Intramuscular and abdominal fat measured by computed tomography and mortality of hemodialysis patients.

BACKGROUND: In hemodialysis patients, high body mass index is associated with low mortality while abdominal obesity relates to increased mortality. We aimed to investigate the association between muscle mass, intramuscular fat and abdominal fat measured by abdominal computed tomography (CT), and mortality in this patients population. METHODS: This two-center retrospective cohort study included hemodialysis patients who underwent abdominal CT between January 2013 and December 2018. Skeletal muscle mass index (SMI), muscle radiation attenuation (MRA) as an index of intramuscular fat, and visceral fat to subcutaneous fat ratio (VSR) were calculated using CT images at the third lumbar vertebral level. Multivariate Cox proportional hazards model was used to determine the independent predictors of all-cause, cardiovascular and non-cardiovascular mortalities. RESULTS: The study included 344 patients (median age 71.0 years; female 33.7%), among whom 145 died during a median follow-up of 4.9 years-46 and 99 from cardiovascular and non-cardiovascular causes, respectively. Lower MRA [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.58-0.87, P = .001] and higher VSR (HR 1.17, 95% CI 1.01-1.37, P = .04) were independently associated with higher all-cause mortality but not with lower SMI (HR 0.87, 95% CI 0.68-1.11, P = .26). Lower MRA (HR 0.51, 95% CI 0.35-0.73, P < .001) and higher VSR (HR 1.29, 95% CI 1.09-1.54, P = .003) were also associated with cardiovascular and non-cardiovascular mortality, respectively. CONCLUSIONS: Intramuscular fat and abdominal fat as measured using abdominal CT in hemodialysis patients are stronger independent predictors of mortality than muscle mass.

Comparison of the association between six different frailty scales and clinical events in patients on hemodialysis.

BACKGROUND: Frailty is associated with adverse outcomes in patients undergoing hemodialysis (HD). However, no study has used various frailty assessments in patients on HD to examine their association with clinical events. In this study, we investigated the association between clinical events and six frailty scales. METHODS: Outpatients who underwent HD between 2018 and 2020 were retrospectively enrolled. Frailty was defined using the Fried Frailty Phenotype, Study of Osteoporotic Fractures (SOF) Index, Short Physical Performance Battery (SPPB), Frail Screening Index, FRAIL scale and Clinical Frailty Scale. Outcomes were clinical events, including a composite of multiple (i.e. recurrent) all-cause hospitalizations, fractures and/or all-cause mortality. The association of clinical events and the frailty scales were investigated using negative binomial regression analysis. RESULTS: Fried Frailty Phenotype [incident rate ratio (IRR), 1.62; 95% confidence interval (CI), 1.49-1.76], SOF Index (IRR, 1.42; 95% CI, 1.10-1.83), SPPB (IRR, 1.79; 95% CI, 1.11-2.88) and Clinical Frailty Scale (IRR, 1.65; 95% CI, 1.04-2.61) were significantly associated with clinical events. However, Frail Screening Index (IRR, 1.38; 95% CI, 0.60-3.18) and FRAIL scale (IRR, 1.30; 95% CI, 0.88-1.92) showed no significant association with clinical events. CONCLUSIONS: Objective frailty assessments (SPPB) and medical staff impression-based frailty (Clinical Frailty Scale) may be useful prognostic predictors for patients on HD. Questionnaire-based frailty assessment should be carefully considered when used as a measurement of frailty.

Decline of instrumental activities of daily living is a risk factor for nutritional deterioration in older adults: a prospective cohort study.

BACKGROUND: The association between functional capacity and the subsequent risk of nutritional deterioration is yet to be understood. The purpose of this study was to elucidate the relationship between functional capacity, comprising instrumental activities of daily living (IADL), intellectual activity, and social function, and future decline in nutritional status. METHODS: The current study is a two-year prospective cohort study. A total of 468 community-dwelling older adults without nutritional risks were enrolled. We used the Mini Nutritional Assessment Screening Form. Functional capacity, including IADL, intellectual activity, and social function, was assessed using the Tokyo Metropolitan Institute of Gerontology Index of Competence at baseline. The nutritional status was reassessed at a 2-year follow-up. Risk ratios (RR) of functional capacity for the incidence of nutritional decline were estimated. RESULTS: Low functional capacity was significantly associated with future deterioration of nutritional status (RR 1.12, 95% confidence interval [CI] 1.02-1.25). Of the subdomains of functional capacity, IADL decline (adjusted RR 2.21, 95% CI 1.18-4.13) was an independent risk factor for the incidence of nutritional risk. Intellectual and social activities were not significant. CONCLUSION: Decline in functional capacity, especially IADL, is a risk factor for future deterioration in nutritional status. Further studies are required to elucidate the effect of interventions for IADL decline on maintaining nutritional status in older adults.

Relationship Between Physical Activity and Estimated Glomerular Filtration Rate in Renal Transplant Recipients: A Cross-sectional Study Analyzing Isotemporal Substitution Model.

OBJECTIVES: Successful renal transplantation reduces mortality rates. However, the decline in the estimated glomerular filtration rate (eGFR) after transplantation is strongly associated with premature mortality in renal transplant recipients (RTRs). Physical activity (PA) is a modifiable lifestyle factor with the potential to maintain or improve eGFR. However, the effects of the type or intensity of PA and sedentary behavior (SB) on eGFR in RTRs remain unclear. The purpose of this study was to clarify the association between accelerometry-measured PA and SB and eGFR in RTRs using isotemporal substitution (IS) analysis. METHODS: A total of 82 renal transplant outpatients participated in this cross-sectional study, of which 65 (average age, 56.9 years; average time post-transplant, 83.0 months) were finally analyzed. All RTRs wore a triaxial accelerometer to measure PA for 7 consecutive days. The measured PA was classified based on intensity into light PA, moderate-to-vigorous PA (MVPA), and SB. The association of each type of PA with eGFR was examined using multi-regression analyses of single-factor, partition, and IS models. The IS model was applied to examine the estimated effects of substituting 30 minutes of SB with an equal amount of time of light PA or MVPA on eGFR. RESULTS: The partition model showed that MVPA was an independent explanatory variable for eGFR (ß = 5.503; P < .05), and the IS model identified that the substitution of time spent in SB with MVPA led to improvements in eGFR (ß = 5.902; P < .05). CONCLUSIONS: The present study suggests that MVPA has an independent and positive association with eGFR, and replacing 30 minutes of SB with MVPA after renal transplantation might lead to the maintenance or improvement of eGFR in RTRs.

The Association of Short Physical Performance Battery With Mortality and Hospitalization in Patients Receiving Hemodialysis.

OBJECTIVE: The Short Physical Performance Battery (SPPB) is recommended for evaluating physical performance in patients on hemodialysis (HD). However, the association between SPPB score and long-term health outcomes in these patients remains unclear. We examined the association of SPPB score with all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization in patients on HD. DESIGN AND METHODS: This retrospective cohort study included 326 patients (median age, 68 years; 62% men) who received outpatient HD therapy. These patients were divided into 2 SPPB groups: low (SPPB ≤9) and high (SPPB >9). We investigated the association of SPPB score and their change over time with health outcomes using Cox regression analysis. RESULTS: Low SPPB score was associated with a higher risk for all-cause mortality (hazard ratio [HR]: 3.19, 95% confidence interval [95% CI]: 1.89-5.38), all-cause hospitalization (HR: 2.01, 95% CI: 1.44-2.82), and cardiovascular hospitalization (HR: 2.20, 95% CI: 1.45-3.35). Additionally, change in SPPB score over 1 year was associated with health outcomes. CONCLUSIONS: Lower SPPB score was significantly associated with a higher risk for all-cause mortality, all-cause hospitalization, and cardiovascular hospitalization. The SPPB may be a valuable indicator for risk stratification in patients on HD. Additionally, preventive treatments may be an effective management strategy in limiting the high mortality and hospitalization rates in patients with decreased SPPB score.

Trajectory of Serum Albumin Prior to Death in Patients Receiving Hemodialysis.

OBJECTIVE: Although some clinical expert guidelines recommend regular monitoring of serum albumin levels in patients undergoing maintenance hemodialysis, little is known about the serum albumin trajectory patterns over time, and it is unclear how the trajectory change before death. METHODS: We performed this retrospective study using data from 421 patients receiving hemodialysis in a dialysis facility. We divided patients into died and survived groups according to whether they died during the observation period. To compare the albumin trajectories during the observation period between the died and survived groups, linear mixed-effect models and a backward timescale from the year of death or study end were used. RESULTS: During the observation period (median, 5.1 years; maximum, 8.4 years), 115 patients receiving dialysis died. The serum albumin level showed steeper decline 3 years before death in the died group than in the survived group. The difference in albumin between the died and survived groups became apparent 3 years before death (difference, 0.08 g/dL; 95% confidence interval, 0.00-0.15 g/dL; P = .04), and the difference widened over time (difference at 1 year before death, 0.24 g/dL; 95% confidence interval, 0.14-0.33 g/dL; P < .001). Furthermore, in an analysis of albumin trajectories according to cause of death, the albumin level showed a downward trend regardless of the cause of death. CONCLUSION: The serum albumin trajectory differed between patients undergoing hemodialysis who died and who survived, supporting the importance of monitoring the albumin trajectory in clinical practice.

Comparative Analysis of Simplified, Objective Nutrition-Associated Markers in Patients Undergoing Hemodialysis.

OBJECTIVE: Protein-energy wasting is prevalent among patients undergoing dialysis. Hence, identifying an optimal index is necessary for the comprehensive measurement of nutritional status. This study evaluated and compared the prognostic significance of the modified creatinine index (mCI) and geriatric nutritional risk index (GNRI), with the principal aim to identify markers that are more closely associated with clinical events in patients undergoing hemodialysis. METHODS: We performed a retrospective cohort study of 472 patients undergoing maintenance hemodialysis (mean age, 66.4 years; 62.9% males). We evaluated the mCI, GNRI, and their respective rates of change over a 1-year period. The outcome analysis included all-cause death, number and duration of all-cause hospitalizations, and number and duration of hospitalizations due to cardiovascular disease. In addition, we analyzed the associations of the mCI, GNRI, and their trajectories with clinical outcomes using Cox proportional hazard regression and negative binomial regression. RESULTS: Over a median 3.6-year follow-up, both the lower mCI (hazard ratio 3.00; 95% confidence interval 2.19, 4.09) and lower GNRI (hazard ratio 1.76; 95% confidence interval 1.45, 2.13) per 1 standard deviation decrease were associated with a higher risk of all-cause death. However, a lower mCI was consistently associated with a higher risk of hospitalization, whereas the GNRI was poorly associated with the risk of hospitalization after adjusting for covariates. Furthermore, although a decline in the mCI over time was associated with a higher risk of each adverse event, a significant association between the change in GNRI and clinical events was not detected. CONCLUSION: The mCI at one timepoint and its trajectory had consistently stronger associations with clinical events than the GNRI in patients undergoing hemodialysis. This study further emphasizes the importance of risk screening using a marker of nutritional status in patients undergoing hemodialysis.

Determinants of Health-Related Quality of Life and Physical Performance-Based Components of Frailty in Patients Undergoing Hemodialysis.

OBJECTIVES: Health-related quality of life (HRQoL) measures capture the patient's experience of the burden of chronic disease and are strongly associated with adverse health-related outcomes across multiple populations. The SF-36 score is the most widely used HRQoL measure among patients with end-stage renal disease. Current understanding of determinants of the physical component summary (PCS) and the mental component summary (MCS) and their association with objectively measured physical performance and activity is limited. METHODS: As an index of HRQoL, we prospectively examined the association of SF-36 and its component scores with physical function among 155 incident dialysis patients from the Hemodialysis Center. We investigated associations of HRQoL with the physical performance-based components of the frailty using multivariate linear and logistic regression after adjustment for confounders. Impaired physical performance was defined as having either slow usual gait speed or weak handgrip strength based on standardized and validated criteria derived from a large cohort study of older adults. RESULTS: The patients had a mean age of 65 ± 11 years, and 52.3% were male. After adjusting confounders, lower PCS was independently associated with decreased physical performance and reduced physical activity, but MCS was not associated. Among the PCS subscales, only physical functioning 10 (PF-10) was consistently associated with outcomes, and every 1 point increase in PF-10 score was associated with 4% lower odds of impaired physical performance (95% confidence interval 2-7, P = .01) after adjustment. CONCLUSIONS: SF-36, especially PF-10, is a valid surrogate that discriminates low physical performance and physical inactivity in the absence of formal physical function testing in patients on hemodialysis. The routine implementation of the PF-10 in clinical care has important clinical implications for medical management and therapeutic decision-making in patients undergoing hemodialysis.

Impact of Physical Activity on Dialysis and Nondialysis Days and Clinical Outcomes Among Patients on Hemodialysis.

OBJECTIVE: Patients undergoing hemodialysis (HD) have different physical activity (PA) patterns on HD and non-HD days. Nonetheless, whether these differences are associated with clinical outcomes remains unclear. We examined the association of PA levels on HD and non-HD days with cardiovascular (CV) hospitalizations and mortality. METHODS: Outpatients undergoing HD from 2002 to 2019 were retrospectively enrolled. The number of steps performed over 3 HD days and 4 non-HD days was recorded via accelerometry. Outcomes were all-cause mortality and a composite of CV hospitalizations and mortality. Patients were divided into two groups, each according to the median number of steps performed on HD (2371 steps/day) and non-HD days (3752 steps/day). Further, we categorized them into 4 groups according to each median values: "more active on HD/more active on non-HD (MM)," "more active on HD/less active on non-HD (ML)," "less active on HD/more active on non-HD (LM)," and "less active on HD/less active on non-HD (LL)." Cox and mixed-effects Poisson regression models were used for these outcomes. RESULTS: We analyzed 512 patients (median follow-up, 3.4 years). Higher PA on HD (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.54-0.65), and non-HD (HR, 0.84; 95% CI, 0.80-0.88) was associated with lower mortality risk, respectively. Further, the ML group (HR, 1.20; 95% CI, 1.13-1.28), LM group (HR, 1.82; 95% CI, 1.53-2.17), and LL group (HR, 1.83; 95% CI, 1.65-2.02) had higher mortality risks than the MM group. Associations of PA with multiple CV hospitalizations and mortality were similar to those between PA and mortality. CONCLUSIONS: Higher PA on HD and non-HD days was associated with lower risks of CV hospitalizations and mortality. However, higher PA levels on either HD or non-HD days alone did not improve clinical outcomes.

Modified Creatinine Index and Clinical Outcomes of Hemodialysis Patients: An Indicator of Sarcopenia?

OBJECTIVE: Sarcopenia (especially muscle mass assessed using gold standard techniques) has been suggested as a poorer predictor of mortality than muscle function in patients undergoing hemodialysis. Appropriate methods to estimate muscle mass for use as a good predictor of clinical outcomes remain to be established. We investigated whether the modified creatinine index (mCI), which is a surrogate marker of muscle mass, could predict mortality and cardiovascular (CV) hospitalizations independent of muscle function and other confounders in patients on hemodialysis. DESIGN AND METHODS: In this retrospective study, outpatients (n = 542; mean age, 65.3 years; 60% men; median dialysis vintage, 29 months; mean BMI, 22.0 kg/m2) undergoing hemodialysis were investigated. The mCI, handgrip strength, and gait speed were assessed and related to all-cause mortality and a composite of CV hospitalizations and all-cause mortality. Cox proportional and mixed-effects negative binomial models were fit for mortality and the composite outcomes. RESULTS: Patients were followed up for a median 3 years (interquartile range: 1.5-5.7). Each per SD increase of mCI (HR:0.63, 95% CI:0.62-0.65), handgrip strength (HR:0.51, 95% CI:0.48-0.54), and gait speed (HR:0.60, 95% CI:0.56-0.64) were significantly associated with lower all-cause mortality rates after adjusting for covariates. The mCI was consistently found to be an independent predictor of mortality after additional adjustment for handgrip strength or gait speed. Furthermore, sarcopenic conditions [i.e., lower mCI, and lower handgrip strength (HR:3.79, 95% CI:2.09-6.87) or slower gait speed (HR:4.20, 95% CI:2.38-7.41)] were significantly associated with a higher risk of mortality after adjusting for covariates. Associations of mCI with multiple CV hospitalizations and mortality were similar to those between mCI and mortality. CONCLUSION: The mCI was a good predictor of clinical outcomes and was comparable to muscle function, including handgrip strength and gait speed. The mCI is likely to provide additional diagnostic and prognostic values for sarcopenia in patients on hemodialysis.

Trajectory of Lean Body Mass Assessed Using the Modified Creatinine Index and Mortality in Hemodialysis Patients.

RATIONALE & OBJECTIVE: Although a declining body mass index (BMI) is associated with higher mortality in patients on hemodialysis, BMI cannot distinguish lean body mass from fat mass. It remains unclear whether changes over time in lean body mass are associated with mortality. We examined the prognostic significance of changes in the modified creatinine index, a proxy for lean body mass. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Outpatients (n=349; mean age, 67.4 years; 60% men) undergoing maintenance hemodialysis 3 times a week at a treatment center. PREDICTOR: Modified creatinine index and BMI trajectories over a 1-year period. OUTCOMES: All-cause mortality. ANALYTICAL APPROACH: We calculated the percentage of change in modified creatinine index and BMI over a 1-year period. Patients were categorized according to change in modified creatinine index/BMI: no decline (≥0%) or decline (<0%). Kaplan-Meier and Cox proportional hazard analyses were performed to examine whether modified creatinine index and BMI trajectories were associated with mortality. RESULTS: During follow-up (median, 1,157 days), 79 patients died. Decreasing modified creatinine index (HR, 1.31; 95% CI, 1.11-1.54) and BMI (HR, 1.25; 95% CI, 1.01-1.54) over time, measured as continuous variables and expressed per 1-standard deviation decrease, were independently associated with higher risk for all-cause mortality. The decline in modified creatinine index/no decline in BMI group (HR, 2.14; 95% CI, 1.04-4.45) and the decline in modified creatinine index/decline in BMI group (HR, 3.05; 95% CI, 1.58-5.90) had higher rates of mortality compared to the no decline in modified creatinine index/decline in BMI group. LIMITATIONS: The absence of a direct measure of lean body and fat mass and limited generalizability to non-Japanese hemodialysis populations. CONCLUSIONS: The modified creatinine index trajectory is independently associated with mortality and provides additional prognostic information to the BMI trajectory in patients on hemodialysis.

Association between sarcopenia and atherosclerosis in elderly patients with ischemic heart disease.

Compared to the general population, elderly patients with cardiovascular disease have a higher prevalence of sarcopenia, and it shows an association with increased mortality risk. Although several studies have indicated that atherosclerosis may cause sarcopenia in community dwelling elderly subjects, the association between sarcopenia and atherosclerosis is not clear in patients with ischemic heart disease (IHD). The present study was performed to examine the association between muscle function and atherosclerosis in elderly patients with IHD. We reviewed the findings of 321 consecutive patients ≥ 65 years old with IHD. Three measures of muscle function were examined, i.e., gait speed, quadriceps isometric strength, and handgrip strength, just before hospital discharge. In addition, we measured intima-media thickness (IMT) as a parameter of arteriosclerosis. To investigate the association between sarcopenia and atherosclerosis, patients were divided into Group H (high), Group M (middle), and Group L (low) according to the tertiles of muscle function, and IMT was compared between the three groups. In addition, we considered the association between IMT thickening and muscle function. The mean age of the study population was 74.1 ± 6.0 years and 73.2% of the patients were men. IMT was compared between groups stratified according to gait speed and quadriceps isometric strength, and the results indicated that IMT was significantly lower in Group H than in Groups L and M (p < 0.05). In addition, gait speed and quadriceps isometric strength were associated with IMT thickening (p < 0.05). Parameters reflecting muscle function of the lower limbs are associated with atherosclerosis in patients with IHD.

Prognostic value of instrumental activity of daily living in initial heart failure hospitalization patients aged 65 years or older.

Although the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC) is useful to assess decline of instrumental activities of daily living (IADL) in Japanese individuals, limited data are available in patients with heart failure (HF). This study was performed to investigate the prognostic value of IADL evaluated by TMIG-IC in initial HF hospitalization patients aged ≥ 65 years. We reviewed 297 elderly HF patients with independent basic ADL before hospitalization. Patients with prior HF were excluded. Five TMIG-IC items were investigated as IADL parameters. Patients with full IADL scores were defined as "independent" and others were defined as "dependent". The endpoint was all-cause mortality, and multivariable analysis was performed to identify IADL risk. The median age was 76 years, and 55% of the patients were male. Forty-one deaths occurred over a median follow-up period of 1.01 years. After adjusting for existing risk factors, including Seattle Heart Failure Score, dependent patients had higher mortality risk than independent patients [hazard ratio 3.64, 95% confidence interval (CI) 1.57-8.43], and mortality risk decreased by 16% for each 1-point increase in IADL score (hazard ratio 0.84, 95% CI 0.71-0.99). In conclusion, limited IADL indicated by TMIG-IC was associated with poorer long-term mortality rate in elderly patients with HF. This inexpensive and easily applicable tool will support decision making in cardiac rehabilitation.

Efficacy of Exercise Therapy Initiated in the Early Phase After Kidney Transplantation: A Pilot Study.

OBJECTIVE: In patients with kidney transplant (KT), frailty is a predictor of adverse outcomes. Outcomes of exercise therapy in patients with KT, particularly the efficacy of early exercise after KT, have not been evaluated. We investigated the effect of exercise intervention beginning early after KT on physical performance, physical activity, quality of life, and kidney function in patients with KT. METHODS: KT recipients who underwent surgery with usual care plus exercise training from a prospective cohort (exercise group; n = 10) and those with usual care alone from a historical cohort (control group; n = 14) were included in this study. Early exercise comprised supervised aerobic training and physical activity instruction from day 6 to 2 months after KT. The following outcomes were measured: 6-minute walking distance, isometric knee extensor strength, gait speed, physical activity, quality of life, and estimated glomerular filtration rate. RESULTS: Analyses of covariance, adjusted for baseline values, revealed significant mean differences between exercise and control groups at 2 months after KT in 6-minute walking distance (+44.4 m, P = .03) and isometric knee extensor strength (+8.1%body weight, P = .03). No significant between-group differences were found in gait speed, physical activity, and quality of life. The analysis of variance for comparison of the area under the recovery curves of estimated glomerular filtration rate after KT revealed no significant difference between groups. CONCLUSION: Supervised aerobic training and physical activity instruction initiated in the early phase after KT can improve physical performance without adversely affecting kidney function.

Usefulness of the Simplified Frailty Scale in Predicting Risk of Readmission or Mortality in Elderly Patients Hospitalized with Cardiovascular Disease.

The simplified frailty scale is a simple frailty assessment tool modified from Fried's phenotypic frailty criteria, which is easy to administer in hospitalized patients. The applicability of the simplified frailty scale to indicate prognosis in elderly hospitalized patients with cardiovascular disease (CVD) was examined.This cohort study was performed in 895 admitted patients ≥ 65 years (interquartile range, 71.0-81.0, 541 men) with CVD. Patients were classified as robust, prefrail, or frail based on the five components of the simplified frailty scale: weakness, slowness, exhaustion, low activity, and weight loss. The primary endpoint was the composite outcome of all-cause mortality and unplanned readmission for CVD.Patients positive for greater numbers of frailty components showed higher risk of all-cause mortality or unplanned CVD-related readmission (P for trend < 0.001). Classification as both frail (adjusted HR: 3.27, 95% confidence interval [CI]: 1.49-7.21, P = 0.003) and prefrail (adjusted HR: 2.19, 95% CI: 1.00-4.79, P = 0.049) independently predicted the composite endpoint compared with robust after adjusting for potential confounding factors. The inclusion of prefrail, frail, and number of components of frailty increased both continuous net reclassification improvement (0.113, P = 0.049; 0.426, P < 0.001; and 0.321, P < 0.001) and integrated discrimination improvement (0.007, P = 0.037; 0.009, P = 0.038; and 0.018, P = 0.002) for the composite endpoint.Higher scores on the simplified frailty scale were associated with increased risk of mortality or readmission in elderly patients hospitalized for CVD.

Pupillary Light Reflex as a New Prognostic Marker in Patients With Heart Failure.

BACKGROUND: Autonomic function can be evaluated based on the pupillary light reflex (PLR). However, the relationship between PLR and prognosis in patients with heart failure (HF) remains unclear. This study was performed to examine whether PLR could be used as a prognostic indicator in patients with HF. METHODS AND RESULTS: A retrospective review was performed in 535 consecutive Japanese patients hospitalized for acute HF (mean age 66.1 ± 13.7 y). PLR was recorded at least 7 days after hospitalization for HF with the use of a pupilometer. Fifty-three patients died over a median follow-up period of 1.3 years (interquartile range 0.6-2.3 y). After adjustment for several preexisting prognostic factors, including Seattle Heart Failure Score (SHFS), PLR as assessed by recovery time (time to 63% redilation) was independently associated with all-cause mortality (hazard ratio 0.50, 95% confidence interval 0.35-0.73; P < .001). The addition of recovery time to SHFS resulted in a significant increase in the area under the curve on receiver-operating characteristic curve analysis (0.69 vs 0.77; P < .001). CONCLUSIONS: PLR assessed by recovery time was an independent predictor of mortality and added prognostic information to the SHFS in patients with HF. Our results suggest that PLR may be useful as a new prognostic marker in HF patients.

Association between frailty and bone loss in patients undergoing maintenance hemodialysis.

Frailty is significantly associated with bone loss in the general population. However, it is unclear whether this association also exists in patients undergoing hemodialysis who have chronic kidney disease-mineral and bone disorder (CKD-MBD). This study aimed to assess the association between frailty and bone loss in patients undergoing hemodialysis. This cross-sectional study included 214 (90 women, 124 men) Japanese outpatients undergoing maintenance hemodialysis three times per week, with a mean age of 67.1 years (women) and 66.8 years (men). Frailty was defined based on criteria set forth by the Cardiovascular Health Study (CHS)-19 (21.1%) women and 47 (37.9%) men were robust, 41 (45.6%) women and 43 (34.7%) men were pre-frail, and 30 (33.3%) women and 34 (27.4%) men were frail. For bone mass, quantitative ultrasound (QUS) parameters (speed of sound, broadband ultrasound attenuation, stiffness index) of the calcaneus were measured. The association between frailty and QUS parameters was determined separately for women and men using multivariate analysis of covariance (ANCOVA), with adjustments for clinical characteristics including age, body mass index, hemodialysis vintage, diabetes, current smoking, serum albumin, phosphate, corrected calcium, intact parathyroid hormone, and medication for CKD-MBD (vitamin D receptor activator, calcimimetics). ANCOVA revealed that all QUS parameters declined significantly with increasing levels of frailty in both sexes (P < 0.05). In conclusion, frailty (as defined by CHS criteria) should be considered a risk factor for bone loss in patients undergoing hemodialysis.

Short-Term Change in Gait Speed and Clinical Outcomes in Older Patients With Acute Heart Failure.

BACKGROUND: Evidence for the prognostic value of gait speed is largely based on a single measure at baseline, so we investigated the prognostic significance of change in gait speed in hospitalized older acute heart failure (AHF) patients.Methods and Results:This retrospective study was performed in a cohort of 388 AHF patients ≥60 years old (mean age: 74.8±7.8 years, 228 men). Routine geriatric assessment included gait speed measurement at baseline and at discharge. The primary outcome of this study was all-cause death. Gait speed increased from 0.74±0.25 m/s to 0.98±0.27 m/s after 13.5±11.0 days. Older age, shorter height and lower hemoglobin level at admission, prior HF admission, and higher baseline gait speed were independently associated with lesser improvement in gait speed. A total of 80 patients died and 137 patients were readmitted for HF over a mean follow-up period of 2.1±1.9 years. In multivariate analyses, change in gait speed showed inverse associations with all-cause death (hazard ratio [HR] per 0.1 m/s increase: 0.83; 95% confidence interval [CI]: 0.73 to 0.95; P=0.006) and with risk of readmission for HF (HR: 0.91; 95% CI: 0.83 to 0.99; P=0.036). CONCLUSIONS: Short-term improvement in gait speed during hospitalization was associated with reduced risks of death and readmission for HF in older patients with AHF.

Respiratory muscle weakness increases dead-space ventilation ratio aggravating ventilation-perfusion mismatch during exercise in patients with chronic heart failure.

BACKGROUND AND OBJECTIVE: Respiratory muscle weakness causes fatigue in these muscles during exercise and thereby increases dead-space ventilation ratio with decreased tidal volume. However, it remains unclear whether respiratory muscle weakness aggravates ventilation-perfusion mismatch through the increased dead-space ventilation ratio. In ventilation-perfusion mismatch during exercise, minute ventilation versus carbon dioxide production (VE/VCO2 ) slope > 34 is an indicator of poor prognosis in patients with chronic heart failure (CHF). We examined the relationship of respiratory muscle weakness with dead-space ventilation ratio and ventilation-perfusion mismatch during exercise and clarified whether respiratory muscle weakness was a clinical predictor of VE/VCO2 slope > 34 in patients with CHF. METHODS: Maximal inspiratory pressure (PImax ) was measured as respiratory muscle strength 2 months after hospital discharge in 256 compensated patients with CHF. During cardiopulmonary exercise test, we assessed minute dead-space ventilation versus VE (VD/VE ratio) as dead-space ventilation ratio and VE/VCO2 slope as ventilation-perfusion mismatch. Patients were divided into low, moderate and high PImax groups based on the PImax tertile. We investigated determinants of VE/VCO2 slope > 34 among these groups. RESULTS: The low PImax group showed significantly higher VD/VE ratios at 50% of peak workload and at peak workload and higher VE/VCO2 slope than the other two groups (P < 0.001, respectively). PImax was a significant independent determinant of VE/VCO2 slope > 34 (odds ratio (OR): 0.67, 95% CI: 0.54-0.82) with area under the receiver operating characteristic curve of 0.812 (95% CI: 0.750-0.874). CONCLUSION: Respiratory muscle weakness was associated with an increased dead-space ventilation ratio aggravating ventilation-perfusion mismatch during exercise in patients with CHF.

Office-Based Physical Assessment in Patients Aged 75 Years and Older with Cardiovascular Disease.

BACKGROUND: The detection of impaired physical performance in older adults with cardiovascular disease is essential for clinical management and therapeutic decision-making. There is a requirement for an assessment tool that can be used conveniently, rapidly, and securely in clinical practice for screening decreased physical performance. OBJECTIVE: The present study was performed to evaluate the association of office-based physical assessments with decreased physical performance and to compare the prognostic capability of these assessments in older adults with cardiovascular disease. METHODS: A total of 1,040 patients aged 75 years and older with cardiovascular disease were included in this analysis. One-leg standing time (OLST) and handgrip strength were measured as office-based physical assessment tools, and short physical performance battery (SPPB), 6-min walk distance, and usual gait speed were also measured at hospital discharge as measurements of physical performance. All-cause mortality was assessed by death registry at the hospital. We examined the association of office-based measures with physical performance and all-cause mortality. RESULTS: The areas under the curve of OLST for SPPB < 10, 6-min walk distance < 300 m, and usual gait speed < 1.0 m/s were 0.87 (95% CI 0.83-0.91), 0.83 (95% CI 0.80-0.86), and 0.81 (95% CI 0.78-0.85), respectively. The discrimination abilities of OLST for decreased physical performance were significantly higher than those of handgrip strength. After adjusting for the effects of patient characteristics, the hazard ratio for all-cause mortality in the < 3 s group for OLST was 1.68 (95% CI 1.06-2.67, p = 0.03). Handgrip strength, however, was not significantly associated with mortality risk in these participants. CONCLUSION: Short OLST, in particular < 3 s, is associated with decreased physical performance and elevated mortality risk in elderly patients with cardiovascular disease. OLST can be conveniently measured in the clinician's office as a screening tool for impaired physical performance.