A Combined Measure of the Triglyceride Glucose Index and Trimethylamine N-Oxide in Risk Stratification of ST-Segment Elevation Myocardial Infarction Patients with High-Risk Plaque Features Defined by Optical Coherence Tomography: A Substudy of the OCTAMI Registry Study.

Background and Aim: An elevated triglyceride-glucose (TyG) level is associated with increased risk of mortality in patients with CAD. Trimethylamine N-oxide (TMAO) has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is correlated with adverse outcomes. However, the incremental prognostic value of TMAO and TyG in the cohort of optical coherence tomography (OCT)-defined high-risk ST-segment elevation myocardial infarction (STEMI) patients is unknown. Methods: We studied 274 consecutive aged ≥18 years patients with evidence of STEMI and detected on pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019. Outcomes: There were 22 (22.68%), 27 (27.84%), 26 (26.80%), and 22 (22.68%) patients in groups A-D, respectively. The baseline characteristics according to the level of TMAO and TyG showed that patients with higher level in both indicators were more likely to have higher triglycerides (p < 0.001), fasting glucose (p < 0.001) and higher incidence of diabetes (p = 0.008). The group with TMAO > median and TyG ≤ median was associated with higher rates of MACEs significantly (p = 0.009) in fully adjusted analyses. During a median follow-up of 2.027 years, 20 (20.6%) patients experienced MACEs. To evaluate the diagnostic value of the TyG index combined with TMAO, the area under the receiver operating characteristic curve for predicting MACEs after full adjustment was 0.815 (95% confidence interval, 0.723-0.887; sensitivity, 85.00%; specificity, 72.73%; cut-off level, 0.577). Among the group of patients with TMAO > median and TyG ≤ median, there was a significantly higher incidence of MACEs (p=0.033). A similar tendency was found in the cohort with hyperlipidemia (p=0.016) and diabetes mellitus (p=0.036). Conclusion: This study demonstrated the usefulness of combined measures of the TyG index and TMAO in enhancing risk stratification in STEMI patients with OCT-defined high-risk plaque characteristics. Trial Registration: This study was registered at ClinicalTrials.gov as NCT03593928.

Lipid Content Distribution and its Clinical Implication in Patients with Acute Myocardial Infarction-Plaque Erosion: Results from the Prospective OCTAMI Study.

AIMS: Plaque erosion (PE) is one of the main plaque phenotypes of acute coronary syndrome (ACS). However, the underlying plaque component and distribution have not been systematically analysed. This study aims to investigate the distribution of lipid and calcium content in culprit lesions assessed by optical coherence tomography (OCT) in patients with PE and explore its relationship with prognosis in a cohort of ST segment elevation myocardial infarction (STEMI) patients. METHODS: A prospective cohort of 576 patients with STEMI was enrolled in our study. After exclusion, 152 PE patients with clear underlying plaque components were ultimately analysed. The culprit lesion was divided into the border zone, external erosion zone and erosion site in the longitudinal view. Each pullback of the culprit lesions was assessed by 3 independent investigators frame-by-frame, and the quantity and distribution of lipid and calcium components were recorded. RESULTS: Of the 152 PE patients, lipid and calcium contents were more likely to exist in the external erosion zone than in the other regions. In particular, a high level of lipid content proximal to the erosion site was significantly associated with plaque vulnerability and a higher incidence of MACEs. CONCLUSION: This study revealed that high level of lipid content in the proximal external erosion zone was related to high-risk plaque characteristics and poor prognosis, which provided a novel method for risk stratification and precise management in patients with plaque erosion.

Atherosclerotic Autoantigen ALDH4A1 as a Novel Immunological Indicator for Plaque Erosion in Patients with ST Segment Elevated Myocardial Infarction.

OBJECTIVE: Aldehyde dehydrogenase 4A1 (ALDH4A1) was recently reported to be a novel autoantigen of atherosclerosis. However, its role in different phenotypes of acute coronary syndrome remains unclear. Herein, we planned to explore the circulating and regional expression of ALDH4A1 in patients with plaque rupture (PR) and plaque erosion (PE) determined by optical coherence tomography (OCT). METHODS AND RESULTS: After applying the inclusion and exclusion criteria, a prospective series of 312 patients with ST segment elevated myocardial infarction (STEMI), including 161 patients with PR and 151 patients with PE determined by OCT, were enrolled for plasma ALDH4A1 testing. In addition, ALDH4A1 was quantified using immunofluorescence in aspirated coronary thrombus samples obtained from 31 patients with PR and 25 patients with PE. In addition, we established an atherosclerosis mouse model and analyzed the distribution of ALDH4A1 expression in different mouse organs. Furthermore, we compared the level of ALDH4A1 in the spleen and carotid artery between Apoe-/- and C57 mice. The results showed that the plasma level of ALDH4A1 was significantly higher in STEMI patients with PE than in those with PR (4.6 ng/mL [2.2-8.7] vs. 3.5 ng/mL [1.6-5.6] p = 0.005). The expression of ALDH4A1 in aspirated coronary thrombi was also significantly higher in patients with PE than in those with PR (mean gray value: 32.0 [23.6-40.6] vs. 16.8 [14.0-24.5], p < 0.001). In animal models, the expression of ALDH4A1 is much higher in the spleen than in other organs, and the level of ALDH4A1 is significantly elevated in the spleen and carotid artery of Apoe-/- mice compared with C57 mice. CONCLUSION: The high levels of ALDH4A1 in the plasma and aspirated coronary thrombi independently correlated with PE in patients with STEMI. These results suggested that ALDH4A1 is involved in the mechanism of PE and serves as a promising biomarker and treatment target for patients with PE.

Prognostic impacts of diabetes status and lipoprotein(a) levels in patients with ST-segment elevation myocardial infarction: a prospective cohort study.

OBJECTS: This study aimed to investigate the impact of lipoprotein(a) [Lp(a)] levels on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI), and to explore if the impact may differ in the diabetes mellitus (DM) and nonDM groups. METHODS: Between March 2017 and January 2020, 1543 patients with STEMI who underwent emergency percutaneous coronary intervention (PCI) were prospectively recruited. The primary outcome was a composite of all-cause death, MI recurrence (reMI), and stroke, known as major adverse cardiovascular events (MACE). Analyses involving the Kaplan-Meier curve, Cox regression, and restricted cubic spline (RCS) were conducted. RESULTS: During the 1446-day follow-up period, 275 patients (17.8%) experienced MACEs, including 141 with DM (20.8%) and 134 (15.5%) without DM. As for the DM group, patients with Lp(a) ≥ 50 mg/dL showed an apparently higher MACE risk compared to those with Lp(a) < 10 mg/dL (adjusted hazard ratio [HR]: 1.85, 95% confidence interval [CI]:1.10-3.11, P = 0.021). The RCS curve indicates that the HR for MACE appeared to increase linearly with Lp(a) levels exceeding 16.9 mg/dL. However, no similar associations were obtained in the nonDM group, with an adjusted HR value of 0.57 (Lp(a) ≥ 50 mg/dL vs. < 10 mg/dL: 95% CI 0.32-1.05, P = 0.071). Besides, compared to patients without DM and Lp(a) ≥ 30 mg/dL, the MACE risk of patients in the other three groups (nonDM with Lp(a) < 30 mg/dL, DM with Lp(a) < 30 mg/dL, and DM with Lp(a) ≥ 30 mg/dL) increased to 1.67-fold (95% CI 1.11-2.50, P = 0.013), 1.53-fold (95% CI 1.02-2.31, P = 0.041), and 2.08-fold (95% CI 1.33-3.26, P = 0.001), respectively. CONCLUSIONS: In this contemporary STEMI population, high Lp(a) levels were linked to an increased MACE risk, and very high Lp(a) levels (≥ 50 mg/dL) significantly indicated poor outcomes in patients with DM, while not for those without DM. TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.

Prognostic significance of serial N-terminal pro-B-type natriuretic peptide levels in patients with acute myocardial infarction: A prospective study.

OBJECTS: This study aimed to investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels at different sampling times and prognosis in patients with acute myocardial infarction (AMI) undergoing emergency percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between March 2017 and January 2020, 1,105 patients with AMI who underwent emergency PCI were included. NT-proBNP levels were measured on days 0, 1, 2, 3, and 7. A composite of all-cause death, MI recurrence (reMI), and rehospitalization due to heart failure, known as major adverse cardiovascular events (MACE), was recorded. During the 36.8-month follow-up, 175 patients (15.8%) experienced MACEs. When patients were grouped based on quartiles of NT-proBNP levels on days 0 and 7, the results demonstrated that patients in quartile 4 showed a substantially increased MACE risk compared to those in quartile 1 (hazard ratio [HR] 2.27, 95% confidence interval [CI]:1.27-4.08, P = .006; HR 2.20, 95%CI:1.23-3.94, P = .008). There were U-shaped relationships between the HR for MACE and NT-proBNP levels on days 2, 3, and 7, as well as peak NT-proBNP (P for nonlinearity = .007, .006, .004, and .009, respectively). A similar relationship was observed in the HR for reMI and NT-proBNP levels on days 2 and 3. For MACE at 3 years, serial NT-proBNP levels improved the predictive accuracy of the Global Registry of Acute Coronary Events (GRACE) risk score (concordance index [C-index]: 0.711; continuous net reclassification improvement [NRI]: 0.192, 95% CI: 0.022-0.445; integrated discrimination improvement [IDI]: 0.034, 95% CI: 0.016-0.064). For all-cause death at 3 years, the combination of NT-proBNP and GRACE score showed excellent performance, with C-index, continuous NRI, and IDI values of 0.801, 0.373 (95%CI: 0.072-0.853), and 0.051 (95%CI: 0.025-0.091), respectively. CONCLUSIONS: Early and sequential measurement of NT-proBNP levels could assist in predicting MACE risk. Moreover, the relationship between MACE risk and NT-proBNP levels was U-shaped. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov NCT: 03593928.

Effect of Triglyceride-Glucose Indices and Circulating PCSK9-Associated Cardiovascular Risk in STEMI Patients with Primary Percutaneous Coronary Artery Disease: A Prospective Cohort Study.

Background and Aims: This study aimed to determine whether convertase subtilisin/kexin type 9 (PCSK9)-associated cardiovascular risk is modulated by triglyceride-glucose (TyG) in ST-segment elevation myocardial infarction (STEMI) patients with primary percutaneous coronary disease (PCI). Methods: A total of 1541 patients with STEMI (aged ≥18 years) undergoing primary PCI were consecutively enrolled between March 2017 and March 2019. Outcomes: When stratifying the overall population according to TyG indices less than or greater than the median (TyG median = 9.07) as well as according to quartiles of PCSK9 levels, higher TyG index levels were significantly associated with all-cause mortality only when TyG levels were 9.07 or higher (ie, relative to quartile 1 [Q1], the adjusted HR for all-cause mortality was 3.20 [95% CI, 0.54-18.80] for Q2, p = 0.199; 7.89 [95% CI, 1.56-40.89] for Q3, p = 0.013; and 5.61 [95% CI, 1.04-30.30] for Q4, p = 0.045. During a median follow-up period of 1.96 years, the HR for all-cause mortality was higher in the subset of patients with TyG ≥median and PCSK9 ≥median (p for trend = 0.023) among those with type 2 diabetes mellitus (T2DM). However, there were no statistically significant differences among the subgroups. Among T2DM patients with a TyG index greater than the median, the Kaplan-Meier curve showed that patients with the highest PCSK9 levels had an increased risk of all-cause mortality (log-rank p = 0.017) and cardiac-cause mortality (log-rank p = 0.037) compared with lower PCSK9 quartile levels. Conclusion: Elevated PCSK9 levels are related to all-cause mortality and cardiac-related mortality when TyG levels are greater than the median, but not when levels are less than the median. This suggests a potential benefit of lowering circulating PCSK9 levels in STEMI patients with insulin resistance.

Prognostic impacts of Lipoxin A4 in patients with acute myocardial infarction: A prospective cohort study.

Lipoxin A4 (LXA4) is one of the specialized pro-resolving lipid mediators proved to suppress the progression of atherosclerosis in vivo, but its clinical impacts in atherosclerotic patients is unclear. In this study, we assessed the prognostic impacts of LXA4 in patients with acute myocardial infarction (AMI). A total of 1569 consecutive AMI patients were prospectively recruited from March 2017 to January 2020. Plasma samples of AMI patients were collected, and LXA4 levels were determined using enzyme-linked immunosorbent assay. The primary outcome was major adverse cardiovascular event (MACE), a composite of all-cause death, recurrent MI, ischemic stroke, or ischemia-driven revascularization. Cox regression was used to assess associations between LXA4 and clinical outcomes. Overall, the median level of LXA4 was 5.637 (3.047-9.014) ng/mL for AMI patients. During a median follow-up of 786 (726-1108) days, high LXA4 (≥ 5.637 ng/mL) was associated with lower risk of MACE (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.60-0.89, P = 0.002), which was sustained in propensity score matching (HR: 0.73, 95% CI: 0.60-0.90, P = 0.004) and inverse probability weighting analysis (HR: 0.74, 95% CI: 0.61-0.90, P = 0.002). Combined with pro-inflammatory biomarker, patients with high levels of LXA4 (≥ 5.637 ng/mL) but low levels of high-sensitivity C-reactive protein (< 5.7 mg/L) acquired the lowest risk of MACE (HR: 0.68, 95% CI: 0.51-0.92, P = 0.012). In sum, high levels of LXA4 were associated with lower risk of recurrent ischemic events for AMI patients, which could serve as new therapeutic target to tackle cardiovascular inflammation.

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction.

Background: As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features. Results: The median RvD1 level was 129.7 (56.6-297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20-3.66, P = 0.010), healed plaques (≥246.4 pg/mL, OR: 2.17, 95% CI: 1.11-4.24, P = 0.023), and calcification (≥293.38 pg/mL, OR: 2.10, 95% CI: 1.21-3.66, P = 0.008) at culprit lesions. Conclusion: Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.

Prognostic Value of Admission Peak NT-proBNP Combined with Culprit Plaque Types for Predicting Cardiovascular Risk in ST-Segment Elevated Myocardial Infarction: An Optical Coherence Tomography Study.

OBJECTIVE: Different culprit plaque phenotypes including plaque rupture (PR) and non-plaque rupture (NPR), and N-Terminal prohormone of brain natriuretic peptide (NT-proBNP) have been reported to influence clinical outcomes in patients with acute coronary syndrome (ACS). We aimed to investigate the prognostic implication of the peak and baseline values at admission for NT-proBNP for major adverse cardiovascular events (MACE) in ST-Segment Elevated Myocardial Infarction (STEMI) patients with different plaque phenotype. METHODS: A total of 428 patients with STEMI undergoing optical coherence tomography (OCT) were enrolled and divided into four groups: PR/Tertile1-2 NT-proBNP (n = 132), PR/Tertile3 NT-proBNP (n = 65), NPR/Tertile1-2 NT-proBNP (n = 154), NPR/Tertlie3 NT-proBNP (n = 77). Baseline and Peak values of NT-proBNP were obtained in the admission period. The MACEs were defined as the composite of all-cause death, recurrence of myocardial infarction and stroke. RESULTS: High levels for peak NT-proBNP were significantly associated with a higher incidence of MACE and death (Log rank p = 0.037 and 0.0012, respectively). In the subgroup with NPR, a high level for peak NT-proBNP was significantly associated with higher incidence of death (Log rank p = 0.0022) but this association was not significant in the subgroup of PR (Log rank p = 0.24). Though plaque types were not associated with adverse event, the combination of NPR and a higher peak value for NT-proBNP indicated higher incidence of death compared with other groups (Log rank p = 0.0017). The area under the receiver operating characteristic curve for predicting death to evaluate the diagnostic value of the peak value for NT-proBNP and plaque types combined with traditional risk factors was 0.843 (95% CI: 0.805-0.876), which is superior to solely traditional risk factors: NRI (26.8% [95% CI: 0.4-53.1%], p = 0.046) and IDI (5.1% [95% CI: 1.0-9.2%], p = 0.016). CONCLUSION: STEMI patients with NPR and a high level for peak NT-proBNP showed higher incidence of death. The peak value of NT-proBNP in combination with plaque types can be used in risk stratification and prediction of death in patients with STEMI.

Association between the Changes in Trimethylamine N-Oxide-Related Metabolites and Prognosis of Patients with Acute Myocardial Infarction: A Prospective Study.

This study aimed to investigate the association between changes in levels of trimethylamine N-oxide (TMAO) and its precursors and the prognosis of patients with acute myocardial infarction (AMI). Patients diagnosed with AMI were prospectively enrolled at Fuwai Hospital between March 2017 and January 2020. TMAO, betaine, choline, and L-carnitine were measured in 1203 patients at their initial admission and 509 patients at their follow-up of one month. Major adverse cardiovascular events (MACE), a composite of all-cause death, recurrence of MI, rehospitalization caused by HF, ischemic stroke, and any revascularization, were followed up. A decision tree by TMAO levels implicated that compared to those with low levels at admission, patients with high TMAO levels at both time points showed an increased risk of MACE (adjusted hazard ratio (HR) 1.59, 95% confidence interval (CI): 1.03-2.46; p = 0.034), while patients with high TMAO levels at admission and low levels at follow-up exhibited a similar MACE risk (adjusted HR 1.20, 95% CI: 0.69-2.06; p = 0.520). Patients with high choline levels at admission and follow-up showed an elevated MACE risk compared to those with low levels at both time points (HR 1.55, 95% CI: 1.03-2.34; p = 0.034). Repeated assessment of TMAO and choline levels helps to identify the dynamic risk of cardiovascular events.

Prognostic Impacts of LL-37 in Relation to Lipid Profiles of Patients with Myocardial Infarction: A Prospective Cohort Study.

Background. In vivo studies show that LL-37 inhibits the progression of atherosclerosis and predicts a lower risk of recurrent ischemia in patients with acute myocardial infarction (AMI), which could be mediated by the modulation of lipid metabolism. The current study aimed to investigate the effects of various lipid contents on the prognostic impacts of LL-37 in patients with AMI. Methods. A total of 1567 consecutive AMI patients were prospectively recruited from March 2017 to January 2020. Patients were firstly stratified into two groups by the median level of LL-37 and then stratified by levels of various lipid contents and proprotein convertase subtilisin/kexin type 9 (PCSK9). Cox regression with multiple adjustments was performed to analyze associations between LL-37, lipid profiles, PCSK9, and various outcomes. The primary outcome was major adverse cardiovascular event (MACE), a composite of all-cause death, recurrent MI, and ischemic stroke. Results. During a median follow-up of 786 (726−1107) days, a total of 252 MACEs occurred. A high level of LL-37 was associated with lower risk of MACE in patients with elevated lipoprotein(a) (≥300 mg/L, hazard ratio (HR): 0.49, 95% confidence interval (CI): 0.29−0.86, p = 0.012) or PCSK9 levels above the median (≥47.4 ng/mL, HR: 0.57, 95% CI: 0.39−0.82, p < 0.001), which was not observed for those without elevated lp(a) (<300 mg/L, HR: 0.96, 95% CI: 0.70−1.31, p = 0.781, pinteraction = 0.035) or PCSK9 (<47.4 ng/mL, HR: 1.02, 95% CI: 0.68−1.54, p = 0.905, pinteraction = 0.032). Conclusions. For patients with AMI, a high level of LL-37 was associated with lower ischemic risk among patients with elevated lp(a) and PCSK9.

Low-density lipoprotein cholesterol in oldest old with acute myocardial infarction: Is lower the better?

BACKGROUND: the relationship between low-density lipoprotein cholesterol (LDL-C) and adverse outcomes among the older people remains controversial. OBJECTIVE: to further clarify the association between admission LDL-C levels and cardiovascular mortality (CVM) among oldest old individuals (≥80 years) with acute myocardial infarction (AMI). DESIGN: a prospective cohort study. SETTING: two-centre. SUBJECTS: a consecutive sample of 1,224 oldest old individuals with AMI admitted to Beijing FuWai and Shenzhen FuWai hospitals. METHODS: all individuals were subdivided according to baseline LDL-C levels (<1.8, 1.8-2.6 and ≥ 2.6 mmol/l) and further stratified by high-sensitivity C-reactive protein (hsCRP) concentrations (<10 and ≥10 mg/l). The primary outcome was CVM. The time from admission to the occurrence of CVM or the last follow-up was analysed in Kaplan-Meier and Cox analyses. RESULTS: the median age of the overall population was 82 years. During an average of 24.5 months' follow-up, 299 cardiovascular deaths occurred. Kaplan-Meier analysis showed that LDL-C < 1.8 mmol/l group had the highest CVM among oldest old individuals with AMI. Multivariate Cox regression analysis further revealed that compared with those with LDL-C levels <1.8 mmol/l, subjects with LDL-C levels ≥2.6 mmol/l (hazard ratio: 0.67, 95% confidence interval: 0.46-0.98) had significantly lower risk of CVM, especially in those with high hsCRP levels. Moreover, when categorising according to LDL-C and hsCRP together, data showed that individuals with low LDL-C and high hsCRP levels had the highest CVM. CONCLUSIONS: LDL-C < 1.8 mmol/l was associated with a high CVM after AMI in oldest old individuals, especially when combined with high hsCRP levels, which may need to be confirmed by randomised controlled trials.

Development and Validation of a Prediction Rule for Major Adverse Cardiac and Cerebrovascular Events in High-Risk Myocardial Infarction Patients After Primary Percutaneous Coronary Intervention.

Background and Aims: We aimed to develop a clinical prediction tool to improve the prognosis of major adverse cardiac and cerebrovascular events (MACCE) among high-risk myocardial infarction (MI) patients undergoing primary percutaneous coronary intervention (PCI). Methods: The present study was a prospective and observational study. A total of 4151 consecutive MI patients who underwent primary PCI at Fuwai Hospital in Beijing, China (January 2010 and June 2017) were enrolled. Forty-eight patients without follow-up data were excluded from the study. The pre-specified criteria (Supplementary Information 1) were chosen to enroll MI patients at high risk for MACCE complications after PCI. Results: The full model included seven variables, with a risk score of 160 points. Derivation and validation cohort models predicting MACCE had C-statistics of 0.695 and 0.673. The area under the curve (AUC) of the survival receiver operating characteristic curve (ROC) for predicting MACCE was 0.991 and 0.883 in the derivation and validation cohorts, respectively. Conclusion: The predicted model was internally validated and calibrated in large cohorts of patients with high-risk MI receiving primary PCI to predict MACCE and showed modest accuracy in the derivation and validation cohorts.

Association between trimethylamine N-oxide and prognosis of patients with acute myocardial infarction and heart failure.

AIMS: This study aimed to investigate the association between trimethylamine N-oxide (TMAO) and the prognosis and association between high-sensitivity C-reactive protein (hsCRP) and TMAO-associated cardiovascular risk in patients with acute myocardial infarction (AMI) complicated by heart failure (HF). METHODS AND RESULTS: A total of 985 patients presenting with AMI and HF were consecutively enrolled at the Fuwai Hospital between March 2017 and January 2020. Patients were stratified into groups according to tertiles of TMAO levels and the median hsCRP levels. The primary endpoint was major adverse cardiac events (MACE), including all-cause death, recurrence of myocardial infarction, and rehospitalization due to HF. During a median follow-up of 716 days, 138 (14.0%) patients experienced MACE. Cox regression analyses showed that the adjusted hazard ratio (HR) for MACE was higher in patients in tertile 3 [TMAO > 9.52 µmol/L, HR: 1.85, 95% confidence interval (CI): 1.18-2.89; P = 0.007] than in tertile 1 (TMAO < 4.74 µmol/L), whereas no significant differences were detected between the patients in tertiles 1 and 2 (TMAO = 4.74-9.52 µmol/L, HR: 0.96, 95% CI: 0.59-1.58; P = 0.874). Restricted cubic spline regression depicted an S-shaped association between TMAO and MACE (P for nonlinearity = 0.012). In the setting of hsCRP above the median level (6.68 mg/L), per unit increase of TMAO was associated with a 20% increase of MACE risk (HR: 1.20, 95% CI: 1.05-1.37, P = 0.009); increasing tertiles of TMAO were significantly associated with a higher risk of MACE (adjusted P = 0.007 for interaction; P < 0.001 for trend across tertiles). The Kaplan-Meier analysis indicated that patients in tertile 3 had a significantly lower event-free survival (P = 0.001) when the hsCRP level was above the median level. No similar association between TMAO and MACE was observed when the hsCRP level was below the median level. CONCLUSIONS: High plasma TMAO levels were independently correlated with poor prognosis in patients with AMI complicated by HF, especially in those with higher hsCRP levels. There was an S-shaped relationship between TMAO and HR for MACE.

High-Risk Culprit Plaque Predicts Cardiovascular Outcomes Independently of Plaque Rupture in ST-Segment Elevation Myocardial Infarction: Insight From Optical Coherence Tomography.

The present study explored the predictive value of culprit high-risk plaque (HRP) detected by optical coherence tomography (OCT) for predicting major adverse cardiovascular events (MACEs) in patients with ST-segment elevation myocardial infarction (STEMI). HRP was defined as the simultaneous presence of four criteria: minimum lumen area <3.5 mm2, fibrous cap thickness <75 µm, lipid plaque with lipid arc extension >180°, and presence of macrophages. Patients (n = 274) were divided into non-HRP group (n = 206) and HRP group (n = 68). MACEs were defined as a composite of all-cause death, myocardial infarction, stroke, and revascularization. During a mean follow-up of 2.2 years, 47 (17.5%) MACEs were observed: 28 (13.6%) in the non-HRP group and 19 (27.9%) in the HRP group (log-rank P = .005). Patients with HRP were 2.05 times more likely to suffer from a MACE than those without HRP (hazards ratio: 2.05, 95% confidence interval: 1.04-4.02, P = .038); MACE risk was comparable between plaque rupture and plaque erosion. In conclusion, HRP was present in 24.8% of STEMI patients and associated with higher cardiovascular risk independent of plaque rupture, suggesting that HRP detected by OCT may help identify patients at high risk of future cardiac events.

The relationship between Hemoglobin A1c and the maximal plaque stress of culprit ruptured plaques in patients with ST-segment elevated myocardial infarction.

BACKGROUND: Plaque rupture occurs when the structural stress inside plaques exceeds the capacity of the overlying fibrous cap. Plaque structural stress has been acknowledged as an index to evaluate the risk of plaque rupture. However, impacting factors associated with the level of plaque structural stress in ST-segment elevated myocardial infarction patients with ruptured plaques remain unknown. METHODS: Based on optical coherence tomography, we analyzed the plaque characteristics and calculated the maximal plaque stress of the culprit lesions in 162 patients with plaque rupture by performing finite element analysis. All enrolled patients were divided into two groups according to the level of maximal plaque stress. Cardiovascular risk factors, laboratory findings and clinical outcomes were compared between the two groups. RESULTS: Hemoglobin A1c (HbA1c) was significantly higher in the high stress group than in the low stress group (7.0% ± 1.8 vs. 6.3% ± 1.2, p = 0.003). The maximal plaque stress of patients with diabetes was significantly higher than that of patients without diabetes (538.7 kPa [346.2-810.6] vs. 425.9 kPa [306.2-571.4], p = 0.006). Moreover, the level of maximal plaque stress was significantly associated with HbA1c (Pearson's correlation coefficient: r = 0.289, P < 0.001). OCT findings showed that the fibrous cap thickness and maximal lipid arc were significantly associated with maximal plaque stress (r = -0.163, p = 0.038; r = 0.194, p = 0.013, respectively). CONCLUSION: OCT-based finite-element analysis showed that HbA1c was independently associated with the level of maximal plaque stress in STEMI patients with plaque rupture, thus indicating the importance of glucose control in patients with coronary atherosclerotic disease.

Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers. METHODS: A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated. RESULTS: PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan-Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094-4.764, P = 0.028), but not in the whole cohort or non-diabetic patients. CONCLUSIONS: The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.

Prognostic Impacts of Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Acute Coronary Syndrome Patients Without Heart Failure.

Background: Despite the recommendations from mainstream guidelines, the use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) for acute coronary syndrome (ACS) patients without heart failure (HF) is controversial, as its evidence is lacking in the era of reperfusion and intensive secondary preventions. This study aimed to investigate the impacts of ACEI/ARB on outcomes of ACS patients without HF treated by percutaneous coronary intervention (PCI). Methods: A total of 2,397 non-HF ACS patients treated by PCI were retrospectively recruited. Prognostic impacts of ACEI/ARB were assessed by unadjusted analysis, followed by propensity score matching (PSM) and propensity score matching weight (PSMW) analysis to control the between-group differences. The primary outcome was a composite of all-cause death and recurrent myocardial infarction (MI). Results: Among the included patients, 1,805 (75.3%) were prescribed with ACEI/ARB at discharge. The median follow-up time was 727 (433-2016) days, with 129 (5.4%) primary endpoint events, consisting of 55 (2.3%) cases of all-cause death and 74 (3.1%) cases of recurrent MI. The use of ACEI/ARB was not associated with significant risk reduction of primary endpoint events in unadjusted analysis (hazard ratio [HR]: 0.95, 95% confidence interval [CI]: 0.64-1.39, p = 0.779), PSM analysis (HR: 0.94, 95% CI: 0.60-1.47, p = 0.784), and PSMW analysis (HR: 0.91, 95% CI: 0.55-1.49, p = 0.704). Similar results were observed for secondary outcomes of all-cause death, cardiac death, and recurrent MI. Conclusion: For ACS patients without HF, the use of ACEI/ARB was not associated with lower risk of death or recurrent MI after PCI.

First report of bacterial leaf spot disease on Pueraria montana var. thomsonii caused by Robbsia andropogonis in China.

Pueraria montana var. thomsonii (Hereinafter referred to as Pmt) belongs to the Leguminosae and is widely distributed in China, Laos, Thailand, Myanmar, Bhutan and other Asian countries. The plant is called "Fenge" in China, and its root is widely used in medicine and food. In recent years, an unknown leaf spot disease of Pmt has occurred in Gaoming, Zhaoqing and Yunfu districts of Guangdong Province in China, where 1,600 hectares of Pmt plants were affected. The incidence rate of plants were more than 80% and led to 10-15% death of Pmt plants in Gaoming district. . In the early stage of the disease, radiating and water-soaking lesions appeared between the main veins and side veins of Pmt leaves. After the spread of the lesions, they formed brown and short strips with yellow haloes around them, which led to leaf shedding, plant death and decline of production. To isolate bacteria, diseased leaves were surface sterilized with 0.6% sodium hypochlorite solution for 30 s, followed by three consecutive rinses in distilled water. The leaves were aseptically macerated, and the macerate streaked on PDA medium. Whitish to dull white, mucoid, raised, round, and translucent colonies were obtained. All isolates were gram-negative and had a single, polar, sheathed flagellum. Sequences (approx. 1,458 bp each) of the 16S rRNA gene amplified from five isolates (FG2, FG3, FG9, FG12 and FG17) using primer pair 27F/1492R (Lane et al,1991) (GenBank Accession Nos. OL677034, OL677351, OL677352, OL677353 and OL677354 respectively) shared 99.93% sequence identity with that of Robbsia andropogonis (Synonyms: Burkholderia andropogonis) (Lopes-Santos et al,2017) type strain LMG2129 (NR104960.1). The specific 410-bp and 704-bp target fragments were also amplified from isolates using R. andropogonis-specific primers Pf/Pr (Bagsic et al,1995) and LJ23f/LJ24R (Duan et al,2009). The four housekeeping genes atpD, lepA, gyrB and rpoD were partially sequenced for FG9 isolates using primers atpD-F3/atpD-R3, lepA-F2/lepA-R, LJ23f/LJ24R and LJ25f/LJ26r (Duan et al,2009; Estrada-De et al,2013) respectively. Multilocus sequence analyses confirmed the isolates from Pmt as R. andropogonis. Physiological and biochemical tests revealed the isolates are negative for oxidase, arginine dihydrolase, saccharose and betaine, and positive for sorbitol, lactose and galactose (Gillis et al,1995; Lopes-Santos et al,2017). In addition, all isolates caused a hypersensitive reaction on leaves of Nicotiana benthamiana and were pathogenic to some crops, including maize (Zea mays), sorghum (Sorghum bicolor), carnation (Dianthus caryophilus), common bean (Phaseolus vulgaris), tomato. Five isolates (FG2, FG3, FG9, FG12 and FG17) pathogenicity were tested twice with a total of three replications per isolate. Two young leaves each of 3-month-old Pmt plants grow in greenhouse were sprayed a bacterial suspension at 108 CFU/ml, then covered the inoculated leaves individually with plastic bags for 24 h, and incubated at 100% relative humidity with 16 h of daylight at 30°C and 8 h of darkness at 22°C in a greenhouse. Radiating and water-soaked lesions with yellow haloes were observed between the main veins and side veins of Pmt leaves 5 days after inoculation and were similar to those caused by R. andropogonis in the field. Koch's postulates were fulfilled by reisolating bacteria from typical lesions on inoculated plants. And the reisolated bacteria were identical to the inoculated ones. To our knowledge, this is the first report of R. andropogonis on Pueraria montana var. thomsonii in China.

Prognostic Value of Age-Adjusted D-Dimer Cutoff Thresholds in Patients with Acute Coronary Syndrome Treated by Percutaneous Coronary Intervention.

BACKGROUND: Associations between D-dimer and outcomes of patients with acute coronary syndrome (ACS) remain controversial. Using age-adjusted D-dimer cutoff thresholds improve the diagnostic accuracy for thrombotic diseases. This study aimed to investigate the prognostic value of age-adjusted D-dimer in ACS patients treated by percutaneous coronary intervention (PCI). METHODS: A total of 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The basal age-adjusted D-dimer threshold was 500 ng/mL and was calculated as age × 10 in patients older than 50 years. Cox regression was used for outcome analysis. C-index, net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the additional prognostic value of age-adjusted D-dimer when combined with established clinical risk factors. The primary outcome was all-cause death. RESULTS: During a median follow-up of 720 days, a total of 225 deaths occurred. High D-dimer level, as defined by age-adjusted thresholds, was an independent predictor for all-cause death (hazard ratio [HR]: 1.75, 95% confidence interval [CI]: 1.32-2.31, P < 0.001), cardiac death (HR: 1.84, 95% CI: 1.30-2.60, P = 0.001), and MACE (HR: 1.48, 95% CI: 1.19-1.83, P < 0.001). Sensitivity and subgroup analysis showed that high D-dimer levels were constantly associated with worse outcomes across common risk factors and comorbidities. Besides, age-adjusted elevation of D-dimer significantly improved the risk predictions for all-cause death when added to the model of established risk factors (C-index: 0.846 vs 0.838, Δ C-index: 0.008, 95% CI: 0.001-0.015, Pdifference = 0.027; NRI: 0.645, 95% CI: 0.464-0.826, P < 0.001; IDI: 0.008, 95% CI: 0.001-0.017, P = 0.048). CONCLUSION: In ACS patients treated by PCI, age-adjusted elevation of D-dimer was an independent predictor for adverse outcomes and improved the risk predictions for long-term mortality.