Coronary artery disease (CAD) is associated with gut microbiota alterations in different populations. Gut microbe-derived metabolites have been proposed as markers of major adverse cardiac events. However, the relationship between the gut microbiome and the different stages of CAD pathophysiology remains to be established by a systematic study. Based on multi-omic analyses (sequencing of the V3-V4 regions of the 16S rRNA gene and metabolomics) of 161 CAD patients and 40 healthy controls, we found that the composition of both the gut microbiota and metabolites changed significantly with CAD severity. We identified 29 metabolite modules that were separately classified as being positively or negatively correlated with CAD phenotypes, and the bacterial co-abundance group (CAG) with characteristic changes at different stages of CAD was represented by Roseburia, Klebsiella, Clostridium IV and Ruminococcaceae. The result revealed that certain bacteria might affect atherosclerosis by modulating the metabolic pathways of the host, such as taurine, sphingolipid and ceramide, and benzene metabolism. Moreover, a disease classifier based on differential levels of microbes and metabolites was constructed to discriminate cases from controls and was even able to distinguish stable coronary artery disease from acute coronary syndrome accurately. Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified the relationships between the features of the gut microbiota and circulating metabolites, providing a new direction for future studies aiming to understand the host–gut microbiota interplay in atherosclerotic pathogenesis.

Background: Coronary thrombosis events continue to be the leading cause of morbidity and mortality worldwide. Recently, emerging evidence has highlighted the role of gut microbiota in cardiovascular disease, but few studies have systematically investigated the gut microbiota variation associated with atherothrombosis. Methods: We conducted multi-omics analysis (metagenomics sequencing and serum metabolomics) on 146 subjects from Peking Union Medical College Hospital-Coronary Artery Disease (PUMCH-CAD) cohort. We analyzed the key strains and metabolic pathways related to coronary artery disease (CAD) development, explored the bacterial functional pathway which contributes to atherothrombosis at strain level in depth. Single strain colonization procedures on germ free mice demonstrated the promotion of platelet activation and thrombotic phenotypes of the disordered gut microbiota. Results: Gut microbiome and serum metabolome shifts were apparent in cases of CAD progression, Bacteroides spp. disturbed the development of CAD by participating in lipopolysaccharide (LPS), menaquinone and methanogenesis pathways. Particularly, coronary thrombosis is characterized by increased circulatory levels of L-tryptophan, which correlate with Bacteroides thetaiotaomicron that has enriched biosynthetic potential. In germ free mice we demonstrate that Bacteroides thetaiotaomicron colonization could induce thrombosis, aggravate platelet hyperreactivity and augment fecal levels of L-tryptophan. Conclusions: The disordered gut microbiota of CAD contributed to the occurrence and development of atherothrombosis. The key members of the bacterial and metabolic features may become biomarkers for predicting the cardiovascular thrombosis event. Targeting the microbial pathway may have the potential to reduce the incidence of cardiovascular disorders. Clinical Trial Registration: ChiCTR2000033897, https://www.chictr.org.cn/showproj.html?proj=55023.

Coronary artery ectasia is defined as a local or diffuse dilatation of the coronary artery more than 1.5 times the diameter of the adjacent normal segment. The etiology of coronary artery ectasia is diverse, and rarely complicated with immunoglobulin G4-related disease (IgG4-related disease). A limited number of cases have been reported, with insidious onset, slow progression but poor prognosis. we report a patient with coronary artery ectasia combined with IgG4-related disease. He has been diagnosed with IgG4-related disease 5 years after his first percutaneous coronary intervention (PCI). Despite routine treatment with steroids, he develops a large coronary aneurysm and eventually died. It is suggested that a thorough evaluation should be performed when coronary artery ectasia is diagnosed. The factors such as manifestations of coronary artery thickening, typical imaging features, other aortas involvement, increased serum IgG4 level, etc. should be considered for early diagnosis of key etiologies.

Background: High blood pressure is a major risk factor for cardiovascular and renal diseases, and lipid metabolism disorders may affect blood pressure through mechanisms such as endothelial inflammation. Remnant cholesterol, a key component of triglyceride-rich lipoproteins, has been recognized as a causal factor for atherosclerosis and metabolic disorders. This study aims to investigate the relationship of remnant cholesterol with blood pressure control in the general US population. Methods: A total of 3915 participants with self-reported hypertension from NHANES from 2007 to 2018 were included in this study. Demographic and behavior parameters, blood pressure, and blood samples were conducted. Remnant cholesterol was estimated as total cholesterol minus low-density lipoprotein cholesterol minus high-density lipoprotein cholesterol. Control of hypertension was defined as systolic blood pressure less than 140 mmHg and diastolic blood pressure less than 90 mmHg in participants with hypertension. Results: The mean age was 56.98 ± 0.28 years, and 2021 (weighted percentage 51.34%) were female. Among all participants, 2650 participants had their blood pressure well controlled. In multivariate logistic regression, the associations between remnant cholesterol and blood pressure control were statistically significant after adjusting age, sex, race/ethnicity, education level, poverty income ratio, smoking and drinking status, metabolic equivalent, HbA1c, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (Model 1: OR=0.74, 95% CI: 0.57– 0.95; Model 2: OR=0.72, 95% CI: 0.55– 0.94; Model 3: OR=0.73, 95% CI: 0.56– 0.93; Model 4: OR=0.60, 95% CI: 0.46– 0.78). The subgroup analysis revealed generally consistent associations with the main results. Conclusion: Remnant cholesterol is associated with blood pressure control. Targeting remnant cholesterol through lifestyle modifications or lipid-lowering therapies may improve blood pressure control in high-risk patients.

Background: Thrombosis is a critical and lethal complication of isolated coronary artery ectasia (iCAE), potentially linked to hemodynamic changes, particularly wall shear stress (WSS) alterations. However, the association between thrombosis and multidirectionality of blood flow, and thus of WSS, is not well defined. Methods: This study retrospectively enrolled 34 patients diagnosed with iCAE. In total, 53 ectatic coronary arteries were identified for hemodynamics analysis, of which 11 had thrombosis and 42 did not. We used an automated workstation for coronary three-dimensional reconstruction and conducted computational fluid dynamics (CFD) analysis. Particularly, we analyzed the mean changes in the following multidirectional WSS metrics at the ectatic segments: time-averaged WSS (TAWSS), oscillatory shear index (OSI), relative residence time (RRT), transverse WSS (transWSS), cross-flow index (CFI), and topological shear variation index (TSVI). Results: Local TAWSS _mean , OSI _mean , RRT _mean , transWSS _mean , CFI _mean , and TSVI _mean of iCAE with thrombosis were significantly higher than those of iCAE without thrombosis ( p < 0.05 for all). Logistic regression analyses indicated that RRT _mean (OR = 1.010, 95% CI: 1.002–1.019, p = 0.021) and transWSS _mean (OR = 1.992, 95% CI: 1.257–2.939, p = 0.003) were independently associated with the risk of thrombosis among patients with iCAE. The RRT _mean + transWSS _mean model [Area Under the Curve (AUC) = 0.911] exhibited a greater capacity for identifying the risk of thrombosis among patients with iCAE compared to maximum vascular diameter (MVD) (AUC = 0.789, p = 0.048). Conclusions: Multidirectional WSS metrics can help identify iCAE with a higher risk of thrombosis. It can improve thrombosis risk stratification.