Abstract 5016: Growth-Differentiation Factor-15 is an Independent Predictor of Cardiovascular Events and Mortality in Patients with Stable Coronary Artery Disease

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Tibor Kempf ◽  
Jan-Malte Sinning ◽  
Anja Quint ◽  
Christoph Bickel ◽  
Christoph Sinning ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Independent Predictor ◽  
Troponin T ◽  
Receiver Operating Curve ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Stable Cad

Circulating levels of the TGF β-related cytokine, growth-differentiation factor-15 (GDF-15), provide independent prognostic information in patients with unstable coronary artery disease (CAD). To explore the prognostic utility of GDF-15 in patients with stable CAD, we analyzed the relation of GDF-15 to mortality and cardiovascular (CV) events in the AtheroGene registry which enrolled consecutive patients with stable angina and at least one stenosis >30% in a larger coronary artery. Patients were followed for a median of 3.6 years. Serum samples for measurement of GDF-15 along with other biomarkers were available from 1352 patients. Two pre-specified cutoff points (1200 and 1800 ng/L) were used to identify different risk groups. 55.9%, 26.4%, and 17.7% of the patients presented with GDF-15 values <1200 ng/L, between 1200 and 1800 ng/L, and >1800 ng/L, respectively. Increasing levels of GDF-15 were related to age (P<0.001), hypertension (P=0.01), diabetes mellitus (P<0.001), low HDL cholesterol (P<0.001), and the extent of CAD (P=0.001). Moreover, significant relations to hsCRP, troponin T, NT-proBNP, and reduced renal function (GFR) were observed (all P<0.001). Increasing levels of GDF-15 were associated with an increased risk of all-cause mortality (P<0.001, log-rank test), CV mortality (P<0.001), and CV events (P<0.001). Receiver operating curve analyses confirmed GDF-15 as a strong marker of 2-year adverse outcomes (area under the curve for all-cause mortality, 0.79; CV mortality, 0.81; CV events, 0.70). By multiple Cox regression analysis, GDF-15 emerged as an independent predictor of all-cause mortality (HR 2.1 per one standard deviation of lnGDF-15 [95% CI 1.6 –2.8], P<0.001), CV mortality (HR 2.2 [95% CI 1.5–3.3], P<0.001), and CV events (HR 1.7 [95% CI 1.3–2.4], P=0.001) after adjustment for baseline characteristics, clinical variables, LDL/HDL ratio, hsCRP, troponin T, NT-proBNP, and GFR. Patients with a GDF-15 level above 1800 ng/L had a highly elevated risk of CV mortality even in the fully adjusted model (HR 5.2 [95% CI 1.6 –16.1], P=0.005). These data identify GDF-15 as a powerful and independent biomarker of mortality and CV events in patients with stable CAD.

Abstract 13448: Impact of Diabetes on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hiromichi Wada ◽  
Takashi Unoki ◽  
masahiro suzuki ◽  
Morihiro Matsuda ◽  
Yoichi Ajiro ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
General Population ◽  
Growth Differentiation Factor 15 ◽  
Diabetic Status ◽  
Differentiation Factor ◽  
Risk Of Mortality ◽  
Artery Disease ◽  
Stable Cad ◽  
The Impact

Background: Diabetes mellitus (DM) is still significantly associated with the risk of mortality in the general population. Higher circulating growth differentiation factor 15 (GDF-15) levels are associated with the risk of mortality in the general population, in patients with DM, and in those with coronary artery disease (CAD). However, whether GDF-15 levels differ according to the diabetic status and whether DM modifies the relationship between GDF-15 and mortality in patients with stable CAD are unclear. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between diabetic status and GDF-15 and the impact of DM on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 797 DM and 663 non-DM patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with DM exhibited significantly higher levels of GDF-15 compared to those without DM (median [interquartile range], 1472 [1049-2258] vs. 1274 [868-1874] pg/mL, respectively; P <0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, DM, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P <0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with DM (HR, 1.52; 95% CI, 1.30-1.79) and in those without DM (HR, 1.57; 95% CI, 1.25-1.96). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with DM, but not in those without DM. Conclusions: Higher levels of GDF-15 were independently associated with DM in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with DM.

scholarly journals Increased Soluble ST2 Predicts Long-term Mortality in Patients with Stable Coronary Artery Disease: Results from the Ludwigshafen Risk and Cardiovascular Health Study

2014 ◽  
Vol 60 (3) ◽  
pp. 530-540 ◽  
Author(s):  
Benjamin Dieplinger ◽  
Margot Egger ◽  
Meinhard Haltmayer ◽  
Marcus E Kleber ◽  
Hubert Scharnagl ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Risk Ratio ◽  
Independent Predictor ◽  
Stable Coronary Artery Disease ◽  
Amino Terminal ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Stable Cad

Abstract BACKGROUND Soluble suppression of tumorigenicity 2 (sST2) has emerged as a strong prognostic biomarker in patients with heart failure and myocardial infarction. The aim of this study was to evaluate the long-term prognostic value of sST2 in patients with stable coronary artery disease (CAD). METHODS sST2 plasma concentrations were measured in 1345 patients with stable CAD referred for coronary angiography at a single tertiary care center. The primary endpoint was all-cause mortality. RESULTS During a median follow-up time of 9.8 years, 477 (36%) patients died. The median sST2 plasma concentration at baseline was significantly higher among decedents than survivors (21.4 vs 18.5 ng/mL; P &lt; 0.001). In multivariate Cox proportional hazards regression analysis, sST2 was an independent predictor of all-cause mortality (risk ratio 1.16 per 1-SD increase in log-transformed values; 95% CI 1.05–1.29; P = 0.004). In the same multivariate analysis, amino-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) were also independent predictors, whereas galectin-3 was not. Patients with sST2 in the highest quartile (&gt;24.6 ng/mL) displayed a 2-fold increased risk of death in univariate analysis, which was attenuated but remained significant in a fully adjusted model (risk ratio 1.39; 95% CI 1.10–1.76; P = 0.006). Further analysis showed that the prognostic impact of sST2 was additive to NT-proBNP and hs-cTnT. Using a multibiomarker approach combining these 3 complementary makers, we demonstrated that patients with all 3 biomarkers in the highest quartiles had the poorest outcome. CONCLUSIONS In this cohort of patients with stable CAD, increased sST2 was an independent predictor of long-term all-cause mortality and provided complementary prognostic information to hs-cTnT and NT-proBNP.

Abstract 13423: Impact of Anemia on Growth Differentiation Factor 15 and Mortality in Patients With Stable Coronary Artery Disease: The ANOX Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Moritake Iguchi ◽  
masahiro suzuki ◽  
Morihiro Matsuda ◽  
Yoichi Ajiro ◽  
Tsuyoshi Shinozaki ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Transforming Growth Factor ◽  
Stable Coronary Artery Disease ◽  
Linear Regression Analysis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Artery Disease ◽  
Stable Cad ◽  
The Impact

Background: Growth differentiation factor 15 (GDF-15) is a stress responsive cytokine of the transforming growth factor superfamily. Circulating levels of GDF-15 are elevated in various conditions including anemia and stable coronary artery disease (CAD), and associated with the risk of mortality in patients with stable CAD. However, whether anemia modifies the relationship between GDF-15 and mortality in patients with stable CAD is unknown. Methods: Using data from a multicenter, prospective cohort of 1460 patients with stable CAD, we assessed the association between anemic status and GDF-15 and the impact of anemia on the association between GDF-15 levels and the risk of all-cause death. GDF-15 was measured in 564 anemic and 896 non-anemic patients enrolled in the ANOX Study. Results: The mean age (standard deviation [SD]) of the patients was 71.7 (9.4) years; 74.4% were men. Patients with anemia exhibited significantly higher levels of GDF-15 compared to those without anemia (median [interquartile range], 1953 [1302-3110] vs. 1175 [838-1579] pg/mL, respectively; P <0.001). Stepwise multiple linear regression analysis revealed that the log-transformed (Ln-) GDF-15 level was independently associated with higher age, diabetes, current smoking, lower estimated glomerular filtration rate, anemia, no use of aspirin, Ln-N-terminal pro-natriuretic peptide, and Ln-high-sensitivity C-reactive protein ( P <0.005 for all). In the entire patient cohort, the GDF-15 level was significantly associated with all-cause death after adjusting for potential clinical confounders (hazard ratio per 1-SD increase [HR], 1.51; 95% confidence interval [CI], 1.33-1.71). This association was still significant in patients with anemia (HR, 1.71; 95% CI, 1.44-2.05) and in those without anemia (HR, 1.44; 95% CI, 1.21-1.71). However, GDF-15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in the entire cohort and in patients with anemia, but not in those without anemia. Conclusions: Higher levels of GDF-15 were independently associated with anemia in patients with stable CAD. The prognostic value of GDF-15 on mortality was pronounced in patients with anemia.

Abstract 15942: Oral Anticoagulation as Compared to Oral Anticoagulation Plus Single Antiplatelet Therapy in Stable Coronary Artery Disease With Af: A Meta-analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Igor Vaz ◽  
Ashish Kumar ◽  
Mariam Shariff ◽  
Rajkumar P Doshi ◽  
Rafael Duarte
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Oral Anticoagulation ◽  
Observational Studies ◽  
Stable Coronary Artery Disease ◽  
Treatment Strategies ◽  
Statistical Heterogeneity ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Stable Cad

Introduction: There are limited data on the appropriate antithrombotic therapy in patients with stable coronary artery disease (CAD) and concurrent atrial fibrillation (AF). The efficacy of using a single antiplatelet (SAP) in addition to oral anticoagulation (OAC) as compared to OAC alone remains controversial, with the earlier regimen associated with increased risk of major bleeding. Methods: A systematic electronic search of the PubMed, EMBASE and Cochrane databases was performed to identify relevant publications. Inclusion criteria were randomized controlled studies (RCTs) and observational studies comparing OAC+SAPT to OAC alone in patients with stable CAD and concurrent AF. All-cause mortality, stroke and myocardial infarction (MI) were the endpoints analyzed. We used the inverse variance method with random-effect model to calculate the hazard ratio (HR) with 95% confidence interval (CI). Statistical heterogeneity was calculated using Higgins I2 statistics. All statistical analysis was performed using RevMan Version 5.3. Results: The final analysis included two RCTs and 3 observational studies comparing OAC+SAPT versus OAC alone in patients with stable CAD and AF. There was no difference in the rate of mortality between the two treatment strategies [HR: 1.13, 95%CI: 0.88-1.46, I2= 71%] [Figure, PANEL A]. Subgroup analysis based on RCTs and observation studies reported similar results. Additionally, there was no difference in the rate of stroke [HR: 1.24, 95%CI: 0.83-1.85, I2= 0%] [Figure, PANEL B]or MI [HR: 0.57, 95%CI: 0.29-1.14, I2= 0%] [Figure, PANEL C] between the two treatment strategies Conclusion: OAC+SAPT as compared to OAC alone in patients with stable CAD and AF was associated with similar rates of all-cause mortality, stroke and MI.

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