Effects of Phase II Cardiac Rehabilitation on Physical Function and Anxiety Levels in Frail Patients.

Background: Frailty is an important prognostic factor in patients with cardiovascular diseases (CVD), and patients with CVD have a high rate of concurrent psycho-emotional stress, as well as depressive mood and anxiety symptoms. Despite this, few reports have examined the effects of the efficacy of Phase II cardiac rehabilitation (CR) in frail patients, including improvements in anxiety levels. Methods and Results: In all, 137 patients (mean [±SD] age 65.8±13.0 years; 71% male) who participated in Phase II CR and were assessed after CR completion were included in this study. Patients were evaluated using the Kihon Checklist (KCL) form at the beginning of CR and were divided into the 3 groups according to KCL scores: frail (n=34, 25%), pre-frail (n=40, 29%), and non-frail (n=63, 46%). Physical function and anxiety levels were compared among the 3 groups. The pre-frail and frail groups had significantly higher state anxiety and trait anxiety than the non-frail group (P<0.01). At the end of Phase II CR, all 3 groups showed significant improvements in the 6-min walking distance (P<0.05). State anxiety improved significantly in the non-frail and pre-frail groups, whereas trait anxiety only improved in the non-frail group. Conclusions: Physical function was improved in frail patients who participated in Phase II CR. However, there was no significant improvement in their level of anxiety.

Use of a deep-learning-based lumen extraction method to detect significant stenosis on coronary computed tomography angiography in patients with severe coronary calcification.

BACKGROUND: Coronary computed tomography angiography examinations are increasingly becoming established as a minimally invasive method for diagnosing coronary diseases. However, although various imaging and processing methods have been developed, coronary artery calcification remains a major limitation in the evaluation of the vascular lumen. Subtraction coronary computed tomography angiography (Sub-CCTA) is a method known to be able to reduce the influence of coronary artery calcification and is therefore feasible for improving the diagnosis of significant stenosis in patients with severe calcification. However, Sub-CCTA still involves some problems, such as the increased radiation dose due to plain (mask) imaging, extended breath-holding time, and misregistration due to differences in the imaging phase. Therefore, we considered using artificial intelligence instead of Sub-CCTA to visualize the coronary lumen with high calcification. Given this background, the present study aimed to evaluate the diagnostic performance of a deep learning-based lumen extraction method (DL-LEM) to detect significant stenosis on CCTA in 99 consecutive patients (891 segments) with severe coronary calcification from November 2015 to March 2018. We also estimated the impact of DL-LEM on the medical economics in Japan. RESULTS: The DL-LEM slightly improved the per-segment diagnostic accuracy from 74.5 to 76.4%, and the area under the curve (AUC) slightly improved from 0.752 to 0.767 (p = 0.030). When analyzing the 228 segments that could not be evaluated because of severe calcification on the original CCTA images, the DL-LEM improved the accuracy from 35.5 to 42.5%, and the AUC improved from 0.500 to 0.587 (p = 0.00018). As a result, DL-LEM analysis could have avoided invasive coronary angiography in 4/99 cases (per patient). From the calculated results, it was estimated that the number of exams that can be avoided in Japan in one year is approximately 747 for invasive coronary angiography, 219 for fractional flow reserve, and 248 for nuclear exam. The total amount of medical fee that could be reduced was 225,629,368 JPY. CONCLUSIONS: These findings suggest that the DL-LEM may improve the diagnostic performance in detecting significant stenosis in patients with severe coronary calcification. In addition, the results suggest that not a small medical economic effect can be expected.

Association Between Constipation and Frailty Components in Patients Undergoing Late Phase II Cardiac Rehabilitation.

BACKGROUND: The Japanese Ministry of Health, Labour and Welfare reported that the overall constipation complaint rates among men and women are 2.5% and 4.6%, respectively. To evaluate the impact of constipation on patients with cardiovascular diseases, we investigated the association between constipation and frailty components in patients undergoing cardiac rehabilitation (CR). METHODS: We enrolled 102 consecutive patients undergoing late phase II CR (mean age: 62.7 ± 13.4 years; 68 (67%) were men). We investigated clinical characteristics, observed defecation status and evaluated frailty components assessed by the Kihon checklist. According to the Clinical Guidelines for Chronic Constipation, the subjects were divided into constipation and non-constipation groups. RESULTS: Constipation was noted in 33 patients (32%). Interestingly, the constipation complaint rate was only 15%. Age was significantly higher in the constipation group than in the non-constipation group; however, no differences in sex, underlying diseases and prevalence rates of coronary risk factors were observed between the two groups. Body mass index, hemoglobin level, albumin level and estimated glomerular filtration rate were significantly lower in the constipation group than in the non-constipation group. The prevalence of frailty was significantly higher in the constipation group than in the non-constipation group. Physical ability, seclusion and depression scores were significantly higher in the constipation group than the non-constipation group. CONCLUSIONS: Constipation was associated with physical function and depression score as components of frailty in patients undergoing CR.

Arterial Stiffness Index and Exercise Tolerance in Patients Undergoing Cardiac Rehabilitation.

Arterial stiffness contributes to the development of cardiovascular disease (CVD). However, the relationship between the arterial stiffness and exercise tolerance in CVD patients with preserved ejection fraction (pEF) and those with reduced EF (rEF) is unclear. We enrolled 358 patients who participated in cardiac rehabilitation and underwent cardiopulmonary exercise testing at Juntendo University Hospital. After excluding 195 patients who had undergone open heart surgery and 20 patients with mid-range EF, the patients were divided into pEF (n = 99) and rEF (n = 44) groups. Arterial stiffness was assessed using arterial velocity pulse index (AVI) and arterial pressure volume index (API) at rest. The patients in the pEF group were significantly older and had a higher prevalence of coronary artery disease than the rEF group. The pEF group had significantly lower AVI levels and higher API levels than the rEF group. In the pEF group, the peak oxygen uptake (peak VO2) and the anaerobic threshold was significantly higher than those in the rEF group. The peak VO2 was significantly and negatively correlated with AVI and API in the pEF group (All, P < 0.05), but not in the rEF group. Multivariate linear regression analyses demonstrated that AVI was independently associated with peak VO2 (ß = -0.34, P < 0.05) in the pEF group. In conclusion, AVI may be a useful factor for assessing exercise tolerance, particularly in CVD patients with pEF.

Relationship Between Kihon Checklist Score and Anxiety Levels in Elderly Patients Undergoing Early Phase II Cardiac Rehabilitation.

BACKGROUND: The frailty state consists of not only physical but also psycho-emotional problems, such as cognitive dysfunction and depression as well as social problems. However, few reports have examined the relationship between frailty and anxiety levels in elderly patients undergoing cardiac rehabilitation (CR). METHODS: We analyzed 255 patients (mean age: 74.9 ± 5.8 years, 67% male) who participated in early phase II CR at Juntendo University Hospital. At the beginning of CR, patients carried out self-assessments based on the Kihon Checklist (KCL) and the State Trait Anxiety Inventory Form (STAI). Patients were divided into three groups: frailty group (n = 99, 39%), pre-frailty group (n = 81, 32%), and non-frailty group (n = 75, 29%) according to the KCL. We assessed results from the KCL scores and its relationship with anxiety levels. RESULTS: Among the three groups, there were no significant differences in age, underlying illnesses, or the prevalence of coronary risk factors. Depressive mood domains of the KCL were significantly higher in the frailty and pre-frailty groups than in the non-frailty groups (3.0 ± 1.5 vs. 1.4 ± 1.2 vs. 0.4 ± 0.6; P < 0.01). The state anxiety level was significantly higher in the frailty group than in the non-frailty group (41.6 ± 0.9 vs. 34.9 ± 1.0; P < 0.01). The trait anxiety levels were significantly higher in the frailty group and pre-frailty group than in the non-frailty group (45.5 ± 0.9 vs. 39.2 ± 1.0 vs. 35.1 ± 1.1; P < 0.01). State anxiety and trait anxiety also showed a significantly positive correlations with the KCL scores (r = 0.32 vs. 0.41, P < 0.01). CONCLUSIONS: Frailty scores were positively correlated not only with physical function but also with depression mood and anxiety levels in elderly patients undergoing early phase II CR. These results suggest that assessment of depressive mood and anxiety is also important in elderly patients undergoing early phase II CR.

The transluminal attenuation gradient in coronary CT angiography for the detection of hemodynamically significant disease: can all arteries be treated equally?

OBJECTIVE: Results of the use of the transluminal attenuation gradient (TAG) at coronary CT angiography (CCTA) to predict hemodynamically significant disease vary widely. This study tested whether diagnostic performance of TAG to predict fractional flow reserve (FFR) ≤ 0.8 is improved when applied separately to subsets of coronary arteries that carry similar physiological flow. METHODS: 28 patients with 64 × 0.5 mm CCTA and invasive FFR in ≥1 major coronary artery were retrospectively evaluated. Two readers assessed TAG in each artery. The receiver operating characteristic (ROC) area under the curve (AUC) was used to assess the diagnostic performance of TAG to detect hemodynamically significant disease following a clinical use rule [negative: FFR > 0.8 or ≤ 25% diameter stenosis (DS) at invasive catheter angiography; positive: FFR ≤ 0.8 or ≥ 90% DS at invasive catheter angiography]. ROC AUC was compared for all arteries pooled together, vs separately for arteries carrying similar physiological flow (Group 1: all left anterior descending plus right-dominant left circumflex; Group 2: right-dominant RCA plus left/co-dominant left circumflex). RESULTS: Of the 84 arteries, 30 had FFR measurements, 30 had ≤25% DS and 13 had ≥90% DS. 11 arteries with 26-89% DS and no FFR measurement were excluded. TAG interobserver reproducibility was excellent (Pearson r = 0.954, Bland-Altman bias: 0.224 Hounsfield unit cm-1). ROC AUC to detect hemodynamically significant disease was higher when considering arteries separately (Group 1 AUC = 0.841, p = 0.039; Group 2 AUC = 0.840, p = 0.188), than when pooling all arteries together (AUC = 0.661). CONCLUSION: Incorporating information on the physiology of coronary flow via the particular vessel interrogated and coronary dominance may improve the accuracy of TAG, a simple measurement that can be quickly performed at the time of CCTA interpretation to detect hemodynamically significant stenosis in individual coronary arteries. Advances in knowledge: The interpretation of TAG may benefit by incorporating information regarding which coronary artery is being interrogated.

Submillisievert imaging protocol using full reconstruction and advanced patient motion correction in 320-row area detector coronary CT angiography.

Radiation exposure remains a concern in the use of coronary CT angiography (CCTA). Full reconstruction (Full) and reconstruction using advanced patient motion correction (APMC) could obtain a lower radiation dose using low tube current scanning in a 320-row Area Detector CT (320-ADCT). The radiation dose for an imaging protocol using Full and APMC in daily practice was estimated. A total of 209 patients who underwent CCTA in 1 rotation scanning with 100 kv and adaptive iterative dose reduction 3D in 320-ADCT were enrolled. Imaging protocols were classified into 3 groups based on estimated slow filling time: (1) slow filling time ≥ 275 msec, Full with 30% of usual tube current (N = 43)(Full30%mA) (2) 206.3 msec ≤ slow filling time < 275 msec, APMC with 50% of usual tube current (N = 48)(APMC50%mA); and (3) 137.5 msec ≤ slow filling time < 206.3 msec, Half reconstruction with usual tube current (N = 118)(Half100%mA). Radiation dose was estimated by the effective dose. The diagnostic accuracy of CCTA was compared with that of invasive coronary angiography in 28 patients. The effective doses of Full30%mA, APMC50%mA, and Half100%mA were 0.77 ± 0.31, 1.30 ± 0.85, and 1.98 ± 0.68, respectively. Of 28 patients, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value in vessel-based analyses were: Full30%mA, 66.7, 82.4, 80.0, 40.0, and 93.3%; APMC50%mA, 100.0, 80.0, 83.3, 50.05, and 100.0%; and Half100%mA, 90.9, 83.0, 86.3, 78.95, and 92.9%, respectively. An imaging protocol using Full30%mA and APMC50%mA was one of the methods how radiation dose could be reduced radiation dose maintained diagnostic accuracy compared to imaging using conventional Half100%mA.

Self-controllable prodromal symptoms of syncope attributed to carotid sinus syndrome during the end stage of cancer: a case report.

BACKGROUND: Carotid sinus syndrome (CSS) can cause prodromal symptoms of syncope such as dizziness and nausea. Patients with end-stage cancer lose self-efficacy associated with reduced activities of daily life (ADL). Herein, we report a case of end-stage cancer in which self-efficacy was enhanced as the patient gained self-control of prodromal symptoms of syncope. CASE PRESENTATION: A 70-year-old patient with end-stage esophageal cancer and enlarged supraclavicular lymph nodes developed CSS. The CSS was a mixed type with both bradycardia and decreased blood pressure, accompanied by prodromal symptoms prior to syncope episodes. The patient incidentally discovered that he could decrease the duration of symptoms by contracting the muscles in his hands and legs. By applying this coping method at the onset of prodromal symptoms, he was also able to reduce the severity and duration of symptoms, which resulted in enhanced self-efficacy. As a result, the frequency of prodromal symptoms also decreased even though ADL improved. CONCLUSION: This patient was diagnosed with vasoinhibitory-predominant mixed-type CSS. The coping method the patient developed seemed to avoid the onset of abrupt blood pressure decrease via peripheral vascular constriction action. Achievement of adequate coping such as self-control of prodromal symptoms enabled our patient to improve his self-efficacy even at the end stages of cancer. This case of enhanced self-efficacy could possibly illustrate a placebo effect for prevention of recurrence.

Incremental predictive value for obstructive coronary artery disease by combination of Duke Clinical Score and Agatston score.

AIMS: Recent study suggests that algorithms such as the Duke Clinical score (DCS) may overestimate the pretest probability. The Agatston score representing the grade of coronary artery calcification can be simply calculated from low-radiation exposure ECG-gated plain CT. In this study, we investigated whether or not more superior diagnostic performance for obstructive coronary artery disease (CAD) can be obtained by combining DCS with the Agatston score. METHODS AND RESULTS: Of 3939 consecutive patients suspected of having stable angina without known CAD who underwent Coronary Computed Tomography Angiography (CCTA) as well as calculation of the DCS and Agatston score at our hospital, 3688 patients were selected as subjects. Obstructive CAD was defined as >50% diameter stenosis on CCTA; we investigated the diagnostic performance based on the area under the curve (AUC) of a receiver operating characteristic (ROC) curve, Net Reclassification Improvement (NRI), and Integrated Discrimination Improvement (IDI). The AUCs of ROCs prepared using the DCS alone and combination of the DCS and Agatston score were 0.7137 and 0.8057, respectively, showing that the diagnostic performance of the combination was significantly superior to DCS alone (P < 0.001). NRI was 0.8132 and IDI was 0.1374, showing that the diagnostic performance was improved by the combination of the DCS and Agatston score compared with DCS alone (P < 0.001). NRI (0.3522) and IDI (0.0287) were improved compared with those of the Agatston score alone (P < 0.001). CONCLUSION: The combination of the DCS and Agatston score improved the diagnostic performance for obstructive CAD compared with DCS alone and Agatston score.

Incremental prognostic value of coronary computed tomographic angiography high-risk plaque characteristics in newly symptomatic patients.

BACKGROUND: The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. METHODS: A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. RESULTS: The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. CONCLUSIONS: Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS.

Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr(-/-)) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr(-/-) mice.

Prognostic Value of Coronary Computed Tomography (CT) Angiography and Coronary Artery Calcium Score Performed Before Revascularization.

BACKGROUND: Cardiac events after revascularization are equally attributable to recurrence at site of culprit lesions and development of nonculprit lesions. We evaluated the hypothesis that coronary computed tomography (CT) angiography and coronary artery calcium score (CACS) performed before revascularization predicts cardiac events after treatment. METHODS AND RESULTS: Among 2238 consecutive patients without known coronary artery disease who underwent coronary CT angiography and CACS, 359 patients underwent revascularization within 30 days after CT; in 337 of 359 (93.9%) follow-up clinical information was available. In addition to known cardiac risk factors, CT findings were evaluated as predictors of cardiac events after revascularization: CACS and the presence of CT-verified high-risk plaque (CT-HRP). Improvement of predictive accuracy by including CT findings was evaluated from a discrimination (Harrell's C-statistics) standpoint. During the follow-up period (median: 673, interquartile range: 47 to 1529 days), a total of 98 cardiac events occurred. Cox proportional hazard model revealed that age, diabetes, triglyceride, CACS, and nonculprit CT-HRP were significant predictors of overall cardiac events. Although not statistically significant, discriminatory power was greater for the model with CACS (C-stat: 63.2%) and the model with both CACS and CT-HRP (65.8%) compared to the model including neither CACS nor CT-HRP (60.7%). CONCLUSIONS: High CACS and the presence of nonculprit CT-HRP performed before revascularization are significant predictors of cardiac events after revascularization.

An adult case of polysplenia syndrome associated with sinus node dysfunction, dextrocardia, and systemic venous anomalies.

A 54-year-old woman was referred to our hospital for symptomatic sinus bradyarrhythmia with a sinus pause of 8 seconds. She was diagnosed with dextrocardia during childhood and discovered to have heterotaxy syndrome when she had an appendectomy during her teenager years. Chest and abdominal examinations by computed tomography showed multiple spleens located on the right side and abnormal drainages of the superior and inferior vena cava. Left isomerism was diagnosed by bilaterally bilobed lungs. Because of a patent bilateral superior vena cava, pacemaker leads were implanted using the right cephalic vein approach. Her fainting symptoms disappeared after pacemaker implantation.

Omega 3 Polyunsaturated Fatty Acids Suppress the Development of Aortic Aneurysms Through the Inhibition of Macrophage-Mediated Inflammation.

BACKGROUND: Dietary intake of ω3 polyunsaturated fatty acids (ω3-PUFAs) reduces progression of atherosclerosis and prevents future cardiovascular events. Macrophages are key players in the pathogenesis of aortic aneurysm. The effects of ω3-PUFAs on abdominal aortic aneurysm (AAA) formation and macrophage-mediated inflammation remain unclear. METHODS AND RESULTS: The AAA model was developed by angiotensin II infusion in apolipoprotein E-deficient mice. Mice were supplemented with eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA). The development of AAA lesions and macrophage infiltration in the aorta were analyzed. Gene expression of inflammatory markers in aortic tissues and peritoneal macrophages were measured by using quantitative polymerase chain reaction. AAA formation and macrophage infiltration were significantly suppressed after EPA and DHA administration. EPA administration and DHA administration significantly decreased the expression of tumor necrosis factor-α, monocyte chemoattractant protein-1, transforming growth factor-ß, matrix metalloproteinases (MMP)-2, MMP-9, and vascular cell adhesion molecule-1 in the aortas. The expression of arginase 2, which is a marker of pro-inflammatory macrophages, was significantly lower and that of Ym1, which is a marker of anti-inflammatory macrophages, and was significantly higher after EPA and DHA administration. The same trends were observed in peritoneal macrophages after EPA and DHA administration. CONCLUSIONS: Dietary intake of EPA and DHA prevented AAA development through the inhibition of aortic and macrophage-mediated inflammation.

Disease duration and severity impacts on long-term cardiovascular events in Japanese patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) increases the mortality and morbidity of cardiovascular disease (CVD). However, the relationship between RA and the risk of CVD in the Japanese population remains unclear. METHODS AND RESULTS: This study comprised 571 RA patients who were admitted to Juntendo University Hospital from January 1990 to December 2000. Cardiovascular events (CVEs) were defined as cardiac death, acute coronary syndrome (ACS), symptomatic stroke, and congestive heart failure. During follow-up (mean 11.7 ± 5.8 years), 7.5% of the patients died from all causes and 11.0% experienced CVEs. The morbidity of stroke and ACS was 3.6 and 2.5 per 1000 person-years, respectively. The mean RA disease duration at enrolment was significantly longer in patients who experienced CVEs than in those who did not experience CVEs (15.0 ± 12.7 years vs. 10. 8 ± 9.7 years; p = 0.01). Physical disabilities due to RA were more severe in patients who experienced CVEs than in those who did not experience CVEs. Patients with a long RA disease duration showed significantly higher event rates (p = 0.033). Cox proportional hazards analysis identified a longer RA duration as an independent risk factor for CVD (hazard ratio 1.57, 95% CI 1.09-2.30, p = 0.02). CONCLUSION: Japanese RA patients showed a relatively high incidence of CVD, despite the fact that they had few coronary risk factors. The RA disease duration was an independent risk factor for CVEs.

High hexacosanoic acid levels are associated with coronary artery disease.

AIMS: Levels of saturated very long chain fatty acids (VLCFAs) are associated with coronary risk factors, including metabolic syndrome (MS), atherogenic lipoproteins, and systemic inflammation. However, the relationship between circulating levels of saturated VLCFA and coronary artery disease (CAD) remains unclear. METHOD: We enrolled 100 consecutive CAD patients and 40 age-, gender-, and body mass index (BMI)-matched healthy control subjects. The levels of hexacosanoic acid (C26:0), a VLCFA, in whole blood were measured by gas-liquid chromatography mass spectrometry. RESULTS: C26:0 levels were significantly higher in the CAD group than in the control group (2.42±0.32 vs. 2.27±0.24 µg/ml, P=0.01) and positively correlated with BMI (r=0.23, P=0.008), triglyceride levels (r=0.22, P=0.01), and hypertension (P=0.01). CAD patients with MS showed the highest C26:0 levels adjusted by hematocrit. Furthermore, adjusted C26:0 levels in CAD patients without MS were higher than those in controls (P=0.02), suggesting that C26:0 levels increased with the presence of CAD independent of MS. Our multivariate analysis revealed that high C26:0 levels in whole blood is an independent marker for CAD even after adjustment for age, gender, BMI, lipid profiles, fasting plasma glucose, and blood pressure. CONCLUSION: High C26:0 levels in whole blood may be an independent marker for identifying the risks of CAD.

High levels of very long-chain saturated fatty acid in erythrocytes correlates with atherogenic lipoprotein profiles in subjects with metabolic syndrome.

AIM: Very long chain saturated fatty acid (VLCFA) levels in erythrocytes are associated with metabolic syndrome (MS). However, the relationship between levels of the VLCFA ligonoceric acid (C24:0) in erythrocytes and the atherogenic lipoprotein profiles and inflammatory state in MS remain unclear. METHODS: Based on the International Diabetes Federation (IDF) definition of MS, 195 apparently healthy males were assigned to either an MS group (n=38) or a non-MS group (n=157). Fatty acid composition of erythrocytes was determined by gas liquid chromatography. RESULTS: Erythrocytes from the MS group had a significantly higher level of C24:0 than cells from the non-MS group (4.06±0.48% versus 3.88±0.34%; p=0.03). C24:0 levels were significantly correlated with several components of MS. The C24:0 levels showed a significant negative correlation with LDL and HDL particle size. Multivariate linear regression analysis showed that C24:0 levels were independently correlated with LDL particle size after adjusting for age and each MS criterion. C24:0 levels were also positively correlated with log-transformed high-sensitivity CRP levels (p=0.04). CONCLUSION: C24:0 levels in erythrocytes are associated with specific atherogenic lipoprotein profiles and inflammation status in subjects with MS.

Elovl6 promotes nonalcoholic steatohepatitis.

UNLABELLED: Nonalcoholic steatohepatitis (NASH) is associated with obesity and type 2 diabetes, and an increased risk for liver cirrhosis and cancer. ELOVL family member 6, elongation of very long chain fatty acids (Elovl6), is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have shown previously that Elovl6 is a major target for sterol regulatory element binding proteins in the liver and that it plays a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further investigate the role of Elovl6 in the development of NASH and its underlying mechanism, we used three independent mouse models with loss or gain of function of Elovl6, and human liver samples isolated from patients with NASH. Our results demonstrate that (1) Elovl6 is a critical modulator for atherogenic high-fat diet-induced inflammation, oxidative stress, and fibrosis in the liver; (2) Elovl6 expression is positively correlated with severity of hepatosteatosis and liver injury in NASH patients; and (3) deletion of Elovl6 reduces palmitate-induced activation of the NLR family pyrin domain-containing 3 inflammasome; this could be at least one of the underlying mechanisms by which Elovl6 modulates the progress of NASH. CONCLUSION: Hepatic long-chain fatty acid composition is a novel determinant in NASH development, and Elovl6 could be a potential therapeutic target for the prevention and treatment of NASH.

Clinical significance of the measurements of urinary liver-type fatty acid binding protein levels in patients with acute coronary syndrome.

BACKGROUND: Recently, much attention has been focused on cardio-renal interaction. Urinary liver-type fatty acid binding protein (U-L-FABP), which is produced in the proximal tubule by renal hypoxia and oxidative stress, has been identified as a useful marker for diagnosis of acute kidney disease and a predictor of future events in chronic kidney disease. However, the clinical significance of U-L-FABP measurements in patients with acute coronary syndrome (ACS) has not been completely evaluated. METHODS AND RESULTS: This study included 50 consecutive patients with ACS [37 with acute myocardial infarction (AMI) and 13 with unstable angina pectoris (UAP)] and 47 subjects without coronary artery disease (control group). U-L-FABP levels, urinary albumin (U-Alb), and other serum parameters were measured at admission and at 24 h after percutaneous coronary intervention. RESULTS: U-L-FABP levels in patients with AMI were significantly higher (p=0.0019), than in control subjects, while patients with UAP did not exhibit such an increase. U-L-FABP levels at admission were positively correlated with brain natriuretic protein levels (p=0.001) and duration of hospitalization (p=0.025). At follow-up angiography, patients with restenosis had significantly higher U-L-FABP (p=0.047) and U-Alb levels (p<0.0001) than those without restenosis. After a median follow-up of 42 months, U-L-FABP levels at second measurement in patients with major adverse cardiocerebrovascular events (MACCEs) were significantly higher than those in patients without MACCEs (p=0.028). After adjusting for confounding factors, high U-L-FABP levels at second measurement were found to be independent factors for MACCEs (p=0.019). CONCLUSIONS: These data suggest that patients with ACS, especially those with AMI, have high U-L-FABP levels, and that U-L-FABP measurements may be useful in identifying high-risk patients for future cardiovascular events after ACS.

Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between azelnidipine and amlodipine on glucose tolerance and endothelial function--a crossover trial (AGENT).

BACKGROUND: Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. METHODS: Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. RESULTS: Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). CONCLUSIONS: These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.