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Exercise capacity (EC) is inversely related to the risk of cardiovascular disease and incident heart failure (HF) in healthy subjects. However, there are no present studies that exclusively evaluate EC and the risk of incident HF in patients with known coronary heart disease (CHD). We aimed to determine the relation between EC and incident HF in patients with an established clinical diagnosis of CHD. We retrospectively identified 8,387 patients (age 61 ± 12 years; 30% women; 33% non-White) with a history of myocardial infarction (MI) or coronary revascularization procedure and no history of HF at the time of a clinically indicated exercise stress test completed between 1991 and 2009. EC was quantified in metabolic equivalents of task (METs) estimated from treadmill testing. Incident HF was identified through June 2010 from administrative databases based on ≥3 encounters with International Classification of Diseases, Ninth Revision 428.x. Cox regression analysis was used to evaluate the risk of incident HF associated with METs. Covariates included age; gender; race; hypertension, diabetes, hyperlipidemia, smoking, and MI; medications for CHD and lung diseases; and clinical indication for treadmill testing. During a median follow-up of 8.2 years (interquartile range 4.7 to 12.4 years) after the exercise test, 23% of the cohort experienced a new HF diagnosis. Lower EC categories were associated with higher HF incidence compared with METs ≥12, with nearly fourfold greater adjusted risk among patients with METslt;6. Per unit increase in METs of EC was associated with a 12% lower adjusted risk for HF. There was no significant interaction based on race (p = 0.06), gender (p = 0.88), age ≤61 years (p = 0.60), history of MI (p = 0.31), or diabetes (p = 0.38). This study reveals that among men and women with CHD and no history of HF, EC is independently and inversely related to the risk of future HF.

To determine whether fitness could improve mortality risk stratification among older adults compared with cardiovascular disease (CVD) risk factors.We examined 6509 patients 70 years of age and older without CVD from the Henry Ford ExercIse Testing Project (FIT Project) cohort. Patients performed a physician-referred treadmill stress test between 1991 and 2009. Traditional categorical CVD risk factors (hypertension, hyperlipidemia, diabetes, and smoking) were summed from 0 to 3 or more. Fitness was grouped as low, moderate, and high (6, 6 to 9.9, and ≥10 metabolic equivalents of task). All-cause mortality was ascertained through US Social Security Death Master files. We calculated age-adjusted mortality rates, multivariable adjusted Cox proportional hazards, and Kaplan-Meier survival models.Patients had a mean age of 75±4 years, and 3385 (52%) were women; during a mean follow-up of 9.4 years, there were 2526 deaths. A higher fitness level (P.001), not lower CVD risk factor burden (P=.31), was associated with longer survival. The age-adjusted mortality rate per 1000 person-years was 56.7 for patients with low fitness and 0 risk factors compared with 24.9 for high fitness and 3 or more risk factors. Among patients with 3 or more risk factors, the adjusted mortality hazard was 0.68 (95% CI, 0.61 to 0.76) for moderate and 0.51 (95% CI, 0.44 to 0.60) for high fitness compared with the least fit.Among persons aged 70 years and older, there was no significant difference in survival of patients with 0 vs 3 or more risk factors, but a higher fitness level identified older persons with good long-term survival regardless of CVD risk factor burden.

Objective To investigate the relationship between maximal exercise capacity measured before severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hospitalization due to coronavirus disease 2019 (COVID-19). Patients and Methods We identified patients (≥18 years) who completed a clinically indicated exercise stress test between 01 January 2016 and 29 February 2020 and had a test for SARS-CoV-2 (i.e., real-time reverse transcriptase polymerase chain reaction test) between 29 February 2020 and 31 May 2020. Maximal exercise capacity was quantified in metabolic equivalents of task (METs). Logistic regression was used to evaluate the likelihood that hospitalization secondary to COVID-19 is related to peak METs, with adjustment for 13 covariates previously identified as associated with higher risk for severe illness from COVID-19. Results We identified 246 patients (age= 59±12 years; 42% male; 75% black race) who had an exercise test and tested positive for SARS-CoV-2. Among these, 89 (36%) were hospitalized. Peak METs were significantly lower (P

Objective To study the association between cardiorespiratory fitness (CRF) and incident stroke types. Patients and Methods We studied a retrospective cohort of patients referred for treadmill stress testing in the Henry Ford Health System (Henry Ford ExercIse Testing Project) without history of stroke. CRF was expressed by metabolic equivalents of task (METs). Using appropriate International Classification of Diseases, Ninth Revision codes, incident stroke was ascertained through linkage with administrative claims files and classified as ischemic, hemorrhagic, and subarachnoid hemorrhage (SAH). Multivariable-adjusted Cox proportional hazards models examined the association between CRF and incident stroke. Results Among 67,550 patients, mean ± SD age was 54±13 years, 46% (n=31,089) were women, and 64% (n=43,274) were white. After a median follow-up of 5.4 (interquartile range 2.7-8.5) years, a total of 7512 incident strokes occurred (6320 ischemic, 2481 hemorrhagic, and 275 SAH). Overall, there was a graded lower incidence of stroke with higher MET categories. Patients with METs of 12 or more had lower risk of overall stroke [0.42 (95% CI, 0.36-0.49)], ischemic stroke [0.69 (95% CI, 0.58-0.82)], and hemorrhagic stroke [0.71 (95% CI, 0.52-0.95)]. Conclusion In a large ethnically diverse cohort of patients referred for treadmill stress testing, CRF is inversely associated with risk for ischemic and hemorrhagic stroke.

Cardiorespiratory fitness (CRF) is inversely associated with atherosclerotic cardiovascular disease (ASCVD) risk. It is unclear whether the prognostic value of CRF differs by baseline estimated ASCVD risk. We studied a retrospective cohort of patients without known heart failure or myocardial infarction (MI) who underwent treadmill stress testing. CRF was measured by metabolic equivalents of task (METs) and ASCVD risk was calculated using the Pooled Cohorts Equations. Multivariable-adjusted Cox regressions analyses examined the association between METs and incident all-cause mortality and MI outcomes stratified by baseline ASCVD risk. The C-index evaluated risk discrimination while net reclassification improvement evaluated reclassification with CRF added to the ASCVD risk score. Our study population consisted of 57,999 patients of mean age 53 (13) years, 49% women, 64% white, 29% black. Over a median follow-up 11 years (interquartile range 8 to 14 years) there were 6,670 (11%) deaths, while there were 1,757 (3.0%) MIs over a median follow-up of 6 years (interquartile range 3 to 8 years). Among patients with ASCVD risk ≥20%, those with METs ≥12 had a 77% lower risk of all-cause mortality (Hazard ratio 0.23 95% confidence interval = 0.20, 0.27) and 67% lower risk of MI (Hazard ratio 0.33 95% confidence interval = 0.24, 0.46) compared to METs6. Similar results were obtained for those with ASCVD risk5%. Addition of METs to ASCVD risk score improved the C-statistic from 0.778 to 0.798 for all-cause mortality and 0.726 to 0.733 for MI (both p0.001). Addition of METs to ASCVD risk score significantly reclassified risk of all-cause mortality (p0.001) but not MI (p = 0.052). In conclusion, CRF is inversely associated with risk of all-cause mortality and MI at all levels of ASCVD risk, and provides incremental risk discrimination and reclassification beyond the ASCVD risk score.

Isolated low high-density lipoprotein cholesterol (HDL-C) is associated with lower fitness and increased mortality. Whether the association between isolated low HDL-C and mortality differs by fitness is uncertain. Patients in the Henry Ford ExercIse Testing Project (FIT Project) completed a physician-referred treadmill stress test and those prescribed lipid-lowering medications or with known cardiovascular disease were excluded. Isolated low HDL-C was defined as HDL-C40 mg/dl for men and50 mg/dl for women with low-density lipoprotein cholesterol (LDL-C) and triglycerides100 mg/dl (n = 688). An optimal lipid panel was defined as HDL-C ≥40 mg/dl for men and ≥50 mg/dl for women with LDL-C and triglycerides100 mg/dl (n = 2,923). Mortality was ascertained through Social Security Death Index linkage. Patients with isolated low HDL-C had a mean age of 48.9 ± 12.9 years and 62.9% were women. Over a mean follow-up of 10.3 ± 5 years, 12.8% of patients with isolated low HDL-C and 8.7% with optimal lipids died. Compared to individuals with optimal lipids, those with isolated low HDL-C who achieved6 METs had a lower survival (p = 0.02), whereas there was no mortality difference for those who achieved 6 to 10 METs (p = 0.13) or ≥10 METs (p = 0.66). In adjusted Cox models, the mortality hazard for those with isolated low HDL-C compared with optimal lipids was 1.73 (95% confidence interval [CI] 1.18 to 2.54), 1.90 (95% CI 1.19 to 3.04), and 0.97 (95% CI 0.53 to 1.78) for the METS categories of6, 6 to 10, and ≥10. In conclusion, individuals with isolated low HDL-C fitness significantly improved risk stratification and only those with lower fitness had an increased totality mortality risk.

We conducted this study to investigate the association of cardiorespiratory fitness and all-cause mortality among patients with chronic kidney disease.We studied a retrospective cohort of patients from the Henry Ford Health System who underwent clinically indicated exercise stress testing with baseline cardiorespiratory fitness and estimated glomerular filtration rate measurement. Cardiorespiratory fitness was expressed as metabolic equivalents of task, and kidney function was categorized into stages according to estimated glomerular filtration rate. Multivariable-adjusted Cox proportional hazard models were used to examine the association between metabolic equivalents of task and all-cause mortality among patients with chronic kidney disease stages 3-5. Discrimination of mortality was assessed using receiver operating characteristic curves, while reclassification was evaluated using net reclassification index (NRI).Among 50,121 participants, the mean age was 55 ± 12.6 years; 47.5% were women, 64.5% were white, and 6877 (13.7%) participants had chronic kidney disease stage 3-5. Over a median follow-up of 6.7 years, 6308 participants died (12.6%). Each 1-unit higher metabolic equivalents of task was associated with a significant 15% reduction in all-cause mortality (hazard ratio 0.85; 95% confidence interval [CI], 0.84-0.87). Metabolic equivalents of task improved discriminatory ability of mortality prediction when added to traditional risk factors and estimated glomerular filtration rate (area under the curve 0.7996; 95% CI, 0.789-0.810 vs 0.759; 95% CI, 0.748-0.770, respectively; P.001). The addition of metabolic equivalents of task to traditional risk factors resulted in significant reclassification (6% for events, 5% for non-events: NRI = 0.13, P.001).Cardiorespiratory fitness improves mortality risk prediction among patients with chronic kidney disease. Cardiorespiratory fitness provides incremental prognostic information when added to traditional risk factors and may help guide treatment options among patients with renal dysfunction.

Objectives To assess the influence of exercise capacity and body mass index (BMI) on 10-year mortality in patients with heart failure (HF) and to synthesize these results with those of previous studies. Patients and Methods This large biracial sample included 774 men and women (mean age, 60±13 years; 372 [48%] black) with a baseline diagnosis of HF from the Henry Ford Exercise Testing (FIT) Project. All patients completed a symptom-limited maximal treadmill stress test from January 1, 1991, through May 31, 2009. Patients were grouped by World Health Organization BMI categories for Kaplan-Meier survival analyses and stratified by exercise capacity ( Results During a mean follow-up of 10.1±4.6 years, 380 patients (49%) died. Kaplan-Meier survival plots revealed a significant positive association between BMI category and survival for exercise capacity less than 4 METs (log-rank, P =.05), but not greater than or equal to 4 METs ( P =.76). In the multivariable-adjusted models, exercise capacity (per 1 MET) was inversely associated, but BMI was not associated, with all-cause mortality (hazard ratio, 0.89; 95% CI, 0.85-0.94; P P =.16, respectively). Conclusion Maximal exercise capacity modified the relationship between BMI and long-term survival in patients with HF, upholding the presence of an exercise capacity-obesity paradox dichotomy as observed over the short-term in previous studies.

Previous studies have demonstrated that cardiorespiratory fitness is a strong marker of cardiovascular health. Machine learning (ML) can enhance the prediction of outcomes through classification techniques that classify the data into predetermined categories. The aim of the analysis is to compare the prediction of 10 years of all-cause mortality (ACM) using statistical logistic regression (LR) and ML approaches in a cohort of patients who underwent exercise stress testing. We included 34,212 patients (55% males, mean age 54 ± 13 years) free of coronary artery disease or heart failure who underwent exercise treadmill stress testing between 1991 and 2009 and had complete 10-year follow-up. The primary outcome of this analysis was ACM at 10 years. The probability of 10-years ACM was calculated using statistical LR and ML, and the accuracy of these methods was calculated and compared. A total of 3,921 patients died at 10 years. Using statistical LR, the sensitivity to predict ACM was 44.9% (95% confidence interval [CI] 43.3% to 46.5%), whereas the specificity was 93.4% (95% CI 93.1% to 93.7%). The sensitivity of ML to predict ACM was 87.4% (95% CI 86.3% to 88.4%), whereas the specificity was 97.2% (95% CI 97.0% to 97.4%). The ML approach was associated with improved model discrimination (area under the curve for ML [0.923 (95% CI 0.917 to 0.928)]) compared with statistical LR (0.836 [95% CI 0.829 to 0.846], p 0.0001). In conclusion, our analysis demonstrates that ML provides better accuracy and discrimination of the prediction of ACM among patients undergoing stress testing.

Background Little is known about the relationship of change in cardiorespiratory fitness and mortality risk in Black patients. This study assessed change in cardiorespiratory fitness and its association with all-cause mortality risk in Black and White patients. Methods This is a retrospective, longitudinal, observational cohort study of 13,345 patients (age = 55 ± 11 years; 39% women; 26% black) who completed 2 exercise tests, at least 12 months apart at Henry Ford Hospital, Detroit, Mich. All-cause mortality was identified through April 2013. Data were analyzed in 2015-2016 using Cox regression to calculate hazard ratios (HR) for risk of mortality associated with change in sex-specific cardiorespiratory fitness. Results Mean time between the tests was 3.4 years (interquartile range 1.9-5.6 years). During 9.1 years (interquartile range 6.3-11.6 years) of follow-up, there were 1931 (14%) deaths (16.5% black, 13.7% white). For both races, change in fitness from Low to the Intermediate/High category resulted in a significant reduction of death risk (HR 0.65 [95% confidence interval (CI), 0.49-0.87] for Black; HR 0.41 [95% CI, 0.34-0.51] for White). Each 1-metabolic-equivalent-of-task increase was associated with a reduced mortality risk in black (HR 0.84 [95% CI, 0.81-0.89]) and white (HR 0.87 [95% CI, 0.82-0.86]) patients. There was no interaction by race. Conclusions Among black and white patients, change in cardiorespiratory fitness from Low to Intermediate/High fitness was associated with a 35% and 59% lower risk of all-cause mortality, respectively.

Whether lower heart rate thresholds (defined as the percentage of age-predicted maximal heart rate achieved, or ppMHR) should be used to determine chronotropic incompetence in patients on beta-blocker therapy (BBT) remains unclear. In this retrospective cohort study, we analyzed 64,549 adults without congestive heart failure or atrial fibrillation (54 ± 13 years old, 46% women, 29% black) who underwent clinician-referred exercise stress testing at a single health care system in Detroit, Michigan from 1991 to 2009, with median follow-up of 10.6 years for all-cause mortality (interquartile range 7.7 to 14.7 years). Using Cox regression models, we assessed the effect of BBT, ppMHR, and estimated exercise capacity on mortality, with adjustment for demographic data, medical history, pertinent medications, and propensity to be on BBT. There were 9,259 deaths during follow-up. BBT was associated with an 8% lower adjusted achieved ppMHR (91% in no BBT vs 83% in BBT). ppMHR was inversely associated with all-cause mortality but with significant attenuation by BBT (per 10% ppMHR HR: no BBT: 0.80 [0.78 to 0.82] vs BBT: 0.89 [0.87 to 0.92]). Patients on BBT who achieved 65% ppMHR had a similar adjusted mortality rate as those not on BBT who achieved 85% ppMHR (p >0.05). Estimated exercise capacity further attenuated the prognostic value of ppMHR (per-10%-ppMHR HR: no BBT: 0.88 [0.86 to 0.90] vs BBT: 0.95 [0.93 to 0.98]). In conclusion, the prognostic value of ppMHR was significantly attenuated by BBT. For patients on BBT, a lower threshold of 65% ppMHR may be considered for determining worsened prognosis. Estimated exercise capacity further diminished the prognostic value of ppMHR particularly in patients on BBT.

Objectives The goal of this study was examine the association between chronotropic incompetence and incident atrial fibrillation (AF). Background Patients with an inadequate heart rate response during exercise may have abnormalities in sinus node function or autonomic tone that predispose to the development of AF. Methods The association between heart rate response and incident AF was examined in 57,402 patients (mean age 54 ± 13 years, 47% female, 64% white) free of baseline AF who underwent exercise treadmill stress testing from the Henry Ford ExercIse Testing (FIT) Project. Age-predicted maximum heart rate (pMHR) values Results Over a median follow-up of 5.0 years (25th to 75th percentiles: 2.6 to 7.8 years), a total of 3,395 (5.9%) participants developed AF. pMHR values Conclusions Our analysis suggests that patients with inadequate heart rate response during exercise have an increased risk of developing AF.

Objective To determine whether sex modifies the relationship between fitness and mortality. Patients and Methods We included 57,284 patients without coronary artery disease or heart failure who completed a routine treadmill exercise test between 1991 and 2009. We determined metabolic equivalent tasks (METs) and linked patient records with mortality data via the Social Security Death Index. Multivariable Cox regression was used to determine the association between sex, fitness, and all-cause mortality. Results There were 29,470 men (51.4%) and 27,814 women (48.6%) with mean ages of 53 and 54 years, respectively. Overall, men achieved 1.7 METs higher than women ( P P =.004). Fitness was inversely associated with mortality in both men (hazard ratio [HR], 0.84 per 1 MET; 95% CI, 0.83-0.85) and women (HR, 0.83 per 1 MET; 95% CI, 0.81-0.84). This relationship did not plateau at high or low MET values. Conclusion Although men demonstrated 1.7 METs higher than women, their survival was equivalent to that of women demonstrating 2.6 METs lower. Furthermore, higher MET values were associated with lower mortality for both men and women across the range of MET values. These findings are useful for tailoring prognostic information and lifestyle guidance to men and women undergoing stress testing.

The purpose of this retrospective, observational study was to describe the relation between exercise workload during cardiac rehabilitation (CR), expressed as metabolic equivalents of task (METs), and prognosis among patients with coronary heart disease. We included patients with coronary heart disease who participated in CR between January 1998 and June 2007. METs were calculated from treadmill workload. Cox regression analysis was used to describe the relationship between METs and time to a composite outcome of all-cause mortality, nonfatal myocardial infarction, or heart failure hospitalization. Among 1,726 patients (36% women; median age 59 years [interquartile range, 52 to 66]), there were 467 events (27%) during a median follow-up of 5.8 years (interquartile range, 2.6 to 8.7). In analyses adjusted for age, sex, Charlson co-morbidity index, hypertension, diabetes, and CR referral diagnosis, METs were independently related to the composite outcome at CR start (Wald chi-square 43, hazard ratio 0.59 [95% confidence interval 0.51 to 0.70]) and CR end (Wald chi-square 47, hazard ratio 0.68 [95% confidence interval 0.61 to 0.76]). Patients exercising below 3.5 METs on exit from CR represent a high-risk group with 1- and 3-year event rates ≥7% and ≥18%, respectively. In conclusion, METs during CR is available at no additional cost and can be used to identify patients at increased risk for an event who may benefit from closer follow-up, extended length of stay in CR, and/or participation in other strategies aimed at maximizing adherence to secondary preventive behaviors and improving exercise capacity.

Objective To examine the effect of objectively measured exercise capacity (EC) on early mortality (EM) after a first myocardial infarction (MI). Patients and Methods This retrospective cohort study included 2061 patients without a history of MI (mean age, 62±12 years; 38% [n=790] women; 56% [n=1153] white) who underwent clinical treadmill stress testing in the Henry Ford Health System from January 1, 1991, through May 31, 2009, and suffered MI during follow-up (MI event proportion, 3.4%; mean time from the exercise test to MI, 6.1±4.3 years). Exercise capacity was categorized on the basis of peak metabolic equivalents (METs) achieved: less than 6, 6 to 9, 10 to 11, and 12 or more METs. Early mortality was defined as all-cause mortality within 28, 90, or 365 days of MI. Multivariable logistic regression models were used to assess the effect of EC on the risk of mortality at each time point post-MI adjusting for baseline demographic characteristics, cardiovascular risk factors, medication use, indication for stress testing, and year of MI. Results The 28-day EM rate was 10.6% overall, and 13.9%, 10.7%, 6.9%, and 6.0% in the less than 6, 6 to 9, 10 to 11, and 12 or more METs categories, respectively ( P P P =.006; 90 days: OR, 0.90; 95% CI, 0.86-0.95; P P Conclusion Higher baseline EC was independently associated with a lower risk of early death after a first MI.

Decreases in systolic blood pressure during exercise may predispose to arrhythmias such as atrial fibrillation (AF) because of underlying abnormal autonomic tone. We examined the association between systolic blood pressure response and incident AF in 57,442 (mean age 54 ± 13 years, 47% women, and 29% black) patients free of baseline AF who underwent exercise treadmill stress testing from the Henry Ford ExercIse Testing project. Exercise systolic blood pressure response was examined as a categorical variable across clinically relevant categories (>20 mm Hg: referent; 1 to 20 mm Hg, and ≤0 mm Hg) and per 1-SD decrease. Cox regression, adjusting for demographics, cardiovascular risk factors, medications, history of coronary heart disease, history of heart failure, and metabolic equivalent of task achieved, was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between systolic blood pressure response and incident AF. Over a median follow-up of 5.0 years, a total of 3,381 cases (5.9%) of AF were identified. An increased risk of AF was observed with decreasing systolic blood pressure response (>20 mm Hg: HR 1.0, referent; 1 to 20 mm Hg: HR 1.09, 95% CI 0.99, 1.20; ≤0 mm Hg: HR 1.22, 95% CI 1.06 to 1.40). Similar results were obtained per 1-SD decrease in systolic blood pressure response (HR 1.08, 95% CI 1.04 to 1.12). The results were consistent when stratified by age, sex, race, hypertension, and coronary heart disease. In conclusion, our results suggest that a decreased systolic blood pressure response during exercise may identify subjects who are at risk for developing AF.

Heart failure (HF) is a morbid condition associated with impaired exercise capacity. Exercise training is an effective strategy to improve functional capacity and quality of life. However, response to exercise training is highly variable and whether there are genetic factors that may impact response

Objectives This study examined the effects of a cardiac rehabilitation (CR) program on functional capacity and health status (HS) in patients with newly implanted left ventricular assist devices (LVADs). Background Reduced functional capacity and HS are independent predictors of mortality in patients with heart failure. CR improves both, and is related to improved outcomes in patients with heart failure; however, there is a paucity of data that describe the effects of CR in patients with LVADs. Methods Enrolled subjects (n = 26; 7 women; age 55 ± 13 years; ejection fraction 21 ± 8%) completed a symptom-limited cardiopulmonary exercise test, the Kansas City Cardiomyopathy Questionnaire (KCCQ), a 6-min walk test (6MW), and single-leg isokinetic strength test before 2:1 randomization to CR versus usual care. Subjects in the CR group underwent 18 visits of aerobic exercise at 60% to 80% of heart rate reserve. Within-group changes from baseline to follow-up were analyzed with a paired t-test, whereas an independent t-test was used to determine differences in the change between groups. Results Within-group improvements were observed in the CR group for peak oxygen uptake (10%), treadmill time (3.1 min), KCCQ score (14.4 points), 6MW distance (52.3 m), and leg strength (17%). Significant differences among groups were observed for KCCQ, leg strength, and total treadmill time. Conclusions Indicators of functional capacity and HS are improved in patients with continuous-flow LVADs who attend CR. Future trials should examine the mechanisms responsible for these improvements, and if such improvements translate into improved clinical outcomes. (Cardiac Rehabilitation in Patients With Continuous Flow Left Ventricular Assist Devices:Rehab VAD Trial [RehabVAD]; NCT01584895 )

Cardiorespiratory fitness (CRF) is a strong predictor of mortality and coronary heart disease. This study further examines the association between CRF and incident stroke types. We studied a retrospective cohort of 67,707 patients referred for treadmill stress testing in the Henry Ford Health

Traditional cardiovascular disease (CVD) risk factors have a decreased predictive strength with increasing age. We sought to determine if fitness could improve risk stratification among older adults at the extremes of CVD risk factor burden. We studied 6,509 patients ≥70 years of age without CVD

Background Clinical trialists involved in projects aimed at assessing the impact of a device or therapy on exercise capacity must select an end point that can detect a therapy-derived change and do so in a manner that is both sensitive to the change and valid. Using baseline data from the Prospective Evaluation of Elastic Restraint to Lessen the Effects of Heart Failure (PEERLESS-HF) trial, we describe the coefficient of variation (CV) for peak oxygen uptake ( o 2 ) and other parameters measured during a cardiopulmonary exercise (CPX) test. Methods Prior to conducting CPX testing, a CPX core laboratory conducted training with testing staff at each site, and a standardized quality assurance protocol was completed. During screening, subjects performed two symptom-limited CPX tests (CPX-0 and CPX-1) within 14 days. Results The CVs for peak o 2 , ventilatory efficiency, and ventilatory-derived anaerobic threshold were 5.9%, 4.8%, and 6.8%, respectively. During CPX-0, the percentage of subjects with a respiratory exchange ratio (RER) o 2 by ≥ 6% during CPX-1 was 47%, compared with 12% of subjects also with an RER o 2 ≥ 6%. Conclusions In a multisite clinical trial setting, we showed that the achieved test-retest reproducibility for peak o 2 can be acceptable, as evidenced by a CV at 5.9%. Until more data are available to identify patients who may demonstrate greater test-retest variance and to avoid repeat testing in all subjects at baseline, clinical trialists might consider repeating tests when RER Trial registration clinicaltrials.gov ; Identifier: NCT00382863

It is unknown if contemporary preventive treatments such as statins or primary percutaneous coronary intervention in patients with coronary heart disease (CHD) have rendered obsolete the use of measured exercise capacity for assessment of future risk and prognosis. Using a sample of patients from 2 clinical sites, most of whom were taking beta-blockade, antiplatelet, and statin therapy, we hypothesized that peak oxygen consumption (Vo(2)) would remain a strong and independent predictor of all-cause and cardiovascular-specific mortality in men and women with CHD.We studied 2,812 patients with CHD between 1996 and 2004. All-cause and cardiovascular disease-specific mortality served as end points.In all men and women and in a subgroup of patients following evidence-based care, peak Vo(2) remained a strong predictor of all-cause death, with every 1 mL x kg(-1) x min(-1) increase in peak Vo(2) associated with an approximate 15% decrease in risk of death. Among men, a peak Vo(2) (mL x kg(-1) x min(-1)) below approximately 15 was associated with the highest risk, whereas a peak Vo(2) above approximately 19 was associated with a low rate and risk for annual all-cause mortality. Among women, a peak Vo(2) below approximately 12 was associated with the highest risk, whereas a peak Vo(2) above approximately 16.5 was associated with the lowest rate and risk for annual all-cause mortality.In men and women with CHD, peak Vo(2) remains an independent predictor of all-cause and cardiovascular-specific mortality.

Background: Chronotropic incompetence (CI) has been associated with cardiovascular mortality. However, its relationship with long-term risk of heart failure (HF) is not well studied. Methods: We included 43,098 participants (mean age 51.7±12.3 years, 47.5% females, 66.6% white) of the FIT project

Background: Prior studies have demonstrated that cardiorespiratory fitness (CRF) is a strong marker of cardiovascular health. Machine learning (ML) can enhance the prediction of outcomes through classification technique that classifies the data into predetermined categories. The aim of the analysis

Background The combined influence of fitness and fatness on mortality risk in diverse populations has not been adequately explored. Our aim was to assess the relative impact of exercise capacity and body mass index (BMI) on all-cause mortality. Methods We included 29,257 men and women (mean age 53 years; 27% African American) from The Henry Ford Exercise Testing (FIT) Project without cardiovascular disease and diabetes mellitus at baseline. All patients completed a symptom-limited maximal treadmill stress test between 1991 and 2009. Patients were grouped for analysis by exercise capacity (≥10 metabolic equivalents of task [METs] and 2 and 2 ), forming 4 subgroups. Independent and joint associations of BMI and exercise capacity with all-cause mortality were assessed using Cox proportional hazard models. Results During a mean follow-up of 10.8 years, 1898 patients (6.5%) died. We observed a strong inverse association between exercise capacity (per 1 MET unit) and all-cause mortality (hazard ratio [95% confidence interval], 0.86 [0.85-0.88]). Body mass index (per 1 BMI unit) was inversely related to mortality (hazard ratio [95% confidence interval], 0.98 [0.97-0.99]). In joint analysis, the highest mortality risk was in the 2 subgroup. Conclusions Reduced exercise capacity was a strong independent risk factor for all-cause mortality in this racially diverse population. Given the comparatively limited impact of BMI, more emphasis should be placed on measuring exercise capacity and developing strategies for its improvement in cardiovascular disease prevention programs.

Background In the general population, the exercise treadmill testing variables of lower resting heart rate, higher peak heart rate, and greater fitness have favorable prognosis for mortality. Patients with obstructive lung disease have increased mortality risk. Furthermore, some pulmonary medications (ie, beta2-agonists) can influence heart rate. We determined whether exercise treadmill test parameters carry the same prognostic value in patients who are using versus not using pulmonary medications. Methods We analyzed data on 69,855 patients (mean age, 55 years) who completed a clinically indicated exercise treadmill test. Patients were defined as having "lung disease" if they were taking medications routinely used to treat obstructive lung disease (n = 6145, 9%). International Classification of Diseases, 9th Revision codes regarding the type of lung disease were not available. Multivariate-adjusted Cox models were used to determine the risk of mortality, major adverse cardiac events, and myocardial infarction over a mean of 11 years follow-up. Results Higher resting heart rate was associated with increased mortality risk, and higher peak heart rate and fitness were associated with decreased risk. No significant interaction for lung disease status was seen for the heart rate variables, but a slightly stronger protective effect was observed for higher fitness among patients with lung disease ( P interaction = .032). The results were similar for major adverse cardiac events and myocardial infarction. Conclusions Heart rate parameters achieved on exercise treadmill tests are equally prognostic among patients using versus not using pulmonary medications. Higher fitness was associated with improved clinical outcomes for both; however, the relative benefit of fitness on survival was even greater in patients using pulmonary medications compared with those not using them.

The incidence of coronary artery disease in allografts after heart transplant is approximately 20% at 2 years and up to 50 to 60% at 5 years. 1,2 A noninvasive assessment of myocardial ischemia in these patients would be useful. Only 1 report has addressed the usefulness of graded exercise tests for the detection of ischemia in patients with heart transplants, and these investigators showed a low sensitivity and predictive value. 3 The purpose of this investigation was to further evaluate the concept that graded exercise testing may not be a useful diagnostic method in such patients.