Abstract 2386: Growth-Differentiation Factor-15 is a Strong Predictor of Adverse Outcomes in Heart Failure: Results from Val-HeFT.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Inder S Anand ◽  
Tibor Kempf ◽  
Heike Tapken ◽  
Tim Allhoff ◽  
Michael Kuskowski ◽  
...  

Background: Growth-Differentiation Factor-15 (GDF-15) is a member of the TGF-β family that is induced in the heart after myocardial injury. In patients with non-ST segment elevation ACS, GDF-15 is increased and provides prognostic information. Its role in heart failure is unknown. Methods & Results: GDF-15 was measured in 1125 Val-HeFT patients at baseline. Baseline median GDF-15 was 2027 ng/L (IQ range 1447 to 2942) and was abnormal (>1200 ng/L) in 86% of patients. Patients with GDF-15 above the median had higher NYHA class, greater volume load, lower LVEF and eGFR, higher hsCRP, norepinephrine, BNP and aldosterone, lower use of beta-blockers and higher use of diuretics (all p<0.01). In a multivariate COX model including all baseline variables, GDF-15 was a significant independent predictor of death (HR, 1.5, 95% CI, 1.06–2.14), first morbid event (HR 1.56, 95% CI, 1.19–2.04), and hospitalizations for HF (HR, 1.93, 95% CI, 1.33–2.80), as was BNP for all the three endpoints (HR, 1.7, 95% CI, 1.27–2.3), (HR 1.84, 95% CI, 1.45–2.35), and (HR, 1.98, 95% CI, 1.43–2.7). Spearman correlation of BNP with GDF-15 was 0.33 p<0.001. To test whether GDF-15 adds prognostic information over that provided by BNP, patients were sub-grouped using the median BNP (96 pg/mL) and GDF-15 (2027 ng/L). Figure shows survival curves for the four subgroups. In a multivariate COX analysis when both GDF-15 and BNP were above the median, the risk of death was nearly three times as great (HR 2.75, 95% CI 1.75–4.30, p<0.001) compared to those with both below the median. Conclusion: GDF-15 is an important prognostic marker in HF, independent of other markers and adds prognostic information to that provided by BNP alone.

2017 ◽  
Vol 68 (3) ◽  
pp. 631-634
Author(s):  
Valeriu Gabi Dinca ◽  
Gheorghe Manole ◽  
Daniel Cochior ◽  
Alexandra Ligia Dinca

The present study aims at determining on the one hand the growth differentiation factor 15 significance as possible risk biomarker for this condition and, on the other hand, the degree of correlation between its serum concentration and the class of inotropism deficit.The value of the current research stems from the very selected theme, the activity of GDF-15, member of the superfamily of cytokines TGF-b recognized as having implication in atherosclerosis, but almost unexplored as role in the myocardiumremodeling processes, more precisely in fibrosis.


2021 ◽  
Author(s):  
Ping-Hsun Wu ◽  
Yi-Ting Lin ◽  
Jia-Sin Liu ◽  
Yi-Chun Tsai ◽  
Mei-Chuan Kuo ◽  
...  

Abstract Background Despite widespread use, there is no trial evidence to inform β-blocker’s (BB) relative safety and efficacy among patients undergoing hemodialysis (HD). We herein compare health outcomes associated with carvedilol or bisoprolol use, the most commonly prescribed BBs in these patients. Methods We created a cohort study of 9305 HD patients who initiated bisoprolol and 11 171 HD patients who initiated carvedilol treatment between 2004 and 2011. We compared the risk of all-cause mortality and major adverse cardiovascular events (MACEs) between carvedilol and bisoprolol users during a 2-year follow-up. Results Bisoprolol initiators were younger, had shorter dialysis vintage, were women, had common comorbidities of hypertension and hyperlipidemia and were receiving statins and antiplatelets, but they had less heart failure and digoxin prescriptions than carvedilol initiators. During our observations, 1555 deaths and 5167 MACEs were recorded. In the multivariable-adjusted Cox model, bisoprolol initiation was associated with a lower all-cause mortality {hazard ratio [HR] 0.66 [95% confidence interval (CI) 0.60–0.73]} compared with carvedilol initiation. After accounting for the competing risk of death, bisoprolol use (versus carvedilol) was associated with a lower risk of MACEs [HR 0.85 (95% CI 0.80–0.91)] and attributed to a lower risk of heart failure [HR 0.83 (95% CI 0.77–0.91)] and ischemic stroke [HR 0.84 (95% CI 0.72–0.97)], but not to differences in the risk of acute myocardial infarction [HR 1.03 (95% CI 0.93–1.15)]. Results were confirmed in propensity score matching analyses, stratified analyses and analyses that considered prescribed dosages or censored patients discontinuing or switching BBs. Conclusions Relative to carvedilol, bisoprolol initiation by HD patients was associated with a lower 2-year risk of death and MACEs, mainly attributed to lower heart failure and ischemic stroke risk.


Vascular ◽  
2021 ◽  
pp. 170853812110261
Author(s):  
Daniel Perren ◽  
Lauren Shelmerdine ◽  
Luke Boylan ◽  
Craig Nesbitt ◽  
James Prentis ◽  
...  

Introduction Acute limb ischaemia (ALI) forms a significant part of the vascular surgery workload and carries with it high rates of morbidity and mortality. Anaemia is also common amongst vascular surgical patients and has been linked with poor outcomes in some subgroups. We aimed to assess the frequency of anaemia in patients with ALI and its impact on survival and complications following revascularisation to help direct future efforts to optimise outcomes in this patient group. Methods A retrospective analysis of prospectively collected departmental data on patients undergoing surgical intervention for ALI between 2014 and 2018 was performed. Anaemia was defined as a pre-operative haemoglobin (Hb) of <120 g/L for women and <130 g/L for men. The primary outcome was overall survival, assessed with the Kaplan–Meier estimator, with application of Cox proportional hazard modelling to adjust for confounding covariates. Results There were 158 patients who underwent treatment for ALI: 89 (56.3%) of these were non-anaemic with a mean Hb of 146 (SD = 18.4), and 69 (43.7%) were anaemic with a mean Hb of 106 (SD = 13.4). Anaemic patients had a significantly higher risk of death than their non-anaemic counterparts on univariate analysis (HR = 2.11, 95% CIs, 1.28–3.5, p = 0.0036). There was ongoing divergence in survival up to around 6 months between anaemic and non-anaemic groups. Under the Cox model, anaemia was similarly significant as a predictor of death (HR = 2.15, 95% CIs, 1.17–3.95, p = 0.013), accounting for recorded comorbidities, medication use and blood transfusion. Conclusions Anaemia is a significant and independent risk factor for death following revascularisation for ALI and can be potentially be modified. Vascular surgical centres should ensure they have robust pathways in place to identify and consider treating anaemia. There is scope for further work to assess how to best optimise a patient’s levels of circulating haemoglobin.


2021 ◽  
Author(s):  
Patrícia Lourenço ◽  
Filipe M. Cunha ◽  
João Ferreira‐Coimbra ◽  
Isaac Barroso ◽  
João‐Tiago Guimarães ◽  
...  

2021 ◽  
Author(s):  
Abhinav Sharma ◽  
Stephen Greene ◽  
Muthiah Vaduganathan ◽  
Marat Fudim ◽  
Andrew P. Ambrosy ◽  
...  

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Serge Masson ◽  
Luciano Moretti ◽  
Ospedale Mazzoni ◽  
Maria Grazia Rossi ◽  
Emanuele Carbonieri ◽  
...  

Elevated albuminuria, a marker of endothelial renal damage, is a risk factor for cardiovascular events in the general population and in patients with diabetes or hypertension. We report here on its association with mortality in a large population of patients with chronic HF. Albuminuria (albumin/creatinine concentration ratio in a morning spot sample, UACR) was determined in 2131 patients with chronic HF enrolled in 77 centers participating to the GISSI-HF trial. Patients were divided according to normal (UACR <30 mg/g) and abnormal urinary excretion of albumin (≥30 mg/g). Association between elevated albuminuria and all-cause mortality was tested by univariable and multivariable analyses. Elevated albuminuria was found in 25.3% of the population (age 67±11 y, 78.9% males, 30.1% NYHA class III-IV, 55.5% hypertension, 26.1% diabetes) and was more frequent in older patients, those with reduced renal function, diabetes or high CRP. Mortality was significantly higher in patients with elevated albuminuria (20.1% at 1000 days) compared to normals (9.0%, p<0.0001). Elevated albuminuria remained an independent risk factor for all-cause mortality (HR [95%CI] 1.47 [1.18 –1.82]) in a Cox model adjusted for clinical risk factors such as age, gender, NYHA class, renal function, diabetes, BMI and blood pressure. About a quarter of the patients enrolled in the GISSI-HF trial had abnormal urinary albumin excretion, a marker for both renal and systemic vascular disease. We show for the first time in a large representative sample that elevated albuminuria is an independent predictor of all-cause mortality in patients with chronic HF.


2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Da Young Lee ◽  
Zhe Jiao ◽  
Andrew Antolic ◽  
Daiana Weiss ◽  
M. Neale Weitzmann ◽  
...  

Background: Cachexia is wasting of normal body tissue and occurs in chronic medical diseases. It is a common complication of heart failure (HF) that is associated with very high mortality. Growth differentiation factor 15 (GDF15) regulates food intake and can cause cancer cachexia. GDF15 is a sensitive biomarker in humans, though its biologic function in HF is unknown. This study investigated the role of GDF15 in HF. Methods: We utilized a genetic mouse model of dilated cardiomyopathy (DCM) caused by a mutation in the phospholamban gene (PLN R9C ). PLN R9C mice have dysregulated cardiac calcium handling (a common feature of nearly all forms of HF) and develop progressive DCM that leads to HF and premature death. Q-PCR and ELISA were performed to assess expression, tissue distribution and circulating levels of GDF15 in PLN R9C and age-matched wild type (WT) mice. A double transgenic mouse was created by crossing our DCM model with a constitutive Gdf15 knock-out (KO). Using this novel model, we quantified food intake, and assessed fat and lean tissue mass by tissue weight at necropsy and by dual-energy X-ray absorptiometry (DXA). Cardiac function was assessed using echocardiography, and histochemistry performed to quantify cardiac fibrosis. Survival was assessed by Kaplan-Meier. Results: GDF15 mRNA (43-fold; p<0.01) and protein (54-fold; p<0.01) were increased in LV tissue, and circulating GDF15 was elevated (8.3-fold; p=0.03) in PLN R9C mice. Gdf15 was expressed at low levels and was not increased in other organs in PLN R9C mice. PLN R9C mice developed cachexia (reduced fat and lean mass by tissue weight, reduced fat mass by DXA vs. WT; p<0.01 for all) and consumed less food (p<0.01 vs. WT). Gdf15 KO in PLN R9C preserved fat and lean tissue mass and resulted in higher food intake (p≤0.01 for all). Gdf15 KO had no effect on cardiac structure or function by echocardiography and PLN R9C / Gdf15 KO mice displayed only a small reduction in cardiac fibrosis relative to PLN R9C mice (3%; p<0.01). Despite this, Gdf15 KO prolonged survival in PLN R9C (29±3 vs. 25±3 weeks; p<0.01). Conclusions: GDF15 is a novel cardiac hormone produced in HF that triggers anorexia and cachexia in HF by an extra-cardiac mechanism.


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