The use of a large number of cardiovascular biomarkers, meant to complement the use of the electrocardiogram, echocardiography cardiac imaging, and clinical symptom assessment, has become a routine in clinical diagnosis, differential diagnosis, risk stratification, and prognosis and guides the management of patients with suspected cardiovascular diseases. There is a broad consensus that cardiac troponin and natriuretic peptides are the preferred biomarkers in clinical practice for the diagnosis of the acute coronary syndrome and heart failure, respectively, while the roles and possible clinical applications of several other potential biomarkers are still under study. This review mainly focuses on the recent studies of the roles and clinical applications of troponin and natriuretic peptides, which seem to be the best‐validated markers in distinguishing and predicting the future cardiac events of patients with suspected cardiovascular diseases. Additionally, the review briefly discusses some of the large number of potential markers that may play a more prominent role in the future.

Background: Observational studies have indicated that depression is associated with coronary artery disease (CAD) and myocardial infarction. Nevertheless, causal associations between depression and cardiovascular diseases remain controversial. Hence, we conducted a Mendelian randomization and mediation analysis to evaluate the associations of depression‐related genetic variants with CAD and myocardial infarction.Methods and Results: Summary statistics from genome‐wide association studies of depression (807 553 individuals), and CAD (60 801 cases, including 43 676 with myocardial infarction, and 123 504 controls) were used. We pooled Mendelian randomization estimates using a fixed‐effects inverse‐variance weighted meta‐analysis and multivariable Mendelian randomization. The mediation effects of potential cardiovascular risk factors on depression‐CAD and myocardial infarction risk were investigated by using mediation analysis. We also explored the relationship of genetic liability to depression with heart failure, atrial fibrillation, and ischemic stroke. Genetic liability to depression was associated with higher CAD (odds ratio [OR], 1.14; 95% CI, 1.06–1.24;P=1.0×10⁻³) and myocardial infarction (OR, 1.21; 95% CI, 1.11–1.33;P=4.8×10⁻⁵) risks. Results were consistent in all sensitivity analyses. Type 2 diabetes mellitus and smoking demonstrated significant mediation effects. Furthermore, our Mendelian randomization analyses revealed that the genetic liability to depression was associated with higher risks of heart failure and small vessel stroke.Conclusions: Genetic liability to depression is associated with higher CAD and myocardial infarction risks, partly mediated by type 2 diabetes mellitus and smoking. The potential preventive value of depression treatment on cardiovascular diseases should be investigated in the future.

Doxorubicin (Dox) is a widely used antitumor agent with dose-dependent and cumulative cardiotoxic effects. Resveratrol (Res) is a natural non-flavonoid polyphenol that can potentially provide cardiovascular benefits. We aimed to estimate the protective effect of Res on Dox-induced cardiotoxicity (DIC) and explore whether it was related to attenuating ferroptosis. We established DIC models in C57BL/6 J mice, H9C2 cardiomyoblasts, and neonatal rat cardiomyocytes (NRCMs). We further treated H9C2 cells with RSL3, a ferroptosis agonist, to investigate whether Res exerted protective effects through inhibiting ferroptosis. Ferrostatin-1 (Fer-1) was applied to suppress ferroptosis. Dox treatment caused cardiac dysfunction and resulted in apparent ferroptotic damage in cardiac tissue, involving increased iron accumulation, glutathione depletion, increased expression of ferroptosis markers, and decreased expression of glutathione peroxidase 4, which were alleviated by Fer-1 and Res administration. These findings were also confirmed in Dox-treated H9C2 cells and NRCMs, with Fer-1 and Res effectively attenuating Dox-induced cytotoxicity and ferroptosis. Furthermore, Res protected H9C2 cells from RSL3-induced ferroptotic cell death, and the protective effect was similar to that of Fer-1. Both Dox and RSL3 treatment increased the phosphorylation levels of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinases; however, these changes were hindered by Res. This study demonstrates that Res effectively alleviates DIC by suppressing ferroptosis possibly through modulating the MAPK signaling pathway. Our results highlight that targeting ferroptosis can be a potential cardioprotective strategy for DIC.

Aims We performed a Mendelian randomization (MR) study to elucidate the associations of ever smoking, lifelong smoking duration, and smoking cessation with heart failure (HF) risk. Methods and results We extracted genetic variants associated with smoking initiation, age at initiation of regular smoking, cigarettes per day, and smoking cessation from the genome‐wide association study and Sequencing Consortium of Alcohol and Nicotine use (1.2 million individuals), as well as a composite lifetime smoking index from the UK Biobank (462 690 individuals). The associations between smoking phenotypes and HF were explored in the Heart Failure Molecular Epidemiology for Therapeutic Targets Consortium (47 309 cases; 930 014 controls) employing inverse variance‐weighted meta‐analysis and multivariable MR. The mediation effects of coronary artery disease and atrial fibrillation on smoking–HF risk were explored using mediation analysis. The odds ratios (ORs) for HF were 1.28 [95% confidence interval (CI), 1.22–1.36; P = 1.5 × 10⁻¹⁸] for ever regular smokers compared with never smokers and 1.25 (95% CI, 1.09–1.44; P = 1.6 × 10⁻³) for current smokers vs. former smokers. Genetic liability to smoking more cigarettes per day (OR, 1.37; 95% CI, 1.20–1.58; P = 6.4 × 10⁻⁶) and a higher composite lifetime smoking index (OR, 1.49; 95% CI, 1.31–1.70; P = 2.5 × 10⁻⁹) were associated with a higher risk of HF. The results were robust and consistent in all sensitivity analyses and multivariable MR after adjusting for HF risk factors, and their associations were independent of coronary artery disease and atrial fibrillation. Conclusions Genetic liability to ever smoking and a higher lifetime smoking burden are associated with a higher risk of HF.

Aims: We aimed to investigate the effect and mechanism of pleiotropic chemokine CCL24 in heart failure. Methods and results: Compared with normal donators, the expression of CCL24 and number of cardiac M2 macrophages in heart were higher in heart failure patients, the same as plasma CCL24. Treatment with CCL24 antibody hindered Ang II (1500 ng/kg/min)–induced cardiac adverse remodeling through preventing cardiac hypertrophy and fibrosis. RNA-seq showed that CCL24/CCR3 axis was involved in immune and inflammatory responses. Single-cell analysis of cytometry by time of flight (CyTOF) revealed that CCL24 antibody decreased the M2 macrophage and monocyte polarization during Ang II stimulation. Immunofluorescence co-localization analysis confirmed the expression of CCR3 in macrophage and fibroblasts. Then, in vitro experiments confirmed that CCL24/CCR3 axis was also involved in cardiac primary fibroblast activation through its G protein–coupled receptor function. Conclusion: CCL24/CCR3 axis plays a crucial part in cardiac remodeling by stimulating M2 macrophage polarization and cardiac fibroblast activation. Graphical Cardiac M2 macrophages, CCL24 and circulation CCL24 increased in heart failure patients. Treatment with CCL24 Ab hindered Ang II induced cardiac structural dysfunction and electrical remodeling. In CCL24 Ab group RNA-seq found that it was related to immune responses and hypertrophic cardiomyopathy, CytoF revealed M2 macrophages and monocytes decreased obviously. In vitro,CCL24 promoted activation and migration of cardiac fibroblast.