INTRODUCTION

While a 600 mg loading dose (LD) of clopidogrel has demonstrated superior inhibition of platelet function compared to 300 mg LD, the clinical evidence supporting this superiority is limited. The debate centers on whether higher clopidogrel LD regimen in percutaneous coronary intervention (PCI) outperforms the standard 300 mg LD, with potential benefits being more pronounced in higher-risk patients. Balancing enhanced platelet inhibition to reduce ischemic events against the associated risk of increased bleeding remains a critical consideration in determining the optimal loading dose of clopidogrel for patients with ischemic heart disease.

A systematic literature search for randomized clinical trials (RCTs) was performed comparing 600 mg with 300 mg LD of clopidogrel using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov and HerdinPH. Studies included those between 2010 and 2023 involving human subjects. The primary efficacy endpoint was a 1-month rate of major adverse cardiac event (MACE) and the primary safety outcome was bleeding adverse effects.

Nine RCTs involving 29,827 patients were included in the efficacy analysis. Mean duration of follow-up was 30 days. Only eight studies were eligible for safety analysis. Compared with standard LD clopidogrel, high LD significantly reduced the incidence of overall MACE (OR: 0.82, 95% CI: 0.74-0.91, p = 0.0002), nonfatal myocardial infarction (OR: 0.56; 95% CI: 0.32-0.99, p = 0.15) and target vessel revascularization (OR: 0.63; 95% CI: 0.41-0.95, p = 0.03), without significant difference in terms of cardiac death (OR: 0.89; 95% CI: 0.76-1.04, p = 0.15) and stroke (OR: 0.92; 95% CI: 0.67-1.26, p = 0.61). However, major bleeding risk was higher in the 600 mg LD (1.9%; 261/13288) compared with 300 mg LD (2.4%; 328/13242) [OR: 1.27; 95% CI: 1.08-1.49, p = 0.005] without significant difference in minor bleeding (OR: 1.05; 95% CI: 0.94-1.17, p = 0.35).

The administration of 600 mg clopidogrel LD reduces the overall risk of MACE with associated increased risk of major bleeding.

Humans ; Myocardial Reperfusion Injury/genetics* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac ; Apoptosis ; Myocardial Ischemia

Humans ; Myocardial Reperfusion Injury/genetics* ; RNA, Long Noncoding/genetics* ; Myocytes, Cardiac ; Apoptosis ; Myocardial Ischemia

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.
Humans ; Male ; Middle Aged ; Aged ; Coronary Artery Disease/diagnostic imaging* ; Stroke Volume ; Myocardial Perfusion Imaging ; Retrospective Studies ; Ventricular Function, Left ; Myocardial Ischemia

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm³ and (105.18±31.16)cm³, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.
Male ; Humans ; Middle Aged ; Aged ; Female ; Coronary Artery Disease/diagnostic imaging* ; Cross-Sectional Studies ; Retrospective Studies ; Myocardial Ischemia/diagnostic imaging* ; Coronary Stenosis ; Calcium

Objective: To analyze the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019, and to study the current burden of disease in relevant populations. Methods: In October 2021, based on data from the global burden of disease 2019 (GBD 2019) study, population attributable fraction (PAF), number of deaths, mortality, disability-adjusted life year (DALY) and DALY rate of Chinese and global populations with different ages and genders in 1990 and 2019 were extracted and analyzed. The rate of change was calculated, the mortality rate was normalized by the age structure of the world standard population, and the causes of disease burden caused by high temperature exposure of Chinese residents were analyzed. Results: In 2019, compared with 1990, the PAF of Chinese and global population decreased by 43.98% and 12.41% respectively, the number of deaths increased by 29.55% and 49.40% respectively, the crude mortality rate increased by 7.81% and 3.30% respectively, the DALY decreased by 48.12% and 14.41% respectively, and the DALY rate decreased by 56.82% and 40.82% respectively. The mortality rate of the ≥70 age group was higher than that of other groups. The disease burden indicators such as PAF, standardized mortality and DALY attributable to high temperature exposure in men were higher than those in women. In 2019, the main cause of DALY affected by high temperature exposure in Chinese population was ischemic heart disease (84400 person-years), and the main cause of death was ischemic heart disease (4900 cases). Conclusion: The burden of diseases attributable to high temperature exposure is still serious in China and the world at large. Targeted interventions should be formulated for men, the elderly and people with occupational exposure, and a sound surveillance system should be established to reduce the burden of diseases caused by high temperature exposure.
Humans ; Male ; Female ; Aged ; Quality-Adjusted Life Years ; Temperature ; Cost of Illness ; China/epidemiology* ; Myocardial Ischemia

INTRODUCTION: Normal stress myocardial perfusion imaging (MPI) carries a favourable prognosis. Conversely, elevated coronary artery calcium (CAC) is associated with increased major adverse cardiovascular events (MACE). There is limited information on the prognosis and management of patients with elevated CAC and normal MPI. We aimed to assess the outcomes of patients with elevated CAC and normal MPI in relation to post-MPI statin use. METHODS: A retrospective review of normal MPI with CAC score >300 was performed between 1 March 2016 and 31 January 2017 in a Singapore tertiary hospital. Patients with known atherosclerotic cardiovascular disease or left ventricular ejection fraction <50% on MPI were excluded. Patient demographics, prescriptions and MACE (cardiac death, nonfatal myocardial infarction and/or ischaemic stroke) at 24 months after MPI were traced using electronic records. Binary logistic regression was used to evaluate for independent predictors of MACE. RESULTS: We included 311 patients (median age 71 years, 56.3% male), of whom 65.0% were on moderate to high-intensity statins (MHIS) after MPI. MACE was significantly lower in the post-MPI MHIS group (3.5% vs. 9.2%, P = 0.035). On univariate binary logistic regression, post-MPI MHIS use was the only significant predictor for MACE (odds ratio [OR] 0.355 [95% confidence interval (CI) 0.131-0.962], P = 0.042), even after multivariate adjustment (adjusted OR 0.363, 95% confidence interval 0.134-0.984, P = 0.046). CONCLUSION Post-MPI MHIS use is associated with lower MACE and is an independent negative predictor for 24-month MACE among patients with normal MPI and CAC >300.
Humans ; Male ; Aged ; Female ; Coronary Artery Disease ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Myocardial Perfusion Imaging/methods* ; Calcium ; Stroke Volume ; Brain Ischemia ; Risk Factors ; Ventricular Function, Left ; Stroke ; Prognosis

Objective: To analyze the clinical characteristics, diagnosis and treatment of anomalous aortic origin of a coronary artery (AAOCA) in children. Methods: There were 17 children diagnosed with AAOCA from January 2013 to January 2022 in Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine.Their clinical manifestations, laboratory and imaging data, treatment and prognosis were retrospectively analyzed. Results: These 17 children included 14 males and 3 females, with the age of (8.7±3.5) years. There were 4 anomalous left coronary artery (ALCA) and 13 anomalous right coronary artery (ARCA). Seven children presented with chest pain or chest pain after exercise, three patients presented with cardiac syncope, one complained chest tightness and weakness, and the other six patients had no specific symptoms. Cardiac syncope and chest tightness occurred in patients with ALCA. Fourteen children had the dangerous anatomical basis of myocardial ischemia caused by coronary artery compression or stenosis on imaging. Seven children had coronary artery repair, of whom two were ALCA and five were ARCA. One patient had received heart transplantation because of heart failure. The incidence of adverse cardiovascular events and poor prognosis in ALCA group was higher than that in ARCA group (4/4 vs. 0/13, P<0.05). They were followed up in the outpatient department regularly for 6 (6, 12) months; except for the one who lost visit, the rest of the patients had a good prognosis. Conclusions: Cardiogenic syncope or cardiac insufficiency usually occurs in ALCA, and adverse cardiovascular events and poor prognosis are more common in ALCA than in ARCA. Early surgical treatment should be considered for children with ALCA and ARCA accompanied by myocardial ischemia.
Female ; Male ; Humans ; Child ; Child, Preschool ; Retrospective Studies ; China ; Coronary Artery Disease ; Myocardial Ischemia ; Heart Failure ; Chest Pain ; Syncope

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.
Male ; Animals ; Rats ; Rats, Sprague-Dawley ; Dalbergia ; Myocardial Ischemia ; Metabolomics ; Heart ; Heart Injuries ; Creatine Kinase, MB Form

BACKGROUND: Previous cardiovascular risk prediction models in Japan have utilized prospective cohort studies with concise data. As the health information including health check-up records and administrative claims becomes digitalized and publicly available, application of large datasets based on such real-world data can achieve prediction accuracy and support social implementation of cardiovascular disease risk prediction models in preventive and clinical practice. In this study, classical regression and machine learning methods were explored to develop ischemic heart disease (IHD) and stroke prognostic models using real-world data. METHODS: IQVIA Japan Claims Database was searched to include 691,160 individuals (predominantly corporate employees and their families working in secondary and tertiary industries) with at least one annual health check-up record during the identification period (April 2013-December 2018). The primary outcome of the study was the first recorded IHD or stroke event. Predictors were annual health check-up records at the index year-month, comprising demographic characteristics, laboratory tests, and questionnaire features. Four prediction models (Cox, Elnet-Cox, XGBoost, and Ensemble) were assessed in the present study to develop a cardiovascular disease risk prediction model for Japan. RESULTS: The analysis cohort consisted of 572,971 invididuals. All prediction models showed similarly good performance. The Harrell's C-index was close to 0.9 for all IHD models, and above 0.7 for stroke models. In IHD models, age, sex, high-density lipoprotein, low-density lipoprotein, cholesterol, and systolic blood pressure had higher importance, while in stroke models systolic blood pressure and age had higher importance. CONCLUSION Our study analyzed classical regression and machine learning algorithms to develop cardiovascular disease risk prediction models for IHD and stroke in Japan that can be applied to practical use in a large population with predictive accuracy.
Humans ; Cardiovascular Diseases/epidemiology* ; Prognosis ; Prospective Studies ; Japan/epidemiology* ; Stroke/etiology* ; Myocardial Ischemia/epidemiology* ; Risk Assessment/methods*