital mortality compared with the younger, but post-discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF-15 or sST2.

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Circulating heart failure biomarkers beyond natriuretic peptides: review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC)

Meijers

Bayés‐Genís

Mebazaa

et al. 2021

European J of Heart Fail

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New biomarkers are being evaluated for their ability to advance the management of patients with heart failure. Despite a large pool of interesting candidate biomarkers, besides natriuretic peptides virtually none have succeeded in being applied into the clinical setting. In this review, we examine the most promising emerging candidates for clinical assessment and management of patients with heart failure. We discuss high-sensitivity cardiac troponins (Tn), procalcitonin, novel kidney markers, soluble suppression of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor-15 (GDF-15), cluster of differentiation 146 (CD146), neprilysin, adrenomedullin (ADM), and also discuss proteomics and genetic-based risk scores. We focused on guidance and assistance with daily clinical care decision-making. For each biomarker, analytical considerations are discussed, as well as performance regarding diagnosis and prognosis. Furthermore, we discuss potential implementation in clinical algorithms and in ongoing clinical trials.

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Levels of Growth Differentiation Factor 15 and Early Mortality Risk Stratification in Cardiogenic Shock

Cited by 6 publications

References 26 publications

The clinical potential of GDF15 as a “ready-to-feed indicator” for critically ill adults

The clinical potential of GDF15 as a “ready-to-feed indicator” for critically ill adults

Mortality risk prediction in elderly patients with cardiogenic shock: results from the CardShock study

Circulating heart failure biomarkers beyond natriuretic peptides: review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC)

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