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Background: The inflammatory burden index (IBI), a novel inflammation-based indicator, to is associated with the presence and prognosis of various diseases. However, few studies have focused on exploring the relationship between IBI and the coronary slow flow phenomenon (CSFP). In this study, we aimed to investigate the predictive value of IBI for CSFP in patients with chest pain and no obstructive coronary artery disease., Methods: A total of 1126 individuals with chest pain and no obstructive coronary arteries were consecutively included in this study. 71 patients developed CSFP were included in the CSFP group. A 1:2 age- and sex-matched patient with normal blood flow and angiographically proven normal coronary arteries was selected as the control group (n = 142). Plasma C-reactive protein (CRP), neutrophil, and lymphocyte counts were measured to determine the value of IBI., Results: The IBI were significantly higher in the CSFP group than in the controls (21.1 ± 6.5 vs. 14.5 ± 6.4, P < 0.001). The IBI increasedelevated with the increase of the numbers of vessels affected by CSFP. Multivariate logistic regression analysis revealed that IBI and body mass index (BMI) were independent predictors of CSFP. Receiver operating characteristic (ROC) curve analysis showed that when IBI was > 15.74, the sensitivity and specificity were 77.5% and 67.6%, respectively, and the area under the ROC curve (AUC) was 0.799 (95% CI: 0.737-0.862, P<0.001)., Conclusion: The IBI may be an independent predictor of CSFP in patients with chest pain and normal coronary arteries. The IBI could improve the predictive value of CSFP compared with the indicators alone., (© 2024. The Author(s).)

Background: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) plays a potential role in cardiovascular diseases. However, its association with angina pectoris remains unclear. Herein, we aimed to explore their relationship., Methods: This cross-sectional retrospective study included the 2009-2018 data from 22,562 adults diagnosed with angina pectoris, retrieved from the National Health and Nutrition Examination Survey (NHANES) database. NHHR was estimated from laboratory data, and angina pectoris diagnosis was ascertained from the NHANES questionnaire., Results: Angina pectoris risk was greater in the highest than in the lowest NHHR tertile (odds ratio [OR] = 1.61; 95% confidence interval (CI), 1.15-2.54; P = 0.006). Weighted logistic regression showed a positive association between NHHR and angina pectoris in the fully adjusted model (OR = 1.17; 95% CI, 1.07-1.28; P = 0.001). Restricted cubic spline analysis showed a linear association (P = 0.6572). Subgroup analyses indicated no significant differences across different stratifications (P > 0.05, all). Random forest analyses and Boruta algorithm corroborated that NHHR is a strong predictor of angina pectoris. Among the eight machine-learning models evaluated for predictive capabilities, the logistic regression model demonstrated the strongest predictive capability, with an area under the curve of 0.831., Conclusions: Our study suggests that NHHR is a risk factor for angina pectoris and may be used for risk prediction and to inform future intervention programs to reduce its incidence., (© 2024. The Author(s).)

Purpose: We aimed to explore the causal relationship between human serum metabolites and angina pectoris., Methods: This study used two-sample Mendelian randomization (MR) analysis to assess the association between 486 serum metabolites and angina pectoris. The analytical methods employed to reduce study bias included inverse variance weighted, MR-Egger, and weighted median method. A comprehensive sensitivity analysis was performed using the leave-one-out method, while instrumental variable pleiotropy was tested with MR-Pleiotropy RESidual Sum and Outlier. Metabolic pathways of angina-associated metabolites were analysed on the MetaboAnalyst metabolomics analysis tool platform., Results: In this study, 42 serum metabolites were found to be strongly associated with angina pectoris. They mainly belonged to seven groups: amino acids, carbohydrates, cofactors and vitamins, lipids, nucleotides, unknown metabolites, and exogenous substances. Pipecolate posed the highest risk for the development of angina pectoris among the 42 serum metabolites. The main metabolic pathways associated with angina pectoris were glycine, serine, threonine metabolism, primary bile acid biosynthesis, and caffeine metabolism., Conclusion: We identified 25 high-risk and 17 protective human serum metabolites associated with angina pectoris. Their associated major metabolic pathways were also determined. The serum metabolite pipecolate was significantly and positively correlated with the risk of angina pectoris. This finding may serve as a valuable reference for testing serum markers associated with angina pectoris., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Adult stem cell therapy via intramyocardial injection of autologous CD34+ stem cells has been shown to improve exercise capacity and reduce angina frequency and mortality in patients with refractory angina (RA). However, the cost of such therapy is a limitation to its adoption in clinical practice. Our goal was to determine whether the less costly, less invasive, and widely accessible, FDA-approved alternative treatment for RA patients, known as enhanced external counterpulsation (EECP), mobilizes endogenous CD34+ stem cells and whether such mobilization is associated with the clinical benefits seen with intramyocardial injection. We monitored changes in circulating levels of CD34+/CD133+ and CD34+/KDR+ cells in RA patients undergoing EECP therapy and in a comparator cohort of RA patients undergoing an exercise regimen known as cardiac rehabilitation. Changes in exercise capacity in both cohorts were monitored by measuring treadmill times (TT), double product (DP) scores, and Canadian Cardiovascular Society (CCS) angina scores between pre- and post-treatment treadmill stress tests. Circulating levels of CD34+/CD133+ cells increased in patients undergoing EECP and were significant (β = -2.38, p = 0.012) predictors of improved exercise capacity in these patients. CD34+/CD133+ cells isolated from RA patients could differentiate into endothelial cells, and their numbers increased during EECP therapy. Our results support the hypothesis that mobilized CD34+/CD133+ cells repair vascular damage and increase collateral circulation in RA patients. They further support clinical interventions that can mobilize adult CD34+ stem cells as therapy for patients with RA and other vascular diseases.

Ritonavir (RTV), which is used in combination with nilmatrelvir (NMV) to treat coronavirus disease 2019 (COVID-19), inhibits cytochrome P450 (CYP) 3A, thereby increasing blood tacrolimus (TAC) levels through a drug-drug interaction (DDI). We experienced a case in which a DDI between the two drugs led to markedly increased blood TAC levels, resulting in vasospastic angina (VSA) and acute kidney injury (AKI). Rifampicin (RFP) was administered to induce CYP3A and promote TAC metabolism. A 60-year-old man with dermatomyositis who was taking 3 mg/day TAC contracted COVID-19. The patient started oral NMV/RTV therapy, and he was admitted to the hospital after 4 days because of chest pain and AKI. On day 5, his blood TAC level increased markedly to 119.8 ng/mL. RFP 600 mg was administered once daily for 3 days, and his blood TAC level decreased to the therapeutic range of 9.6 ng/mL on day 9, leading to AKI improvement. Transient complete atrioventricular block and nonsustained ventricular tachycardia were present during chest pain. In the coronary spasm provocation test, complete occlusion was observed in the right coronary artery, leading to a diagnosis of VSA. VSA and AKI are possible side effects of high blood TAC levels caused by DDI, and attention should be paid to cardiovascular side effects such as VSA and AKI associated with increased blood levels of TAC when it is used together with NMV/RTV. When blood levels of TAC increase, oral RFP can rapidly decrease TAC blood levels and potentially reduce its toxicity., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Background: Currently, atherosclerotic cardiovascular disease is the major cause of mortality world-wide. Inflammatory processes are postulated to be a major driving force for coronary plaque initiation and progression and can be evaluated by simple inflammatory markers from whole blood count analysis. Among hematological indexes, systemic inflammatory response index (SIRI) is defined as a quotient of neutrophils and monocytes, divided by lymphocyte count. The aim of the present retrospective analysis was to present the predictive role of SIRI for coronary artery disease (CAD) occurrence., Methods: There were 256 patients (174 [68%] men and 82 [32%] women) in the median (Q1-Q3) age of 67 (58-72) years enrolled into retrospective analysis due to angina pectoris equivalent symptoms. A model for predicting CAD was created based on demographic data and blood cell parameters reflecting an inflammatory response., Results: In patients with single/complex coronary disease the logistic regression multivariable analysis revealed predictive value of male gender (odds ratio [OR]: 3.98, 95% confidence interval [CI]: 1.38-11.42, p = 0.010), age (OR: 5.57, 95% CI: 0.83-0.98, p = 0.001), body mass index (OR: 0.89, 95% CI: 0.81-0.98, p = 0.012), and smoking (OR: 3.66, 95% CI: 1.71-18.22, p = 0.004). Among laboratory parameters, SIRI (OR: 5.52, 95% CI: 1.89-16.15, p = 0.029) and red blood cell distribution width (OR: 3.66, 95% CI: 1.67-8.04, p = 0.001) were found significant., Conclusions: Systemic inflammatory response index, a simple hematological index, may be helpful in patients with angina equivalent symptoms to diagnose CAD. Patients presenting with SIRI above 1.22 (area under the curve: 0.725, p < 0.001) have a higher probability of single and complex coronary disease.

Vitamin D (VD) insufficiency is common among patients with diabetes in French Guiana. The study aimed to evaluate the prevalence of VD deficiency in the different type of diabetes encountered and to analyze the relationship between VD deficiency and diabetes complications., Methods: An observational study was conducted between May 2019 and May 2020 in French Guiana, based on data from the CODIAM study (Diabetes Cohort in French Amazonia), describing the characteristics of patients with diabetes mellitus. Among 600 patients enrolled with diabetes, 361 had an available VD assay., Results: The mean 25(OH)VD (hydroxycalciferol) level was 27.9 ng/mL. The level of VD was inversely proportional to the HbA1c (glycated hemoglobin) level. Patients with angina pectoris had a greater proportion of deficiencies VD < 20 ng/mL than those without angina. By contrast, patients with retinopathy had higher vitamin D concentrations than those without retinopathy. There was no association between vitamin D and arteriopathy, stroke, nephropathy and polyneuropathy. VD deficiency was more frequent in women, and in patients with a high school education., Conclusion: The prevalence of VD deficiency was high in patients with diabetes in French Guiana, emphasizing the importance of VD supplementation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca 2+ -binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Background: Complement activation has been associated with atherosclerosis, atherosclerotic plaque destabilization and increased risk of cardiovascular events. Complement component 7 (CC7) binds to the C5bC6 complex which is part of the terminal complement complex (TCC/C5b-9). High-sensitivity C-reactive protein (hsCRP) is a sensitive marker of systemic inflammation and may reflect the increased inflammatory state associated with cardiovascular disease., Aim: To evaluate the associations between CC7 and total- and cardiac mortality in patients hospitalized with chest-pain of suspected coronary origin, and whether combining CC7 with hsCRP adds prognostic information., Methods: Baseline levels of CC7 were related to 60-months survival in a prospective, observational study of 982 patients hospitalized with a suspected acute coronary syndrome (ACS) at 9 hospitals in Salta, Argentina. A cox regression model, adjusting for conventional cardiovascular risk factors, was fitted with all-cause mortality, cardiac death and sudden cardiac death (SCD) as the dependent variables. A similar Norwegian population of 871 patients was applied to test the reproducibility of results in relation to total death., Results: At follow-up, 173 patients (17.7%) in the Argentinean cohort had died, of these 92 (9.4%) were classified as cardiac death and 59 (6.0%) as SCD. In the Norwegian population, a total of 254 patients (30%) died. In multivariable analysis, CC7 was significantly associated with 60-months all-cause mortality [hazard ratio (HR) 1.26 (95% confidence interval (CI), 1.07-1.47) and cardiac death [HR 1.28 (95% CI 1.02-1.60)], but not with SCD. CC7 was only weakly correlated with hsCRP (r = 0.10, p = 0.002), and there was no statistically significant interaction between the two biomarkers in relation to outcome. The significant association of CC7 with total death was reproduced in the Norwegian population., Conclusions: CC7 was significantly associated with all-cause mortality and cardiac death at 60-months follow-up in chest-pain patients with suspected ACS., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01377402, NCT00521976., (© 2021. The Author(s).)

Angina and no obstructive coronary artery disease (CAD) have an unfavorable prognosis, possibly due to diffuse myocardial fibrosis (DMF). In DMF the proteoglycans biglycan and versican are actively remodeled by matrix metalloproteinase. We investigated biglycan and versican in females with angina and possible DMF assessed by cardiac magnetic resonance (CMR). Seventy-one females with angina and no obstructive CAD were included. Asymptomatic females served as controls. Versican and biglycan were measured and CMR was performed measuring extracellular volume. Biglycan and versican levels were higher in symptomatic females compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p < 0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p < 0.001) and moderately correlated to extracellular volume (r 2 = 0.38, p<0.001 and r 2 = 0.26, p = 0.015). Turnover of biglycan and versican was increased in angina females compared with controls and associated with extracellular volume, supporting a link between angina with no obstructive CAD and fibrotic remodeling., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)

Background: Elevated levels of high-sensitive cardiac troponin T (hs-cTnT) are linked to poor prognosis among emergency department (ED) patients., Objective: Examine the effect of our ED risk assessment among patients with suspected acute coronary syndrome (ACS) and elevated baseline hs-cTnT levels., Design: Observational cohort study of 16776 ED patients with chest pain or dyspnoea and a hs-cTnT sample analyzed at the time of the ED visit. Of these 1480 patients were sent home with elevated hs-cTnT levels (>14 ng/L)., Methods: Analysis of clinical and laboratory data from the local hospital and data from the National Board of Health and Welfare., Results: Admitted patients had 11% and discharged patients had 1.2% 90-day mortality indicating effective risk assessment of patients with suspected ACS. However, if the suspected ACS patient presented with hs-cTnT between 14 and 22 ng/L, the 90-day mortality was 4.1% among discharged and 6.7% among admitted patients. Among discharged patients, an hs-cTnT level above 14 ng/L was a higher independent risk factor for 90-day mortality (HR 3.3, 95% CI 2.9-3.7, p  < 0.001) than if the patient was triaged as a high-risk patient (HR 1.6, 95% CI 1.1-1.8, p  < 0.001)., Conclusions: Our ED risk assessment was less effective among patients presenting with elevated hs-cTnT levels.

Hypokalemia is a common electrolyte disturbance and is related to poor prognosis in patients with cardiovascular disease. However, the role of hypokalemia in patients with vasospastic angina (VSA) has not yet been studied. The present study enrolled 1454 patients diagnosed with VSA according to ergonovine provocation test results and available admission serum potassium data. The primary outcome was a composite of cardiac death, acute coronary syndrome, and new-onset life-threatening arrhythmia. Based on a hypokalemia definition as serum potassium concentration ≤ 3.5 mEq/L, the hypokalaemia group included 70 patients (4.8%). The median potassium levels were 3.4 mEq/L [interquartile range (IQR) 3.3-3.5] in the hypokalemia group and 4.1 mEq/L (IQR 3.9-4.3) in the no-hypokalemia group. The median follow-up duration was 764 days. Primary outcomes occurred in seven patients (10.0%) in the hypokalemia group and 51 patients (3.7%) in the no-hypokalemia group. The Kaplan-Meier analysis showed a higher cumulative incidence of primary outcomes in the hypokalemia group compared to that in the no-hypokalemia group (log-rank P = 0.014). Multivariate Cox regression analysis also showed that hypokalemia was an independent predictor of primary outcomes. In conclusion, hypokalemia at admission was associated with adverse clinical outcomes in VSA.

Epidemiological evidence on the relationship between lipid profile and cardiovascular disease (CVD) events in young adults remains insufficient. Thus, we sought to explore the association of lipid profile with subsequent CVD among young adults. Medical records of 1,451,997 young adults (20 to 49 years old) without prior history of CVD and not taking lipid lowering medications were extracted from the Japan Medical Data Center, a nationwide epidemiological database. We conducted multivariable Cox regression analyses to identify the association between lipid profile and the subsequent risk of CVD and used multiple imputation for missing data on body mass index, waist circumference, hypertension, diabetes mellitus, and cigarette smoking in our database. The mean age was 39.0 ± 7.4 years, and 58.5% were men. After a mean follow-up of 1,148 ± 893 days, myocardial infarction, angina pectoris, stroke, and heart failure developed in 1,638 (0.1%), 15,887 (1.1%), 5,593 (0.4%), and 14,351 (1.0%) subjects, respectively. Multivariable Cox regression analyses including covariates after multiple imputation for missing values demonstrated that LDL-C ≥ 140 mg/dL, HDL-C < 40 mg/dL, and triglycerides ≥ 150 mg/dL were independently associated with the incidence of myocardial infarction, angina pectoris, and heart failure. However, they were not associated with the incidence of stroke. Multivariable Cox regression analyses including the number of abnormal lipid profiles and covariates showed that the incidence of myocardial infarction, angina, and heart failure increased stepwise with the number of abnormal lipid profiles. However, the number of abnormal lipid profiles was not associated with the subsequent risk of stroke. In conclusion, the comprehensive analysis of a nationwide epidemiological database demonstrated a close relationship between lipid profile and subsequent CVD, suggesting the importance of maintaining an optimal lipid profile for the primary prevention of CVD in young generations., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain., Methods: Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used., Results: Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge., Conclusion: Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI., Prospero Registration: CRD42019154716., (© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background Elevated levels of serum homocysteine, via impaired nitric oxide production, and coronary microvascular dysfunction are associated with increased risk of major adverse cardiovascular events. However, whether serum homocysteine levels and coronary microvascular endothelial dysfunction (CMED) are linked remains unknown. Methods and Results This study included 1418 patients with chest pain or an abnormal functional stress test and with nonobstructive coronary artery disease (<40% angiographic stenosis), who underwent CMED evaluation with functional angiography and had serum homocysteine levels measured. Patients were classified as having normal microvascular function versus CMED. Patients in the CMED group (n=743; 52%) had higher mean age (52.1±12.2 versus 50.0±12.4 years; P <0.0001), higher body mass index (29.1 [25.0-32.8] versus 27.5 [24.2-32.4]; P =0.001), diabetes mellitus (12.5% versus 9.4%; P =0.03), and fewer women (63.5% versus 68.7%; P =0.04) compared with patients in the normal microvascular function group. However, they had lower rates of smoking history, and mildly lower low-density lipoprotein cholesterol levels. Serum homocysteine levels were significantly higher in patients with CMED, and the highest quartile of serum homocysteine level (>9 µmol/L) was an independent predictor of CMED (odds ratio, 1.34 [95% CI, 1.03-1.75]; P =0.03) after adjustment for age; sex; body mass index; chronic kidney disease (CKD); diabetes mellitus; smoking exposure; low-density lipoprotein cholesterol; high-density lipoprotein cholesterol and triglycerides; and aspirin, statin, and B vitamin use. Conclusions Patients with CMED have significantly higher levels of serum homocysteine. Elevated serum homocysteine levels were associated with a significantly increased odds of an invasive diagnosis of CMED. The current study supports a potential role for homocysteine for diagnosis and target treatment in the patients with early coronary atherosclerosis.

Introduction: The clinical effectiveness of a 'rule-out' acute coronary syndrome (ACS) strategy for emergency department patients with chest pain, incorporating a single undetectable high-sensitivity cardiac troponin (hs-cTn) taken at presentation, together with a non-ischaemic ECG, remains unknown., Methods: A randomised controlled trial, across eight hospitals in the UK, aimed to establish the clinical effectiveness of an undetectable hs-cTn and ECG (limit of detection and ECG discharge (LoDED)) discharge strategy. Eligible adult patients presented with chest pain; the treating clinician intended to perform investigations to rule out an ACS; the initial ECG was non-ischaemic; and peak symptoms occurred <6 hours previously. Participants were randomised 1:1 to either the LoDED strategy or the usual rule-out strategy. The primary outcome was discharge from the hospital within 4 hours of arrival, without a major adverse cardiac event (MACE) within 30 days., Results: Between June 2018 and March 2019, 632 patients were randomised; 3 were later withdrawn. Of 629 patients (age 53.8 (SD 16.1) years, 41% women), 7% had a MACE within 30 days. For the LoDED strategy, 141 of 309 (46%) patients were discharged within 4 hours, without MACE within 30 days, and for usual care, 114 of 311 (37%); pooled adjusted OR 1.58 (95% CI 0.84 to 2.98). No patient with an initial undetectable hs-cTn had a MACE within 30 days., Conclusion: The LoDED strategy facilitates safe early discharge in >40% of patients with chest pain. Clinical effectiveness is variable when compared with existing rule-out strategies and influenced by wider system factors., Trial Registration Number: ISRCTN86184521., Competing Interests: Competing interests: EC has received funding from Abbott Diagnostics for related research and honoraria for education from Roche., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators were involved in the pathogenesis of atherosclerosis. This study sought to investigate the effects of proatherogenic inflammatory and antiatherogenic inflammatory mediators on the proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations. We measured the expression levels of proatherogenic inflammatory/antiatherogenic inflammatory cytokines. This included interleukin-1 β (IL-1 β ), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor- α (TNF- α ), high-sensitivity C-reactive protein (hs-CRP), interleukin-10 (IL-10), interleukin-17 (IL-17), interleukin-13 (IL-13), and interleukin-37 (IL-37) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions after coronary stent implantations. Levels of IL-1 β , IL-6, IL-8, TNF- α , and hs-CRP were remarkably increased ( P < 0.001), and levels of IL-10, IL-17, IL-13, and IL-37 were remarkably lowered ( P < 0.001) in the elderly patients with the proximal, middle, and distal coronary artery reocclusions. Imbalances of proatherogenic inflammatory and antiatherogenic inflammatory mediators may be involved in the formation and progression of proximal, middle, and distal coronary artery reocclusions in elderly patients after coronary stent implantations., Competing Interests: The authors declare that they have no competing interests regarding the publication of this article., (Copyright © 2020 Xia Li et al.)

We investigated if brain-derived neurotrophic factor (BDNF) accumulation after glucose intake could predict cardiovascular outcomes. We enrolled patients admitted for angiography due to angina. After their conditions stabilized, serum BDNF levels were detected at 0, 30, and 120 min during oral glucose tolerance test (OGTT). Area under the curve (AUC) of BDNF was calculated. The first occurrence of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality served as the primary composite endpoint. Of 480 enrolled patients, 428 completed the follow-up, and 36 primary endpoint events occurred during a median follow-up of 4.4 years. The area under the receiver operating characteristic curve significantly increased from 0.61 (95% confidence interval (CI): 0.52-0.73) for the Framingham risk score (FRS) alone model to 0.72 (95%CI: 0.63-0.81) for the AUC of BDNF plus FRS model ( p = 0.016) for predicting the primary endpoint, but not to 0.65 (95%CI: 0.55-0.75) for the fasting BDNF plus FRS model ( p = 0.160). Grouped by median AUC of BDNF of 38.0 (ng/mL) × h, the low BDNF group had a significantly higher risk of the endpoint than the high BDNF group (hazard ratio = 3.410, 95%CI: 1.520-7.653, p = 0.003). In conclusion, AUC of BDNF during OGTT could be superior to fasting BDNF for predicting a low cardiovascular risk.

Objective: We assessed the diagnostic and prognostic implications of early cardiac magnetic resonance (CMR), CMR-based deformation imaging and conventional risk factors in patients with troponin-positive acute chest pain and non-obstructed coronary arteries., Methods: In total, 255 patients presenting between 2009 and 2019 with troponin-positive acute chest pain and non-obstructed coronary arteries who underwent CMR in ≤7 days were followed for a clinical endpoint of all-cause mortality. Cine movies, T2-weighted and late gadolinium-enhanced images were evaluated to establish a diagnosis of the underlying heart disease. Further CMR analysis, including left ventricular strain, was carried out., Results: CMR (performed at a mean of 2.7 days) provided the diagnosis in 86% of patients (54% myocarditis, 22% myocardial infarction (MI) and 10% Takotsubo syndrome and myocardial contusion (n=1)). The 4-year mortality for a diagnosis of MI, myocarditis, Takotsubo and normal CMR patients was 10.2%, 1.6%, 27.3% and 0%, respectively. We found a strong association between CMR diagnosis and mortality (log-rank: 24, p<0.0001). Takotsubo and MI as the diagnosis, age, hypertension, diabetes, female sex, ejection fraction, stroke volume index and most of the investigated strain parameters were univariate predictors of mortality; however, in the multivariate analysis, only hypertension and circumferential mechanical dispersion measured by strain analysis were independent predictors of mortality., Conclusions: CMR performed in the early phase establishes the proper diagnosis in patients with troponin-positive acute chest pain and non-obstructed coronary arteries and provides additional prognostic factors. This may indicate that CMR could play an additional role in risk stratification in this patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives : Guidelines recommend a single high-sensitivity cardiac troponin T (hs-cTnT) ≤14 ng/L measured ≥6 h after chest pain onset combined with a GRACE score <140 and the patient being pain-free for ruling out myocardial infarction (MI). There is however little data on the performance of this strategy. We therefore aimed to evaluate the diagnostic accuracy of a hs-cTnT ≤14 ng/L measured ≥6 h after chest pain onset when combined with GRACE score or other clinical risk stratification tools. Design : This was a secondary analysis of a prospective observational study, which enrolled emergency department (ED) chest pain patients. The hs-cTnT strategy was combined with HEART, TIMI, EDACS, GRACE score and ED physician's overall assessment of patient history and ECG. The primary outcome was MI, and the secondary outcome was 30-day major adverse cardiac events (MACE). Results : All tested diagnostic strategies were shown to have a negative predictive value (NPV) ≥99.5% for ruling out MI. Using HEART, TIMI, EDACS or ECG + patient history also resulted in a NPV ≥98% for ruling out 30-day MACE. An isolated hs-cTnT ≤14 ng/L measured ≥6 h after chest pain onset and the combination with GRACE score both had a NPV <98% for ruling out 30-day MACE. Conclusion : A single hs-cTnT ≤14 ng/L obtained ≥6 h from chest pain onset, with and without GRACE score, reliably ruled out MI but did not perform well for ruling out 30-day MACE. These results question current guideline recommendations, and indicate that HEART, EDACS, TIMI, or ECG + patient history strategies should be the preferred risk stratification tools.

Introduction: Cardiovascular disease (CAD) associated with death and disability remains a serious medical problem. In some patients the initial clinical coronary artery disease presentation is stable angina pectoris., Aim: The aim of the study was to evaluate the effect of EECP therapy with or without trimetazidine (TMZ) in patients with refractory angina via modulating peripheral monocyte expression of Toll like receptor2 (TLR2) and its downstream signaling., Methods: This is a double-blind randomized prospective study in which 88 stable refractory angina patients allocated into two groups, Enhanced External Counter Pulsation (EECP) group: included 44 patients with stable refractory angina, and were treated with EECP-Therapy. TMZ-EECP group: included 44 patients with stable refractory angina, we gave TMZ 35 mg twice daily in addition to EECP-Therapy., Results: TLR2 expression in peripheral monocyte investigated by flow cytometry and 8-iso-prostaglandin F2β (8-iso-PGF2 β), interleukin1β (IL-1β), heat shock protein 60 (HSP60) and monocytes chemoattractant protein-1(MCP-1) were also measured before the EECP-therapy and before giving TMZ to patients, and after 35 hours of EECP treatment (7 consecutive weeks). Inhibition in TLR2 expression in peripheral monocyte was observed among the EECP group (P<0.05). Inflammatory cytokine MCP-1 was remarkably decreased in both study groups but (heat shock protein 60 (HSP60), MCP-1 and interleukin-1β (IL-1β)) significantly decreased levels were observed among the TMZ-EECP group (P<0.05). Also, the oxidative stress biomarker 8-iso-prostaglandin F2β (8-iso-PGF2β) was decreased in both study groups but significantly decreased levels were observed among the TMZ-EECP group (P<0.05). TMZ and EECP therapy in patients with stable refractory angina remarkably decreased the inflammatory markers HSP60, MCP-1 and IL-1β in serum levels also the decreased levels were found in serum levels of oxidative stress marker 8-iso-PGF2β serum level., Conclusion: EECP-therapy decreased the expression of TLR2 on peripheral monocytes in patients with chronic stable refractory angina which yield improvement in the quality of patients' life by decreasing the frequency of angina episodes, decreasing the Short-acting nitrate use and change the exercise tolerance and distance., Competing Interests: The authors declare no conflict of interest., (© 2020 Saad Rasool Shaker, Fadhil Al-Amran, Ghizal Fatima, Hayder Al-Aubaid, Najah R. Hadi.)

Coronary artery anomalies are rare congenital variants of coronary artery anatomy accounting second most common cause of sudden cardiac death in young competitive athletes. A single ostium coronary artery anomalous is an extremely rare variant with an incidence of less than 0.004%. They may present as chest pain, arrhythmia, or sudden death. Recently, advanced imaging techniques such as computed tomography and magnetic resonance imaging coronary angiography are becoming the alternatives investigation for diagnosis. We reported a rare case of 50 years old lady who presented with acute chest pain with normal electrocardiography, echocardiography, and cardiac markers. Coronary Computed tomography angiography revealed anomalous coronary artery anatomy with both right and left coronary artery arising from the large common trunk of the right coronary cusp, left main coronary artery having trans-septal course, there was no flow-limiting coronary artery disease. She was medically managed with a single antiplatelet, beta-blocker, and statin therapy.

Associations between elevated C-reactive protein (CRP) levels and the angina pectoris risk have been reported for many years, but the results remain controversial. To address this issue, a meta-analysis was therefore conducted. Eligible studies were identified by searching PubMed, EMBASE, Cochrane library, and web of science up to January 2019. Altogether, 10 prospective cohort studies and 11 case-control studies were included, and they were published from 1997 to 2013 and summed up to 18,316 samples totally. The pooled mean difference of CRP levels was 4.44 (95% confidence interval 2.71 to 6.17) between angina patients and healthy controls. The combined odds ratio of CRP for major adverse cardiac events in angina patients was 1.67 (95% CI 1.23 to 2.26). In conclusion, the meta-analysis indicated that elevated CRP levels were associated with angina pectoris, especially unstable angina pectoris, and were probably a risk factor of major adverse cardiac events., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Accumulating evidence suggests that C-type lectin-like receptor-2 (CLEC-2) plays an important role in atherothrombosis. In this case-control study, we investigated the association between CLEC-2 and incidence of coronary artery disease (CAD). A total of 216 patients, including 14 cases of stable angina pectoris (SAP, non-ACS) and 202 cases of acute coronary syndrome (ACS), and 89 non-CAD control subjects were enrolled. Plasma levels of soluble CLEC-2 (sCLEC-2) were measured using the enzyme-linked immunosorbent assay (ELISA). Compared with the control group (65.69 (55.36-143.22) pg/mL), the plasma levels of sCLEC-2 were significantly increased in patients with CAD (133.67 (88.76-220.09) pg/mL) and ACS (134.16 (88.88-225.81) pg/mL). The multivariate adjusted odds ratios (95% confidence interval) of CAD reached 2.01 (1.52-2.66) (P trend < 0.001) for each 1-quartile increase in sCLEC-2. Restricted cubic splines showed a positive dose-response association between sCLEC2 and CAD incidence (P linearity < 0.001). The addition of sCLEC-2 to conventional risk factors improved the C statistic (0.821 vs. 0.761, P = 0.004) and reclassification ability (net reclassification improvement: 57.45%, P < 0.001; integrated discrimination improvement: 8.27%, P < 0.001) for CAD. In conclusion, high plasma sCLEC-2 is independently associated with CAD risk, and the prognostic value of sCLEC-2 may be evaluated in future prospective studies.

Competing Interests: Competing interests: The authors are all members of the International Federation of Clinical Chemists Committee on Clinical Applications of Cardiac Bio-Markers (C-CB).

Background: Impaired epicardial coronary vasomotion is a potential mechanism of angina and a predictor of adverse cardiovascular outcomes in patients without angiographic evidence of obstructive coronary artery disease (CAD). We sought to evaluate the association of asymmetric dimethylarginine (ADMA)-a marker of nitric oxide-mediated vascular dysfunction-with epicardial coronary vasomotor dysfunction in this select population., Methods: Invasive testing for epicardial vasomotor dysfunction was performed using intracoronary acetylcholine in the left anterior descending coronary artery. Impaired vasomotor response was defined as a luminal constriction of >20% on quantitative coronary angiography. Plasma ADMA levels were measured using high performance liquid chromatography. A robust multivariate linear mixed-effect model approach and Akaike information criterion were used to determine predictors of vasomotor dysfunction., Results: In 191 patients with angina in the absence of obstructive CAD, abnormal epicardial vasomotion was observed in 137 (71.7%) patients. Median ADMA rose as the extent of impairment progressed: none (0.48 [0.44-0.59] μM), any (0.51 [0.46-0.60] μM, p = 0.12), focal (0.54 [0.49,0.61] μM, p = 0.17), and diffuse (0.55 [0.49,0.63] μM, p = 0.02). In unadjusted analysis, ADMA was highly predictive of vasomotor dysfunction (χ 2 =15.1, p = 0.002). Notably, ADMA remained a significant predictor even after adjusting for other factors in the best fit model (χ 2 =10.0, p = 0.02)., Conclusions: ADMA is an independent predictor of epicardial coronary vasomotor dysfunction in patients with angina in the absence of obstructive CAD. These data support a very early mechanistic role of ADMA in the continuum of atherosclerotic heart disease., (Copyright © 2019 Elsevier B.V. All rights reserved.)

BACKGROUND The aim of the present study was to investigate the clinical predictive value of pre-infarction angina (PIA) combined with mean platelet volume to lymphocyte count ratio (MPVLR) for no-reflow phenomenon and short-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS A total of 1009 STEMI patients who had undergone PCI were enrolled and subdivided into 4 groups based on the occurrence of PIA and the presence of MPVLR above or below the cutoff value. Analysis of the predictors of the no-reflow phenomenon and 90-day mortality was conducted. Further, evaluation and comparison of the clinical predictive value of PIA, MPVLR, and their combination were done. RESULTS Both MPVLR (odds ratio [OR]=1.476, 95% confidence interval [CI]: 1.401 to 1.756, P <0.001; hazard ratio [HR]=1.430, 95% CI: 1.287 to 1.643, P <0.001) and PIA (OR=0.905, 95% CI: 0.783 to 0.986, P <0.001; HR=0.878, 95% CI: 0.796 to 0.948, P <0.001) were independent predictors of no-reflow phenomenon and 90-day mortality. Spearman's rank correlation test revealed that MPVLR (r=-0.297, P <0.001), monocyte to lymphocyte count ratio (MLR) (r=-0.211, P <0.001) and neutrophil to lymphocyte count ratio (NLR) (r=-0.389, P <0.001) in peripheral blood were significantly negatively correlated with postoperative left ventricular ejection fraction (LVEF). Upon comparing the area under curve (AUC), the MPVLR combined with PIA achieved better performance in differentiating no-reflow phenomenon (AUC=0.847, 95% CI: 0.821 to 0.874) and 90-day mortality (AUC=0.790, 95% CI: 0.725 to 0.855), than the GRACE score, MPVLR and PIA alone, and had similar performance to all other pairwise combinations of the GRACE score, MPVLR and PIA. CONCLUSIONS High MPVLR and PIA were independent predictors of the no-reflow phenomenon and 90-day mortality in patients with STEMI after PCI. Moreover, Combined application of MPVLR and PIA can effectively predict the occurrence of the no-reflow phenomenon and 90-day mortality.

The aims of this study were to evaluate the efficacy of corn silk decoction on lipid profile in patients with angina pectoris. PubMed, Cochrane, Embase, Google Scholar, Chongqing VIP Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, and Wanfang database were searched up to January 2019 for randomized controlled trials that assessed the impact of corn silk decoction on total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol in patients with angina pectoris. Study evaluation and synthesis methods were in accordance with the Cochrane Handbook, and data were analyzed using Review Manager (version 5.3) software. Random effects model was applied in this systematic review and meta-analysis to compensate for potential heterogeneity among the included studies. A total of four randomized controlled trials were eligible for meta-analysis. Pooled results of these studies indicated that corn silk decoction might improve high-density lipoprotein cholesterol and reduce total cholesterol, triglycerides, and low-density lipoprotein cholesterol in patients with angina pectoris. Subgroup analyses showed that corn silk decoction or modified corn silk decoction plus conventional pharmaceutical treatment could have favorable effects on blood lipids. However, the lack of blinding in most studies may have led to overestimation of these effects. Further studies with better design are needed to confirm these findings., (© 2019 John Wiley & Sons, Ltd.)

Women more often present with angina and non-obstructive coronary artery disease (ANOCA) and have poorer clinical outcomes than men. These findings may be related to sex associated differences in inflammation and thrombogenicity. Consecutive patients (n = 134) with ANOCA (luminal diameter stenosis < 50%) undergoing elective cardiac catheterization were included in post hoc analysis of Multi-Analyte, thrombogenic, and Genetic Markers of Atherosclerosis (MAGMA, NCT01276678) study. Patients with prior revascularization, coronary artery bypass grafting or myocardial infarction were excluded. Blood for thromboelastography, oxidized LDL β2-glycoprotein complex (AtherOx), oxidized-LDL, lipid profile, and urine for 11-dehydrothromboxane B 2 (dTxB 2 ) were obtained before catheterization. All women (n = 75) were post-menopausal and tended to be older than men (61.4 ± 10.6 vs. 58.6 ± 9.9 year, p = 0.12), and were significantly more thrombogenic with higher thrombin-induced platelet-fibrin strength (TIP-FCS, mm) (68.0 ± 4.5 vs. 64.5 ± 6.2 mm, p = 0.001), clotting index (0.35 ± 2.22 vs. - 0.72 ± 2.75, p = 0.02), K (measure of the speed to reach 20 mm of clot strength from an amplitude of 2 mm) (2.2 ± 1.6 vs. 1.7 ± 0.5 min, p = 0.01), and fibrinogen activity (degrees) (66.6 ± 7.1 vs. 62.9 ± 7.5, p = 0.009). Markers of inflammation were not significantly different between the two groups. Women had higher total cholesterol, total LDL, LDL subtypes 1 and 2, total HDL, HDL subtypes 2 and 3, and ApoA1 (p < 0.05 for all). On multivariate regression, TIP-FCS remained significantly higher in women (p < 0.0001). Women with ANOCA are more thrombogenic than men. This fundamental difference in thrombogenicity may affect gender-related outcomes and warrants further investigation.

Coronary artery spasm (CAS) is one of the mechanisms of angina pectoris. Unlike the diagnosis of acute myocardial infarction which is based on the elevation of cardiac markers, the diagnosis of CAS is difficult and sometimes requires sophisticated and risky provocative test which is not widely accepted in China. There is no well-established biomarker for the diagnosis or prediction of CAS. However, there are some biomarkers proven to be associated with the occurrence of CAS. For example, inflammatory factors including C-reactive protein and cytokines, lipoprotein (a), and cystatin-C might be precipitating factor for CAS. Rho-kinase as a mediator involved in multiple mechanisms of CAS, serotonin, and endothelin-1 as powerful vasoconstrictors leading to vasospasm were all observed being elevated in patients with CAS. Thioredoxin and nitrotyrosine reflected the oxidative status and could be observed to be elevated after the occurrence of CAS. In some cases doubted to be CAS without the evidence of provocative test, the blood test for the biomarkers mentioned above could be useful for the diagnosis of CAS., Competing Interests: The authors declare that there is no conflict of interest., (Copyright © 2019 Liang Li et al.)

Background: A decade ago, statin persistence was < 50% after 1 year, and recent short-term analyses have revealed very little progress in improving statin persistence, even in patients with a prior cardiovascular (CV) event. Data on longer-term statin persistence are lacking. We measured long-term statin persistence in patients with high CV risk., Methods: This retrospective administrative claims analysis of the Optum Research Database included patients aged ≥ 45 years with diabetes and/or atherosclerotic CV disease (ASCVD) who had a statin prescription filled in 2010. It included an elevated triglycerides (TG) cohort of patients with index date in 2010 and TG ≥ 150 mg/dL (n = 23,181) and a propensity-matched comparator cohort with TG < 150 mg/dL and high-density lipoprotein cholesterol > 40 mg/dL (n = 23,181). Both cohorts were followed for ≥ 6 months up to March 2016., Results: The probability of remaining on a prescription fill for index statin therapy was 47% after 1 year and 19% after 5 years in both cohorts. Statin persistence was worse among women than men, and among younger versus older patients (P < 0.001 for all comparisons). After 5 years, the probability of remaining on a prescription fill for index statin was < 25% across all subgroups assessed including patients with and without baseline revascularization, heart failure, peripheral artery disease and renal disease. Similar results were observed in a subcohort analysis of patients with TG 200-499 mg/dL., Conclusions: Long-term statin persistence after 5 years is alarmingly low (< 25%) and is a public health concern.

Background: Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis., Objectives: The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a)., Methods: In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays., Results: Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham., Conclusion: Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina., (Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Currently, there are no clinical scores for risk stratification of low-risk patients with chest pain. We aimed to examine the association between mean platelet volume (MPV) and risk for adverse clinical outcomes in patients with chest pain discharged from internal medicine wards following acute coronary syndrome (ACS) rule-out., Patients and Methods: Included were patients who were admitted to internal medicine wards and were discharged following an ACS-rule-out during 2010-2016. The primary endpoint was the composite of all-cause mortality and hospital admission due to ACS at 30-days following hospital discharge., Results: Included in the study were12 440 patients who were divided into three groups according to MPV. The composite endpoint of 30-day all-cause mortality and hospital admission for ACS occurred more frequently among patients with high MPV. Each one-point increase in MPV was associated with an 18% increase in the risk for the composite endpoint (P = 0.02). Considering patients with MPV less than 7.8 fl as the reference group yielded adjusted hazard ratios for the composite endpoint that was significantly higher in patients in the high MPV tertile ( > 8.8 fl) (hazard ratio 1.6; 95% confidence interval = 1.1-2.5; P = 0.04). Each one-point increase in MPV was associated with an 11% increase in the risk for 1-year all-cause mortality (P = 0.01) and a 10% increase in the risk for 1-year ACS (P = 0.04)., Conclusion: We found an independent association between high MPV and the risk of death and ACS among patients with chest pain who were discharged from internal medicine wards following an ACS-rule-out. MPV may be combined in the risk stratification of patients with chest pain.

Fibroblast growth factor 21 (FGF21) is a metabolic hormone having anti-oxidative and anti-hypertrophic effects. However, the regulation of FGF21 expression during acute myocardial infarction (AMI) remains unclear. We tested blood samples from 50 patients with AMI and 43 patients with stable angina pectoris (sAP) for FGF21, fatty acid binding protein 4 (FABP4), a protein secreted from adipocytes in response to adrenergic lipolytic signal, and total and individual fatty acids. Compared with sAP patients, AMI patients had higher serum FGF21 levels on admission, which were significantly correlated with peak FABP4 and saturated fatty acids (SFAs) but not with peak levels of cardiac troponin T. In mice, myocardial ischemia rapidly induced FGF21 production by the heart, which accompanied activation of AMP-activated protein kinase (AMPK)-dependent pathway. Like AICAR, an activator of AMPK, catecholamines (norepinephrine and isoproterenol) and SFAs (palmitate and stearate) significantly increased FGF21 production and release by cardiac myocytes via AMPK activation. Recombinant FGF21 induced its own expression as well as members of down-stream targets of AMPK involved in metabolic homeostasis and mitochondrial biogenesis in cardiac myocytes. These findings suggest that adrenergic overdrive and resultant adipose tissue lipolysis induce cardiac AMPK-FGF21 feed-forward loop that potentially provides cardioprotection against ischemic damage.

Background: More sensitive troponin assays have the potential to better evaluate patients with suspected acute coronary syndrome (ACS). Meanwhile, they may result in avoidable diagnostic testing., Hypothesis: Our aim was to determine the clinical impact of implementing a more sensitive cardiac troponin I (cTnI) assay in patients with acute non-traumatic chest pain presenting to the emergency department (ED)., Methods: This is a pre-post cohort study. A total of 1201 consecutive patients with acute non-traumatic chest pain or equivalent ischemic symptoms suggestive of ACS were allocated to two groups according to the cTnI assay used. The outcomes included the ED length of stay (LOS), hospital admission rate, the use of procedures and the incidence of major adverse cardiac events (MACE) at 30 days., Results: The introduction of the more sensitive troponin assay shortened ED LOS (odds ratio [OR] 0.39, 95% confidence interval [CI] 0.28-0.54) regarding patients discharged home directly, increased the hospital admission rate (OR 1.43, 95% CI 1.12-1.84), the use of echocardiography (OR 1.58, 95% CI 1.22-2.06), coronary computed tomography angiography (OR 1.78, 95% CI 1.04-3.06), coronary angiography (OR 1.53, 95% CI 1.10-2.12) and percutaneous coronary intervention (OR 2.42, 95% CI 1.58-3.70) regarding patients discharged or admitted. The incidence of MACE did not decrease significantly (OR 0.61, 95% CI 0.27-1.37)., Conclusions: The introduction of the more sensitive troponin assay appeared to result in less time spent in the ED regarding patients discharged home directly, but prompted more hospitalizations and procedures without impacting the incidence of MACE., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Objective: To analyze the correlation of lipoprotein(a) [Lp(a)] with the clinical stability and severity of coronary artery stenosis in patients with coronary artery disease (CAD)., Methods: A total of 531 patients undergoing coronary angiography in Nanfang Hospital between January, 2013 and December, 2016 were enrolled in this study. At the cutoff Lp(a) concentration of 300 mg/L, the patients were divided into high Lp(a) group ( n =191) and low Lp(a) group ( n =340). In each group, the patients with an established diagnosis of CAD based on coronary angiography findings were further divided into stable angina pectoris (SAP) group and acute coronary syndrome (ACS) group. The correlation between the severity of coronary artery stenosis and Lp(a) was evaluated., Results: The patients in high and low Lp(a) groups showed no significant differences in age, gender, body mass index, smoking status, hypertension, or diabetes ( P &gt;0.05). Multivariate logistic regression analysis revealed that age, gender, and serum levels of low-density lipoprotein cholesterol (LDL-C) and Lp(a) were independent risk factors for CAD in these patients. A high Lp(a) level was associated with an increased risk of CAD (OR=2.443, 95%CI: 1.205-4.951, P =0.013). The patients with a high Lp(a) level were at a significantly higher risk of CAD than those with a low Lp(a) level irrespective of a low or high level of LDL-C ( P =0.006 and 0.020). In the patients with CAD, the ACS group had a significantly higher Lp(a) level than the SAP group ( P &lt; 0.001); the proportion of the patients with high Gensini scores was significantly greater in high Lp(a) group than in low Lp(a) group (17.3% vs 5.6%, P =0.026), and a linear relationship was found between Lp(a) level and Gensini score (R=0.130, P =0.006)., Conclusions: Serum level of Lp(a) is an independent risk factor for CAD, and an increased Lp(a) is the residual risk for CAD. In patients with CAD, a high Lp(a) level is associated with the clinical instability and severity of coronary artery stenosis.

Background: To investigate the early diagnostic and prognostic value of microRNA-1 in patients with acute chest pain., Methods: This study enrolled 341 patients attacked by chest pain within 3 h, and another 100 volunteers as control group. Circulating microRNA-1 was collected and determined by real-time quantitative reverse transcription-polymerase chain reaction. The clinical follow-up period was 720 days., Results: There were 174 patients in acute myocardial infarction (AMI) group, 167 in non-AMI group. The relative expression of microRNA-1 was significantly increased within 3 h in AMI group, and it continued rising within 12 h, lower at 24 h than that 12 h in AMI group without reperfusion therapy. Otherwise, microRNA-1 concentration was markedly low at 12 h after primary percutaneous coronary intervention in AMI group. The 95% reference range of circulating microRNA-1 was 0.171-0.653. It was significantly available for microRNA-1 to early diagnose AMI with an optimal cutoff value of 2.215 and diagnostic accuracy could be improved when combined with cardiac troponin I. It was not statistically significant for microRNA-1 to forecast future AMI but might prognose mortality of 720 days in chest pain patients. In patients with chest pain, microRNA-1 concentration was high with major adverse cardiac events within 30 days, low with high overall survival within 720 days., Conclusions: Circulating microRNA-1 might diagnose early AMI and predict the prognosis of patients with chest pain.

Objective: We investigated whether echocardiography may help identify, among patients admitted with a suspect of non-ST-segment elevation acute myocardial infarction (NSTEMI), those with athero-thrombotic coronary artery disease (CAD)., Patients and Methods: We studied consecutive patients admitted with a clinical suspect of first NSTEMI. Echocardiography was assessed within 24 hours from admission. Patients were divided into two groups, according to the results of coronary angiography: 1) patients with obstructive stenosis (≥ 50%) and/or images of thrombosis in one or more coronary arteries (CAD group); 2) patients with no evidence of obstructive coronary arteries (NOCAD group)., Results: Of 101 patients enrolled in the study, 53 (52.5%) showed obstructive CAD and 48 (47.5%) NOCAD. At echocardiographic examination, regional wall motion abnormalities were found in 52.8% of patients in the CAD group and 43.7% in the NOCAD group (p=0.43). Left ventricle ejection fraction was 56.4±6.8 vs. 54.7±9.8% (p=0.30) and wall motion score index was 1.16±0.26 vs. 1.21±0.32 (p=0.39) in the two groups, respectively. A multivariable logistic regression independent predictors of obstructive CAD included age, male gender, typical angina, diabetes and hypertension., Conclusions: Our data showed that, in patients with acute chest pain and increased serum troponin T concentration, routine standard echocardiography does not significantly improve the diagnostic accuracy for the presence of obstructive CAD.

Objectives: Chest pain is a common complaint in the emergency department (ED), and it is a challenge to identify low-risk chest pain patients eligible for early discharge. We aimed to develop a simple objective decision rule to exclude 30-day major adverse cardiac events (MACE) in ED chest pain patients., Design: We analyzed prospectively included patients presenting with chest pain. Low risk patients were identified with the clinical objective rule-out evaluation (CORE). CORE was based on high sensitivity cardiac troponin T (hs-cTnT) tests at ED presentation (0 h) and 2 h later together with a simplified risk score consisting of four objective variables: age ≥65 years and a history of arterial disease, hypertension or diabetes. For the patient to be classified as low risk in the CORE rule, hs-cTnT had to be ≤14 ng/L both at 0 and 2 h, and the sum of the risk score had to be 0. The primary outcome was MACE within 30 days., Results: Among the 751 patients in the final analysis, 90 (11.9%) had a MACE. CORE identified 248 (33%) of patients as low risk with a sensitivity of 98.9% (CI 93.1-99.9) and a negative predictive value of 99.6% (95% CI 97.4-100) for 30-day MACE. Adding the ED physician's interpretation of the ECG to CORE did not improve diagnostic performance., Conclusion: A simple objective decision rule (CORE) identified one-third of all patients as having a very low 30-day risk of MACE. These patients may potentially be discharged without additional investigations for acute coronary syndrome.

Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease ( CVD ) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE , and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow-up of 4.2 years, 4066 CVD events were recorded. In a random-effects meta-analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12-1.50; P<0.001; I 2 =68.3%). There was evidence for presence of publication bias ( P value from Egger's test=0.013). Correction for publication bias using the trim-and-fill method reduced the risk ratio to 1.21 (95% confidence interval, 1.03-1.42; P<0.001). The risk ratios did not vary significantly by population type, geographical region, statistical adjustment, sample or assay type, age, sex, or length of follow-up. Conclusions In populations at high CVD risk, elevated circulating osteoprotegerin levels are associated with a higher risk for future CVD events. The magnitude of association appears weaker than in the general population.

Introduction: Postprandial hyperglycemia plays a pivotal role in cardiovascular disease. However, few studies have investigated associations between the severity of coronary artery disease (CAD) and postprandial glucose levels in angina patients without known diabetes before coronary angiography., Methods: Subjects who were admitted for coronary angiography due to angina and were in stable condition after discharge were recruited. A standard 75-g oral glucose tolerance test (OGTT) was performed at outpatient visits approximately 2-4 weeks after hospital discharge, and fasting and post-challenge blood glucose were measured. Twenty-six volunteers in our hospital staff served as the healthy group. CAD severity was graded using the SYNTAX and Jeopardy scoring systems., Results: The subjects in the angina group had a higher body mass index, higher fasting glucose, and higher 2-h postprandial glucose than those in the healthy group. The SYNTAX and Jeopardy scores were significantly associated with 2-h postprandial blood glucose (correlation coefficients = 0.164 and 0.187, respectively) but not with fasting glucose. Linear regression analyses revealed that SYNTAX and Jeopardy scores were independently associated with glucose levels at 120 min after OGTT (SYNTAX 95%CI = 0.003-0.103; Jeopardy score 0.002-0.027) but not with fasting glucose., Conclusion: CAD severity is associated with blood glucose levels after oral glucose challenge in patients without known diabetes before coronary angiography, suggesting that CAD patients should be routinely screened for post-challenge blood glucose., Competing Interests: The authors have declared that no competing interests exist.

Background and Aims: While a plethora of biomarkers have been shown to be associated with coronary artery disease, studies assessing biomarkers in coronary microvascular dysfunction (CMD) are few. We investigated associations between cardiovascular protein biomarkers and non-endothelium dependent CMD assessed by positron emission tomography (PET)., Methods: In 97 women with angina pectoris and no significant obstructive coronary artery disease (<50% stenosis on invasive coronary angiography), CMD was defined as myocardial blood flow reserve (MBFR) < 2.5 by rubidium-82 PET. Blood samples were analyzed with a cardiovascular disease proteomic panel encompassing 92 biomarkers. The relation between MBFR and biomarkers was evaluated with age-adjusted regression analysis., Results: Median age was 62 years (range 31-79), median MBFR was 2.7 (range 1.2-4.7) and 32% had non-endothelium dependent CMD (MBFR<2.5). Four biomarkers were significantly correlated with MBFR: Galectin-4 (Gal4, p = 0.008), growth differentiation factor 15 (GDF15, p = 0.026), tissue-type plasminogen activator (tPA, p = 0.030) and von Willebrand factor (vWF, p = 0.018), while 12 biomarkers showed a trend for correlation (0.05 ≤ p < 0.15). Of the 16 identified biomarkers, 10 are involved in pro-inflammatory pathways., Conclusions: In a panel of 92 cardiovascular protein biomarkers, 4 were significantly associated with non-endothelium dependent CMD in women: Gal4, GDF15, tPA and vWF, suggesting that inflammatory status and coagulation changes are associated with impaired microvascular dilatation. Further confirmatory studies are needed to corroborate these findings., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The therapeutic effect of statins on the stabilization of atherosclerotic plaques has been affirmed. In recent years, the inhibition of matrix metalloproteinases (MMPS) of tetracycline drug doxycycline has attracted more and more attention. In this paper, we observed the effect of atorvastatin and doxycycline on exercise tolerance in patients with stable angina pectoris. The results showed that there was no significant difference in the clinical efficacy of the two groups and the effect on the exercise tolerance (P<0.05). There were 4 cases of mild gastrointestinal reaction in the doxycycline group and no other serious adverse reactions. The total effective rate of treatment in the doxycycline group was 93.3%. Doxycycline treatment significantly reduced the frequency of angina pectoris and the incidence of cardiovascular events, and the treatment effect was better. To sum up, we think doxycycline is a safe, cheap, therapeutic drug to stabilize plaque.

Rationale: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS)., Objective: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS., Methods and Results: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P =0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS., Conclusions: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality., (© 2018 American Heart Association, Inc.)

Background: Hong Kong (HK) and Guangzhou (GZ) are cities in China with different healthcare systems. This study aimed to compare 30-day and 6-month mortality and characteristics of patients with suspected cardiac chest pain admitted to two emergency departments (ED) in HK and GZ., Methods: A prospective observational study enrolled patients with suspected cardiac chest pain presenting to EDs in the Prince of Wales Hospital (PWH), HK and the Second Affiliated Hospital of Guangzhou Medical University (AHGZMU),GZ. The primary outcome was 30-day and 6-month mortality., Results: In total, 996 patients were recruited, 407 cases from GZ and 589 cases from HK.The 30-day and 6-month mortality of chest patients were 3.7% and 4.7% in GZand 0.3% and 1.9% in HK, respectively. Serum creatinine level (Cr) was an independent factor for 30-day mortality whilst Cr and systolic blood pressure (SBP) were independent factors for 6-month mortality. In Cox regression analysis, unadjusted and adjusted hazard ratios for 30-day and 6-month mortality in GZ were significantly increased., Conclusion: The 30-day and 6-month mortality of patients with suspected cardiac chest pain in Guangzhou were higher than in Hong Kong due to due to different baseline clinical characteristics of patients and different distributions of diagnoses, which were associated with different healthcare systems. Serum creatinine and SBP were independent factors for 30-day and 6-month mortality.