Use of Sex-Specific Clinical and Exercise Risk Scores to Identify Patients at Increased Risk for All-Cause Mortality.

Importance: Risk assessment tools for exercise treadmill testing may have limited external validity. Cardiovascular mortality has decreased in recent decades, and women have been underrepresented in prior cohorts. Objectives: To determine whether exercise and clinical variables are associated with differential mortality outcomes in men and women and to assess whether sex-specific risk scores better estimate all-cause mortality. Design, Setting, and Participants: This retrospective cohort study included 59 877 patients seen at the Cleveland Clinic Foundation (CCF cohort) from January 1, 2000, through December 31, 2010, and 49 278 patients seen at the Henry Ford Hospital (FIT cohort) from January 1, 1991, through December 31, 2009. All patients were 18 years or older and underwent exercise treadmill testing. Data were analyzed from January 1, 2000, to October 27, 2011, in the CCF cohort and from January 1, 1991, to April 1, 2013, in the FIT cohort. Main Outcomes and Measurements: The CCF cohort was divided randomly into derivation and validation samples, and separate risk scores were developed for men and women. Net reclassification, C statistics, and integrated discrimination improvement were used to compare the sex-specific risk scores with other tools that have all-cause mortality as the outcome. Discrimination and calibration were also evaluated with these sex-specific risk scores in the FIT cohort. Results: The CCF cohort included 59 877 patients (59.4% men; 40.5% women) with a median (interquartile range [IQR]) age of 54 (45-63) years and 2521 deaths (4.2%) during a median follow-up of 7 (IQR, 4.1-9.6) years. The FIT cohort included 49 278 patients (52.5% men; 47.4% women) with a median (IQR) age of 54 (46-64) years and 6643 deaths (13.5%) during a median (IQR) follow-up of 10.2 (7-13.4) years. C statistics for the sex-specific risk scores in the CCF validation sample were higher (0.79 in women and 0.81 in men) than C statistics using other tools in women (0.70 for Duke Treadmill Score; 0.74 for Lauer nomogram) and men (0.72 for Duke Treadmill Score; 0.75 for Lauer nomogram). Net reclassification and integrated discrimination improvement were superior with the sex-specific risk scores, mostly owing to correct reclassification of events. The sex-specific risk scores in the FIT cohort demonstrated similar discrimination (C statistic, 0.78 for women and 0.79 for men), and calibration was reasonable. Conclusions and Relevance: Sex-specific risk scores better estimate mortality in patients undergoing exercise treadmill testing. In particular, these sex-specific risk scores help to identify patients at the highest residual risk in the present era.

Predictors of long-term outcomes in patients with hypertrophic cardiomyopathy undergoing cardiopulmonary stress testing and echocardiography.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) have exercise intolerance due to left ventricular outflow tract (LVOT) obstruction, mitral regurgitation, and left ventricular dysfunction. We sought to study predictors of outcomes in HCM patients undergoing cardiopulmonary stress testing (CPT). METHODS: We studied 1,005 HCM patients (50 ± 14 years, 64% men, 77% on ß-blockers) who underwent CPT with echocardiography. Clinical, echocardiographic, and exercise variables (peak oxygen consumption [VO2] and heart rate recovery [HRR] at first minute postexercise) were recorded. End point was a composite of death, appropriate defibrillator discharges, resuscitated sudden death, stroke, and heart failure admission. RESULTS: Mean left ventricular ejection fraction (LVEF), postexercise LVOT gradient, and peak VO2 were 62% ± 6%, 92 ± 51 mm Hg, and 21 ± 6 mL kg(-1) min(-1), respectively. Despite 789 patients (78%) being in New York Heart Association classes I to II, only 8% achieved >100% age-gender predicted peak VO2, whereas 77% and 15% achieved 50% to 100% and <50%, respectively. Left ventricular outflow tract gradient ≥30 mm Hg was observed in 83% patients, whereas 23% had abnormal HRR. More than 5.5 ± 4 years, there were 94 (9%) events; 511 (50%) patients underwent surgery for LVOT obstruction. Multivariable Cox proportional analysis demonstrated % age-gender predicted peak VO2 (hazard ratio [HR] 0.96 [0.93-0.98]), normal vs abnormal HRR (HR 0.48 [0.32-0.73]), higher LVEF (HR 0.96 [0.93-0.98]), surgery (0.53 [0.33-0.83]), and atrial fibrillation (HR 1.65 [1.04-2.60]) were associated with outcomes (all P < .05). CONCLUSIONS: In HCM patients undergoing CPT, a higher % of achieved age-gender predicted VO2 and surgical relief of LVOT obstruction were associated with better outcomes, whereas abnormal HRR, atrial fibrillation, and lower LVEF were associated with worse outcomes.

Discordance of aortic remodeling with clinical outcomes in patients treated with endovascular repair for uncomplicated type B aortic dissection.

Uncomplicated type B aortic dissection is managed with anti-impulse therapy since surgery offers no additional long-term survival advantage. In recent years, thoracic endovascular repair (TEVAR) has been forwarded as a treatment strategy that may retard aortic growth, lower rupture risk, and improve clinical outcome compared to medical management in patients with uncomplicated type B aortic dissection. Although aortic remodeling often serves as a surrogate measure of treatment success in trials of aortic dissection, there is, in fact, little evidence to suggest that aortic remodeling confers a clinical advantage in this patient cohort. TEVAR likely will not be widely recommended for the patient with uncomplicated type B aortic dissection until a prospective comparative clinical trial demonstrates a clear clinical advantage of TEVAR over medical management. Measures of aortic remodeling are poor surrogate measures of treatment success in this patient population.

Age influences anthropometric and fitness-related predictors of bone mineral in men.

OBJECTIVE: This study assessed the influence of age on the predictors of bone mineral in men. METHODS: Middle-age (n = 41, 54 +/- 4 yrs) and older (n = 40, 69 +/- 5 yrs) men underwent grip and knee extensor strength tests, total body dual-energy X-ray absorptiometry with regional analyses and a graded exercise treadmill test. RESULTS: Bone-free lean mass (BFLM) and, to a lesser extent, fat mass (FM) were correlated with bone mineral variables in middle-age men. In older men, BFLM and, to a lesser extent, FM were related to bone mineral content (BMC) at most sites, but inconsistently to bone mineral density (BMD). Knee extensor strength related to bone mineral (BMC and BMD) at most sites in middle-age men, but none in older men. Grip strength inconsistently related to bone mineral in both groups. Aerobic capacity related to bone mineral in middle-age men, but none in older men. In multiple regression, body weight or BFLM predicted bone mineral in middle-age men (R2 = 0.33-0.68) and BMC in older men (R2 = 0.33-0.50). Predictors of BMD were inconsistent in older men. CONCLUSIONS: Relationships of body composition, muscular strength and aerobic capacity to bone mineral are stronger in middle-age versus older men.

Changes in bone mineral and body composition following coronary artery bypass grafting in men.

This study investigated bone mineral and body composition changes after coronary artery bypass grafting (CABG) in men. Twenty-six men 50 to 79 years of age underwent CABG for multivessel coronary disease. Dual-energy x-ray absorptiometry was performed before surgery and 3 months and 1 year after treatment to assess bone mineral content (BMC), bone mineral density (BMD), and body composition. Through 3 months after treatment, BMD decreased at the total body, arms, and pelvis. BMC of the arm decreased and losses at the total body and legs approached significance. Fat-free mass decreased in the arms and total body but not in the legs. Neither total body nor regional fat mass changed. At the 1-year follow-up visit, 15 of the initial 26 subjects returned for dual-energy x-ray absorptiometry. Compared with before treatment, BMD decreased at the total body and legs, whereas losses at the arms approached significance. Arm BMC decreased over the 1-year post-treatment period. No changes were observed in body composition. In conclusion, CABG and the ensuing convalescence period results in considerable arm bone mineral losses through 1 year after treatment.

Knee extensor and flexor torque development with concentric and eccentric isokinetic training.

This study assessed muscular torque and rate of torque development following concentric (CON) or eccentric (ECC) isokinetic training. Thirty-eight women were randomly assigned to either CON or ECC training groups. Training consisted of knee extension and flexion of the nondominant leg three times per week for 20 weeks (SD = 1). Eccentric training increased ECC knee extension and flexion peak torque more than CON training. The ECC group improved acceleration time and time to peak torque with ECC movements versus the CON group. Slow-velocity ECC isokinetic training yielded greater ECC and similar CON torque development gains versus CON training over the course of 20 weeks in young women.

Association between exercise capacity and left ventricular geometry in overweight patients with mild systemic hypertension.

The purpose of this study was to determine the relation between left ventricular (LV) geometry and exercise capacity in unmedicated, hypertensive patients. Analysis of the data revealed peak oxygen consumption (ml kg(-1) min(-1)) for concentric hypertrophy (corrected mean +/- SE 23.5 +/- 1.2) was significantly less (F = 3.68, p <0.02) than the concentric remodeling (28.1 +/- 1.2) and normal (27.3 +/- 0.6) geometries. The LV geometric pattern was found to be associated with exercise capacity in unmedicated, hypertensive patients, such that patients with concentric hypertrophy showed reduced capacity.

Relationship between exercise systolic blood pressure and left ventricular geometry in overweight, mildly hypertensive patients.

OBJECTIVE: To examine the association between the graded exercise systolic blood pressure (SBP) response and left ventricular (LV) geometric structure in patients with untreated mild hypertension. PARTICIPANTS: The study included 80 sedentary, overweight patients (43 female and 37 male) with unmedicated high normal blood pressure or stage 1-2 hypertension. METHODS: An echocardiogram was used to determine LV mass and the relative wall thickness (RWT) in relation to the chamber dimension. Participants performed a maximal graded exercise test, and the SBP was recorded at workloads of 2, 4 and 6 metabolic equivalents and at peak exercise. Separate statistical models were used to determine the influence of LV mass indexed for height(2.7) (LVMIh) and RWT on submaximal exercise SBP and peak exercise SBP, controlling for resting SBP, age, gender, ethnicity and body mass index. RESULTS: A greater RWT was associated with a higher submaximal SBP level (P = 0.038). Neither LVMIh (P = 0.989) nor the interaction of RWT and LVMIh (P = 0.787) were related to the submaximal SBP. None of the main or interaction effects of RWT and LVMIh were associated with the peak exercise SBP level. CONCLUSION: Increases in RWT were associated with higher submaximal exercise SBP responses in a sample of overweight, unmedicated hypertensives. These results suggest that RWT is an important determinant of the association between cardiac mass and exercise SBP response.

Predicting exercise training outcome from cardiac rehabilitation.

PURPOSE: This study was conducted to identify predictors of training effect after 6 months of supervised exercise for cardiac rehabilitation patients. METHODS: Data at baseline and after 6 months of supervised exercise from 60 patients with coronary artery disease were used for this study. All the patients exercised 3 days per week for 5 to 9 months. Attendance exceeded 70%. The training effect was independently evaluated by the change in rate-pressure product at a 5-metabolic equivalent (MET) workload (RPP5), and the change in estimated peak METs (METPK) during treadmill testing. Baseline variables were examined to identify predictors of change in RPP5 and METPK separately using multiple linear regression. RESULTS: A reduction in RPP5 (-23 +/- 33 bpm x mm Hg x 10(2); P<.0001) and an increase in METPK (2.1 +/- 1.7 METs; P<.0001) were found after training. Baseline fitness was the best predictor of training effect. Inverse relations were found between baseline scores and change scores for RPP5 (r=-0.68; P<.001) and METpk (r=-0.39; P=.002). Beta-blocker status also was useful for predicting change in RPP5. No association was found between training effect and age, revascularization status, or exercise-induced ischemia. CONCLUSIONS: Training effect has limited predictability using baseline variables. No baseline patient characteristics other than high initial fitness were related to reduced training effect. Therefore, patients with clinical characteristics similar to those evaluated in this study can achieve a training effect successfully and are eligible for cardiac rehabilitation. The findings of this study support previous research related to this topic.

Adaptation of pulmonary oxygen consumption slow component following 6 weeks of exercise training above and below the lactate threshold in untrained men.

STUDY OBJECTIVES: To examine the effects of 6 weeks of exercise training above or below the lactate threshold (LT) on the slow component (SC) of pulmonary oxygen consumption (.VO(2)). DESIGN: Randomized controlled trial. SETTING: University human performance laboratory. PARTICIPANTS: Apparently healthy, untrained men (n = 18). INTERVENTIONS: Subjects were randomized to one of three groups: high-intensity exercise training (HI) [above the LT], moderate-intensity exercise training (MOD) [below the LT], or no exercise training (CON). Exercise groups performed cycle ergometry 4 d/wk for 6 weeks. Total work throughout training was constant between groups. MEASUREMENTS AND RESULTS: Maximal cycle ergometry was performed at baseline and after training to assess power output at the LT (WLT), .VO(2) at the LT (.VO(2)LT), and peak .VO(2) (.VO(2)PK). High-intensity, constant-load cycling was performed at baseline and weeks 1, 2, 4, and 6 to assess SC adaptations. WLT, .VO(2)LT, and .VO(2)PK increased after 6 weeks in both exercise groups compared to the CON group (p < 0.05), although there were no differences between the training groups. SC of .VO(2) decreased 44% in the HI group following 1 week of exercise training vs MOD (20%, p < 0.05) and CON (12%, p < 0.01) groups. The SC attenuation was more prominent at all time points in the HI group compared to the MOD group. Total SC attenuation over the 6-week training period did not differ between the HI (71%) and MOD (57%) groups. CONCLUSIONS: Training at HI or MOD produced similar improvements in the LT, .VO(2), and power output at peak exertion when total work output was held constant. Attenuation of the SC with training above and below the LT were similar, although above-LT training promoted faster SC adaptations.

Recovery of self-reported functional capacity after coronary artery bypass surgery.

STUDY OBJECTIVES: This study was conducted to determine the effects of age, gender, comorbid conditions, and exercise on the recovery of self-reported functional capacity after coronary artery surgery, and to identify predictors of 1-year functional capacity. PATIENTS: One hundred ninety-eight patients undergoing coronary artery bypass graft surgery. MEASUREMENTS AND RESULTS: Self-reported functional capacity was evaluated before surgery, and 3 months and 1 year postoperatively using the Veterans Specific Activity Questionnaire (VSAQ). Patients were classified into groups based on age, gender, comorbid conditions, and postoperative exercise. Repeated-measures analysis of variance was used to determine if groups differed with respect to functional capacity recovery and multiple linear regression was used to identify predictors of 1-year VSAQ score. A significant time by age interaction was found (p = 0.0001), with a more protracted recovery for older patients. There were significant group effects for gender (p = 0.0001), and presence of comorbid conditions (p = 0.0009); however, there were no time/group interactions for these variables. A significant group effect was found for postoperative exercise (p = 0.0001), with a trend toward group/time interaction (p = 0.096). Predictors of 1-year functional capacity were VSAQ score in the year prior to surgery and performance of regular aerobic exercise in the postoperative period. CONCLUSIONS: This study suggests that older patients attain good self-reported functional outcomes after surgery; however, the time course for recovery is more protracted than for younger patients. Functional capacity in the year prior to surgery and postoperative exercise are key predictors of 1-year functional capacity.

Use of the SF36 general health status survey to document health-related quality of life in patients with coronary artery disease: effect of disease and response to coronary artery bypass graft surgery.

OBJECTIVE: The purpose of this study was to determine if the SF36 general health status survey has the sensitivity to detect physical function impairments before surgery and the expected improvement in health-related quality of life variables after elective coronary artery bypass graft (CABG) surgery. DESIGN: A prospective, nonrandomized study design was used. OUTCOME MEASURES: The SF36 general health status survey comprises 36 multiple choice questions sorted into 8 categories, or subscales, that describe overall health status. The scores of this survey were used to measure the outcome. INTERVENTION: The SF36 was administered before surgery and at 12-month follow-up. Patients were also queried about the occurrence of angina with normal activities of daily living. RESULTS: Before surgery (n = 81), scores for all SF36 subscales (with the exception of mental health) were lower than published normative data, indicating the disease burden of coronary artery disease. At 12-month follow-up, scores in 6 of 8 subscales improved significantly; general health and role-emotional scores did not change. These changes in SF36 scores at follow-up paralleled a decreased occurrence of angina; before CABG surgery, 75% of patients (61 of 81) had angina; at 12-month follow-up, only 3.7% of patients (3 of 81) had angina. CONCLUSIONS: The SF36 can be used effectively to document changes in health-related quality of life variables in patients with coronary artery disease after CABG surgery.