Association between biomarkers of zinc and copper status and heart failure: a meta-analysis. ESC heart failure AIMS:Previous studies have investigated the relationship between heart failure (HF) and levels of zinc and copper, but conflicting results have been reported. This meta-analysis aims to clarify the role of zinc and copper in HF progression by examining the associations between HF and concentrations of these minerals. METHODS AND RESULTS:We utilized STATA 12.0 software to calculate the standard mean difference (SMD) and 95% confidence interval (CI) for serum zinc and copper levels in patients with HF compared with healthy controls (HCs). The meta-analysis indicated a lower serum zinc level in patients with HF compared with HCs, using a random effects model (SMD = -0.77; 95% CI: -1.01, -0.54; I = 61.9%, the P-value for Q test = 0.002). Additionally, the meta-analysis showed an increased serum copper level in patients with HF compared with HCs, using a random effects model (SMD = 0.66; 95% CI: 0.09, 1.23; I = 93.8%, the P-value for Q test < 0.001). Meta-regression analysis indicated that publication year, age, and gender were not responsible for heterogeneity across studies. CONCLUSIONS:This meta-analysis demonstrates that patients with HF have lower serum zinc and higher copper concentrations compared with healthy subjects. However, the potential of zinc supplementation as a therapy for HF should be approached with caution. The heterogeneity among the included studies was found to be high. It is recommended that further well-designed large sample studies be conducted to validate these findings. 10.1002/ehf2.14837

Galectin-3 levels and long-term all-cause mortality and hospitalization in heart failure patients: a meta-analysis. ESC heart failure AIMS:This meta-analysis investigated the dose-response relationship between circulating galectin-3 levels and adverse outcomes in patients with heart failure (HF). METHODS AND RESULTS:PubMed and Embase were screened for studies on galectin-3 and HF. The outcomes of interest were all-cause mortality (ACM), and all-cause mortality or HF-related rehospitalization (ACM/HFR), with a follow-up time of more than 6 months. For categorical variables, comparisons between groups with the highest and lowest galectin-3 levels were pooled. For continuous variables, the risks of ACM and ACM/HFR increase per 1-standard deviation (SD) and 1-unit after logarithmic transformation galectin-3 levels were pooled. A random-effects model was employed to calculate the pooled results, and all pooled results were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Besides, a dose-response analysis was performed. Twenty-four cohort studies were included. In HF patients, higher circulating galectin-3 levels were significantly associated with a higher risk of long-term ACM (HR, 1.65; 95% CI 1.28-2.13; I = 66%), and 1 ng/mL increase in galectin-3 was associated with a 4% (HR, 1.04; 95% CI 1.02-1.06; P = 0.002) increase in hazard. Similarly, higher circulating galectin-3 levels were significantly associated with a higher risk of long-term ACM/HFR (HR, 1.52; 95% CI, 1.15 to 2.00; I = 76%), and 1 ng/mL increase in galectin-3 was associated with a 3% (HR, 1.03; 95% CI 1.02-1.04; P < 0.001) increase in hazard. An increase of 1-SD in galectin-3 units was associated with a 29% increased hazard of long-term ACM (HR 1.29; 95% CI 1.13-1.48; I = 42%) and a 22% increased hazard of ACM/HFR (HR 1.22; 95% CI 1.07-1.38; I = 60%). Similarly, an increase of 1-log in galectin-3 units was associated with a 98% higher hazard of long-term ACM (HR 1.98; 95% CI 1.48-2.65; I = 41%) and an 83% higher hazard of ACM/HFR in HF patients (HR 1.83; 95% CI 1.02-3.28; I = 7%). Correlation analysis showed a moderate positive correlation between baseline galectin-3 and N terminal pro brain natriuretic peptide levels (r = 0.48, P = 0.045) and a weak negative correlation with eGFR (r = -0.39, P = 0.077). CONCLUSIONS:Higher circulating galectin-3 levels after hospitalization of HF patients are linearly and positively associated with the risk of long-term ACM and ACM/HFR. 10.1002/ehf2.14813

Natriuretic peptides and C-reactive protein in in heart failure and malnutrition: a systematic review and meta-analysis. ESC heart failure BACKGROUND:Heart failure (HF) and malnutrition exhibit overlapping risk factors, characterized by increased levels of natriuretic peptides and an inflammatory profile. The aim of this study was to compare the differences in plasma brain natriuretic peptide (BNP), N-terminal-pro B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) in patients with HF and malnutrition versus normal nutrition. METHODS:From inception until July 2023, the databases, PubMed, Scopus, Web of Science, and Cochrane Library were searched. To examine the association among malnutrition [controlling nutritional status (CONUT) score ≥2; Geriatric Nutritional Risk Index (GNRI) score <92] with BNP, NT-proBNP and CRP in patients with HF, a meta-analysis using a random-effects model was conducted (CRD42023445076). RESULTS:A significant association of GNRI with increased levels of BNP were demonstrated [mean difference (MD): 204.99, 95% confidence interval (CI) (101.02, 308.96, I = 88%, P < 0.01)], albeit no statistically significant findings were shown using CONUT [MD: 158.51, 95% CI (-1.78 to 318.79, I = 92%, P = 0.05)]. GNRI [MD: 1885.14, 95% CI (1428.76-2341.52, I = 0%, P < 0.01)] and CONUT [MD: 1160.05, 95% CI (701.04-1619.07, I = 0%, P < 0.01)] were associated with significantly higher levels of NT-proBNP. Patients with normal GNRI scores had significantly lower levels of CRP [MD: 0.50, 95% CI (0.12-0.88, I = 87%, P = 0.01)] whereas significantly higher levels of CRP were observed in those with higher CONUT [MD: 0.40, 95% CI (0.08-0.72, I = 88%, P = 0.01)]. Employing meta-regression, age was deemed a potential moderator between CRP and GNRI. CONCLUSIONS:Normal nutrition scores in patients with HF are linked to lower BNP, NT-proBNP, and CRP levels compared with malnourished counterparts. Despite the significant link between CRP and malnutrition, their relationship may be influenced in older groups considering the sensitivity of GNRI due to ageing factors. 10.1002/ehf2.14851

Circulating brain-derived neurotrophic factor levels and heart failure: A systematic review and meta-analysis. ESC heart failure AIMS:Biomarkers are paramount for managing heart failure (HF) patients as prognostic and therapeutic efficacy index tools. Systemic levels of brain-derived neurotrophic factor (BDNF) can add to the HF biomarker scenario, allowing for potentiated efficacy in diagnosis, prognostic stratification, and prediction of patient response to a given therapeutic intervention because BDNF is one of the primary rulers of myocardial function. Yet, whether BDNF is a reliable clinical biomarker awaits clinical validation. Hence, we aimed to answer this relevant question via a systematic review and meta-analysis of existing studies. METHODS AND RESULTS:International databases, including PubMed, Scopus, Embase, and the Web of Science, were comprehensively searched for studies assessing BDNF levels in patients with HF versus non-HF controls or as a prognostic factor for HF complications. Data were extracted and analysed by random-effect meta-analysis. Standardized mean difference (SMD) and 95% confidence intervals (CIs) were computed to pool the results of studies. We included 11 studies in the final review, among which six underwent meta-analysis. These studies analysed 1420 HF patients, with a mean age of 65.4 ± 11.2 years. Meta-analysis revealed that patients with HF had significantly lower circulating BDNF levels than healthy controls (SMD -2.47, 95% CI -4.39 to -0.54, P-value = 0.01). Moreover, patients with higher New York Heart Association functional classification had lower levels of BDNF. Adverse clinical outcomes such as all-cause mortality and HF rehospitalization were also associated with lower levels of BDNF in individual studies. CONCLUSIONS:BDNF levels are decreased in patients with HF. Most importantly, we observed an association between lower BDNF levels and poor prognosis in patients with HF. Our study supports BDNF as an easy-to-dose diagnostic and prognostic biomarker to be implemented in clinical practice for HF. Further studies are warranted to address this ability specifically. 10.1002/ehf2.14916