Growth Differentiation Factor-15 Is a Useful Prognostic Marker in Patients With Heart Failure With Preserved Ejection Fraction

Izumiya, Yasuhiro; Hanatani, Shinsuke; Kimura, Yuichi; Takashio, Seiji; Yamamoto, Eiichiro; Kurihara, Hiroaki; Tokitsu, Takanori; Rokutanda, Taku; Araki, Satoshi; Tsujita, Kenichi; Tanaka, Tomoko; Yamamuro, Megumi; Kojima, Sunao; Tayama, Shinji; Kaikita, Koichi; Hokimoto, Seiji; Ogawa, Hisao

doi:10.1016/j.cjca.2013.12.010

Cited by 65 publications

(45 citation statements)

References 21 publications

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“…However, increased levels of GDF-15 have been observed in patients with AMI, heart failure, and cardiomyopathy. 6,7,[10][11][12][13]26) In the heart, GDF-15 levels increase in response to stress associated with tissue injury and inflammation, including myocardial ischemia. The induction of GDF-15 in cardiomyocytes because of myocardial ischemia in a mouse model of cardiac ischemia and reperfusion injury suggest that it could be a protective factor.…”

Section: Discussionmentioning

confidence: 99%

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Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

et al. 2016

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SummaryInflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). KaplanMeier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 -1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ 2 = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF-15 provided an incremental prognostic value over clinical features. (Int Heart J 2016; 57: 11-17) Key words: Coronary artery disease, Growth differentiation factor-15, Prognosis I nflammatory biomarkers have been proposed for use in the risk stratification of patients with cardiovascular (CV) disease. 1-7) Patients with acute myocardial infarction (AMI) are at significant risk for recurrent CV events, such as death, recurrent MI, and heart failure. Novel biomarkers for patients with AMI are of interest because they may reveal pivotal disease mechanisms and potential therapeutic targets. 8)High-sensitivity C reactive protein (hs-CRP); growth differentiation factor-15 (GDF-15), a member of the transforming growth factor-β superfamily; and ST2, a member of the interleukin-1 receptor family, are strongly associated with CV events in AMI patients. [9][10][11][12][13][14][15][16] In clinically stable patients with acute decompensated heart failure, high levels of B-type natriuretic peptide (BNP) at the end of a hospitalization are strong, independent markers of CV events compared with levels during the acute phase.17) Secondary prevention of CV events is a crucial factor for the prognostic improvement in patients with AMI, and novel biomarkers provide important information about patient management if the biomarkers contribute to the risk stratification in these patients. However, the prognostic significance of inflammatory biomarkers for risk stratification in stable post-MI outpatients is poorly understood. Editorial p.1The aims of this study were to 1) compare the prognostic significance of inflammatory biomarkers for predicting C...

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Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6][7] Patients with acute myocardial infarction (AMI) are at significant risk for recurrent CV events, such as death, recurrent MI, and heart failure. Novel biomarkers for patients with AMI are of interest because they may reveal pivotal disease mechanisms and potential therapeutic targets.…”

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confidence: 99%

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

et al. 2016

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“…GDF15 has also been reported as a nonspecific biomarker for many diseases, including cancer, cardiac, pulmonary, renal, and gynecological disease (Izumiya et al 2014;Kempf and Wollert 2013;Trovik et al 2014;Yang et al 2014). Since several of these conditions are highly prevalent in m.3243A>G carriers (de Laat et al 2012;Hirano et al 2002), including kidney failure (Breit et al 2012), diabetes mellitus (Dominguez-Rodriguez et al 2014), and cardiomyopathy (Montoro-Garcia et al 2012), the contribution of these conditions to the concentration of GDF15 was studied in more detail.…”

Section: Discussionmentioning

confidence: 99%

“…GDF15 was already known as a quite nonspecific biomarker for cancer, as well as cardiac, pulmonary, renal, and gynecological disease (Izumiya et al 2014;Kempf and Wollert 2013;Trovik et al 2014;Yang et al 2014;Breit et al 2012;Montoro-Garcia et al 2012). However, the concentrations reported in these disorders are within the 1.000-7.000 pg/ mL range (Dominguez-Rodriguez et al 2014;Ho et al 2013;Izumiya et al 2014;Montoro-Garcia et al 2012;Trovik et al 2014), whereas concentrations as high as 85.252 pg/mL were reported in patients with mitochondrial disease (Kalko et al 2014). A child with the m.3243A>G mutation, the most commonly observed mutation leading to mitochondrial disease, was reported to have a concentration of 6.999 pg/ mL (reference value, 380 pg/mL (95%CI, 59-701 pg/mL)).…”

Section: Introductionmentioning

confidence: 99%

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

et al. 2015

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In this observational cohort study, we examined the prognostic value of growth and differentiation factor 15 (GDF15) in indicating and monitoring general mitochondrial disease severity and progression in adult carriers of the m.3243A>G mutation.Ninety-seven adult carriers of the m.3243A>G mutation were included in this study. The Newcastle mitochondrial disease adult scale was used for rating mitochondrial disease severity. In parallel, blood was drawn for GDF15 analysis by ELISA. Forty-nine carriers were included in a follow-up study. In a small subset of subjects of whom an echocardiogram was available from general patient care, myocardial deformation was assessed using two-dimensional speckle-tracking strain analysis.A moderate positive correlation was found between the concentration of GDF15 and disease severity (r ¼ 0.59; p < 0.001). The concentration of serum GDF15 was higher in m.3243A>G carriers with diabetes mellitus, cardiomyopathy, and renal abnormalities. After a 2-year follow-up, no significant correlation was found between the change in disease severity and the change in the concentration of GDF15 or between the GDF15 level at the first assessment and the change in disease severity. In the subcohort of patients of whom an echocardiogram was available, the concentration of GDF15 correlated moderately to longitudinal global strain (r ¼ 0.55; p ¼ 0.006; n ¼ 23) but not to circumferential or radial strain.Our results indicate that serum GDF15 is not a strong surrogate marker for general mitochondrial disease severity. Its value in indicating myocardial deformation should be confirmed in a prospective longitudinal study.

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“…Given these findings, Izumiya et al [66] tested the hypothesis that GDF-15 provides an incremental prognostic value in HFpEF. In their study, high GDF-15 levels showed a positive association with NYHA class and BNP levels and strongly predicted cardiovascular events.…”

Section: Novel Biomarkersmentioning

confidence: 99%

Clinical Application of Biomarkers in Heart Failure with a Preserved Ejection Fraction: A Review

et al. 2016

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Heart failure with a preserved ejection fraction (HFpEF) is increasingly prevalent and a leading cause of morbidity and mortality worldwide. HFpEF has a complex pathophysiology, with recent evidence suggesting that an interaction of cardiovascular and noncardiovascular comorbidities (e.g. obesity, hypertension, diabetes, coronary artery disease, and chronic kidney disease) induces an inflammatory state that eventually leads to myocardial structural and functional alterations. Current ACCF/AHA guidelines suggest incorporation of biomarkers along with clinical and imaging tools to establish the diagnosis and disease severity in heart failure (HF). However, the majority of data on biomarkers relating to their levels, or their role in accurate diagnosis, prognostication, and disease activity, has been derived from studies in undifferentiated HF or HF with a reduced EF (HFrEF). As the understanding of the mechanisms underlying HFpEF continues to evolve, biomarkers reflecting different pathways including neurohormonal activation, myocardial injury, inflammation, and fibrosis have a clinical utility beyond the diagnostic scope. Accordingly, in this review article we describe the various established and novel plasma biomarkers and their emerging value in diagnosis, prognosis, response, and guiding of targeted therapy in patients with HFpEF.

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Growth Differentiation Factor-15 Is a Useful Prognostic Marker in Patients With Heart Failure With Preserved Ejection Fraction

Cited by 65 publications

References 21 publications

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

Serum GDF15 Levels Correlate to Mitochondrial Disease Severity and Myocardial Strain, but Not to Disease Progression in Adult m.3243A>G Carriers

Clinical Application of Biomarkers in Heart Failure with a Preserved Ejection Fraction: A Review

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