With an increasing global burden of coronary artery disease (CAD), early detection and timely management of risk factors are crucial to reduce morbidity and mortality in such patients. Diabetes mellitus (DM) is considered an independent risk factor for the development of CAD. Metformin, an anti-diabetic drug, has been shown in pre-clinical and clinical studies, to lower the cardiovascular events in the DM patients. Growing evidence suggests that metformin has a protective effect on coronary artery beyond its hypoglycemic effects. Given its global availability, route of administration and cost, metformin provides an alternate/additional therapeutic option for primary and secondary prevention of CAD in DM and non-diabetics alike. Future prospective cohort-based studies and randomized clinical trials are needed to identify ‘at-risk’ population who may potentially benefit from metformin.

The specific mechanism of pulmonary arterial hypertension (PAH) remains elusive. The present study aimed to explore the underlying mechanism of PAH through the identity of novel biomarkers for PAH using metabolomics approach. Serum samples from 40 patients with idiopathic PAH (IPAH), 20 patients with congenital heart disease‐associated PAH (CHD‐PAH) and 20 healthy controls were collected and analysed by ultra‐high‐performance liquid chromatography coupled with high‐resolution mass spectrometry (UPLC‐HRMS). Orthogonal partial least square‐discriminate analysis (OPLS‐DA) was applied to screen potential biomarkers. These results were validated in monocrotaline (MCT)‐induced PAH rat model. The OPLS‐DA model was successful in screening distinct metabolite signatures which distinguished IPAH and CHD‐PAH patients from healthy controls, respectively (26 and 15 metabolites). Unbiased analysis from OPLS‐DA identified 31 metabolites from PAH patients which were differentially regulated compared to the healthy controls. Our analysis showed dysregulation of the different metabolic pathways, including lipid metabolism, glucose metabolism, amino acid metabolism and phospholipid metabolism pathways in PAH patients compared to their healthy counterpart. Among these metabolites from dysregulated metabolic pathways, a panel of metabolites from lipid metabolism and fatty acid oxidation (lysophosphatidylcholine, phosphatidylcholine, perillic acid, palmitoleic acid, N‐acetylcholine‐d‐sphingomyelin, oleic acid, palmitic acid and 2‐Octenoylcarnitine metabolites) were found to have a close association with PAH. The results from the analysis of both real‐time quantitative PCR and Western blot showed that expression of LDHA, CD36, FASN, PDK1 GLUT1 and CPT‐1 in right heart/lung were significantly up‐regulated in MCT group than the control group.

Background: Statins are routinely prescribed to lower cholesterol and have been demonstrated to have significant benefits in atherosclerotic cardiovascular disease. However, whether statin therapy has effects on cancer risk remains controversial. In this study, we investigated the influence of statin therapy on cancer incidence and mortality by conducting a comprehensive meta-analysis of randomized controlled trials. Methods: Systematic searches by Cochrane, Embase, Medline, and PubMed were performed to locate data from eligible randomized controlled trials related to statin therapy and oncology. Our main endpoints were cancer incidence and mortality. Fixed-effects models were used in this study. Results: This meta-analysis comprised thirty-five randomized controlled studies. Twenty-eight included studies reported cancer incidence, and eighteen reported cancer mortality. The pooled results indicated no reduction in cancer incidence with statins compared to placebo [OR = 0.99, 95% CI (0.95, 1.03)]. In addition, statins did not decrease cancer mortality [OR = 0.99, 95% CI (0.91, 1.07)]. This study also performed a number of subgroup analyses, which showed no effect of statins on cancer subtypes such as genitourinary and breast cancer. Neither the type of statin nor long-term treatment with statins had an effect on cancer incidence and mortality. Conclusion: Through comprehensive analysis, we found that statin therapy does not reduce cancer incidence or mortality while protecting the cardiovascular system. Trial registration: Prospero CRD42022377871.

The uric acid-to-HDL-cholesterol ratio (UHR), a novel marker of metabolism and inflammation, has been investigated in various diseases. However, its potential associations with the incidence of cardiovascular disease (CVD) and dyslipidemia remain unclear. This study aimed to examine the relationships between the UHR and the incidence of CVD and dyslipidemia. The primary objective was to evaluate the role of the UHR in predicting CVD and dyslipidemia, whereas the secondary objective was to analyze the predictive effects of the UHR in different subgroups. We conducted a cross-sectional analysis using data from the 2001–2018 National Health and Nutrition Examination Survey (NHANES), which included 6,370 adults aged 18–80 years. Weighted binary logistic regression and subgroup analyses were performed to evaluate the independent associations between the UHR and the risk of various cardiovascular conditions, including overall CVD, congestive heart failure, myocardial infarction, angina, coronary heart disease, and dyslipidemia. To investigate potential nonlinear relationships between the UHR and these outcomes, restricted cubic spline modeling was applied to further elucidate the associations. Among the 6,370 participants included in the study, 559 were diagnosed with CVD. Elevated UHR values were strongly associated with a greater incidence of CVD and its subtypes, including congestive heart failure, myocardial infarction, angina, and coronary heart disease (all P < 0.001). After accounting for weighted factors, participants in the higher UHR quartiles presented progressively higher rates of CVD: Quartile 1 (4.7%), Quartile 2 (6.3%), Quartile 3 (7.4%), and Quartile 4 (11%). A nonlinear relationship between the UHR and the risk of developing CVD was identified through restricted cubic spline (RCS) analysis. Among the subgroup of 4,117 participants with dyslipidemia, multivariable linear regression analysis demonstrated a significant positive association between the UHR and dyslipidemia (OR 17.38, 95% CI 16.24–18.60). This association remained robust even after adjusting for covariates (OR 11.65, 95% CI 8.995–15.17). RCS analysis further confirmed the nonlinear nature of this relationship. Subgroup analysis revealed no significant interaction between the UHR and overall CVD or CVD-related variables, such as congestive heart failure, myocardial infarction, angina, or coronary heart disease. However, for dyslipidemia, BMI showed a significant interaction, indicating that the positive association between the UHR and dyslipidemia risk is influenced by participants’ BMI. A high UHR is associated with an increased risk of various cardiovascular conditions and dyslipidemia. The incorporation of routine UHR monitoring into clinical practice can support the early identification of high-risk individuals, facilitate timely interventions, and reduce the burden of cardiovascular and metabolic diseases.

Pulmonary hypertension (PH) is one of the most devastating cardiovascular diseases worldwide and it draws much attention from numerous scientists. As an indispensable part of pulmonary artery, smooth muscle cells are worthy of being carefully investigated. To elucidate the pathogenesis of PH, several theories focusing on pulmonary artery smooth muscle cells (PASMC), such as hyperproliferation, resistance to apoptosis, and cancer theory, have been proposed and widely studied. Here, we tried to summarize the studies, concentrating on the role of PASMC in the development of PH, feasible molecular basis to intervene, and potential treatment to PH.

Gut microbiota and its metabolites play an important role in maintaining host homeostasis. Pulmonary arterial hypertension (PAH) is a malignant clinical syndrome with a frightening mortality. Pulmonary vascular remodeling is an important feature of PAH, and its pathogenesis is not well established. With the progress of studies on intestinal microbes in different disease, cumulative evidence indicates that gut microbiota plays a major role in PAH pathophysiology. In this review, we will systematically summarize translational and preclinical data on the correlation between gut dysbiosis and PAH and investigate the role of gut dysbiosis in the causation of PAH. Then, we point out the potential significance of gut dysbiosis in the diagnosis and treatment of PAH as well as several problems that remain to be resolved in the field of gut dysbiosis and PAH. All of this knowledge of gut microbiome might pave the way for the extension of novel pathophysiological mechanisms, diagnosis, and targeted therapies for PAH.