Association of Changes in Physical Activity and Adiposity With Mortality and Incidence of Cardiovascular Disease: Longitudinal Findings From the UK Biobank

ObjectiveTo examine the association of changes in physical activity and adiposity with all-cause mortality and incident cardiovascular disease (CVD).MethodsPhysical activity, body mass index (BMI), body fat percentage, waist circumference, and waist to hip ratio changes were categorized on the basis of public health and clinical guidelines. Among 29,610 participants (mean ± SD follow-up, 5.1±2.1 years), 545 deaths and 2970 CVD events occurred. Participants were observed from baseline (March 13, 2006, to October 10, 2010) and follow-up (August 1, 2012 to November 9, 2018) assessment through March 31, 2021.ResultsCompared with stable-insufficient physical activity, increasing physical activity to meet guidelines at follow-up was associated with lower all-cause mortality (hazard ratio, 0.64 [0.49 to 0.85]) and CVD (0.83 [0.72 to 0.96]) risk. This risk was similar to that of those who achieved physical activity guidelines at both time points (all-cause mortality, 0.74 [0.60 to 0.92]; CVD, 0.88 [0.79 to 0.99]). For obese and overweight participants, decreasing BMI category was associated with a lower CVD risk (0.70 [0.47 to 1.04]) similar to the risk of those who had a healthy weight at both time points (0.85 [0.76 to 0.96]). In the joint analyses, the only combination that lowered all-cause mortality and CVD risk was physical activity increase and adiposity decrease over time (eg, CVD risk: BMI, 0.64 [0.42 to 0.96]; body fat percentage, 0.76 [0.55 to 0.97]; waist circumference, 0.66 [0.48 to 0.89]; waist to hip ratio, 0.78 [0.62 to 0.97]) compared with the reference group (stable physical activity and adiposity).ConclusionIncreases in physical activity to meet guidelines lowered all-cause mortality and CVD risk equal to that of those who continually met guidelines. The risk was effectively eliminated in those who had concurrent adiposity decrease.     

Physical Activity and Mortality Across Levels of Adiposity: A Prospective Cohort Study From the UK Biobank

ObjectiveTo examine the combined and stratified associations of physical activity and adiposity measures, modelled as body mass index (BMI), abdominal adiposity (waist circumference), and body fat percentage (BF) with all-cause mortality.Patients and MethodsUsing the UK Biobank cohort, we extracted quintiles of self-reported weekly physical activity. Categories of measured BMI, waist circumference, and BF were generated. Joint associations between physical activity-adiposity categories and mortality were examined using Cox proportional hazards models adjusted for demographic, behavioral, and clinical covariates. Physical activity-mortality associations were also examined within adiposity strata. Participants were followed from baseline (2006 to 2010) through January 31, 2018.ResultsA total of 295,917 participants (median follow-up, 8.9 years, during which 6684 deaths occurred) were included. High physical activity was associated with lower risk of premature mortality in all strata of adiposity except for those with BMI ≥35 kg/m². Highest risk (HR, 1.54; 95% CI; 1.33 to 1.79) was observed in individuals with low physical activity and high BF as compared with the high physical activity–low BF referent. High physical activity attenuated the risk of high adiposity when using BF (HR, 1.24; 95% CI; 1.04 to 1.49), but the association was weaker with BMI (HR, 1.45; 95% CI; 1.21 to 1.73). Physical activity also attenuated the association between mortality and high waist circumference.ConclusionLow physical activity and adiposity were both associated with a higher risk of premature mortality, but high physical activity attenuated the increased risk with adiposity irrespective of adiposity metric, except in those with a BMI ≥35 kg/m².     

Comparative Relevance of Physical Fitness and Adiposity on Life Expectancy: A UK Biobank Observational Study

ObjectiveTo investigate the extent to which 2 measures of physical fitness—walking pace and handgrip strength—are associated with life expectancy across different levels of adiposity, as the relative importance of physical fitness and adiposity on health outcomes is still debated.Patients and MethodsUsual walking pace (self-defined as slow, steady/average, brisk), dynamometer-assessed handgrip strength, body mass index (BMI), waist circumference, and body-fat percentage determined at baseline in the UK Biobank prospective cohort study (March 13, 2006, to January 31, 2016). Life expectancy was estimated at 45 years of age.ResultsThe median age and BMI of the 474,919 participants included in this analysis were 58.2 years and 26.7 kg/m², respectively; over a median follow-up of 6.97 years, 12,823 deaths occurred. Participants reporting brisk walking pace had longer life expectancies across all levels of BMIs, ranging from 86.7 to 87.8 years in women and 85.2 to 86.8 years in men. Conversely, subjects reporting slow walking pace had shorter life expectancies, being the lowest observed in slow walkers with a BMI less than 20 kg/m² (women: 72.4 years; men: 64.8 years). Smaller, less consistent differences in life expectancy were observed between participants with high and low handgrip strength, particularly in women. The same pattern of results was observed for waist circumference or body-fat percentage.ConclusionBrisk walkers were found to have longer life expectancies, which was constant across different levels and indices of adiposity. These findings could help clarify the relative importance of physical fitness and adiposity on mortality.     

Association of Self-reported Walking Pace With Type 2 Diabetes Incidence in the UK Biobank Prospective Cohort Study

ObjectiveTo investigate the association between self-reported walking pace and type 2 diabetes (T2D) incidence and whether it differed by physical activity levels and walking time.MethodsThere were 162,155 participants (mean age, 57.1 years; 54.9% women) from the UK Biobank prospective study, recruited between 2006 and 2010, included in the study. Walking pace was self-reported and classified as brisk, average, or slow. Total physical activity and walking time were self-reported using the International Physical Activity Questionnaire. Association between walking pace and T2D incidence and the potential moderating role of physical activity and walking time were investigated using Cox proportional hazards models.ResultsThe median follow-up was 7.4 (interquartile range, 6.7 to 8.2) years. There were 4442 participants in whom T2D developed during the follow-up period. In the fully adjusted model (sociodemographic factors, diet, body mass index, and physical activity), average walking pace (hazard ratio [HR], 1.28; 95% CI, 1.14 to 1.44) and slow walking pace (HR, 1.91; 95% CI, 1.62 to 2.24) were associated with a higher T2D risk compared with brisk walking among women. Among men, average walking pace (HR, 1.28; 95% CI, 1.17 to 1.40) and slow walking pace (HR, 1.73; 95% CI, 1.50 to 1.99) were also associated with higher T2D risk. Compared with slow walkers, brisk walkers have the same diabetes incidence rate 18.6 and 16.0 years later, for women and men, respectively.ConclusionAverage and slow walking pace was associated with a higher risk of incident T2D in both men and women, independent of major confounding factors. The associations were consistent across different physical activity levels and walking time.     

DXA Versus Clinical Measures of Adiposity as Predictors of Cardiometabolic Diseases and All-Cause Mortality in Postmenopausal Women

ObjectiveTo investigate whether dual-energy x-ray absorptiometry (DXA) estimates of adiposity improve risk prediction for cardiometabolic diseases over traditional surrogates, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) in older women.Patients and MethodsWe analyzed up to 9744 postmenopausal women aged 50 to 79 years participating in the Women’s Health Initiative who underwent a DXA scan and were free of cardiovascular disease and diabetes at baseline (October 1993 to December 1998) and followed through September 2015. Baseline BMI, WC, WHR, and DXA-derived percent total-body and trunk fat (%TrF) were incorporated into multivariable Cox proportional hazards models to estimate the risk of incident diabetes, atherosclerosis-related cardiovascular diseases (ASCVDs), heart failure, and death. Concordance probability estimates assessed the relative discriminatory value between pairs of adiposity measures.ResultsA total of 1327 diabetes cases, 1266 atherosclerotic cardiovascular disease (ASCVD) cases, 292 heart failure cases, and 1811 deaths from any cause accrued during a median follow-up of up to 17.2 years. The largest hazard ratio observed per 1 standard deviation increase of an adiposity measure was for %TrF and diabetes (1.77; 95% CI, 1.66-1.88) followed by %TrF and broadly defined ASCVD (1.22; 95% CI, 1.15-1.30). These hazard ratios remained significant for both diabetes (1.47; 95% CI, 1.37-1.57) and ASCVD (1.22; 95% CI, 1.14-1.31) even after adjusting for the best traditional surrogate measure of adiposity, WC. Percentage of trunk fat was also the only adiposity measure to demonstrate statistically significant improved concordance probability estimates over BMI, WC, and WHR for diabetes and ASCVD (all P<0.05).ConclusionDXA-derived estimates of abdominal adiposity in postmenopausal women may allow for substantially improved risk prediction of diabetes over standard clinical risk models. Larger DXA studies with complete lipid biomarker profiles and clinical trials are needed before firm conclusions can be made.     

Artificial Intelligence Application in Graves Disease: Atrial Fibrillation,Heart Failure and Menstrual Changes

ObjectiveTo study the utility of artificial intelligence (AI)–enabled electrocardiograms (ECGs) in patients with Graves disease (GD) in identifying patients at high risk of atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF), and to study whether AI-ECG can reflect hormonal changes and the resulting menstrual changes in GD.Patients and MethodsPatients diagnosed with GD between January 1, 2009, and December 31, 2019, were included. We considered AF diagnosed at 30 days or fewer before or any time after GD and de novo HFrEF not explained by ischemia, valve disorder, or other cardiomyopathy at/after GD diagnosis. Electrocardiograms at/after index condition were excluded. A subset analysis included females younger than 45 years of age to study the association between ECG-derived female probability and menstrual changes (shorter, lighter, or newly irregular cycles).ResultsAmong 430 patients (mean age, 50±17 years; 337 (78.4%) female), independent risk factors for AF included ECG probability of AF (hazard ratio [HR], 1.5; 95% CI, 1.2 to 1.6 per 10%; P<.001), older age (HR, 1.05; 95% CI, 1.03 to 1.07 per year; P<.001), and overt hyperthyroidism (HR, 3.9; 95% CI, 1.2 to 12.7; P=.03). The C-statistic was 0.85 for the combined model. Among 495 patients (mean age, 52±17 years; 374 (75.6%) female), independent risk factors for HFrEF were ECG probability of low ejection fraction (HR, 1.4; 95% CI, 1.1 to 1.6 per 10%; P=.001) and presence of AF (HR, 8.3; 95% CI, 2.2 to 30.9; P=.002), and a C-statistic of 0.89 for the combined model. Lastly, of 72 females younger than 45 years, 30 had menstrual changes at time of GD and had a significantly lower AI ECG–derived female probability [median 77.3; (IQR 57.9 to 94.4)% vs. median 97.7 (IQR 92.4 to 99.5)%, P<.001].ConclusionAI-enabled ECG identifies patients at risk for GD-related AF and HFrEF and was associated with menstrual changes in women with GD.     

Gait- and Posture-Related Factors Associated With Changes in Hip Pain and Physical Function in Patients With Secondary Hip Osteoarthritis: A Prospective Cohort Study

ObjectiveTo identify gait- and posture-related factors associated with changes in hip pain and physical function in patients with hip osteoarthritis (OA).DesignProspective cohort study.SettingClinical biomechanics laboratory of a university.ParticipantsConsecutive sampling of female patients with mild-to-moderate secondary hip OA (N=30).Main Outcome MeasuresHip pain (visual analog scale) and physical function (physical component summary of the Medical Outcomes Study 36-Item Short-Form Health Survey) were measured at baseline and 12 months later. With changes in hip pain and physical function as dependent variables, linear regression analyses were performed with gait- and posture-related factors as independent variables with and without adjustment for age, joint space width, and hip pain or physical function at baseline. Posture-related factors included angles of thoracic kyphosis, lumbar lordosis, sacral inclination, spinal inclination, and spinal mobility. Gait-related factors were walking speed, steps per day, joint angles, external hip joint moment impulses, and daily cumulative hip moments.ResultsMultiple linear regression analyses showed that limited hip extension (adjusted standardized B coefficient [95% confidence interval]: −0.52 [−0.88 to −0.17]) and limited external rotation angles (−0.51 [−0.85 to −0.18]) during walking were associated with the worsening of hip pain. An increased thoracic kyphosis (−0.54 [−0.99 to −0.09]), less sacral anterior tilt (0.40 [0.01-0.79]), reduced thoracic spine mobility (0.59 [0.23-0.94]), less steps per day (0.53 [0.13-0.92]), and a slower walking speed (0.45 [0.04-0.86]) were associated with deterioration in physical function.ConclusionsGait- and posture-related factors should be considered when assessing risk and designing preventive interventions for the clinical progression of secondary hip OA.     

Association of Therapy Time Per Day With Functional Outcomes and Rate of Recovery in Older Adults After Elective Joint Replacement Surgery

ObjectivesTo explore the association between therapy minutes per length of stay (LOS) day (TMLD), functional outcomes, and rate of functional recovery among older adults after elective hip or knee replacement surgery across postacute (PAC) settings.DesignSecondary analysis of data collected for an observational cohort study from 2005 to 2010.SettingFour inpatient rehabilitation facilities (IRF) and 7 skilled nursing facilities (SNF).ParticipantsAdults aged 65 years or older (N=162) with Medicare fee-for-service insurance and a primary diagnosis of elective hip or knee replacement.InterventionsNot applicable.Main Outcome MeasuresFIM mobility and self-care measures at discharge.ResultsThe TMLD was divided into high, medium, and low categories. Participants were grouped into low, medium, and high gain rate groups based on their average change in mobility and self-care FIM measures per LOS day. Gain rate and TMLD groups were crossmapped to create 9 gain-TMLD groups separately for mobility and self-care. There were no significant differences in admission mobility or self-care measures by gain rate and TMLD trajectory or by facility type (IRF or SNF). TMLD was not significantly associated with discharge mobility measures. Participants in high gain trajectories attained independence with mobility and self-care tasks at discharge regardless of TMLD. Those in low gain trajectories needed supervision or assistance on all mobility tasks. Older age and greater pain at discharge were significantly associated with lower odds of being in the medium or high gain rate groups.ConclusionsFor clinicians and facility managers who must care for patients with constrained resources, the shift to value-based reimbursement for rehabilitation services in PAC settings has reinvigorated the question of whether the duration of therapy provided influences patient outcomes. Three hours of daily therapy after joint replacement surgery may exceed what is necessary for recovery. Postsurgical pain management remains a significant challenge in older adults.     

A Longitudinal Study Exploring Learning Environment Culture and Subsequent Risk of Burnout Among Resident Physicians Overall and by Gender

ObjectiveTo explore the relationship between learning environment culture and the subsequent risk of developing burnout in a national sample of residents overall and by gender.MethodsFrom April 7 to August 2, 2016, and May 26 to August 5, 2017, we surveyed residents in their second (R2) and third (R3) postgraduate year. The survey included a negative interpersonal experiences scale (score range 1 to 7 points, higher being worse) assessing psychological safety and bias, inclusion, respect, and justice; an unfair treatment scale (score range 1 to 5 points, higher being worse), and two items from the Maslach Burnout Inventory. Individual responses to the R2 and R3 surveys were linked.ResultsThe R2 survey was completed by 3588 of 4696 (76.4%) residents; 3058 of 3726 (82.1%) residents completed the R3 survey; and 2888 residents completed both surveys. Women reported more negative interpersonal experiences (mean [SD], 3.00 [0.83] vs 2.90 [0.85], P<.001) and unfair treatment (66.5% vs. 58.7%, P<.001) than men at R2. On multivariable analysis, women at R3 were more likely than their male counterparts to have burnout (odds ratio, 1.23; 95% CI, 1.02 to 1.48; P=.03). Both men and women who reported more negative interpersonal experiences at R2 were more likely to have burnout at R3 (odds ratio, 1.32; 95% CI, 1.14 to 1.52; P<.001). The factors contributing to burnout did not vary in effect magnitude by gender.ConclusionThese findings indicate women residents are more likely to have burnout relative to men in the third year of residency. Negative culture predicted subsequent burnout 1 year later among both men and women. Differences in burnout were at least partly due to differing levels of exposure to negative interactions for men versus women rather than a negative interaction having a differential impact on the well-being of men versus women.     

Sex Differences in Outcomes of Patients With Chronic Aortic Regurgitation: Closing the Mortality Gap

ObjectiveTo examine contemporary clinical differences between men and women with hemodynamically significant chronic aortic regurgitation (AR).Patients and MethodsWe retrospectively identified 1072 consecutive patients with moderate to severe or severe AR diagnosed between February 21, 2004, and April 29, 2019. Echocardiographic data, aortic valve surgical intervention (AVS), and all-cause death were analyzed.ResultsAt baseline, the 189 women in the study group were older than the 883 men (mean ± SD age, 64±18 years vs 58±17 years), had more advanced symptoms, and had larger left ventricular end-systolic dimension index (LVESDi) (all P<.001) despite similar AR severity. An LVESDi of greater than 20 mm/m² was noted in 60 of 92 asymptomatic women (65%) vs 225 of 559 asymptomatic men (40%) (P<.001). Median follow-up was 5.6 years (interquartile range, 2.5 to 10.0 years). Female sex was associated with less AVS (P=.009), and overall 10-year survival was better in men (76%±2%) than in women (64%±5%) (P=.004). However, 10-year post-AVS survival was similar between the sexes (P=.86), and women had better left ventricular reverse remodeling than men regarding end-diastolic dimension (P=.02). Multivariable independent predictors of death were age, advanced symptoms, LVESDi, ejection fraction, and AVS (all P≤.03) but not female sex. When compared with the age-matched US population, women exhibited a 1.3-fold increased relative risk of death (P=.0383) while men had similar survival (P=.11).ConclusionIn contemporary practice, women with AR continue to exhibit an overall survival penalty not related to female sex but to late referral markers, including more advanced symptoms, larger LVESDi, and less AVS. Nonetheless, women in our study exhibited outstanding post-AVS left ventricular remodeling and had good post-AVS survival, a step forward toward closing the sex-related mortality gap. The high percentage of LVESDi of 20 mm/m² or greater in asymptomatic women represents a window of opportunity for advanced-symptom prevention and timely AR surgical correction that may close the mortality gap.     

Inverse Association of Handgrip Strength With Risk of Heart Failure

ObjectiveTo evaluate the nature, magnitude, and specificity of the association between handgrip strength (HGS) and heart failure (HF) risk.Patients and MethodsHandgrip strength was assessed at baseline from March 1, 1998, to December 31, 2001, by use of a hand dynamometer in the Finnish Kuopio Ischemic Heart Disease prospective population-based cohort of 770 men and women aged 61 to 74 years without a history of HF. Relative HGS was obtained by dividing the absolute value by body weight. Hazard ratios (HRs) with 95% CIs were estimated with Cox regression models. We used multiple imputation to account for missing data.ResultsDuring a median (interquartile range) follow-up of 17.1 (11.3-18.3) years, 177 HF events were recorded. Handgrip strength was continually associated with risk of HF, consistent with a curvilinear shape. On adjustment for several established risk factors and other potential confounders, the HR (95% CI) for HF was 0.73 (0.59-0.91) per 1 SD increase in relative HGS. Comparing the top vs bottom tertiles of relative HGS, the corresponding adjusted HR was 0.55 (0.38-0.81). The association remained similar across several clinical subgroups. Imputed results were broadly similar to the observed results.ConclusionRelative HGS is inversely and continually associated with the future risk of HF in the general population. Studies are warranted to evaluate whether HGS may be a useful prognostic tool for HF in the general population and to determine whether resistance exercise training may lower the risk of HF.     

High-Intensity Interval Training in Cardiac Rehabilitation: Impact on Fat Mass in Patients With Myocardial Infarction

ObjectiveTo examine the effect of high-intensity interval training (HIIT) on body fat mass and distribution in patients with myocardial infarction (MI) who underwent cardiac rehabilitation (CR).Patients and MethodsWe retrospectively screened 391 consecutive patients with MI enrolled in CR between September 1, 2015, and February 28, 2018. We included 120 patients who completed 36 CR sessions and underwent pretest-posttest dual-energy x-ray absorptiometry; 90 engaged in HIIT, and 30 engaged in moderate-intensity continuous training (MICT). High-intensity interval training included 4 to 8 alternating intervals of high- (30-60 seconds at a rating of perceived exertion [RPE] of 15-17 [Borg scale range, 6-20]) and low-intensity (1-5 minutes at RPE <14), and MICT performed for 20 to 45 minutes of exercise at an RPE of 12 to 14. Body weight, fat mass, and lean mass were measured via dual-energy x-ray absorptiometry with lipid profile measured via clinical procedures.ResultsThe HIIT and MICT groups were similar in age (67 vs 67 years), sex (26.7% [24 of 90 patients in the HIIT group] vs 26.7% [8 of 30 in the MICT group), and body mass index (30.3 vs 29.5 kg/m²) at baseline. The HIIT group had greater reductions in body fat percentage (P<.001), fat mass (P<.001), abdominal fat percentage (P<.001), waist circumference (P=.01), total cholesterol (P=.002), low-density lipoprotein cholesterol (P<.001), and triglycerides (P=.006). Improvements in total body mass and body mass index were not different across groups. After matching exercise duration, exercise intensity, and energy expenditure, HIIT-induced improvements in total fat mass (P=.02), body fat percentage (P=.01), and abdominal fat percentage (P=.02) persisted.ConclusionOur data suggest that supervised HIIT results in significant reductions in total fat mass (P<.001) and abdominal fat percentage (P<.001) and improved lipid profile in patients with MI who undergo CR.     

Osteoporosis and Its Association With Cardiovascular Disease,Respiratory Disease,and Cancer: Findings From the UK Biobank Prospective Cohort Study

ObjectiveTo investigate sex-specific associations of osteoporosis with incidence of and mortality from cardiovascular disease (CVD), respiratory disease, and cancer as well as with all-cause mortality.MethodsIn total, 305,072 participants (53% [161,383] women) of UK Biobank were included in this study (2007-2010). Self-reported diagnosis of osteoporosis at baseline was the exposure of interest. The outcomes were CVD, respiratory disease, chronic obstructive pulmonary disease (COPD), all cancer, and prostate and breast cancer incidence and mortality and all-cause mortality. Associations between osteoporosis and outcomes were investigated using Cox proportional hazards models.ResultsIn men, osteoporosis was associated with a higher incident risk of all respiratory diseases (hazard ratio [HR], 1.26; 95% CI, 1.06 to 1.50) including COPD (HR, 1.82; 95% CI, 1.38 to 2.40). Men with osteoporosis also had a higher mortality risk from all causes (HR, 1.71; 95% CI, 1.38 to 2.11), CVD (HR, 1.68; 95% CI, 1.19 to 2.37), respiratory disease (HR, 2.35; 95% CI, 1.70 to 3.24), and COPD (HR, 3.64; 95% CI, 2.24 to 5.91). These associations persisted after adjustment for age, body mass index, and comorbidities. Women with osteoporosis had a higher risk of incident CVD (HR, 1.24; 95% CI, 1.97 to 1.44), respiratory disease (HR, 1.23; 95% CI, 1.13 to 1.33), and COPD (HR, 1.29; 95% CI, 1.10 to 1.52). Women with osteoporosis also had a higher mortality risk from respiratory disease (HR, 1.31; 95% CI, 1.00 to 1.72) and breast cancer (HR, 1.60; 95% CI, 1.14 to 2.26).ConclusionCompared with women, men with osteoporosis had a higher risk of all-cause mortality, mortality from respiratory diseases including COPD, and cancer incidence. Osteoporosis was strongly associated with respiratory disease and COPD in both sexes, even after full adjustment for covariates, although men with osteoporosis experienced a higher risk of adverse outcomes.     

Sex Differences in Management and Outcomes Among Patients With High-Risk Pulmonary Embolism: A Nationwide Analysis

ObjectiveTo examine the sex differences in management and outcomes among patients with high-risk acute pulmonary embolism (PE).Patients and MethodsThe Nationwide Readmissions Database was used to identify hospitalizations with high-risk PE from January 1, 2016, to December 31, 2018. Differences in use of advanced therapies, in-hospital mortality, and bleeding events were compared between men and women.ResultsA total of 125,901 weighted hospitalizations with high-risk PE were identified during the study period; 46.3% were women (n=58,253). Women were older and had a higher prevalence of several comorbidities and risk factors of PE such as morbid obesity, diabetes mellitus, chronic pulmonary disease, heart failure, and metastatic cancer. Systemic thrombolysis and catheter-directed interventions were more commonly used among women; however, mechanical circulatory support was less frequently used. In-hospital mortality was higher among women in the unadjusted analysis (30.7% vs 27.8%, P<.001) and after propensity score matching (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.08 to 1.25; P<.001), whereas the rates of intracranial hemorrhage and non–intracranial hemorrhage were not different. On multivariate regression analysis, female sex (OR, 1.18; 95% CI, 1.15 to 1.21; P<.001) was independently associated with increased odds of in-hospital mortality.ConclusionIn this contemporary observational cohort of patients admitted with high-risk PE, women had higher rates of in-hospital mortality despite receiving advanced therapies more frequently, whereas the rate of major bleeding events was not different from men. Efforts are needed to minimize the excess mortality observed among women.     

Lower Extremity Arterial Disease as a Predictor of Incident Atrial Fibrillation and Cardiovascular Events

ObjectiveTo evaluate the relationship between peripheral arterial disease (PAD) and incident atrial fibrillation (AF) and its clinical and pathophysiologic implications on ischemic stroke and all-cause mortality.Patients and MethodsWe identified all adult patients in the Mayo Clinic Health System without a previous diagnosis of AF undergoing ankle-brachial index (ABI) testing for any indication from January 1, 1996, to June 30, 2018. Retrospective extraction of ABI data and baseline echocardiographic data was performed. The primary outcome of interest was incident AF. The secondary outcomes of interest were incident ischemic stroke and all-cause mortality.ResultsA total of 33,734 patients were included in the study. After adjusting for demographic and comorbidity variables, compared with patients who had normal ABI (1.0 to 1.39), there was an increased risk of incident AF in patients with low ABI (<1.0) (adjusted hazard ratio, 1.14; 95% CI, 1.06 to 1.22) and elevated ABI (≥1.4) (adjusted hazard ratio, 1.18; 95% CI, 1.06 to 1.31). The risk was greater in patients with increasing severity of PAD. Patients with abnormal ABIs had an increased risk of ischemic stroke and all-cause mortality. We found that patients with PAD and incident AF have certain baseline echocardiographic abnormalities.ConclusionIn this large cohort of ambulatory patients undergoing ABI measurement, patients with PAD were at increased risk for incident AF, ischemic stroke, and mortality. In these high-risk patients with abnormal ABI, particularly severe PAD and cardiac structural abnormalities, routine monitoring for AF and management of cardiovascular risk factors may be warranted.     

Long-Term Risk of Major Adverse Cardiac Events in Atrial Fibrillation Patients on Direct Oral Anticoagulants

ObjectiveTo determine the association between direct oral anticoagulant (DOAC) use and risk of major adverse cardiac events (MACEs) in patients with atrial fibrillation (AF).Patients and MethodsThis study is a single-center prospective observational cohort study including 2366 outpatients with non-valvular AF on treatment with DOACs or vitamin K antagonists (VKAs) from February 2008 for patients on VKA and September 2013 for patients on novel oral anticoagulants. The primary endpoint was the incidence of MACE including fatal and non-fatal myocardial infarction (MI), cardiac revascularization, and cardiovascular death.ResultsThe mean age was 75.1±9.0 years; 44.7% were women. During a mean follow-up of 33.3±21.9 months (6567 patients/years) 133 MACEs occurred (2.03%/year): 79 MI/cardiac revascularization and 54 cardiovascular deaths. Of these, 101 were on VKAs (2.42%/year) and 32 on DOACs (1.34%/year; log-rank test P=.040). This difference was evident also considering MI alone (1.53%/year and 0.63%/year in the VKA and DOAC group, respectively, log-rank test P=.009). At multivariable Cox proportional hazard regression analysis, use of DOACs was associated with a lower risk of MACE (hazard ratio, 0.636; 95% CI, 0.417 to 0.970; P=.036) and MI (hazard ratio, 0.497; 95% CI, 0.276 to 0.896; p=.020). Sensitivity analysis showed that this association was consistent in younger patients (<75 years), in patients with anemia, and in those without chronic obstructive pulmonary disease and heart failure. We also found that both dabigatran and apixaban/rivaroxaban were associated with a lower rate of MACE, with similar efficacy between full and low doses.ConclusionDOACs are associated with a lower risk of MACE in patients with AF independently from dosage.     

Comparison Between Common Performance-Based Tests and Self-Reports of Physical Function in People With Multiple Sclerosis: Does Sex or Gender Matter?

ObjectiveTo estimate the extent to which sex or gender differences affect the relations between tests of physical performance and self-reports about function in everyday life activities. Ecological validity is an important psychometric property when choosing tests of physical function, because they need to relate to everyday function. In multiple sclerosis (MS), the EQUI scale, modified Canadian Aerobic Fitness Test, grip strength, vertical jump, push-up, partial curl-up, gait speed (comfortable or fast), 6-minute walk test, and 9-hole peg test are commonly used but the extent to which they relate to everyday function is understudied and the extent to which ecological validity of these tests differ between women and men is unknown.DesignA cross-sectional analysis was conducted on a random sample of men and women recruited for a study on the life effect of MS. Correlations between pairs of performance outcome (PerfO) and self-reported outcome (SRO) items pairs of variables with theoretical coherence were calculated and gender effects identified using linear regression.SettingParticipants were recruited from MS clinic at Montreal Neurological Hospital.ParticipantsThe sample (N=188) consisted of 140 women and 48 men with MS.InterventionsNot applicable.ResultsThe mean age ± SD of the participants was 43±10. Sixty PerfO and SRO items yielded 165 theoretically linked pairs separately for women and men. Of these 330 possible pairs, 77 pairs (23%) had correlations ≥0.8, showing strong support for the link between performance tests and everyday function; 203 pairs provided moderate support (r≥0.5). Thirty-one pairs had a statistically significant interaction with gender with men having higher correlations than women (n=27/31).ConclusionThe results support the ecological validity for physical performance tests, particularly balance tests and particularly for men. The observation that many indicators of everyday function derived from SROs were related to physical performance supports the routine use of SROs in clinical practice to guide therapy to meet the needs of clients with MS.     

Effects of Performance-Based Training on Gait and Balance in Individuals With Incomplete Spinal Cord Injury

ObjectiveTo determine changes in balance and gait following a task-specific, performance-based training protocol for overground locomotor training (OLT) in individuals with motor-incomplete spinal cord injury (iSCI).DesignConvenience sample, prepilot and postpilot study.SettingHuman performance research laboratory.ParticipantsAdults (N=15; 12 men and 3 women; mean age [y] ± SD, 41.5±16.9), American Spinal Injury Association Impairment Scale C or D, >6 months post-spinal cord injury.InterventionsTwo 90-minute OLT sessions per week over 12 to 15 weeks. OLT sessions were built on 3 principles of motor learning: practice variability, task specificity, and progressive overload (movement complexity, resistance, velocity, volume). Training used only voluntary movements without body-weight support, robotics, electrical stimulation, or bracing. Subjects used ambulatory assistive devices as necessary.Main Outcome MeasuresBerg Balance Scale (BBS), Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI) gait parameters, spatiotemporal measures of gait (step length, step width, percent stance, stance:swing ratio) from 7 participants who walked across a pressure-sensitive walkway.ResultsFourteen participants completed the OLT protocol and 1 participant completed 15 sessions due to scheduled surgery. The BBS scores showed a mean improvement of 4.53±4.09 (P<.001). SCI-FAI scores showed a mean increase of 2.47±3.44 (P=.01). Spatiotemporal measures of gait showed no significant changes.ConclusionThis pilot demonstrated improvements in balance and selected gait characteristics using a task-specific, performance-based OLT for chronic iSCI.