OBJECTIVE: Observational studies have shown inconsistent associations of loneliness or social isolation (SI) with ischemic heart disease (IHD), with unknown mediators. METHODS: Using data from genome-wide association studies of predominantly European ancestry, we performed a bidirectional two-sample Mendelian Randomization (MR) study to estimate causal effects of loneliness ( N = 487,647) and SI traits on IHD ( N = 184,305). SI traits included whether individuals lived alone, participated in various types of social activities, and how often they had contact with friends or family ( N = 459,830 to 461,369). A network MR study was conducted to evaluate the mediating roles of 20 candidate mediators, including metabolic, behavioral and psychological factors. RESULTS: Loneliness increased IHD risk ( OR= 2.129; 95% confidence interval [ CI]: 1.380 to 3.285), mediated by body fat percentage, waist-hip ratio, total cholesterol, and low-density lipoprotein cholesterol. For SI traits, only fewer social activities increased IHD risk ( OR= 1.815; 95% CI: 1.189 to 2.772), mediated by hypertension, high-density lipoprotein cholesterol, triglycerides, fasting insulin, and smoking cessation. No reverse causality of IHD with loneliness and SI was found. CONCLUSION These findings suggested more attention should be paid to individuals who feel lonely and have fewer social activities to prevent IHD, with several mediators as prioritized targets for intervention.
Loneliness/psychology* ; Humans ; Mendelian Randomization Analysis ; Social Isolation ; Myocardial Ischemia/etiology* ; Male ; Female ; Middle Aged ; Genome-Wide Association Study ; Risk Factors ; Aged

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*

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α₂ adrenoceptor (α₂AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α₂AR-mediated sympathetic-sensory coupling.
Animals ; Ganglia, Spinal ; Hyperalgesia/etiology* ; Myocardial Ischemia/complications* ; Pain, Referred/complications* ; Rats ; Sympathetic Nervous System

Coronary Artery Disease/complications* ; Death, Sudden, Cardiac/etiology* ; Humans ; Myocardial Ischemia/diagnosis*

BACKGROUND: Ischemic heart disease (IHD/ICD10: I20-I25) is the second leading cause of deaths in Japan and accounts for 40% of deaths due to heart diseases. This study aimed to calculate the economic burden of IHD using the cost of illness (COI) method and to identify key factors that drive the change of the economic burden of IHD. METHODS: We calculated the cost of illness (COI) every 3 years from 1996 to 2014 using governmental statistics. We then predicted the COI for every 3 years starting from 2017 up to 2029 using the fixed and variable model estimations. Only the estimated future population was used as a variable in the fixed model estimation. By contrast, variable model estimation considered the time trend of health-related indicators over the past 18 years. We derived the COI from the sum of direct and indirect costs (morbidity and mortality). RESULTS: The past estimation of COI slightly increased from 1493.8 billion yen in 1996 to 1708.3 billion yen in 2014. Future forecasts indicated that it would decrease from 1619.0 billion yen in 2017 to 1220.5 billion yen in 2029. CONCLUSION The past estimation showed that the COI of IHD increased; in the mixed model, the COI was predicted to decrease with the continuing trend of health-related indicators. The COI of IHD in the future projection showed that, although the average age of death increased by social aging, the influence of the number of deaths and mortality cost decreased.
Aged ; Cost of Illness ; Female ; Forecasting ; Humans ; Japan ; Male ; Middle Aged ; Models, Theoretical ; Myocardial Ischemia ; economics ; etiology

PURPOSE: Recent evidence suggests that early repolarization (ER) is related with myocardial ischemia. Compression of coronary artery by a myocardial bridging (MB) can be associated with clinical manifestations of myocardial ischemia. This study aimed to evaluate the associations of MB in patients with ER. MATERIALS AND METHODS: In consecutive patients (n=1303, age, 61±12 years) who had undergone coronary angiography, we assessed the prevalence and prognostic implication of MB in those with ER (n=142) and those without ER (n=1161). RESULTS: MB was observed in 54 (38%) and 196 (17%) patients in ER and no-ER groups (p<0.001). In multivariate analysis, MB was independently associated with ER (odd ratio: 2.9, 95% confidence interval: 1.98–4.24, p<0.001). Notched type ER was more frequently observed in MB involving the mid portion of left anterior descending coronary artery (LAD) (69.8% vs. 30.2%, p=0.03). Cardiac event was observed in nine (6.3%) and 22 (1.9%) subjects with and without ER, respectively. MB was more frequently observed in sudden death patients with ER (2 out of 9, 22%) than in those without ER (0 out of 22). CONCLUSION: MB was independently associated with ER in patients without out structural heart disease who underwent coronary angiography. Notched type ER was closely related with MB involving the mid portion of the LAD. Among patients who had experienced cardiac events, a higher prevalence of MB was observed in patients with ER than those without ER. Further prospective studies on the prognosis of MB in ER patients are required.
Aged ; Coronary Angiography ; Electrocardiography ; Electrophysiological Phenomena ; Female ; Humans ; Male ; Middle Aged ; Myocardial Bridging/*complications/*diagnostic imaging/epidemiology/physiopathology ; Myocardial Ischemia/*etiology/physiopathology ; Odds Ratio ; Prevalence ; Prognosis ; Prospective Studies

To explore the protective effects of right coronary artery ischemic preconditioning and post-conditioning on myocardial ischemia reperfusion injury in rabbit heart.
 Methods: A total of 30 rabbits were randomly divided into 4 groups: a control group (n=7), an ischemia reperfusion group (IR group, n=8), an ischemic preconditioning group (IPC group, n=8) and an ischemic post-conditioning group (IPO group, n=7). Venous blood samples were taken at pre-operation, 1 and 6 h post-operation, and the concentration of serum creatine kinase isoenzyme (CK-MB) and cardiac troponin-T (cTn-T) were measured. The infarct area of cardiac muscle was calculated.
 Results: Compared with the IR group, the levels of CK-MB and cTn-T at 1 and 6 h post-operation in the IPC group and the IPO group were reduced (all P<0.05). Compared with the IR group, the infarct size in the IPC group and the IPO group was significantly decreased, with significant difference (both P<0.05) .
 Conclusion: Right coronary artery ischemic preconditioning and post-conditioning exert significant protective effects on the myocardial ischemia reperfusion injury in New Zealand rabbits.
Animals ; Coronary Vessels ; Creatine Kinase, MB Form ; blood ; Heart ; Ischemia ; Ischemic Postconditioning ; Ischemic Preconditioning ; Ischemic Preconditioning, Myocardial ; Myocardial Infarction ; etiology ; pathology ; physiopathology ; prevention & control ; Myocardial Ischemia ; complications ; therapy ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; Rabbits ; Troponin T ; blood

Conventional coronary angiography (CAG) has limitations in evaluating lesions producing ischemia. Three dimensional quantitative coronary angiography (3D-QCA) shows reconstructed images of CAG using computer based algorithm, the Cardio-op B system (Paieon Medical, Rosh Ha'ayin, Israel). The aim of this study was to evaluate whether 3D-QCA can reliably predict ischemia assessed by myocardial fractional flow reserve (FFR) < 0.80. 3D-QCA images were reconstructed from CAG which also were evaluated with FFR to assess ischemia. Minimal luminal diameter (MLD), percent diameter stenosis (%DS), minimal luminal area (MLA), and percent area stenosis (%AS) were obtained. The results of 3D-QCA and FFR were compared. A total of 266 patients was enrolled for the present study. FFR for all lesions ranged from 0.57 to 1.00 (0.85 +/- 0.09). Measurement of MLD, %DS, MLA, and %AS all were significantly correlated with FFR (r = 0.569, 0609, 0.569, 0.670, respectively, all P < 0.001). In lesions with MLA < 4.0 mm2, %AS of more than 65.5% had a 80% sensitivity and a 83% specificity to predict FFR < 0.80 (area under curve, AUC was 0.878). 3D-QCA can reliably predict coronary lesions producing ischemia and may be used to guide therapeutic approach for coronary artery disease.
Aged ; Coronary Angiography/*methods ; Coronary Circulation ; Coronary Stenosis/etiology/*physiopathology/*radiography ; Female ; *Fractional Flow Reserve, Myocardial ; Humans ; Imaging, Three-Dimensional/*methods ; Male ; Myocardial Ischemia/complications/physiopathology/*radiography ; Radiographic Image Enhancement/methods ; Radiographic Image Interpretation, Computer-Assisted/methods ; Reproducibility of Results ; Sensitivity and Specificity

To study the therapeutic effect and possible mechanism of icariin on myocardial ischemia-reperfusion injury ( MIRI) model in diabetes rats. The model of diabetic rats were induced by Streptozotocin (STZ), then the model of MIRI was established by ligating the reversible left anterior descending coronary artery for 30 min, and then reperfusing for 120 min. totally 40 male SD were randomly divided into five groups: the control group (NS), the ischemia reperfusion group (NIR), the diabetes control group (MS), the diabetic ischemia reperfusion group (MIR) and the diabetic ischemia reperfusion with icariin group (MIRI). The changes in blood glucose, body weight and living status were observed; the enzyme activity of serum CK-MB, LDH, GSH-Px and myocardium SOD and the content MDA and NO in myocardium were detected; the myocardial pathological changes were observed by HE staining; the myocardial Caspase-3, the Bcl-2, Bax protein expressions were detected by Western blot. The result showed that the diabetes model was successfully replicated; myocardial ischemia-reperfusion injury was more serious in diabetes rats; icariin can increase NO, SOD, GSH-Px, Bcl-2 protein expression, decrease MDA formation, CK-MB and LDH activities and Caspase-3 and Bcl-2 protein expressions and myocardial damage. The result suggested that icariin may play a protective role against ischemia reperfusion myocardial injury in diabetes rats by resisting oxidative stress and inhibiting cell apoptosis.
Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Creatine Kinase ; metabolism ; Diabetes Mellitus, Type 2 ; complications ; Drugs, Chinese Herbal ; administration & dosage ; Flavonoids ; administration & dosage ; Humans ; Ischemia ; drug therapy ; etiology ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; etiology ; metabolism ; physiopathology ; Myocardium ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism

Humans ; Myocardial Ischemia ; etiology