Dataset Information

New Cardiovascular Biomarkers in Ischemic Heart Disease-GDF-15, A Probable Predictor for Ejection Fraction.

ABSTRACT: BACKGROUND:Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls. METHODS AND RESULTS:CAD patients were divided into three groups according to their EF as measured by the biplane Simpson method (53-84%, 31-52%, ?30%). Overall, 361 subjects were analyzed. In total, 155 CAD patients had an EF of 53-84%, 71 patients had an EF of 31-52%, and 23 patients had an EF of ?30% as compared to 112 healthy controls (age 51.3 ± 9.0 years, 44.6% female). Mean ages according to EF were 62.1 ± 10.9, 65.2 ± 10.1, and 66.6 ± 8.2 years, respectively, with females representing 29.0, 29.6, and 13.0%. suPAR, GDF-15, H-FABP, and sST2 values were significantly higher in CAD patients and showed an exponential increase with decreasing EF. In a multiple logistic regression model, GDF-15 (p = 0.009), and NT-brain natriuretic peptide (p = 0.003) were independently associated with EF. CONCLUSION:Biomarkers such as suPAR, GDF-15, H-FABP, and sST2 are increased in CAD patients, especially in highly impaired EF. Besides NT-proBNP as a well-known marker for risk prediction, GDF-15 may be an additional tool for diagnosis and clinical follow-up.

SUBMITTER: Dalos D

PROVIDER: S-EPMC6678676 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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New Cardiovascular Biomarkers in Ischemic Heart Disease-GDF-15, A Probable Predictor for Ejection Fraction.

Dalos Daniel D Spinka Georg G Schneider Matthias M Wernly Bernhard B Paar Vera V Hoppe Uta U Litschauer Brigitte B Strametz-Juranek Jeanette J Sponder Michael M

Journal of clinical medicine 20190627 7

<h4>Background</h4>Various biomarkers have been associated with coronary artery disease (CAD) and ischemic heart failure. The aim of this study was to investigate the correlation of serum levels of soluble urokinase-type plasminogen activator receptor (suPAR), growth differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), and soluble suppression of tumorigenicity 2 (sST2) with left ventricular ejection fraction (EF) in CAD patients and controls.<h4>Methods and results ...[more]

PMID: 31252588

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Project description:Importance:Nearly half of all patients with heart failure have preserved ejection fraction (HFpEF) as opposed to reduced ejection fraction (HFrEF), yet associations of biomarkers with future heart failure subtype are incompletely understood. Objective:To evaluate the associations of 12 cardiovascular biomarkers with incident HFpEF vs HFrEF among adults from the general population. Design, Setting, and Participants:This study included 4 longitudinal community-based cohorts: the Cardiovascular Health Study (1989-1990; 1992-1993 for supplemental African-American cohort), the Framingham Heart Study (1995-1998), the Multi-Ethnic Study of Atherosclerosis (2000-2002), and the Prevention of Renal and Vascular End-stage Disease study (1997-1998). Each cohort had prospective ascertainment of incident HFpEF and HFrEF. Data analysis was performed from June 25, 2015, to November 9, 2017. Exposures:The following biomarkers were examined: N-terminal pro B-type natriuretic peptide or brain natriuretic peptide, high-sensitivity troponin T or I, C-reactive protein (CRP), urinary albumin to creatinine ratio (UACR), renin to aldosterone ratio, D-dimer, fibrinogen, soluble suppressor of tumorigenicity, galectin-3, cystatin C, plasminogen activator inhibitor 1, and interleukin 6. Main Outcomes and Measures:Development of incident HFpEF and incident HFrEF. Results:Among the 22 756 participants in these 4 cohorts (12 087 women and 10 669 men; mean [SD] age, 60 [13] years) in the study, during a median follow-up of 12 years, 633 participants developed incident HFpEF, and 841 developed HFrEF. In models adjusted for clinical risk factors of heart failure, 2 biomarkers were significantly associated with incident HFpEF: UACR (hazard ratio [HR], 1.33; 95% CI, 1.20-1.48; P < .001) and natriuretic peptides (HR, 1.27; 95% CI, 1.16-1.40; P < .001), with suggestive associations for high-sensitivity troponin (HR, 1.11; 95% CI, 1.03-1.19; P = .008), plasminogen activator inhibitor 1 (HR, 1.22; 95% CI, 1.03-1.45; P = .02), and fibrinogen (HR, 1.12; 95% CI, 1.03-1.22; P = .01). By contrast, 6 biomarkers were associated with incident HFrEF: natriuretic peptides (HR, 1.54; 95% CI, 1.41-1.68; P < .001), UACR (HR, 1.21; 95% CI, 1.11-1.32; P < .001), high-sensitivity troponin (HR, 1.37; 95% CI, 1.29-1.46; P < .001), cystatin C (HR, 1.19; 95% CI, 1.11-1.27; P < .001), D-dimer (HR, 1.22; 95% CI, 1.11-1.35; P < .001), and CRP (HR, 1.19; 95% CI, 1.11-1.28; P < .001). When directly compared, natriuretic peptides, high-sensitivity troponin, and CRP were more strongly associated with HFrEF compared with HFpEF. Conclusions and Relevance:Biomarkers of renal dysfunction, endothelial dysfunction, and inflammation were associated with incident HFrEF. By contrast, only natriuretic peptides and UACR were associated with HFpEF. These findings highlight the need for future studies focused on identifying novel biomarkers of the risk of HFpEF.

Project description:Patients with heart failure (HF) and coronary artery disease (CAD) have a high risk for cardiovascular (CV) events including HF hospitalization, stroke, myocardial infarction (MI) and sudden cardiac death (SCD). The present study evaluated associations of proteomic biomarkers with CV outcome in patients with CAD and HF with reduced ejection fraction (HFrEF), shortly after a worsening HF episode. We performed a case-control study within the COMMANDER HF international, double-blind, randomized placebo-controlled trial investigating the effects of the factor-Xa inhibitor rivaroxaban. Patients with the following first clinical events: HF hospitalization, SCD and the composite of MI or stroke were matched with corresponding controls for age, sex and study drug. Plasma concentrations of 276 proteins with known associations with CV and cardiometabolic mechanisms were analyzed. Results were corrected for multiple testing using false discovery rate (FDR). In 485 cases and 455 controls, 49 proteins were significantly associated with clinical events of which seven had an adjusted FDR < 0.001 (NT-proBNP, BNP, T-cell immunoglobulin and mucin domain containing 4 (TIMD4), fibroblast growth factor 23 (FGF-23), growth differentiation factor-15 (GDF-15), pulmonary surfactant-associated protein D (PSP-D) and Spondin-1 (SPON1)). No significant interactions were identified between the type of clinical event (MI/stroke, SCD or HFH) and specific biomarkers (all interaction FDR > 0.20). When adding the biomarkers significantly associated with the above outcome to a clinical model (including NT-proBNP), the C-index increase was 0.057 (0.033-0.082), p < 0.0001 and the net reclassification index was 54.9 (42.5 to 67.3), p < 0.0001. In patients with HFrEF and CAD following HF hospitalization, we found that NT-proBNP, BNP, TIMD4, FGF-23, GDF-15, PSP-D and SPON1, biomarkers broadly associated with inflammation and remodeling mechanistic pathways, were strong but indiscriminate predictors of a variety of individual CV events.

Project description:AimsThe aim of the study was to assess the association of P-selectin with outcomes in heart failure with preserved ejection fraction (HFpEF).Methods and resultsThis is a prospective, observational study of 130 HFpEF patients who underwent clinical profiling, blood sampling, 6 min walk testing, Minnesota Living with Heart Failure Questionnaire evaluation, echocardiography, cardiovascular magnetic resonance imaging, calculation of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk scores, and blinded plasma P-selectin measurement. Patients were followed up for the endpoint of all-cause mortality. The HFpEF subgroup with higher P-selectin levels [overall median 26 372, inter-quartile range (19 360-34 889) pg/mL] was associated with lower age, higher heart rate, less prevalent atrial fibrillation, more frequent current smoking status, and lower right ventricular end-diastolic volumes. During follow-up (median 1428 days), there were 38 deaths. Following maximal sensitivity and specificity receiver operating characteristic curve analysis, P-selectin levels above 35 506 pg/mL were associated with greater risk of all-cause mortality [hazard ratio (HR) 2.700; 95% confidence interval (CI) 1.416-5.146; log-rank P = 0.002]. Following multivariable Cox proportional hazards regression analysis and when added to MAGGIC scores, only P-selectin (adjusted HR 1.707; 95% CI 1.099-2.650; P < 0.017) and myocardial infarction detected by cardiovascular magnetic resonance imaging (HR 2.377; 95% CI 1.114-5.075; P < 0.025) remained significant predictors. In a final model comprising all three parameters, only P-selectin (HR 1.447; 95% CI 1.130-1.853; P < 0.003) and MAGGIC scores (HR 1.555; 95% CI 1.136-2.129; P < 0.006) remained independent predictors of death. Adding P-selectin (0.618, P = 0.035) improved the area under the receiver operating characteristic curve for mortality prediction for MAGGIC scores (0.647, P = 0.009) to 0.710, P < 0.0001.ConclusionsPlasma P-selectin is an independent predictor of mortality and provides incremental prognostic information beyond MAGGIC scores in HFpEF.

Dataset Information

New Cardiovascular Biomarkers in Ischemic Heart Disease-GDF-15, A Probable Predictor for Ejection Fraction.

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New Cardiovascular Biomarkers in Ischemic Heart Disease-GDF-15, A Probable Predictor for Ejection Fraction.

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