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Background No reports explicitly examined the relationship between work defined as a certain type of social participation or role and the protective effect on the prognosis of patients with heart failure (HF) by preventing frailty. Therefore, this study examined whether social participation through work before admission relates to future adverse events in HF patients aged ≥65 years, and whether each frailty domain mediates the association between work and prognosis as a second analysis of a multi-centered prospective study (FRAGILE-HF study). Methods We retrospectively reviewed 1,332 older patients with HF whose work status before admission to the hospital were investigated. We assessed the physical, cognitive, and social domains of frailty and performed causal mediation analysis to examine the mediating relationship of each frail domain between work status before admission and 1-year combined events (HF-related readmission and all-cause death). Results The subjects’ median age was 81 years, and 56.9% (758/1,332) were male. Among the three domains of frailty, work before admission reduced only social frailty after adjusting for confounding factors (odds ratio: 0.505, 95% confidence interval: 0.364-0.701). Patients with work before admission had a significantly better prognosis (hazard ratio: 0.720, 95% confidence interval: 0.523-0.989). Only social frailty partly mediated the relationship between work status and combined events (p Conclusions Work status before admission is associated with 1-year combined events, in part through social frailty.

Aims There have been no investigations of the prevalence and clinical implications of coexistence of anaemia and frailty in older patients hospitalized with heart failure (HF) despite their association with adverse health outcomes. The present study was performed to determine the prevalence and prognostic value of the coexistence of anaemia and frailty in hospitalized older patients with HF. Methods and results We performed post hoc analysis of consecutive hospitalized HF patients ≥65 years old enrolled in the FRAGILE‐HF, which was the prospective, multicentre, observational study. Anaemia was defined as haemoglobin

Background and Aims Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. Methods and Results We included 1,332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19–3.16; P=0.008 for men; HR, 1.63; 95% CI, 0.84–3.13; P=0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13–3.31; P=0.017 for men; HR, 3.18; 95% CI, 1.59–5.64; P=0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P=0.806 for frailty; P=0.254 for sarcopenia). Conclusions Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. Clinical trials This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

In elderly patients with acute heart failure (AHF), clinical outcome is adversely affected by frailty. Although a number of potentially effective interventions for frailty have been reported, little is known about the effects of rehabilitation programs in frail elderly AHF patients. We postulated that addition of electrical muscle stimulation (EMS), which induces muscle contraction without requiring patient volition, to early rehabilitation would be efficacious in frail elderly AHF patients. The ACTIVE-EMS (Effects of Acute Phase Intensive Electrical Muscle Stimulation in Frail Elderly Patients With AHF; UMIN000019551) trial is a multicenter, randomized controlled trial that will enroll 80 patients from 3 hospitals in Japan. AHF patients age ≥ 75 years positive for frailty, defined as Short Physical Performance Battery score 4 to 9, will be randomly assigned to receive early rehabilitation program only or EMS add-on therapy for 2 weeks. The primary endpoint of the trial is the change in quadriceps isometric strength between baseline and 2 weeks, with changes in physical function and cognitive function, and clinical safety and feasibility of EMS therapy as secondary outcomes. ACTIVE-EMS is the first randomized trial to evaluate the clinical effectiveness of adding EMS therapy to early rehabilitation in frail elderly AHF patients. The results of this study will provide insight for the development of appropriate rehabilitation programs for this high-risk population.

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an endogenous inhibitor of vascular endothelial growth factor, which is involved in cardiovascular remodeling and atherosclerosis development. To examine the predictive role of sFlt-1 levels in patients with asymptomatic heart failure, we measured circulating sFlt-1 in patients with or without coronary artery disease (CAD). We analyzed 88 Japanese patients with CAD or patients at high risk for atherosclerosis and who were undergoing total risk management for cardiovascular disease prevention. Circulating sFlt-1 levels correlated with the increase in plasma brain natriuretic peptide levels (ΔBNP) from baseline to the observed levels 5 years later in CAD patients, patients with previous myocardial infarction, and men. ΔBNP levels correlated with sFlt-1 levels in the high-sFlt-1 patients with CAD (r = 0.511, P < 0.01). In all patients, end-systolic volume index (ΔESVI) increased in correlation with a decrease in left ventricular ejection fraction (ΔEF) in the long-term observation, independent of their history of myocardial infarction (ΔESVI = 2.5 mL/m(2) increase/year). Baseline level of sFlt-1 was independent of ΔESVI or ΔEF. The present 5-year observational study demonstrated that high sFlt-1 levels predicted moderate increases in BNP levels in CAD patients. Moreover, ΔBNP was correlated with ΔESVI/year in CAD patients with high-sFlt-1 levels. These data suggest that high sFlt-1 levels may be an effective biomarker to predict the progression of heart failure in patients with CAD.

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.