Search

Abstract The risk of cardiovascular complication in a diabetes patient is similar to that in a nondiabetic patient with a history of myocardial infarction. Although intensive control of glycemia achieved by conventional antidiabetic agents decreases microvascular complications such as retinopathy and nephropathy, no marked effect has been reported on macrovascular complications or all-cause mortality. Evidence from VADT, ACCORD, and ADVANCE would suggest that glycemic control has little effect on macrovascular outcomes. Moreover, in the case of ACCORD, intensive glycemic control may be associated with an increased risk of mortality. There is sufficient evidence that suggests that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease in diabetes patients. However, there are no prospective clinical trials supporting the recommendation that lowering postprandial blood glucose leads to lower risk of cardiovascular outcomes. Mitiglinide is a short-acting insulinotropic agent used in type 2 diabetes treatment. It has a rapid stimulatory effect on insulin secretion and reduces postprandial plasma glucose level in patients with type 2 diabetes. Because of its short action time, it is unlikely to exert adverse effects related to hypoglycemia early in the morning and between meals. Mitiglinide reduces excess oxidative stress and inflammation, plays a cardioprotective role, and improves postprandial metabolic disorders. Moreover, mitiglinide add-on therapy with pioglitazone favorably affects the vascular endothelial function in type 2 diabetes patients. These data suggest that mitiglinide plays a potentially beneficial role in the improvement of postprandial hyperglycemia in type 2 diabetes patients and can be used to prevent cardiovascular diseases. Although the results of long-term, randomized, placebo-controlled trials for determining the cardiovascular effects of mitiglinide on clinical outcomes are awaited, this review is aimed at summarizing substantial insights into this topic.

Abstract Background Metabolic syndrome (MetS) is associated with an increased risk of the development of atherosclerotic cardiovascular disease (CVD). Interleukin-18 (IL-18), which is a pleiotropic proinflammatory cytokine with important regulatory functions in the innate immune response system, plays a crucial role in vascular pathologies. IL-18 is also a predictor of cardiovascular death in patients with CVD and is involved in atherosclerotic plaque destabilization. Results In order to determine if circulating levels of IL-18 can serve as a specific biomarker for distinguishing MetS patients from pre-MetS subjects, we studied 78 patients with visceral fat deposition and 14 age-matched control subjects. Increased levels of IL-18 were observed more frequently in patients with MetS than in pre-MetS subjects and were positively associated with waist circumference. Serum levels of IL-18 were significantly reduced by a change in weight caused by lifestyle modifications. There was a significant interaction between waist circumference and serum IL-18 concentration. Weight loss of at least 5% of the body weight caused by lifestyle modification decreased IL-18 circulating levels relative to the reduction in waist circumference and blood pressure, suggesting that this degree of weight loss benefits the cardiovascular system. Conclusion IL-18 may be a useful biomarker of the clinical manifestations of MetS and for the management of the risk factors of CVD.

Abstract Background Glucagon-like peptide-1 (GLP-1) is an incretin hormone that has a wide range of effects on glucose metabolism and cardiovascular function (e.g., improving insulin sensitivity, reduction in appetite, modulation of heart rate, blood pressure and myocardial contractility). Metabolic syndrome (MetS) is associated with an increased risk of developing atherosclerotic cardiovascular diseases. Novel glycemic control drugs, the dipeptidyl-peptidase-4 (DPP-4) inhibitors, work by inhibiting the inactivation of incretin hormones, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In spite of good effects of these drugs in diabetic patients, circulating levels of incretins and their role in MetS are largely unknown. Methods To examine relationships between incretin hormones and MetS risk factors, we measured circulating levels of incretins in obese high-risk patients for cardiovascular disease. Fasting serum GLP-1 and GIP levels were measured by ELISA. We performed a cross-sectional analysis of metabolic variables in the fasting state in two subject groups: with MetS (n = 60) and pre-MetS (n = 37). Results Fasting levels of Serum GLP -1 in the peripheral circulation were significantly increased correlated with the accumulation of MetS risk factors components (r = 0. 470, P < 0.001). There was a significant interaction between circulating GLP-1 and GIP, serum high-density lipoprotein cholesterol, triglyceride, and serum uric acid concentrations but not waist circumference, fasting glucose, HbA1c, or presence of diabetes. Conclusion Circulating levels of GLP-1 in relation to the accumulation in MetS factors suggested that MetS patients with elevated levels of GLP-1 are high-risk patients for cardiovascular disease, independent with the presence of diabetes.

Abstract Background Ezetimibe (Zetia®) is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia. Statin, an inhibitor of cholesterol synthesis, is the first-choice drug to reduce low-density lipoprotein-cholesterol (LDL-C) for patients with hypercholesterolemia, due to its strong effect to lower the circulating LDL-C levels. Because a high dose of statins cause concern about rhabdomyolysis, it is sometimes difficult to achieve the guideline-recommended levels of LDL-C in high-risk patients with hypercholesterolemia treated with statin monotherapy. Ezetimibe has been reported to reduce LDL-C safely with both monotherapy and combination therapy with statins. Results To investigate the effect of ezetimibe as "add-on" therapy to statin on hypercholesterolemia, we examined biomarkers and vascular endothelial function in 14 patients with hypercholesterolemia before and after the 22-week ezetimibe add-on therapy. Ezetimibe add-on therapy reduced LDL-C by 24% compared with baseline (p < 0.005), with 13 patients (93%) reaching their LDL cholesterol goals. Of the Ezetimibe add-on therapy significantly improved not only LDL-C, high-density lipoprotein-cholesterol (HDL-C), and apolipoprotein (apo)B levels, but also reduced levels of triglyceride (TG), the ratio of LDL/HDL-C, the ratio of apoB/apoA-I, and a biomarker for oxidative stress (d-ROMs). Furthermore, ezetimibe add-on therapy improved vascular endothelial function in high-risk patients with hypercholesterolemia. Conclusion In conclusion, ezetimibe as add-on therapy to statin might be a therapeutic good option for high-risk patients with atherosclerosis.

Perme intensive care unit (ICU) mobility score is a comprehensive mobility assessment tool; however, its usefulness and validity for patients after cardiovascular surgery remain unclear. We investigated the association between the Perme Score and clinical outcomes after cardiovascular surgery. We retrospectively enrolled 249 consecutive patients admitted to the ICU after cardiac and/or major vascular surgery. The Perme Score contains categories on mental status, potential mobility barriers, muscle strength and mobility level and was assessed within 2 days after surgery. The outcomes of physical recovery were the number of days until 100-m ambulation achievement and 6-min walk distance (6MWD) at hospital discharge. The endpoint was a composite outcome of all-cause mortality and/or all-cause unplanned readmission. We analyzed the associations of the Perme Score with physical recovery and the incidence of clinical events. After adjusting for clinical confounding factors, a higher Perme Score was an independent factor of earlier achievement of 100-m ambulation (hazard ratio: 1.039, 95% confidence interval [CI]: 1.012-1.066) and higher 6MWD (β: 0.293, P = .001). During the median follow-up period of 1.1 years, we observed an incidence rate of 19.4/100 person-years. In the multivariate Poisson regression analysis, a higher Perme Score was significantly and independently associated with lower rates of all-cause death/readmission (incident rate ratio: 0.961, 95% CI: 0.930-0.992). The Perme Score within 2 days after cardiovascular surgery was associated with physical recovery during hospitalization and clinical events after discharge. Thus, it may be useful for predicting clinical outcomes., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to disclose., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Introduction: The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition., Methods: We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress., Results: Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx., Conclusion: We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention., Introduction: The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a factor X inhibitor, on the glycocalyx under oxidative stress condition., Methods: We examined the impact of rivaroxaban on human umbilical vein endothelial cells exposed to acute and chronic H2O2-induced oxidative stress., Results: Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx., Conclusion: We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Background: Patients with cardiovascular disease (CVD) are often contending with various comorbidities including cognitive decline. Cognitive decline is a risk marker for adverse outcomes in these patients. On the other hand, cardiovascular rehabilitation (CVR) improves clinical outcomes. However, it remains uncertain whether CVR is associated with favorable outcomes in patients with CVD and cognitive decline. Therefore, the present study aimed to investigate whether CVR is associated with favorable outcomes in patients with CVD and cognitive decline., Methods: We reviewed 4232 patients admitted for CVD. Cognitive function was assessed using the Mini-Cog at hospital discharge, and a score of <3 was defined as cognitive decline. We measured the 6-min walking distance (6MWD) at discharge and 5 months after CVR prescription for participants in outpatient CVR. The primary outcome was change in exercise tolerance (Δ6MWD), and the secondary outcome was composite events (all-cause death and/or re-admission due to CVD). We compared Δ6MWD between patients with and without cognitive decline and examined the association between outpatient CVR participation and composite events., Results: Of all patients, 768 had cognitive decline. There was no significant difference in Δ6MWD between the cognitive decline and non-cognitive decline groups, even after adjusting for confounders [estimated mean difference: 2.20 m; 95 % confidence interval (CI): -0.60-5.00 m]. Additionally, participation in outpatient CVR was associated with lower rate of composite events, regardless of cognitive decline [adjusted hazard ratio (aHR): 0.589; 95 % CI: 0.552-0.627 in the cognitive decline group and aHR: 0.767; 95 % CI: 0.742-0.793 in the non-cognitive decline group]. An interaction was observed based on the presence of cognitive decline (p = 0.011)., Conclusion: Regardless of cognitive decline, participation in outpatient CVR was associated with increased exercise tolerance. Furthermore, outpatient CVR was linked to reduced composite events in both, with particularly potent association in cognitively impaired patients., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Heart rate typically increases during postural changes from a supine to a standing position due to autonomic and hemodynamic factors. Changes in heart rate during orthostasis may reflect the extent of autonomic dysfunction in patients with heart failure (HF). Thus, orthostatic heart rate changes may be useful for evaluating autonomic function and may predict prognosis. This study examined the association between orthostatic heart rate changes and prognosis in patients with HF., Methods and Results: We included 320 patients with HF in sinus rhythm (median age 70 years, 70.9% men) who were admitted to Kitasato University Hospital for HF treatment and whose heart rate was evaluated in the supine and upright positions during the stable period before discharge. We calculated heart rate changes based on supine and upright heart rate. We examined the association of orthostatic heart rate changes with patient prognosis (i.e., a composite of all-cause mortality or rehospitalization for HF). During the follow-up period (median 3.8 years; interquartile range 0.8-7.0 years), 129 events occurred. Orthostatic heart rate changes were associated with low composite event rates (log-rank P=0.015). After adjusting for potential confounders, increasing orthostatic heart rate changes were associated with decreased composite event rates (adjusted hazard ratio 0.954; 95% confidence interval 0.925-0.985; P=0.004)., Conclusions: In patients with HF, poor orthostatic heart rate changes were associated with a worse prognosis.

Background: Patients with heart failure (HF) often suffer from hepato-renal dysfunction. The associations between hepato-renal function changes and mortality remain unclear. Further, the effect of cardiac rehabilitation (CR) on mortality and motor functions in patients with HF and hepato-renal dysfunction requires investigation., Methods: We reviewed 2522 patients with HF (63.2 % male; median age: 74 years). The association between changes in hepato-renal function assessed by the Model for End-stage Liver Disease eXcluding INR (MELD-XI) score and mortality was examined. The association of CR participation with mortality and physical functions was investigated in patients with HF with decreased, unchanged, and increased MELD-XI scores., Results: During the follow-up period, 519 (20.6 %) patients died. Worsened MELD-XI score was independently associated with all-cause death [adjusted hazard ratio (aHR): 1.099; 95 % confidence interval (CI): 1.061-1.138; p < 0.001]. CR participation was associated with low mortality, even in the increased MELD-XI score group (aHR: 0.498; 95 % CI: 0.333-0.745; p < 0.001). Trajectory of the MELD-XI score was not associated with physical function changes. There were no time by MELD-XI score interaction effects on handgrip strength (p = 0.084), leg strength (p = 0.082), walking speed (p = 0.583), and 6-min walking distance (p = 0.833) in patients participating in outpatient CR., Conclusions: Hepato-renal dysfunction predicts high mortality. CR participation may be helpful for a better prognosis of patients with HF and hepato-renal dysfunction., Competing Interests: Declaration of competing interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The present study aimed to investigate the association between physical activity before the incidence of cardiovascular disease (CVD) and clinical outcomes in cancer survivors., Methods and Results: We analyzed 904 cancer survivors (median age [interquartile range] 75 [68-80] years; 297 [32.9%] patients were female) who required hospitalization for treatment of CVD. The amount of physical activity 1 month before the admission was assessed using the 3-question (3Q) assessment tool, and categorized as minimal, low, adequate, and high according to physical activity level. The primary outcome was the composite events of all-cause death and/or rehospitalization for CVD up to 1 year after discharge. The total amount of physical activity was identified in 544 (60.2%) patients in the minimal group, 95 (10.5%) in the low group, 253 (28.0%) in the adequate group, and 12 (1.3%) in the high group. A total of 686 (75.9%) patients completed follow up, with 252 (27.9%) composite events occurring. Even after adjustment for various confounders, higher physical activity was significantly associated with a lower composite event rate (adjusted hazard ratio [95% confidence interval] 0.859 [0.833-0.900])., Conclusions: High physical activity in cancer survivors was associated with a lower composite event rate after treatment for CVD. Assessment of prehospital physical activity using the 3Q score may be useful in their risk stratification., Competing Interests: K.K., J.A. are members of Circulation Reports’ Editorial Team. All authors declare that there is no conflict of interest., (Copyright © 2024, THE JAPANESE CIRCULATION SOCIETY.)

Aims: SARC-F ≥ 4 points are used for detecting sarcopenia; however, finding a lower SARC-F cut-off value may lead to early detection of sarcopenia. We investigated the SARC-F score with the highest sensitivity and specificity values to identify sarcopenia in older patients with cardiovascular disease (CVD). Motor performances were also examined for each SARC-F score., Methods and Results: This retrospective cross-sectional study examined the sensitivity and specificity of every 1-point increase in the SARC-F score to predict sarcopenia. Eligible participants included patients with CVD (≥65 years old) who were admitted for acute CVD treatment and participated in cardiac rehabilitation. Patients completed the SARC-F questionnaire and the sarcopenia assessment. Area under the curves (AUCs) were investigated for the ability to predict sarcopenia. Multivariable linear regression was used to compare the mean value of physical functions (e.g. walking speed, leg strength, and 6 min walking distance) of each SARC-F score. A total of 1066 participants (63.8% male; median age: 76 years) were included. Sarcopenia was present in 401 patients. A SARC-F cut-off ≥2 presented the optimal balance between sensitivity (68.3%) and specificity (55.6%) to detect sarcopenia (AUCs = 0.658; 95% confidence interval: 0.625-0.691). When the patients had low scores (1-3), every 1 point increase in the SARC-F score was associated with lower physical functions such as lower muscle strength and shorter walking distance (all P < 0.001)., Conclusion: A SARC-F cut-off ≥2 was optimal for screening sarcopenia, and even a low SARC-F score is useful in detecting sarcopenia and low physical function at an early stage in patients with CVD., Competing Interests: Conflict of interest: The authors have no conflicts of interest directly relevant to the content of this article. Although M.Y. has no conflict of interest related to the conduct of this study, he holds company stock (<5% of the total) and receives a salary as one of the directors of an employer., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Cardiac remodeling is defined as cellular interstitial changes that lead dysfunction of the heart after injury. Placental growth factor (PlGF), a member of the VEGF family, has been reported to regulate cardiac hypertrophy in hemodynamic state. We therefore analyze the function of PlGF during cardiac remodeling using cardiac cells and fibroblasts, under Angiotensin II (AngII) stimulation., Methods: PlGF overexpressed mouse embryonic fibroblasts derived from C57BL/6 mice, were made by deficient retrovirus vector, designated as C57/PlGF. Only retrovirus vector introduced C57 cells (C57/EV) were used as control. After AngII stimulation, wound scratching assay and MTT proliferation assay with or without p38 MAPK inhibitor, SB205580 were performed in retrovirally-introduced C57 cells. Reactive oxygen species (ROS) production, NF-kB activation, IL-6 and TNF-α production were also measured. Then we assessed AngII-induced cell proliferation of mouse cardiac fibroblasts (CFs) and rat primary cardiomyocytes incubating with C57/PlGF conditioned-medium., Results: The PlGF production in C57/PlGF were confirmed by ELISA (1093.48 ± 3.5 pg/ml, ±SE). AngII-induced cell migration, proliferation and H 2 O 2 production were increased in C57/PlGF compared with C57/EV. SB205580 inhibited the AngII-induced cell proliferation in C57/PlGF. In C57/PlGF cells, NF-kB activation was higher, followed by up-regulation of IL-6 and TNF-α production. CFs and cardiomyocytes proliferation increased when stimulated with C57/PlGF conditioned-medium., Discussion: The activation of fibroblast is stimulated by PlGF signaling via p38 MAPK/NF-kB pathway accompanied by elevation of ROS and inflammatory response. Furthermore, these signals stimulate the activation of CFs and cardiomyocytes, indicating that high circulating level of PlGF have a potential to regulate cardiac remodeling., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Lisa Kitasato reports financial support was provided by Japan Society for the Promotion of Science. Minako Yamaoka-Tojo reports financial support was provided by Japan Society for the Promotion of Science. Lisa Kitasato reports financial support was provided by Bayer Academic Support. Lisa Kitasato reports financial support was provided by SRL research grant. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)