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Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6-minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12. Primary outcomes were change in 6-minute walk distance and short physical performance battery at 6-month follow-up and have been reported previously. Secondary outcomes were change in 6-minute walk and short physical performance battery at 12-month follow-up and are reported here. A group of 134 participants (86%) completed the 12-month follow-up. At 6-month follow-up, compared with control, 6-minute walk distance improved in the treadmill exercise group (+36.1 m, 95% CI =13.9-58.3, P=0.001). Between 6- and 12-month follow-up, 6-minute walk distance significantly declined (-28.6 m, 95% CI=-52.6 to -4.5, P=0.020) and physical activity declined -272 activity units (95% CI =-546 to +2, P=0.052) in the treadmill exercise group compared with controls. At 12-month follow-up, 6 months after completing supervised treadmill exercise, change in 6-minute walk distance was not different between the treadmill exercise and control groups (+7.5, 95% CI =-17.5 to +32.6, P=0.56). There were no differences in short physical performance battery change between either exercise group and control at 6-month or 12-month follow-up. Conclusions A 6-month supervised treadmill exercise intervention that improved 6-minute walk distance at 6-month follow-up did not have persistent benefit at 12-month follow-up. These results do not support a durable benefit of supervised treadmill exercise in peripheral artery disease. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Identifier: NCT 00106327.

Estimations based on the available equations for predicting oxygen uptake (V̇O2) from treadmill speed of locomotion are not appropriate for individuals with Down syndrome (DS). We aimed at developing prediction models for peak absolute oxygen uptake (V̇O2peak) and peak heart rate (HRpeak) based on retrospective data from a healthy population with and without Down syndrome (DS). A cross-sectional analysis of V̇O2peak and HRpeak was conducted in 196 and 187 persons with and without DS, respectively, aged from 16 to 45 yr. Nonexercise data alone versus combined with HRpeak were used to develop equations predictive of absolute V̇O2peak. Prediction equations for HRpeak were also developed. Two additional samples of participants (30 with, 29 without DS) enabled model cross-validation. Relative V̇O2peak and HRpeak were lowest for persons with DS across all ages (~40% and 20 beats·min-1, respectively). For persons with DS, V̇O2peak predictions provided no differences compared with actual values. Predicted HRpeak was similar to actual values in both groups of participants. Large limits of agreement were obtained for V̇O2peak (DS: 735, non-DS: 558.2 mL·min-1) and HRpeak (DS: 24.8, non-DS: 16.6 beats·min-1). Persons with DS exhibit low levels of V̇O2peak and HRpeak in all age groups included in this study. It is possible to estimate absolute V̇O2peak in persons with DS using nonexercise variables. HRpeak can be accurately estimated in groups of people with and without DS. Yet, because of large limits of agreement, caution is advised if using these equations for individual estimations of V̇O2peak or HRpeak in either population. [ABSTRACT FROM AUTHOR]

Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6‐minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12. Primary outcomes were change in 6‐minute walk distance and short physical performance battery at 6‐month follow‐up and have been reported previously. Secondary outcomes were change in 6‐minute walk and short physical performance battery at 12‐month follow‐up and are reported here. A group of 134 participants (86%) completed the 12‐month follow‐up. At 6‐month follow‐up, compared with control, 6‐minute walk distance improved in the treadmill exercise group (+36.1 m, 95% CI=13.9‐58.3, P=0.001). Between 6‐ and 12‐month follow‐up, 6‐minute walk distance significantly declined (−28.6 m, 95% CI=−52.6 to −4.5, P=0.020) and physical activity declined −272 activity units (95% CI=−546 to +2, P=0.052) in the treadmill exercise group compared with controls. At 12‐month follow‐up, 6 months after completing supervised treadmill exercise, change in 6‐minute walk distance was not different between the treadmill exercise and control groups (+7.5, 95% CI=−17.5 to +32.6, P=0.56). There were no differences in short physical performance battery change between either exercise group and control at 6‐month or 12‐month follow‐up. Conclusions A 6‐month supervised treadmill exercise intervention that improved 6‐minute walk distance at 6‐month follow‐up did not have persistent benefit at 12‐month follow‐up. These results do not support a durable benefit of supervised treadmill exercise in peripheral artery disease. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Identifier: NCT00106327.

Background Little is known about the association between dairy intake and risk of functional disability in the elderly. Objectives We examined the influence of dairy intake on the development of declining functional capacity and activities of daily living (ADL) in a prospective cohort study of an elderly population. Methods A total of 859 community-dwelling Japanese residents, aged ≥65 y without functional disability, were followed up for 7 y. Functional capacity impairment was defined as a Tokyo Metropolitan Institute of Gerontology Index of Competence score of ≤12, and ADL disability was defined as a Barthel Index score of ≤95. Dairy intake was evaluated using a 150-item semiquantitative food frequency questionnaire, grouped into quartiles. The RR of dairy intake on incident functional disability was computed using a Poisson regression model. Results The multivariable-adjusted RR of impaired functional capacity decreased significantly with increasing dairy intake levels (RR [95% CI]: quartile 1, 1.00 [reference]; quartile 2, 0.85 [0.71, 1.02]; quartile 3, 0.81 [0.68, 0.98]; and quartile 4, 0.74 [0.61, 0.90]; P -trend = 0.001). Regarding the three subscales of functional capacity, the inverse association between dairy intake and risk for impairment of intellectual activity and social role remained significant (P -trend = 0.0009 and 0.02, respectively), but such an association was not observed for instrumental ADL. The multivariable-adjusted risk of ADL disability also decreased weakly but significantly with elevating dairy intake (P -trend = 0.04). A similar association was seen for severity of functional disability (P -trend = 0.002). However, the magnitude of these associations was attenuated after further adjustment for protein intake. Conclusion Our findings suggest that higher dairy intake is associated with a lower risk of functional disability and its progression in the elderly, probably via an increase in protein intake. [ABSTRACT FROM AUTHOR]

Background Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done. Methods and Results We conducted a subanalysis of 3 single‐center, randomized, and blinded clinical trials: (1) TAC‐HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON‐DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1‐year cardiac structure and function and quality‐of‐life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within‐group, P=0.002) compared to ICM (1.5%; within‐group, P=0.14; between‐group, P=0.003). Similarly, stroke volume increased in DCM by 10.59 mL (P=0.046) versus ICM (−0.2 mL; P=0.73; between‐group, P=0.02). End‐diastolic volume improved only in ICM (10.6 mL; P=0.04) and end‐systolic volume improved only in DCM (17.8 mL; P=0.049). The sphericity index decreased only in ICM (−0.04; P=0.0002). End‐diastolic mass increased in ICM (23.1 g; P

BackgroundFrailty is associated with greater mortality; however, whether frail patients primarily die of cardiovascular disease (CVD) or non‐CVD causes is unknown. Methods and ResultsWe assessed the cause of death in relation to frailty status, measured at baseline, among 3135 community‐dwelling older men in the MrOS Sleep (Outcomes of Sleep Disorders in Older Men) study. Absolute probability and risk of CVD mortality associated with frailty status were estimated with traditional methods that used censoring and newer methods that considered non‐CVD mortality as a competing risk. Of the 3135 men (mean age: 76.4±5.6 years), 475 (15.2%) were frail. During an average follow‐up of 9.2 years, 1275 (40.7%) men died, including 445 (34.9%) from CVD and 828 (64.9%) from non‐CVD causes (2 deaths unadjudicated). Both CVD and non‐CVD mortality risk increased with frailty. Cumulative absolute probability of CVD death at 10 years among frail men was 23.8% (20.2–27.6%) using the competing risk method versus 32.5% (27.3–37.8%) using the traditional Kaplan–Meier method (41.5% [95% confidence interval, 36.9–45.9%] and 48.6% [95% confidence interval, 43.6–53.4%], respectively, for non‐CVD mortality). The multivariable‐adjusted risk of CVD death among frail versus robust men was 1.38 (95% confidence interval, 0.99–1.92) using the competing risk method versus 1.84 (95% confidence interval, 1.35–2.51) using the traditional Cox proportional hazards method. ConclusionsAmong community‐dwelling older men, ≈35% of the deaths were due to CVD. Frail men were at increased risk of CVD death, but ignoring the competing risk of non‐CVD mortality overestimated their long‐term probability and relative risk of CVD death.

The hand, one of the most versatile but mechanically redundant parts of the human body, suffers more and longer than other body parts after stroke. One of the rehabilitation paradigms, task-oriented rehabilitation, encourages motor repeatability, the ability to produce similar motor performance over repetitions through compensatory strategies while taking advantage of the motor system's redundancy. The previous studies showed that stroke survivors inconsistently performed a given motor task with limited motor solutions. We hypothesized that stroke survivors would exhibit deficits in motor repeatability and adaptive compensation compared to healthy controls in during repetitive force-pulse (RFP) production tasks using multiple fingers. Seventeen hemiparetic stroke survivors and seven healthy controls were asked to repeatedly press force sensors as fast as possible using the four fingers of each hand. The hierarchical variability decomposition model was employed to compute motor repeatability and adaptive compensation across finger-force impulses, respectively. Stroke survivors showed decreased repeatability and adaptive compensation of force impulses between individual fingers as compared to the control ( p < 0.05). The stroke survivors also showed decreased pulse frequency and greater peak-to-peak time variance than the control ( p < 0.05). Force-related variables, such as mean peak force and peak force interval variability, demonstrated no significant difference between groups. Our findings indicate that stroke-induced brain injury negatively affects their ability to exploit their redundant or abundant motor system in an RFP task. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are limited data describing the functional status (FS) of children after heart transplant (HT). We sought to describe the FS of children surviving at least 1 year after HT, to evaluate the impact of HT on FS, and to identify factors associated with abnormal FS post-HT. METHODS: Organ Procurement and Transplantation Network data were used to identify all US children <21 years of age surviving ≥1 year post-HT from 2005 to 2014 with a functional status score (FSS) available at 3 time points (listing, transplant, ≥1 year post-HT). Logistic regression and generalized estimating equations were used to identify factors associated with abnormal FS (FSS≤8) post-HT. RESULTS: A total of 1633 children met study criteria. At the 1-year assessment, 64% were "fully active/no limitations" (FSS=10), 21% had "minor limitations with strenuous activity" (FSS=9); and 15% scored ≤8. In comparison with listing FS, FS at 1 year post-HT increased in 91% and declined/remained unchanged in 9%. A stepwise regression procedure selected the following variables for association with abnormal FS at 1 year post-HT: ≥18 years of age (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.7), black race (OR, 1.5; 95% CI, 1.1-2.0), support with ≥inotropes at HT (OR, 1.7; 95% CI, 1.2-2.5), hospitalization status at HT (OR, 1.5; 95% CI, 1.0-2.19), chronic steroid use at HT (OR, 1.5; 95% CI, 1.0-2.2), and treatment for early rejection (OR, 2.0; 95% CI, 1.5-2.7). CONCLUSION: Among US children who survive at least 1 year after HT, FS is excellent for the majority of patients. HT is associated with substantial improvement in FS for most children. Early rejection, older age, black race, chronic steroid use, hemodynamic support at HT, and being hospitalized at HT are associated with abnormal FS post-HT. [ABSTRACT FROM AUTHOR]

The ability to control redundant motor effectors is one of hallmarks in human motor control, and the topic has been studied extensively over several decades since the initial inquiries proposed by Nicholi Bernstein. However, our understanding of the influence of stroke on the control of redundant motor systems is very limited. This study aimed to investigate the effect of stroke-related constraints on multi-finger force control abilities in a visuomotor task. Impaired (IH) and less-impaired hands (LH) of 19 hemiparetic stroke survivors and 19 age-matched control subjects were examined. Each hand repeatedly produced isometric forces to match a target force of 5 N shown on a computer screen using all four fingers. The hierarchical variability decomposition (HVD) model was used to separate force-matching errors (motor performance) into task-relevant measures (accuracy, steadiness, and reproducibility). Task-irrelevant sources of variability in individual finger force profiles within and between trials (flexibility and multiformity) were also quantified. The IH in the stroke survivors showed deficits in motor performance attributed mainly to lower accuracy and reproducibility as compared to control hands ( p < 0.05). The LH in stroke survivors showed lower reproducibility and both hands in stroke also had higher multiformity than the control hands ( p < 0.05). The findings from our HVD model suggest that accuracy, reproducibility, and multiformity were mainly impaired during force-matching task in the stroke survivors. The specific motor deficits identified through the HVD model with the new conceptual framework may be considered as critical factors for scientific investigation on stroke and evidence-based rehabilitation of this population. [ABSTRACT FROM AUTHOR]

Background: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) differ in histopathology and prognosis. Although transendocardial delivery of mesenchymal stem cells is safe and provides cardiovascular benefits in both, a comparison of mesenchymal stem cell efficacy in ICM versus DCM has not been done., Methods and Results: We conducted a subanalysis of 3 single-center, randomized, and blinded clinical trials: (1) TAC-HFT (Transendocardial Autologous Mesenchymal Stem Cells and Mononuclear Bone Marrow Cells in Ischemic Heart Failure Trial); (2) POSEIDON (A Phase I/II, Randomized Pilot Study of the Comparative Safety and Efficacy of Transendocardial Injection of Autologous Mesenchymal Stem Cells Versus Allogeneic Mesenchymal Stem Cells in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction); and (3) POSEIDON-DCM (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy). Baseline and 1-year cardiac structure and function and quality-of-life data were compared in a post hoc pooled analysis including ICM (n=46) and DCM (n=33) patients who received autologous or allogeneic mesenchymal stem cells. Ejection fraction improved in DCM by 7% (within-group, P =0.002) compared to ICM (1.5%; within-group, P =0.14; between-group, P =0.003). Similarly, stroke volume increased in DCM by 10.59 mL ( P =0.046) versus ICM (-0.2 mL; P =0.73; between-group, P =0.02). End-diastolic volume improved only in ICM (10.6 mL; P =0.04) and end-systolic volume improved only in DCM (17.8 mL; P =0.049). The sphericity index decreased only in ICM (-0.04; P =0.0002). End-diastolic mass increased in ICM (23.1 g; P <0.0001) versus DCM (-4.1 g; P =0.34; between-group, P =0.007). The 6-minute walk test improved in DCM (31.1 m; P =0.009) and ICM (36.3 m; P =0.006) with no between-group difference ( P =0.79). The New York Heart Association class improved in DCM ( P =0.005) and ICM ( P =0.02; between-group P =0.20). The Minnesota Living with Heart Failure Questionnaire improved in DCM (-19.5; P =0.002) and ICM (-6.4; P =0.03; δ between-group difference P =0.042) patients., Conclusions: Mesenchymal stem cell therapy is beneficial in DCM and ICM patients, despite variable effects on cardiac phenotypic outcomes. Whereas cardiac function improved preferentially in DCM patients, ICM patients experienced reverse remodeling. Mesenchymal stem cell therapy enhanced quality of life and functional capacity in both etiologies., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifiers: TAC-HFT: NCT00768066, POSEIDON: NCT01087996, POSEIDON-DCM: NCT01392625., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Frailty is associated with greater mortality; however, whether frail patients primarily die of cardiovascular disease (CVD) or non-CVD causes is unknown., Methods and Results: We assessed the cause of death in relation to frailty status, measured at baseline, among 3135 community-dwelling older men in the MrOS Sleep (Outcomes of Sleep Disorders in Older Men) study. Absolute probability and risk of CVD mortality associated with frailty status were estimated with traditional methods that used censoring and newer methods that considered non-CVD mortality as a competing risk. Of the 3135 men (mean age: 76.4±5.6 years), 475 (15.2%) were frail. During an average follow-up of 9.2 years, 1275 (40.7%) men died, including 445 (34.9%) from CVD and 828 (64.9%) from non-CVD causes (2 deaths unadjudicated). Both CVD and non-CVD mortality risk increased with frailty. Cumulative absolute probability of CVD death at 10 years among frail men was 23.8% (20.2-27.6%) using the competing risk method versus 32.5% (27.3-37.8%) using the traditional Kaplan-Meier method (41.5% [95% confidence interval, 36.9-45.9%] and 48.6% [95% confidence interval, 43.6-53.4%], respectively, for non-CVD mortality). The multivariable-adjusted risk of CVD death among frail versus robust men was 1.38 (95% confidence interval, 0.99-1.92) using the competing risk method versus 1.84 (95% confidence interval, 1.35-2.51) using the traditional Cox proportional hazards method., Conclusions: Among community-dwelling older men, ≈35% of the deaths were due to CVD. Frail men were at increased risk of CVD death, but ignoring the competing risk of non-CVD mortality overestimated their long-term probability and relative risk of CVD death., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background and Purpose: Functional capacity is a predictor, as well as a consequence, of stroke. However, little research has been done to examine whether higher-level functional capacity above basic activities of daily living is a predictor of stroke., Methods: We followed 1493 Japanese community-dwelling adults aged ≥60 years (mean age, 70.1 years) who were independent in basic activities of daily living and had no history of stroke. Baseline data were collected using a self-administered questionnaire. Higher-level functional capacity was measured using the total score and 3 subscales (instrumental activities of daily living, intellectual activity, and social role) derived from the Tokyo Metropolitan Institute of Gerontology Index of Competence. Adjusted hazard ratios and 95% confidence intervals were calculated by the Cox proportional hazards model., Results: During a mean follow-up of 10.4 years, 191 participants developed a first stroke. Impaired higher-level functional capacity based on total score of the Tokyo Metropolitan Institute of Gerontology Index of Competence was significantly associated with stroke (hazard ratio, 1.64; 95% confidence interval, 1.15-2.33). Among the 3 subscales, only intellectual activity was significantly associated with stroke (hazard ratio, 1.64; 95% confidence interval, 1.21-2.22). Social role was significantly associated with stroke only among those aged ≥75 years (hazard ratio, 1.78; 95% confidence interval, 1.07-2.98)., Conclusions: Impaired higher-level functional capacity, especially in the domain of intellectual activity, was a predictor of stroke, even among community-dwelling older adults with independent basic activities of daily living at baseline. Monitoring of higher-level functional capacity might be useful to detect those at higher risk of developing stroke in the future., (© 2016 American Heart Association, Inc.)

Background: Few studies have investigated functional capacity self-assessment tools in either prediction of future major adverse cardiac outcomes beyond all-cause mortality or direct comparisons with clinically available biomarkers., Methods and Results: We estimated functional capacity using the Duke Activity Status Index (DASI) questionnaire in 8987 sequential stable patients without acute coronary syndrome who were undergoing elective diagnostic coronary angiography with 3-year follow-up of major adverse cardiac events (death, nonfatal myocardial infarction, or stroke). A low DASI score provided independent prediction of a 4.8-fold increase in future risk of incident major adverse cardiac events at 3 years (quartiles 1 versus 4 hazard ratio [95% CI] 4.76 [4.03 to 5.61], P<0.001), and a 3.8-fold increased risk after adjusting for traditional risk factors (3.77 [3.15 to 4.51], P<0.001). The prognostic value of the DASI score was evident in both primary and secondary prevention cohorts, with and without heart failure, as well as high and low C-reactive protein and B-type natriuretic peptide levels. The DASI score reclassified 15% of patients (P<0.001) beyond traditional risk factors in predicting future MACE., Conclusion: A simple self-assessment tool of functional capacity in stable patients undergoing elective diagnostic cardiac evaluation provides independent and incremental prognostic value for prediction of both significant coronary angiographic disease and long-term adverse clinical events., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)