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.

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.

Associations of Culprit Vessel Size and Plaque Characteristics in Patients with ST-Segment Elevation Myocardial Infarction.

Background: Small vessel disease (SVD) widely exists in patients with acute coronary syndrome. However, the plaque characteristic of SVD has not been investigated. Methods: Optical coherence tomography (OCT) of culprit lesion was examined in 576 patients with ST-segment elevation myocardial infarction (STEMI) and finally 404 patients with qualified images were analysed of plaque phenotypes and microstructure. The cohort was divided into three groups according to vessel diameters of culprit lesion which were measured by OCT. Major adverse cardiac events (MACEs) were recorded of each patient and compared among patients with different vessel diameters and plaque phenotypes. Results: Gender, age and body mass index (BMI) were significantly different among patients with different diameters of culprit vessels (98.4% vs. 85.7% vs.71.4%, p < 0.001; 40.0 ± 7.0 vs. 54.9 ± 6.6 vs. 68.9 ± 5.8, p < 0.001; 28.4 ± 4.0 vs. 25.8 ± 2.9 vs. 25.2 ± 3.0, p < 0.001, respectively). Moreover, patients with diameters of culprit lesion > 3 mm presented with more incidence of plaque rupture and macrophage (57.7% vs. 42.1% vs. 46.2%, p = 0.015, 55.1% vs. 41.0% vs. 36.9%, p = 0.010). Total MACE did not differ among groups of different vessel diameters and plaque phenotypes. Conclusions: Vessel size of culprit lesion is significantly associated with plaque phenotype in patients with STEMI. However, patients with different diameters and plaque phenotypes showed no significant difference of clinical outcomes. Clinical Trial Registration: NCT03593928.

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.

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.

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.

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.

RNA-seq identifies circulating miRNAs as potential biomarkers for plaque rupture in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Plaque rupture (PR) and plaque erosion (PE) are the two major pathological phenotypes in acute coronary syndrome. Since microRNAs have been found to be involved in the mechanisms of PR and PE, we investigated the diagnostic utility of microRNAs in differentiating between patients with PR and patients with PE. METHODS: MicroRNA sequencing was performed on plasma from 21 patients with PR, 20 patients with PE and 17 healthy control subjects (HCs). 24 miRNAs were selected for validation in 20 PR patients and 20 PE patients and 8 miRNAs were further validated in an independent replication cohort (82 patients with PR, 84 patients with PE and 59 HCs) by applying quantitative real-time polymerase chain reaction. Then we analyzed pathways associated with significant miRNAs in PR. RESULTS: MiR-744-3p, miR-324-3p and miR-330-3p were significantly upregulated in the PR group compared with the PE group (Log10miR-744-3p: 0.26[--0.28-1.57] versus -0.41[-0.83--0.03], padj < 0.001; Log10miR-324-3p: 0.40[-0.09-0.84] versus -0.12[-0.53-0.29], padj < 0.001; Log10miR-330-3p: 0.34[0.08-0.93] versus -0.07[-0.65-0.22], padj < 0.001), The area under the receiver operating characteristic curve for the combination of these three miRNAs in distinguishing between PR from PE in training and test set was 0.764 (0.679-0.850, sensitivity = 86.2%, specificity = 54.4%, P < 0.001) and 0.768 (0.637-0.898, sensitivity,65.4%, specificity:80.0%, P = 0.001), respectively. CONCLUSION: A set of circulating microRNAs (miR-744-3p, miR-330-3p, and miR-324-3p) is associated with PR and has clinical utility as a diagnostic marker for distinguishing the plaque phenotype in STEMI patients.

Triglyceride glucose index combined with plaque characteristics as a novel biomarker for cardiovascular outcomes after percutaneous coronary intervention in ST-elevated myocardial infarction patients: an intravascular optical coherence tomography study.

BACKGROUND AND AIM: This prospective study explored plaque morphology according to the underlying culprit lesion pathology (rupture versus erosion) in relation to the triglyceride glucose (TyG) index in patients with acute ST-elevated myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention and optical coherence tomography (OCT) for culprit lesions to elucidate the effects of the TyG index and type of plaque on the incidence of major adverse cardiovascular events (MACEs). METHODS AND OUTCOMES: A total of 274 patients with STEMI aged ≥ 18 years who underwent pre-intervention OCT imaging of culprit lesions between March 2017 and March 2019 were enrolled. The TyG index was calculated using the formula ln[fasting TG (mg/dL) × fasting glucose (mg/dL)/2]. Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the TyG tertiles. MACEs were defined as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke. In fully adjusted analyses, the middle tertile of TyG was significantly associated with greater rates of MACEs in patients with PR but not in those with PE (relative to the low tertile, HR [hazard ratio], 6.01; 95% confidence interval [CI], 1.25-28.88; P = 0.025). Cox regression models indicated a significantly higher HR for MACEs in patients in the middle tertile of TyG than in those in the low tertile of TyG after full additional adjustment (HR, 5.45; 95% CI, 1.10-27.09; P = 0.038). However, being in the high tertile of TyG independently and significantly increased the risk of major bleeding events among patients with PE (HR, 2.50; 95% CI, 1.11-5.65; P = 0.028). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the TyG index combined with the morphological characteristics of plaque after full adjustment was 0.881 (sensitivity = 94.74%, specificity = 78.04%, cut-off level = 0.73). Kaplan-Meier curves were generated for the cumulative incidence of MACEs for up to a median of 1.98 years stratified by tertiles of TyG among the PR and PE subgroups. Among patients with PR, there were significant differences among the tertiles of TyG (p = 0.030). CONCLUSION AND RELEVANCE: Microstructural OCT features of culprit lesions in combination with the TyG index, a surrogate estimate of insulin resistance, can be used in clinical practice to support risk stratification and predict adverse events in patients with STEMI.

Liraglutide reduces coronary endothelial cells no-reflow damage through activating MAPK/ERK signaling pathway.

Coronary no-reflow damage is caused by endothelial cell damage although little drug is available to intervene in coronary no-reflow. Liraglutide is a kind of anti-diabetic drug and its cardioprotective role has been widely reported. In this study, we explored the role of liraglutide in regulating coronary endothelial cell damage. We used hydrogen peroxide to mimic coronary no-reflow damage in vitro. After exposure to hydrogen peroxide, endothelial cells' viability was significantly reduced, an effect that was followed by an increase in cell apoptosis. Interestingly, liraglutide treatment obviously upregulated endothelial cell viability and thus prevented cell apoptosis. Further, we also found that liraglutide inhibited the activation of caspase-3 in hydrogen peroxide-treated endothelial cells. Besides, cellular metabolism, as reflected by mitochondrial membrane potential, was disrupted by hydrogen peroxide and reversed to normal levels with liraglutide. Further, we found that the ERK pathway is a potential downstream effector of liraglutide. Administration of liraglutide significantly promoted the activation of ERK and this effect may contribute to endothelial cell survival. Altogether, our results illustrated that hydrogen peroxide-mediated endothelial cell damage could be attenuated by liraglutide through modulation of the MAPK/ERK signaling pathway. This finding will pave a novel road for the intervention of coronary no-reflow damage in patients suffering from myocardial infarction.

Prognostic impacts of ß-blockers in acute coronary syndrome patients without heart failure treated by percutaneous coronary intervention.

BACKGROUND: The use of ß-blockers for acute coronary syndrome (ACS) patients without heart failure (HF) is controversial, and lacks of evidence in the era of reperfusion and intensive secondary preventions. This study aimed to investigate the prognostic impacts of ß-blockers on patients with ACS but no HF treated by percutaneous coronary intervention (PCI). METHODS: A total of 2397 consecutive patients with ACS but no HF treated by PCI were retrospectively recruited from January 2010 to June 2017. Univariable Cox regression was used to assess the prognostic impacts of ß-blockers, followed by adjusted analysis, one-to-one propensity score matching (PSM), and inverse probability treatment weighting (IPTW) analysis, in order to control for systemic between-group differences. The primary outcome was all-cause death. RESULTS: Among the included patients, 2060 (85.9%) were prescribed with ß-blockers at discharge. The median follow-up time was 727 (433-2016) days, with 55 (2.3%) cases of all-cause death. Unadjusted analysis showed that the use of ß-blockers was associated with lower risk of death (hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.23-0.76, P = 0.004), which was sustained in adjusted analysis (HR: 0.53, 95% CI: 0.29-0.98, P = 0.044), PSM analysis (HR: 0.44, 95% CI: 0.20-0.96, P = 0.039) and IPTW analysis (HR: 0.49. 95% CI: 0.35-0.70, P < 0.001). Risk reduction was also seen in ß-blocker users for cardiac death, but not for major adverse cardiovascular events. CONCLUSIONS: The use of ß-blockers was associated with reduced long-term mortality for ACS-PCI patients without HF.

Prognostic Value of D-dimer in patients with acute coronary syndrome treated by percutaneous coronary intervention: a retrospective cohort study.

BACKGROUND: Associations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI). METHODS: In this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death. RESULTS: During a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420-1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14-2.20, P = 0.007) and high (≥ 1150 ng/mL, HR: 1.98, 95 % CI: 1.36-2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P difference = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P difference = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P difference < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %). CONCLUSIONS: For ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.

Prognostic value of characteristics of plaque combined with residual syntax score among patients with STEMI undergoing primary PCI: an intravascular optical coherence tomography study.

AIM: The present study aimed to explore these characteristics, particularly thin-cap fibroatheroma (TCFA), in relation to residual syntax score (rSS) in patients who presented with acute MI. METHODS AND OUTCOMES: A total of 434 consecutive patients with MI aged ≥18 years who had STEMI underwent primary PCI. Notably, compared with other subgroups, the presence of TCFA in culprit lesions and a higher level of rSS, were significantly associated with MACE. When rSS was divided into three groups, high rSS levels were associated with a higher incidence of MACE, in the subgroups of without TCFA (P = 0.005), plaque erosion (P = 0.045), macrophage infiltration (P = 0.026), and calcification (P = 0.002). AUC of ROC curve was 0.794 and 0.816, whereas the AUC of the survival ROC was 0.798 and 0.846. CONCLUSION: The results of this study could be used in clinical practice to support risk stratification. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov as NCT03593928 .

Prevalence and impact of metabolic syndrome in patients with multivessel coronary artery disease and acute coronary syndrome.

BACKGROUND AND AIMS: Metabolic syndrome (MetS) is associated with increased incidence of diabetes and cardiovascular diseases in patients initially free from these diseases. However, its prognostic value in patients with established coronary artery diseases remains controversial. Therefore, we aimed to illustrate the prevalence and investigate the impact of MetS in patients with multivessel coronary artery disease (MVD) and acute coronary syndrome (ACS). METHODS AND RESULTS: This was a large registry of consecutive patients with ACS referred to primary percutaneous coronary intervention (PCI) and those with MVD were eligible for this analysis. MetS was defined based on modified Adult Treatment Panel III definition. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction and stroke. A total of 2532 patients were included in the current analysis and 993 (39.2%) of them had MetS. The prevalence of MetS increased from 2010 to 2016 (p for trend = 0.005). In patients over 60 years old, the prevalence of MetS decreased with aging (p for trend = 0.002). Female subjects had a higher prevalence than their male counterparts (61.5% verse 32.9% and p < 0.001). Over a median follow-up of 2.3 years, MetS was not significantly associated with MACE (adjusted 95% CI from 0.92 to 1.54). CONCLUSION: MetS was frequently observed in patients with MVD and ACS. Patients with MetS were more likely to be young and female. However, it was not an independent predictor for MACE after primary PCI in those patients.

Association of plasma trimethylamine N-Oxide level with healed culprit plaques examined by optical coherence tomography in patients with ST-Segment elevation myocardial infarction.

BACKGROUND AND AIMS: Healed plaque is a hallmark of previous regional plaque rupture or erosion. We hypothesized that the plasma level of trimethylamine N-oxide (TMAO) is related to healed culprit plaque in ST-segment elevation myocardial infarction (STEMI) patients. METHODS AND RESULTS: A prospective cohort of 206 patients with STEMI, who were examined by optical coherence tomography (OCT) was enrolled in our study. After exclusion, 156 patients were categorized into healed plaque (n = 54) and nonhealed plaque (n = 102) groups. Plasma TMAO levels were detected by stable isotope dilution liquid chromatography tandem mass spectrometry in these two groups. Increased age and low BMI were more common in patients with healed plaques than in those without healed plaques. Through OCT observation, plaque rupture (81.5% vs. 45.1%, p < 0.001), thin cap fibroatheroma (TCFA) and macrophages (42.6% vs. 20.6%, p = 0.004, 70.4% vs. 26.5%, p < 0.001, respectively) were more frequently seen in patients with healed plaques than in those without healed plaques. The TMAO level in patients with healed plaques was significantly higher than that in patients with nonhealed plaques (3.9 µM [2.6-5.1] vs. 1.8 µM [1.0-2.7], p < 0.001). Furthermore, the receiver operating characteristic curve showed that TMAO can be used as a potential biomarker to predict healed plaque presence with a cutoff value of 2.9 µM (AUC = 0.810, sensitivity: 72.2%, specificity: 81.4%). CONCLUSIONS: Healed plaque in STEMI patients is associated with a high level of plaque vulnerability and inflammation. A high level of plasma TMAO can be a useful biomarker to differentiate STEMI patients with healed culprit plaques.

A feasibility study of using silkworm larvae as a novel in vivo model to evaluate the biotoxicity of ionic liquids.

Ionic liquids (ILs) have been reported to be a potential water and soil pollutant, whose toxicity has gained much attention in recent years. In this work, silkworm larvae were used as a novel in vivo model to assess the biotoxicity of ILs, which were performed by three steps. The first step was to determine the susceptibility of different silkworm strains to ILs. Data showed that Jingsong×haoyue was the most susceptible one among three silkworm strains (Jingsong×haoyue, P50, and Yi16) for evaluating the biological effects of ILs. The second step was to compare the toxicity of ILs with different structures using the larvae of Jingsong×haoyue. It was found that three representative ILs, 1-octyl-3-methylimidazole chloride ([C8mim]Cl), N-octyl-3-methylpyridine chloride ([C8mpy]Cl), and 1-octyl-3-methylimidazole tetrafluoroborate ([C8mim]BF4), had significant toxic effects on the growth and development of the larvae with 24 h median lethal concentration (24 h-LC50) values of 112.3, 156.3, and 68.9 µg g-1, respectively, indicating that the types of anions and cations had impacts on the toxicity of ILs. The last step was targeted at investigating responses of the larvae to the exposure of ILs. It was observed that remarkable physiological and biochemical responses occurred in different tissues of the larvae. For example, activities of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) in different tissues increased significantly to form an active protective mechanism for alleviating the toxic effects of ILs. Additionally, an increase of malondialdehyde (MDA) contents was found in the larvae. The data suggested that ILs could induce lipid peroxidation and cellular damage, which may be the main reason for toxicity of ILs to the larvae. Therefore, silkworm larvae could be used as a susceptible and reliable in vivo model to evaluate the toxicity of ILs, and the results are helpful to reveal their toxic mechanism to insects.

Molecular response mechanisms of silkworm (Bombyx mori L.) to the toxicity of 1-octyl-3-methylimidazole chloride based on transcriptome analysis of midguts and silk glands.

In a previous study, silkworm larvae were used as a novel model to assess the biotoxicity of ILs, which showed that ILs could cause significant physiological and biochemical changes in midguts and silk glands of the larvae, and result in the death of larvae. In order to investigate the toxicity of 1-octyl-3-methylimidazole chloride ([C8mim]Cl) to the larvae at molecular level, RNA-sequencing technology was used to construct transcriptomic profiles of midguts and silk glands in this work. Results showed that a lot of differentially expressed genes (DEGs) were effectively screened out through bioinformatics software based on the transcriptome data and reference genome. To give more detail, 5118 and 2211 DEGs (926 and 822 DEGs) were obtained in the midguts (silk glands) when the larvae were exposed to [C8mim]Cl for 6 and 12 h, respectively, relative to the controls. In addition, gene ontology (GO) analysis suggested that the DEGs could be divided into three categories (i.e., biological process, cellular component, and molecular function), and were involved in multiple organelle functions and complex biological processes. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the DEGs were enriched in a variety of pathways, such as signal transduction, apoptosis, glycolysis, peroxisome, autophagy, hippo signaling pathway, arginine and proline metabolism. Results of quantitative real-time PCR and histopathological observation indicated that molecular mechanism of the larvae against [C8mim]Cl toxicology may be attributed to cell apoptosis regulation via both the mitochondrial pathway and the death receptor-initiated pathway. Thus, these results provided useful data for exploring the toxicity of ILs to insects at molecular level.

Association between Variation of Troponin and Prognosis of Acute Myocardial Infarction before and after Primary Percutaneous Coronary Intervention.

BACKGROUND: Circulating levels of cardiac troponin I (cTnI) after ST-segment elevation myocardial infarction (STEMI) were considered as prognostic factors for predicting the incidence of major adverse cardiovascular events (MACE). △cTnI is the difference between peak cTnI after primary percutaneous coronary intervention (PPCI) and cTnI on initial admission. PURPOSE: This study aimed to assess the relationship between △cTnI, the ratio of △cTnI to cTnI on initial admission, and the incidence of MACE during the follow-up period. METHODS: A total of 2596 patients with cTnI measured upon admission and one-time measurement of cTnI during hospitalization were enrolled. RESULTS: In the adjusted models of the survival receiver operating characteristic (ROC) curve, △cTnI and the ratio of △cTnI to cTnI on initial admission have stronger discrimination power of MACE (area under curve (AUC) 0.730 and 0.717) compared with peak cTnI after PPCI and cTnI at admission (AUC 0.590, 0.546). Multivariate Cox regression analysis identified △cTnI (hazard ratio (HR) 1.018, 95% confidence interval (CI) 1.001 to 1.035) as a relevant factor for MACE during follow-up. △cTnI was divided into quartiles, and maximum △ cTnI between 4.845 and 19.073 ng/ml comprised more patients with anterior wall myocardial infarction (p < 0.001), higher GRACE score (p = 0.038), CK-MB (p = 0.023), and Myoglobin (p < 0.001). On the K-M survival curves, the incidence of MACE, mortality, and angina pectoris were significantly higher in the group with maximum △cTnI (p = 0.035, 0.049, 0.026). CONCLUSION: The △cTnI level and the ratio of △cTnI have stronger discrimination power of predicting the incidence of MACE. The group with maximum △cTnI has higher incidence of MACE, mortality, and angina pectoris during the follow-up period.

Ticagrelor Versus Clopidogrel in Patients with Late or Very Late Stent Thrombosis.

PURPOSE: To compare the effect of ticagrelor with clopidogrel in reducing the risk of ischemic cardiovascular events in patients with late or very late stent thrombosis (LST/VLST) after primary percutaneous coronary intervention (PCI). METHODS: A total of 4538 patients with acute coronary syndrome were screened for angiographically determined LST/VLST. Two hundred and forty-one patients were included in the analysis and grouped according to ticagrelor (n = 81) or clopidogrel (n = 160) at discharge. The clinical outcome was major adverse cardiovascular events (MACE) defined as death, myocardial infarction (MI), ischemic stroke, and revascularization during the 1-yr follow-up period. RESULTS: After propensity score matching, 65 pairs were generated. The incidence of MACE was significantly lower in the ticagrelor group compared with the clopidogrel group (9.3% vs. 21.5%, log-rank p = 0.048). However, no difference was observed in event rates of death, MI, ischemic stroke, and revascularization between the ticagrelor group and the clopidogrel group. CONCLUSION: Following successful primary PCI, patients with LST/VLST who received ticagrelor had fewer ischemic cardiovascular events at 1-yr follow-up, compared with those who received clopidogrel.

Combined with ticagrelor, 50 mg aspirin daily can reduce bleeding events without increasing ischemic risk compared with 75-100 mg aspirin daily in coronary artery disease patients: insights from the TIFU (Ticagrelor in Fuwai Hospital) study.

Patients treated with ticagrelor and aspirin usually suffer from bleeding events, especially mild bleeding which is one of the main factors reducing patients' adherence to ticagrelor. The objective of this study is to investigate the efficacy and safety of ticagrelor combined with a lower dose of aspirin (50 mg) than that recommended by guidelines (75-100 mg). In this study, we prospectively enrolled 1220 patients who take ticagrelor in the hospital. After excluding the patients who did not take ticagrelor after discharge or lost to follow-up, the remaining 1066 patients were divided into two aspirin dose groups: 75-100 mg (n = 744) and 50 mg (n = 322). The rates of major adverse cardiovascular events (MACEs), bleeding events and ticagrelor adherence were compared between the two groups. MACEs risk was not significantly different between the two groups (OR = 0.563, 95% CI: 0.244-1.300, P = .179). However, 50 mg aspirin was associated with a lower risk of any Bleeding Academic Research Consortium (BARC) bleeding events (OR = 0.605, 95% CI: 0.399-0.713, P = .001), also lower BARC bleeding events (OR = 0.639, 95% CI: 0.468-0.872, P = .005). Moreover, lower-dose aspirin was associated with a lower rate of ticagrelor withdrawal (OR = 0.459, 95% CI: 0.279-0.754, P = .002), mainly because of the decrease in ticagrelor withdrawal due to bleeding (OR = 0.378, 95% CI: 0.156-0.916, P = .031). After propensity score matching (PSM), a total of 317 patients in each group were matched. The MACEs composite was not significantly different between the two matched groups and 50 mg aspirin was associated with a lower risk of bleeding events and low ticagrelor withdrawal before and after multivariate adjustment. In conclusion, among patients who took ticagrelor (90 mg twice daily), 50 mg aspirin daily is associated with a lower rate of bleeding events and ticagrelor withdrawal but does not increase the MACE risk compared with 75-100 mg aspirin daily.