Publications by authors named "Tsukasa Yagi"

37 Publications

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

Crit Care Med 2021 Jul 2. Epub 2021 Jul 2.

1 Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, Manhasset, NY. 2 Department of Emergency Medicine, Northshore University Hospital, Manhasset, NY. 3 Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY. 4 Biostatistics Unit, Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CCM.0000000000005180DOI Listing
July 2021

Pneumatosis Intestinalis in the Setting of COVID-19: A Single Center Case Series From New York.

Front Med (Lausanne) 2021 4;8:638075. Epub 2021 Jun 4.

Department of Surgery, North Shore University Hospital, Manhasset, NY, United States.

This case series reviews four critically ill patients infected with severe acute respiratory syndrome coronavirus 2 (SARSCoV2) [coronavirus disease 2019 (COVID-19)] suffering from pneumatosis intestinalis (PI) during their hospital admission. All patients received the biological agent tocilizumab (TCZ), an interleukin (IL)-6 antagonist, as an experimental treatment for COVID-19 before developing PI. COVID-19 and TCZ have been independently linked to PI risk, yet the cause of this relationship is unknown and under speculation. PI is a rare condition, defined as the presence of gas in the intestinal wall, and although its pathogenesis is poorly understood, intestinal ischemia is one of its causative agents. Based on COVID-19's association with vasculopathic and ischemic insults, and IL-6's protective role in intestinal epithelial ischemia-reperfusion injury, an adverse synergistic association of COVID-19 and TCZ can be proposed in the setting of PI. To our knowledge, this is the first published, single center, case series of pneumatosis intestinalis in COVID-19 patients who received tocilizumab therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.638075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212022PMC
June 2021

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

Ann Nutr Metab 2021 May 26:1-8. Epub 2021 May 26.

Department of Medicine, Division of Cardiology, Nihon University School of Medicines, Tokyo, Japan.

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 (β = -0.045, p < 0.0001) and habitual alcohol intake (β = -0.051, p < 0.0001) as significant but weak, negative, and independent determinants of the NLR. Conversely, the presence of metabolic syndrome (β = 0.046, p < 0.0001), the presence of treatment for diabetes mellitus (β = 0.054, p < 0.0001), and the presence of treatment for hypertension (β = 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000515915DOI Listing
May 2021

Treatment With Vasopressor Agents for Cardiovascular Shock Patients With Poor Renal Function; Results From the Japanese Circulation Society Cardiovascular Shock Registry.

Front Med (Lausanne) 2021 3;8:648824. Epub 2021 May 3.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

According to the guidelines for cardiogenic shock, norepinephrine is associated with fewer arrhythmias than dopamine and may be the better first-line vasopressor agent. This study aimed to evaluate the utility of norepinephrine vs. dopamine as first-line vasopressor agent for cardiovascular shock depending on the presence and severity of renal dysfunction at hospitalization. This was a secondary analysis of the prospective, multicenter Japanese Circulation Society Cardiovascular Shock Registry (JCS Shock Registry) conducted between 2012 and 2014, which included patients with shock complicating emergency cardiovascular disease at hospital arrival. The analysis included 240 adult patients treated with norepinephrine alone ( = 98) or dopamine alone ( = 142) as the first-line vasopressor agent. Primary endpoint was mortality at 30 days after hospital arrival. The two groups had similar baseline characteristics, including estimated glomerular filtration rate (eGFR), and similar 30-day mortality rates. The analysis of the relationship between 30-day mortality rate after hospital arrival and vasopressor agent used in patients categorized according to the eGFR-based chronic kidney disease classification revealed that norepinephrine as the first-line vasopressor agent might be associated with better prognosis of cardiovascular shock in patients with mildly compromised renal function at admission (0.0 vs. 22.6%; = 0.010) and that dopamine as the first-line vasopressor agent might be beneficial for cardiovascular shock in patients with severely compromised renal function [odds ratio; 0.22 (95% confidence interval 0.05-0.88; = 0.032)]. Choice of first-line vasopressor agent should be based on renal function at hospital arrival for patients in cardiovascular shock. http://www.umin.ac.jp/ctr/, Unique identifier: 000008441.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2021.648824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126606PMC
May 2021

Assessment of Cerebral Blood Oxygenation by Near-Infrared Spectroscopy before and after Resuscitation in a Rat Asphyxia Cardiac Arrest Model.

Adv Exp Med Biol 2021 ;1269:311-315

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Clinical investigators have focused on the real-time evaluation of cerebral blood oxygenation (CBO) by near-infrared spectroscopy (NIRS) during cardiopulmonary resuscitation (CPR). A previous study showed that an abrupt increase of oxy-hemoglobin (Hb) level and tissue oxygenation index (TOI) was associated with the timing of return of spontaneous circulation (ROSC). However, it is not clear how TOI alters before and after CPR including a period of cardiac arrest (CA). Therefore, this study aimed to assess CBO with asphyxia CA and its association with CPR to ROSC in rats. Male Sprague-Dawley rats were used. We attached NIRS (NIRO-200NX, Hamamatsu Photonics, Japan) from the nasion to the upper cervical spine in rats. A ten-minute asphyxia was given to induce CA. After CA, mechanical ventilation was restarted, and manual CPR was performed. We examined the mean arterial pressure (MAP), end-tidal carbon dioxide (ETCO), and Oxy/Deoxy-Hb and TOI. Out of 14 rats, 11 obtained sustained ROSC. After the induction of asphyxia, a rapid drop of TOI was observed, followed by a subsequent increase of Oxy-Hb, Deoxy-Hb, and TOI with CPR. Recent CPR guidelines suggest the use of ETCO during CPR since its abrupt increase is a reasonable indicator of ROSC. In this study, abrupt increases in MAP, ETCO, and TOI were observed at the time of ROSC. TOI can be an alternative to ETCO for identifying ROSC after CA, and it also has the capability of monitoring CBO during and after CPR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-48238-1_49DOI Listing
May 2021

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

Adv Exp Med Biol 2021 ;1269:277-281

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

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 (Okuma et al. Intensive Care Med Exp 7(1), 2019). 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 in understanding the mechanism of how and why adrenaline alters the neurological outcomes of CA post resuscitation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-48238-1_44DOI Listing
May 2021

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

Adv Exp Med Biol 2021 ;1269:265-269

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-48238-1_42DOI Listing
May 2021

Near-Infrared Spectroscopy Might Help Prevent Onset of Cerebral Hyperperfusion Syndrome.

Adv Exp Med Biol 2021 ;1269:63-67

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

Cerebral hyperperfusion syndrome (CHS) is a rare but fatal perioperative complication after surgical correction of carotid stenosis. Despite numerous treatment options for preventing CHS, it does occur in some patients. We developed the outlet gate technique (OGT), in which the embolic balloon was deflated gradually in accordance with the ratio of oxygen saturation measured by a brain oximeter of the ipsilateral brain region to that in the contralateral region. Between June 2017 and May 2018, 39 patients with carotid stenosis underwent endovascular carotid revascularization procedures; of these, 20 underwent the procedure with the OGT. CBO was measured five times in those 20 patients: before the procedure, with the embolic protection device (EPD) on, with the EPD off, during the procedure, and after the procedure. Preventive treatment options were used more frequently in these patients, and although their surgical status seemed more complicated, perioperative complications were not increased. There were almost significant differences between CBO values except between those during and after the procedure with the OGT. This showed that the OGT allowed for stabilization of the CBO and thus has the potential to prevent CHS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-48238-1_10DOI Listing
May 2021

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

Adv Exp Med Biol 2021 ;1269:39-43

Feinstein Institute for Medical Research, Northwell Health System, Manhasset, NY, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-48238-1_6DOI Listing
May 2021

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.

Nutr Metab Cardiovasc Dis 2021 05 13;31(5):1434-1444. Epub 2021 Jan 13.

Department of Medicine, Division of Cardiology, Nihon University School of Medicines, Tokyo, Japan.

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 (β = -0.056, p = 0.004) and habitual aerobic exercise (β = -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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.numecd.2020.12.031DOI Listing
May 2021

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

Circ J 2021 Mar 4. Epub 2021 Mar 4.

Department of Cardiovascular Medicine, Kyushu University.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-20-0655DOI Listing
March 2021

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

Perfusion 2021 Feb 26:267659121998545. Epub 2021 Feb 26.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0267659121998545DOI Listing
February 2021

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.

Heart Vessels 2021 Jul 7;36(7):924-933. Epub 2021 Jan 7.

Department of Medicine, Division of Cardiology, Nihon University School of Medicines, Tokyo, Japan.

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 (β =  - 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00380-020-01769-9DOI Listing
July 2021

Plasma metabolomics supports the use of long-duration cardiac arrest rodent model to study human disease by demonstrating similar metabolic alterations.

Sci Rep 2020 11 12;10(1):19707. Epub 2020 Nov 12.

Laboratory for Critical Care Physiology, Feinstein Institutes for Medical Research, 350 Community Dr, Manhasset, NY, 11030, USA.

Cardiac arrest (CA) is a leading cause of death and there is a necessity for animal models that accurately represent human injury severity. We evaluated a rat model of severe CA injury by comparing plasma metabolic alterations to human patients. Plasma was obtained from adult human control and CA patients post-resuscitation, and from male Sprague-Dawley rats at baseline and after 20 min CA followed by 30 min cardiopulmonary bypass resuscitation. An untargeted metabolomics evaluation using UPLC-QTOF-MS/MS was performed for plasma metabolome comparison. Here we show the metabolic commonality between humans and our severe injury rat model, highlighting significant metabolic dysfunction as seen by similar alterations in (1) TCA cycle metabolites, (2) tryptophan and kynurenic acid metabolites, and (3) acylcarnitine, fatty acid, and phospholipid metabolites. With substantial interspecies metabolic similarity in post-resuscitation plasma, our long duration CA rat model metabolically replicates human disease and is a suitable model for translational CA research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-76401-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665036PMC
November 2020

Administration of eicosapentaenoic acid may alter lipoprotein particle heterogeneity in statin-treated patients with stable coronary artery disease: A pilot 6-month randomized study.

J Cardiol 2020 11 4;76(5):487-498. Epub 2020 Jul 4.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo Japan.

Background: We hypothesized that the addition of eicosapentaenoic acid (EPA) to ongoing statin therapy could change the particle heterogeneity of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles, even in stable coronary artery disease (CAD) patients.

Methods: We assigned CAD patients already receiving statin therapy to one of two groups: an EPA group (1800 mg/day; n = 30) and a control group (n = 30). A gel permeation high-performance liquid chromatography method was used to measure the particle concentration and number of lipoprotein subclasses.

Results: In the EPA group, significant decreases of both the concentration and number of medium LDL (p = 0.0002 and 0.0001), small LDL (p = 0.0004 and 0.0005) and very small LDL (p = 0.0005 and 0.002) particles were observed. Conversely, the concentration and number of large HDL particles increased significantly (p = 0.024 and 0.048). The concentration of very large HDL particles also increased significantly (p = 0.028). Furthermore, significant correlations between the variables that showed significant changes in the LDL and HDL particle subclasses, and the EPA/arachidonic acid (AA) ratio were found. No other significant associations of lipoprotein particle heterogeneity with the serum EPA/AA ratio were noted in either the control group or the EPA group. Interestingly, univariate and multivariate regression analyses revealed that increased serum lecithin-cholesterol acyltransferase activity, a key enzyme of HDL cholesterol efflux, was a predictor for increased above-mentioned HDL particles subclasses.

Conclusions: Administration of EPA might alter both LDL and HDL particle heterogeneity, causing decreased concentration and number of smaller LDL particles and increased concentration and number of larger HDL particles. Furthermore, addition of EPA to ongoing statin therapy appears to be capable of increasing the EPA/AA ratio, which might have an anti-atherosclerotic effect on lipoprotein particle heterogeneity, even in stable CAD patients with well-controlled serum lipid levels.

Clinical Trial Registration: UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2020.06.006DOI Listing
November 2020

The serum uric acid level in females may be a better indicator of metabolic syndrome and its components than in males in a Japanese population .

J Cardiol 2020 07 24;76(1):100-108. Epub 2020 Feb 24.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: Although the level of uric acid (UA) is higher in males, increased UA level in females was reported to be closely associated with prevalence of metabolic syndrome (Mets) leading to atherosclerotic cardiovascular disease (ASCVD). Few data exist regarding the gender diferences in relationship between the serum UA levels and cardo-metabolic risk in the Japanese population, which generally contains a lower proportion of obesity than Western populations.

Methods: This cross-sectional study was designed to investigate, by gender, the association between the serum UA level and abdominal obesity, and thereby cardio-metabolic risk i.e. presence of Mets and its components using a sample of 8567 apparently healthy subjects females: n = 3334, males: n = 5233 at the Health Planning Center of Nihon University Hospital between September 2015 and August 2016.

Results: Receiver operating characteristic analysis was performed to reveal the accuracy of serum UA level as a predictor of abdominal obesity based on the Japanese criteria of Mets (females vs. males: area under the curve, 0.751 vs 0.609). Furthermore, the serum UA level and proportion of abdominal obesity rose with increasing age in females; in males, however, these parameters did not change in parallel with age. Furthermore, the serum UA levels in females reflected a status of cardio-metabolic risk when compared with males in a multi-logistic regression analysis. It is particularly worth noting that in the above-mentioned multivariate logistic regression analysis, the odds ratio of hyperuricemia in females was generally 1.3-2.5 times higher than that in males.

Conclusions: Compared with males, increased serum UA level in females might be involved in abdominal obesity and cardio-metabolic risk, possibly leading to the development of ASCVD even in a Japanese population. This may be due to gender differences affecting the development of abdominal obesity and changes in the serum UA levels with age.

Clinical Trial Registration: UMIN (http://www.umin.ac.jp/) Study ID: UMIN000035901retrospectively registered 1 March 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2020.01.011DOI Listing
July 2020

Application of Peripheral Near Infrared Spectroscopy to Assess Risk Factors in Patient with Coronary Artery Disease: Part 2.

Adv Exp Med Biol 2020 ;1232:355-360

NEWCAT Research Institute, Department of Electrical and Electronic Engineering, Nihon University College of Engineering, Koriyama, Japan.

Epicardial adipose tissue (EAT) is associated with visceral fat and various cardiac disorders, such as atrial fibrillation and adverse cardiovascular events. Therefore, it is important to develop a simple and non-invasive inspection method to assess EAT, to prevent unfavorable cardiac events. This study assessed correlations between near-infrared spectroscopy (NIRS) changes induced by a vascular occlusion test (VOT) and EAT volume measured by cardiac computed tomography (CCT) in patients with suspected coronary artery disease. We also assessed correlations between body mass index (BMI) and EAT volume in the same population. In addition, these correlations were compared in patients treated with statin therapy and in those without statin therapy. A NIRS probe was set on the right thenar eminence, and brachial artery blood flow was blocked for 3 min before being released. A negative correlation was found between oxyhemoglobin (ΔOHb) and EAT volume in the overall study population (r = -0.236, p = 0.03). Interestingly, although a strong correlation was observed in patients without statin therapy (r = -0.488, p < 0.001), this correlation was not observed in patients with statin therapy (r = 0.157, p = 0.34). These findings suggest that NIRS measurements with VOT may be a useful method to identify patients with high EAT volume and high cardiovascular risks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-34461-0_45DOI Listing
January 2020

Application of Peripheral Near Infrared Spectroscopy to Assess Risk Factors in Patient with Coronary Artery Disease: Part 1.

Adv Exp Med Biol 2020 ;1232:331-337

NEWCAT Research Institute, Department of Electrical and Electronic Engineering, Nihon University College of Engineering, Koriyama, Tokyo, Japan.

Obesity, a risk factor of coronary artery disease, is known to cause peripheral microcirculatory disturbances. This study evaluated the relationship between the degree of obesity and peripheral microcirculatory disturbances, using peripheral near infrared spectroscopy (NIRS) with a vascular occlusion test (VOT). We compared correlations between the NIRS parameter changes induced by VOT and body mass index (BMI) in patients with and without statin therapy. A NIRS probe was set on the right thenar eminence, brachial artery blood flow was blocked for 3 min, and then released. Although total hemoglobin (ΔcHb), deoxyhemoglobin (ΔHHb) and tissue oxygenation index (ΔTOI) were not correlated with BMI, a significant negative correlation was found between oxyhemoglobin (ΔOHb) and BMI in the overall study population (r = -0.255, p-value 0.02). In addition, a significant negative correlation was found between ΔOHb and BMI in patients without statin therapy (r = -0.353, p-value 0.02) but not in patients with statin therapy (r = -0.181, p-value 0.27). These findings suggest that ΔOHb may be a useful indicator to assess peripheral microcirculation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-34461-0_42DOI Listing
January 2020

Usefulness of a New Device to Monitor Cerebral Blood Oxygenation Using NIRS During Cardiopulmonary Resuscitation in Patients with Cardiac Arrest: A Pilot Study.

Adv Exp Med Biol 2020 ;1232:323-329

Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Tokyo, Japan.

Recent guidelines on cardiopulmonary resuscitation (CPR) have stressed the necessity to improve the quality of CPR. Our previous studies demonstrated the usefulness of monitoring cerebral blood oxygenation (CBO) during CPR by near-infrared spectroscopy (NIRS). The present study evaluates whether the NIRO-CCR1, a new NIRS device, is as useful in the clinical setting as the NIRO-200NX. We monitored CBO in 20 patients with cardiac arrest by NIRS. On the arrival of patients at the emergency department, the attending physician immediately assessed whether the patient was eligible for this study after conventional advanced life support and, if eligible, measured CBO in the frontal lobe by NIRS. We found that in all patients, the cerebral blood flow waveform was in synchrony with the chest compressions. Moreover, the tissue oxygenation index increased following cardiopulmonary bypass (CPB) in patients undergoing CPB, including one patient in whom CBO was monitored using the NIRO-CCR1. In addition, although the NIRO-CCR1 could display the pulse rate (Tempo) in real time, Tempo was not always detected, despite detection of the cerebral blood flow waveform. This suggested that chest compressions may not have been effective, indicating that the NIRO-CCR1 also seems useful to assess the quality of CPR. This study suggests that the NIRO-CCR1 can measure CBO during CPR in patients with cardiac arrest as effectively as the NIRO-200NX; in addition, the new NIRO-CCR1 may be even more useful, especially in prehospital fields (e.g. in an ambulance), since it is easy to carry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-34461-0_41DOI Listing
January 2020

Relative Ratios Enhance the Diagnostic Power of Phospholipids in Distinguishing Benign and Cancerous Ovarian Masses.

Cancers (Basel) 2019 Dec 26;12(1). Epub 2019 Dec 26.

Feinstein Institutes for Medical Research, Northwell Health System, Manhasset, NY 11030, USA.

Ovarian cancer remains a highly lethal disease due to its late clinical presentation and lack of reliable early biomarkers. Protein-based diagnostic markers have presented limitations in identifying ovarian cancer. We tested the potential of phospholipids as markers of ovarian cancer by utilizing inter-related regulation of phospholipids, a unique property that allows the use of ratios between phospholipid species for quantitation. High-performance liquid chromatography mass spectrometry was used to measure phospholipid, lysophospholipid, and sphingophospholipid content in plasma from patients with benign ovarian masses, patients with ovarian cancer, and controls. We applied both absolute and relative phospholipid ratios for quantitation. Receiver operating characteristic analysis was performed to test the sensitivity and specificity. We found that utilization of ratios between phospholipid species greatly outperformed absolute quantitation in the identification of ovarian cancer. Of the phospholipids analyzed, species in phosphatidylcholine (PC), lysophosphatidylcholine (LPC), and sphingomyelin (SM) were found to have great biomarker potential. LPC(20:4)/LPC(18:0) carried the greatest capacity to differentiate cancer from control, SM(d18:1/24:1)/SM(d18:1/22:0) to differentiate benign from cancer, and PC(18:0/20:4)/PC(18:0/18:1) to differentiate benign from control. These results demonstrate the potential of plasma phospholipids as a novel marker of ovarian cancer by utilizing the unique characteristics of phospholipids to further enhance the diagnostic power.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12010072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016589PMC
December 2019

Agreement between actual and synthesized right-sided and posterior electrocardiographic leads in identifying ischemia.

Am J Emerg Med 2020 07 18;38(7):1346-1351. Epub 2019 Nov 18.

Department of Emergency Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Manhasset, NY, United States.

Objective: A 12-lead electrocardiogram (ECG) is the standard of care for chest pain patients. However, 12-lead ECGs have difficulty detecting ischemia of the right ventricle or posterior wall of the heart. New technology exists to mathematically synthesize these leads from a 12-lead ECG; however, this technology has not been evaluated in the emergency department (ED). We assessed the level of agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations, ST depressions, and T wave inversions in ED patients.

Methods: Actual 12- and 18-lead ECGs were acquired and synthesized 18-lead ECGs were produced based on waveforms from 12-lead ECGs. A blinded cardiologist interpreted the actual and synthesized 18-lead ECGs to identify the presence of abnormalities. Using actual 18-lead ECGs as the reference, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and kappa of synthesized 18-lead ECGs in identifying abnormalities were determined.

Results: Data from 295 patients were analyzed. There was 100% agreement between synthesized 18-lead ECGs and actual 18-lead ECGs in identifying ST elevations and ST depressions (sensitivity, specificity, PPV, and NPV of 100%, and kappa of 1.00). Synthesized 18-lead ECGs had 95% sensitivity, 80% specificity, 97% PPV, and 70% NPV in identifying T wave inversions, when compared with actual 18-lead ECGs (kappa: 0.70).

Conclusion: Synthesized 18-lead ECGs demonstrated 100% agreement with actual 18-lead ECGs in the identification of ST elevations and ST depressions and good agreement in the identification of T wave inversions in a sample of patients ED patients with complaints suspicious of cardiac origin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajem.2019.10.044DOI Listing
July 2020

Combination of cardiac and thoracic pump theories in rodent cardiopulmonary resuscitation: a new method of three-side chest compression.

Intensive Care Med Exp 2019 Dec 2;7(1):62. Epub 2019 Dec 2.

The Feinstein Institute for Medical Research, Northwell Health System, 350 Community Dr. Manhasset, Manhasset, NY, 11030, USA.

Background: High-quality cardiopulmonary resuscitation (HQ-CPR) is of paramount importance to improve neurological outcomes of cardiac arrest (CA). The purpose of this study was to evaluate chest compression methods by combining two theories: cardiac and thoracic pumps.

Methods: Male Sprague-Dawley rats were used. Three types of chest compression methods were studied. The 1-side method was performed vertically with 2 fingers over the sternum. The 2-side method was performed horizontally with 2 fingers, bilaterally squeezing the chest wall. The 3-side method combined the 1-side and the 2-side methods. Rats underwent 10 min of asphyxial CA. We examined ROSC rates, the left ventricular functions, several arterial pressures, intrathoracic pressure, and brain tissue oxygen.

Results: The 3-side group achieved 100% return of spontaneous circulation (ROSC) from asphyxial CA, while the 1-side group and 2-side group achieved 80% and 60% ROSC, respectively. Three-side chest compression significantly shortened the time for ROSC among the groups (1-side, 105 ± 36.0; 2-side, 141 ± 21.7; 3-side, 57.8 ± 12.3 s, respectively, P < 0.05). Three-side significantly increased the intrathoracic pressure (esophagus, 7.6 ± 1.9, 7.3 ± 2.8, vs. 12.7 ± 2.2; mmHg, P < 0.01), the cardiac stroke volume (the ratio of the baseline 1.2 ± 0.6, 1.3 ± 0.1, vs. 2.1 ± 0.6, P < 0.05), and the common carotid arterial pressure (subtracted by femoral arterial pressure 4.0 ± 2.5, 0.3 ± 1.6, vs. 8.4 ± 2.6; mmHg, P < 0.01). Three-side significantly increased the brain tissue oxygen (the ratio of baseline 1.4±0.1, 1.3±0.2, vs. 1.6 ± 0.04, P < 0.05).

Conclusions: These results suggest that increased intrathoracic pressure by 3-side CPR improves the cardiac output, which may in turn help brain oxygenation during CPR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40635-019-0275-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889262PMC
December 2019

Administration of eicosapentaenoic acid may alter high-density lipoprotein heterogeneity in statin-treated patients with stable coronary artery disease: A 6-month randomized trial.

J Cardiol 2020 03 20;75(3):282-288. Epub 2019 Sep 20.

Department of Cardiology, Nihon University Hospital, Tokyo Japan.

Background: Combined statin plus eicosapentaenoic acid (EPA) therapy might be a potentially effective treatment option to prevent coronary artery disease (CAD). The serum EPA/arachidonic acid (AA) ratio has been identified as a potential new risk marker for CAD. Few data exist whether administration of EPA could affect high-density lipoprotein (HDL) particle size. We hypothesized that the addition of EPA to ongoing statin therapy may result in altered HDL heterogeneity.

Methods: We conducted this 6-month, single-center, prospective, randomized open-label clinical trial to investigate the effect of the additional administration of EPA on the HDL heterogeneity (HDL, HDL and HDL/HDL ratio) in stable CAD patients receiving treatment with statins. We assigned stable CAD patients already receiving statin therapy to the EPA group (1800mg/day: n=50) or the control group (n=50).

Results: A significant decrease in the serum HDL level (-4.7% vs. -0.5%, p=0.037), but not of the serum HDL level, and a significant increase in the HDL/HDL ratio (5.5% vs. -5.1%, p=0.032) were observed in the EPA group as compared to the control group. Multiple regression analysis with adjustments for coronary risk factors identified the achieved EPA/ AA ratio as an independent and significant predictor of an increase of the HDL/HDL ratio (β=0.295, p=0.001). Furthermore, the change in the serum cholesterol ester transfer protein mass was positively correlated with the change in the EPA/AA ratio in the EPA group (r=0.286, p=0.044), but not in the control group (r=0.121, p=0.401).

Conclusion: Administration of EPA might decrease the serum HDL level, resulting in an increase in the HDL/HDL ratio. Furthermore, increased EPA/AA ratio by the addition of EPA to ongoing statin therapy might be an indicator of an increase in the HDL/HDL ratio, thereby regulating HDL particle size.

Clinical Trial Registration: UMIN (http://www.umin.ac.jp/) Study ID: UMIN000010452.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jjcc.2019.08.011DOI Listing
March 2020

Usefulness of multimodality cardiac imaging in a patient with ST elevation myocardial infarction caused by two giant coronary artery aneurysms.

BMJ Case Rep 2019 Aug 4;12(8). Epub 2019 Aug 4.

Cardiology, Kawaguchi Municipal Medical Center, Kawaguchi, Japan.

Coronary artery aneurysm (CAA) is a rare cause of myocardial infarction. However, only a few studies have investigated this aspect. An 84-year-old woman with a history of hypertension presented with nausea. showed ST elevation in the inferior leads, and coronary angiography revealed two giant CAAs in the right coronary artery. Percutaneous coronary intervention was difficult because of risk of CAA rupture. Thus, these aneurysms were further evaluated using multimodality cardiac imaging to determine the treatment. MRI using late gadolinium enhancement revealed structural features of the aneurysms and the viability of the myocardium. Only antithrombotic medication was administered on the basis of the results of the multimodality cardiac imaging. Here, we report a rare case of a patient diagnosed with ST elevation myocardial infarction caused by thrombosis in giant CAAs using multimodality cardiac imaging, particularly MRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bcr-2019-229995DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6685413PMC
August 2019

Challenges and Inconsistencies in Using Lysophosphatidic Acid as a Biomarker for Ovarian Cancer.

Cancers (Basel) 2019 Apr 11;11(4). Epub 2019 Apr 11.

Center for Immunology and Inflammation, Feinstein Institute for Medical Research, 350 Community Dr., Manhasset, NY 11030, USA.

Increased detection of plasma lysophosphatidic acid (LPA) has been proposed as a potential diagnostic biomarker in ovarian cancer, but inconsistency exists in these reports. It has been shown that LPA can undergo an artificial increase during sample processing and analysis, which has not been accounted for in ovarian cancer research. The aim of this study is to provide a potential explanation about how the artificial increase in LPA may have interfered with previous LPA analysis in ovarian cancer research. Using an established LC-MS method, we measured LPA and other lysophospholipid levels in plasma obtained from three cohorts of patients: non-cancer controls, patients with benign ovarian tumors, and those with ovarian cancer. We did not find the LPA level to be higher in cancer samples. To understand this inconsistency, we observed that LPA content changed more significantly than other lysophospholipids as a function of plasma storage time while frozen. Additionally, only LPA was found to be adversely impacted by incubation time depending on the Ethylenediaminetetraacetic acid (EDTA) concentration used during blood drawing. We also show that the inhibition of autotaxin effectively prevented artificial LPA generation during incubation at room temperature. Our data suggests that the artificial changes in LPA content may contribute to the discrepancies reported in literature. Any future studies planning to measure plasma LPA should carefully design the study protocol to consider these confounding factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers11040520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521627PMC
April 2019

Prognostic Value of Neurological Status on Hospital Arrival for Short-Term Outcome in Patients With Cardiovascular Shock - Sub-analysis of the Japanese Circulation Society Cardiovascular Shock Registry.

Circ J 2019 05 3;83(6):1247-1253. Epub 2019 Apr 3.

The Japanese Circulation Society Shock Registry Scientific Committee.

Background: Consciousness disturbance is one of the major clinical signs associated with shock state, but its prognostic value has not been previously evaluated in cardiovascular shock patients. We aimed to evaluate the prognostic value of neurological status for 30-day mortality in cardiovascular shock patients without out-of-hospital cardiac arrest (OHCA). Methods and Results: Patients with out-of-hospital onset cardiovascular shock were recruited from the Japanese Circulation Society Shock Registry. Neurological status upon hospital arrival was evaluated using the Japan Coma Scale (JCS). Patients were divided into 4 groups according to the JCS: alert, JCS 0; awake, JCS 1-3 (not fully alert but awake without any stimuli); arousable, JCS 10-30 (arousable with stimulation); and coma JCS 100-300 (unarousable). The primary endpoint was 30-day all-cause death. In total, 700 cardiovascular shock patients without OHCA were assessed. The coma group was associated with a higher incidence of 30-day all-cause death compared with other groups (alert, 15.3%; awake, 24.4%; arousable, 36.8%; coma, 48.5%, P<0.001). Similar trends were observed in etiologically divergent subgroups (acute coronary syndrome, non-ischemic arrhythmia, and aortic disease). On multivariate Cox regression analysis, arousable (hazard ratio [HR], 1.82; 95% CI: 1.16-2.85, P=0.009) and coma (HR, 2.72; 95% CI: 1.76-4.22, P<0.001) (reference: alert) independently predicted 30-day mortality.

Conclusions: Neurological status upon hospital arrival was useful to predict 30-day mortality in cardiovascular shock patients without OHCA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1253/circj.CJ-18-1323DOI Listing
May 2019

A cross-sectional and longitudinal study between association of n-3 polyunsaturated fatty acids derived from fish consumption and high-density lipoprotein heterogeneity.

Heart Vessels 2018 May 20;33(5):470-480. Epub 2017 Nov 20.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Decreased high-density lipoprotein (HDL) particle size, cholesterol poor, apolipoprotein A-I-rich HDL particles leading to smaller HDL particle size, may be associated with an anti-atherosclerotic effect. The data are sparse regarding the relationship between n-3 polyunsaturated fatty acids [n-3 PUFAs: eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA)] and HDL particle size. This study was designed as a hospital-based cross-sectional study to investigate the relationship between the serum levels of n-3 PUFAs and the HDL-cholesterol/apolipoprotein A-1 ratio, as estimated by the HDL particle size, in patients with the presence of one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). Six hundred and forty sequential patients were enrolled in this study. The serum levels of EPA and DHA showed a strong correlation (r = 0.736, p < 0.0001). However, in a multivariate regression analysis after adjustment for ASCVD risk factors, increased serum DHA (β = - 0.745, p = 0.021), but not serum EPA (β = - 0.414, p = 0.139) or EPA + DHA (β = 0.330, p = 0.557) level, was identified as an independent indicator of decreased HDL particle size. In 476 patients followed up for at least 6 months, the absolute change (Δ) in the HDL-cholesterol/apolipoprotein A-1 ratio decreased significantly as the quartile of the Δ DHA level increased (p = 0.014), whereas no significant difference in the Δ HDL-cholesterol/apolipoprotein A-1 ratio was noted with the increase in the quartile of the Δ EPA level. Moreover, a multivariate regression analysis identified increased DHA level and decreased estimated low-density lipoprotein (LDL) particle size measured relative to the mobility value of LDL with polyacrylamide gel electrophoresis (i.e., relative LDL migration: LDL-Rm value), as independent predictors of decreased HDL-cholesterol/apolipoprotein A-1 ratio (β = - 0.171, p = 0.0003 and β = - 0.142, p = 0.002). The results suggest that increased serum DHA level, but not EPA level, might be associated with decreased HDL-cholesterol/apolipoprotein A-1 ratio, an indicator of estimated HDL particle size. Further studies are needed to investigate the useful clinical indices and outcomes of these patients. Clinical Trial Registration Information UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010603.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00380-017-1082-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5911278PMC
May 2018

Relation between low-density lipoprotein cholesterol/apolipoprotein B ratio and triglyceride-rich lipoproteins in patients with coronary artery disease and type 2 diabetes mellitus: a cross-sectional study.

Cardiovasc Diabetol 2017 10 2;16(1):123. Epub 2017 Oct 2.

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: The low-density lipoprotein cholesterol/apolipoprotein B (LDL-C/apoB) ratio has conventionally been used as an index of the LDL-particle size. Smaller LDL-particle size is associated with triglyceride (TG) metabolism disorders, often leading to atherogenesis. We investigated the association between the LDL-C/apoB ratio and TG metabolism in coronary artery disease (CAD) patients with diabetes mellitus (DM).

Methods: In the cross-sectional study, the LDL-C/apoB ratio, which provides an estimate of the LDL-particle size, was calculated in 684 consecutive patients with one additional risk factor. The patients were classified into 4 groups based on the presence or absence of CAD and DM, as follows: CAD (-) DM (-) group, n = 416; CAD (-) DM (+) group, n = 118; CAD (+) DM (-) group, n = 90; CAD (+) DM (+) group, n = 60.

Results: A multi-logistic regression analysis after adjustments for coronary risk factors revealed that the CAD (+) DM (+) condition was an independent predictor of the smallest LDL-C/apoB ratio among the four groups. Furthermore, multivariate regression analyses identified elevated TG-rich lipoprotein (TRL)-related markers (TG, very-LDL fraction, remnant-like particle cholesterol, apolipoprotein C-II, and apolipoprotein C-III) as being independently predictive of a smaller LDL-particle size in both the overall subject population and a subset of patients with a serum LDL-C level < 100 mg/dL. In the 445 patients followed up for at least 6 months, multi-logistic regression analyses identified increased levels of TRL-related markers as being independently predictive of a decreased LDL-C/apoB ratio, which is indicative of smaller LDL-particle size.

Conclusions: The association between disorders of TG metabolism and LDL heterogeneity may account for the risk of CAD in patients with DM. Combined evaluation of TRL-related markers and the LDL-C/apoB ratio may be of increasing importance in the risk stratification of CAD patients with DM. Further studies are needed to investigate the useful clinical indices and outcomes of these patients. Clinical Trial Registration UMIN (http://www.umin.ac.jp/) Study ID: UMIN000028029 retrospectively registered 1 July 2017.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-017-0606-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5625702PMC
October 2017

Association of plasminogen activator inhibitor-1 and low-density lipoprotein heterogeneity as a risk factor of atherosclerotic cardiovascular disease with triglyceride metabolic disorder: a pilot cross-sectional study.

Coron Artery Dis 2017 Nov;28(7):577-587

aDepartment of Health Planning Center bDepartment of Cardiology, Nihon University Hospital cDivision of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: We hypothesized that an increase in plasminogen activator inhibitor 1 (PAI-1) might reduce low-density lipoprotein (LDL) particle size in conjunction with triglyceride (TG) metabolism disorder, resulting in an increased risk of atherosclerotic cardiovascular disease (ASCVD).

Methods: This study was carried out as a hospital-based cross-sectional study in 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital. The estimated LDL-particle size was measured as relative LDL migration using polyacrylamide gel electrophoresis with the LipoPhor system.The plasma PAI-1 level, including the tissue PA/PAI-1 complex and the active and latent forms of PAI-1, was determined using a latex photometric immunoassay method.

Results: A multivariate regression analysis after adjustments for ASCVD risk factors showed that an elevated PAI-1 level was an independent predictor of smaller-sized LDL-particle in both the overall patients population (β=0.209, P<0.0001) and a subset of patients with a serum low-density lipoprotein cholesterol (LDL-C) level lower than 100 mg/dl (β=0.276, P<0.0001). Furthermore, an increased BMI and TG-rich lipoprotein related markers [TG, remnant-like particle cholesterol, apolipoprotein (apo) B, apo C-II, and apo C-III] were found to be independent variables associated with an increased PAI-1 level in multivariate regression models. A statistical analysis of data from nondiabetic patients with well-controlled serum LDL-C levels yielded similar findings. Furthermore, in the 310 patients followed up for at least 6 months, a multiple-logistic regression analysis after adjustments for ASCVD risk factors identified the percent changes of the plasma PAI-1 level in the third tertile compared with those in the first tertile as being independently predictive of decreased LDL-particle size [odds ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02].

Conclusion: The plasma PAI-1 levels may be determined by the degree of obesity and TG metabolic disorders. These factors were also shown to be correlated with a decreased LDL-particle size, increasing the risk of ASCVD, even in nondiabetic patients with well-controlled serum LDL-C levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000521DOI Listing
November 2017

The Ratio of Eicosapentaenoic Acid (EPA) to Arachidonic Acid may be a Residual Risk Marker in Stable Coronary Artery Disease Patients Receiving Treatment with Statin Following EPA Therapy.

Am J Cardiovasc Drugs 2017 Oct;17(5):409-420

Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.

Background: We investigated the relationship between the eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio and non-high-density lipoprotein cholesterol (non-HDL-C) level, a major residual risk of coronary artery disease (CAD), in statin-treated CAD patients following EPA therapy.

Methods: We conducted a 6-month, prospective, randomized clinical trial to investigate the effect of the additional administration of EPA on the EPA/AA ratio and the serum non-HDL-C level in stable CAD patients receiving statin treatment. We assigned CAD patients already receiving statin therapy to an EPA group (1800 mg/day; n = 50) or a control group (n = 50).

Results: A significant reduction in the serum non-HDL-C level was observed in the EPA group, compared with the control group (-9.7 vs. -1.2%, p = 0.01). A multiple-regression analysis with adjustments for coronary risk factors revealed that achieved EPA/AA ratio was more reliable as an independent and significant predictor of a reduction in the non-HDL-C level at a 6-month follow-up examination (β = -0.324, p = 0.033) than the absolute change in the EPA/AA ratio. Interestingly, significant negative correlations were found between the baseline levels and the absolute change values of both non-HDL-C and triglyceride-rich lipoproteins, both markers of residual risk of CAD, indicating that patients with a higher baseline residual risk achieved a greater reduction.

Conclusion: The present results suggest that the achieved EPA/AA ratio, but not the absolute change in EPA/AA ratio, following EPA therapy might be a useful marker for the risk stratification of CAD among statin-treated patients with a high non-HDL-C level.

Clinical Trial Registration: UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000010452.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40256-017-0238-zDOI Listing
October 2017
-->