Dataset Information

Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study.

ABSTRACT:

Aims

To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial.

Methods and results

Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 participants with complete data. The relationship between these biomarkers and the primary composite endpoint of heart failure hospitalization or cardiovascular death over 28 months of follow-up (n = 834) was evaluated using Cox proportional hazards regression, the c-statistic and the net reclassification index (NRI). After adjustment, the hazard ratio (HR) for the composite outcome in the top tertile of the distribution compared to the lowest tertile for each biomarker was: NT-proBNP 3.96 (95% CI 3.16-4.98), hsTnT 3.09 (95% CI 2.47-3.88), MR-proADM 2.28 (95% CI 1.83-2.84), copeptin 1.66 (95% CI 1.35-2.04), cystatin C 1.92 (95% CI 1.55-2.37), and hsCRP 1.51 (95% CI 1.27-1.80). A basic clinical prediction model was improved on addition of each biomarker individually, most strongly by NT-proBNP (NRI +62.3%, P < 0.001), but thereafter was only improved marginally by addition of hsTnT (NRI +33.1%, P = 0.004). Further addition of biomarkers did not improve discrimination further. Findings were similar for all-cause mortality.

Conclusion

Once NT-proBNP is included, only hsTnT moderately further improved risk stratification in this group of chronic heart failure with reduced ejection fraction patients with moderate anaemia. NT-proBNP and hsTnT far outperform other emerging biomarkers in prediction of adverse outcome.

SUBMITTER: Welsh P

PROVIDER: S-EPMC6607475 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Publications

Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study.

Welsh Paul P Kou Lei L Yu Changhong C Anand Inder I van Veldhuisen Dirk J DJ Maggioni Aldo P AP Desai Akshay S AS Solomon Scott D SD Pfeffer Marc A MA Cheng Sunfa S Gullestad Lars L Aukrust Pål P Ueland Thor T Swedberg Karl K Young James B JB Kattan Michael W MW Sattar Naveed N McMurray John J V JJV

European journal of heart failure 20170927 2

<h4>Aims</h4>To test the prognostic value of emerging biomarkers in the Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) trial.<h4>Methods and results</h4>Circulating cardiac [N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hsTnT)], neurohumoral [mid-regional pro-adrenomedullin (MR-proADM) and copeptin], renal (cystatin C), and inflammatory [high-sensitivity C-reactive protein (hsCRP)] biomarkers were measured at randomization in 1853 part ...[more]

PMID: 28960777

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Project description:Background Randomized clinical trials in populations with heart failure with reduced ejection fraction may not be reflective of the general population with heart failure with reduced ejection fraction. Our study assessed the representativeness of the GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patient population in Kaiser Permanente Southern California. Methods and Results We identified 9770 patients with a diagnosis of heart failure with reduced ejection fraction from 2014 to 2018 using electronic health records. Four mutually exclusive cohorts were created, including GALACTIC-HF-ineligible cohorts: (1) not taking guideline-directed medical therapy (GDMT) and (2) taking GDMT; and GALACTIC-HF-eligible cohorts with: (3) ejection fraction (EF) ≤28% and (4) EF 29% to 35%. Patients were followed for 30-day and 1-year mortality and 30-day, 180-day, and 1-year hospitalization. Overall, 3626 (37.1%) met GALACTIC-HF inclusion criteria with EF ≤35%, and 2367 (65.3%) of those individuals had EF ≤28%. The risk of 1-year mortality was lower among all cohorts versus the GALACTIC-HF-ineligible cohort not taking GDMT (hazard ratio, 0.80 [95% CI, 0.70-0.91], 0.84 [95% CI, 0.72-0.98], and 0.62 [95% CI, 0.51-0.75] for the GALACTIC-HF-ineligible cohort taking GDMT and GALACTIC-HF-eligible cohorts with EF ≤28% and 29%-35%, respectively). Compared with the GALACTIC-HF-ineligible cohort not taking GDMT, the short-term hospitalization risk at 30 and 180 days were similar for both GALACTIC-HF-eligible cohorts and the hospitalization risk at 1 year was similar for the GALACTIC-HF-eligible cohort with EF ≤28%. Conclusions A large portion of patients with heart failure with reduced ejection fraction with low EF met inclusion criteria for the GALACTIC-HF trial and, despite being on GDMT, had hospitalization rates similar to those not taking GDMT, suggesting potential benefits from other innovative treatments.

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:Approximately half of heart failure patients have a normal ejection fraction, a condition designated as heart failure with preserved ejection fraction (HFpEF). This heart failure subtype disproportionately affects women and the elderly and is commonly associated with other cardiovascular comorbidities, such as hypertension and diabetes. HFpEF is increasing at a steady rate and is predicted to become the leading cause of heart failure within a decade. HFpEF is characterized by impaired diastolic function, thought to be due to concentric remodeling of the heart along with increased stiffness of both the extracellular matrix and myofilaments. In addition, oxidative stress and inflammation are thought to have a role in HFpEF progression, along with endothelial dysfunction and impaired nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling. Surprisingly a number of clinical studies have failed to demonstrate any benefit of drugs effective in heart failure with systolic dysfunction in HFpEF patients. Thus, HFpEF is one of the largest unmet needs in cardiovascular medicine, and there is a substantial need for new therapeutic approaches and strategies that target mechanisms specific for HFpEF. This conclusion is underscored by the recently reported disappointing results of the RELAX trial, which assessed the use of phosphodiesterase-5 inhibitor sildenafil for treating HFpEF. In animal models, endothelial nitric oxide synthase activators and If current inhibitors have shown benefit in improving diastolic function, and there is a rationale for assessing matrix metalloproteinase 9 inhibitors and nitroxyl donors. LCZ696, a combination drug of angiotensin II receptor blocker and neprilysin inhibitor, and the aldosterone receptor antagonist spironolactone are currently in clinical trial for treating HFpEF. Here we present an overview of the etiology and diagnosis of HFpEF that segues into a discussion of new therapeutic approaches emerging from basic research and drugs currently in clinical trial that primarily target diastolic dysfunction or imbalanced ventricular-arterial coupling.

Dataset Information

Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study.

Aims

Methods and results

Conclusion

Publications

Prognostic importance of emerging cardiac, inflammatory, and renal biomarkers in chronic heart failure patients with reduced ejection fraction and anaemia: RED-HF study.

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