Stress-induced stenotic vascular remodeling via reduction of plasma omega-3 fatty acid metabolite 4-oxoDHA by noradrenaline.

Stress has garnered significant attention as a prominent risk factor for inflammation-related diseases, particularly cardiovascular diseases (CVDs). However, the precise mechanisms underlying stress-driven CVDs remain elusive, thereby impeding the development of preventive and therapeutic strategies. To explore the correlation between plasma lipid metabolites and human depressive states, liquid chromatography-mass spectrometry (LC/MS) based analysis of plasma and the self-rating depression (SDS) scale questionnaire were employed. We also used a mouse model with restraint stress to study its effects on plasma lipid metabolites and stenotic vascular remodeling following carotid ligation. In vitro functional and mechanistic studies were performed using macrophages, endothelial cells, and neutrophil cells. We revealed a significant association between depressive state and reduced plasma levels of 4-oxoDHA, a specific omega-3 fatty acid metabolite biosynthesized by 5-lipoxygenase (LO), mainly in neutrophils. In mice, restraint stress decreased plasma 4-oxoDHA levels and exacerbated stenotic vascular remodeling, ameliorated by 4-oxoDHA supplementation. 4-oxoDHA enhanced Nrf2-HO-1 pathways, exerting anti-inflammatory effects on endothelial cells and macrophages. One of the stress hormones, noradrenaline, reduced 4-oxoDHA and the degraded 5-LO in neutrophils through the proteasome system, facilitated by dopamine D2-like receptor activation. Our study proposed circulating 4-oxoDHA levels as a stress biomarker and supplementation of 4-oxoDHA as a novel therapeutic approach for controlling stress-related vascular inflammation.

Home Blood Pressure-based Guidance Did Not Increase Anti-albuminuric Effects on Diagnostic Provision of Microalbuminuria in School Workers: A Miyagi Karoshi Prevention Study.

Objective We examined whether home blood pressure (BP)-based behavioural guidance had an additional anti-albuminuric effect on school workers with the simple diagnostic provision of microalbuminuria. Methods Of 169 school staff diagnosed with microalbuminuria (30-299.9 mg/gCr) in the annual 2019 health check-up, 91 agreed to receive home-BP-based guidance. Guidance comprised, for subjects with ≥135/85 mmHg, 5 days mean of home BP measurements, or encouraging medical consultation and lifestyle guidance; lifestyle guidance for subjects with BP 125-134/80-84 mmHg; and adequate lifestyle guidance for subjects BP <125/80 mmHg, if necessary. The main outcome was a change in the frequency of microalbuminuria the following year. Subjects with menstruation were excluded from analysis. Finally, there were 48 and 43 participants in guided and the non-guided groups, respectively. Results The guided and non-guided groups demonstrated similar baseline clinical data. Their prescription rates for hypertension (39.6 vs. 41.9 %) and diabetes (18.8 vs. 30.2 %) were similar. One year later, microalbuminuria was present in 31.2% and 30.2% of the guided and non-guided groups (n.s.), respectively, suggesting a ~70% risk reduction of microalbuminuria in both groups. Sensitivity analysis, excluding patients treated for hypertension or diabetes at baseline, demonstrated essentially similar results. In conclusion, the risk reduction of microalbuminuria was nearly 70% for both the home-BP-based guidance and non-guidance groups. Conclusion These data suggest that home BP-based guidance did not increase anti-albuminuric effects on simple diagnostic provision of microalbuminuria in school workers.

Effectiveness of Saireito, a Traditional Japanese Kampo Herbal Medication, on Pacemaker-Related Pleural Effusion: A Case Report.

BACKGROUND Post-cardiac injury syndrome, including pleural effusion as a delayed complication of permanent pacemaker implantation, has rarely been reported. To resolve pleural effusion, prolonged chest tube placement is often required. Anti-inflammatory agents combined with diuretics are also often prescribed. Saireito, a Japanese herbal medication, which is a combination of Goreisan and Shousaikoto, has both anti-inflammatory and water-modulation properties and has been used for edema (lymph edema, cerebral edema) and inflammation (chronic nephritis). CASE REPORT We describe a 71-year-old woman with a history of syncope and bradycardia who underwent dual permanent pacemaker implantation (placed in the right chest because of a persistent left superior vena cava) without complications. Two months later, she came to the hospital as an outpatient with a dry cough, and was diagnosed with right-sided pleural effusion. A pleural fluid analysis revealed exudative effusion, according to Light's criteria. The fluid was negative for infectious etiology. Chest X-ray, computed tomography, and echocardiography revealed no signs of pericardial effusion or perforation of the pacemaker lead to outside the heart. The pleural effusion persisted despite use of anti-inflammatory medication for several weeks and diuretics for a short period. Saireito was administered with good response; the pleural effusion resolved completely and there was no deterioration of renal function. CONCLUSIONS The present case highlights the clinical significance of Saireito as an effective therapeutic agent for late-onset pacemaker-related pleural effusion, without adverse effects such as renal dysfunction.

A Case of Takotsubo Cardiomyopathy with a Rare Transition Pattern of Left Ventricular Wall Motion Abnormality.

BACKGROUND Takotsubo cardiomyopathy is characterized by apical ballooning and excessive constriction of the base of heart. However, reverse takotsubo cardiomyopathy, wherein ballooning from the mid-ventricle to the base of the heart occurs with excessive constriction of the apex, has also been reported. We report a case of a transition from atypical wall motion abnormality to a typical takotsubo cardiomyopathy pattern. CASE REPORT A 54-year-old woman was following excessive sugar and dietary restrictions because of concerns regarding her blood sugar levels while receiving treatment for diabetes at another hospital. She presented at our hospital with general malaise and chest discomfort after several days of significantly increased workload. On admission, blood tests showed elevated cardiac enzymes. Electrocardiogram showed ST elevation of V2-V3 and poor R-wave enhancement of the anterior precordial lead. Coronary angiography showed no significant stenosis; however, left ventricular (LV) angiography showed a decrease in mid-ventricular wall motion. On the basis of these findings, she was diagnosed with a reverse takotsubo cardiomyopathy. We initiated conservative treatment for her condition. During her treatment, the LV wall motion showed a typical pattern of the apical ballooning that is characteristic of takotsubo cardiomyopathy. This LV wall motion was normalized on day 22 of the onset. CONCLUSIONS We observed a rare case of takotsubo cardiomyopathy where the pattern of LV wall motion abnormality changed over time. This case suggests that it is necessary to follow up LV abnormality over time rather than rely on single-point observations in cases with takotsubo cardiomyopathy.

Area-Based Medicine in the Super-Ageing Society in Japan.

Japan's health insurance system has reached a critical turning point owing to a decreasing birthrate, increasing longevity, and changes in disease trends. The Japanese government is promoting the establishment of a community-based integrated care system aimed at maintaining the dignity of elderly individuals and supporting independent living. This care system will ensure medical and nursing care, preventive measures, and independent living support. This type of care system should be based on the characteristics of individual geographical areas, as there are marked regional variations in patterns of aging, lifestyle, and the adequacy of local medical care. Therefore, it is important that medical services are tailored to fit the kind of medical care needed by residents of each geographical area and to provide medical services accordingly. In this paper, we propose a need for area-based medicine, whereby medical care is provided according to the characteristics of individual geographical areas in super-ageing societies such as that of Japan. J. Med. Invest. 67 : 40-43, February, 2020.

Clinical Features of Spontaneous Isolated Dissection of Abdominal Visceral Arteries.

BACKGROUND: Spontaneous isolated dissection of abdominal visceral arteries without aortic dissection is rare and its pathology and prognosis are not yet clear; therefore, therapeutic strategies for this disease have not been established. The present multi-institution investigational study analyzed the clinical features of patients with spontaneous isolated dissection of abdominal visceral arteries. METHODS: A total of 36 patients diagnosed as spontaneous isolated dissection of abdominal visceral arteries from January 2010 to October 2016 were enrolled. The medical data of the patients were retrospectively reviewed. Imaging characteristics were evaluated. Spontaneous isolated dissection of abdominal visceral arteries was detected on upper abdominal computed tomography examination in almost patients, and was detected on magnetic resonance imaging in one patient. RESULTS: Of the 36 cases, 26 cases involved the superior mesenteric artery dissection, nine involved the celiac artery, two involved the splenic artery, one involved the common hepatic artery, one involved the gastroduodenal artery and one involved the left gastric artery. Among the 36 patients, 20 had hypertension and 14 were current smokers. Additionally, only one patient had diabetes and four patients had dyslipidemia. Moreover, 32 cases complained of pain including abdominal pain and back pain, one had cough and three had no symptoms. Of the 36 patients, 34 cases (94.4%) were treated conservatively, and two (5.6%) required intravascular treatment. All patients were discharged without complications. CONCLUSIONS: Our findings indicate that hypertension and smoking might be closely involved in the pathogenesis of spontaneous isolated dissection of abdominal visceral arteries, whereas dyslipidemia and diabetes might be less involved. Additionally, few asymptomatic patients were accidentally diagnosed, indicating that the absence of symptoms cannot be used to rule out the presence of this disease. Randomized clinical trials cannot be performed because a considerable number of cases are required. Therefore, detailed descriptions of clinical features, as provided in our report, are important.

Prevention of thrombotic disorders by antithrombotic diet and exercise: evidence by using global thrombosis tests.

Prevention of thrombotic disorders has priority over treatment. There are only two pathologically relevant tests which are suitable for measuring the overall thrombotic status both in experimental conditions and in humans. The Global Thrombosis Test (GTT) and the Global Parallel-Plate Thrombosis Test can detect the pathologically relevant global thrombotic status. These tests have been successfully used for monitoring the effect of antithrombotic drugs and for developing novel antithrombotic agents. By using GTT, varieties of fruits, vegetables, and regular physical exercise have been tested for the effect on global thrombotic status. This review discusses the published evidence for the benefit of diet of selected fruit and vegetable varieties and doing regular physical exercise on improving thrombotic status. Future clinical trials monitored by GTT or Global Parallel-Plate Thrombosis Test could decide on the effectiveness of an experimentally proven antithrombotic diet with regular physical exercise in the prevention of thrombotic diseases.

Overwork accelerates thrombotic reaction: implications for the pathogenesis of Karoshi.

Work-related stressors are potential causes of cardiovascular diseases (CVDs) and stroke; however, the pathophysiological mechanisms by which occupational stress induces and exacerbates CVDs remain unclear. The global thrombosis test (GTT) is a novel in vitro assay for evaluating both thrombotic reactions and subsequent thrombolysis. The time required to form an occlusive thrombus with the GTT, called as the occlusion time (OT), and the time to lyse the thrombus, the lysis time (LT), are markers of thrombotic and thrombolytic reactions, respectively. We investigated the impact of work-related stress on the thrombotic and thrombolytic reactions in 46 healthy medical residents. Off-duty or on-duty blood samples were collected on the mornings of non-work days or after the night duty on the emergent room respectively. The duration of sleep was significantly shorter during night duty than during off-duty nights [2.25 (1.0, 3.0) h vs. 6.0 (5.0, 7.0) h; p < 0.001]. Baseline OT was 310.3 (260.9, 437.7) s. whereas the on-duty OT was significantly shortened [284.2 (230.5, 355.8) s; p < 0.01]. LT was significantly prolonged during overwork conditions compared with off-duty conditions [1547 (1346, 1908) s vs. 1470 (1219, 1692) s; p < 0.05]. Overwork accelerates the thrombotic reactions. These reactions might explain the pathogenesis of overwork-related CVDs. The GTT is a good tool for evaluating of the level of fatigue.

Increased double product on Monday morning during work.

It has been reported that cardiovascular events often occur on Monday morning, especially in the young working population. Because hypertension is a major cardiovascular risk, we examined whether blood pressure was elevated on Monday, especially in the morning during work. However, there were no weekly rhythms in blood pressure itself. Instead, we found significant interactions between the double product (systolic blood pressure × heart rate) and weekly (high on Monday) and circadian (high in the morning) rhythms. Further studies are required to determine whether Monday morning preference in cardiovascular events is caused by increased double product.

A Case with Recurrent Free-Floating Ball Thrombi in Left Atrium.

BACKGROUND A free-floating ball thrombus in the left atrium is a rare clinical condition. However, the diagnosis of this condition has been facilitated by the advent and development of echocardiography and multi-detector row computed tomography (MDCT) and several cases have been reported. CASE REPORT We report a case of a 75-year-old woman who had recurrent giant spherical thrombi in the left atrium. She was diagnosed with chronic atrial fibrillation at 52 years of age. A pacemaker implantation was performed at 54 years of age because of a complete atrioventricular block; and mitral valve replacement was performed for severe mitral regurgitation at 62 years of age. She had a history of cerebral infarction and she was under treatment for chronic heart failure. Despite intensive anticoagulant therapy, she developed ball thrombi in the left atrium three times in six months. During hospitalization for acute myocardial infarction treated with percutaneous catheter intervention, transthoracic echocardiography and computed tomography (CT) revealed a free-floating giant spherical thrombus in the left atrium. She was treated with intensive anticoagulation therapy and the left atrial ball thrombus disappeared; however, two ball thrombi in the left atrium and left atrial appendage recurred after three months. Surgical removal of the thrombi and closure of the left atrial appendage were performed. Unfortunately, a ball thrombus in the left atrium recurred again after a further three months. CONCLUSIONS The present case highlights the difficulty of treating refractory thrombi in the left atrium.

A Simultaneous Evaluation of Occupational Stress and Depression in Patients with Lifestyle-related Diseases.

Objective Karoshi, which is the Japanese term for death from over-work, is usually the extreme result of cardiovascular diseases, and occupational stress plays a pivotal role in the pathogenesis. Depression is closely associated with atherosclerotic cardiovascular disease. The present study was undertaken to examine the relationship between occupational stress and depression. Methods We enrolled 231 consecutive outpatients with lifestyle-related diseases such as diabetes, hyperlipidemia and hypertension were enrolled. Occupational stress was measured by qualitative constructs assessing job control, job demands, and worksite social support using a job content questionnaire (JCQ). The job strain index measured by the ratio of job demands to job control was used as an indicator of the occupational stress. Depression was evaluated by the Self-rating Depression Scale (SDS). Results A univariate linear regression analysis showed the SDS scores to be positively correlated with job demands and the job strain index and negatively correlated with job control and worksite social support. Multiple regression analyses to predict the SDS scores demonstrated that job demands were positively associated with SDS scores and job control and worksite social support were negatively associated with SDS scores after controlling for other variables. The job strain index was positively related to SDS scores. Conclusion Occupational stress expressed as the job strain index was strongly associated with depression. By simultaneously using the SDS and JCQ, the health conditions of patients could be classified based on occupational stress and mental stress, and this classification could help to promote a healthy work environment and guide individual workers.

Global Thrombosis Test - a possible monitoring system for the effects and safety of dabigatran.

BACKGROUND: Dabigatran is an alternative to warfarin (WF) for the thromboprophylaxis of stroke in patients with non-valvular atrial fibrillation (NVAF). The advantage of dabigatran over WF is that monitoring is not required; however, a method to monitor the effect and the safety of dabigatran is not currently available. The Global Thrombosis Test (GTT) is a novel method to assess both clot formation and lysis activities under physiological conditions. OBJECTIVE: The aim of this study was to evaluate whether treatment with dabigatran might affect shear-induced thrombi (occlusion time [OT], sec) by the GTT, and to investigate the possibility that the GTT could be useful as a monitoring system for dabigatran. PATIENTS/METHODS: The study population consisted of 50 volunteers and 43 NVAF patients on WF therapy, who were subsequently switched to dabigatran. Using the GTT, the thrombotic status was assessed one day before and 1 month after switching anticoagulation from WF to dabigatran. RESULTS: The OT was 524.9 ± 17.0 sec in volunteers whereas that of NVAF patients on WF therapy was 581.7 ± 26.3 sec. The switch from WF to dabigatran significantly prolonged OT (784.5 ± 19.3 sec). One patient on WF therapy and 12 patients on dabigatran therapy were shown to have OT > 900 sec. CONCLUSION: The GTT could be used to assess the risk of dabigatran-related bleeding complications.

Vasospastic Angina in Identical Twins.

BACKGROUND: The clinical conditions of various diseases, including coronary artery disease, are determined by genetics and the environment. Previous investigations noted the significance of genetic mutations and polymorphisms in cases of coronary spasm. CASE REPORT: We report on monozygotic identical twins who almost simultaneously presented with vasospastic angina. The 58-year-old younger twin was admitted to our hospital because of persistent chest pain. An electrocardiogram showed an inverted T wave in the left precordial leads. Coronary angiographies revealed a short left main trunk (LMT) and 50% stenosis at the proximal portion of the left anterior descending artery (LAD). Infusion of acetylcholine to his left coronary artery caused marked vasoconstriction associated with a sensation of chest oppression. Nitroglycerine completely reversed this response. Based on these findings, we diagnosed Twin A with vasospastic angina. At nearly the same time, his identical twin brother was diagnosed with vasospastic angina at another hospital. Comparison of both coronary angiograms indicated similar structure of coronary vessels, including short LMT and mild stenosis at the proximal portion of LAD. CONCLUSIONS: These 2 cases highlight the importance of genetic factors in the pathogenesis of vasospastic angina. It may be important for individuals to receive medical attention if their identical twin presents with vasospastic angina.