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Objective: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) Blood Pressure Trial reported no differences in most cardiovascular disease (CVD) outcomes between intensive and standard blood pressure therapy in individuals with diabetes mellitus (DM) and hypertension. Many such individuals are centrally obese. Here we evaluate whether the trial outcomes varied by the level of central obesity.Research Design and Methods: The cohort included 4,687 people (47.7% women) with DM and hypertension. Mean age was 62.2, and mean follow-up was 4.7 years. Participants were randomly assigned to one of two blood pressure treatment strategies: intensive (systolic <120 mmHg) or standard (systolic <140 mmHg). Sex-specific quartiles of waist-to-height ratio were used as the measure of central obesity. The primary ACCORD outcome (a composite of nonfatal myocardial infarction [MI], nonfatal stroke, or CVD death) and three secondary outcomes (nonfatal MI, fatal or nonfatal stroke, and CVD death) were examined using proportional hazard models.Results: There was no evidence that the effect of intensively lowering blood pressure differed by quartile of waist-to-height ratio for any of the four outcomes (P > 0.25 in all cases). Controlling for waist-to-height quartile had no significant impact on previously published results for intensive blood pressure therapy. Waist-to-height ratio was significantly related to CVD mortality (hazard ratio 2.32 [95% CI 1.40-3.83], P = 0.0009 comparing the heaviest to lightest quartiles), but not to the other outcomes (P > 0.09 in all cases).Conclusions: Intensive lowering of blood pressure versus standard treatment does not ameliorate CVD risk in individuals with DM and hypertension. These results did not vary by quartile of waist-to-height ratio. [ABSTRACT FROM AUTHOR]

Initial research established the feasibility of exercise training in patients with heart failure, as well as associated physiological benefits. This review summarizes the findings from over two dozen single-site studies that address the effect of exercise training on exercise capacity and cardiovascular and peripheral function. In addition, it incorporates the results from two meta-analyses and a recently completed multi-center trial, all of which studied the effects of exercise training on clinical outcomes. The major conclusions from these studies are that exercise training is safe; improves health status and exercise capacity; helps attenuate much of the abnormal pathophysiology that develops with heart failure; and yields a modest reduction in clinical events. The magnitude of the clinical benefits appears related to the volume of exercise completed. Future research is needed to identify which patient subgroups might benefit the most from exercise training, the optimal exercise dose or load needed to lessen disease-related symptoms and maximize clinical benefit, and the effects of exercise training in patients with heart failure and preserved left ventricular systolic function. [ABSTRACT FROM AUTHOR]

Context: Guidelines recommend that exercise training be considered for medically stable outpatients with heart failure. Previous studies have not had adequate statistical power to measure the effects of exercise training on clinical outcomes.Objective: To test the efficacy and safety of exercise training among patients with heart failure.Design, Setting, and Patients: Multicenter, randomized controlled trial of 2331 medically stable outpatients with heart failure and reduced ejection fraction. Participants in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) were randomized from April 2003 through February 2007 at 82 centers within the United States, Canada, and France; median follow-up was 30 months.Interventions: Usual care plus aerobic exercise training, consisting of 36 supervised sessions followed by home-based training, or usual care alone.Main Outcome Measures: Composite primary end point of all-cause mortality or hospitalization and prespecified secondary end points of all-cause mortality, cardiovascular mortality or cardiovascular hospitalization, and cardiovascular mortality or heart failure hospitalization.Results: The median age was 59 years, 28% were women, and 37% had New York Heart Association class III or IV symptoms. Heart failure etiology was ischemic in 51%, and median left ventricular ejection fraction was 25%. Exercise adherence decreased from a median of 95 minutes per week during months 4 through 6 of follow-up to 74 minutes per week during months 10 through 12. A total of 759 patients (65%) in the exercise training group died or were hospitalized compared with 796 patients (68%) in the usual care group (hazard ratio [HR], 0.93 [95% confidence interval {CI}, 0.84-1.02]; P = .13). There were nonsignificant reductions in the exercise training group for mortality (189 patients [16%] in the exercise training group vs 198 patients [17%] in the usual care group; HR, 0.96 [95% CI, 0.79-1.17]; P = .70), cardiovascular mortality or cardiovascular hospitalization (632 [55%] in the exercise training group vs 677 [58%] in the usual care group; HR, 0.92 [95% CI, 0.83-1.03]; P = .14), and cardiovascular mortality or heart failure hospitalization (344 [30%] in the exercise training group vs 393 [34%] in the usual care group; HR, 0.87 [95% CI, 0.75-1.00]; P = .06). In prespecified supplementary analyses adjusting for highly prognostic baseline characteristics, the HRs were 0.89 (95% CI, 0.81-0.99; P = .03) for all-cause mortality or hospitalization, 0.91 (95% CI, 0.82-1.01; P = .09) for cardiovascular mortality or cardiovascular hospitalization, and 0.85 (95% CI, 0.74-0.99; P = .03) for cardiovascular mortality or heart failure hospitalization. Other adverse events were similar between the groups.Conclusions: In the protocol-specified primary analysis, exercise training resulted in nonsignificant reductions in the primary end point of all-cause mortality or hospitalization and in key secondary clinical end points. After adjustment for highly prognostic predictors of the primary end point, exercise training was associated with modest significant reductions for both all-cause mortality or hospitalization and cardiovascular mortality or heart failure hospitalization.Trial Registration: clinicaltrials.gov Identifier: NCT00047437. [ABSTRACT FROM AUTHOR]

Context: Individuals with diabetes are at increased risk for cardiovascular disease (CVD), but more aggressive targets for risk factor control have not been tested.Objective: To compare progression of subclinical atherosclerosis in adults with type 2 diabetes treated to reach aggressive targets of low-density lipoprotein cholesterol (LDL-C) of 70 mg/dL or lower and systolic blood pressure (SBP) of 115 mm Hg or lower vs standard targets of LDL-C of 100 mg/dL or lower and SBP of 130 mm Hg or lower.Design, Setting, and Participants: A randomized, open-label, blinded-to-end point, 3-year trial from April 2003-July 2007 at 4 clinical centers in Oklahoma, Arizona, and South Dakota. Participants were 499 American Indian men and women aged 40 years or older with type 2 diabetes and no prior CVD events.Interventions: Participants were randomized to aggressive (n=252) vs standard (n=247) treatment groups with stepped treatment algorithms defined for both.Main Outcome Measures: Primary end point was progression of atherosclerosis measured by common carotid artery intimal medial thickness (IMT). Secondary end points were other carotid and cardiac ultrasonographic measures and clinical events.Results: Mean target LDL-C and SBP levels for both groups were reached and maintained. Mean (95% confidence interval) levels for LDL-C in the last 12 months were 72 (69-75) and 104 (101-106) mg/dL and SBP levels were 117 (115-118) and 129 (128-130) mm Hg in the aggressive vs standard groups, respectively. Compared with baseline, IMT regressed in the aggressive group and progressed in the standard group (-0.012 mm vs 0.038 mm; P < .001); carotid arterial cross-sectional area also regressed (-0.02 mm(2) vs 1.05 mm(2); P < .001); and there was greater decrease in left ventricular mass index (-2.4 g/m(2.7) vs -1.2 g/m(2.7); P = .03) in the aggressive group. Rates of adverse events (38.5% and 26.7%; P = .005) and serious adverse events (n = 4 vs 1; P = .18) related to blood pressure medications were higher in the aggressive group. Clinical CVD events (1.6/100 and 1.5/100 person-years; P = .87) did not differ significantly between groups.Conclusions: Reducing LDL-C and SBP to lower targets resulted in regression of carotid IMT and greater decrease in left ventricular mass in individuals with type 2 diabetes. Clinical events were lower than expected and did not differ significantly between groups. Further follow-up is needed to determine whether these improvements will result in lower long-term CVD event rates and costs and favorable risk-benefit outcomes.Trial Registration: clinicaltrials.gov Identifier: NCT00047424. [ABSTRACT FROM AUTHOR]

Background. The Public Access Defibrillation (PAD) Trial found an overall doubling in the number of out-of-hospital cardiac arrest (CA) survivors when a lay responder team was equipped with an automated external defibrillator (AED), compared with cardiopulmonary resuscitation (CPR) alone. Objectives. To describe the types of facilities that participated in the trial and to report the incidence of CA and survival in these different types of facilities. Methods. In this post-hoc analysis of PAD Trial data, the physical characteristics of the participating facilities and the numbers of presumed CAs, treatable CAs, and survivors are reported for each category of facilities. Results. There were 625 presumed CAs at 1,260 participating facilities. Just under half (n = 291) of the presumed CAs were classified as treatable CAs. Treat-able CAs occurred at a rate of 2.9 per 1,000 person-years of exposure; rates were highest in fitness centers (5.1) and golf courses (4.8) and lowest in office complexes (0.7) and hotels (0.7). Survival from treatable CA was highest in recreational complexes (0.5), public transportation sites (0.4), and fitness centers (0.4) and lowest in office complexes (0.1) and residential facilities (0.0). Conclusions. During the PAD Trial, the exposure-adjusted rate of treatable CA was highest in fitness centers and golf courses, but the incidence per facility was low to moderate. Survival from treatable cardiac arrest was highest in recreational complexes, public transportation facilities, and fitness centers. Key words: public-access defibrillation; cardiac arrest; survival; automated external defibrillator. [ABSTRACT FROM AUTHOR]

Objective: Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1-6.9 mmol/l as impaired fasting glucose (IFG) and <6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6-6.9 mmol/l and normal fasting glucose to <5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG.Research Design and Methods: We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality.Results: Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by approximately 40% in the 6.1-6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased.Conclusions: These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results. [ABSTRACT FROM AUTHOR]

Background: We examined secular trends in leisure-time physical activities (LTPA) in health-conscious men (n = 1359) from 1958 to 1998 and in women (n = 839) from 1978 to 1998, who were participants of the Baltimore Longitudinal Study of Aging (BLSA).Methods: LTPA was the self-reported time spent performing 97 activities, and was converted to metabolic equivalent of oxygen uptake (MET) minutes per day. Evaluations of LTPA were averaged for each decade. The prevalence of a sedentary lifestyle in each decade was assessed based on compliance with widely publicized recommendations for participation in physical activity. All analyses were adjusted for age, education, and race differences across decades.Results: Median high-intensity LTPA, defined as activities >/=6 METs, increased from 30 to 80 MET min/day from the 1960s to the 1990s for men (P < 0.01) but did not change between the 1970s and the 1990s in women. Moderate-intensity LTPA, defined as 4-5.9 METs, did not change significantly over these periods in either sex. The percentage of sedentary men, defined as those performing <40 MET min/day of high-intensity LTPA, declined across the four decades, whereas for women it did not change significantly.Conclusions: In a health-conscious sample across a broad age range, national recommendations appear to have made modest progress in decreasing the proportion of sedentary adults. [ABSTRACT FROM AUTHOR]

A questionnaire was administered to a random sample of family practitioners, internists, cardiologists, and geriatricians to examine the current management of heart failure patients with preserved versus reduced left ventricular systolic function. In patients with preserved systolic function, electrocardiogram at rest, chest x-ray, echocardiography, digitalis, angiotensin-converting enzyme inhibitors, and restriction of dietary sodium and physical activity are used less often, whereas calcium channel blockers and beta blockers are given more often than to patients with reduced systolic function. [ABSTRACT FROM AUTHOR]

High-physical activity levels are associated with reduced risk of symptomatic coronary artery disease (CAD). However, there are a number of reports of exercise-related sudden death and myocardial infarction in aerobically trained athletes. This study compared the prevalence of exercise-induced silent myocardial ischemia on maximum graded exercise tests with tomographic thallium scintigraphy in 70 master male athletes (63 +/- 6 years, mean +/- SD) (maximum aerobic capacity, VO2max >40 ml/kg/min) and in 85 healthy untrained men (61 +/- 7 years) with no history of CAD. The prevalence of silent ischemia (exercise-induced ST-segment depression on electrocardiogram and perfusion abnormalities on thallium scintigraphy) was similar in athletes and untrained men; 16% of the athletes (11 of 70) had silent ischemia compared with 21% of the untrained men (chi-square = 0.81, p = 0.36). No athletes had hyperlipidemia, systemic hypertension, or diabetes mellitus. However, the apolipoprotein E4 allele was present in 9 of the 11 athletes with silent ischemia compared with 2 of 32 athletes with normal exercise tests (chi-square = 24, p = 0.0001). These results suggest that older male athletes with the apolipoprotein E4 allele are at increased risk for the development of exercise-induced silent ischemia. [ABSTRACT FROM AUTHOR]

Although early cardiac computed tomographic angiography (CCTA) might improve the management of emergency department (ED) patients with acute chest pain, it could also result in increased testing, costs, and radiation exposure. ROMICAT II was a randomized comparative effectiveness trial enrolling patients 40 to 74 years old without known coronary artery disease who presented to the ED with chest pain but without ischemic electrocardiographic (ECG) changes or elevated initial troponin and who required further risk stratification. Overall, 1000 patients at 9 sites within the United States were randomized to either CCTA as the first diagnostic test following serial biomarkers or to standard of care, which included no testing or functional testing such as exercise ECG, stress radionuclide imaging, or stress echocardiography. Test results were provided to ED physicians, yet patient management was not driven by a study protocol in either arm. Data were collected on diagnostic testing, cardiac events, and cost of medical care for the index hospitalization and during the following 28 days. The primary end point was length of hospital stay. Secondary end points were cumulative radiation exposure, resource utilization, and costs of competing strategies. Tertiary end points were institutional, physician, and patient characteristics associated with primary and secondary outcomes. Rate of missed acute coronary syndrome within 28 days was the safety end point. The ROMICAT II will provide rigorous data on whether CCTA is more efficient than standard of care in the management of patients with acute chest pain at intermediate risk for acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Background: Because of the scarcity of data available from direct comparisons of age and gender groups using the same relative training stimulus, it is unknown whether older individuals can increase their muscle mass as much as young individuals and whether women can increase as much as men in response to strength training (ST). In addition, little is known about whether the hypertrophic response to ST is affected by myostatin genotype, a candidate gene for muscle hypertrophy.Methods: Eleven young men (25 +/- 3 years, range 21-29 years), 11 young women (26 +/- 2 years, range 23-28 years), 12 older men (69 +/- 3 years, range 65-75 years), and 11 older women (68 +/- 2 years, range 65-73 years) had bilateral quadriceps muscle volume measurements performed using magnetic resonance imaging (MRI) before and after ST and detraining. Training consisted of knee extension exercises of the dominant leg three times per week for 9 weeks. The contralateral limb was left untrained throughout the ST program. Following the unilateral training period, the subjects underwent 31 weeks of detraining during which no regular exercise was performed. Myostatin genotype was determined in a subgroup of 32 subjects, of which five female subjects were carriers of a myostatin gene variant.Results: A significantly greater absolute increase in muscle volume was observed in men than in women (204 +/- 20 vs 101 +/- 13 cm3, p < .01), but there was no significant difference in muscle volume response to ST between young and older individuals. The gender effect remained after adjusting for baseline muscle volume. In addition, there was a significantly greater loss of absolute muscle volume after 31 weeks of detraining in men than in women (151 +/- 13 vs 88 +/- 7 cm3, p < .05), but no significant difference between young and older individuals. Myostatin genotype did not explain the hypertrophic response to ST when all 32 subjects were assessed. However, when only women were analyzed, those with the less common myostatin allele exhibited a 68% larger increase in muscle volume in response to ST (p = .056).Conclusions: Aging does not affect the muscle mass response to either ST or detraining, whereas gender does, as men increased their muscle volume about twice as much in response to ST as did women and experienced larger losses in response to detraining than women. Young men were the only group that maintained muscle volume adaptation after 31 weeks of detraining. Although myostatin genotype may not explain the observed gender difference in the hypertrophic response to ST, a role for myostatin genotype may be indicated in this regard for women, but future studies are needed with larger subject numbers in each genotype group to confirm this observation. [ABSTRACT FROM AUTHOR]

Background: Current knowledge of age-associated increases in blood pressure is based primarily on unscreened population studies that may not be representative of healthy men and women. We examined longitudinal patterns of change in blood pressure in healthy male and female volunteers from the Baltimore Longitudinal Study of Aging (BLSA).Methods: Longitudinal mixed-effects regression models are used to estimate the age-associated changes in blood pressure in 1307 men (age 17-97) and 333 women (age 18-93) who have been followed for up to 32 years (mean: 8.4 years for men and 3.4 years for women) and who have been screened for health problems or medications that affect blood pressure.Results: On average, systolic pressure is relatively stable in men and women until approximately age 45, increases at 5-8 mm Hg per decade in middle age, then accelerates in men and stabilizes in women. Diastolic pressure increases at 1 mm Hg per decade at all ages in men, whereas in women the rate of change in diastolic pressure increases in middle age and then plateaus and may decline after age 70. Additional findings include: (a) BLSA cross-sectional and longitudinal findings are more similar than has been observed in studies of unscreened samples; (b) there is no evidence of a gender cross-over in this group of healthy men and women; and (c) compared to previous studies of unscreened samples, healthy BLSA men and women show a weaker association between baseline blood pressure and subsequent rate of blood pressure change.Conclusions: These findings suggest that several previously described age-associated patterns of blood pressure change partially reflect the effects of hypertension and its treatment, rather than intrinsic age changes in the blood pressure of healthy individuals. [ABSTRACT FROM AUTHOR]

An increased rate of cardiac symptoms at combat theater hospitals brings concerns about the predeployment health of Army National Guard (ARNG) soldiers on the basis of older age, lower fitness level, and sedentary lifestyle than active duty troops. The purpose of this study was to examine the association of physical fitness, reported physical activity (PA), and coronary risk factors to calculated 10-year hard coronary heart disease (CHD) risk in 136 ARNG soldiers, aged 18-53 years, who failed the 2-mile run of the Army Physical Fitness Test (APFT). The APFT score, derived from a composite of 2-mile run time, sit-ups, and push-ups, related inversely to 10-year CHD risk (r = -0.23, p < 0.01) but no relationship with CHD risk was observed for PA. APFT scores were positively associated with high-density lipoprotein (HDL) cholesterol and inversely with triglycerides, total cholesterol:HDL ratio, diastolic blood pressure, and body mass index (BMI). No relationship existed between PA and any of the CHD risk factors. We conclude that a higher APFT score is associated with a healthier CHD risk factor profile and is a predictor of better predeployment cardiovascular health. [ABSTRACT FROM AUTHOR]

Purpose: To examine the effects of strength training on glucose homeostasis in older individuals, to compare the responses of older men to those of older women, and to determine the time course of responses after training.Methods: Twenty previously untrained older persons (12 M, 8 F, ages 65-75) participated in a 6-month whole-body strength training program 3 days per week using Keiser K-300 air powered resistance machines. Plasma concentrations of glucose and insulin were measured before training after ~12 hr of fasting during a standardized oral glucose tolerance test and again ~24, 48, and 72 hr after training. One-repetition maximum (1-RM) strength was measured for seven exercises, and % fat and fat free mass were measured by dual-energy x-ray absorptiometry before and after the strength training program.Results: Both genders significantly improved their 1-RM strength values for the upper body (men 24%; women 21%) and lower body (men 21%; women 25%) exercises, all p < 0.01. There were no significant reductions in plasma glucose or insulin areas under the oral glucose tolerance test curve in the strength training group as a whole, but the men showed a trend for a greater reduction in insulin total areas than women, p = 0.07. The men also had significant reductions in insulin responses at fasting, p < 0.05, and a trend for a reduction at the 90-min time point, p = 0.06, whereas the women showed increases at these same time points.Conclusion: It appears that strength training produces a more favorable insulin response in older men than in older women. [ABSTRACT FROM AUTHOR]

Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) was a multicenter, randomized controlled trial designed to examine the safety and efficacy of aerobic exercise training versus usual care in 2,331 patients with systolic heart failure (HF). In HF-ACTION patients with rest transthoracic echocardiographic measurements, the predictive value of 8 Doppler echocardiographic measurements-left ventricular (LV) diastolic dimension, mass, systolic (ejection fraction) and diastolic (mitral valve peak early diastolic/peak late diastolic [E/A] ratio, peak mitral valve early diastolic velocity/tissue Doppler peak early diastolic myocardial velocity [E/E'] ratio, and deceleration time) function, left atrial dimension, and mitral regurgitation severity-was examined for a primary end point of all-cause death or hospitalization and a secondary end point of cardiovascular disease death or HF hospitalization. Also compared was the prognostic value of echocardiographic variables versus peak oxygen consumption (Vo(2)). Mitral valve E/A and E/E' ratios were more powerful independent predictors of clinical end points than the LV ejection fraction but less powerful than peak Vo(2). In multivariate analyses for predicting the primary end point, adding E/A ratio to a basic demographic and clinical model increased the C-index from 0.61 to 0.62, compared with 0.64 after adding peak Vo(2). For the secondary end point, 6 echocardiographic variables, but not the LV ejection fraction or left atrial dimension, provided independent predictive power over the basic model. The addition of E/E' or E/A to the basic model increased the C-index from 0.70 to 0.72 and 0.73, respectively (all p values <0.0001). Simultaneously adding E/A ratio and peak Vo(2) to the basic model increased the C-index to 0.75 (p <0.0005). No echocardiographic variable was significantly related to the change from baseline to 3 months in exercise peak Vo(2). In conclusion, the addition of echocardiographic LV diastolic function variables improves the prognostic value of a basic demographic and clinical model for cardiovascular disease outcomes. [ABSTRACT FROM AUTHOR]

Left ventricular diastolic dysfunction (LVDD) has been reported to have strong correlation with exercise capacity. However, this relationship has not been studied extensively in community-dwelling older adults. Data on pulse and tissue Doppler echocardiographic estimates of resting early (E) and atrial (A) transmitral peak inflow and early (Em) mitral annular velocities, and six-minute walk test were obtained from 89 community-dwelling older adults (mean age, 74; range, 65-93 years; 54% women), without a history of heart failure. Overall, 47% had cardiovascular morbidity and 60% had normal diastolic function (E/A 0.75-1.5 and E:Em <10). Among the 36 individuals with LVDD, 83%, 14% and 3% had grade I (E/A <0.75, regardless of E/E(m)), II (E/A 0.75-1.5 and E/E(m) ≥10) and III (E/A>1.5 and E/E(m) ≥10) LVDD, respectively. Those with LVDD were older (77 versus 73 years; p = 0.001) and had a trend for higher prevalence of cardiovascular morbidity (58% versus 40%; p = 0.083). LVDD negatively correlated with six-minute walk distance (1013 versus 1128 feet; R = -0.25; p = 0.017). This association remained significant despite adjustment for cardiovascular morbidity (R = -0.35; p = 0.048), but lost significance when adjusted for age (R = -0.32; p = 0.105), age and cardiovascular morbidity (R = -0.38; p = 0.161), and additional adjustment for sex, race, body mass index, and systolic blood pressure (R = -0.44; p = 0.365). In conclusion, most community-dwelling older adults without heart failure had normal left ventricular diastolic function or grade-I LVDD. Although LVDD was associated with decreased performance on a six-minute walk test, that association was no longer evident after adjustment for age, body mass index and cardiovascular morbidity. [ABSTRACT FROM AUTHOR]

To compare the effects of a pedometer-based behavioral intervention (Fitness for Life [FFL] program) and a traditional high-intensity fitness (TRAD) program on physical activity (PA), Army Physical Fitness Test (APFT), and coronary heart disease risk factors in Army National Guard members who failed the APFT 2-mile run. From a pool of 261 Army National Guard, a total of 156 were randomized to TRAD or FFL for 24 weeks consisting of a 12-week progressive conditioning program followed by 12 weeks of maintenance. For both groups, the total APFT score and 2-mile run time/score improved from baseline to 12 weeks (FFL: down 7.4%, p = 0.03; TRAD: down 5%, p = 0.08) but at 24 weeks they had regressed toward baseline. PA improved modestly and coronary risk profile changed minimally in both groups. A pedometer-based exercise intervention had results similar to a high-intensity program for improving PA, APFT, and 2-mile run times/score. Neither group sustained the improved run times over the 12 weeks of maintenance. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to determine the effect of age on the hemodynamic response to prolonged submaximal aerobic exercise in healthy volunteers.Background: Reductions in peak work rate, heart rate (HR), and left ventricular (LV) emptying but higher blood pressure (BP) and systemic vascular resistance occur in healthy older versus younger humans during short bursts of graded maximal aerobic exercise. However, the effect of aging on the cardiovascular response to prolonged exercise at submaximal work rates typical of daily aerobic activities remains unknown.Methods: We evaluated cardiovascular performance throughout prolonged submaximal upright cycle ergometry in 40 carefully screened healthy untrained volunteers, 8 men and 12 women <50 years old, mean = 37 +/- 8 years (younger), and 10 men and 10 women >/=50 years old, mean = 66 +/- 9 years (older), during upright cycle exercise at 70% of peak cycle oxygen consumption (VO(2)) to exhaustion or a maximum of 120 min. Cardiac volumes were acquired by gated blood pool scans with (99m)Tc at rest and every 10 min throughout exercise.Results: Duration of exercise was similar in younger ([81 +/- 28 min] versus older [71+/- 29 min] subjects, p = NS). At 10 min of exercise in the steady state, older subjects demonstrated lower VO(2) (1.1 +/- 0.2 l/min vs. 1.3 +/- 0.3 l/min) and lower HR (118 +/- 17 vs. 135 +/- 11 beats/min, p < 0.001) but larger end-diastolic (80 +/- 11 ml/m(2) vs. 73 +/- 8 ml/m(2), p = 0.03) and end-systolic volume index (ESVI) 20 +/- 6 ml/m(2) vs. 17 +/- 4 ml/m(2), p < 0.05) than younger ones. Between 10 min and exercise termination, with VO(2) held constant in both groups, increases in HR (14.0 +/- 12.4 beats/min vs. 5.9 +/- 11.5 beats/min, p = 0.04), cardiac index (1.6 +/- 1.0 l/min/m(2) vs. 0.8 +/- 1.1 l/min/m(2), p = 0.03), and LV ejection fraction (7.1 +/- 4.0% vs. 2.9 +/- 4.4%, p = 0.003) were greater in younger than older subjects, respectively, as was the reduction in ESVI (-5.1 +/- 3.0 ml/m(2) vs. -1.8 +/- 3.3 ml/m(2), p = 0.002), despite similar declines in systolic BP (-12.3 +/- 6.3 mm Hg vs. -12.1 +/- 15.0 mm Hg, p = NS).Conclusions: Thus, age-associated deficits in chronotropic and LV systolic reserve performance occur during prolonged submaximal upright cycle ergometry, analogous to those observed during graded maximal exercise. [ABSTRACT FROM AUTHOR]

Both high peak oxygen consumption (VO(2)) and high levels of leisure time physical activity (LTPA) are associated with a reduced risk of cardiovascular morbidity and mortality. We examined the contributions of LTPA and peak VO(2) to the risk of coronary events (CEs) in healthy younger (< or = 65 years, n = 522) and older (>65 years, n = 167) men from the Baltimore Longitudinal Study of Aging. LTPA derived from self reports of time spent in 97 activities were converted into METs-minutes/24 hours and grouped into high (> or = 6 METs), moderate- (4 to 5.9 METs), and low-intensity LTPA (<4 METs). Cardiorespiratory fitness was determined by measuring peak VO(2) during a maximal treadmill exercise test. Over a mean follow-up of 13.4 +/- 6.3 years, CEs occurred in 63 men. After accounting for coronary risk factors, proportional-hazards analyses showed a relative CE risk of 0.53 (p <0.0001) for a SD increase in peak VO(2) in younger men and 0.61 (p = 0.024) in older men, whereas total LTPA was unrelated to coronary risk in either age group. When the 3 LTPA intensity levels were substituted for total LTPA in the model, peak VO(2) remained the only predictor of events in younger men, whereas high-intensity LTPA (RR = 0.39 for tertile 3 vs tertiles 1 and 2, p = 0.016) and peak VO(2) (RR = 0.61/SD increase, p = 0.024) were of similar importance in older men. Thus, in healthy younger men, higher cardiorespiratory fitness but not LTPA predicts a reduced risk of coronary heart disease, independent of conventional risk factors. For older men, high-intensity LTPA and fitness appear to be of similar importance in reducing coronary risk. [ABSTRACT FROM AUTHOR]

Aims: Benefits of mineralocorticoid receptor antagonists (MRAs) in heart failure with preserved and mildly reduced ejection fraction (HFpEF/HFmrEF) have not been established. Conventional randomized controlled trials are complex and expensive. The Spironolactone Initiation Registry Randomized Interventional Trial in Heart Failure with Preserved Ejection Fraction (SPIRRIT-HFpEF) is a unique pragmatic registry-based randomized controlled trial., Methods: SPIRRIT-HFpEF is a multicentre, prospective, randomized, open-label, blinded endpoint trial conducted on platforms in the Swedish Heart Failure Registry (SwedeHF) and the United States (US) Trial Innovation Network. Patients with HFpEF/HFmrEF are randomized 1:1 to spironolactone (or eplerenone) in addition to usual care, versus usual care alone. The primary outcome is total number of cardiovascular deaths and hospitalizations for heart failure. Outcomes are collected from Swedish administrative complete coverage registries and a US call centre and subsequently adjudicated. Simple eligibility criteria were based on data available in SwedeHF: heart failure as outpatient or at discharge from hospital, left ventricular ejection fraction ≥40%, N-terminal pro-B-type natriuretic peptide >300 ng/L (in sinus rhythm) or >750 ng/L (in atrial fibrillation), with pre-specified adjustment for elevated body mass index, and chronic loop diuretic use. Power and sample size assessments were based on an event-driven design allowing enrolment over approximately 6 years, and application of hazard ratios from the TOPCAT trial, Americas subset. The final sample size is expected to be approximately 2400 patients., Conclusion: SPIRRIT-HFpEF will be informative on the effectiveness of generic MRAs in HFpEF and HFmrEF, and on the feasibility of conducting pragmatic and registry-based trials in heart failure and other chronic conditions., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aging is associated with a significant decline in aerobic capacity assessed by maximal exercise oxygen consumption (V̇o 2max ). The relative contributions of the specific V̇o 2 components driving this decline, namely cardiac output (CO) and arteriovenous oxygen difference (A - V)O 2 , remain unclear. We examined this issue by analyzing data from 99 community-dwelling participants (baseline age: 21-96 yr old; average follow-up: 12.6 yr old) from the Baltimore Longitudinal Study of Aging, free of clinical cardiovascular disease. V̇o 2peak , a surrogate of V̇o 2max , was used to assess aerobic capacity during upright cycle ergometry. Peak exercise left ventricular volumes, heart rate, and CO were estimated using repeated gated cardiac blood pool scans. The Fick equation was used to calculate (A - V)O 2 diff,peak from CO peak and V̇o 2peak . In unadjusted models, V̇o 2peak , (A - V)O 2 diff,peak , and CO peak declined longitudinally over time at steady rates with advancing age. In multiple linear regression models adjusting for baseline values and peak workload, however, steeper declines in V̇o 2peak and (A - V)O 2 diff,peak were observed with advanced entry age but not in CO peak . The association between the declines in V̇o 2peak and (A - V)O 2 diff,peak was stronger among those ≥50 yr old compared with their younger counterparts, but the difference between the two age groups did not reach statistical significance. These findings suggest that age-associated impairment of peripheral oxygen utilization during maximal exercise poses a stronger limitation on peak V̇o 2 than that of CO. Future studies examining interventions targeting the structure and function of peripheral muscles and their vasculature to mitigate age-associated declines in (A - V)O 2 diff are warranted. NEW & NOTEWORTHY The age-associated decline in aerobic exercise performance over an average of 13 yr in community-dwelling healthy individuals is more closely associated with decreased peripheral oxygen utilization rather than decreased cardiac output. This association was more evident in older than younger individuals. These findings suggest that future studies with larger samples examine whether these associations vary across the age range and whether the decline in cardiac output plays a greater role earlier in life. In addition, studies focused on determinants of peripheral oxygen uptake by exercising muscle may guide the selection of preventive strategies designed to maintain physical fitness with advancing age.

Competing Interests: Dr Fleg reports employment by the National Heart, Lung, and Blood Institute during the conduct of the study. Drs O’Brien, Berger, Kwong, and Maron and Z. Huang report grants from the National Heart, Lung, and Blood Institute during the conduct of the study. Dr Reynolds reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study. She receives support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study) and Biotelemetry Inc (donation of telemetry monitors for an unrelated research study). Dr Reynolds is also a consultant for HeartFlow. Dr Chaitman reports grants from the National Heart, Lung, and Blood Institute, and personal fees from Merck, NovoNordisk, Sanofi, Lilly, Johnson and Johnson, Daiichi Sankyo, Tricida, Relypsa, Imbria, and Xylocor outside the submitted work. Dr Berman receives software royalties from Cedars-Sinai Medical Center outside the submitted work. Dr Min reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; other from Cleerly Inc, grants and other from GE Healthcare, and other from Arineta outside the submitted work. Dr Bangalore reports grants from the National Heart, Lung, and Blood Institute during the conduct of the study; grants and personal fees from Abbott Vascular; and personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr Hochman is principal investigator for the ISCHEMIA trial for which, in addition to support by the National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular, Medtronic, Inc, Abbott Laboratories (formerly St Jude Medical, Inc), Royal Philips NV (formerly Volcano Corporation), Arbor Pharmaceuticals, LLC, AstraZeneca Pharmaceuticals, LP, Merck Sharp & Dohme Corp, and Omron Healthcare, Inc, and financial donations were provided by Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr Hochman is also the PI of ISCHEMIA-EXTEND. The other authors report no conflicts. The content of this article is solely the responsibility of the authors and does not necessarily represent the views of the National Heart, Lung, and Blood Institute, the National Institutes of Health, or the United States Department of Health and Human Services.