A Nonexercise Estimate of Cardiorespiratory Fitness Using a Symptom Questionnaire and Clinical Variables.

PURPOSE: Cardiorespiratory fitness (CRF) has recently been recognized as a risk factor for mortality, but it is not routinely measured in clinical settings. The purpose of this study was to assess a nonexercise method to estimate CRF (eCRF) and its association with mortality in a clinically referred population. METHODS: A symptom tool, termed the Veterans Specific Activity Questionnaire (VSAQ), and nonexercise clinical variables were obtained from 1545 clinically referred subjects (60 ± 13 yr), and followed for a mean of 5.6 ± 4.2 yr. The VSAQ along with nonexercise clinical and historical variables was used to develop a multivariate model to predict achieved CRF from maximal exercise testing. Proportional hazards analysis was used to assess the association between measured and eCRF and all-cause mortality. RESULTS: The eCRF model was significantly associated with achieved CRF (multiple R = 0.67, P < .001). Mean achieved CRF from maximal treadmill testing and eCRF were similar (8.6 ± 5.0 metabolic equivalents [METs] vs 8.7 ± 4.7 METs respectively, P = .27). Achieved CRF and eCRF performed similarly for predicting mortality. After full adjustment, each 1 MET higher increment in achieved CRF and eCRF was associated with 19% and 26% reductions in mortality risk, respectively. Compared with the lowest fit group (<5 METs), the highest CRF groups (>11 METs) had 88% and 87% lower risks for mortality for achieved CRF and eCRF, respectively. CONCLUSIONS: A multivariable nonexercise model featuring a symptom questionnaire combined with clinical variables that are readily available during a typical clinical encounter had a reasonably strong association with achieved CRF and exhibited prognostic characteristics that were similar to achieved CRF.

Physical Activity, Cardiorespiratory Fitness, and Population-Attributable Risk.

OBJECTIVE: To determine population-attributable risk (PAR) and exposure impact number (EIN) for mortality associated with impaired cardiorespiratory fitness (CRF), physical inactivity, and other risk markers among veteran subjects. METHODS: The sample included 5890 male subjects (mean age 58±15) who underwent a maximal exercise test for clinical reasons between January 1, 1992, and December 31, 2014. All-cause mortality was the end point. Cox multivariable hazard models were performed to determine clinical, demographic, and exercise-test determinants of mortality. Population-attributable risks and EIN for the lowest quartile of CRF and for inactive behavior were analyzed, accounting for competing events. RESULTS: There were 2728 deaths during a mean ± standard deviation follow-up period of 9.9±5.8 years. Having low CRF (<5.0 metabolic equivalents [METs]) was associated with an approximate 3-fold higher risk of mortality and a PAR of 12.9%. Each higher MET achieved on the treadmill was associated with a 15% reduction in mortality (hazard ratio [HR]=0.85; 95% confidence interval [CI], 0.83 to 0.88; P<.001). Nearly half the sample was inactive, and these subjects had a 23% higher mortality risk and a PAR of 8.8%. The least fit quartile (<5.0 METs) had relative risks of ≈6.0 compared with the most-fit group (HR=5.99; 95% CI, 4.9 to 7.3). The least-active tertile had ≈2-fold higher risks of mortality vs the most active subjects (HR=1.9; 95% CI, 0.91 to 4.1). The lowest EIN was observed for low fitness (3.8; 95% CI, 3.4 to 4.3, P<.001), followed by diabetes, smoking, hypertension, and physical inactivity (all P<.001 except for diabetes, P=.008). CONCLUSION: Both higher CRF and physical activity provide protection against all-cause mortality in subjects referred for exercise testing for clinical reasons. Encouraging physical activity with the aim of increasing CRF would have a significant impact on reducing mortality.

Exercise blood pressure, cardiorespiratory fitness and mortality risk.

OBJECTIVE: To assess the cardiorespiratory fitness (CRF) impact on the association between exercise blood pressure (BP) and mortality risk. PATIENTS AND METHODS: We assessed CRF in 15,004 US Veterans (mean age 57.5 ± 11.2 years) who completed a standardized treadmill test between January 1, 1988 and July 28, 2017 and had no evidence of ischemia. They were classified as Unfit or Fit according to the age-specific metabolic equivalents (METs) achieved <50% (6.2 ± 1.6 METs; n = 8440) or ≥ 50% (10.5 ± 2.4 METs; n = 6264). To account for the impact of resting systolic BP (SBP) on outcomes, we calculated the difference (Peak SBP-Resting SBP) and termed it SBP-Reserve. We noted a significant increase in mortality associated with SBP-Reserve ≤52 mmHg and stratified the cohort accordingly (SBP-Reserve ≤52 mmHg and > 52 mmHg). We applied multivariable Cox models to estimate hazard ratios (HR) and 95% confidence interval (CIs) for outcomes. RESULTS: Mortality risk was significantly elevated only in Unfit individuals with SBP-Reserve ≤52 mmHg compared to those with SBP-Reserve >52 mmHg (HR = 1.35; CI: 1.24-1.46; P < 0.001). We then assessed the CRF and SBP-Reserve interaction on mortality risk with Fit individuals with SBP-Reserve >52 mmHg serving as the referent. Mortality risk was 92% higher (HR = 1.92%; 95% CI: 1.77-2.09; P < 0.001) in Unfit individuals with SBP-Reserve ≤52 mmHg and 47% higher (HR = 1.47; 95% CI: 1.33-1.62; P < 0.001) in those with SBP-Reserve >52 mmHg. CONCLUSION: Low CRF was associated with increased mortality risk regardless of peak exercise SBP. The risk was substantially higher in individuals unable to augment their exercise SBP >52 mmHg beyond resting levels.

Association between cardiorespiratory fitness, obesity, and incidence of atrial fibrillation.

BACKGROUND: The interaction between cardiorespiratory fitness (CRF) and incidence of atrial fibrillation (AF) and the interaction between obesity and incidence of AF have been explored separately. Therefore, we evaluated the association between CRF, body mass index (BMI), and risk of developing AF in a cohort of middle-aged and older US Veterans. METHODS: Symptom limited exercise tests (ETT) were conducted among 16,397 Veterans (97% male) from January 9,1987 to December 31,2017. No history of AF was evident at the time of the ETTs. CRF was expressed as quartiles of peak metabolic equivalents (METs) achieved within each age decile. Weight status was classified as normal (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2), obese (BMI 30-35 kg/m2), or severely obese (BMI > 35 kg/m2). Multivariable Cox proportional hazards regression models were used to compare the association between BMI, CRF categories, and incidence of AF. RESULTS: Over a median follow-up of 10.7 years, 2,155 (13.1%) developed AF. Obese and severely obese subjects had 13% and 32% higher risks for incidence of AF, respectively, vs. normal weight subjects. Overweight and obese subjects in the most fit quartile had 50% decline in AF risk compared to the least-fit subjects. Severely obese subjects had marked increases in AF risk (~50-60%) regardless of fitness level. Risk of developing AF increases with higher BMI and lower CRF. CONCLUSION: Improving CRF should be advocated when assessing those at risk for developing AF.

Cardiorespiratory Fitness and Health Care Costs in Diabetes: The Veterans Exercise Testing Study.

BACKGROUND: This study aimed to determine the association between cardiorespiratory fitness and healthcare expenditures among individuals with and without diabetes. METHODS: Health care costs were quantified among 3924 consecutive men (mean age 58 ± 11 years) referred for a maximal exercise test, and compared according to presence (n = 2457) and absence (n = 1467) of diabetes and fitness. Fitness was classified into 4 categories based on age-stratified quartiles of peak metabolic equivalents: least-fit (5.1 ± 1.5 metabolic equivalents; n = 1044), moderately-fit (7.6 ± 1.5 metabolic equivalents; n = 938), fit (9.4 ± 1.5 metabolic equivalents; n = 988), and highly-fit (12.4 ± 2.2 metabolic equivalents; n = 954). Annual costs per subject were quantified over an 8-year period. RESULTS: Age, BMI, and presence of cardiovascular disease (CVD) were similar between subjects with and without diabetes. After adjusting for age and presence of CVD, annual costs per person were higher among diabetics vs. non-diabetics. Individuals with and without diabetes in the highly-fit category had annual costs (US dollars x 103) (mean ± standard deviation) that were on average $32,178 and $30,816 lower, respectively, than individuals in the least-fit category. For each 1-metabolic equivalent higher fitness, annual cost savings per person were $5,193 and $3,603 for individuals with and without diabetes, respectively. CONCLUSIONS: Higher fitness is associated with lower health care costs. Cost savings associated with higher fitness are particularly evident among individuals with diabetes. The economic burden of diabetes may be reduced through interventions that target improvements in fitness.

How Do Physical Activity and Health Vary Among Younger, Middle-Aged, and Older Adults With and Without Disability?

Physical activity (PA) and health were compared in younger (YA; 18-44 years), middle-aged (MA; 45-64 years), and older (OA; ≥65 years) adults with disability (PWD), functional limitation (PFL), or without disability (PWoD). Disability occurred in YA (PWD: 2.3%; PFL: 14.3%), MA (PWD: 8.5%; PFL: 23.8%), and OA (PWD: 14.9%; PFL: 26.6%). Not meeting aerobic/muscle-strengthening PA recommendations was frequent in YA (PWD: 50.7%; PFL: 42.5%; PWoD: 35.8%), MA (PWD: 56.7%; PFL: 44.0%; PWoD: 35.6%), and OA (PWD: 57.8%; PFL: 44.1%; PWoD: 33.1%). Among PWD, YA and MA met muscle, strengthening recommendations more frequently than did OA; PFL did more aerobic PA than PWD. The presence of chronic diseases, female gender, White race, lower education, and less income were associated with being PWD or PFL. Those with greater PA were less likely to be PWD or PFL. Results suggest increasing public health efforts to promote healthy lifestyles in MA and OA.

Single-Blind, Randomized, Controlled Clinical Trial of Exercise in Ambulatory Spinal Muscular Atrophy: Why are the Results Negative?

BACKGROUND: The benefits of exercise on long-term health and well-being are well established. The possible benefits of exercise in Spinal Muscular Atrophy (SMA) have not been explored in a controlled clinical trial format. OBJECTIVE: To assess the effects of exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients. METHODS: Fourteen participants, ages 10-48 years, were randomized to control and exercise cohorts after a 1 month lead-in period. The exercise group received 6 months of intervention. Thereafter, both groups received the intervention for the remaining 12 months. Participants were monitored for a total of 19 months. Exercise included individualized home-based cycling and strengthening. The primary outcome measure was distance walked during the six-minute walk test (6MWT). Secondary outcomes included strength, function, exercise capacity, quality of life and fatigue. RESULTS: Twelve participants completed the first 7 months of the study, and 9 completed all 19 months. At baseline, the groups were similar on all clinical variables. There were no group changes at any time point in the 6MWT, fatigue, or function. Percent-predicted VO2 max improved 4.9% in all participants in 6 months (p = 0.036) (n = 10). CONCLUSION: Daily exercise is safe in ambulatory SMA and should be encouraged. We did not uncover any deleterious effects on strength, function, or fatigue. Our study documented a reduction in oxidative capacity and a blunted conditioning response to exercise possibly representing an important insight into underlying pathophysiological mechanisms. These findings also may be linked causally to mitochondrial depletion in SMA and warrant further study.

A Randomized, Controlled Clinical Trial of Exercise in Patients with Spinal Muscular Atrophy: Methods and Baseline Characteristics.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a recessively-inherited neuromuscular disease characterized by weakness and muscle atrophy. Although anecdotal benefits from exercise have been noted, and despite promising pre-clinical and pilot reports, the effect of exercise has not been addressed in a controlled trial in SMA. OBJECTIVE: To assess the effects of exercise on measures of function, strength, and exercise capacity in ambulatory SMA patients. METHODS/DESIGN: An evaluator-blinded, randomized, controlled trial of aerobic and strengthening exercise in 14 ambulatory SMA patients aged 8-50 years. Patients will be randomized to either the exercise or control arm after the 1 month lead in period. During the first 6-months, the exercise group will receive the intervention while the other group serves as a control. After those 6 months, both groups will receive the intervention. The last 6-months of the study are designed to mimic real-world conditions where all participants are encouraged to continue on their own. Participants will be monitored throughout this 19 month study and will have in-person visits every three months. The primary outcome measure is the change in the total distance walked over 6-months on the six minute walk test (6MWT). Secondary outcome measures include maximal oxygen uptake (VO2 max), functional and strength assessments, pulmonary function, fatigue, and quality of life. DISCUSSION: The result of this prospective, single blinded, randomized and controlled clinical trial of exercise on an established functional outcome measure will have impact on clinical practice by providing important guidance to clinical management of SMA patients.

Performance of the timed "up & go" test in spinal muscular atrophy.

INTRODUCTION: The timed "up & go" (TUG) test is a quick measure of balance and mobility. TUG scores correlate with clinical, functional, and strength assessment and decline linearly over time. Reliability and validity have not been tested in spinal muscular atrophy (SMA). METHODS: Fifteen ambulatory SMA participants performed TUG testing and strength, functional, and clinical assessments. Intraclass correlation coefficients quantified test-retest reliability. Convergent validity was determined using Pearson correlation coefficients. RESULTS: Test-retest reliability was excellent for all participants. TUG was associated significantly with total leg and knee flexor strength, as well as the Hammersmith Functional Motor Scale Expanded, the 10-meter walk/run, and 6-minute walk tests. TUG findings were not associated with knee extensor strength, pulmonary function, or fatigue. CONCLUSIONS: In SMA, the TUG test is easily administered, reliable, and correlates with established outcome measures. TUG testing is a potentially useful outcome measure for clinical trials and a measure of disability in ambulatory patients with SMA.

Falls and spinal muscular atrophy: exploring cause and prevention.

INTRODUCTION: Falls can cause injury and may compromise function in spinal muscular atrophy (SMA) patients. Weakness and gait variability are associated with falls in other neurological disorders, and fatigue is well documented in SMA. The relationship of weakness, fatigue, and gait variability to falls has never been investigated. METHODS: Seven ambulatory patients with SMA completed a falls history questionnaire, 6MWT, gait analysis, and strength testing. Pearson correlation coefficients were used to examine associations between these variables. RESULTS: All 7 subjects reported falls in the previous year. Stride-length variability was significantly associated with falls, unlike strength, fatigue, or other gait variables. CONCLUSIONS: Stride-length variability was the key variable associated with falls. Preventive strategies to avoid falls should be incorporated into patient management plans. Gait analysis provides actionable information not revealed by standard assessments and should be included in clinical trials designed to address the prevention of falls in the SMA population.