| 1. |
- Eggers, Kai M., 1962-, et al.
(author)
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Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain
- 2008
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 29:19, s. 2327-2335
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Journal article (peer-reviewed)abstract
- AIMS: Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain. METHODS AND RESULTS: Sixty-nine per cent of the patients presented with GDF-15 levels above the previously defined upper reference limit (1200 ng/L). The risks of the composite endpoint of death or (recurrent) MI after 6 months were 1.3, 5.1, and 12.6% in patients with normal (<1200 ng/L), moderately elevated (1200-1800 ng/L), or markedly elevated (>1800 ng/L) levels of GDF-15 on admission, respectively (P < 0.001). By multivariable analysis that included clinical characteristics, ECG findings, peak cardiac troponin I levels within 2 h (cTnI(0-2 h)), N-terminal pro-B-type natriuretic peptide, C-reactive protein, and cystatin C, GDF-15 remained an independent predictor of the composite endpoint. The ability of the ECG combined with peak cTnI(0-2 h) to predict the composite endpoint was markedly improved by addition of GDF-15 (c-statistic, 0.74 vs. 0.83; P < 0.001). CONCLUSION: GDF-15 improves risk stratification in unselected patients with acute chest pain and provides prognostic information beyond clinical characteristics, the ECG, and cTnI.
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| 2. |
- Eggers, Kai M., 1962-, et al.
(author)
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Growth-differentiation factor-15 for long-term risk prediction in patients stabilized after an episode of non-ST-segment-elevation acute coronary syndrome
- 2010
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In: Circulation: Cardiovascular Genetics. - 1942-3268. ; 3:1, s. 88-96
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growth-differentiation factor-15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome. This study assessed the time course and the long-term prognostic relevance of GDF-15 levels measured repetitively in patients with non-ST-segment-elevation acute coronary syndrome during 6 months after the acute event. METHODS AND RESULTS: GDF-15 and other biomarkers were measured at randomization, after 6 weeks, and after 3 and 6 months in 950 patients with non-ST-segment-elevation acute coronary syndrome included in the FRagmin and Fast Revascularization during InStability in Coronary artery disease II study. Study end points were death, recurrent myocardial infarction, and their composite during 5-year follow-up. Median GDF-15 levels decreased slightly from 1357 ng/L at randomization to 1302 ng/L at 6 months (P<0.001). GDF-15 was consistently related to cardiovascular risk factors and biochemical markers of hemodynamic stress, renal dysfunction, and inflammation. Moreover, GDF-15 was independently related to the 5-year risk of the composite end point when measured at both 3 months (adjusted hazard ratio, 1.8 [1.0 to 3.0]) and 6 months (adjusted hazard ratio, 2.3 [1.3 to 4.1]). Serial measurements of GDF-15 at randomization and 6 months helped to identify patient cohorts at different levels of risk, with patients with persistently elevated GDF-15 levels >1800 ng/L having the highest rate of the composite end point. CONCLUSIONS: GDF-15 is independently related to adverse events in non-ST-segment-elevation acute coronary syndrome both in the acute setting and for at least 6 months after clinical stabilization. Therefore, continued research on GDF-15 should be focused on the usefulness of GDF-15 for support of clinical management in acute and chronic ischemic heart disease.
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| 3. |
- Kempf, Tibor, et al.
(author)
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Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay
- 2007
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In: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53:2, s. 284-291
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growth-differentiation factor 15 (GDF15) is a member of the transforming growth factor beta (TGF-beta) cytokine superfamily. There has been increasing interest in using circulating GDF15 as a biomarker in patients, for example those with cardiovascular disease. METHODS: We developed an IRMA that uses a polyclonal, affinity chromatography-purified goat antihuman GDF15 IgG antibody, assessed the preanalytic characteristics of GDF15, and determined circulating GDF15 concentrations in 429 apparently healthy elderly individuals and 153 patients with chronic heart failure (CHF). RESULTS: The assay had a detection limit of 20 ng/L, an intraassay imprecision of < or =10.6%, and an interassay imprecision of < or =12.2%. Specificity was demonstrated with size-exclusion chromatography, parallel measurements with polyclonal and monoclonal anti-GDF15 antibody, and lack of cross-reactivity with TGF-beta. The assay was not appreciably influenced by the anticoagulant matrix or unrelated biological substances. GDF15 was stable at room temperature for 48 h and resistant to 4 freeze-thaw cycles. Apparently healthy, elderly individuals presented with a median GDF15 concentration of 762 ng/L (25th-75th percentiles, 600-959 ng/L). GDF15 concentrations were associated with age and with cystatin C and C-reactive protein concentrations. CHF patients had increased GDF15 concentrations that were closely related to disease severity. CONCLUSION: The IRMA can detect GDF15 in human serum and plasma with excellent sensitivity and specificity. The reference limits and confounding variables defined for apparently healthy elderly individuals and the favorable preanalytic characteristics of GDF15 are expected to facilitate future studies of GDF15 as a biomarker in various disease settings, including CHF.
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| 4. |
- Kempf, Tibor, et al.
(author)
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Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction
- 2007
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 28:23, s. 2858-2865
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Journal article (peer-reviewed)abstract
- Aims Growth-differentiation factor-15 (GDF-15) is a transforming growth factor-beta-related cytokine that is induced in the heart following ischaemia-reperfusion injury. We explored the prognostic utility of GDF-15 in patients with ST-segment elevation myocardial infarction (STEMI) receiving fibrinolytic therapy. Methods and results Circulating levels of GDF-15 were determined by an immunoradiometric assay in 741 STEMI patients who were included in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT)-2 and ASSENT-plus trials. About 72.7% of the patients presented with GDF-15 levels >= 1200 ng/L, the upper limit of normal in apparently healthy elderly individuals. Increased levels of GDF-15 were associated with a higher risk of death during 1-year follow-up. Mortality rates at 1 year were 2.1, 5.0, and 14.0% in patients with GDF-15 levels < 1200, 1200-1800, and > 1800 ng/L, respectively (P < 0.001). GDF-15 remained an independent predictor of mortality after adjustment for clinical variables, troponin T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). GDF-15 provided prognostic information in clinically relevant patient subgroups, defined according to age, gender, cardiovascular risk factors, haemodynamic status, and the TIMI risk score. Moreover, GDF-15 added prognostic information to the established biomarkers of adverse prognosis in STEMI, troponin T, and NT-proBNP. Conclusion GDF-15 is a new biomarker in STEMI that provides prognostic information beyond established clinical and biochemical markers.
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| 5. |
- Wollert, Kai C, et al.
(author)
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Growth Differentiation Factor 15 for Risk Stratification and Selection of an Invasive Treatment Strategy in Non-ST-Elevation Acute Coronary Syndrome
- 2007
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In: Circulation. - 0009-7322 .- 1524-4539. ; 116:14, s. 1540-1548
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Journal article (peer-reviewed)abstract
- Background— An invasive treatment strategy improves outcomein patients with non–ST-elevation acute coronary syndromeat moderate to high risk. We hypothesized that the circulatinglevel of growth differentiation factor 15 (GDF-15) may improverisk stratification. Methods and Results— The Fast Revascularization duringInStability in Coronary artery disease II (FRISC-II) trial randomizedpatients with non–ST-elevation acute coronary syndrometo an invasive or conservative strategy with a follow-up for2 years. GDF-15 and other biomarkers were determined on admissionin 2079 patients. GDF-15 was moderately elevated (between 1200and 1800 ng/L) in 770 patients (37.0%), and highly elevated(>1800 ng/L) in 493 patients (23.7%). Elevated levels ofGDF-15 independently predicted the risk of the composite endpoint of death or recurrent myocardial infarction in the conservativegroup (P=0.016) but not in the invasive group. A significantinteraction existed between the GDF-15 level on admission andthe effect of treatment strategy on the composite end point.The occurrence of the composite end point was reduced by theinvasive strategy at GDF-15 levels >1800 ng/L (hazard ratio,0.49; 95% confidence interval, 0.33 to 0.73; P=0.001), between1200 and 1800 ng/L (hazard ratio, 0.68; 95% confidence interval,0.46 to 1.00; P=0.048), but not <1200 ng/L (hazard ratio,1.06; 95% confidence interval, 0.68 to 1.65; P=0.81). Patientswith ST-segment depression or a troponin T level >0.01 µg/Lwith a GDF-15 level <1200 ng/L did not benefit from the invasivestrategy. Conclusions— GDF-15 is a potential tool for risk stratificationand therapeutic decision making in patients with non–ST-elevationacute coronary syndrome as initially diagnosed by ECG and troponinlevels. A prospective randomized trial is needed to validatethese findings.
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