Plasma trimethylamine N-oxide (TMAO) is associated with coronary atherosclerotic plaque and cardiovascular disease risk, but associations between gut microbes in acute coronary syndrome (ACS) and post-ST-segment elevation myocardial infarction (post-STEMI) events are unknown. We investigated associations between gut microbial taxa and systemic TMAO levels and the possible TMAO contribution to incident post-STEMI cardiovascular events. Patients and Methods. A total of 60 patients, including 30 with unstable angina pectoris (UAP), 30 post-STEMI and 30 healthy controls, were enrolled from June to November 2017. Metagenomic sequencing was performed and TMAO and IL-6 were detected. Results. Minimal discriminators of gut microbial taxa (top 40) distinguished ACS patients from controls. Serum TMAO levels were positively associated with increased abundance of Aerococcaceae, Ruminococcaceae_UCG.005, Ruminococcaceae_UCC.014 and X. Eubacterium_fissicatena, and decreased abundance of Lachnospiraceae_FCS020 (P < 0.05). Elevated serum TMAO levels correlated independently with ACS (P < 0.05). Risk stratification for incident major adverse cardiovascular events (MACE) improved at one year in patients with serum TMAO levels ≦2.19 µM. Serum interleukin-6 levels were not significantly increased in patients with ACS and post-STEMI MACE. Conclusions. ACS and incident post-STEMI MACE may be associated with the gut bacteria choline metabolite TMAO. The specific gut microbial taxa identified in association with serum TMAO levels may be potential predictive biomarkers for accurate diagnosis of ACS onset.

Myocardial ischemia/reperfusion (I/R) injury is a significant complication following acute myocardial infarction (AMI) and lacks effective therapies. The involvement of gut microbiota in regulating ferroptosis during myocardial I/R injury has not been thoroughly explored. This study aimed to investigate the effect of Lactobacillus on myocardial I/R injury and explore its potential mechanisms. One hundred fifty eight patients with ST-elevation myocardial infarction (STEMI) were enrolled in our prospective observational study. The correlations between Lactobacillus levels and myocardial injury markers, inflammatory factors, oxidative stress, and ferroptosis were evaluated. Furthermore, 30 rats were treated with Lactobacillus or vehicle control for 4 weeks, followed by myocardial I/R surgery. The protective effects of Lactobacillus against I/R injury were assessed by quantifying myocardial apoptosis, inflammation, oxidative stress, and ferroptosis. In addition, the above results were verified in vitro. The signaling pathways were investigated through the knockdown and overexpression of sirtuin 1 (Sirt1) and nuclear factor erythroid 2-related factor 2 (Nrf2). In clinical study, Lactobacillus levels were significantly negatively correlated with myocardial injury markers, inflammatory factors, and malondialdehyde (MDA), but positively correlated with glutathione (GSH). In rats, Lactobacillus decreased the levels of myocardial injury markers, reduced the size of the myocardial infarction area, ameliorated the disordered myocardial cell arrangement, and improved cardiac function. In both in vivo and in vitro studies, Lactobacillus inhibited cardiomyocyte apoptosis by upregulated B-cell lymphoma-2 (Bcl-2), downregulated Bcl-2 associated X (Bax), and caspase-3. Furthermore, Lactobacillus decreased inflammatory factors, MDA, reactive oxygen species (ROS) levels, and increased superoxide dismutase (SOD) activity. For ferroptosis, Lactobacillus upregulated the expression of glutathione peroxidase 4 (GPX4) and downregulated the expressions of acyl-CoA synthetase long-chain family member 4 (ACSL4) and transferrin receptor protein 1 (TfR1). Finally, knockdown and overexpression of Sirt1 and Nrf2 in vitro demonstrated that Lactobacillus exerted the effect by upregulating the Sirt1/Nrf2/HO-1 pathway. Our findings reveals that Lactobacillus protects against myocardial I/R injury by inhibiting apoptosis, inflammation, oxidative stress, and ferroptosis through the Sirt1/Nrf2/HO-1 signaling axis, suggesting a novel probiotic-based therapeutic potential for I/R injury.

Bile acids play crucial roles in various metabolisms, as well as Lactobacillus in the intestine. But studies on their roles in acute coronary syndrome (ACS) are still insufficient. The aim of this study was to investigate their role and potential association with the severity of coronary lesions and the prognosis of ACS. Three hundred and sixty ACS patients were selected. Detection of gut Lactobacillus levels was done through 16S rDNA sequence analysis. Evaluation of the extent of lesions was done using the SYNTAX (SS) score. Mediation analysis was used to assess the relationship between serum total bile acid (TBA), Lactobacillus, atherosclerotic lesions and prognosis of ACS. Logistic regressive analysis disclosed that serum TBA and Lactobacillus were independent predictors of coronary lesions (high vs. low SS: serum TBA adjusted odds ratio (aOR) = 0.8, 95% confidence interval (CI): 0.6–0.9, p < .01; Lactobacillus: aOR = 0.9, 95% CI: 0.9–1.0, p = .03). According to multivariate Cox regression analysis, they were negatively correlated with the overall risk of all-cause death (serum TBA: adjusted hazard ratio (aHR) = 0.1, 95% CI: 0.0–0.6, p = .02; Lactobacillus: aHR = 0.6, 95% CI: 0.4–0.9, p = .01), especially in acute myocardial infarction (AMI) but not in unstable angina pectoris (UAP). Ulteriorly, mediation analysis showed that serum TBA played an important role as a mediation effect in the following aspects: Lactobacillus (17.0%, p < .05) → SS association (per 1 standard deviation (SD) increase), Lactobacillus (43.0%, p < .05) → all-cause death (per 1 SD increase) and Lactobacillus (45.4%, p < .05) → cardiac death (per 1 SD increase). The lower serum TBA and Lactobacillus level in ACS patients, especially in AMI, was independently linked to the risk of coronary lesions, all-cause death and cardiac death. In addition, according to our mediation model, serum TBA served as a partial intermediate in predicting coronary lesions and the risk of death by Lactobacillus, which is paramount to further exploring the mechanism of Lactobacillus and bile acids in ACS. KEY MESSAGES Lower level of serum total bile acid (TBA) was highly associated with the severity of coronary lesions, myocardial damage, inflammation and gut Lactobacillus in acute coronary syndrome (ACS) patients, especially in acute myocardial infarction (AMI). Lower level of serum TBA was highly associated with mortality (including all-cause death and cardiac death) in patients with ACS, especially with AMI. Serum TBA had a partial mediating effect rather than regulating effect between gut Lactobacillus and coronary lesions and prognosis of ACS.

Background: Myeloperoxidase (MPO) and global registry of acute coronary events (GRACE) risk scores were independently used to predict adverse outcomes in patients with acute coronary syndrome (ACS). However, the relationship between MPO level and GRACE score, and whether the combination of MPO and GRACE can better predict major adverse cardiovascular events (MACEs) in patients with acute non-ST-segment elevation myocardial infarction (NSTEMI), have not been previously investigated.Methods: A prospective cohort of 271 consecutive patients with NSTEMI were enrolled in this study. Plasma MPO levels were measured by ELISA. Baseline demographic and clinical information was collected, and GRACE scores were calculated at admission. The correlation between MPO and MACEs was evaluated with the GRACE score during a 1-year follow-up.Results: The results showed that plasma MPO level was correlated with inflammatory indices (including high-sensitivity C-reactive protein (hs-CRP), leukocyte count, neutrophil count, and fibrinogen), N-terminal pro-B type natriuretic peptide (NT-proBNP), and hypersensitive troponin T (hsTNT) levels (All p-values < 0.05), and there was a statistically significant correlation between plasma MPO level and GRACE score (r = 0.22, p < 0.001). The Kaplan-Meier curves showed that patients with higher MPO levels had lower event-free survival (Log-rank P < 0.001). The multivariate Cox model showed MPO was an independent risk factor for 1-year MACEs in patients with NSTEMI (HR: 3.85, 95% CI: 1.4–10.6, p = 0.009). Subgroup analysis showed that MPO was a strong prognostic biomarker, and its prognostic value was more significant in patients with age >65 years and N-terminal pro-B type natriuretic peptide (NT-proBNP) level >1,000 pg/ml. For high-risk patients with GRACE scores, a higher level of MPO has a higher prognostic value.Conclusion: Elevated plasma MPO levels are associated with high inflammatory status and GRACE scores in patients with NSTEMI. For high-risk patients with GRACE scores, higher MPO levels were more predictive of future MACEs.

Background: In recent years, the hospital admission rate of non-ST-elevation myocardial infarction (NSTEMI) patients has exhibited an increasing trend, and a forthcoming transition from ST-elevation myocardial infarction (STEMI) to NSTEMI has been observed in China. The association between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and major adverse cardiac events (MACEs) within 12 months after discharge among patients with NSTEMI remains unclear. Methods: A total of 1,357 consecutively admitted NSTEMI patients were from the TAMI cohort. The patients’ baseline demographic and clinical information were collected, and follow-up was carried out for 12 months. The primary outcome was composite MACEs consisting of all-cause death, hospital admission for unstable angina, hospital admission for heart failure, non fatal recurrent myocardial infarction, and target lesion revascularization (TLR). We adopted a Cox proportional hazard model to analyze the effect of NT-proBNP on MACEs and quantified the added prognostic value of NT-proBNP on the Global Registry of Acute CoronaryEvents (GRACE) risk score using the Harrell C-index, NRI, and IDI. Results: The overall average follow-up period was 313 days. In total, 211 (15.55%) patients suffered from at least one MACE, and 97 patients were lost to follow-up, with a median follow-up time of 147 days. As the NT-proBNP level increased, a significant uptrend in the incidence of composite MACEs, all-cause death, and heart failure was observed. The multivariable Cox model revealed that NT-proBNP was an independent risk factor for composite MACEs [medium- vs. low-, HR: 2.19 (1.45–3.32), P=0.0002]; [high- vs. low-, HR: 3.07 (1.78–5.29), P<0.0001], as well as for all-cause death and heart failure. Subgroup analysis indicated that NT-proBNP was a robust prognostic biomarker, and the prognostic value was more evident for patients older than 60 years and whose LVEF was less than 40%. NT-proBNP (log-scale) was moderately correlated with the GRACE score (r=0.58, P<0.0001). The Harrell C-index of NT-proBNP combined with the GRACE score was 0.7715, which was higher than that of the GRACE score alone (0.7149) for predicting composite MACEs, and this improvement was verified by significant IDI (0.064, 95% CI: 0.027–0.106). Conclusions: NT-proBNP is a robust long-term prognostic biomarker for patients diagnosed with NSTEMI, especially for older patients and those with impaired cardiac ejection function. Combined usage of NT-proBNP levels with the GRACE score might help identify a subset of NSTEMI patients at a particularly high risk of MACEs 12 months after discharge.