Mitochondrial energy metabolism-associated Predictive model constriction for coronary artery disease(CAD) of acute myocardial infarction(AMI) patients via integrative bioinformatic analysis.

Coronary artery diseases (CAD) are main causes of morbidity and hospitalisation in western countries and CAD patients are at considerable risk of suffering further cardiac events. The development and evaluation of secondary prevention programmes therefore an important task. This thesis includes investigations on CAD patients admitted to a secondary prevention programme at Malmö University Hospital, Malmö, Sweden. Four weeks after discharge from the hospital, consecutive male and female patients aged 50-70 years with acute myocardial infarction (AMI) or treated with coronary artery bypass grafting (CABG) surgery were randomised to a hospital organised preventive intervention or to usual follow-up at their general practitioners. In the three studies using this randomised design, 87 (study II), 90 (study IV), and 106 (study V) intervention patients were available for evaluation. In addition, without randomisation, lipid levels at four weeks after the event was compared with levels estimated within 24 hours after onset of symptoms in 141 AMI patients (study I), and quality of life (QL) were estimated by questionnaire at one month and at one year after the event in 266 AMI, 94 CABG, and 16 percutaneous transluminal coronary angioplasty (PTCA) patients (study III). The prevention programme was effective in improving food habits but showed no impact on smoking habits or physical exercise in AMI patients (study II). The intervention also did not show any significant improvement in working capacity in AMI and CABG patients. However, working capacity improved in both intervention and reference CABG patients, most probably due to improved coronary circulation from the surgery (study IV). Cholesterol levels decreased significantly in AMI and CABG intervention patients as compared to the corresponding reference patients. This difference most likely was due to a higher frequency of lipid lowering drugs used in the intervention patients (study V). The prevention programme also decreased body mass index significantly in AMI but not in CABG patients (study V). In AMI patients receiving thrombolysis, cholesterol levels estimated within 24 hours after onset of symptoms and at four weeks after the event were virtually equal. In AMI patients not receiving thrombolysis, the lipid estimates from four weeks after the event were slightly, but significantly, above the within 24 hours from onset of symptoms estimates (study I). One month after the event, both somatic and psychological aspects of QL were negatively affected in AMI and CABG patients compared to population controls. One year after the event, patients differed from controls mainly in somatic symptoms (study III). Thus, the intervention programme was most successful in affecting lipid levels and food habits in AMI patients. QL was considerably affected in patients following an cardiac event, especially during the initial recovery phase. In addition, in patients receiving thrombolysis, cholesterol levels estimated four weeks after an AMI are reasonably valid estimates of baseline values and may be used to decide about lipid lowering interventions.

IL-6 and its receptors in coronary artery disease and acute myocardial infarction

According to the literature, 40-60% of patients with acute myocardial infarction (AMI) have obstructive multivessel coronary artery disease (CA) and 8.8% of patients have non-obstructive CA lesions. And it is around these two groups of patients that there are active discussions and disputes regarding the choice of optimal treatment tactics and further prognosis. The aim of the study was to study clinical and laboratory features of development and course of primary AMI in patients with multi-and single-vessel obstructive lesion of the CA compared with patients with non-obstructive CA lesions. Methods. The study has included patients hospitalized "through the ambulance channel" in the Department of cardiac intensive care of municipal clinical hospital named after S. S. Yudin Moscow with a diagnosis "primary acute myocardial infarction", ACS with and without ST segment elevation, unstable angina in 2015-2016. The diagnosis of acute myocardial infarction (AMI) was established at the hospital stage according to the criteria of the "Third universal definition of myocardial infarction" in 2012. The study included 1240 patients who underwent coronary angiography (CAG) no later than 12 hours from the time of admission. The first group (comparison group) consisted of patients with AMI and the first detected multivessel obstructive atherosclerotic lesion of CA (664 patients), the second (interest group) consisted of patients with AMI and non-obstructive atherosclerotic lesion of CA (96 patients) meeting the MINOCA criteria. The third group consisted of patients with single-vessel obstructive lesion and complete acute occlusion of the CA (272 patients). Patients with hemodynamically significant lesions of the left CA trunk were not included in the study. The clinical and laboratory features of the course of acute primary myocardial infarction in patients with obstructive and non-obstructive coronary atherosclerosis were studied. The generally accepted statistical processing methods were used. A year after discharge from the hospital, 727 patients (468 patients from the 1st group, 78 from the 2nd group, 181 from the 3rd group) were interviewed by means of a structured telephone survey about the course of the disease (collection of medical history). The median follow-up was 12 months. (interquartile range 11-13 months). The endpoints were: re-hospitalization for any reason, re-coronary event, death. The received answers are entered into questionnaires and statistically processed. Results and conclusions. In patients with AMI and non-obstructive atherosclerotic CA lesion, pain behind the sternum is observed one and a half times less often (54.2%) than in patients with obstructive CA lesion (MOAPCA 86.1%, OAPCA 89.7%) and the cardiac co duction system is almost three times more likely to be affected ( 30% versus 8.4% and 12%). Only 12.5% of patients in this group had an abnormal Q wave (Q - myocardial infarction) on the ECG, therefore, a smaller volume of myocardial damage and a lower level of troponin than in patients of groups 1 and 3. During the first year after the development of AMI, patients with obstructive coronary atherosclerosis did not experience repeated coronary events, there were no indications for conducting CAG, PCI or CABG, in contrast to patients with obstructive lesion of CA. For multivascular obstruction (group 1), PCI was performed in 9.6% of patients and 3.8% of CABG. PCI was performed in group 3 with obstructive single-vessel lesion of CA in 7.7% of patients. In patients with AMI and obstructive single-vessel atherosclerotic lesion of CA (group 3), two and a half times less often (9.1%) myocardial reperfusion injury is observed, while in patients with multivascular obstructive CA defeat, this syndrome was observed in 21.3%.

Introduction Residual inflammatory risk (RIR) following acute myocardial infarction (AMI) patients is associated with recurrent major adverse cardiovascular events. Atherosclerotic plaque quantification using computed tomographic coronary angiography (CTCA) can specifically identify inflamed plaque characteristics. We compared plaque burden and tissue composition in AMI patients with those of stable coronary artery disease (CAD) patients to identify imaging markers of RIR. Purpose We aimed to identify signs of residual inflammation in recent AMI patients via CTCA atheroma quantification. We hypothesised that recent AMI patients have plaque characteristics suggestive of inflammation. Methods 108 patients recruited from multiple sites with AMI <1 month were propensity-matched via CAD risk factors (age, gender, diabetes, hypertension, hyperlipidaemia, smoking and family history of CAD) with stable CAD patients in a 1:1 ratio. Propensity matched recent AMI and stable CAD patient cohorts had similar profiles: age (60±9.7 vs 57±10.0 years), gender (91.7% vs 92.6% male), diabetes (13.9% vs 15.7%), hypertension (44.4% vs 50.9%) and hyperlipidaemia (50.9% vs 63.9%, p>0.05 for all). Total plaque burden (total lesion volume/total vessel volume) and plaque composition (fibrous fatty [fibrofatty, FF, 31 – 130 HU], necrotic core [NC, -30 – 30 HU], fibrous [131 – 350 HU] and calcium [> 350 HU]) were extracted from CTCA scans and aggregated per patient. Culprit lesions of recent AMI patients were excluded from the analysis due to the fact that coronary stents would affect plaque characterisation. Multivariate linear regression, corrected for CAD risk factors, was used to compare these parameters between the two cohorts. Results Recent AMI patients and stable CAD patients had similar total plaque burden (β=0.001±0.013, p=0.950, Figure 1a). Patients with recent AMI had higher non-calcified plaque volume ratio (β=0.071±0.026, p<0.05, Figure 1b) due to higher FF (β=0.094±0.019, Figure 1d) and NC (β=0.025 ± 0.005, Figure 1e) plaque volume (p<0.05 for all), but less fibrous plaque volume (β = -0.048±0.019, p<0.05, Figure 1c). Conclusions Recent AMI patients had a greater non-calcified plaque burden than stable CAD patients due to larger FF and NC plaque burden. Since FF and NC components indicate ongoing inflammation in the plaque, while fibrous content indicates resolved inflammation; increased NC and FF burden suggest increased coronary plaque inflammation in non-culprit lesions of recent AMI patients, supporting the presence of residual inflammation in recent AMI patients.Figure 1

Serum adropin levels are decreased in patients with acute myocardial infarction

BackgroundEarly repolarization pattern (ERP) was associated with sudden cardiac death in recent studies. However, the associations between ERP and coronary artery disease (CAD), and ERP and cardiac death caused by acute myocardial infarction (MI) remains unclear.MethodsWe retrospectively enrolled consecutive 1,545 CAD patients and 908 non‐CAD subjects as control group which were confirmed by coronary angiograph. The CAD patients include stable CAD, acute MI patients, and old MI patients. Multivariate logistic regression was employed to evaluate the relationship between ERP and CAD, and ERP and cardiac death caused by acute MI.ResultsOf the 1,545 CAD subjects, there were 1,029 stable CAD patients, 404 acute MI patients, and 112 old MI patients. The incidence of ERP was much higher among patients with CAD than without CAD subjects (20.1% vs. 6.2%, p < .001) after adjusting for major cardiovascular risk factors. No significant correlation was observed between lead region of ERP on 12‐lead ECG and single abnormal artery. Of the 404 acute MI patients, 342 patients survived and 62 patients died. Incidence of ERP was higher in non‐survivor than survivor patients with acute MI (24.2% vs. 17.5%, p = .006) after adjustment for major cardiovascular risk factors.ConclusionThe incidence of ERP was higher in CAD patients than subjects without CAD and in non‐survivor patients than survivor patients with acute MI. The lead region of ERP on 12‐lead ECG was not associated with single abnormal coronary artery.

Coronary artery disease (CAD) patients are at high ischemic risk, and new biomarkers reflecting atherosclerotic disease severity and coronary plaque vulnerability are required. The Brain-Derived Neurotrophic Factor (BDNF) affects endothelial and macrophage activation suggesting its involvement in atherosclerotic plaque behavior. To investigate whether plasma BDNF is associated with in vivo coronary plaque features, assessed by optical coherence tomography (OCT), in both acute myocardial infarction (AMI) and stable angina (SA) patients, we enrolled 55 CAD patients (31 SA and 24 AMI), and 21 healthy subjects (HS). BDNF was lower in CAD patients than in HS (p < 0.0001), and it decreased with the presence, clinical acuity and severity of CAD. The greater BDNF levels were associated with OCT features of plaque vulnerability in overall CAD as well as in SA and AMI patients (p < 0.03). Specifically, in SA patients, BDNF correlated positively with macrophages’ infiltration within atherosclerotic plaque (p = 0.01) and inversely with minimal lumen area (p = 0.02). In AMI patients a negative correlation between BDNF and cap thickness was found (p = 0.02). Despite a small study population, our data suggest a relationship between BDNF and coronary plaque vulnerability, showing that vulnerable plaque is positively associated with plasma BDNF levels, regardless of the clinical CAD manifestation.

Coronary artery disease (CAD) and acute myocardial infarction (AMI) are the leading causes of death worldwide. Since only a subset of CAD patients develops myocardial infarction, it is likely that unique factors predispose to AMI. Circulating microRNAs represent diagnostic powerful biomarkers for detection of heart injuries and patients’ risk stratification. Using an array-based approach, the expression of 84 circulating miRNAs was analyzed in plasma of pooled stable CAD patients (CAD; n = 5) and unstable CAD patients (AMI_T0; n = 5) enrolled within 24 hours from an AMI event. The array experiments showed 27 miRNAs differentially expressed with a two-fold up- or down-regulation (10 up- and 17 down-regulated miRNAs). Among them, miR-423-5p dis-regulation was confirmed in a larger case study (n = 99). Circulating miR-423-5p resulted to be significantly down-regulated within 24 hours from the AMI event (FC = -2, p≤0.05). Interestingly, miR-423-5p expression resulted to be increased (FC = +2; p≤0.005) in a subgroup of the same AMI patients (AMI_T1; n = 11) analyzed after 6 months from the acute event. We extended miR-423-5p expression study on PBMCs (peripheral blood mononuclear cells), confirming also in this tissue its up-regulation at 6 months post-AMI. Receiver operating characteristic analyses (ROC) were performed to detect the power of miR-423-5p to discriminate stable and unstable CAD. In plasma, miR-423-5p expression accurately distinguishes stable and unstable CAD patients (AUC = 0.7143, p≤0.005). Interestingly, the highest discriminatory value (AUC = 0.8529 p≤0.0005) was identified in blood cells, where miR-423-5p expression is able to differentiate unstable CAD patients during an acute event (AMI_T0) from those at six months post-AMI (AMI_T1). Furthermore, cellular miR-423-5p may discriminate also stable CAD patients from unstable CAD patients after six months post-AMI (AUC = 0.7355 p≤0.05). The results of this pilot-study suggest that miR-423-5p expression level both in plasma and blood cells, could represent a new promising biomarker for risk stratification of CAD patients.

Objective Although blood thrombogenicity seems to be one of the determinant factors for the development of acute myocardial infarction (MI), it has not been dealt with in-depth. This study aimed to investigate blood thrombogenicity and its change in acute MI patients.Methods and Results We designed a prospective, observational study that included 51 acute MI patients and 83 stable coronary artery disease (CAD) patients who underwent cardiac catheterization, comparing thrombogenicity of the whole blood between: (1) acute MI patients and stable CAD patients; and (2) acute and chronic phase in MI patients. Blood thrombogenicity was evaluated by the Total Thrombus-Formation Analysis System (T-TAS) using the area under the flow pressure curve (AUC30) for the AR-chip. Acute MI patients had significantly higher AUC30than stable CAD patients (median [interquartile range], 1,771 [1,585–1,884] vs. 1,677 [1,527–1,756],p = 0.010). Multivariate regression analysis identified acute MI with initial TIMI flow grade 0/1 as an independent determinant of high AUC30(β = 0.211,p = 0.013). In acute MI patients, AUC30decreased significantly from acute to chronic phase (1,859 [1,550–2,008] to 1,521 [1,328–1,745],p = 0.001).Conclusion Blood thrombogenicity was significantly higher in acute MI patients than in stable CAD patients. Acute MI with initial TIMI flow grade 0/1 was significantly associated with high blood thrombogenicity by multivariate analysis. In acute MI patients, blood thrombogenicity was temporarily higher in acute phase than in chronic phase.

Is Toll-like receptor responsiveness a marker and predictor of coronary artery disease?

Patients with stable coronary artery disease (CAD) are at an increased risk of acute myocardial infarction (AMI), particularly among older individuals. Developing a reliable model to predict AMI occurrence in these patients holds the potential to expedite early diagnosis and intervention. This study is aimed at establishing a circulating amino acid-assisted model, incorporating amino acid profiles alongside clinical variables, to predict AMI risk. A cohort of 874 CAD patients from two independent centers was analyzed. Plasma amino acid levels were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) employing a targeted metabolomics approach. This methodology incorporated 13C isotope-labeled internal standards for precise quantification of 27 amino acids. Univariate logistic regression was applied to identify differentially expressed amino acids that distinguished between stable CAD and AMI patients. To assess prediction performance, receiver operating characteristic (ROC) curve and nomogram analyses were utilized. Five amino acids—lysine, methionine, tryptophan, tyrosine, and N6-trimethyllysine—emerged as potential biomarkers (p < 0.05), exhibiting significant differences in their expression levels across the two centers when comparing stable CAD with AMI patients. For AMI risk prediction, the base model, utilizing 12 clinical variables, achieved areas under the curve (AUC) of 0.7387 in the discovery phase (n = 623) and 0.8205 in the external validation set (n = 251). Notably, the integration of these five amino acids into the prediction model significantly enhanced its performance, increasing the AUC to 0.7651 in the discovery phase (Delong's test, p = 1.43e‐02) and to 0.8958 in the validation set (Delong's test, p = 8.91e‐03). In conclusion, the circulating amino acid-assisted model effectively enhances the prediction of AMI risk among CAD patients, indicating its potential clinical utility in facilitating early detection and intervention.

Malondialdehyde-acetaldehyde adducts (MAA) have been implicated in atherosclerosis. The purpose of this study was to investigate the role of MAA in atherosclerotic disease. Serum samples from controls (n = 82) and patients with; non-obstructive coronary artery disease (CAD), (n = 40), acute myocardial infarction (AMI) (n = 42), or coronary artery bypass graft (CABG) surgery due to obstructive multi-vessel CAD (n = 72), were collected and tested for antibody isotypes to MAA-modifed human serum albumin (MAA-HSA). CAD patients had elevated relative levels of IgG and IgA anti-MAA, compared to control patients (p<0.001). AMI patients had a significantly increased relative levels of circulating IgG anti-MAA-HSA antibodies as compared to stable angina (p<0.03) or CABG patients (p<0.003). CABG patients had significantly increased relative levels of circulating IgA anti-MAA-HSA antibodies as compared to non-obstructive CAD (p<0.001) and AMI patients (p<0.001). Additionally, MAA-modified proteins were detected in the tissue of human AMI lesions. In conclusion, the IgM, IgG and IgA anti-MAA-HSA antibody isotypes are differentially and significantly associated with non-obstructive CAD, AMI, or obstructive multi-vessel CAD and may serve as biomarkers of atherosclerotic disease.

Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute myocardial infarction.

Common community infections and the risk for coronary artery disease and acute myocardial infarction: Evidence for chronic over-expression of tumor necrosis factor alpha and vascular cells adhesion molecule-1

Whether serum calcium is associated with heart systolic function in patients with established coronary artery disease (CAD) and acute myocardial infarction (AMI) remains to be elucidated. This study is aimed to assess the association between serum calcium and left ventricular systolic dysfunction in a Chinese population of CAD. The cross-sectional study included 5938 CAD patients with and without AMI in China. The factors associated with AMI and left ventricular ejection fraction (LVEF) were evaluated. The data showed that AMI patients had lower serum calcium levels (2.11 ± 0.13 vs 2.20 ± 0.10 mmol/l, P < 0.001) than those without AMI. Multiple logistic regression analysis exhibited that serum calcium (OR: 0.000, 95% CI: 0.000–0.001) was one of the independent factors correlated with AMI. CAD patients with and without AMI when LVEF <50% had lower serum calcium levels than those when LVEF ≥50% respectively. Serum calcium was independently associated with LVEF and LVEF <50% in CAD patients with and without AMI respectively using multivariate analysis. The independent association between serum calcium and LVEF still existed among CAD patients when LVEF ≥50%. Serum calcium levels are significantly decreased following AMI. Low serum calcium is independently correlated with left ventricular systolic dysfunction in CAD patients with and without AMI.