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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: 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.)

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.)

Background: Diagnosing sarcopenia in heart failure (HF) patients is important, but how to assess skeletal muscle mass in HF patients with fluid retention is controversial. We aimed to examine the association between sarcopenia, defined by different skeletal muscle mass measurements, and clinical outcomes in older HF patients., Methods: We included 546 older HF patients (≥ 65 years) who were assessed for sarcopenia at discharge (median age 77 years, 309 males). Sarcopenia was diagnosed using grip strength, usual gait speed, and skeletal muscle mass according to international criteria. We used mid-upper arm circumference (MUAC), mid-upper arm muscle circumference (MAMC), calf circumference (CC), and skeletal muscle mass index (SMI) assessed by bioelectrical impedance analysis to assess skeletal muscle mass and defined sarcopenia in each of these measurements. Prognostic outcomes were composite events (all-cause death and HF rehospitalization) and cardiovascular disease (CVD) events (CVD death and CVD rehospitalization). Quality of life (QOL) was assessed using the 36-item Short-Form Health Survey physical functioning (SF-36PF) score., Results: The sarcopenia defined by MUAC [hazard ratio (HR): 2.50; 95 % confidence interval (95 % CI): 1.64-3.81; p < 0.001] or MAMC (HR: 1.98; 95 % CI: 1.35-2.92; p = 0.001) were associated with higher composite event rates than the non-sarcopenia. The sarcopenia defined by MUAC (HR: 1.88; 95 % CI: 1.25-2.83; p = 0.002) or MAMC (HR: 1.70; 95 % CI: 1.16-2.49; p = 0.007) were associated with higher CVD event rates than the non-sarcopenia. The sarcopenia defined by CC or SMI were not associated with prognoses. The sarcopenia defined by MUAC, MAMC, or CC were associated with low SF-36PF scores (all p < 0.05)., Conclusions: These results suggest that a diagnosis of sarcopenia based on MUAC or MAMC rather than CC or SMI reflects prognosis and QOL in older HF patients., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: Sarcopenia in patients with heart failure (HF) is associated with poor prognosis. Cardiac rehabilitation (CR) decreases the incidence of adverse events in patients with HF. However, the clinical implications of improving sarcopenia status through CR remain unclear. This study investigated the relationship between the changes in sarcopenia status in patients with HF undergoing outpatient CR and the risk of mortality and adverse events., Design: This was a retrospective cohort study of patients hospitalized at the Kitasato University Hospital Cardiovascular Center for the treatment of HF between January 2007 and December 2020., Setting and Participants: Patients with HF whose sarcopenia status was assessed at hospital discharge and following at least 3 months of outpatient CR were included. Based on the sarcopenia status, all patients were divided into 3 groups: patients without sarcopenia at discharge (ie, robust), patients with sarcopenia at discharge but no sarcopenia following CR (ie, improved), and patients with sarcopenia at discharge and following CR (ie, unimproved)., Methods: Cox regression analysis was used to examine the risk of all-cause death associated with the 3 sarcopenia status groups., Results: Of 546 patients with HF (median age: 70 years; male: 63.6%), 377 (69.0%), 54 (9.9%), and 115 (21.1%) were classified as robust, improved, and unimproved, respectively. Multivariate Cox regression analysis showed that the unimproved group had a significantly greater risk of all-cause death when compared to the robust group [hazard ratio (HR) 2.603, 95% CI 1.375-4.930, P = .004], but it did not differ from the improved group (HR 1.403, 95% CI 0.598-3.293, P = .43)., Conclusions and Implications: No improvement in sarcopenia status in patients with HF undergoing outpatient CR was associated with a higher risk of all-cause death. Sarcopenia may be an important target to improve the prognosis of patients with HF., Competing Interests: Disclosure K.K. received funding outside the submitted work from Eiken Chemical Co, Ltd and SoftBank Cor Ltd. The other authors have no conflicts of interest to declare., (Copyright © 2023 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Sarcopenia is associated with risks of various adverse outcomes, and the assessment of skeletal muscle mass is necessary for its diagnosis. However, heart failure (HF) is a syndrome characterised by fluid retention, which affects muscle mass measurements. Different measurement methods have been reported to have different prognostic implications. We investigated the association between skeletal muscle mass metrics measured with the use of bioelectrical impedance analysis (BIA) and anthropometric measures and prognosis in patients with HF., Methods: The findings of 869 consecutive patients with HF were reviewed. We investigated the skeletal muscle mass index (SMI) measured with the use of BIA, the mid-upper arm circumference (MUAC), the arm muscle circumference (AMC), and the calf circumference (CC), and the patients were divided into 3 groups according to the sex-specific tertiles of the skeletal muscle mass metrics. The end points were all-cause death and readmission due to HF., Results: The high MUAC and AMC groups showed significantly better prognoses than their respective low groups (combined events: high MUAC group hazard ratio [HR] 0.559, 95% confidence interval [CI] 0.395-0.789 [P < 0.01]; high AMC group HR 0.505, 95% CI 0.359-0.710 [P < 0.01]), although high SMI and high CC were not associated with better prognoses., Conclusions: Among patients with HF, MUAC and AMC are more associated with prognosis than SMI and CC, which are recommended in preexisting sarcopenia guidelines. MUAC and AMC may also be useful measures in sarcopenia assessments., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: This study was conducted to verify whether serum cholinesterase (ChE) is useful in predicting prognosis and discriminating undernutrition status compared to existing low-nutrition indices of blood chemical tests in patients with heart failure (HF)., Methods and Results: A total of 1617 patients (1204 older patients) with HF who evaluated ChE during hospitalization were recruited for this study. The primary outcome was all-cause death, and multivariate survival analysis was performed. We drew a receiver operating characteristic curve for all-cause death, some undernutrition status, such as low body mass index, thin mid-upper arm circumference, low grip strength, and slow gait speed. The area under the curve was used to compare the predictive ability of ChE with some existing nutritional parameters, such as blood biochemical tests, controlling nutritional status (CONUT), and the geriatric nutritional risk index (GNRI). After adjusting for 29 variables, higher ChE significantly decreased the risk of all-cause death (per 10 increase, hazard ratio: 0.975, 95% confidence interval: 0.952-0.998), and this trend was maintained for older patients (per 10 increase, hazard ratio: 0.972, 95% confidence interval: 0.947-0.997). ChE was moderately correlated with CONUT and GNRI, but the predictive ability for all-cause death was higher for ChE relative to both scores. ChE tended to have an almost consistently high predictive ability compared with other blood biochemical tests., Conclusions: ChE was associated with all-cause death and an almost consistently higher predictive ability for all-cause death and undernutrition status in comparison to existing blood chemical tests and nutritional scores., Competing Interests: Conflicts of interest Mr. Kamiya has received research funding from Eiken Chemical Co., Ltd. The other authors have nothing to declare., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Complex multi-organ interactions such as coexistence of hepato-renal dysfunction in heart failure (HF) adversely affects patient prognosis. However, the association between liver/kidney dysfunction and frailty and effects of their coexistence on HF prognosis remain unclear., Methods: This retrospective cohort study included 922 patients with HF (median age, 72 years; interquartile range: 62-79 years). All patients underwent hepato-renal function testing using the model for end-stage liver disease, excluding international normalized ratio (MELD-XI) score and frailty score. Frailty was measured using a composite of four markers: handgrip strength, gait speed, serum albumin, and activities of daily living status, combined into a total frailty score (range 0-12). Patients were assigned to a frailty score <5 (without frailty) or ≥5 (frailty) group. The multivariable logistic regression model was used to analyze the association between MELD-XI score and frailty; the prognostic value of high MELD-XI score and frailty coexistence was investigated. The endpoint was all-cause mortality., Results: After adjusting for covariates and dividing by the median MELD-XI score, the high MELD-XI score group [odds ratio: 1.663, 95 % confidence interval (CI): 1.200-2.304, p = 0.002] was significantly associated with frailty, compared with the low MELD-XI score group. One hundred and fifty deaths occurred during follow-up (median, 2.13 years; interquartile range, 0.93-4.09 years). Patients in the high MELD-XI score/frailty group had a significantly higher mortality risk, even after adjusting for HF severity (hazard ratio: 4.326, 95 % CI: 2.527-7.403, p < 0.001)., Conclusions: Hepato-renal dysfunction is associated with frailty in patients with HF, which affects patient prognosis., Brief Summary: This study showed that hepato-renal dysfunction in patients with HF, as assessed by the model for end-stage liver disease excluding international normalized ratio (MELD-XI) score, is associated with frailty, even after adjusting for factors involved in the frailty or severity of HF. Additionally, high MELD-XI score combined with frailty is associated with a poorer prognosis. These results suggest that hepato-renal dysfunction and frailty can be used for risk stratification in patients with HF., Competing Interests: Declaration of competing interest The author(s) declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022. Published by Elsevier Ltd.)

Objectives: To compare the Fried criteria for frailty diagnosis with the Frailty Screening Index (FSI) and the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale in older patients with cardiovascular disease (CVD)., Design: We conducted a retrospective 1-year follow-up cohort study of adult inpatients who participated in a cardiac rehabilitation program between June 2016 and September 2018., Setting and Participants: We included 1472 Japanese patients age 65 years and older with CVD. After excluding 765 patients with incomplete frailty measurements, 707 patients were included in the analysis., Methods: Frailty and physical function were measured before hospital discharge according to each of the 3 definitions. Outcomes were all-cause mortality and physical dysfunction., Results: The prevalence of frailty according to the Fried criteria, the FRAIL scale, and the FSI was 213 (30.1%), 181 (25.6%), and 186 (26.3%), respectively. The FSI and the FRAIL scale showed moderate agreement with the Fried criteria [vs FSI: K = 0.52, 95% confidence interval (CI): 0.45-0.59; vs FRAIL scale: K = 0.45, 95% CI: 0.37-0.52; all P < .001]. We found a significant correlation between all-cause mortality and frailty assessed by all of the definitions, even after multivariate adjustment [FSI: hazard ratio (HR): 2.43, 95% CI: 1.30-4.58, P = .006; FRAIL scale: HR: 2.32, 95% CI: 1.21-4.45, P = .011; Fried criteria: HR: 1.99, 95% CI: 1.04-3.82, P = .038). However, the prediction accuracy of the FRAIL scale was higher than that of the FSI and comparable to that of the Fried criteria for physical dysfunction., Conclusions and Implications: The FSI and the FRAIL scale showed moderate agreement with the Fried criteria regarding frailty diagnostic performance and had comparable prognostic value. However, only the FRAIL scale was as accurate as the Fried criteria in screening for physical dysfunction., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Although oxygen uptake (VO 2 ) during exercise stress is a surrogate marker for prognosis in patients with cardiovascular disease (CVD), the stress test is sometimes difficult to perform owing to patient conditions, such as ageing or comorbidities. We investigated the relationships between VO 2 during usual gait with physical function and prognosis in patients with CVD., Methods: This single-centre observational study enrolled consecutive patients who were hospitalized for CVD treatment. Isometric quadriceps strength (QS) and 6-min walk distance (6MWD) as physical functions, and VO 2 during usual gait speed were measured at hospital discharge. We assessed the changes in VO 2 per body weight between at rest and during gait divided by gait speed (VO 2 /kg/gait) and analysed the relationships of VO 2 /kg/gait with physical functions and composite incidences of all-cause death or unplanned readmission after discharge., Results: In 367 patients (age, 65 ± 13 years; females, 34%), 112 clinical events occurred. VO 2 /kg/gait showed significant negative correlations to QS (β = -0.114, p = 0.024) and 6MWD (β = -0.163, p < 0.001) after adjusting for confounding factors. High VO 2 /kg/gait was significantly associated with a high rate of clinical events (hazard ratio for 1 standard deviation of VO 2 /kg/gait, 1.36; 95% confidence interval, 1.11-1.66). This association was also observed in subgroups of older age and frailty., Conclusions: High VO 2 during usual gait was a relevant factor for low physical function and poor prognosis in patients with CVD and even in older age and frailty, meaning that VO 2 during usual gait might be a novel and useful marker in clinical practice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Aims: Although muscle dysfunctions are widely known as a poor prognostic factor in patients with cardiovascular disease, no study has examined whether the addition of low skeletal muscle density (SMD) assessed by computed tomography (CT) to muscle dysfunctions is useful. This study examined whether SMDs can strengthen the predictive ability of muscle dysfunctions for adverse events in patients who underwent cardiovascular surgery., Methods and Results: We retrospectively reviewed 853 patients aged ≥40 years who had preoperative CT for risk management purposes and who measured muscle dysfunctions (weakness: low grip strength and slowness: slow gait speed). Low SMD based on transverse abdominal CT images was defined as a mean Hounsfield unit of the psoas muscle <45. All definitions of muscle dysfunction (weakness only, slowness only, weakness or slowness, weakness and slowness), the addition of SMDs was shown to significantly improve the continuous net reclassification improvement and integrated discrimination improvement for adverse events in all analyses (p < 0.05). Low SMDs combined with each definition of muscle dysfunction had the highest risk of all-cause death (hazard ratio: lowest 3.666 to highest 6.002), and patients with neither low SMDs nor muscle dysfunction had the lowest risk of all-cause and cardiovascular-related events., Conclusion: The addition of SMDs consistently increased the predictive ability of muscle dysfunctions for adverse events. Our results suggest that when CT is performed for any clinical investigation, the addition of the organic assessment of skeletal muscle can strengthen the diagnostic accuracy of muscle wasting., Competing Interests: Declaration of competing interest The authors have no conflict of interests to declare., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Dynapenia, defined as age-associated loss of skeletal muscle strength, is associated with increased mortality rate, poor activities of daily living, and reduced quality of life. Therefore, dynapenia appears to be a better independent predictor of mortality than sarcopenia in the elderly. However, the prognostic utility of dynapenia in patients with cardiovascular disease (CVD) is not clear. This study was performed to examine the prognostic utility of dynapenia defined by the criteria of Manini et al. in patients with CVD., Methods: The findings of 4192 consecutive patients ≥30 years old (median [interquartile range (IQR)] age 69 [60-76] years, 2874 males) with CVD were reviewed. Grip strength and quadriceps isometric strength (QIS) were measured just before hospital discharge, and low grip strength (<26 kg in males and <18 kg in females), low QIS (<45.0% body mass [BM] and <35.0% BM in males and females, respectively) were considered to indicate dynapenia. The endpoint was all-cause mortality., Results: A total of 507 deaths occurred during follow-up (median 2.0 years, IQR 0.8-4.4 years). The overall prevalence of dynapenia was 33.6% and increased with age (p for trend < 0.01). Females showed a significantly higher prevalence rate of dynapenia than males (43.3% vs. 29.2%, respectively; p < 0.01). Patients with dynapenia showed higher all-cause mortality rate than non-dynapenia patients (adjusted hazard ratio: 1.84; 95% confidence interval: 1.51-2.23; p < 0.01)., Conclusions: Dynapenia has a high prevalence among patients with CVD and is associated with increased mortality rate., Competing Interests: Conflict of interest The authors declare there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background: This study was performed to test the hypothesis that low quadriceps isometric strength (QIS) is associated with greater risk of mortality and has the additive prognostic significance to the severity of heart failure (HF) and gait speed in older patients with HF., Methods: A retrospective cohort study was performed in 1273 patients ≥ 60 years of age with HF (mean age 75 ± 8 years, 59.1% men); all of whom were evaluated during hospitalization for usual gait speed and maximal QIS. The QIS was expressed relative to body mass (% BM). The endpoint was all-cause mortality., Results: Over a median follow-up period of 1.59 years (interquartile range, 0.58 to 3.42 years), 224 patients died. The cutoff value based on the Youden index for the QIS discriminating those at high risk of mortality was 36.2% BM for overall, and we defined less than this cutoff point of QIS as low QIS. After adjustment for the HF risk score, the hazard ratio in low QIS was 1.55 for overall (95% confidence interval [CI], 1.17-2.06). The addition of low QIS to the HF risk score and gait speed was associated with significant increases in both net reclassification improvement (NRI, 0.239 for overall; 95% CI, 0.096-0.381) and integrated discrimination improvement (IDI, 0.004 for overall; 95% CI, 0.001-0.009) for all-cause mortality., Conclusion: Low QIS was strongly associated with poor prognosis and showed complementary prognostic predictive capability to the HF risk score and gait speed in older patients with HF., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The Global Leadership Initiative on Malnutrition (GLIM) published a new international standard for defining malnutrition in 2018. The GLIM criteria were compared with the European Society for Clinical Nutrition and Metabolism (ESPEN) criteria in relation to physical function and mortality risk in patients with cardiovascular disease (CVD)., Methods: A total of 921 CVD patients ≥ 20 years old (67.8 ± 13.4 years, 631 men) hospitalised for heart failure, acute coronary syndrome and other conditions were stratified according to the presence or absence of malnutrition according to the GLIM and ESPEN criteria. Physical function was assessed by measuring grip strength, 6-minute walking distance and quadriceps isometric strength before hospital discharge, and the endpoint was all-cause mortality., Results: During the median follow-up period of 2.3 years (interquartile range, 0.9-3.5 years), 194 deaths occurred in the study population. Malnutrition defined by the GLIM criteria was significantly associated with low physical function. Malnutrition defined by both the GLIM and ESPEN criteria was significantly related to all-cause mortality (P < 0.05)., Conclusions: Malnutrition defined according to the GLIM criteria was a predictor of both low physical function and mortality in patients with CVD., Competing Interests: Conflicts of interest The authors declare there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

In atherosclerosis patients, vascular endothelial dysfunction is commonly observed alongside damage of the vascular endothelial glycocalyx, an extracellular matrix bound to and encapsulating the endothelial cells lining the blood vessel wall. Although atherosclerotic risk factors have been reported in severe patients with coronavirus disease 2019 (COVID-19), the exact mechanisms are unclear. The mortality associated with the COVID-19 outbreak is increased by comorbidities, including hypertension, diabetes, obesity, chronic obstructive pulmonary disease (COPD), and cardiovascular disease. Besides, older individuals and smokers have significantly worse outcomes. Interestingly, these comorbidities and risk factors are consistent with the pathophysiology that causes vascular endothelial glycocalyx damage. Moreover, vascular glycocalyx dysfunction causes microvascular leakage, which results in interstitial pulmonary abnormal shadows (multiple patchy shadows with a ground glass inter-pneumonic appearance). This is frequently followed by severe acute respiratory distress syndrome (ARDS), closely related to coagulo-fibrinolytic changes contributing to disseminated intravascular coagulation (DIC) and Kawasaki disease shock syndrome, as well as inducing activation of the coagulation cascade, leading to thromboembolism and multiple organ failure. Notably, SARS-CoV-2, the causative virus of COVID-19, binds to ACE2, which is abundantly present not only in human epithelia of the lung and the small intestine, but also in vascular endothelial cells and arterial smooth muscle cells. Moreover, COVID-19 can induce severe septic shock, and sepsis can easily lead to systemic degradation of the vascular endothelial glycocalyx. In the current review, we propose new concepts and therapeutic goals for COVID-19-related vascular endothelial glycocalyx damage, based on previous vascular endothelial medicine research., (Copyright © 2020 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

Background: The early prediction of frailty at discharge in elderly patients hospitalized with heart failure (HF) is essential for clinical management and therapeutic decision-making. This study was performed to examine whether the rising time from bed measured immediately after admission can be used as a predictor of frailty in these patients., Methods: A retrospective cohort study was performed in a population of 387 consecutive elderly patients with HF. Rising time from bed was measured within 2 days after admission when cardiac rehabilitation was started. Frailty was assessed at hospital discharge using a composite of four markers as a frailty score (range, 0-12): gait speed, handgrip strength, serum albumin, and activities of daily living status. The patients were divided into two groups based on frailty score <5 (non-frail) or ≥5 (frail)., Results: The study population had a mean age of 75 years and 63.6 % were men. The median rising time was 6.8s, and 53.5 % were classified as frail. After adjustment for various factors, rising time was independently associated with frailty (odds ratio=1.10; 95 % confidence index=1.04-1.18). The area under the receiver operating characteristics curve of rising time for frailty was 0.71, and the cut-off value for rising time to identify those at high risk of frailty was 7.1s., Conclusions: Rising time from bed measured within 2 days after admission was shown to be an independent predictor of frailty at hospital discharge in elderly patients hospitalized for HF., (Copyright © 2019 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Endothelial glycocalyx covers the endothelium and maintains vascular integrity. However, its association with the severity and vulnerability of coronary artery disease (CAD) remains to be elucidated., Methods: A total of 259 consecutive patients with stable CAD requiring percutaneous coronary intervention (PCI) were prospectively enrolled. Patients were classified into 2 groups according to the median value of serum syndecan-1, which is a core component of the endothelial glycocalyx (lower syndecan-1 group [syndecan-1 <99.0 ng/mL], n = 130; higher syndecan-1 group [syndecan-1 ≥99.0 ng/mL], n = 129). Severity of CAD and focal plaque vulnerability in culprit lesion were evaluated using angiography and optical coherence tomography., Results: There was no significant difference in clinical characteristics between the lower syndecan-1 group and the higher syndecan-1 group other than the prevalence of family history of CAD (19 vs. 32%, p = 0.022), prior PCI history (45 vs. 60%, p = 0.015) and estimated glomerular filtration rate (57.8 ± 17.2 vs. 50.9 ± 25.6 ml/min/1.73 m 2 , p = 0.011). Although disease severity on angiogram was comparable between the 2 groups, the prevalence of lipid-rich plaque (40 vs. 19%, p = 0.004) and thin-cap fibroatheroma (20 vs. 6%, p = 0.006) was significantly higher in the lower syndecan-1 group than the higher syndecan-1 group. Lower syndecan-1 level was independently associated with higher prevalence of lipid-rich plaque (odds ratio 3.626, 95% confidence interval 1.535-8.566, p = 0.003)., Conclusions: Lower syndecan-1 level was associated with higher prevalence of vulnerable plaque in patients with CAD. This finding suggests the association between impaired endothelial glycocalyx and the development of vulnerable plaque., Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Although respiratory muscle weakness (RMW) is known to predict prognosis in patients with heart failure with reduced ejection fraction (HFrEF), RMW prevalence and its prognosis in those with preserved ejection fraction (HFpEF) remain unknown. We aimed to investigate whether the RMW predicted mortality in HFpEF patients., Methods: We conducted a single-centre observational study with consecutive 1023 heart failure patients (445 in HFrEF and 578 in HFpEF). Maximal inspiratory pressure (PI max ) was measured to assess respiratory muscle strength at hospital discharge, and RMW was defined as PI max <70% of predicted value. Endpoint was all-cause mortality after hospital discharge, and we examined the influence of RMW on the endpoint., Results: Over a median follow-up of 1.8 years, 134 patients (13.1%) died; of these 53 (11.9%) were in HFrEF and 81 (14.0%) in HFpEF. RMW was evident in 190 (42.7%) HFrEF and 226 (39.1%) HFpEF patients and was independently associated with all-cause mortality in both HFrEF (adjusted hazard ratio [HR]: 2.13, 95% confidence interval [CI]: 1.17-3.88) and HFpEF (adjusted HR: 2.85, 95% CI: 1.74-4.67) patients. Adding RMW to the multivariate logistic regression model significantly increased area under the receiver-operating characteristic curve (AUC) for all-cause mortality in HFpEF (AUC including RMW: 0.78, not including RMW: 0.74, P = 0.026) but not in HFrEF (AUC including RMW: 0.84, not including RMW: 0.82, P = 0.132)., Conclusions: RMW was observed in 39% of HFpEF patients, which was independently associated with poor prognosis. The additive effect of RMW on prognosis was detected only in HFpEF but not in HFrEF., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Aim: Arm circumference (AC) and nutritional screening tools have been shown to have prognostic capability in patients with cardiovascular disease (CVD). This study aimed to compare the prognostic predictive capabilities of AC and nutritional screening tools in older patients with CVD., Methods and Results: The study population consisted of 949 admitted patients ≥60 years old with CVD. Patients underwent AC measurement and nutritional screening before hospital discharge. We used the controlling nutritional status index (CONUT), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index (PNI) as nutritional screening tools. The end point of the study was all-cause mortality. The mean age of the study population was 72.3 ± 7.2 years, and 68.2% of the patients were male. A total of 130 deaths occurred over a median follow-up period of 2.2 years (interquartile range, 1.1-3.8 years). After adjusting for other prognostic factors, AC (hazard ratio [HR]: 0.59; p < 0.001), CONUT (HR: 0.82; p = 0.016), GNRI (HR: 0.77; p = 0.040), and PNI (HR: 0.80; p = 0.014) were significant predictors of mortality. However, adding AC to the multivariate-adjusted model (0.739 vs. 0.714, respectively; p = 0.037), but not CONUT, GNRI, or PNI (0.724, 0.717, and 0.723 vs. 0.714; p = 0.072, p = 0.306, and p = 0.127, respectively), significantly increased the area under the curve on receiver operating characteristic curve., Conclusions: AC, but not nutritional screening tools, plays a complementary role to preexisting prognostic factors for predicting prognosis in older patients with CVD., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: A simple and inexpensive tool for screening of sarcopenia would be helpful for clinicians. The present study was performed to determine whether the SARC-F questionnaire is useful in screening of patients with cardiovascular disease (CVD) for impaired physical function., Design: Cross-sectional study., Setting: Single university hospital., Participants: A total of 235 Japanese patients ≥65 years old admitted to our hospital for CVD., Measurements: SARC-F, handgrip strength, leg strength, respiratory muscle strength, standing balance, usual gait speed, Short Physical Performance Battery (SPPB) score, and 6-minute walking distance were measured before discharge from hospital. The patients were divided into 2 groups according to SARC-F score: SARC-F < 4 (nonsarcopenia group) and SARC-F ≥ 4 (sarcopenia group)., Results: The sarcopenia prevalence rate was 25.5% and increased with age (P trend < .001). The sarcopenia group (SARC-F score ≥ 4) had significantly lower handgrip strength, leg strength, and respiratory muscle strength, poorer standing balance, slower usual gait speed, lower SPPB score, and shorter 6-minute walking distance compared to the nonsarcopenia group (SARC-F score < 4). Patients in the sarcopenia group had consistently poorer physical function even after adjusting for covariates., Conclusion: The SARC-F questionnaire is a useful screening tool for impaired physical function in elderly CVD patients. These findings support the use of the SARC-F for screening in hospital settings., (Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Measurement of the ankle brachial index (ABI) is a simple, noninvasive means of diagnosing peripheral arterial disease, and has been shown to be associated with mortality rate. Here, we examined the association between ABI and physical function in patients with heart failure (HF)., Methods: The study population consisted of 524 admitted patients (67.2±13.9years, 343 males) with HF. Blood pressure and the ABI were determined by oscillometry. Prior to hospital discharge, ABI, 6-minute walking distance, walking velocity, handgrip strength, quadriceps isometric strength, and standing balance were determined. The 524 patients were divided according to ABI as follows: ABI≤0.90 (low ABI), ABI 0.91 to 0.99 (borderline ABI), and ABI 1.00 to 1.40 (normal ABI)., Results: Lower ABI values were associated with shorter 6-minute walking distance (p trend=0.001), slower walking velocity (p trend=0.023), and poorer standing balance (p trend=0.048). There were no significant associations between ABI and handgrip strength or quadriceps isometric strength. After adjusting for potential confounders, patients with ABI≤0.90 had shorter 6-minute walking distance compared to those with ABI 1.00 to 1.40 (adjusted mean value: 344m vs. 395m, respectively, p<0.001). There were no significant differences in any of the other physical function parameters examined., Conclusions: In patients with HF, low ABI is associated with the magnitude of impairment in walking endurance., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study was performed to investigate the complementary role of arm circumference to body mass index (BMI) in risk stratification of patients with heart failure (HF)., Background: High BMI is associated with improved survival in patients with HF. However, it does not discriminate between fat and lean muscle as a predominant factor., Methods: BMI, waist circumference (WC), and mid-upper arm circumference (MUAC) were evaluated in 570 consecutive Japanese patients with HF (mean age 67.4 ± 14.0 years). Patients were stratified into low and high groups according to BMI, WC, and MUAC and combined into low- or high-BMI and low- or high-WC groups or low- or high-BMI and low- or high-MUAC groups. The endpoint was all-cause mortality., Results: Seventy deaths occurred over a median follow-up period of 1.5 years (interquartile range: 0.7 to 2.8 years). After adjusting for several pre-existing prognostic factors, including Seattle Heart Failure Score and exercise capacity, BMI (hazard ratio [HR]: 0.68; p = 0.016), WC (HR: 0.76; p = 0.044), and MUAC (HR: 0.52; p < 0.001) were all inversely associated with prognosis. Compared with the high-BMI/high-WC group, both the low-BMI/high-WC and low-BMI/low-WC groups showed comparably poorer prognosis. However, the low-BMI/low-MUAC group but not the low-BMI/high-MUAC group showed poorer prognosis than the high-BMI/high-MUAC group. Adding MUAC to BMI (0.70 vs. 0.63, p = 0.012) but not WC to BMI (0.64 vs. 0.63, p = 0.763) significantly increased the area under the curve on receiver-operating characteristic curve analysis., Conclusions: MUAC, but not WC, plays a complementary role to BMI in predicting prognosis in patients with HF., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Stroke prevention by warfarin, a vitamin K antagonist, has been an integral part in the management of atrial fibrillation. Vitamin K-dependent matrix Gla protein (MGP) has been known as a potent inhibitor of arterial calcification and osteoporosis. Therefore, we hypothesized that warfarin therapy affects bone mineral metabolism, vascular calcification, and vascular endothelial dysfunction., Methods: We studied 42 atrial fibrillation patients at high-risk for atherosclerosis having one or more coronary risk factors. Twenty-four patients had been treated with warfarin for at least 12 months (WF group), and 18 patients without warfarin (non-WF group). Bone alkaline phosphatase (BAP) and under carboxylated osteocalcin (ucOC) and receptor activator of nuclear factor-kappa B ligand (RANKL) were measured as bone metabolism markers. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) index measured by Endo-PAT2000 was used as an indicator of vascular endothelial function., Results: There were no significant differences in patient background characteristics and other clinical indicators between the two groups. In WF group, the ucOC levels were significantly higher than those in the non-WF group (10.3 ± 0.8 vs. 3.4 ± 0.9 ng/mL; P < 0.01), similarly, the RANKL levels in the WF group were higher than those in the non-WF group (0.60 ± 0.06 vs. 0.37 ± 0.05 ng/mL; P = 0.007). Moreover, RH-PAT index was significantly lower in the WF group compared to those in the non-WF group (1.48 ± 0.11 vs. 1.88 ± 0.12; P = 0.017)., Conclusions: Long-term warfarin therapy may be associated with bone mineral loss and vascular calcification in 60-80 year old hypertensive patients.