Autophagy has been thought as a novel cell death mechanism involving in the pathophysiological process of myocardial infarction (MI), and modulation of autophagy may be considered as a promising treatment modality for MI. Dysglycemia was associated with higher mortality in patients with MI. We hypothesize that autophagy may be a potential pathway through which dysglycemia has an impact on the outcomes of MI. In this review, we summarize the function of autophagy in the conditions of MI and the regulatory effects of dysglycemia on autophagy. Four main impacts of autophagy on MI under dysglycemia have been revealed. The first one is that autophagy limits the infarct size via inhibited mTOR. The second one is that autophagy promotes the survival of cardiomyocytes through depleted ATP. The third one is that autophagy protects cardiac myocytes from imparing by way of degradation. The last one is that autophagy maintenance of LV function through FoxO1. Therefore, the ability to modulate autophagy may represent as a potential and promising therapeutic strategy in limiting MI caused by dysglycemia. However, elucidation of precise ways of autophagy in mediating MI caused by dysglycemia, as well as when and how autophagy is manipulated remains us to research.
Objective and methods: We investigated the hypothesis that serum low-density lipoprotein cholesterol (LDL-C) reduction by ezetimibe is associated with the improvement in postprandial hyperlipidemia by performing an oral fat loading test before and 24 weeks after ezetimibe treatment in diabetic (n = 29) and non-diabetic (n= 30) male patients with coronary artery disease (CAD).Results: Serum LDL-C levels were significantly reduced by ezetimibe in both groups (diabetic, from 120.3 +/- 39.4 to 79.5 +/- 23.2mg/dL, p < 0.001; non-diabetic, from98.2 +/- 41.7 to 76.7 +/- 29.2mg/dL, p < 0.001), and the mean reduction in serumLDL-Cwas greater in diabetic than non-diabetic patients (-32.0 vs.-19.0%, p= 0.004). The area under the curve (AUC) for triglyceride (TG) and remnant-like particle cholesterol (RLP-C) decreased significantly in both groups. When compared with the reduction before and after treatment in AUC of TG (Delta AUC(0-6h) TG) and RLP-C (Delta AUC(0-6h) RLP-C), they were significantly greater in diabetic than non-diabetic patients (Delta AUC(0-6h) TG, -28.9 vs. -12.2%, p = 0.028;Delta AUC(0-6h) RLP-C, -27.8 vs. -12.3%, p = 0.007). In diabetic patients,Delta AUC(0-6h) TG and Delta AUC(0-6h) RLP-C in the highest tertile of serum LDL-C reduction were significantly greater than those in the lowest tertile (Delta AUC(0-6h) TG,-34.1 vs.-20.9%, p= 0.012;.AUC(0-6h) RLP-C,-34.5 vs.-15.1%, p = 0.024).Conclusions: These findings suggest that serum LDL-C reduction by ezetimibe might be associated with the improvement of postprandial hyperlipidemia in diabetic patients with CAD. (C) 2016 The Author(s). Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license
Background: It is unclear whether the addition of dipeptidyl peptidase-4 inhibitors (DPP4-I) to statins may cause coronary plaque regression in type 2 diabetes mellitus (T2DM) patients with coronary artery disease (CAD). Methods and results: Seventy-five T2DM patients with CAD who underwent percutaneous coronary intervention under intravascular ultrasound (IVUS) guidance were randomized to receive DPP4-I sitagliptin (sitagliptin group) or not to receive DPP4-I (non-DPP4-I group) as an add-on treatment to statins, and were followed-up for 8-12 months. Patients with analyzable IVUS examinations of the non-culprit segment were included in the primary analysis. Sitagliptin group (n = 28) and non-DPP4-I group (n = 24) had significant (p < 0.05) and similar reduction in low-density lipoprotein cholesterol levels (-12 +/- 24 and -12 +/- 23 mg/dL), and had no significant changes in hemoglobin A(1c) levels. Nominal change in percent atheroma volume (PAV), the primary endpoint, was not significant in both the sitagliptin and non-DPP4-I groups [mean (95% CI): + 1.1% (-0.5 to 2.7%) and 0.2% (-1.5 to 1.9%)]. The difference in change in PAV between sitagliptin and non-DPP4-I groups was also not significant [0.89% (-1.46%-3.25%)]. Conclusions: The addition of sitagliptin to statins did not cause coronary plaque regression in T2DM with CAD. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.
Back ground: Cardiotoxicity confines the usage of Adriamycin in clinical practice as it can develop cardiac impediments up to 10 years after the termination of therapy. Even though, no specific therapeutic strategies are available for treating adriamycin-induced cardiotoxicity, beta-adrenergic blockers (beta B) and angiotensin-converting enzyme (ACE) inhibitors are known to prevent its progression into failure. In this scenario, we attempted to compare the pharmacological outcome of sub-acute beta B and ACE inhibitor treatments in preventing adriamycin-induced cardiotoxicity by analysing the differences between them.Methods: Rats received a single bolus dose of adriamycin (10mg/kg) on day one and treated with either Carvedilol (10mg/kg) (CAR) or Captopril (50 mg/kg) (CAP) once daily for 28 days. Cardiac morphology, systolic and diastolic functions were evaluated by 2D trans-thoracic echocardiography. Cardiac Troponin and Ck MB levels were measured to analyse the myocyte damage. Myocardial lipid peroxidation, IL1 beta levels and caspase 3 activity were evaluated as the markers of oxidative stress, inflammation and apoptosis respectively.Results: Both treatments had reduced the adriamycin induced cardiotoxicity. Whereas CAP treatment showed a better reduction of inflammation, superior preservation of posterior wall architecture and enhanced improvement in relative wall thickness when compared to CAR. Oxidative stress, caspase 3 activity and markers of myocyte damage were better recovered with CAR treatment while other parameters were found to be identically attenuated.Conclusion: The present study found an identical therapeutic outcome from ACE inhibition and beta blockade with a better attenuation of inflammation and structural preservation with ACE inhibition and superior antioxidant and antiapoptotic effect with beta B treatment. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license
Background: Patients with Chagas heart disease (CHD) usually present progressive fatigue and dyspnea. The inspiratorymuscleweakness (IMW) may be a marker of exercise intolerance during disease progression. However, the factors related to IMWin CHD patients still remain unknown.Methods: Forty-eight CHD patients aged 56.4 (53.3-59.5) yearswere selected and underwent respiratorymuscle strength, echocardiography, Cardiopulmonary Exercise Testing and International Physical Activity Questionnaire (IPAQ). The sample was stratified according to the percentage (%) of maximum inspiratory pressure (MIP) achieved in preserved muscle strength (MIP > 70%) or IMW (MIP >= 70%). Chi-square and Poisson regression analysis was performed to verify the predictors of IMW.Results: The % MIP predicted correlated with left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVDd) and minute ventilation-carbon dioxide production slope (VE/VCO2 slope). Significant differences in the IPAQ scores (p = 0.036), LVEF (p = 0.020) and VE/VCO2 slope (p = 0.008) were found between groups with preserved inspiratory muscle strength and with IMW. In multivariate analysis, sedentary patients and those with reduced LVEF and impaired VE/VCO2 slope had 6.3, 5.5 and 1.2-fold increased risk for IMW, respectively.Conclusion: The sedentary lifestyle, reduced LVEF and impaired VE/VCO2 slope showed to be independent predictors of IMW, probably by the association between these variables and the presence of inflammation in CHD patients. The detection of IMW may be helpful in identifying patients at high risk based on echocardiographic and functional aspects without much operating costs. (C) 2016 Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license
Introduction: Recent studies have shown that in chronic kidney disease (CKD) 25(OH) D deficiency or insufficiency is a significant risk factor for cardiovascular diseases (CVDs), sudden cardiac death (SCD) and mortality. Premature ventricular complexes (PVCs) are very common in patients with CKD, hypertension, obesity, sleep apnea, and structural heart disease. Often PVCs in the structurally normal heart are considered benign, although they seem to be associated with a more than two-fold higher risk of cardiovascular complications, including stroke disease and death.Aim: In the present study we aimed to evaluate the influence of different 25(OH) D levels on the changes of the numbers of PVCs in all patients, assessed by 24-hour-Holter monitoring 3 months after beta-blocker onset.Methods and results: We conducted a prospective, longitudinal study of 824 patients with PVCs and CKD (estimated glomerular filtration rate measured by MDRD equation, between 16 and 59 mL/min/1.73 m(2)). All patients were treated with a beta-blocker (bisoprolol 10 mg daily). We observed that the 3 groups presented a significant decrease in the number of PVCs from baseline 26,091 +/- 3327 (25(OH) D deficiency group), 25,902 +/- 3501 (25(OH) D insufficiency group), and 25,554 +/- 3637 (25(OH) D sufficiency group) to 20,554 +/- 3782, 19,885 +/- 3945 and 15,433 +/- 4059, respectively, after 3 months of beta-blocker therapy (P < 0.0001 for the comparisons between time points in the same group). However at the 3rd month after bisoprolol onset, comparisons between 25(OH) D deficiency vs. 25(OH) D sufficiency groups showed a mean difference of 5121 PVCs (P < 0.0001), and comparisons between 25(OH) D insufficiency vs. 25(OH) D sufficiency groups showed a mean difference of 4452 PVCs (P < 0.0001). No difference was observed between 25(OH) D deficiency vs. 25(OH) D insufficiency groups (P= 0.3181).Conclusions: We suggest that the effectiveness of beta-blocker treatment for PVCs in CKD patients was observed in all 25(OH) D levels. However, the responsiveness was higher in patients with a normal range of 25(OH) D in comparison to patients with deficiency or insufficiency in 25(OH) D levels. Whether vitamin D supplementation increases the efficacy of beta-blocker mediated suppression of PVCs requires further evaluation. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license
Objective: Familial hypercholesterolemia (FH), an autosomal dominant genetic disorder, is often diagnosed in young age and cholesterol accumulation in tissues produces common clinical manifestations including cutaneous xanthomas, premature atherosclerosis, and poor response to medical therapy. The main objective was to investigate the patients of hoFH from China.Patients: Over the past 4 years, a cohort of 8 patients with severe FH phenotype due to the characteristic cutaneous xanthomas and extremely high low density lipoprotein cholesterol (LDL-C) levels from the national lipid clinics were enrolled. Genotype information was obtained.Results: Of them, 7 patients had severe coronary atherosclerosis, 6 had family history of hypercholesterolemia, 2 had family history of premature coronary atherosclerosis. The patients had untreated LDL-C of > 13 mmol/L, and received maximal medical therapy. Importantly but not surprisingly, the lipid profile was not significantly improved by the current available concomitant use of rosuvastatin and ezetimibe. In genetic analysis, all patients had the mutations responsible to the FH phenotype and showed to be more heterogeneous than their clinical phenotype.Conclusion: In a conclusion, we found a relatively common recruitment of this type of patients in our hospital, which might have an important clinical implication for the identification and management of the patients with FH in China. (C) 2017 Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license
Introduction: Recent studies have shown that in chronic kidney disease (CKD) 25(OH) D deficiency or insufficiency are a significant risk factor for cardiovascular diseases, sudden cardiac death andmortality. The high incidence of premature ventricular complexes (PVCs) have increasingly been recognized as a primary cause for worsening left ventricular systolic function and heart failure in some patients, specialty when these subjects are under optimal treatment and have implantable cardiac defibrillator (ICD) with cardiac resynchronization therapy (CRT), because the great amount of PVCs reduces the percentage of cardiac resynchronization.Aim: Our aimwas to evaluate the influence of reposition of cholecalciferol in patients with deficiency of vitamin D in the changes of the numbers of PVCs, and consequently in the percentage of cardiac resynchronization time, during 6 months of followup.Methods and results: We conducted a prospective, longitudinal study of 56 patients with high incidence of PVCs, heart failure under optimal treatment, ICD + CRT, deficiency of vitamin D (<= 20 ng/mL) and CKD (estimated glomerular filtration rate measured by MDRD equation, between 16 and 59 mL/min/1.73 m(2)). All patients were treated with cholecalciferol. We observed significant ameliorating after cholecalciferol onset in the number of PVCs, CRT % time, renal function, vitamin D levels and plasmatic ions at the 6th month of followup vs. baseline. Conclusions: We suggest that the effectiveness of cholecalciferol reposition for subjects with high incidence of PVCs, heart failure under optimal treatment, ICD + CRT, deficiency of vitamin D and CKD, restoring the function of the CRT, bringing the biventricular pacing to nearby 97%. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BYNCND license
Background: The risk of liver injury is greatly of concern in China due to higher prevalence of hepatitis. In this study, we evaluated the association between the use of statins and the elevation of aminotransferase (ALT) in "real-world" clinical practice. Methods: 4489 patients were divided into statins group (62%) and no statins group (38%) according to their status of medications. Detections of ALT were performed within 24 h after admission. The association of elevation of ALT and statins was analyzed. Results: The percentage of patients with ALT > 1 x ULN(Upper Limit of Normal), was higher in statins group than that in no statins group (OR = 1.27, 95% CI 1.08-1.493), but after adjusting risk factors the OR value was 1.043(95% CI 0.851-1.278) with no statistical difference. Similarly, no differences were found regarding percentages of patients with ALT > 3 x ULN. Types of statins were usual in clinical practice and dosages of statins used were moderate in > 90% of patient. We failed to find differences among the types and the dosage of statins except lovastatin. In addition, the relation of statin use duration to elevated ALT was evaluated. The higher proportion of elevated ALT in patients with stain use <1 month was detected compared those with stain use = 3 months (OR = 1.408, 95% CI 1.111-1.783). Conclusion: The data, firstly, provided two important information regarding the real status of liver dysfunction in Chinese patients who used moderate statins: 1) no relations between statin variety and ALT elevation; 2) statin-induced liver dysfunction frequently found in < 1 month. Further study may be needed to confirm our findings. (C) 2017 The Authors. Published by Elsevier Ireland Ltd.
