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High fructose intake has been implicated in obesity and metabolic syndrome, which are related to increased cardiovascular mortality. However, few studies have experimentally examined the role of renin–angiotensin system blockers and calcium channel blockers (CCB) in obesity. We investigated the effects of valsartan (an angiotensin II receptor blocker) and amlodipine (a CCB) on lipolysis through the potential mechanism of PU.1 inhibition. We observed that high fructose concentrations significantly increased adipose size and triglyceride, monoacylglycerol lipase, adipose triglyceride lipase, and stearoyl-CoA desaturase-1 (SCD1), activating transcription factor 3 and PU.1 levels in adipocytes in vitro. Subsequently, PU.1 inhibitor treatment was able to reduce triglyceride, SCD1, and PU.1 levels. In addition, elevated levels of triglyceride and PU.1, stimulated by a high fructose concentration, decreased with valsartan and amlodipine treatment. Overall, these findings suggest that high fructose concentrations cause triacylglycerol storage in adipocytes through PU.1-mediated activation. Furthermore, valsartan and amlodipine treatment reduced triacylglycerol storage in adipocytes by inhibiting PU.1 activation in high fructose concentrations in vitro. Thus, the benefits of valsartan and amlodipine in lipolysis may be through PU.1 inhibition in fructose-induced adiposity, and PU.1 inhibition might have a potential therapeutic role in lipolysis in fructose-induced obesity. [ABSTRACT FROM AUTHOR]

Keiji Hirai, Junki Morino, Saori Minato, Shohei Kaneko, Katsunori Yanai, Yuko Mutsuyoshi, Hiroki Ishii, Momoko Matsuyama, Taisuke Kitano, Mitsutoshi Shindo, Akinori Aomatsu, Haruhisa Miyazawa, Kiyonori Ito, Yuichiro Ueda, Susumu Ookawara, Yoshiyuki Morishita Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, Saitama, JapanCorrespondence: Keiji HiraiDivision of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-Cho, Omiya-Ku, Saitama City, Saitama 330-8503, JapanTel +81-48-647-2111Fax +81-48-647-6831Email keijihirai@kfy.biglobe.ne.jpIntroduction and Objectives: We investigated the efficacy and safety of sodium-glucose cotransporter-2 (SGLT-2) inhibitors as an add-on therapy in patients with advanced-stage diabetic kidney disease taking renin-angiotensin system (RAS) blockers.Materials and Methods: Changes in glycated hemoglobin (HbA1c), urine protein-to-creatinine ratio (UACR), body weight, systolic blood pressure, and annual change in estimated glomerular filtration rate (eGFR) were retrospectively analyzed in 20 patients after 12 months of SGLT-2 inhibitor administration (mean eGFR: 22.8 ± 9.7 mL/min/1.73 m2). All patients had advanced-stage diabetic kidney disease and were taking RAS blockers. Twenty patients matched with similar propensity scores who were not taking SGLT-2 inhibitors served as the control group.Results: The annual change in eGFR improved significantly from − 8.6 ± 12.5 mL/min/1.73 m2/year to − 2.6 ± 5.0 mL/min/1.73 m2/year after 12 months by SGLT-2 inhibitor administration (p < 0.05), but did not change in the control group. Other clinical parameters, such as HbA1c, UACR, body weight, blood pressure, serum lipids, and electrolytes did not change in either group. No adverse effects were observed by taking SGLT-2 inhibitors.Conclusion: Using SGLT-2 inhibitors as an add-on therapy may have beneficial effects on renal function in patients with advanced-stage diabetic kidney disease taking RAS blockers without any adverse effects.Keywords: advanced-stage diabetic kidney disease, renin-angiotensin system blocker, sodium-glucose cotransporter-2 inhibitor

High fructose intake has been implicated in obesity and metabolic syndrome, which are related to increased cardiovascular mortality. However, few studies have experimentally examined the role of renin–angiotensin system blockers and calcium channel blockers (CCB) in obesity. We investigated the effects of valsartan (an angiotensin II receptor blocker) and amlodipine (a CCB) on lipolysis through the potential mechanism of PU.1 inhibition. We observed that high fructose concentrations significantly increased adipose size and triglyceride, monoacylglycerol lipase, adipose triglyceride lipase, and stearoyl-CoA desaturase-1 (SCD1), activating transcription factor 3 and PU.1 levels in adipocytes in vitro. Subsequently, PU.1 inhibitor treatment was able to reduce triglyceride, SCD1, and PU.1 levels. In addition, elevated levels of triglyceride and PU.1, stimulated by a high fructose concentration, decreased with valsartan and amlodipine treatment. Overall, these findings suggest that high fructose concentrations cause triacylglycerol storage in adipocytes through PU.1-mediated activation. Furthermore, valsartan and amlodipine treatment reduced triacylglycerol storage in adipocytes by inhibiting PU.1 activation in high fructose concentrations in vitro. Thus, the benefits of valsartan and amlodipine in lipolysis may be through PU.1 inhibition in fructose-induced adiposity, and PU.1 inhibition might have a potential therapeutic role in lipolysis in fructose-induced obesity.

Although several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis. Methods: We performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a ß-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a ß-blocker (787 patients), or the combination of a ß-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04–3.34 yr). Results: After adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with ß-blocker–based antihypertensive therapy. The combination of a RAS blocker with a ß-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05–2.69; ß-blocker: HR: 1.59; 95% CI: 1.01–2.50; antihypertensive medication other than a RAS blocker or ß-blocker: HR: 1.67; 95% CI: 1.08–2.58). Discussion: Our data suggested that the combination of a RAS blocker and a ß-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.

Background Although current guidelines now define heart failure with midrange ejection fraction (HFmrEF) as HF with a left ventricular EF of 40% to 49%, there are limited data on response to guideline‐directed medical therapy in patients with HFmrEF. The current study aimed to evaluate the association between β‐blocker, renin‐angiotensin system blocker (RASB), or aldosterone antagonist (AA) treatment with clinical outcome in patients with HFmrEF. Methods and Results We performed a patient‐level pooled analysis on 1144 patients with HFmrEF who were hospitalized for acute HF from the KorHF (Korean Heart Failure) and KorAHF (Korean Acute Heart Failure) registries. The study population was divided between use of β‐blocker, RASB, or AA to evaluate the guideline‐directed medical therapy in patients with HFmrEF. Sensitivity analyses, including propensity score matching and inverse‐probability‐weighted methods, were performed. The use of β‐blocker in the discharge group showed significantly lower rates of all‐cause mortality compared with those who did not use a β‐blocker (β‐blocker versus no β‐blocker, 30.7% versus 38.2%; hazard ratio, 0.758; 95% confidence interval, 0.615–0.934; P=0.009). Similarly, the RASB use in the discharge group was associated with the lower risk of mortality compared with no use of RASB (RASB versus no RASB, 31.9% versus 38.1%; hazard ratio, 0.76; 95% confidence interval, 0.618–0.946; P=0.013). However, there was no significant difference in all‐cause mortality between AA and no AA in the discharge group (AA versus no AA, 34.2% versus 34.0%; hazard ratio, 1.063; 95% confidence interval, 0.858–1.317; P=0.578). Multiple sensitivity analyses showed similar trends. Conclusions For treatment of acute HFmrEF after hospitalization, β‐blocker and RASB therapies on discharge were associated with reduced risk of all‐cause mortality. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01389843.

Aims: It remains unclear if patients with acute heart failure syndrome (AHFS) need to reach the maximally tolerated doses of renin-angiotensin system blockers (RASBs) or beta-blockers (BBs) to obtain a survival benefit. This study evaluated the dose-response relationship between RASBs or BBs and survival in AHFS patients., Methods and Results: In total, 5331 patients in the Korean Acute Heart Failure registry were analysed based on the doses of RASBs and BBs at discharge. In AHFS patients, RASB use at discharge was associated with a significant reduction in all-cause mortality risk. This effect was dose-dependent for heart failure with reduced ejection fraction (HFrEF) but did not attain statistical significance for heart failure with preserved ejection fraction (HFpEF). BB use at discharge was associated with reduced all-cause mortality in HFrEF patients but not in HFpEF patients. In an additional analysis of 4613 patients with dosage information at the first post-discharge follow-up visit, a significantly higher mortality risk was associated with the maintenance or withdrawal of RASBs compared with up-titrating the dose in HFrEF patients., Conclusion: Using RASBs or BBs at discharge was associated with improved survival. A dose-response relationship between RASBs and all-cause mortality was evident in AHFS patients with a reduced ejection fraction but not BBs. It is important to initiate and up-titrate RASBs to the maximally tolerated dose in AHFS patients during the transition period, especially for patients with a reduced ejection fraction., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: In the general population, metabolic syndrome (MetS) is correlated with visceral fat and a risk factor for cardiovascular disease (CVD); however, little is known about the significance of abdominal fat and its association with inflammation and medication use in peritoneal dialysis (PD) patients. We investigated the relationship of visceral fat area (VFA) with C-reactive protein (CRP) levels and medication use in PD patients and followed their clinical outcomes. Methods: In a prospective study from February 2009 to February 2012, we assessed diabetes mellitus (DM) status, clinical and PD-associated characteristics, medication use, CRP levels, components of MetS, and VFA in 183 PD patients. These patients were categorized into 3 groups based on MetS and DM status: non-MetS (group 1, n = 73), MetS (group 2, n = 65), and DM (group 3, n = 45). VFA was evaluated by computed tomography (CT) and corrected for body mass index (BMI). Results: Patients in group 1 had smaller VFAs than patients in groups 2 and 3 (3.2 ± 1.8, 4.6 ± 1.9, and 4.9 ± 2.0 cm2/[kg/m2], respectively, P < 0.05) and lower CRP levels (0.97 ± 2.31, 1.27 ± 2.57, and 1.11 ± 1.35 mg/dL, respectively, P < 0.05). VFA increased with the number of criteria met for MetS. After adjusting for age, body weight, and sex, CRP and albumin levels functioned as independent positive predictors of VFA; on other hand, the use of reninangiotensin system blockers was inversely correlated with VFA in PD patients without DM. In the survival analysis, DM patients (group 3) had the poorest survival among the 3 groups, but no significant differences were found between groups 1 and 2. Conclusion: This study showed that VFA and MetS are associated with CRP levels but cannot predict survival in PD patients without DM. The complex relationship of nutritional parameters to VFA and MetS may explain these results. The type of antihypertensive medication used was also associated with the VFA. The mechanisms behind these findings warrant further investigation. [ABSTRACT FROM AUTHOR]

Catheter ablation of atrial fibrillation (AF) may modify the atrial substrate and isolate AF triggers but reversing and preventing further atrial remodeling should be attempted specific postinterventional medication regimen. Inhibition of the renin-angiotensin system may be integral in interfering with structural remodeling of the atria during AF. Specifically, angiotensin receptor blocker - owing to their high local atrial effectiveness in blocking angiotensin-mediated pathways - may help to improve rhythm outcome after AF interventions. Optimum success of an aggressive AF intervention can only be achieved when patients selection for specific postinterventional pharmacological agents is optimized. [ABSTRACT FROM AUTHOR]

Elevated C-reactive protein (CRP) levels have been associated with increased cardiovascular risk in hypertensive adults. The aim of this study was to determine whether plasma CRP level is more predictive of left ventricular hypertrophy (LVH) than is ambulatory blood pressure (BP) in hypertensive children. Baseline and 12-month follow-up measures of BP, body mass index (BMI), low-density lipoprotein/high density lipoprotein cholesterol, left ventricular mass (LVM), and CRP data collected from 48 newly diagnosed, untreated hypertensive children were analyzed. CRP was measured by a highly sensitive nephelometric method. Left ventricular mass index (LVMI) was calculated as LVM/height2.7, and LVH was defined as LVMI >38.6 g/m2.7 being the cut-point for the 95th percentile found in healthy children. Average systolic BP (SBP), diastolic BP (DBP), SBP index, and DBP index were calculated. All patients received hydrochlorothiazide therapy in combination with angiotensin converting enzyme inhibitor treatment. Five patients also had angiotensin receptor blocker therapy to reach the target BP (<95th percentile corrected for age and gender). In a multiple regression analysis, LMVI was correlated with CRP, BMI, SBP, and SBP index. CRP alone explained 77% of the variance of LVMI, whereas BMI, SBP, and SBP index explained only 1.3, 0.3, and 0.4% of the variance, respectively. CRP was also the most significant correlate of follow-up LVH. In conclusion, elevated CRP level is significantly associated with LVH in children with essential hypertension. BP reduction with renin–angiotensin system blocker and hydrochlorothiazide therapy reduces LVH while lowering CRP level. [ABSTRACT FROM AUTHOR]

Background Although current guidelines now define heart failure with midrange ejection fraction ( HF mr EF ) as HF with a left ventricular EF of 40% to 49%, there are limited data on response to guideline-directed medical therapy in patients with HF mr EF . The current study aimed to evaluate the association between β-blocker, renin-angiotensin system blocker ( RASB ), or aldosterone antagonist ( AA ) treatment with clinical outcome in patients with HF mr EF . Methods and Results We performed a patient-level pooled analysis on 1144 patients with HF mr EF who were hospitalized for acute HF from the Kor HF (Korean Heart Failure) and Kor AHF (Korean Acute Heart Failure) registries. The study population was divided between use of β-blocker, RASB , or AA to evaluate the guideline-directed medical therapy in patients with HF mr EF . Sensitivity analyses, including propensity score matching and inverse-probability-weighted methods, were performed. The use of β-blocker in the discharge group showed significantly lower rates of all-cause mortality compared with those who did not use a β-blocker (β-blocker versus no β-blocker, 30.7% versus 38.2%; hazard ratio, 0.758; 95% confidence interval, 0.615-0.934; P=0.009). Similarly, the RASB use in the discharge group was associated with the lower risk of mortality compared with no use of RASB ( RASB versus no RASB , 31.9% versus 38.1%; hazard ratio, 0.76; 95% confidence interval, 0.618-0.946; P=0.013). However, there was no significant difference in all-cause mortality between AA and no AA in the discharge group ( AA versus no AA , 34.2% versus 34.0%; hazard ratio, 1.063; 95% confidence interval, 0.858-1.317; P=0.578). Multiple sensitivity analyses showed similar trends. Conclusions For treatment of acute HFmrEF after hospitalization, β-blocker and RASB therapies on discharge were associated with reduced risk of all-cause mortality. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01389843.

Background: Several human studies reported that the combined use of renin-angiotensin system blockers (RASBs) and vitamin D receptor activators (VDRAs) resulted in decreased urinary protein excretion. However, it is unknown whether this combination therapy influences the incidence of cardiovascular (CV) events in dialysis patients., Methods: The study was a multicenter nonrandomized prospective cohort analysis including 1,518 patients. Patients were classified into 4 groups based on medications prescribed before dialysis initiation: those who did not receive RASBs or oral VDRAs (N group), those receiving only RASBs, those receiving only VDRAs, and those receiving a combination of RASBs and VDRAs (RD group). CV events after dialysis initiation were compared using the log-rank test. Factors contributing to the incidence of CV events were examined using multivariate Cox proportional hazard regression analysis., Results: Significant differences were observed in the incidence of CV events and all-cause mortality between the 4 groups ( p = 0.021 and p = 0.001, respectively). Cox proportional hazard analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (hazard ratio [HR] = 0.65, 95% confidence interval [CI]: 0.50-0.86, p = 0.002). Multivariate analysis revealed that the incidence of CV events was significantly lower in the RD group than in the N group (HR = 0.66, 95% CI: 0.47-0.93, p = 0.016)., Conclusion: Combination therapy with RASBs and VDRAs in patients before dialysis initiation was associated with a reduction in CV events during maintenance dialysis.

Introduction: Although several studies suggest that the prognosis of hypertensive dialysis patients can be improved by using antihypertensive drug therapy, it is unknown whether the prescription of a particular class or combination of antihypertensive drugs is beneficial during hemodialysis., Methods: We performed a propensity score matching study to compare the effectiveness of various classes of antihypertensive drugs on cardiovascular (CV) mortality in 2518 incident hemodialysis patients in Spain. The patients had initially received antihypertensive therapy with a renin-angiotensin system (RAS) blocker (728 patients), a ß-blocker (679 patients), antihypertensive drugs other than a RAS blocker or a ß-blocker (787 patients), or the combination of a ß-blocker and a RAS inhibitor (324 patients). These patients were followed for a maximum of 5 years (median: 2.21 yr; range: 1.04-3.34 yr)., Results: After adjustment for baseline CV risk covariates, no significant differences were observed in the risk of CV mortality between patients taking a RAS blocker and patients treated with ß-blocker-based antihypertensive therapy. The combination of a RAS blocker with a ß-blocker was associated with better CV survival than either agent alone (RAS blocker: hazard ratio [HR]: 1.68; 95% confidence interval [CI] 1.05-2.69; ß-blocker: HR: 1.59; 95% CI: 1.01-2.50; antihypertensive medication other than a RAS blocker or ß-blocker: HR: 1.67; 95% CI: 1.08-2.58)., Discussion: Our data suggested that the combination of a RAS blocker and a ß-blocker could improve survival in hemodialysis patients. Further prospective randomized controlled trials are necessary to confirm the beneficial effects of this combination of antihypertensive drugs in patients undergoing hemodialysis.

Introduction: Heart failure (HF) is a medical condition with a rapidly increasing incidence both in Taiwan and worldwide. The objective of the TSOC-HFrEF registry was to assess epidemiology, etiology, clinical management, and outcomes in a large sample of hospitalized patients presenting with acute decompensated systolic HF., Methods: The TSOC-HFrEF registry was a prospective, multicenter, observational survey of patients presenting to 21 medical centers or teaching hospitals in Taiwan. Hospitalized patients with either acute new-onset HF or acute decompensation of chronic HFrEF were enrolled. Data including demographic characteristics, medical history, primary etiology of HF, precipitating factors for HF hospitalization, presenting symptoms and signs, diagnostic and treatment procedures, in-hospital mortality, length of stay, and discharge medications, were collected and analyzed., Results: A total of 1509 patients were enrolled into the registry by the end of October 2014, with a mean age of 64 years (72% were male). Ischemic cardiomyopathy and dilated cardiomyopathy were diagnosed in 44% and 33% of patients, respectively. Coronary artery disease, hypertension, diabetes, and chronic renal insufficiency were the common comorbid conditions. Acute coronary syndrome, non-compliant to treatment, and concurrent infection were the major precipitating factors for acute decompensation. The median length of hospital stay was 8 days, and the in-hospital mortality rate was 2.4%. At discharge, 62% of patients were prescribed either angiotensin-converting enzyme-inhibitors or angiotensin receptor blockers, 60% were prescribed beta-blockers, and 49% were prescribed mineralocorticoid receptor antagonists., Conclusions: The TSOC-HFrEF registry provided important insights into the current clinical characteristics and management of hospitalized decompensated systolic HF patients in Taiwan. One important observation was that adherence to guideline-directed medical therapy was suboptimal.