Triglyceride/high-density lipoprotein cholesterol ratio may be a better index of cardiometabolic risk in women than in men in Japan.

BACKGROUND AND AIMS: Few data exist regarding the gender differences in the relationship between triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio and cardiometabolic risk leading to atherosclerotic cardiovascular disease (ASCVD). We investigated, by gender, the association between the TG/HDL-C ratio and metabolic syndrome (MetS) and its components in the Japanese, who are less obese than their Western counterparts. METHODS AND RESULTS: A population consisting of 10,373 participants (average age, 47.6 ± 12.6 years, 60.9 % men) at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020 was studied using a cross-sectional study method. The TG/HDL-C ratio and proportion of visceral obesity increased approximately parallelly with age in women; however, these parameters did not change proportionally with age in men. Accordingly, receiver operating characteristic analysis revealed the accuracy of the TG/HDL-C ratio as a predictor of visceral obesity based on the Japanese MetS criteria (women vs. men: area under the curve, 0.797 vs. 0.712, p < 0.0001; sensitivity, 82.4 % vs. 59.9 %; specificity, 61.1 % vs. 71.1 %; cutoff value, 1.075 vs. 1.933, respectively). Furthermore, a higher TG/HDL-C ratio in women reflected the status of MetS and its components compared with men in multi-logistic regression analysis. CONCLUSION: An increased TG/HDL-C ratio in women may be involved in MetS and its components compared to men. We may pay attention to visceral obesity and increased TG/HDL-C ratio to prevent ASCVD risk in women, even in the Japanese population, which generally contains a lower proportion of obesity than in Western populations.

Association of Higher N-3 Polyunsaturated Fatty Acid Consumption and Aerobic Exercise with Lower Neutrophil-to-Lymphocyte Ratio: Implications of Anti-Atherosclerotic Effect of Fish Consumption.

INTRODUCTION: N-3 polyunsaturated fatty acids (n-3 PUFAs), abundant in oily fish, exert anti-inflammatory cardiovascular protective effects. We aimed to investigate the association between fish-derived n-3 PUFAs, lifestyle habits, and neutrophil-to-lymphocyte ratio (NLR), an atherosclerotic cardiovascular disease (ASCVD) marker. METHODS: This cross-sectional study included 6,950 participants with no history of ASCVD, who underwent annual health check-ups (average age, 46.3 ± 13.0 years; male:female ratio, 58.8%) between April 2019 and March 2020 at the Health Planning Center, Nihon University Hospital. We calculated n-3 PUFA consumption using a questionnaire and the Japan National Health and Nutrition Survey. RESULTS: The average fish consumption frequency and fish-derived n-3 PUFA consumption were 2.20 ± 1.28 days/week and 5.20 ± 3.11 g/week, respectively. A higher fish-derived n-3 PUFA consumption was associated with a lower NLR. Multiple-stepwise regression analysis revealed that higher fish-derived n-3 PUFA consumption and more aerobic exercise habits were significant independent determinants of lower NLR. Furthermore, higher fish-derived n-3 PUFA consumption was associated with habitual aerobic exercise habits. CONCLUSION: Thus, higher fish-derived n-3 PUFA consumption and more aerobic exercise habits may be synergistically associated with lower NLR. This association may explain the preventive effects of fish consumption on the ASCVD risk.

The interaction of ATP11C-b with ezrin contributes to its polarized localization.

ATP11C, a member of the P4-ATPase family, translocates phosphatidylserine and phosphatidylethanolamine at the plasma membrane. We previously revealed that its C-terminal splice variant ATP11C-b exhibits polarized localization in motile cell lines, such as MDA-MB-231 and Ba/F3. In the present study, we found that the C-terminal cytoplasmic region of ATP11C-b interacts specifically with ezrin. Notably, the LLxY motif in the ATP11C-b C-terminal region is crucial for its interaction with ezrin as well as its polarized localization on the plasma membrane. A constitutively active, C-terminal phosphomimetic mutant of ezrin was colocalized with ATP11C-b in polarized motile cells. ATP11C-b was partially mislocalized in cells depleted of ezrin alone, and exhibited greater mislocalization in cells simultaneously depleted of the family members ezrin, radixin and moesin (ERM), suggesting that ERM proteins, particularly ezrin, contribute to the polarized localization of ATP11C-b. Furthermore, Atp11c knockout resulted in C-terminally phosphorylated ERM protein mislocalization, which was restored by exogenous expression of ATP11C-b but not ATP11C-a. These observations together indicate that the polarized localizations of ATP11C-b and the active form of ezrin to the plasma membrane are interdependently stabilized.

Preserving Brain LPC-DHA by Plasma Supplementation Attenuates Brain Injury after Cardiac Arrest.

OBJECTIVE: Cardiac arrest (CA) is a major health burden with brain damage being a significant contributor to mortality. We found lysophosphatidylcholine (LPC), including a species containing docosahexaenoic acid (LPC-DHA), was significantly decreased in plasma post-CA, supplementation of which significantly improved neurological outcomes. The aim of this study is to understand the protective role of LPC-DHA supplementation on the brain post-CA. METHODS: We first evaluated associations between the plasma level of LPC-DHA and neurological injury and outcomes of human patients with CA. We then utilized a rat CA model and cell cultures to investigate therapeutic and mechanistic aspects of plasma LPC-DHA supplementation. RESULTS: We found that decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of the difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased levels of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocytes, and expression of various inflammatory and mitochondrial dynamics genes. We also observed deceased severity of metabolic alterations with LPC-DHA supplementation using untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. INTERPRETATION: The observed neuroprotection accompanied with normalized brain LPC-DHA level by plasma supplementation implicate the importance of preventing the decrease of brain LPC-DHA post-CA for attenuating brain injury. Furthermore, the data supports the causative role of decreased plasma LPC-DHA for brain damage after CA. ANN NEUROL 2022;91:389-403.

Higher frequency of fish intake and healthy lifestyle behaviors may be associated with a lower platelet count in Japan: Implication for the anti-atherosclerotic effect of fish intake.

BACKGROUND: Habitual fish intake and healthier lifestyles are associated with a lower risk of atherosclerotic cardiovascular disease (ASCVD). Higher platelet counts (PLCs) are reportedly associated with higher ASCVD events. We aimed to investigate the association between fish intake and lifestyle with PLCs. METHODS: We conducted a cross-sectional study in a cohort of 9329 participants (average age: 46.9 ± 12.9 years; 58.9% men) with no history of ASCVD registered at the Health Planning Center of Nihon University Hospital in 2019. RESULTS: The average fish intake frequency was 2.15 ± 1.28 days/week. As fish intake frequency increased (0, 1, 2, 3, 4, 5, 6, and 7 days), PLC decreased significantly (p < 0.0001). Multivariable logistic regression analysis showed that higher fish intake frequency tended to be a determinant of lower PLC. Aerobic exercise habits and sleep duration were independent negative determinants of PLC. Cigarette smoking habits were a positive independent determinant of PLC. Furthermore, with increasing fish intake frequency, the proportion of participants with habitual aerobic exercise, non-smoking habits, and longer sleep duration increased (p < 0.0001 for all). Higher n-3 polyunsaturated fatty acid (n-3 PUFA), calculated based on data from the Japanese National Health and Nutrition Survey, intake was associated with a lower PLC. CONCLUSION: Higher fish intake and healthier lifestyle behaviors may be comprehensively associated with lower PLCs. The intake of N-3 PUFA with anti-inflammatory effects, rich in fish, may also be related to the lower PLC. This association may explain the preventive effects of fish intake on ASCVD risk.

Habitual fish consumption and healthy lifestyle behaviours may be associated with higher total serum bilirubin level and anti-inflammatory activity: a cross-sectional study.

Habitual fish consumption and a healthy lifestyle are associated with lower atherosclerotic CVD (ASCVD) risk. Mildly elevated bilirubin, an end product of Hb metabolism, may be associated with anti-inflammatory effects, suppressing ASCVD risk. No data exist on the relationship between fish consumption, total serum bilirubin (TSB) and inflammation in clinical settings. We conducted a cross-sectional study between April 2019 and March 2020 in a cohort of 8292 participants (average age, 46·7 (sd 12·9) years and 58·9 % men) with no history of ASCVD and TSB concentrations < 2·0 mg/dl. Multiple stepwise regression analysis showed Hb concentrations were a solid positive determinant of TSB concentrations (ß = 0·302, P< 0·0001). Fish consumption (ß = 0·025, P= 0·019) and aerobic exercise (ß = 0·021, P= 0·043) were statistically weak but significantly positive determinants of TSB concentrations. Cigarette smoking negatively affected TSB concentrations (ß = −0·104, P< 0·0001). Moreover, with increasing fish consumption, the proportion of participants with a habit of cigarette smoking decreased, and that of participants who engaged in aerobic exercises increased (P< 0·0001 for both). Furthermore, as TSB concentrations increased, the leukocyte counts and C-reactive protein concentrations decreased (P< 0·0001 for both). In conclusion, despite the lesser relevance given to TSB concentrations than Hb concentrations, higher fish consumption and healthier lifestyle behaviours related to fish consumption habits may be additively or synergistically associated with higher TSB concentrations and anti-inflammatory activity, leading to attenuated ASCVD risk. Further investigations are needed to clarify the causal relationships between these factors.

Clinical picture of the duration of venoarterial extracorporeal membrane oxygenation: analysis from JROAD-DPC.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for critically ill patients all over the world; however, comprehensive survey regarding the relationship between VA-ECMO duration and prognosis is limited. We conducted a survey of VA-ECMO patients in the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), which was a health insurance claim database study among cardiovascular centers associated with the Japan Circulation Society, between April 2012 and March 2016. Out of 13,542 VA-ECMO patients, we analyzed 5766 cardiovascular patients treated with VA-ECMO. 68% patients used VA-ECMO only for 1 day and 93% had VA-ECMO terminated within 1 week. In multivariate analysis, the hazard ratio of 1-day support was significantly high at 1.72 (95% confidence intervals; 95% CI 1.53-1.95) (p < 0.001), while that of 2-day [0.60 (95% CI 0.49-0.73)], 3-day [0.75 (95% CI 0.60-0.94)], 4-day [0.43 (95% CI 0.31-0.60)] and 5-day support [0.62 (95% CI 0.44-0.86)] was significantly low. Comprehensive database analysis of JROAD-DPC revealed that cardiovascular patients who were supported with VA-ECMO for 2-5 days showed lower mortality. The optimal VA-ECMO support window should be investigated in further studies.

Neurological Improvement via Lysophosphatidic Acid Administration in a Rodent Model of Cardiac Arrest-Induced Brain Injury.

Lysophosphatidic acid (LPA) serves as a fundamental constituent of phospholipids. While prior studies have shown detrimental effects of LPA in a range of pathological conditions, including brain ischemia, no studies have explored the impact of LPA in the context of cardiac arrest (CA). The aim of this study is to evaluate the effects of the intravenous administration of an LPA species containing oleic acid, LPA (18:1) on the neurological function of rats (male, Sprague Dawley) following 8 min of asphyxial CA. Baseline characteristics, including body weight, surgical procedure time, and vital signs before cardiac arrest, were similar between LPA (18:1)-treated (n = 10) and vehicle-treated (n = 10) groups. There was no statistically significant difference in 24 h survival between the two groups. However, LPA (18:1)-treated rats exhibited significantly improved neurological function at 24 h examination (LPA (18:1), 85.4% ± 3.1 vs. vehicle, 74.0% ± 3.3, p = 0.045). This difference was most apparent in the retention of coordination ability in the LPA (18:1) group (LPA (18:1), 71.9% ± 7.4 vs. vehicle, 25.0% ± 9.1, p < 0.001). Overall, LPA (18:1) administration in post-cardiac arrest rats significantly improved neurological function, especially coordination ability at 24 h after cardiac arrest. LPA (18:1) has the potential to serve as a novel therapeutic in cardiac arrest.

Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

OBJECTIVES: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival. DESIGN: Clinical case control study followed by translational laboratory study. SETTING: Research institution. PATIENTS/SUBJECTS: Adult cardiac arrest patients and male Sprague-Dawley rats. INTERVENTIONS: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle. MEASUREMENTS AND MAIN RESULTS: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect. CONCLUSIONS: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

Inadequate sleep duration may attenuate the anti-inflammatory effects of fish consumption in a healthy Japanese population: a cross-sectional study.

High fish consumption may be associated with lower inflammation, suppressing atherosclerotic CVD (ASCVD). Long sleep duration, as well as short sleep, may contribute to inflammation, thus facilitating ASCVD. This study investigated the overall association between fish consumption, sleep duration and leucocytes count. We conducted a cross-sectional study between April 2019 and March 2020 with a cohort of 8947 apparently healthy participants with no history of ASCVD (average age, 46·9 ± 12·3 years and 59 % males). The average frequency of fish consumption and sleep duration were 2·13 ± 1·26 d/week and 6·0 ± 0·97 h/d. Multivariate linear regression analysis revealed that increased fish consumption was an independent determinant of sleep duration (ß = 0·084, P < 0·0001). Additionally, habitual aerobic exercise (ß = 0·059, P < 0·0001) or cigarette smoking (ß = −0·051, P < 0·0001) and homoeostasis model assessment-insulin resistance (HOMA-IR) (ß = −0·039, P = 0·01) were independent determinants of sleep duration. Furthermore, multivariate linear regression analysis identified fish consumption as an independent determinant of leucocytes count (ß = −0·091, P < 0·0001). However, a significant U-shaped curve was found between leucocytes count and sleep duration, with 6­7 h of sleep as the low value (P = 0·015). Higher fish consumption may be associated with a lower leucocytes count in the presence of adequate sleep duration and healthy lifestyle behaviors. However, long sleep duration was also related to increased inflammation, even in populations with high fish consumption. Further studies are needed to clarify the causality between these factors.

Combined Higher Frequency Fish Consumption and Healthy Lifestyle May Lower the Triglyceride/HDL-C Ratio in Middle-Aged Japanese Males: Anti-Atherosclerotic Effect of Fish Consumption.

BACKGROUND: Fish consumption may be associated with a low risk of coronary artery disease. We aimed to investigate whether higher fish consumption results in improved lifestyle behaviors and thus lower triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio - a predictor of atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This cross-sectional study included 2,947 middle-aged Japanese males with no history of ASCVD or lipid-modifying therapy, who presented at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. We performed an analysis of variance using fish consumption as a categorical variable (0-2 days, 3-4 days, or 5-7 days per week). The serum TG/HDL-C ratio in the 5-7 days fish consumption group was significantly lower than those in the 0-2 and 3-4 days fish consumption groups (p < 0.0001 and p < 0.01, respectively). Multiple regression stepwise analysis revealed that weekly fish consumption negatively and independently determined the TG/HDL-C ratio (ß = -0.061, p = 0.001). As fish consumption increased, the proportion of subjects with smoking habits decreased (p = 0.014), those engaging in aerobic exercises and aggressive daily physical activity increased (p < 0.0001 for both), and those with alcohol habit increased (p < 0.0001). In addition, we developed the risk stratification for ASCVD by combining the serum HDL-C level and the serum TG/HDL-C ratio with fish consumption. CONCLUSION: Increased frequency of fish consumption and improved lifestyle behaviors due to daily fish intake may work additively to lower the serum TG/HDL-C ratio. These associations may explain why high fish consumption is associated with a lower risk of ASCVD. Our findings may help physicians and nutritionists in treating patients with heart diseases and metabolic conditions by recommending a high fish diet in middle-aged Japanese males.

Oxyhaemoglobin Level Measured Using Near-Infrared Spectrometer Is Associated with Brain Mitochondrial Dysfunction After Cardiac Arrest in Rats.

Cerebral blood oxygenation (CBO), measured using near-infrared spectroscopy (NIRS), can play an important role in post-cardiac arrest (CA) care as this emerging technology allows for noninvasive real-time monitoring of the dynamic changes of tissue oxygenation. We recently reported that oxyhaemoglobin (oxy-Hb), measured using NIRS, may be used to evaluate the quality of chest compressions by monitoring the brain tissue oxygenation, which is a critical component for successful resuscitation. Mitochondria are the key to understanding the pathophysiology of post-CA oxygen metabolism. In this study, we focused on mitochondrial dysfunction, aiming to explore its association with CBO parameters such as oxy-Hb and deoxyhaemoglobin (deoxy-Hb) or tissue oxygenation index (TOI). Male Sprague-Dawley rats were used in the study. We applied NIRS between the nasion and the upper cervical spine. Following 10 min of CA, the rats underwent cardiopulmonary resuscitation (CPR) with a bolus injection of 20 µg/kg epinephrine. At 10 and 20 min after CPR, brain, and kidney tissues were collected. We isolated mitochondria from these tissues and evaluated the association between CBO and mitochondrial oxygen consumption ratios. There were no significant differences in the mitochondrial yields (10 vs. 20 min after resuscitation: brain, 1.33 ± 0.68 vs. 1.30 ± 0.75 mg/g; kidney, 19.5 ± 3.2 vs. 16.9 ± 5.3 mg/g, respectively). State 3 mitochondrial oxygen consumption rates, known as ADP-stimulated respiration, demonstrated a significant difference at 10 vs. 20 min after CPR (brain, 170 ± 26 vs. 115 ± 17 nmol/min/mg protein; kidney, 170 ± 20 vs. 130 ± 16 nmol/min/mg protein, respectively), whereas there was no significant difference in ADP non-dependent state 4 oxygen consumption rates (brain, 34.0 ± 6.7 vs. 31.8 ± 10 nmol/min/mg protein; kidney, 29.8 ± 4.8 vs. 21.0 ± 2.6 nmol/min/mg protein, respectively). Consequently, the respiratory control ratio (RCR = state 3/state 4) showed a significant difference over time, but this was only noted in the brain (brain, 5.0 ± 0.29 vs. 3.8 ± 0.64; kidney, 5.8 ± 0.53 vs. 6.2 ± 0.25 nmol/min/mg protein, respectively). The oxy-Hb levels had a dynamic change after resuscitation, and they had a significant association with the RCR of the brain mitochondria (r = 0.8311, p = 0.0102), whereas deoxy-Hb and TOI did not (r = -0.1252, p = 0.7677; r = 0.4186, p = 0.302, respectively). The RCRs of the kidney mitochondria did not have a significant association with CBO (oxy-Hb, r = -0.1087, p = 0.7977; deoxy-Hb, r = 0.1565, p = 0.7113; TOI, r = -0.1687, p = 0.6896, respectively). The brain mitochondrial respiratory dysfunction occurred over time, and it was seen at the time points between 10 and 20 min after CPR. The oxy-Hb level was associated with brain mitochondrial dysfunction during the early post-resuscitation period.

Effect of Atorvastatin on Microcirculation Evaluated by Vascular Occlusion Test with Peripheral Near-Infrared Spectroscopy.

The vascular occlusion test (VOT) with peripheral near-infrared spectroscopy (NIRS) is a non-invasive method to evaluate peripheral microcirculation. Statin therapy is widely used for patients with dyslipidaemia and contributes to reducing low-density lipoprotein cholesterol (LDL-C) levels and adverse cardiovascular events. However, it is not yet clear whether statin treatment improves peripheral microcirculation assessed by VOT with NIRS. In the present study, using VOT with NIRS, we evaluated the effect of statin therapy on peripheral microcirculation in patients with dyslipidaemia before and after statin therapy. METHODS: A total of six consecutive patients with dyslipidaemia who had not received statin therapy (6 males, mean age 71.8 ± 7.4 years) were enrolled. All patients were administered atorvastatin and their peripheral microcirculation assessed using VOT with NIRS (NIRO-200NX, Hamamatsu Photonics K.K., Japan) before and after statin therapy. The NIRS probe was attached to the right thenar eminence and brachial artery blood flow was blocked for 3 min at 50 mmHg above the resting systolic blood pressure. Maximum and minimum values of NIRS parameters after the VOT were used to determine concentration changes for total haemoglobin (ΔcHb), oxyhaemoglobin (ΔO2Hb), deoxyhaemoglobin (ΔHHb), and tissue oxygenation index (ΔTOI). RESULTS: During the follow-up period (mean 30.3 ± 6.5 days), LDL-C level decreased from 129.7 ± 26.3 to 67.5 ± 20.2 mg/dL (p-value = 0.031), ΔTOI increased from 24.0 ± 5.3 to 33.7 ± 6.3% (p-value = 0.023), and ΔO2Hb increased from 16.4 ± 5.3 to 20.0 ± 6.6 µmol/L (p-value = 0.007). ΔcHb and ΔHHb did not change significantly. CONCLUSION: ΔO2Hb and ΔTOI were significantly increased during the follow-up period. These findings suggest that ΔO2Hb and ΔTOI could assess the improvement of peripheral microcirculation by statin therapy. Compared to ΔTOI, ΔO2Hb seems to be a more useful parameter to evaluate peripheral microcirculation.

Venovenous extracorporeal membrane oxygenation for acute respiratory distress syndrome due to an acute type B aortic dissection: a case report.

Acute type B aortic dissection is sometimes complicated by acute respiratory failure requiring mechanical ventilation. Herein, we describe our experience in a rare acute type B aortic dissection-associated respiratory failure case culminating in acute respiratory distress syndrome. The patient was a 45-year-old man admitted with a complaint of sudden chest pain radiating to his back. On computed tomography, an acute type B aortic dissection was diagnosed. He had no dyspnea on admission, but his respiratory function subsequently deteriorated, and severe acute respiratory distress syndrome was diagnosed on Day 4. Venovenous extracorporeal membrane oxygenation with anticoagulation plus continuous renal replacement therapy for oliguria improved the oxygenation, and the patient was weaned from the extracorporeal membrane oxygenation on Day 8. This patient fully recovered without worsening the aortic dissection, using venovenous extracorporeal membrane oxygenation with anticoagulation plus a continuous renal replacement therapy.

Institutional Characteristics and Prognosis of Acute Myocardial Infarction With Cardiogenic Shock in Japan　- Analysis From the JROAD/JROAD-DPC Database.

BACKGROUND: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients.Methods and Results:In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%. CONCLUSIONS: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Gender differences in the associations among fish intake, lifestyle, and non-HDL-C level in Japanese subjects over the age of 50 years: Anti-atherosclerotic effect of fish consumption.

BACKGROUND AND AIMS: Higher fish consumption may lead to the suppression of atherogenesis. The present study was aimed at investigating the gender differences in association with the frequency of fish intake, lifestyle behaviors and serum non-high-density lipoprotein cholesterol (non-HDL-C) levels. METHODS AND RESULTS: This cross-sectional study was conducted in a cohort of 4320 (2479 males, 1570 females) healthy Japanese subjects over 50 years of age registered at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. The average weekly frequency of fish intake was 2.58 ± 1.39 days in males and 2.42 ± 1.36 days in females. In males, the serum non-HDL-C level decreased significantly as the weekly frequency of fish intake (0-1 days, 2-3 days, 4-5 days, or 6-7 days) increased (p < 0.0001). Multiple stepwise regression analysis identified the weekly frequency of fish intake (ß = -0.056, p = 0.004) and habitual aerobic exercise (ß = -0.063, p = 0.001) as independent determinants of the serum non-HDL-C level. On the other hand, no such associations were observed in females. However, the proportion of subjects engaging in habitual aerobic exercise increased as the frequency of fish intake increased even among females. CONCLUSIONS: A higher frequency of fish intake may be associated with healthier lifestyle behaviors and lower non-HDL-C levels in males, but not in females. There appear to be gender differences in the relationships between the intake of fish and lifestyle behaviors on lipid metabolism. CLINICAL TRIAL REGISTRATION: umin (http://www.umin.ac.jp/) Study ID: UMIN000035899.

Association among daily fish intake, white blood cell count, and healthy lifestyle behaviors in an apparently healthy Japanese population: implication for the anti-atherosclerotic effect of fish consumption.

Higher fish consumption has been reported to be associated with a lower incidence of coronary artery disease. We hypothesized that a higher frequency of fish intake may be associated with lower peripheral white blood cell (WBC) counts, a marker of chronic inflammation, which is known to be involved in the development of atherosclerotic cardiovascular disease (ASCVD), and a healthy lifestyle. This cross-sectional study was conducted between April 2018 and August 2018 at the Health Planning Center of Nihon University Hospital in a cohort of 4105 apparently healthy subjects. The average frequency of fish intake was 2.3 ± 1.3 days per week. The WBC count decreased significantly as the frequency of fish intake (0-2 days, 3-4 days, or 5-7 days per week) increased (s < 0.0001). Multivariate linear regression analysis identified higher weekly frequency of fish intake as a significant independent determinant of a lower WBC count (ß = - 0.051, p = 0.001). Furthermore, as the weekly frequency of fish intake increased, the proportion of habitual cigarette smokers decreased (p = 0.021), that of subjects engaging in habitual aerobic exercises increased (p < 0.0001), and the weekly alcohol intake frequency increased (p < 0.0001). Moreover, the above-mentioned lifestyle behaviors were also independent determinants of the WBC count. These results suggest that a high frequency of fish intake might be associated with healthier lifestyle behaviors as well as lower WBC counts, and thus may both exert beneficial anti-inflammatory effects and represent a component of healthier lifestyle behaviors associated with a lower risk of ASCVD in Japanese. This association may be partially related to the preventive effects of a higher fish intake on ASCVD events. CLINICAL TRIAL REGISTRATION: UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000039197 retrospectively registered 1 February 2020.

Higher Frequency of Fish Intake May Be Associated with a Lower Neutrophil/Lymphocyte Ratio: Anti-Atherosclerotic Effects of Fish Consumption.

BACKGROUND: Higher fish consumption has been reported to be associated with a lower incidence of coronary artery disease (CAD). An elevated neutrophil/lymphocyte ratio (NLR), a marker of systemic inflammation, is reportedly associated with the development of adverse CAD events. We hypothesized that a higher fish intake was associated with a lower NLR. METHODS AND RESULTS: This cross-sectional study was conducted in a cohort of 8,237 Japanese subjects who had no history of atherosclerotic cardiovascular disease registered at the Health Planning Center of Nihon University Hospital between April 2018 and March 2019. The average weekly frequency of fish intake was 2.32 ± 1.31 days. The NLR decreased significantly as the weekly frequency of fish intake (0 day, 1-2 days, 3-4 days, or 5-7 days) increased (p = 0.001). A multiple stepwise regression analysis identified the weekly frequency of fish intake (ß = -0.045, p < 0.0001) and habitual alcohol intake (ß = -0.051, p < 0.0001) as significant but weak, negative, and independent determinants of the NLR. Conversely, the presence of metabolic syndrome (ß = 0.046, p < 0.0001), the presence of treatment for diabetes mellitus (ß = 0.054, p < 0.0001), and the presence of treatment for hypertension (ß = 0.043, p < 0.0001) were significant positive and independent determinants of the NLR. CONCLUSIONS: The present results suggest that a higher frequency of fish intake appears to be associated with a lower NLR, suggesting an anti-systemic inflammation effect. This association may partially explain the preventive effects of a higher fish intake on CAD events.

Effect of Adrenaline on Cerebral Blood Oxygenation Measured by NIRS in a Rat Asphyxia Cardiac Arrest Model.

Adrenaline is an important pharmacologic treatment during cardiac arrest (CA) for resuscitation. Recent studies suggest that adrenaline increases the likelihood of return of spontaneous circulation (ROSC) but does not contribute to improving neurological outcomes of CA. The mechanisms have not been elucidated yet. A bimodal increase in mean arterial pressure (MAP) is observed after adrenaline injection in rodent CA models [17]. In this study, we focused on alteration of systemic arterial pressure in conjunction with the measurement of cerebral blood oxygenation (CBO) such as oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) by near-infrared spectroscopy (NIRS). Male Sprague-Dawley rats were used. We attached NIRS between the nasion and the upper cervical spine. Rats underwent 10-minute asphyxia to induce CA. Then, cardiopulmonary resuscitation (CPR) was started, followed by a 20 µg/kg of bolus adrenaline injection at 30 seconds of CPR. This injection accelerated the first increase in MAP, and ROSC was observed with an abrupt increase in CBO. Interestingly, the second increase in MAP, once it exceeded a certain value, was accompanied by paradoxical decreases of Oxy-Hb and TOI, while Deoxy-Hb increased. Based on this finding, we compared Oxy-Hb, Deoxy-Hb, and TOI at the first MAP ≈ 100 mmHg and the second MAP ≈ 100 mmHg. The average of Oxy-Hb and TOI from the 13 animals significantly decreased at the second increase in MAP over 100 mmHg, while Deoxy-Hb significantly increased. NIRS identified a decrease in Oxy-Hb after ROSC. These findings may be a clue to understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post-resuscitation.

Evaluation of the Quality of Chest Compression with Oxyhemoglobin Level by Near-Infrared Spectroscopy in a Rat Asphyxia Cardiac Arrest Model.

The real-time evaluation of chest compression during cardiopulmonary resuscitation is important to increase the chances of survival from a cardiac arrest (CA). In addition, cerebral oxygen level measured by near-infrared spectroscopy (NIRS) plays an important role as an indicator of return of spontaneous circulation. Recently, we developed a new method to improve the quality of chest compression using a thoracic pump in conjunction with the classic cardiac pump in a rat asphyxia CA model. This study evaluated the quality of chest compression using NIRS in male Sprague-Dawley rats. NIRS was attached between the nasion and the upper cervical spine, and rats underwent 10 minute asphyxia CA. After CA, we alternately performed three different types of chest compression (cardiac, thoracic, and cardiac plus thoracic pumps) every 30 seconds for up to 4 and a half minutes. We measured the oxyhemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb), and tissue oxygenation index (TOI) and compared these values between the groups. Oxy-Hb was significantly different among the groups (cardiac, thoracic, and cardiac plus thoracic, 1.5 ± 0.9, 4.4 ± 0.7, and 5.9 ± 2.1 µmol/L, p < 0.01, respectively), while Deoxy-Hb and TOI were not (Deoxy-HB -2.7 ± 1.2, -1.1 ± 3.2, and -1.6 ± 10.1 µmol/L; TOI, 1.8 ± 1.8, 5.5 ± 1.3, and 9.5 ± 8.0%, respectively). Oxy-Hb showed potential to evaluate the quality of chest compression in a rat asphyxia CA model.