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

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

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

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

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.

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

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

Assessment of sex differences in associations between sleep duration and lipid/glucose metabolism in urban Japan: a cross-sectional study.

Inadequate sleep durations (short or long) are related to worsening of lipid/glucose metabolism, leading to atherosclerotic cardiovascular diseases (ASCVD). Few data exist on sex differences in this relationship that, to date, has been scarcely reported. This cross-sectional study included 6678 men and 4700 women at the Health Planning Center of Nihon University Hospital, located in the center of Tokyo, between September 2015 and October 2016. The prevalence of diabetes and dyslipidemia in the participants was 3.3% and 6.5%, respectively. Sleep duration was divided into five categories: < 5 h, 5-6 h, 6-7 h, 7-8 h, and ≥ 8 h. We examined the odds ratio (OR) and 95% confidence interval (CI) of lipid/glucose metabolism-related markers for the reference value defined in each guideline with 6-7 h as the reference of comparison. In men, a sleep duration of < 5 h was associated with ORs of 1.32 and 1.33 (95% CI, 1.01-1.73 and 1.02-1.74) for LDL-C level ≥ 120 mg/dL and non-HDL-C level of ≥ 150 mg/dL (defined as "borderline hyper" by the Japan Atherosclerosis Society Guidelines for Prevention of ASCVD 2017), respectively. Moreover, a sleep duration of < 5 h was associated with an OR of 1.77 (1.33-2.35) for fasting blood glucose of ≥ 100 mg/dL (defined as "high" by a specialized lifestyle checkup program in Japan). In women, sleep duration of < 5 h was associated with an OR of 1.70 (1.24-2.33) for HbA1c level of ≥ 5.6% (defined as "high" by a specialized life style checkup program in Japan). However, there was no association between sleep duration and serum lipid profile. Inadequate short sleep duration was as a potential risk factor of adverse lipid and/or glucose metabolism in both sexes. However, there were sex differences in associations between sleep duration and lipid/glucose metabolism in urban Japan. To further reduce risks of ASCVD, it is of particular importance to emphasize adequate sleep duration in both sexes.Trial registration UMIN ( http://www.umin.ac.jp/ ) Study ID: UMIN000037643 retrospectively registered on August 9, 2019.

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

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

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.

Incremental Predictive Value of Coronary Calcium Score in Risk Stratification of Coronary Revascularization in Patients With Normal or Mild Ischemia Using Nuclear Myocardial Perfusion Single Photon Emission Computed Tomography.

BACKGROUND: The incremental predictive value of the coronary artery calcium score (CACS) for risk stratification of coronary revascularization in patients with normal or mildly abnormal nuclear myocardial perfusion single photon emission computed tomography (MPS) scores is unknown.Methods and Results:We analyzed 528 patients in whom CACS was calculated and who underwent stress MPS within 3 months. Patients with known coronary artery disease, prior coronary revascularization, and those undergoing hemodialysis were excluded. Patients were followed-up with coronary revascularization based on the evidence of physiological ischemia defined by fractional flow reserve or severe coronary stenosis (≥90%). CACS was significantly associated with the summed stress score (SSS) from MPS assessment. Multivariate logistic regression analysis showed that high CACS (≥300; odds ratio [OR] 5.44, 95% confidence interval [CI] 2.28-13.0) and SSS (OR 1.29, 95% CI 1.18-1.40) were significant (P<0.001) predictors of future coronary revascularization. The log-rank test showed that high CACS stratified coronary revascularization in normal SSS (0-3; P<0.001) or mildly abnormal SSS (4-8; P=0.028) groups, whereas high CACS did not significantly stratify coronary revascularization in moderate to severe SSS (≥9; P=0.757). CONCLUSIONS: Risk stratification using CACS with a cut-off value 300 may have incremental predictive value for revascularization in patients with normal or mildly abnormal MPS.

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

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

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

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

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

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

Association between the ratio of serum n-3 to n-6 polyunsaturated fatty acids and acute coronary syndrome in non-obese patients with coronary risk factor: a multicenter cross-sectional study.

BACKGROUND: Previous studies have reported that being overweight, obese, or underweight is a risk factor for ischemic cardiovascular disease (CVD); however, CVD also occurs in subjects with ideal body mass index (BMI). Recently, the balance of n-3/n-6 polyunsaturated fatty acids (PUFAs) has received attention as a risk marker for CVD but, so far, no study has been conducted that investigates the association between BMI and the balance of n-3/n-6 PUFAs for CVD risk. METHODS: We evaluated the association between n-3/n-6 PUFA ratio and acute coronary syndrome (ACS) in three BMI-based groups (< 25: low BMI, 25-27.5: moderate BMI, and ≥ 27.5: high BMI) that included 1666 patients who visited the cardiovascular medicine departments of five hospitals located in urban areas in Japan. RESULTS: The prevalence of ACS events was 9.2, 7.3, and 10.3% in the low, moderate, and high BMI groups, respectively. We analyzed the relationship between ACS events and several factors, including docosahexaenoic acid/arachidonic acid (DHA/AA) ratio by multivariate logistic analyses. In the low BMI group, a history of smoking (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.40-4.35) and low DHA/AA ratio (OR: 0.30, 95% CI: 0.12-0.74) strongly predicted ACS. These associations were also present in the moderate BMI group but the magnitude of the association was much weaker (ORs are 1.47 [95% CI: 0.54-4.01] for smoking and 0.63 [95% CI: 0.13-3.10] for DHA/AA). In the high BMI group, the association of DHA/AA (OR: 1.98, 95% CI: 0.48-8.24) was reversed and only high HbA1c (OR: 1.46, 95% CI: 1.03-2.08) strongly predicted ACS. The interaction test for OR estimates (two degrees of freedom) showed moderate evidence for reverse DHA/AA ratio-ACS associations among the BMI groups (P = 0.091). CONCLUSIONS: DHA/AA ratio may be a useful marker for risk stratification of ACS, especially in non-obese patients.

Association of daily fish intake with serum non-high-density lipoprotein cholesterol levels and healthy lifestyle behaviours in apparently healthy males over the age of 50 years in Japanese: Implication for the anti-atherosclerotic effect of fish consumption.

BACKGROUND AND AIM: Higher fish consumption has been reported to be associated with a lower incidence of coronary artery disease (CAD). We hypothesized that higher fish intake may be associated with lower serum level of non-high-density lipoprotein cholesterol (non-HDL-C) levels, representing the entire dyslipidemia spectrum, and a healthy lifestyle. METHODS AND RESULTS: This cross-sectional study was conducted in a population of 1270 apparently healthy males over the age of 50 years without lipid-modifying therapy at the Health Planning Center of Nihon University Hospital between April and August 2018. The average number of days of fish intake per week was 2.6 ± 1.4. We performed analysis of variance using fish consumption as a categorical variable (0-1 day, 2-3 days, 4-5 days, or 6-7 days per week). The serum non-HDL-C levels in the 6-7 days fish intake group were significantly lower than those in the 0-1 and 2-3days fish intake groups. Furthermore, with increasing frequency of fish intake per week, the proportion of subjects with cigarette smoking decreased (p = 0.026), that of subjects engaging in habitual aerobic exercises increased (p = 0.034), and the sleep duration of the subjects increased (p < 0.0001). CONCLUSIONS: These results suggest that a high frequency of fish intake, that is a fish intake of 6-7 days per week, was associated with healthier lifestyle behaviours as well as lower non-HDL-C levels, and thus may represent a component of a healthy lifestyle associated with a lower risk of CAD in Japanese males over the age of 50. CLINICAL TRIAL REGISTRATION: UMIN (http://www.umin.ac.jp/). STUDY ID: UMIN000035899.

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.

Does administration of eicosapentaenoic acid increase soluble thrombomodulin level in statin-treated patients with stable coronary artery disease?

Interventions targeting the serum eicosapentaenoic acid (EPA)/arachidonic acid (AA) ratio could be useful for the prevention of coronary artery disease (CAD). Few data exist regarding the effects of administration of EPA on the serum levels of soluble thrombomodulin (sTM) as a marker of endothelial damage, or on the relationship between the sTM and EPA/AA ratio in patients with CAD receiving statin treatment. We assigned stable CAD patients already receiving statin therapy to an EPA group (1800 mg/day: n = 50) or control group (n = 50). A significant increase of the sTM level was observed in the EPA group as compared to that in the control group 0.40 (0.10/0.70) FU/mL vs. 0.20 (0/0.40) FU/mL, p = 0.004 at the 6-month follow-up examination. Multivariate regression analysis after adjustments for coronary risk factors and changes of the serum lipid levels identified an increased EPA/AA ratio as an independent predictor of increased serum sTM level (ß = 0.244, p = 0.02). The results suggest that an increased sTM level caused by additional administration of EPA to statin might be associated with an increased EPA/AA ratio. The increase of the serum sTM after administration of EPA might reflect an increase of the TM expression on the endothelial surface rather than endothelial damage in CAD patients under statin treatment.Clinical Trial Registration Information UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010452.

A longitudinal study of the association of the eicosapentaenoic acid/arachidonic acid ratio derived from fish consumption with the serum lipid levels: a pilot study.

It has been demonstrated that regular fish consumption is associated with a reduced mortality from atherosclerotic cardiovascular disease (ASCVD). However, data are scarce regarding the correlation between the changes in the serum eicosapentaenoic acid/arachidonic acid (EPA/AA) ratio associated with regular fish consumption and the changes in the serum lipid profile variables. This study was designed as a hospital-based longitudinal study to investigate the relationship between the changes in the serum EPA/AA ratio and changes of the serum lipid levels in patients with one or more risk factors for ASCVD. In 475 patients followed-up for at least 1 year, univariable and multivariable regression analyses conducted after adjustments for the risk factors of ASCVD revealed that the absolute change of the EPA/AA ratio (∆EPA/AA ratio) was independently and significantly associated with the changes of the serum levels of low-density lipoprotein cholesterol (LDL-C) (ß = - 0.129, p = 0.005), triglyceride (TG) (ß = - 0.108, p = 0.019), non-high-density lipoprotein cholesterol (non-HDL-C) (ß = - 0.149, p = 0.001), and TG/HDL-C ratio, a marker of the LDL particle size (ß = - 0.104, p = 0.02), while not being correlated with any other lipid parameters. On the other hand, while the ∆ docosahexaenoic acid (DHA)/AA ratio was inversely correlated with the changes of the serum HDL-C level and positively correlated with the changes of the TG/HDL-C ratio, possibly serving to promote development of atherosclerosis. The results suggest that an increase of the EPA/AA ratio might be associated with decrease of the serum levels of LDL-C, TG and non-HDL-C levels, as well as with an increase of the TG/HDL-C ratio, which represents increased LDL particle size, all of which play a role in the development of ASCVD. A high EPA/AA ratio, but not DHA/AA ratio, derived from fish consumption might reduce the risk of ASCVD through reducing the risk of development of atherosclerosis.Clinical Trial Registration Information: UMIN ( http://www.umin.ac.jp/ ), Study ID: UMIN000010603.

Increased triglyceride/high-density lipoprotein cholesterol ratio may be associated with reduction in the low-density lipoprotein particle size: assessment of atherosclerotic cardiovascular disease risk.

Hypertriglyceridemia, which often leads to both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolic disorders, is a strong risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). We hypothesized that the triglyceride (TG)/HDL cholesterol (TG/HDL-C) ratio may be more useful for estimation of the LDL-particle size, as a well-known risk factor for ASCVD, as compared to the serum TG level per se. Polyacrylamide gel electrophoresis was used in this study to estimate the LDL-particle size [relative LDL migration (LDL-Rm value)] in 649 consecutive patients with one additional risk factor for ASCVD. Multivariable regression analysis identified both serum TG (ß = 0.556, p < 0.0001) and the serum TG/HDL-C ratio (ß = 0.607, p < 0.0001) as independent indicators of the LDL-particle size. In terms of evaluation of the accuracy of indicators of LDL-Rm values equal to or greater than 0.40, which are suggestive of the presence of large amounts of small-dense LDL and represent the upper limit (mean + 2 standard deviation) of the normal range in this population, both the serum TG level and serum TG/HDL-C ratio showed high accurate areas under the receiver-operating characteristic curve (0.900 vs. 0.914), but with a negative likelihood ratio of 0.506 vs. 0.039, indicating that the TG/HDL-C ratio model is superior for excluding patients with values below the cutoff value and with LDL-Rm values ≥ 0.40. Furthermore, in 456 patients followed up for at least 1 year, multivariable regression analysis identified increased serum TG/HDL-C ratio as an independent predictor of a decreased LDL-particle size. These results suggest that the serum TG/HDL-C ratio may be more useful for assessing the risk of ASCVD as compared to the serum TG level per se. To reduce the risk of ASCVD, it may be important to focus not only on changes of the serum LDL-C, but also on those of the serum TG/HDL-C ratio.