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.

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.

Associations of higher fish consumption and lifestyle with lower monocyte/HDL-C ratio in a Japanese population: Implication for the anti-atherosclerotic effect of fish consumption.

BACKGROUND: High fish consumption may be involved in lowering inflammation, resulting in the suppression of atherosclerotic cardiovascular disease (ASCVD) development. The monocyte/high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is reported as a novel inflammatory marker of the development of atherosclerosis. We investigated the relationship between fish consumption, MHR, and lifestyle behaviors and explored the foundation of risk stratification of ASCVD using serum HDL-C, MHR, and fish consumption. METHODS: We conducted a cross-sectional study among 6841 adults at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020. We calculated the amount of fish consumption based on Japan's National Nutrition Survey results. RESULTS: The median (interquartile range) fish consumption was 111.4 (67.2/169.2) g per week. As fish consumption increased, MHR decreased significantly (p < 0.0001). Multivariate linear regression analysis identified increased fish consumption as an independent negative determinant of a decreased MHR (ß = -0.050, p < 0.0001). Additionally, healthier lifestyle behaviors (sleep duration and cigarette smoking habit) were also significantly associated with MHR (ß = -0.025, p = 0.027 and ß = 0.146, p < 0.0001, respectively). Furthermore, risk stratification of ASCVD could be developed by combining the HDL-C level and fish consumption with the MHR, indicating that even with similar HDL-C levels, higher MHR and lower fish consumption are associated with a higher risk of ASCVD. Multi-logistic regression analysis with the MHR quartile as an independent variable also showed that the increase in quartile was associated with the exacerbation of visceral obesity and glucose/lipid markers. CONCLUSIONS: A higher fish consumption may be associated with a lower MHR as well as healthier lifestyle behaviors. Moreover, we proposed the concept of risk stratification through relationships with MHR, HDL-C, and fish consumption to reduce ASCVD risk. Further studies are required to dissect the causal relationships between these results.

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.

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.

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.

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

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.

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

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.

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

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 (ΔO2Hb) and BMI in the overall study population (r = -0.255, p-value 0.02). In addition, a significant negative correlation was found between ΔO2Hb 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 ΔO2Hb may be a useful indicator to assess peripheral microcirculation.

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

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 (ΔO2Hb) 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.

Combined Evaluation of the Plasma Arginine Vasopressin and Noradrenaline Levels May be a Useful Predictor of the Prognosis of Patients with Acute Decompensated Heart Failure.

Few data exist regarding the association of plasma arginine vasopressin (AVP) and noradrenaline (NA) levels with subsequent cardiac events in acute decompensated heart failure (ADHF) patients. We measured plasma AVP and NA levels in ADHF patients on admission. In the follow-up (median: 487 days) of 291 patients, 41 cardiac events (cardiac death or re-hospitalization due to HF) were documented. The plasma AVP (26.4 versus 15.5 pg/mL, P = 0.014) and plasma NA (2347 versus 1524 pg/mL, P = 0.007) levels in the cardiac events group were significantly higher than those in the non-cardiac events group. The multivariable hazard ratios (HR) (95% confidence intervals [CI]) in the first tertile (1T) versus the third tertile (3T) of plasma AVP and NA levels were 2.97 (1.06-8.32) and 3.34 (1.21-9.26) for cardiac events, respectively. Group High (3T of combined AVP and NA) had a significantly higher incidence of cardiac events than Group Low (1T of combined groups) (HR: 3.50, 95% CI: 1.17-10.42, P = 0.017). Similarly, the relative risk ratio of cardiac events according to this stratification was more than that of plasma AVP or NA level alone (3.51, 2.65, and 2.95). Higher levels of plasma AVP and NA measured on admission may be associated with the incidence of cardiac events. Combined evaluation of these two parameters may be useful for assessing the prognosis of ADHF survivors.

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

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 (ß = - 0.745, p = 0.021), but not serum EPA (ß = - 0.414, p = 0.139) or EPA + DHA (ß = 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 (ß = - 0.171, p = 0.0003 and ß = - 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.

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.

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.

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.

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 (ß=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 (ß=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.

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.

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 (ß = -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.

Impact of Adding Eicosapentaenoic Acid to Statin Therapy on Plasma Pentraxin 3 Level in Patients with Stable Coronary Artery Disease: A 6-Month, Randomized Controlled Study.

BACKGROUND: We hypothesized that the additional administration of eicosapentaenoic acid (EPA) in patients with stable coronary artery disease (CAD) receiving statin has the potential to lower the serum pentraxin 3 (PTX3) level, an indicator of plaque stabilization. METHODS: We randomly assigned CAD patients already receiving statin therapy to an EPA group (1800 mg/day, n = 53) or control group (n = 53). RESULTS: No significant difference was found in the change in the plasma PTX3 level between the groups. However, in a subgroup analysis, a significant percentage reduction in the plasma PTX3 level was observed in patients receiving strong statin compared with the patients receiving moderate statin in the EPA group (-5.6 vs. 14.7 %, p = 0.0082), while no such difference in the percentage change in the plasma PTX3 level was noted between the two same statin subgroups in the control group. A multiple logistic regression analysis identified the addition of EPA to ongoing strong statin treatment as an independent predictor of PTX3 level reduction. Furthermore, even in patients with relatively well-controlled serum lipid levels, pretreatment with EPA added to ongoing statin therapy reduced serum non-high-density lipoprotein cholesterol and triglyceride-rich lipoproteins as residual risk factors. CONCLUSION: Through this study design, the results could not support the hypothesis that adding EPA in patients with stable CAD receiving varying degrees of statin treatment reduces the plasma PTX3 level comprehensively. However, addition of EPA to ongoing strong statin treatment, but not ongoing moderate statin treatment, may reduce the plasma PTX3 level, possibly leading to coronary plaque stabilization. CLINICAL TRIAL REGISTRATION INFORMATION: UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010452.