Modest Gains After an 8-Week Exercise Program Correlate With Reductions in Non-traditional Markers of Cardiovascular Risk.

Background: Although engaging in physical exercise has been shown to reduce the incidence of cardiovascular events, the molecular mechanisms by which exercise mediates these benefits remain unclear. Based on epidemiological evidence, reductions in traditional risk factors only accounts for 50% of the protective effects of exercise, leaving the remaining mechanisms unexplained. The objective of this study was to determine whether engaging in a regular exercise program in a real world clinical setting mediates cardiovascular protection via modulation of non-traditional risk factors, such as those involved in coagulation, inflammation and metabolic regulation. Methods and Results: We performed a prospective, cohort study in 52 sedentary patients with cardiovascular disease or cardiovascular risk factors at two tertiary medical centers between January 1, 2016 and December 31, 2019. Prior to and at the completion of an 8-week exercise program, we collected information on traditional cardiovascular risk factors, exercise capacity, and physical activity and performed plasma analysis to measure levels of fibrinolytic, inflammatory and metabolic biomarkers to assess changes in non-traditional cardiovascular risk factors. The median weight change, improvement in physical fitness, and change in physical activity for the entire cohort were: -4.6 pounds (IQR: +2 pounds, -11.8 pounds), 0.37 METs (IQR: -0.076 METs, 1.06 METs), and 252.7 kcals/week (IQR: -119, 921.2 kcals/week). In addition to improvement in blood pressure and cholesterol, patients who lost at least 5 pounds, expended at least 1,000 additional kcals/week, and/or achieved ≥0.5 MET increase in fitness had a significant reduction in plasminogen activator inhibitor-1 [9.07 ng/mL (95% CI: 2.78-15.35 ng/mL); P = 0.026], platelet derived growth factor beta [376.077 pg/mL (95% CI: 44.69-707.46 pg/mL); P = 0.026); and angiopoietin-1 [(1104.11 pg/mL (95% CI: 2.92-2205.30 pg/mL); P = 0.049)]. Conclusion: Modest improvements in physical fitness, physical activity, and/or weight loss through a short-term exercise program was associated with decreased plasma levels of plasminogen activator inhibitor, platelet derived growth factor beta, and angiopoietin, which have been associated with impaired fibrinolysis and inflammation.

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.

PCI Alternative Using Sustained Exercise (PAUSE): Rationale and trial design.

Cardiovascular disease (CVD) currently claims nearly one million lives yearly in the US, accounting for nearly 40% of all deaths. Coronary artery disease (CAD) accounts for the largest number of these deaths. While efforts aimed at treating CAD in recent decades have concentrated on surgical and catheter-based interventions, limited resources have been directed toward prevention and rehabilitation. CAD is commonly treated using percutaneous coronary intervention (PCI), and this treatment has increased exponentially since its adoption over three decades ago. Recent questions have been raised regarding the cost-effectiveness of PCI, the extent to which PCI is overused, and whether selected patients may benefit from optimal medical therapy in lieu of PCI. One alternative therapy that has been shown to improve outcomes in CAD is exercise therapy; exercise programs have been shown to have numerous physiological benefits, and a growing number of studies have demonstrated reductions in mortality. Given the high volume of PCI, its high cost, its lack of effect on survival and the potential for alternative treatments including exercise, the current study is termed "PCI Alternative Using Sustained Exercise" (PAUSE). The primary aim of PAUSE is to determine whether patients randomized to exercise and lifestyle intervention have greater improvement in coronary function and anatomy compared to those randomized to PCI. Coronary function and anatomy is determined using positron emission tomography combined with computed tomographic angiography (PET/CTA). Our objective is to demonstrate the utility of a non-invasive technology to document the efficacy of exercise as an alternative treatment strategy to PCI.

Association between cardiorespiratory fitness, obesity, and health care costs: The Veterans Exercise Testing Study.

BACKGROUND/OBJECTIVE: Obesity is a chronic disease, a risk factor for other chronic conditions and for early mortality, and is associated with higher health care utilization. Annual spending among obese individuals is at least 30% higher vs. that for normal-weight peers. In contrast, higher cardiorespiratory fitness (CRF) is related to many health benefits. We sought to examine the association between CRF and health care costs across the spectrum of body mass index (BMI). METHODS: Data from 3,924 men (58.1 ± 11.1 years, 29.2 ± 5.3 kg.m-2) who completed a maximal exercise test for clinical reasons and to estimate CRF were recorded prospectively at the time of testing. Cost data (USD) from each subject during a 6-year period after the exercise test were merged with the exercise database and compared according to BMI and estimated CRF (CRFe). Subjects were categorized as normal-weight (BMI < 25.0 kg.m-2), overweight (BMI 25.0-29.9 kg.m-2), and obese (BMI ≥ 30.0 kg.m-2). We also formed four CRFe categories based on age-stratified quartiles of metabolic equivalents (METs) achieved: least-fit (5.1 ± 1.5 METs; n = 1,044), moderately-fit (7.6 ± 1.5 METs; n = 938), fit (9.4 ± 1.5 METs; n = 988), and highly-fit (12.4 ± 2.2 METs; n = 954). RESULTS: Average annual costs per person adjusted for age and presence of cardiovascular disease were $37,018, $40,572, and $45,683 for normal-weight, overweight, and obese subjects, respectively (p < 0.01). For each 1-MET incremental increase in CRFe, annual cost savings per person were $3,272, $4,252, and $6,103 for normal-weight, overweight, and obese subjects, respectively. Stratified by CRFe categories, annual costs for normal-weight, overweight, and obese subjects in the highest CRFe quartile were $28,028, $31,669, and $32,807 lower, respectively, compared to subjects in the lowest CRFe quartile (p < 0.01). CONCLUSION: Higher CRFe is associated with lower health care costs. Cost savings were particularly evident in obese subjects, suggesting that the economic burden of obesity may be reduced through interventions that target improvements in CRF.

Association Between Cardiorespiratory Fitness and Health Care Costs: The Veterans Exercise Testing Study.

OBJECTIVE: To determine the association between cardiorespiratory fitness (CRF) and annual health care costs in Veterans. PATIENTS AND METHODS: The sample included 9942 subjects (mean age, 59±11 years) undergoing a maximal exercise test for clinical reasons between January 2005 and December 2012. Cardiorespiratory fitness, expressed as a percentage of age-predicted peak metabolic equivalents (METs) achieved, was categorized in quartiles. Total and annualized health care costs, derived from the Veterans Administration Allocated Resource Center, were compared using multiple regression, controlling for demographic and clinical characteristics. RESULTS: A gradient for reduced health care costs was observed as CRF increased, with subjects in the least-fit quartile having approximately $14,662 (P<.001) higher overall costs per patient per year compared with those in the fittest quartile, after controlling for potential confounding variables. Each 1-MET higher increment in fitness was associated with a $1592 annual reduction in health care costs (5.6% lower cost per MET), and each higher quartile of fitness was associated with a $4163 annual cost reduction per patient. The effect of CRF was more pronounced among subjects without cardiovascular disease (CVD), suggesting that the results were not driven by the possibility that less-fit individuals had greater CVD. Cost savings attributable to higher fitness were greatest in overweight and obese subjects, with lower savings observed among those individuals with a body mass index less than 25 kg/m2. In a model including historical, clinical, and exercise test responses, heart failure was the strongest predictor of health care costs, followed by CRF (P<.01). CONCLUSION: Low CRF is associated with higher health care costs. Efforts to improve CRF may not only improve health but also result in lower health care costs.

Exercise adherence in the elderly: Experience with abdominal aortic aneurysm simple treatment and prevention.

Poor adherence to health-related behaviors can have serious health consequences. Cardiac rehabilitation has been documented to have physiological and psychosocial benefits; however, optimizing adherence to exercise in patients with cardiovascular disease is a particular challenge. We recently completed a large, 6-year randomized trial of exercise training in elderly patients with abdominal aortic aneurysm (AAA) disease (50-85 years), which provided an opportunity to describe adherence strategies in this unique group of elderly individuals. Patients were randomized to exercise therapy or usual care. Using a case-management approach, a combination of center and home-based training was used during which patients trained for up to 3 years. We observed that overall, 84% of subjects in the exercise group completed ≥1 year in the study, achieving a mean energy expenditure of 1,999 ± 1,030 kcals per week. Subjects in the exercise group were more likely to drop out of the study as compared with usual care, though none of the reasons for dropping out were associated with exercise participation (eg, exercise-related injury). Reasons for withdrawal included orthopedic problems, lost physician coverage, time constraints, and AAA repair. Although the groups were matched for AAA size at baseline, there was a trend for more AAA repairs among usual care subjects versus those in the exercise group (12 [17.6%] vs 5 [6.9%], P = 0.09). The case-managed approach to optimizing adherence used was reasonably successful in achieving a training response (ie, improvement in exercise capacity) in elderly patients with AAA, a group for whom little is previously known regarding the effects of rehabilitation.

The Impact of Fitness on Surgical Outcomes: The Case for Prehabilitation.

In recent years, a growing body of research has demonstrated that an individual's fitness level is a strong and independent marker of risk for cardiovascular and all-cause mortality. In addition, modest improvements in fitness through exercise intervention have been associated with considerable health outcome benefits. These studies have generally assessed fitness as a baseline marker in traditional epidemiological cohorts. However, there has been a recent recognition that fitness powerfully predicts outcomes associated with a wide range of surgical interventions. The concept of 'prehabilitation' is based on the principle that patients with higher functional capability will better tolerate a surgical intervention, and studies have shown that patients with higher fitness have reduced postoperative complications and demonstrate better functional, psychosocial, and surgery-related outcomes. This review focuses on the impact of fitness on surgical outcomes and provides a rationale in support of routine application of prehabilitation in the management of patients undergoing surgery.

Agreement between activity-monitoring devices during home rehabilitation: a substudy of the AAA STOP trial.

As part of a home-based rehabilitation program, 24 older adult patients (71 ± 3 years) with abdominal aortic aneurysm (AAA) disease underwent 3 days (12 awake hr/day) of activity monitoring using an accelerometer (ACC), a pedometer, and a heart rate (HR) monitor, and recorded hourly activity logs. Subjects then underwent an interview to complete a 3-day activity recall questionnaire (3-DR). Mean energy expenditure (EE) in kcals/ day for HR, ACC, and 3-DR were 1,687 ± 458, 2,068 ± 529, and 1,974 ± 491, respectively. Differences in EE were not significant between 3-DR and ACC, but HR differed from both ACC (p < .001) and 3-DR (p < .01). ACC and 3-DR had the highest agreement, with a coefficient of variation of 7.9% and r = .86. Thus, ACC provided a reasonably accurate reflection of EE based the criterion measure, an activity recall questionnaire. ACC can be effectively used to monitor EE to achieve an appropriate training stimulus during home-based cardiac rehabilitation.

A randomized trial of exercise training in abdominal aortic aneurysm disease.

PURPOSE: Screening programs and greater public awareness have increased the recognition of early abdominal aortic aneurysm (AAA) disease. No medical therapy has proven effective in limiting AAA progression, and little is known regarding the safety and efficacy of exercise training in these patients. We evaluated the safety and efficacy of up to 3 yr of training in patients with early (≤5.5 cm) AAA disease. METHODS: One hundred and forty patients with small AAAs (72 ± 8 yr) were randomized to exercise training (n = 72) or usual care (n = 68). Exercise subjects participated in a combination of in-house and home training for up to 3 yr. Cardiopulmonary exercise testing (CPX) was performed at baseline and 3, 12, 24, and 36 months. Comparisons were made for AAA expansion, safety, CPX responses, and weekly energy expenditure. RESULTS: The average duration of participation was 23.4 ± 9.6 months; 81% of subjects completed ≥1 year. No adverse clinical events or excessive AAA growth rates related to training occurred. Exercise subjects expended a mean 1999 ± 1030 kcal·wk. Increases in peak exercise time and estimated METs occurred at the 3-month and 1-, 2-, and 3-yr evaluations (P < 0.01 between groups). A significant between-group interaction occurred for V˙O2 at the ventilatory threshold (P = 0.02), and submaximal heart rate was significantly reduced among exercise subjects. Neither exercise status nor level of fitness significantly influenced rate of AAA enlargement. CONCLUSIONS: These results support the safety and efficacy of training in patients with small AAA, a population for which few previous data are available. Despite advanced age and comorbidities, training up to 3 yr was well tolerated and sustainable in AAA patients. Training did not influence rate of AAA enlargement.

Cardiopulmonary exercise testing in small abdominal aortic aneurysm: profile, safety, and mortality estimates.

AIM: Few data are available regarding exercise testing in patients with abdominal aortic aneurysm (AAA) disease. The purpose of this study was to evaluate safety and to characterize the hemodynamic and cardiopulmonary (CPX) response to exercise in a large group of patients with AAA. METHODS: Three hundred and six patients with AAA ≥3.0 to ≤5.0 cm (mean 72 ± 8 years) underwent CPX as part of a randomized trial of exercise training. CPX and hemodynamic responses, ischemic events, rhythm disturbances, and risk estimates based on treadmill scores were quantified and compared to an age-matched group of 2155 veterans referred for exercise testing for clinical reasons. RESULTS: Peak VO(2) was similar between patients with AAA and the referral group (20.0 ± 6 ml/kg/min; 77 percent of age-predicted and 20.3 ± 7 ml/kg/min; 80 percent of age-predicted, respectively). The incidence of exercise-induced hypotension and hypertension was higher in AAA patients versus the referral group (2.9 and 3.6 percent vs <1.0 percent, p < 0.001), but there were no occurrences of ventricular tachycardia (≥3 beats) or other serious events in the AAA subjects. The Duke Treadmill Score and VA Treadmill Scores, which estimate annual cardiovascular events and all-cause mortality, respectively, were similar between groups. CONCLUSIONS: Patients with AAA have a slightly higher incidence of hyper- and hypotensive responses to exercise than age-matched referrals, but no serious events related to CPX occurred. AAA patients can undergo maximal CPX safely and have risk scores based on treadmill test results that are similar to age-matched referral subjects. These findings extend recent studies using sub-maximal evaluations to stratify risk in patients considered for surgery, and support the routine use of exercise testing for risk evaluation and the functional assessment of patients with AAA.

Effect of gender on computerized electrocardiogram measurements in college athletes.

BACKGROUND: Broad criteria for classifying an electrocardiogram (ECG) as abnormal and requiring additional testing prior to participating in competitive athletics have been recommended for the preparticipation examination (PPE) of athletes. Because these criteria have not considered gender differences, we examined the effect of gender on the computerized ECG measurements obtained on Stanford student athletes. Currently available computer programs require a basis for "normal" in athletes of both genders to provide reliable interpretation. METHODS: During the 2007 PPE, computerized ECGs were recorded and analyzed on 658 athletes (54% male; mean age, 19 +/- 1 years) representing 22 sports. Electrocardiogram measurements included intervals and durations in all 12 leads to calculate 12-lead voltage sums, QRS amplitude and QRS area, spatial vector length (SVL), and the sum of the R wave in V5 and S wave in V2 (RSsum). RESULTS: By computer analysis, male athletes had significantly greater QRS duration, PR interval, Q-wave duration, J-point amplitude, and T-wave amplitude, and shorter QTc interval compared with female athletes (all P < 0.05). All ECG indicators of left ventricular electrical activity were significantly greater in males. Although gender was consistently associated with indices of atrial and ventricular electrical activity in multivariable analysis, ECG measurements correlated poorly with body dimensions. CONCLUSION: Significant gender differences exist in ECG measurements of college athletes that are not explained by differences in body size. Our tables of "normal" computerized gender-specific measurements can facilitate the development of automated ECG interpretation for screening young athletes.

Addition of the electrocardiogram to the preparticipation examination of college athletes.

OBJECTIVE: Although the use of standardized cardiovascular (CV) system-focused history and physical examination is recommended for the preparticipation examination (PPE) of athletes, the addition of the electrocardiogram (ECG) has been controversial. Because the impact of ECG screening on college athletes has rarely been reported, we analyzed the findings of adding the ECG to the PPE of Stanford athletes. DESIGN: For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database. SETTING: Although the use of standardized CV-focused history and physical examination are recommended for the PPE of athletes, the addition of the ECG has been controversial. Because the feasibility and outcomes of ECG screening on college athletes have rarely been reported, we present findings derived from the addition of the ECG to the PPE of Stanford athletes. For the past 15 years, the Stanford Sports Medicine program has mandated a PPE questionnaire and physical examination by Stanford physicians for participation in intercollegiate athletics. In 2007, computerized ECGs with digital measurements were recorded on athletes and entered into a database. MAIN OUTCOME MEASURES: Six hundred fifty-eight recordings were obtained (54% men, 10% African-American, mean age 20 years) representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete right bundle branch block (RBBB) (13%), right axis deviation (RAD) (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for left ventricular hypertrophy (LVH) were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7%, and only 5 men had abnormal Q-waves. Sixty-three athletes (10%) were judged to have distinctly abnormal ECG findings possibly associated with conditions including hypertrophic cardiomyopathy or arrhythmogenic right ventricular dysplasia/cardiomyopathy. These athletes were offered further testing but this was not mandated according to the research protocol. RESULTS: Six hundred fifty-three recordings were obtained (54% men, 7% African American, mean age 20 years), representing 24 sports. Although 68% of the women had normal ECGs, only 38% of the men did so. Incomplete RBBB (13%), RAD (10%), and atrial abnormalities (3%) were the 3 most common minor abnormalities. Sokolow-Lyon criteria for LVH were found in 49%; however, only 27% had a Romhilt-Estes score of >or=4. T-wave inversion in V2 to V3 occurred in 7% and only 5 men had abnormal Q-waves. Sixty-five athletes (10%) were judged to have distinctly abnormal ECG findings suggestive of arrhythmogenic right ventricular dysplasia, hypertrophic cardiomyopathy, and/or biventricular hypertrophy. These athletes will be submitted to further testing. CONCLUSIONS: Mass ECG screening is achievable within the collegiate setting by using volunteers when the appropriate equipment is available. However, the rate of secondary testing suggests the need for an evaluation of cost-effectiveness for mass screening and the development of new athlete-specific ECG interpretation algorithms.

Adding an electrocardiogram to the pre-participation examination in competitive athletes: a systematic review.

No matter how rare, the death of young athletes is a tragedy. Can it be prevented? The European experience suggests that adding the electrocardiogram (ECG) to the standard medical and family history and physical examination can decrease cardiac deaths by 90%. However, there has not been a randomized trial to demonstrate such a reduction. While there are obvious differences between the European and American experiences with athletes including very differing causes of athletic deaths, some would highlight the European emphasis on public welfare vs the protection of personal rights in the USA. Even the authors of this systematic review have differing interpretation of the data: some of us view screening as a hopeless battle against Bayes, while others feel that the ECG can save lives. What we all agree on is that the USA should implement the American Heart Association 12-point screening recommendations and that, before ECG screening is mandated, we need to gather more data and optimize ECG criteria for screening young athletes.