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.

Background: Gut microbiota dysbiosis can contribute to the progression of atherosclerosis. We investigated the association of the gut microbiota and the severity of coronary artery lesions and prognosis of patients with ACS.Methods: In this case-control study, 402 ACS patients and 100 controls were enrolled from June 2017 to December 2018. The number of bacterial species was determined by real-time PCR. A SYNTAX score was calculated for all ACS patients based on their coronary angiography results.Results: Compared with the healthy controls, the gut microbial levels in Escherichia coli, Streptococcus, and Enterobacteriaceae were significantly increased in ACS patients, while the Lactobacillus level was significantly decreased. Lactobacillus level was as an independent predictor of disease severity on the coronary angiography [high vs. low SYNTAX score: adjusted odds ratio (aOR) = 0.024, 95% confidence interval (CI): 0.004–0.155] and myocardial necrosis [high vs. low cardiac troponin T (cTNT): aOR = 0.317, 95% CI: 0.099–0.914]. Subsequently, a higher Lactobacillus level was associated with a lower risk of an all-cause death [adjusted hazard ratio (aHR) = 0.239; 95% CI: 0.093–0.617] and major adverse cardiac events (MACE) in ACS patients (aHR = 0.208; 95% CI: 0.081–0.531). After stratifying by the type of ACS, a higher Lactobacillus level was significantly associated with the decreased risks of high SYNTAX score, all-cause death, and MACE in the STEMI subgroup but not in the NSTEMI and UAP subgroups.Conclusions: Lower Lactobacillus levels may indicate a higher risk of a more severe coronary atherosclerotic lesions and myocardial necrosis and worse prognosis for patients with ACS, particularly in the STEMI subgroup.

Background: The effects of metabolic syndrome (MS) on premature myocardial infarction (PMI) are not clear to date. This study aimed to investigate the impact of MS and its components on clinical severity and long-term prognosis in patients with PMI.Methods: We enrolled 772 patients aged ≤45 years old who were diagnosed with acute myocardial infarction (AMI) at our hospital consecutively between 2015 and 2020. The patients were divided into an MS group and non-MS group. The parameters of clinical severity were compared using regression analysis. Patients were followed for median of 42 months for major adverse cardiovascular events (MACE).Results: Hyperglycemia was associated with multi-vessel disease [odds ratio(OR)=1.700, 95% confidence interval (CI)=1.172-2.464, P=0.005] and Syntax score ≥33 (OR=2.736, 95% CI=1.241-6.032, P=0.013). Increased MACE were observed in the MS group(17.9% vs 10.3%, P=0.004).The Kaplan-Meier curve also showed significant differences (P< 0.001). MS was an independent risk factor for MACE. Of each component of MS, BMI ≥28 kg/m² (hazard ratio [HR]=2.022, 95% CI =1.213-3.369, P=0.007] and hyperglycemia (HR=2.904, 95% CI=1.847-4.567, P&lt;0.001) were independent risk factors for MACE.Conclusions: In patients with PMI, 1) hyperglycemia usually indicates more severe lesions; 2) MS as a whole was an independent risk factor for MACE; 3) BMI ≥28.0 kg/m² and hyperglycemia were associated with MACE.

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: Lp(a) and LDL-C are both risk factors of atherosclerotic cardiovascular disease (ASCVD). But there was a contradiction point in LDL-C and Lp(a) control. The appropriate level of LDL-C and Lp(a) in the prevention of ASCVD is still pending. Objective: To investigate the correlation of Lp(a) and coronary atherosclerotic lesion, and find out the balance point in LDL-C and Lp(a) control. Method: 3449 patients were divided to coronary atherosclerotic heart disease (CAHD) Group and Non-CAHD Group based on the result of coronary angiography. The clinical characteristics were compared, and Logistic regressions were applied to find the CAHD risk factors in total, High-LDL-C Group (LDL-C ≥ 100 mg/dL) and Low-LDL-C Group (LDL-C < 100 mg/dL) patients. Spearman correlation analysis of Lp(a), LDL-C and Gensini Score was performed in patients with different LDL-C concentration. Results: Except male and diabetes, the traditional CAHD risk factors were well matched between two groups. But triglyceride, LDL-C and Lp(a) were higher, HDL-C and Apo-A1 were lower in CAHD group (2771). In the Logistic regression analysis, diabetes, LDL-C and Lp(a) are risk factors of CAHD in all patients, while in High-LDL-C Group, they were age, LDL-C, non-HDL-C and ApoB, in Low-LDL-C Group, they were age, Lp(a) and ApoB. Lp(a) correlated with Gensini with coefficient r = 0.41 in all patients, 0.67 in Low-LDL-C Group and 0.32 in High-LDL-C Group. The coefficient r for Lp(a) and Gensini decreased, while the r for LDL-C and Gensini increased with LDL-C concentration increasing. The two fitted lines of rs crossed at LDL-C = 2.7 mmol/L (104 mg/dL). Conclusion: Lp(a) was the risk factor of CAHD in patients with LDL-C < 100 mg/dL. The correlation between Lp(a) and Gensini was influenced by LDL-C concentration, and the correlation was stronger than LDL-C when LDL-C < 104 mg/dl.