Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients

Background Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. Methods We enrolled 319 consecutive CVD patients aged >= 40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). Results The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P <0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P <0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). Conclusion High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM

Elevated Circulating Levels of Inflammatory Markers in Patients with Acute Coronary Syndrome

Objective. We evaluated inflammatory cytokines and chemokine in peripheral blood mononuclear cells (PBMCs) in patients with either acute coronary syndrome (ACS) or stable coronary artery disease (CAD). Methods. We enrolled 20 ACS patients and 50 stable CAD patients without previous history of ACS who underwent cardiac catheterization. Patients with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2 and C-reactive protein of ≥1.0 mg/dL were excluded. Blood samples were collected from the patients just before catheterization, and PBMCs were isolated from the whole blood. The levels of inflammatory cytokines and chemokine were measured by using real-time quantitative polymerase chain reaction and immunoassays. Results. The expression of tumor necrosis factor alpha (TNF-α), interleukin- (IL-) 6, IL-10, IL-23A, IL-27, and IL-37 was significantly higher in the ACS group than in the CAD group (P<0.05). In contrast, the expression of IL-33 was significantly lower in the ACS group than in the CAD group (P<0.05). The ACS patients had higher plasma levels of TNF-α, IL-6, and IL-10 in the ACS group than in the CAD group. Conclusion. Circulating levels of pro-/anti-inflammatory cytokines, including IL-23A, IL-27, IL-33, and IL-37, may be associated with the pathogenesis of atherosclerosis in ACS patients

Preliminary Pilot Study of Combined Effects of Physical Activity and Achievement of LDL-Cholesterol Target on Coronary Plaque Volume Changes in Patients with Acute Coronary Syndrome

Background: We investigated the combined effects of physical activity (PA) and aggressive low-density lipoprotein cholesterol (LDL-C) reduction on the changes in coronary plaque volume (PV) in patients with acute coronary syndrome (ACS) using volumetric intravascular ultrasound (IVUS) analysis. Methods: We retrospectively analyzed data from two different prospective clinical trials that involved 101 ACS patients who underwent percutaneous coronary intervention (PCI) and assessed the non-culprit sites of PCI lesions using IVUS at baseline and at the follow-up. After PCI, all the patients participated in early phase II comprehensive cardiac rehabilitation. Patients were divided into four groups based on whether the average daily step count, measured using a pedometer, was 7000 steps of more and whether the follow-up LDL-C level was &lt;70 mg/dL. At the time of follow-up, we examined the correlation of changes in the PV with LDL-C and PA. Results: The baseline characteristics of the four study groups were comparable. At the follow-up, plaque regression in both the achievement group (PA and LDL-C reduction) was higher than that in the other three groups. In addition, plaque reduction independently correlated with increased PA and reduction in LDL-C level. Conclusions: Combined therapy of intensive PA and achievement of LDL-C target retarded coronary PV in patients with ACS

Voluntary exercise and cardiac remodeling in a myocardial infarction model

We investigated the effects of voluntary exercise after myocardial infarction (MI) on cardiac function, remodeling, and inflammation. Male C57BL/6J mice were divided into the following four groups: sedentary + sham (Sed-Sh), sedentary + MI (Sed-MI), exercise + sham (Ex-Sh), and exercise + MI (Ex-MI). MI induction was performed by ligation of the left coronary artery. Exercise consisting of voluntary wheel running started after the operation and continued for 4 weeks. The Ex-MI mice had significantly increased cardiac function compared with the Sed-MI mice. The Ex-MI mice showed significantly reduced expression levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and IL-10 in the infarcted area of the left ventricle compared with the Sed-MI mice. In the Ex-MI mice, the expression levels of fibrosis-related genes including collagen I and III were decreased compared to the Sed-MI mice, and the expression levels of IL-1β, IL-6, follistatin-like 1, fibroblast growth factor 21, and mitochondrial function-related genes were significantly elevated in skeletal muscle compared with the Sed mice. The plasma levels of IL-6 were also significantly elevated in the Ex-MI group compared with the Sed-MI groups. These findings suggest that voluntary exercise after MI may improve in cardiac remodeling associated with anti-inflammatory effects in the myocardium and myokine production in the skeletal muscles

Low Docosahexaenoic Acid, Dihomo-Gamma-Linolenic Acid, and Arachidonic Acid Levels Associated with Long-Term Mortality in Patients with Acute Decompensated Heart Failure in Different Nutritional Statuses

The clinical significance of polyunsaturated fatty acids (PUFAs) in acute decompensated heart failure (ADHF) in various nutritional statuses remains unclear. For this study, we enrolled 267 patients with ADHF admitted to the cardiac intensive care unit at Juntendo University hospital between April 2012 and March 2014. The association between long-term mortality, the geriatric nutritional risk index (GNRI), and levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), dihomo-gamma-linolenic acid (DGLA), and arachidonic acid (AA) was investigated. The median age was 73 (64–82) years, and mortality was 29% (62 patients). The event-free survival rates for all-cause death were higher in patients with high PUFA levels or GNRI than in those with low PUFA levels or GNRI (p &lt; 0.05 for all). In particular, high DGLA in the low-GNRI group and high DHA or AA in the high-GNRI group were associated with high event-free survival (p &lt; 0.05 for all). After accounting for confounding variables, DHA, DGLA, and AA, but not EPA, were associated with long-term mortality (p &lt; 0.01 for all). This study concludes that in patients with ADHF, decreased levels of DHA, DGLA, and AA are independently associated with long-term mortality in the various nutritional statuses

Associations among circulating levels of follistatin-like 1, clinical parameters, and cardiovascular events in patients undergoing elective percutaneous coronary intervention with drug-eluting stents.

ObjectivesFollistatin-like 1 (FSTL1) is a glycoprotein secreted by skeletal muscle cells and cardiac myocytes. Previous studies showed that serum FSTL1 concentrations were increased in acute coronary syndrome and chronic heart failure. The aim of this study was to assess the associations among plasma FSTL1 concentration, clinical parameters, and whether FSTL1 concentration could predict cardiovascular events in patients with elective percutaneous coronary intervention (PCI).Methods and resultsA consecutive series of 410 patients who underwent elective PCI with drug-eluting stents (DES) were enrolled between August 2004 and December 2006 at Juntendo University hospital. We measured plasma FSTL1 levels prior to elective PCI and assessed the association among FSTL1 levels, clinical parameters, and occurrence of major adverse cardiac or cerebrovascular events (MACCE) defined as cardiac death, nonfatal myocardial infarction, unstable angina, stroke, and hospitalization for heart failure. FSTL1 concentration was positively correlated with high-sensitivity C-reactive protein (hsCRP), serum creatinine, and N-terminal pro b-type natriuretic peptide (all P ConclusionHigh plasma FSTL1 may be a predictor of cardiovascular events in patients who underwent elective PCI with DES, especially with preserved renal function and low hsCRP

Correlation of Nutritional Indices on Admission to the Coronary Intensive Care Unit with the Development of Delirium

Background: Delirium is a common occurrence in patients admitted to the intensive care unit and is related to mortality and morbidity. Malnutrition is a predisposing factor for the development of delirium. Nevertheless, whether the nutritional status on admission anticipates the development of delirium in patients with acute cardiovascular diseases remains unknown. Objective: This study aims to assess the correlation between the nutritional status on admission using the nutritional index and the development of delirium in the coronary intensive care unit. Design: We examined 653 consecutive patients (mean age: 70 &#177; 14 years) admitted to the coronary intensive care unit of Juntendo University Hospital between January 2015 and December 2016. We evaluated three nutritional indices frequently used to assess the nutritional status, i.e., Geriatric Nutritional Risk Index (GNRI), Prognostic Nutritional Index (PNI), and Controlling Nutritional Status (CONUT). We defined delirium as patients with a delirium score &gt;4 using the Intensive Care Delirium Screening Checklist. Results: Delirium was present in 58 patients. All nutritional indices exhibited a tendency for malnutrition in the delirium group compared with the non-delirium group (GNRI, 86.5 &#177; 9.38 versus 91.6 &#177; 9.89; PNI, 36.4 &#177; 6.95 versus 41.6 &#177; 7.62; CONUT, 5.88 &#177; 3.00 versus 3.61 &#177; 2.56; for all, p &lt; 0.001). Furthermore, the maximum delirium score increased progressively from the low- to the high-risk group, as evaluated by each nutritional index (GNRI, PNI, CONUT; for all, p &lt; 0.001). A multivariate analysis revealed that the PNI and CONUT were independent risk factors for the occurrence of delirium. Conclusions: A marked correlation exists between the nutritional index on admission, especially PNI and CONUT, and the development of delirium in patients with acute cardiovascular diseases, suggesting that malnutrition assessment upon admission could help identify patients at high risk of developing delirium

Possible Role of NADPH Oxidase 4 in Angiotensin II-Induced Muscle Wasting in Mice

Background: Muscle wasting is a debilitating phenotype associated with chronic heart failure (CHF). We have previously demonstrated that angiotensin II (AII) directly induces muscle wasting in mice through the activation of NADPH oxidase (Nox). In this study, we tested the hypothesis that deficiency of NADPH oxidase 4 (Nox4), a major source of oxidative stress, ameliorates AII-induced muscle wasting through the regulation of redox balance.Methods and Results: Nox4 knockout (KO) and wild-type (WT) mice were used. At baseline, there were no differences in physical characteristics between the WT and KO mice. Saline (vehicle, V) or AII was infused via osmotic minipumps for 4 weeks, after which, the WT + AII mice showed significant increases in Nox activity and NOX4 protein compared with the WT + V mice, as well as decreases in body weight, gastrocnemius muscle weight, and myocyte cross-sectional area. These changes were significantly attenuated in the KO + AII mice (27 ± 1 vs. 31 ± 1 g, 385 ± 3 vs. 438 ± 13 mg, and 1,330 ± 30 vs. 2281 ± 150 μm2, respectively, all P &lt; 0.05). The expression levels of phospho-Akt decreased, whereas those of muscle RING Finger-1 (MuRF-1) and MAFbx/atrogin-1 significantly increased in the WT + AII mice compared with the WT + V mice. Furthermore, nuclear factor erythroid-derived 2-like 2 (Nrf2) and the expression levels of Nrf2-regulated genes significantly decreased in the WT + AII mice compared with the WT + V mice. These changes were significantly attenuated in the KO + AII mice (P &lt; 0.05).Conclusion: Nox4 deficiency attenuated AII-induced muscle wasting, partially through the regulation of Nrf2. The Nox4–Nrf2 axis may play an important role in the development of AII-induced muscle wasting

Additional file 1: of Decreased circulating dihomo-gamma-linolenic acid levels are associated with total mortality in patients with acute cardiovascular disease and acute decompensated heart failure

Serum fatty acids profiles of survivors and nonsurvivors. (XLSX 32 kb