Acute Coronary Events Risk Research Articles

Variability of the Plasma Lipidome and Subclinical Coronary Atherosclerosis

While the risk of acute coronary events has been associated with biological variability of circulating cholesterol, the association with variability of other atherogenic lipids remains less understood. We evaluated the longitudinal variability of 284 lipids and investigated their association with asymptomatic coronary atherosclerosis. Approach and Results: Circulating lipids were extracted from fasting blood samples of 83 community-sampled symptom-free participants (age 41-75 years), collected longitudinally over 6 months. Three types of coronary plaque volume (calcified, lipid-rich, and fibrotic) were quantified using computed tomography coronary angiogram. We first deconvoluted between-subject (CVg) and within-subject (CVw) lipid variabilities. We then tested whether the mean lipid abundance was different across groups categorized by Framingham risk score and plaques phenotypes (lipid-rich, fibrotic, and calcified). Finally, we investigated whether visit-to-visit variability of each lipid was associated with plaque burden. Most lipids (72.5%) exhibited higher CVg than CVw. Among the lipids (n=145) with 1.2-fold higher CVg than CVw, 26 species including glycerides and ceramides were significantly associated with Framingham risk score and the 3 plaque phenotypes (false discovery rate <0.05). In an exploratory analysis of person-specific visit-to-visit variability without multiple testing correction, high variability of 3 lysophospholipids (lysophosphatidylethanolamines 16:0, 18:0, and lysophosphatidylcholine O-18:1) was associated with lipid-rich and fibrotic (noncalcified) plaque volume while high variability of diacylglycerol 18:1_20:0, triacylglycerols 52:2, 52:3, and 52:4, ceramide d18:0/20:0, dihexosylceramide d18:1/16:0, and sphingomyelin 36:3 was associated with calcified plaque volume. High person-specific longitudinal variation of specific nonsterol lipids is associated with the burden of subclinical coronary atherosclerosis. Larger studies are needed to confirm these exploratory findings.

Application of machine learning to predict the occurrence of arrhythmia after acute myocardial infarction

BackgroundEarly identification of the occurrence of arrhythmia in patients with acute myocardial infarction plays an essential role in clinical decision-making. The present study attempted to use machine learning (ML) methods to build predictive models of arrhythmia after acute myocardial infarction (AMI).MethodsA total of 2084 patients with acute myocardial infarction were enrolled in this study. (All data is available on Github: https://github.com/wangsuhuai/AMI-database1.git). The primary outcome is whether tachyarrhythmia occurred during admission containing atrial arrhythmia, ventricular arrhythmia, and supraventricular tachycardia. All data is randomly divided into a training set (80%) and an internal testing set (20%). Apply three machine learning algorithms: decision tree, random forest (RF), and artificial neural network (ANN) to learn the training set to build a model, then use the testing set to evaluate the prediction performance, and compare it with the model built by the Global Registry of Acute Coronary Events (GRACE) risk variable set.ResultsThree ML models predict the occurrence of tachyarrhythmias after AMI. After variable selection, the artificial neural network (ANN) model has reached the highest accuracy rate, which is better than the model constructed using the Grace variable set. After applying SHapley Additive exPlanations (SHAP) to make the model interpretable, the most important features are abnormal wall motion, lesion location, bundle branch block, age, and heart rate. Among them, RBBB (odds ratio [OR]: 4.21; 95% confidence interval [CI]: 2.42–7.02), ≥ 2 ventricular walls motion abnormal (OR: 3.26; 95% CI: 2.01–4.36) and right coronary artery occlusion (OR: 3.00; 95% CI: 1.98–4.56) are significant factors related to arrhythmia after AMI.ConclusionsWe used advanced machine learning methods to build prediction models for tachyarrhythmia after AMI for the first time (especially the ANN model that has the best performance). The current study can supplement the current AMI risk score, provide a reliable evaluation method for the clinic, and broaden the new horizons of ML and clinical research.Trial registration Clinical Trial Registry No.: ChiCTR2100041960.

Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.

CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of newACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64±11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.

Machine Learning Based Analysis of Heart and Cardiac Substructures for Radiation-Induced Cardiac Toxicity From Breast Cancer Radiotherapy

Radiation-induced cardiac toxicity is an importantissue of breast RT. Although a relationship between mean heart dose and acute coronary event (ACE) risk was reported in previous study, the specific relationships between doses to cardiac structures or their sub-regions and subsequent toxicity have not been well defined. In this study, we studied the effect of radiation on specific heart segments on subsequent cardiac toxicity.From the 1294 patients with breast cancer where previously demonstrated a relationship between mean heart dose and ACE, 21 patients who developed HF following breast RT and 39 with ACE were identified after an independent review by cardiologists. The study included 21 and 39 controls for respective toxicity who were matched according to age, comorbidities, and physical activity. For each patient who received radiotherapy, substructures were manually drawn, and then dose-distribution parameters of heart and substructures (Mean, Maximum (Max) dose, Relative volume at least given dose from 5-50 Gy in 5 Gy increments) were collected from CT planning data. To specify most critical regions for developing ACE, analysis using High-dimensional Cox regression model (SNet) was performed to reveal the effect of radiation on specific heart segments on subsequent cardiac toxicity.In HF (n = 42) and ACE (n = 78) cohorts, characteristics between case and control were well matched. Mean time to develop heart failure, acute coronary events were 40.0 months and 42.2 months, respectively. In HF cohort, there was no significant difference not only in the mean heart dose (3.7 Gy vs 3.1 Gy, P = 0.652), but also in the mean left ventricle (LV) (5.0 Gy vs 4.1 Gy, P = 0.587), mean right ventricle (RV) (4.8 Gy vs 3.6 Gy, P = 0.473). On the other hand, in ACE cohort, there was significant difference in mean dose of heart (2.9 Gy vs 1.3 Gy, P = 0.015), left atrium (LA) (1.0 Gy vs 0.5 Gy, P = 0.008), LV (3.7 Gy vs 1.5 Gy, P = 0.028), left anterior descending artery (LAD) (6.6 Gy vs 2.4 Gy, P = 0.028) and right atrium (RA) (1.5 Gy vs 0.9 Gy, P = 0.025). In univariate analysis, mean dose of heart, LA, LV, LAD and RA was significant factors for acute coronary event free survival. ((Heart; P = 0.006, Hazard ratio (HR) 1.139, 95% Confidence Interval (CI) 1.035-1.253) (LA; P = 0.002, HR 1.735, 95% CI 1.209-2.490), (LV; P = 0.018, HR 1.079, 95% CI 1.012-1.150), (LAD; P = 0.031, HR 1.032, 95% CI 1.002-1.064), (RA; P = 0.008, HR = 1.307, 95% CI 1.068-1.598)). For predicting ACE risk for breast cancer patients, SNet model suggested nomogram based on mean and max LA dose, LAD V10, 15, 20, mean heart dose, mean RA dose and RV V35 in the order of higher predicted point variation. Based on this risk stratification model, event free survival significantly showed difference (P = 0.013).There was significant difference between cardiac substructure dose parameters in ACE cohort, but not in HF cohort. Further analysis using convolution neural network will be performed to specify most critical region to be spared.

Gut leakage markers in response to strenuous exercise in patients with suspected coronary artery disease

Abstract Introduction Although regular physical activity is associated with reduced risk of cardiovascular disease (CVD), acute vigorous exercise seems to transiently increase the risk of acute coronary events in patients with underlying CVD. Some studies have reported regular physical activity to associate with microbial diversity, whereas elevated levels of gut leakage markers have been shown after strenuous exercise in healthy individuals. Any predictive value of a temporary increase in gut leakage markers on the risk of coronary events in susceptible individuals is unknown. Purpose We aimed to explore gut leakage markers in response to a bout of strenuous exercise in patients with symptoms of chronic coronary syndrome (CCS). We hypothesized that gut leakage markers would increase after acute strenuous exercise, and that the increase would be higher in patients with angiographically verified CAD. Methods Patients referred to exercise stress testing or coronary angiography due to symptoms suggestive of CCS were included (n=327). A maximal exercise ECG stress test was performed using a bicycle ergometer. Venous blood samples were drawn at rest prior to the test and within 5 min after the test ended, for analysis of soluble cluster of differentiation 14 (sCD14), lipopolysaccharide-binding protein (LBP) and intestinal fatty-acid binding protein (I-FABP) by ELISAs. Quantification of lipopolysaccharide (LPS) and relative quantification of gene expression of the toll-like receptor 4 (TLR4) in circulating leukocytes was performed in a subset of patients (n=101). Patients then underwent coronary angiography, and were grouped according to the degree of CAD. Results Of the 287 patients who completed the exercise stress test and coronary angiography, 69 (24%) had no CAD, 88 (31%) had non-significant CAD and 130 (45%) had significant CAD. Mean exercise duration was 10:05±4:46 min and the duration did not differ between the groups. There were no significant differences in resting levels of gut leakage markers between the groups. In the total population, sCD14, LBP and LPS increased significantly after exercise (p&amp;lt;0.0001, all), whereas I-FABP did not. The gene expression of TLR4 decreased significantly after exercise (p&amp;lt;0.0001). There were no differences in exercise-induced changes in any of the measured markers between groups with no CAD, non-significant CAD and significant CAD. Conclusion In patients with symptoms suggestive of CCS, LPS, LBP and sCD14 increased significantly after strenuous exercise, suggesting that even short bouts of vigorous exercise are associated with gut leakage. The decrease in gene expression of TLR4 may be discussed to be compensatory to the increase in LPS or possibly reflecting an increase in TLR4 translation in response to LPS. The presence of CAD or not did not seem to impact exercise-induced increase in gut leakage markers. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Stein Erik Hagen Foundation for Clinical Heart Research, Olso, Norway

External validation of the Global Registry of Acute Coronary Events (GRACE) risk score: insights from the FORCE-ACS registry

Abstract Background Acute coronary syndrome (ACS) patients are a heterogeneous group with a varying risk of in-hospital and long-term mortality. Clinical risk scores play an important role in estimating these risks. Among the available risk scores, the Global Registry of Acute Coronary Events (GRACE) risk score is most used in routine clinical practice. Given the temporal improvements in both the in-hospital and long-term survival for ACS patients, continued validation of the GRACE risk score in contemporary patient cohorts is warranted. Moreover, the performance of the GRACE risk score in important subgroups with specific risk profiles has received limited attention. Purpose To assess the performance of the GRACE risk score for predicting in-hospital and one-year mortality in a contemporary, unselected cohort of ACS patients. Methods The study population consisted of ACS patients enrolled in the FORCE-ACS registry. To assess model discrimination, c-statistics were computed from the area under the receiver operator characteristic curve. Calibration was visually assessed by plotting observed versus predicted mortality and tested using the Hosmer-Lemeshow goodness-of-fit test. Indices of calibration and discrimination were also assessed in subgroups based on sex, age, type of ACS and bleeding risk (according to the PRECISE-DAPT score). Results In total, 2,587 ACS patients (median age 68 years, 28.4% women) who were enrolled in the FORCE-ACS registry between January 2015 and June 2018 were used for model validation. The in-hospital and one-year mortality rates were 2.4% and 6.3%, respectively. The discriminative ability of the GRACE risk score was good for in-hospital mortality (c-statistic 0.87, 95% CI: 0.82–0.91) and one-year mortality (c-statistic 0.82, 95% CI: 0.78–0.85) (Figure 1). The GRACE risk score predicted one-year mortality less well in patients at high risk of bleeding (c-statistic 0.68 vs. 0.78 in patients at low risk of bleeding, p=0.04). We did not observe statistically significant differences in discrimination for predicting in-hospital or one-year mortality between other subgroups. In the overall cohort, calibration of the GRACE risk score for in-hospital morality was adequate (Hosmer-Lemeshow test: p=0.11), but the GRACE risk score overestimated the in-hospital mortality risk in patients &amp;lt;75 years and patients at low risk of bleeding (Figure 2). The GRACE risk score overestimated the one-year mortality risk (Hosmer-Lemeshow test: p&amp;lt;0.01) in the overall cohort, particularly in patients &amp;lt;75 years, men and patients at low risk of bleeding (Figure 2). Conclusion The GRACE risk score remains a useful tool for predicting in-hospital and one-year mortality, although absolute risk at one year might be overestimated in contemporary ACS patients. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The FORCE-ACS registry is supported by grants from ZonMw, the St. Antonius Research Fund and AstraZeneca Figure 1. Discrimination of the GRACE risk scoreFigure 2. Calibration of the GRACE risk score

Association of quality indicators for acute myocardial infarction and mortality: feasibility and validation study using linked nationwide registry data

BackgroundQuality indicators (QIs) have been increasingly used as tools to assess and improve the quality of care for acute myocardial infarction (AMI). However, it is not known if it is feasible to use the 2020 iteration of international AMI QIs using routinely collected data and, if so, whether higher performance is associated with improved outcomes.ObjectiveTo investigate if routine data are available to measure care quality against the 2020 European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) QIs for AMI, investigate whether higher performance is associated with reduced mortality, and to report quality of care during the COVID-19 pandemic.MethodsCohort study of linked data from the AMI and percutaneous coronary intervention (PCI) registries in England and Wales with outcome data from the Civil Registration of Deaths Register between 2017 and 2020 (representing 236 743 patients from 186 hospitals). Baseline ischaemic risk was estimated using the Global Registry of Acute Coronary Events (GRACE) risk score. The likelihood of attainment for each QI based on GRACE risk was quantified using logistic regression and the association with mortality at 30 days, 6 months, 1 year and long-term (maximum 1243 days) was obtained from Cox proportional hazard models.ResultsOf 26 QIs, 17 (65.3%) could be directly measured using nationwide registry data and were each inversely associated with risk-adjusted 1-year and long-term mortality. At 30 days, the measured QIs with exception of early invasive coronary angiography for non-ST elevation myocardial infarction, were associated with improved survival, and the QIs that had the greatest magnitude for a reduction in mortality were the prescription of secondary prevention medications at discharge; hazard ratio 0.13 (95% CI 0.12–0.14) for statins, 0.16 (95% CI 0.15–0.18) for adequate P2Y12 inhibition, and 0.18 (95% CI 0.17–0.20) for dual antiplatelet therapy (Figure 1). The magnitude of association between the composite QI (CQI) and survival attenuated over time, with greater long-term survival gains observed for the high GRACE risk compared with low- and intermediate-risk (Figure 2). During the first UK lockdown there was an improvement in the attainment for 62.5% of the measured QIs compared with before the COVID-19 pandemic, with a higher attainment for the CQI (43.8% to 45.2%, odds ratio 1.06, 95% CI 1.02–1.10).ConclusionCare quality for AMI may be evaluated using routinely collected clinical data from the national registries, whereby higher performance is associated with reduced mortality. Such QIs will have a role in monitoring hospital care as demonstrated for COVID-19.Funding AcknowledgementType of funding sources: None. Figure 2. QI association with long-term mortality

Serum lactic acid level predicts poor myocardial perfusion and in-hospital outcomes in patients undergoing primary percutaneous coronary intervention

Abstract Background Elevated serum lactic acid level is associated with poor outcomes in patients with critical diseases like shock. However, the clinical implication of this biomarker in patients with acute myocardial infarction remains unclear. Purpose We aimed to explore the predictive power of serum lactic acid level on admission for in-hospital outcomes in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Methods Consecutive patients undergoing pPCI with available data on serum lactid acid level were evaluated for eligbility in this retrospective cohort study. The primary outcome was all-cause death during hospitalization. Enzymatic infarct size and major adverse cardiovascular events (MACE, defined as a combination of all-cause death, recurrent myocardial infarction, and unplanned repeated revascularization) were considered secondary outcomes. Independent preditors of in-hospital death were determined by multiple logisic regression analysis. Odds ratio (OR) with 95% confidence interval (CI) was used to demonstrate the association. The predictive power of serum latictic acid level for in-hospital death was evaluated through receiver operator characteristic curve, which generated C-statictic. A combination model was further constructed by adding serum latictic acid level to the Global Registry of Acute Coronary Events (GRACE) risk score (LA-GRACE risk score). The linear dependence between serum lactic acids level and othe clinical variables was analysed using Spearman rank correlation. Results Of the 302 patients enrolled in the current analysis, 15 (5.0%) died during hospitalization. Serum lactic acid level (OR=1.657, 95% CI: 1.115 to 2.463, p=0.012)and left ventricular ejection fraction (OR=0.858, 95% CI: 0.767 to 0.959, p=0.007) were the only two independent predictors of in-hospital death. The C-statistic of serum lactic acid level for predicting in-hospital death was 0.886 (95% CI: 0.793 to 0.979). The LA-GRACE risk score improved the C-statistic of the GRACE score from 0.898 to 0.911 (p=0.294), with continuous net reclassification improvement of 0.567 (p=0.023) and integrated discrimination improvement of 0.206 (p=0.003). High serum lactic acid level was also asscoiated with larger enzymatic infarct size (p=0.002) and MACE (p=0.004). Further, it significantly correlated with white blood cell counts (r=0.264, p&amp;lt;0.001), serum creatinine level (r=0.189, p=0.001), and systolic blood pressure (r=−0.122, p=0.034). Conclusion Serum lactic acid level on admission is asscoiated with poor myocardial perfusion and in-hospital outcomes in patients with acute myocardial infarction undergoing pPCI. It may contribute to better risk stratification in these populations. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This study was supported by the National Program on Key Basic Research Project of China (Grant No: 2019YFC0840601 and 2014CBA02003), National Natural Science Foundation of China (Grant No: 81870267, 81970295, 81521001, 81670318 and 81570314), Grant of Shanghai Shenkang on Key Clinical Research Project (Grant No: SHDC2020CR2015A and SHDC12019104), Grant of Shanghai Science and Technology Committee (Grant No: 19MC1910300, 18411950200 and 20JC1410800), Key Medical and Health Projects of Xiamen Province (No: 3502Z20204004), Grant of Shanghai Municipal Commission of Health and Family Planning (Grant No: 2017YQ057), Grant of Zhongshan Hospital Affiliated to Fudan University (Grant No: 2018ZSLC01), VG Funding of Clinical Trials (2017-CCA-VG-036) and Merck Funding (Xinxin-merck-fund-051). ROC of lactic acid and GRACE score

The risk-treatment paradox in acute coronary syndrome patients: insights from the FORCE-ACS registry

Abstract Background Acute coronary syndrome (ACS) patients at high risk might benefit most from guideline-recommended interventions. However, it is well recognized that the delivery of guideline-directed care is inversely related to the estimated mortality risk, the so called risk-treatment paradox. Purpose To assess the existence of the risk-treatment paradox in a contemporary cohort of ACS patients and its possible association with one-year mortality. Methods The study population consisted patients enrolled in the FORCE-ACS registry who survived their initial admission. All ACS patients were stratified into low, intermediate or high mortality risk based on the Global Registry of Acute Coronary Events (GRACE) risk score. Optimal guideline-recommended care was defined as undergoing coronary angiography during initial hospital admission and receiving all outpatient medications with a class I guideline recommendation (i.e. aspirin, P2Y12-inhibitor, beta-blocker, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker and cholesterol-lowering drug). Aspirin and/or a P2Y12-inhibitor on top of an oral anticoagulant was also considered as optimal guideline-recommended care. The cumulative incidence of one-year mortality between optimal and suboptimal managed patients, within each GRACE risk score stratum, was estimated. Results In total, 2,524 patients who were enrolled between January 2015 and June 2018 were included. Based on the GRACE risk score, 46.9% of patients were classified as low-risk, 37.6% as intermediate-risk and 15.5% as high-risk. Overall, 49.8% of patients received optimal guideline-recommended care. Among the different risk strata, 54.9% of the low-risk, 49.1% of the intermediate-risk and 36.1% of the high-risk patients received optimal guideline-recommended care (Table 1). DAPT or DAT treatment (95.3% overall) did not differ between the risk categories. Beta-blockers were prescribed less frequently (69.6% overall), butprescription rates did not differ between the risk categories. ACE-inhibitors/ARBs were prescribed in 74.1% of all patients, but less often in high risk patients. Cholesterol lowering-drugs were prescribed in almost all patients (94.9% overall), but less frequently in high risk patients. Overall, 93.9% of patients underwent coronary angiography (CAG), high-risk patients had a statistically significant lower likelihood of undergoing CAG. In all risk categories, optimal guideline-recommended care was associated with a lower one-year mortality as compared to sub-optimal treatment (5.7% vs. 15.6% in high-risk) (Fig. 1). Conclusion Patients at higher estimated mortality risk, based on the GRACE-risk score, are less likely to receive guideline-recommended care. Although, the absolute benefit from guideline-recommended care appears to be greater in high-risk patients. Receiving guideline-recommended care was associated with a statistically significant better prognosis in intermediate- and high-risk patients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): ZonMW Netherlands TopZorgSt. Antonius Research funds Figure 1. All-cause mortality

Cysteine-Rich Angiogenic Inducer 61 Improves Prognostic Accuracy of GRACE (Global Registry of Acute Coronary Events) 2.0 Risk Score in Patients With Acute Coronary Syndromes.

BackgroundIt remains unclear whether the novel biomarker cysteine‐rich angiogenic inducer 61 (CCN1) adds incremental prognostic value to the GRACE 2.0 (Global Registry of Acute Coronary Events) risk score and biomarkers high‐sensitivity Troponin T, hsCRP (high‐sensitivity C‐reactive protein), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) in patients with acute coronary syndromes.Methods and ResultsPatients referred for coronary angiography with a primary diagnosis of acute coronary syndromes were enrolled in the Special Program University Medicine – Acute Coronary Syndromes and Inflammation cohort. The primary/secondary end points were 30‐day/1‐year all‐cause mortality and the composite of all‐cause mortality or myocardial infarction as used in the GRACE risk score. Associations between biomarkers and outcome were assessed using log‐transformed biomarker values and the GRACE risk score (versions 1.0 and 2.0). The incremental value of CCN1 beyond a reference model was assessed using Harrell’s C‐statistics calculated from a Cox proportional‐hazard model. The P value of the C‐statistics was derived from a likelihood ratio test. Among 2168 patients recruited, 1732 could be analyzed. CCN1 was the strongest single predictor of all‐cause mortality at 30 days (hazard ratio [HR], 1.77 [1.31, 2.40]) and 1 year (HR, 1.81 [1.47, 2.22]). Adding CCN1 alone to the GRACE 2.0 risk score improved C‐statistics for prognostic accuracy of all‐cause mortality at 30 days (0.87–0.88) and 1 year (0.81–0.82) and when combined with high‐sensitivity Troponin T, hsCRP, NT‐proBNP for 30 days (0.87–0.91), and for 1‐year follow‐up (0.81–0.84). CCN1 also increased the prognostic value for the composite of all‐cause mortality or myocardial infarction.ConclusionsCCN1 predicts adverse outcomes in patients with acute coronary syndromes adding incremental information to the GRACE risk score, suggesting distinct underlying molecular mechanisms.RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01000701.

Persistence of Lipoproteins and Cholesterol Alterations after Sepsis: Implication for Atherosclerosis Progression.

(1) Background: Sepsis is one of the most common critical care illnesses with increasing survivorship. The quality of life in sepsis survivors is adversely affected by several co-morbidities, including increased incidence of dementia, stroke, cardiac disease and at least temporary deterioration in cognitive dysfunction. One of the potential explanations for their progression is the persistence of lipid profile abnormalities induced during acute sepsis into recovery, resulting in acceleration of atherosclerosis. (2) Methods: This is a targeted review of the abnormalities in the long-term lipid profile abnormalities after sepsis; (3) Results: There is a well-established body of evidence demonstrating acute alteration in lipid profile (HDL-c ↓↓, LDL-C -c ↓↓). In contrast, a limited number of studies demonstrated depression of HDL-c levels with a concomitant increase in LDL-C -c in the wake of sepsis. VLDL-C -c and Lp(a) remained unaltered in few studies as well. Apolipoprotein A1 was altered in survivors suggesting abnormalities in lipoprotein metabolism concomitant to overall lipoprotein abnormalities. However, most of the studies were limited to a four-month follow-up and patient groups were relatively small. Only one study looked at the atherosclerosis progression in sepsis survivors using clinical correlates, demonstrating an acceleration of plaque formation in the aorta, and a large metanalysis suggested an increase in the risk of stroke or acute coronary event between 3% to 9% in sepsis survivors. (4) Conclusions: The limited evidence suggests an emergence and persistence of the proatherogenic lipid profile in sepsis survivors that potentially contributes, along with other factors, to the clinical sequel of atherosclerosis.

Addition of Plasma Myeloperoxidase and Trimethylamine N-Oxide to the GRACE Score Improves Prediction of Near-Term Major Adverse Cardiovascular Events in Patients With ST-Segment Elevation Myocardial Infarction.

Background: The Global Registry of Acute Coronary Events (GRACE) risk score (GRS) is an established powerful model in predicting prognosis of patients with acute coronary syndrome. However, it does not contain pathophysiological biomarkers. Myeloperoxidase (MPO) and trimethylamine N-oxide (TMAO) are novel biomarkers of different pathophysiological processes of acute myocardial infarction, and each of them predicts risk of adverse clinical outcomes. We aimed to investigate whether the addition of MPO and TMAO could improve a GRS-based prediction model in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A prospective cohort of 444 consecutive patients with STEMI who underwent primary percutaneous coronary intervention were enrolled in this study. Plasma levels of MPO and TMAO were measured using samples collected before the interventional procedure. GRS at admission was calculated. Death and nonfatal myocardial infarction were recorded as major adverse cardiac events (MACEs). Kaplan–Meier survival analysis with Cox proportional-hazards regression was used to identify predictive values of MPO and TMAO. Area under the receiver-operator characteristic curve (AUC) and net reclassification improvement (NRI) were calculated to evaluate the increment of predictive value for the combination of MPO and TMAO with GRS in predicting adverse clinical outcomes. Results: During 6 months follow-up, 27 patients suffered MACEs. Both MPO (hazard ratio [HR]: 2.55, 95% confidence interval [CI]: 1.11–5.87; p < 0.05) and TMAO (HR: 4.50, 95% CI: 1.78–11.40, p < 0.01) predicted MACEs at 6 months. The AUC for MPO, TMAO, GRS, and their combination in predicting risk of MACEs at 6 months is 0.642, 0.692, 0.736, and 0.760, respectively. The addition of MPO and TMAO significantly improved the net reclassification of GRS for predicting MACEs at 6 months (NRI: 0.42, p = 0.032). Conclusion: Plasma MPO and TMAO each predict near-term risk of adverse outcomes in patients with STEMI. Furthermore, the combination of MPO and TMAO with GRS enables more accurate prediction of cardiovascular events compared with GRS alone.

Admission Hyperglycemia is Associated with Global Registry of Acute Coronary Events Score and Complications Following Acute Myocardial Infarction During 1-Year Follow-Up.

We explored the effect of admission hyperglycemia (AH) on the Global Registry of Acute Coronary Events (GRACE) risk score and major adverse cardiovascular and cerebrovascular event (MACCE) incidence during 1-year follow-up in acute myocardial infarction (AMI) patients. In this retrospective observational study enrolling 1098 AMI patients, hyperglycemia was defined as blood glucose level ≥180mg/dl at admission. Overall, 158 and 84 patients of 272 diabetic and 826 non-diabetic patients were diagnosed with AH, respectively. Glucose levels at admission were closely associated with the GRACE score in patients with/without diabetes. MACCEs occurred in 222 patients; patients with AH showed significantly higher MACCE incidence (28.1%). Multivariate Cox logistic regression analysis indicated that AH was an independent risk factor for 1-year MACCEs. Subgroup analysis demonstrated that hyperglycemia increases MACCE risk in non-diabetic patients but not in diabetic patients. The admission glucose level combined with GRACE risk score showed a certain predictive value for MACCE incidence according to ROC analysis (OR = 0.798, p < .001). AH was strongly associated with a higher GRACE risk score in ST-segment elevation myocardial infarction patients. Thus, AH was an independent risk factor and had a high predictive value for MACCE during 1-year follow-up after AMI.

Clusters of psycho-social risk factors in patients with coronary heart disease.

Background and Aims: Background: Clusters of psycho-social factors are associated with increased risk for acute coronary events in patients with cardio-vascular diseases. There are no data on prevalence of psycho-social clusters in coronary heart disease patients in Kyrgyz Republic. Aim: to study the type and prevalence of psycho-social factors clusters in patients with coronary heart disease (CHD).

Current Management Guidelines on Hyperlipidemia: The Silent Killer.

Given the high incidence of cardiovascular events in the United States, strict control of modifiable risk factors is important. Pharmacotherapy is helpful in maintaining control of modifiable risk factors such as elevated lipids or hypercholesterolemia. Hypercholesterolemia can lead to atherosclerotic disease which may increase the risk of acute coronary events. Statin therapy has long been a mainstay in the treatment of hypercholesterolemia, but while highly regarded, statin therapy also has side effects that may lead to patient noncompliance. Therefore, various medicines are being developed to manage hypercholesterolemia. This paper will discuss the role that lipids play in the pathophysiology of atherosclerotic disease, review the current lipid management guidelines, and discuss new treatment options that are alternatives to statin therapy.

Association of Major Adverse Cardiovascular Events in Patients With Stroke and Cardiac Wall Motion Abnormalities.

BackgroundThe association of cardiac wall motion abnormalities (CWMAs) in patients with stroke who have major adverse cardiovascular events (MACE) remains unclear. The purpose of this study was to estimate the 50‐month risk of MACE, including stroke recurrence, acute coronary events, and vascular death in patients with stroke who have CWMAs.Methods and ResultsWe performed a retrospective analysis of prospectively collected acute stroke data (acute stroke and transient ischemic attack) over 50 months by electronic medical records. Data included demographic and clinical information, vascular imaging, and echocardiography data including CWMAs and MACE. Of a total of 2653 patients with acute stroke/transient ischemic attack, CWMA was observed in 355 (13.4%). In patients with CWMAs, the embolic stroke of undetermined source (50.7%) was the most frequent index stroke subtype and stroke recurrences (P=0.001). In multivariate Cox regression after adjustment for demographics, traditional risk, and confounding factors, CWMA was independently associated with a higher risk of MACE (adjusted hazard ratio [HR], 1.74; 95% CI, 1.37–2.21 [P=0.001]). Similarly, CWMA independently conferred an increased risk for ischemic stroke recurrence (adjusted HR, 1.50; 95% CI, 1.01–2.17 [P=0.04]), risk of acute coronary events (aHR, 2.50; 95% CI, 1.83–3.40 [P=0.001]) and vascular death (adjusted HR, 1.57; 95% CI, 1.04–2.40 [P=0.03]), in comparison to the patients with stroke without CWMA.ConclusionsIn a multiethnic cohort of ischemic stroke with CWMA, CWMA was associated with 1.7‐fold higher risks of MACE independent of established risk factors. Embolic stroke of undetermined source was the most common stroke association with CWMA. Patients with stroke should be screened for CWMA to identify those at higher risk of MACE.

Quality of acute myocardial infarction care in England and Wales during the COVID-19 pandemic: linked nationwide cohort study

Background and objectiveThe impact of the COVID-19 pandemic on the quality of care for patients with acute myocardial infarction (AMI) is uncertain. We aimed to compare quality of AMI care...

Pubertal Body Mass Index Change Is Associated With Adult Coronary Atherosclerosis and Acute Coronary Events in Men.

OBJECTIVE: The aim with the present study was to evaluate the association between pubertal body mass index (BMI) change and adult coronary artery calcification (CAC) score and risk of acute coronary events. APPROACH AND RESULTS: We included 37 672 men from the BMI Epidemiology Study and calculated their pubertal BMI change (BMI at 20 years−BMI at 8 years). Coronary artery computed tomography analysis of CAC score, midlife BMI, and major risk factors for coronary heart disease were available for a sub-cohort through linkage with the SCAPIS (Swedish Cardio Pulmonary Bioimage Study) cohort (n=922). Information on first acute coronary events was retrieved from Swedish national registers (n=37 672, events n=1873). Pubertal BMI change (odds ratio per SD increase, 1.32 [1.14–1.52]), but not childhood BMI, was associated with middle age CAC score ≥1. This association for pubertal BMI change was maintained after adjustment for midlife BMI at CAC analysis and in a model including major cardiovascular risk factors. Individuals who became overweight during puberty (hazard ratio, 2.11 [1.79–2.49]), but not those overweight at 8 years who normalized their weight during puberty, had substantially increased risk of acute coronary events compared with men who were never overweight. Among subjects with an acute coronary event, individuals with pubertal onset overweight were at increased risk of death due to the event. CONCLUSIONS: Pubertal BMI change is an independent predictor of CAC score and risk of acute coronary events in adult men. Excessive BMI increase during puberty may initiate the coronary atherosclerotic process, thereby increasing the risk and severity of adult acute coronary events.

External validation of the GRACE risk score 2.0 in the contemporary all‐comers GLOBAL LEADERS trial

This study aimed to assess the predictive ability of the Global Registry of Acute Coronary Events (GRACE) risk score 2.0 in contemporary acute coronary syndrome (ACS) patients, and its relation to antiplatelet strategies. The predictive value of the GRACE risk score in the contemporary ACS cohort and the appropriate antiplatelet regimen according to the risk remain unclear. This is a subgroup analysis of the all-comers, randomized GLOBAL LEADERS trial, comparing ticagrelor monotherapy versus conventional dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI). The GRACE risk score 2.0 with 1-year mortality prediction was implemented. The randomized antiplatelet effect was assessed in predefined three GRACE risk-groups; low-risk (GRACE <109), moderate-risk (GRACE 109-140), and high-risk (GRACE >140). The GRACE risk score was available in 6,594 out of 7,487 ACS patients among whom 1,743, 2,823, and 2,028 patients were classified as low-risk, moderate-risk, and high-risk, respectively. At 1 year, all-cause mortality occurred in 120 patients (1.8%). The discrimination ability of the GRACE model was moderate (C-statistic=0.742), whereas 1-year mortality risk was overestimated (mean predicted mortality rate: 3.9%; the Hosmer-Lemeshow chi-square: 21.47; p=0.006). There were no significant interactions between the GRACE risk strata and effects of the ticagrelor monotherapy on ischemic or bleeding outcomes at 1 year compared to the reference strategy. The GRACE risk score 2.0 is valuable in discriminating high risk ACS patients, however, the recalibration of the score is recommended for better risk stratification. There is no significant differences in efficacy and safety of ticagrelor monotherapy across the three GRACE risk strata.

Should we redifine Hypertensive response in stress test to better predict cardiovascular risk?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Systolic blood pressure (SBP) rise during exercise is normal, but some patients present with hypertensive response to exercise (HRE). The clinical implication of such phenomenon is not fully elucidated, and treatment strategies are still uncertain. Purpose To evaluate the relationship between HRE and the development of major cardiovascular events (MACE) - death, acute coronary syndrome (ACS) and stroke. Methods Single-center retrospective study of consecutive patients submitted to exercise test (ET) from 2012 to 2015. Patient’s demographics, baseline clinical characteristics, vital signs during ET and MACE occurrence during follow-up were analysed. HRE was defined as a peak systolic blood pressure (PSBP) &amp;gt;210 mmHg in men and &amp;gt;190 mmHg in women, or a rise of the SBP of 60 mmHg in men or 50 mmHg in women or as a diastolic blood pressure &amp;gt;90 mmHg or a rise of 10 mmHg. Results We included 458 patients with HRE (76% men, 57.5 ± 10.83 years). The most frequent comorbidities were hypertension (83%) and dyslipidaemia (61%). During a mean follow-up of 60 ± 2 months, the incidence of MACE was 9.2% with ACS being the most frequent (4.2%), followed by mortality (3.8%) and stroke (2.1%). Patients with inconclusive ET had a fourfold higher risk of acute coronary events (OR 4.1, CI 95% 1.55-11.14, p = 0.005). Baseline SBP and PSBP were predictors of MACE occurrence (OR 1.022, CI 95% 1.004-1.04, p = 0.016, OR 1.031 CI 95% 1.012-1.051, p = 0.001, respectively) and were both associated with cardiovascular hospitalization (p = 0.006; p &amp;lt; 0.001, respectively). PSBP had moderate ability to predict hospitalization of cardiovascular (CV) cause (AUC 0.71, p &amp;lt; 0.001) with a cut-off of 193 mmHg (sensibility 91%, specify 40%) and had moderate ability to predict MACE (AUC 0.67, p &amp;lt; 0.001) with a cut-off of 198 mmHg (sensibility 78.6%, specify 46.1%). Regarding mortality, antihypertensive therapy prior to ET was protective (p = 0.042), with no difference between different classes of drugs. Conclusion Our data reveal a high rate of MACE occurrence between patients with HRE. The finding of diagnosed hypertension as a protective factor of stroke may be explained by the cardioprotective effect of antihypertensive drugs. An increased risk of ACS between patients with an inconclusive ET should lead to consider then for further investigation. HRE should be considered as part of CV risk assessment and adjusted lower HRE cut-off values should be considered in order to better predict MACE occurrence, particularly in high risk patients. Abstract Figure.