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| 8. |
- Eggers, Kai M., et al.
(author)
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Clinical and prognostic implications of circulating pentraxin 3 levels in non ST-elevation acute coronary syndrome
- 2013
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 46:16-17, s. 1655-1659
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Journal article (peer-reviewed)abstract
- Objectives: Pentraxin 3 (PTX3) is the prototype of the long pentraxin family. PTX3 is involved in inflammatory processes affecting the cardiovascular system, and PTX3 levels have been shown to be elevated and independently prognostic in ST-elevation myocardial infarction. Data on PTX3 levels in non-ST-elevation acute coronary syndrome (NSTE-ACS), in contrast, are limited. The aim of the present analysis was to investigate the implications of PTX3 levels in a fairly large sample of NSTE-ACS patients and in comparison to levels of C-reactive protein (CRP). Design and methods: We measured levels of PTX3 and CRP in both 82 healthy controls and 401 NSTE-ACS patients from the GUSTO IV study, and studied the associations of these biomarkers to clinical data and 1-year mortality. Results: NSTE-ACS patients had significantly higher median PTX3 levels compared to healthy controls (3.8 vs. 1.9 mu g/L; p < 0.001). PTX3 levels in patients with NSTE-ACS were independently related to female sex and cardiac troponin T levels, but not to age or cardiovascular risk factors. PTX3 levels were higher in patients who died within 1 year but did not emerge as an independent predictor of 1-year mortality (adjusted OR 1,2 [95% Cl 0.6-2.31). This was in contrast to CRP (adjusted OR 1.5 [95% Cl 1.1-2.3]). Neither PTX3 nor CRP yielded significant discriminative value regarding mortality prediction. Conclusions: PTX3 levels are elevated in NSTE-ACS. However, the prognostic information provided by PTX3 levels is limited and inferior compared to CRP. Our data, thus, do not support the measurement of PTX3 in patients with NSTE-ACS.
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| 9. |
- Eggers, Kai M., 1962-, et al.
(author)
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ST2 and mortality in non-ST-segment elevation acute coronary syndrome
- 2010
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In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 159:5, s. 788-794
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Journal article (peer-reviewed)abstract
- BACKGROUND: ST2 is a member of the interleukin-1 receptor family that is up-regulated in conditions associated with increased myocardial strain. ST2 has been shown to be independently predictive of adverse outcome in heart failure and ST-segment elevation myocardial infarction, but its prognostic value in non-ST-elevation acute coronary syndrome (NSTE-ACS) has not been established. METHODS: We measured ST2 at randomization and after 24, 48, and 72 hours in 403 NSTE-ACS patients from the GUSTO IV study, and studied its kinetics and its associations to clinical baseline factors and 1-year mortality. RESULTS: Median ST2 levels decreased from 28.4 U/mL at randomization to 21.8 U/mL at 72 hours (P < .001). Peak levels were noted 6 to 17 hours after symptom onset. Randomization ST2 levels were independently associated to N-terminal pro-B-type natriuretic peptide but otherwise exhibited only weak relations to cardiovascular risk factors and comorbidities, and biomarkers of myocardial necrosis or inflammation. ST2 was related to 1-year mortality independently of clinical risk indicators (odds ratio 2.3 [95% CI 1.1-4.6], P = .03) but lost its predictive value after additional adjustment for prognostic biomarkers, in particular N-terminal pro-B-type natriuretic peptide. CONCLUSIONS: ST2 levels are elevated early in NSTE-ACS and predict 1-year mortality. Our data indicate that ST2 represents an interesting novel pathophysiologic pathway in the setting of ischemia-related myocardial dysfunction. However, future prospective evaluations in larger populations are needed before the clinical utility of ST2 can be determined.
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| 11. |
- Hernández, Adrián V., et al.
(author)
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Effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST segment elevation acute coronary syndromes : benefit and harm in different age subgroups
- 2007
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In: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 93:4, s. 450-455
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. METHODS: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60-69, 70-79, > or =80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). RESULTS: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5-4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients > or =80 years had half of the NNT and a third of the NNH of patients <60 years. CONCLUSIONS: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted.
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| 12. |
- James, Stefan K., et al.
(author)
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A rapid troponin I assay is not optimal for determination of troponin status and prediction of subsequent cardiac events at suspicion of unstable coronary syndromes.
- 2004
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In: International Journal of Cardiology. - 0167-5273 .- 1874-1754. ; 93:2-3, s. 113-120
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Journal article (peer-reviewed)abstract
- BACKGROUND: Troponin is a specific marker of myocardial damage. For early prediction of coronary events in patients with suspicion of acute coronary syndromes the assay also needs to be highly sensitive. METHODS AND RESULTS: A rapid troponin I assay was performed prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial. A quantitative troponin T analysis was later performed on blood samples obtained at randomization by a central laboratory. There was an agreement between the rapid troponin I assay and troponin T (< or =/>0.1 microg/l) in 3596 (80.9%) patients. A positive rapid troponin I was identifying any elevation of troponin T (>0.01 microg/l) in 1990 patients (90.4%) whereas a negative rapid troponin I was corresponding to negative troponin T (< or =0.01 microg/l) in only 1217 patients (54.2%). Patients with a positive versus negative rapid troponin I had an increased risk of death or myocardial infarction at 30 days (9.3 vs. 5.9%; odds ratio, O.R. 1.64; 95% confidence interval, 1.31-2.06). Troponin T elevation (>0.1 microg/l) provided a better (10.5 v. 4.9%, O.R. 2.26; C.I. 1.79-2.85) risk stratification. Regardless of a positive or a negative rapid troponin I, the troponin T result (>0.1 vs. < or =0.1 microg/l) stratified the patients into high and low risk of events at 30 days, (10.3 vs. 5.7%, P=0.002) and (11.5 vs. 4.8%, P<0.001), respectively. CONCLUSION: In a population with non-ST elevation acute coronary syndrome a positive rapid troponin I assay is a specific indicator of troponin elevation and a predictor of early outcome. However, a negative rapid troponin I is not a reliable indicator of the absence of myocardial damage and does not indicate a low risk of subsequent cardiac events. A rapid troponin I assay was performed prior to inclusion in 4447 acute coronary syndrome patients in the GUSTO-IV trial and related to a centrally analyzed quantitative troponin T test. A positive rapid troponin I was well corresponding to any elevation of troponin T (>0.01 microg/l) and predicted an unfavorable outcome at 30 days. However, a negative rapid troponin I was corresponding to troponin T < or =0.01 microg/l in only half of the patients. Troponin T >0.1 microg/l vs. < or =0.1 microg/l provided a better risk stratification than the rapid troponin I result. For patients with troponin T elevation (>0.1 microg/l) the 30 day event rate was high regardless of the rapid troponin I result.
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| 13. |
- James, Stefan K., 1964-, et al.
(author)
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Troponin-T and N-terminal pro-B-type natriuretic peptide predict mortality benefit from coronary revascularization in acute coronary syndromes : a GUSTO-IV substudy
- 2006
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 48:6, s. 1146-1154
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This study was designed to evaluate biomarkers for selection of patients with non-ST-segment elevation acute coronary syndromes (ACS) that derive mortality benefit from revascularization. BACKGROUND: Biomarkers are essential for identification of patients at increased risk, which may be reduced by revascularization. METHODS: During the initial 30 days, 2,340 patients of 7,800 (30%) with non-ST-segment elevation ACS in the GUSTO (Global Utilization of Strategies To open Occluded arteries)-IV trial underwent coronary revascularization. The 1-year mortality was calculated in 30-day survivors stratified by status of revascularization and levels of biomarkers. A propensity score for receiving revascularization was constructed and included in a survival analysis that also included the time point of revascularization as a time-dependent covariate. RESULTS: Elevation of troponin-T or N-terminal pro-B-type natriuretic peptide (NT-proBNP) was associated with a high mortality. In patients with either or both of these markers elevated, a lower mortality following revascularization was observed. In contrast, patients without elevation of these markers had low 1-year mortality without any reduction in mortality following revascularization. In fact, in patients with normal levels of both troponin-T and NT-proBNP, a significant increase in 1-year mortality after revascularization was observed. Elevation of C-reactive protein, interleukin-6, creatinine clearance, and ST-segment depression was also related to a higher mortality. However, independent of these markers, mortality was lower after revascularization. CONCLUSIONS: Markers of troponin-T and NT-proBNP not only assist in risk stratification of patients with non-ST-segment elevation ACS but also appear to identify patients who have a reduced mortality associated with early coronary revascularization.
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| 14. |
- James, Stefan K., 1964-, et al.
(author)
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Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (A GUSTO IV substudy)
- 2006
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In: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 97:2, s. 167-172
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Journal article (peer-reviewed)abstract
- The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.
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| 15. |
- James, Stefan, et al.
(author)
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N-Terminal Pro–Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease : A Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV Substudy
- 2003
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In: Circulation. - 0009-7322 .- 1524-4539. ; 108:3, s. 275-281
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Journal article (peer-reviewed)abstract
- BACKGROUND: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. METHODS AND RESULTS: NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile. CONCLUSIONS: The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.
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- James, Stefan, et al.
(author)
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Troponin T levels and risk of 30-day outcomes in patients with the acute coronary syndrome : prospective verification in the GUSTO-IV trial
- 2003
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In: American Journal of Medicine. - 0002-9343 .- 1555-7162. ; 115:3, s. 178-184
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Journal article (peer-reviewed)abstract
- BACKGROUND: A third-generation troponin T assay with improved precision and a lower detection limit has been developed. However, the appropriate cutoff for identifying patients with the acute coronary syndrome who are at low risk of subsequent mortality has not been established. METHODS: A retrospective evaluation of data from the Fragmin and fast Revascularization during InStability in Coronary artery disease II (FRISC-II) trial suggested that a cutoff below 0.1 microg/L for troponin T levels might be more useful in risk stratification. A prospective validation of two cutoff levels (0.03 microg/L and 0.01 microg/L) was performed in 7115 patients with non-ST-elevation acute coronary syndrome from the Global Utilization of Strategies To open Occluded arteries IV (GUSTO-IV) trial. RESULTS: Patients with troponin T levels >0.1 microg/L had greater 30-day mortality (5.5% [201/3679]) than did those with levels CONCLUSION: Using a cutoff of
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| 19. |
- Lenderink, Timo, et al.
(author)
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Patients using statin treatment within 24 h after admission for ST-elevation acute coronary syndromes had lower mortality than non-users : a report from the first Euro Heart Survey on acute coronary syndromes
- 2006
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:15, s. 1799-1804
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Journal article (peer-reviewed)abstract
- Aims: Statins provide effective secondary prevention in cardiovascular disease. However, it remains uncertain how soon statins should be started after an acute coronary syndrome (ACS). Recently published trials suggest starting before discharge. We hypothesize that statins should be initiated without delay. Methods and results: Data from a large cohort of 10 484 consecutive patients with an ACS were analysed. Of this cohort, 1426 first-time statin receivers and survivors of the first 24 h were compared with 6771 first-day survivors not receiving statin therapy. A propensity score for the likelihood of receiving statin therapy within 24 h was developed and used with other established risk factors in a multivariable analysis. There was a significantly reduced all-cause 7-day mortality in patients receiving early statin therapy [0.4 vs. 2.6%, unadjusted hazard ratio (HR) 0.16, 95% confidence interval (CI) 0.08-0.37, adjusted HR 0.34, 95% CI 0.15-0.79]. Statistical significance was observed in patients presenting with STE-ACS (adjusted HR 0.17, 95% CI 0.04-0.70) and not in NSTE-ACS patients. However, no statistical evidence of heterogeneity in treatment effect was observed between these groups. Conclusion: These data suggest that very early statin therapy is associated with reduced mortality in patients presenting with STE-ACS; however, these findings have to be confirmed by prospective, randomized controlled trials before firm treatment recommendations can be given.
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| 21. |
- Westerhout, Cynthia M., et al.
(author)
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No prognostic significance of chronic infection with Chlamydia pneumoniae in acute coronary syndromes : insights from the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial
- 2007
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In: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 154:2, s. 306-312
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although relationships between chronic Chlamydia pneumoniae (Cpn) infection and the risk of coronary events in stable coronary artery disease patients have been reported, a similar link in acute coronary syndrome (ACS) patients has not been consistently observed. METHODS: In a nested case-control substudy of the Global Utilization of Strategies to Open Occluded Arteries IV Acute Coronary Syndromes trial, 295 cases (30-day death/myocardial infarction [MI]) were matched by age, sex, baseline creatine kinase-myocardial kinase, and smoking status with 295 control subjects. To test the hypothesis on 1-year mortality, another subset (n = 276) was drawn from the 590-patient cohort; 138 patients who died at 1 year plus the matching controls who survived at 1 year. We measured Cpn IgG and IgA antibody titers in baseline serum with microimmunofluorescence. Conditional logistic regression was used to quantify the prognostic relevance seropositivity (IgG > or = 1:32; IgA > or = 1:16) and elevated titer levels. RESULTS: The prevalence of Cpn IgG and IgA was similar between cases and controls (30-day death/MI: IgG, 80% vs 85%, P = .126; IgA, 45% vs 37%, P = .079), and were not statistically significant predictors of 30-day death/MI after baseline adjustment. Likewise, the 1-year death cohort had comparable proportions of Cpn IgG and IgA among cases and controls (86% vs 91% [P = .265] and 49% vs 43% [P = .334], respectively), and did not add prognostic value. CONCLUSIONS: These findings are in concert with study results suggesting that chronic Cpn infection is not associated with 30-day death/MI or 1-year mortality in non-ST elevation ACS.
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| 22. |
- Westerhout, Cynthia M., et al.
(author)
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Predictors of stroke within 30 days in patients with non-ST-segment elevation acute coronary syndromes
- 2006
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In: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 27:24, s. 2956-2961
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Journal article (peer-reviewed)abstract
- AIMS: Stroke is an uncommon but serious complication after non-ST-segment elevation acute coronary syndrome (NSTE-ACS). We aimed to identify predictors of stroke within 30 days in patients who suffered NSTE-ACS. METHODS AND RESULTS: We pooled data from six trials (n=31 402) that randomized NSTE-ACS patients either to platelet glycoprotein (GP) IIb/IIIa receptor blockers or to placebo/control therapy. Potential predictors of stroke included treatment, demographic, and clinical characteristics. We identified predictors using univariable and multivariable logistic models, and their performance was evaluated with calibration (Hosmer-Lemeshow test) and discrimination (c-statistic). We found 228 (0.7%) all-cause strokes: 155 (0.5%) non-haemorrhagic, 20 (0.06%) haemorrhagic, and 53 without computed tomography (CT) confirmation. Patients with any type of stroke had a 30-day mortality of 25%. Randomization to GP IIb/IIIa receptor blockers was not significantly associated with all-cause stroke [OR (95% CI) 1.08 (0.83-1.41)]. Older age [OR per 10-year increase 1.5 (1.3-1.7)], prior stroke [2.1 (1.4-3.1)], and elevated heart rate [per 10-beat increase 1.1 (1.0-1.2)] were the strongest predictors of 30-day all-cause stroke. Similar predictors were found for non-haemorrhagic and haemorrhagic strokes. Smoking, previous myocardial infarction, diabetes, and hypertension were not independent predictors of all-cause stroke. The multivariable model to predict all-cause stroke was well calibrated, but its discrimination was only moderate [c-statistic 0.69 (0.65-0.72)]. CONCLUSION: Stroke is a rare complication occurring early after NSTE-ACS, but is associated with high mortality. We found no evidence that GP IIb/IIIa receptor blockers increase stroke risks. A few clinical characteristics predicted higher stroke risks. Thus, incident strokes in NSTE-ACS patients remain largely unexplained.
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| 23. |
- Westerhout, Cynthia M., et al.
(author)
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Short- and long-term risk stratification in acute coronary syndromes : the added value of quantitative ST-segment depression and multiple biomarkers
- 2006
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In: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 48:5, s. 939-947
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Journal article (peer-reviewed)abstract
- OBJECTIVES: The purpose of this study was to develop 30-day and 1-year risk stratification models for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients that incorporate quantitative ST-segment depression and novel biomarkers. BACKGROUND: Several novel biomarkers have changed the risk profile of ACS; thus, the reassessment of traditional indicators such as ST-segment depression in this new context is warranted. METHODS: Multivariable logistic regression was used to identify significant predictors of 30-day death and death/myocardial infarction (MI) and 1-year mortality in 7,800 NSTE-ACS patients enrolled in the GUSTO-IV (Global Utilization of Strategies to Open Occluded Arteries-IV ACS) trial between 1998 and 2000. RESULTS: Among all other predictors, the degree of ST-segment depression had the highest prognostic value for 30-day death, 30-day death/MI, and 1-year death. Troponin T (TnT), creatinine clearance, N-terminal pro-brain natriuretic peptide (NT-proBNP), heart rate, and age were also highly influential on adverse outcomes. Unlike TnT and NT-proBNP, C-reactive protein was only predictive of long-term death. In contrast to mortality, the contribution of TnT to predicting 30-day death/MI increased, whereas NT-proBNP's role was attenuated. The discriminatory power was excellent (c-index [adjusted for over-optimism]: 0.82 [30-day death]; 0.72 [30-day death/MI]; 0.81 [1-year]). CONCLUSIONS: In this large contemporary study of NSTE-ACS patients, novel insights into risk stratification were observed-in particular, the utility of quantitative ST-segment depression and multiple biomarkers. Collection of these indicators in future NSTE-ACS populations is recommended to evaluate generalizability and clinical application of these findings.
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| 24. |
- Wollert, Kai C., et al.
(author)
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Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome
- 2007
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In: Circulation. - 0009-7322 .- 1524-4539. ; 115:8, s. 962-971
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Journal article (peer-reviewed)abstract
- BACKGROUND: Growth-differentiation factor-15 (GDF-15) is a member of the transforming growth factor-beta cytokine superfamily that is induced in the heart after ischemia-and-reperfusion injury. Circulating levels of GDF-15 may provide prognostic information in patients with non-ST-elevation acute coronary syndrome. METHODS AND RESULTS: Blood samples were obtained on admission from 2081 patients with acute chest pain and either ST-segment depression or troponin elevation who were included in the Global Utilization of Strategies to Open Occluded Arteries (GUSTO)-IV Non-ST-Elevation Acute Coronary Syndrome trial and from a matching cohort of 429 apparently healthy individuals. GDF-15 levels were determined by immunoradiometric assay. Approximately two thirds of patients presented with GDF-15 levels above the upper limit of normal in healthy controls (1200 ng/L); one third presented with levels >1800 ng/L. Increasing tertiles of GDF-15 were associated with an enhanced risk of death at 1 year (1.5%, 5.0%, and 14.1%; P<0.001). By multiple Cox regression analysis, only the levels of GDF-15 and N-terminal pro-B-type natriuretic peptide, together with age and a history of previous myocardial infarction, contributed independently to 1-year mortality risk. Receiver operating characteristic curve analyses further illustrated that GDF-15 is a strong marker of 1-year mortality risk (area under the curve, 0.757; best cutoff, 1808 ng/L). At this cutoff value, GDF-15 added significant prognostic information in patient subgroups defined by age; gender; time from symptom onset to admission; cardiovascular risk factors; previous cardiovascular disease; and the risk markers ST-segment depression, troponin T, N-terminal pro-B-type natriuretic peptide, C-reactive protein, and creatinine clearance. CONCLUSIONS: GDF-15 is a new biomarker of the risk for death in patients with non-ST-elevation acute coronary syndrome that provides prognostic information beyond that provided by established clinical and biochemical markers.
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