Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml⁻¹ and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68−0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64−0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68−0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70−1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929.

Background: Systemic oxidative stress is involved in the development of hypertension, whereas carotenoids are a group of natural antioxidants. Our study aims to evaluate the relationships between the serum concentrations of major carotenoids and mortality in hypertensive adults. Methods and Results: Data on 5 serum carotenoids from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001–2006 were included. Outcome measures (all‐cause and cardiovascular mortality) were identified from the National Death Index through December 31, 2019. Multiple Cox proportional hazards regression and restricted cubic spline analyses were performed to determine the association between carotenoid levels and outcomes. A total of 8390 hypertensive adults were included in the analysis. At a median follow‐up duration of 16.6 years, all‐cause and cardiovascular mortality occurred in 4005 (47.74%) and 1205 (14.36%) participants, respectively. Compared with the lowest quartiles, the highest quartiles of 5 major serum carotenoids were associated with lower risk of all‐cause mortality, with multivariable‐adjusted hazard ratios (HRs) of 0.63 (95% CI, 0.56–0.71) for α‐carotene, 0.70 (95% CI, 0.61–0.80); for β‐carotene, 0.67 (95% CI, 0.58–0.76); for β‐cryptoxanthin, 0.74 (95% CI, 0.64–0.86) for lycopene; and 0.72 (95% CI, 0.63–0.83) for lutein/zeaxanthin. For cause‐specific mortality, this association with the fourth quartile of serum carotenoids was evident for a reduced rate of cardiovascular mortality, with a 32% reduction for α‐carotene (HR, 0.68 [95% CI, 0.55–0.86]), a 29% reduction for β‐cryptoxanthin (HR, 0.71 [95% CI, 0.56–0.89]), and a 26% reduction for lycopene (HR, 0.74 [95% CI, 0.59–0.94]), but not for β‐carotene and lutein/zeaxanthin. In addition, we found that serum α‐carotene, β‐carotene, β‐cryptoxanthin, and lutein/zeaxanthin levels were nonlinearly related to all‐cause mortality with inflection points of 2.43, 8.49, 5.12, and 14.17 μg/dL, respectively. Serum α‐carotene, β‐cryptoxanthin, and lutein/zeaxanthin concentrations showed nonlinear associations with cardiovascular mortality with inflection points of 2.31, 5.26, and 15.40 μg/dL, respectively. Conclusions: Findings suggest that higher serum carotenoid concentrations were associated with lower risks of all‐cause and cardiovascular mortality in hypertensive adults.

Cobalt exposure has adverse health effects on the cardiovascular system in occupational and laboratory studies, but these effects have not been assessed in the general population. We aimed to determine whether serum cobalt levels had relationship with the prevalence of cardiovascular disease (CVD) in the general population. Using data from the National Health and Nutrition Examination Survey (NHANES) (2015–2016), we performed the cross-sectional study. We analyzed the baseline characteristics of 3389 participants (1623 men and 1766 women). Generalized linear models and restricted cubic spline plots curve were undertaken to elucidate the relationship. Stratified subgroup analysis was tested to exclude interaction between different variates and cobalt. Our results showed that the adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for CVD prevalence across the quartiles of cobalt were 0.94 (0.67, 1.30), 1.55 (1.15, 2.10), and 1.74 (1.28, 2.35) compared with lowest quartile. The restricted cubic spline curve also suggested nonlinear and positive association between cobalt and CVD (P for nonlinearity = 0.007). In summary, our cross-sectional results verify that higher cobalt levels are associated with a higher prevalence of cardiovascular disease.

Objective: This study aimed to analyze immune-related genes and immune cell components in the peripheral blood of patients with acute myocardial infarction (AMI). Methods: Six datasets were obtained from the GEO repository comprising 88 healthy samples and 215 AMI samples. We performed the weighted gene co-expression analysis (WGCNA) and five machine learning (ML) methods to identify immune-related genes and construct diagnostic models. CIBERSORT algorithm was adopted for the assessment of the degree of immune infiltration. Finally, RT-PCR, immunofluorescence double and immunohistochemistry were conducted to analyze the expression level of the identification of featured immune-related genes and localization relationship in heart tissue of AMI mouse model. Results: A total of 496 immune-related DEGs were obtained between AMI and normal samples. WGCNA finally determined the co-expression modules that showed the most significantly positively associated with AMI (r=0.41; P< 0.001). Among the five ML models, XGBoost had the highest AUC (0.849) and accuracy (0.812) to discriminate patients with AMI from normal in the validation sets. Furthermore, we found that the proportion of chemokine receptor (CCR), macrophages, neutrophils, and Treg cells in the AMI groups was significantly higher than that in the normal groups. In vitro RT-PCR verification revealed that SOCS3, MMP9, and AQP9 expression increased significantly in the AMI mouse model. Among the 22 immune cells, AQP9, MMP9, and SOCS3 displayed the strongest positive correlation with neutrophils. In MI-mice, MPO stained strongly along the lateral cardiomyocytes, whereas it was weaker in sham mice. Combined immunofluorescence was observed in same parts of the cytoplasm of cardiomyocytes in myocardial infarction area, indicating co-localization of MPO with MMP9 and SOCS3 in these areas, respectively. Conclusion: Immune-related genes and immune cells are intimately related to AMI. Constructing different ML models based on these biomarkers could be a valuable approach to diagnosing AMI in clinical practice.

Background: Inflammation is one of the major pathways in the progression of hypertension (HTN), and the related inflammatory markers have demonstrated certain predictive values. The current study aimed to integrate these markers to construct an inflammatory prognostic scoring (IPS) system and to assess the prognostic values of IPS in patients with HTN. Methods: A total of 9846 adult participants with HTN from NHANES 1999– 2010 were enrolled and followed up. Demographic characteristics and the related laboratory results for the 12 inflammatory markers were collected. LASSO-COX regression, Kaplan–Meier, restricted cubic spline COX regression (RCS), receiver operator characteristic curve (ROC), and random survival forests (RSF) analysis were applied to explore the values of individual and IPS parameters. Results: At the census date of follow-up, 2387 (24.2%) were identified as all-cause deaths and 484 (4.9%) as cardiovascular deaths. All inflammatory markers showed certain prognostic values. Then, based on the LAASO analysis, LDH, ALP, LYM, NLR, MLR, SIRI, and RDW were included in the construction of the IPS system. The higher IPS had significantly worse long-term prognosis in Kaplan–Meier analysis (p log-rank < 0.001). Also, IPS remained an independent prognosticator compared to the lowest quartile (All p for trend < 0.001), and the ROC showed satisfactory values in the long-term prognosis of both cardiovascular and all-cause mortality. RCS further showed a linear association of IPS with cardiovascular mortality and all-cause mortality (p for non-linearity > 0.05). Two different algorithms of RSF, variable importance and minimal depth, to evaluate the prognostic importance showed that IPS was the best in survival prediction. Conclusion: Our results highlight that a higher IPS (system integrating the inflammatory markers) was associated with the increased risk of cardiovascular and all-cause mortality in patients with HTN, suggesting that IPS is a useful method for risk stratification in HTN.

Background: The safety of prescribing angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) during acute kidney injury (AKI) remains unclear. We aimed to investigate the associations of ACEI/ARB therapy in AKI with the risk of mortality, acute kidney disease (AKD), and hyperkalemia.Methods: We conducted a retrospective monocentric study, which included patients in Massachusetts between 2008 and 2019 from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Propensity score matching was performed for the endpoint analysis. The association between ACEI/ARB therapy and mortality was assessed using Cox proportional hazards regression models. Logistic regression was used to assess the risk of AKD and hyperkalemia.Results: Among the 19,074 individuals with AKI admitted to the intensive care unit (ICU), 3,244 (17.0%) received ACEI/ARBs, while 15,830 (83.0%) did not. In the propensity score-matched sample of 6,358 individuals, we found a decreased risk of mortality in those who received ACEI/ARBs compared to those who did not (hazard ratio [HR] for ICU mortality: 0.34, 95% confidence interval [CI]: 0.27–0.42); HR for in-hospital mortality: 0.47, 95% CI: 0.39–0.56; HR for 30-day mortality: 0.47, 95% CI: 0.40–0.56; HR for 180-day mortality: 0.53, 95% CI: 0.45–0.62). However, the use of ACEI/ARBs was associated with a higher risk of AKD (risk ratio [RR]: 1.81; 95% CI: 1.55–2.12). There was no significant association between ACEI/ARBs and an increased risk of hyperkalemia (RR: 1.21; 95% CI: 0.96–1.51).Conclusions: ACEI/ARB treatment during an episode of AKI may decrease all-cause mortality, but increases the risk of AKD. Future randomized controlled trials are warranted to validate these findings.