Association between the 110-kDa C-terminal agrin fragment and skeletal muscle decline among community-dwelling older women.

BACKGROUND: C-terminal agrin fragment (CAF) is a biomarker for neuromuscular junction degradation. This study aimed to investigate whether 110-kDa CAF (CAF110) was associated with the presence and incidence of low muscle mass and strength. METHODS: This cross-sectional retrospective cohort study comprised women aged ≥65 years. We measured muscle mass using a dual-energy X-ray absorptiometry scanner, hand-grip strength, and blood sampling between 2011 and 2012. A follow-up study with the same measurements was conducted between 2015 and 2017. Low muscle mass and strength were defined as an appendicular skeletal muscle mass index <5.4 kg/m2 and hand-grip strength <18 kg, respectively. The CAF110 level was measured using enzyme-linked immunosorbent assay kits. RESULTS: In total, 515 women (74.3 ± 6.3 years) were included in this cross-sectional analysis. Of these, 101 (19.6%) and 128 (24.9%) women presented with low muscle mass and strength, respectively. For low muscle mass, the odds ratios (ORs) of the middle and highest CAF110 tertile groups, compared with the lowest group, were 1.93 (95% confidence interval: 1.09-3.43; P = 0.024) and 2.15 (1.22-3.80; P = 0.008), respectively. After adjusting for age, the ORs remained significant: 1.98 (1.11-3.52; P = 0.020) and 2.27 (1.28-4.03; P = 0.005), respectively. Low muscle strength ORs of all the CAF110 tertile groups were not significant. In the longitudinal analysis, 292 and 289 women were assessed for incidents of low muscle mass and strength, respectively. Of those, 34 (11.6%) and 20 (6.9%) women exhibited low muscle mass and strength, respectively. For incident low muscle mass, the crude OR of the CAF110 ≥ the median value group was marginally higher than that of the CAF110 < median value group (median [interquartile range]: 1.98 [0.94-4.17] (P = 0.072). After adjusting for age and baseline muscle mass, the OR was 2.22 [0.97-5.06] (P = 0.058). All low muscle strength ORs of the median categories of CAF110 were not significant. CONCLUSIONS: CAF110 was not associated with low muscle strength. However, CAF110 may be a potential marker for the incidence of low muscle mass.

Hip and vertebral fracture risk after initiating antidiabetic drugs in Japanese elderly: a nationwide study.

INTRODUCTION: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ). MATERIALS AND METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs. RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively. CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

Impact of weight loss in patients with heart failure with preserved ejection fraction: results from the FLAGSHIP study.

AIMS: Weight loss (WL) is a poor prognostic factor for patients with heart failure (HF) with reduced ejection fraction. However, its prognostic impact on patients with HF with preserved ejection fraction (HFpEF) remains unestablished. The evidence regarding the effects of obesity on the prognosis of WL is also unclear. We aimed to identify the risk factors for WL and examine the association between WL and prognosis of HFpEF in obese and non-obese patients. METHODS AND RESULTS: In this multicentre cohort study, the data of 573 patients hospitalized with HFpEF [median age: 78 years (interquartile range, 71-84 years); 49.2% female] were identified from hospital databases. WL was defined as ≥5% weight reduction within 6 months after discharge. Obesity was defined according to Japanese criteria as body mass index ≥25 kg/m2 . The main study outcomes were all-cause mortality and HF rehospitalization between 6 and 24 months after hospital discharge. Logistic regression analysis and Cox proportional hazards regression analysis were performed to identify independent the risk factors associated with WL and to calculate the hazard ratios (HRs) associated with adverse outcomes. The prevalence of obesity at discharge was 21.1%. At 6 month follow-up, WL occurred in 17.4% and 10.8% of the obese and non-obese patients, respectively. Onset of WL in non-obese patients was associated with prior hospitalization for HF [odds ratio (OR) 2.39, 95% confidence interval (CI) 1.22-4.68, P = 0.011] and high levels of brain natriuretic peptide (OR 2.32, CI 1.17-4.60, P = 0.015). In obese patients, WL was associated with the use of mineralocorticoid receptor antagonists (OR 3.26, CI 1.08-9.76, P = 0.03) and vasopressin receptor antagonists (OR 6.61, CI 2.03-21.2, P = 0.001). During 1021.3 person-years of follow-up, 31 patients died, and upon 1081.0 person-years follow-up, 84 patients required rehospitalization for HF. In proportional hazards analysis, WL was associated with all-cause mortality (HR 5.12, CI 2.08-12.5, P < 0.001) and HF rehospitalization (HR 2.63, CI 1.38-5.01, P = 0.003) after adjustment for confounders in non-obese patients, but not in obese patients. CONCLUSIONS: Weight loss should be considered as an indicator for monitoring worsening of HF condition in non-obese patients with HFpEF. WL was not associated with adverse events in obese patients with HFpEF, possibly due to appropriate fluid management during follow-up.

Natto Intake is Inversely Associated with Osteoporotic Fracture Risk in Postmenopausal Japanese Women.

BACKGROUND: The direct association between intake of Japanese fermented soybeans, namely natto, and bone mineral density (BMD) is known. However, the association with osteoporotic fractures has not been studied. OBJECTIVE: This study aimed to investigate whether habitual natto intake is associated with a risk of osteoporotic fractures. METHODS: This prospective cohort study included 1417 postmenopausal Japanese women who were enrolled in the Japanese Population-Based Osteoporosis cohort study in 1996, 1999, 2002, and 2006 and were aged ≥45 y at baseline. The intake of natto, tofu, and other soybean products was surveyed with use of a FFQ at baseline. Fractures were ascertained in follow-up surveys conducted in 1999, 2002, 2006, and 2011/2012. Osteoporotic fracture was the primary outcome and was defined as a clinical fracture occurring without strong external force, diagnosed with radiographs by a medical doctor. HRs with 95% CIs were estimated with Cox proportional hazard models. RESULTS: During the 17,699 person-years of follow-up (median, 15.2 y), 172 women experienced osteoporotic fractures. After adjustment for age and BMD at the total hip, the HRs compared with those of < 1 pack (approximately 40 g)/wk natto intake were 0.72 (95% CI: 0.52, 0.98) and 0.51 (95% CI: 0.30, 0.87) for 1-6 and ≥7 packs/wk, respectively. After further adjustment for BMI, history of osteoporotic fractures, history of myocardial infarction or stroke, diabetes mellitus, current smoking, alcohol intake, frequency of tofu and other soybean product intakes, and dietary calcium intake, the HRs were 0.79 (95% CI: 0.56, 1.10) and 0.56 (95% CI: 0.32, 0.99) for 1-6 and ≥7 packs/wk, respectively. Frequency of tofu or other soybean product intakes had no association with the risk of osteoporotic fractures. CONCLUSIONS: Habitual natto intake may be associated with a reduced risk of osteoporotic fractures independent of confounding factors, including BMD, in Japanese postmenopausal women. This trial was registered at umin.ac.jp as UMIN 000032869.

Combined effects of obesity and objectively-measured daily physical activity on the risk of hypertension in middle-aged Japanese men: A 4-year prospective cohort study.

BACKGROUND: The combined effects of physical inactivity and obesity on hypertension have been recognized; however, previous studies evaluated physical activity using questionnaires. We aimed to examine the effects of physical activity, measured using an accelerometer, and obesity on hypertension onset. METHODS: At baseline, 426 middle-aged Japanese men who were not on antihypertensive medications were included. Physical activity was measured for 7 consecutive days using an accelerometer. Mean daily moderate to vigorous physical activity (MVPA) and step count (SC) were calculated. Low MVPA and low SC were each defined as the first tertile. Obesity was defined as ≥25 kg/m2 of body mass index. The onset of hypertension was defined as receiving antihypertensive agents during the 4-year follow-up. The combined effects of obesity and physical inactivity on hypertension were examined using Cox regression analysis. Potential confounders included age, smoking, alcohol consumption, daily salt intake, dyslipidemia, diabetes mellitus, and systolic and diastolic blood pressures. RESULTS: Cox regression analysis revealed that both obesity and low MVPA predicted hypertension in patients, independent of confounders (hazard ratio [HR]: 2.64, 95% confidence interval [CI]: 1.08-6.42, p = 0.033), unlike obesity alone (HR: 1.50, 95% CI: 0.50-3.26, p = 0.590). Stratification by obesity and SC revealed similar hypertension risks among the two groups (Obesity with low SC [HR: 2.10, 95% CI 0.88-5.24, p = 0.089]; Obesity without low SC [HR: 1.72, 95% CI 0.93-4.01, p = 0.082]). CONCLUSIONS: Here, findings suggest that the coexistence of obesity and decreased MVPA may increase the risk of hypertension onset.

Risk factors for disability progression among Japanese long-term care service users: A 3-year prospective cohort study.

AIM: To examine the predictive ability of memory deterioration and grip strength for disability progression among those who utilized the home-help service. METHODS: We prospectively followed a cohort of community-dwelling older people who were aged 65 years or older, certified support level 1-2 or care level 1-2 and home-help service users provided by Consumers' Cooperatives in Aichi and Kanagawa prefecture. Memory capability, grip strength, chronic conditions and other indices were surveyed at baseline. Disability progression was defined as being certified care level 3 or higher, or institutionalization during 3-year follow up. RESULTS: We assessed 417 older adults, of which 386 were included (7.4% excluded). In multivariate Cox regression analyses, a higher eligibility level and memory deterioration were independently associated with a higher hazard ratio. When chronic conditions were entered in the model, cancer and low grip strength were additionally associated. CONCLUSIONS: The findings of the present study show that memory deterioration is a risk factor for disability progression. Also, grip strength might be a risk factor with consideration of chronic conditions. The cause-effect relationship of those factors and disability progression would be a future challenging issue. Geriatr Gerontol Int 2017; 17: 568-574.

Mechanical ventilatory assistance may reduce dyspnea during walking especially in patients with impaired cardiopulmonary function early after cardiovascular surgery.

BACKGROUND: To determine which patients effectively respond to ventilatory assistance (VA) and to examine the factors influencing patient response in patients who underwent cardiovascular (CV) surgery. METHODS: We conducted the first walking session after surgery either with or without VA in a randomized order. The patients walked with 3cmH2O of inspiratory pressure support. We measured dyspnea and leg fatigue during initial walking either with or without VA by using a modified Borg scale. Ventilatory parameters were measured by mechanical ventilation before and immediately after walking. Lung function and maximal inspiratory pressure (MIP) were measured and chest radiographs were analyzed by the same cardiac surgeon on the same day as walking. RESULTS: From the total of 74 patients who underwent CV surgery, 56 patients were successively enrolled in the study. Thirty-five out of 56 patients had dyspnea and 18 patients (30% of the total patients) effectively responded to VA (responders). Minute ventilation/estimated maximum voluntary ventilation immediately after walking significantly decreased with VA, and MIP was lower in responders than in non-responders after surgery. The responders revealed greater pulmonary edema scores than non-responders. CONCLUSIONS: The findings of the present study suggest that VA may possibly facilitate successful mobilization early after CV surgery, especially in patients with impaired cardiopulmonary function.