Hemodynamic effects of unloading the old heart.

A reduction in upright exercise capacity with aging in healthy individuals is accompanied by acute left ventricular (LV) dilatation and impaired LV ejection. To determine whether acute vasodilator administration would improve LV ejection during exercise, sodium nitroprusside (NP) was administered to 16 healthy subjects, ages 64-84 yr, who had been screened for the absence of coronary heart disease by prior exercise thallium scintigraphy. Infusion of NP (0. 3-1.0 microgram. kg(-1). min(-1)), titrated to reduce the resting mean arterial pressure 10% (and eliminate the late augmentation of carotid arterial pressure), increased LV ejection fraction (EF) compared with placebo during upright, maximal graded cycle exercise at all work rates and permitted an equivalent stroke volume and stroke work from a smaller end-diastolic volume. The maximum increase in exercise EF in older subjects during NP infusion was equal to that in healthy, younger (22-39 yr) control subjects. The maximum cycle work rate and cardiac index were unchanged compared with placebo. Thus combined preload and afterload reduction with NP in older individuals improves overall LV ejection phase function: exercise LV stroke work is reduced, EF is increased, and stroke volume is maintained in the setting of a reduced ventricular size. These findings suggest that at least some of the age-associated decline in cardiac function during maximal aerobic exercise may be secondary to adverse loading conditions.

Expanded blood volumes contribute to the increased cardiovascular performance of endurance-trained older men.

To determine whether expanded intravascular volumes contribute to the older athlete's higher exercise stroke volume and maximal oxygen consumption (VO2 max), we measured peak upright cycle ergometry cardiac volumes (99mTc ventriculography) and plasma (125I-labeled albumin) and red cell (NaCr51) volumes in 7 endurance-trained and 12 age-matched lean sedentary men. The athletes had approximately 40% higher VO2 max values than did the sedentary men and larger relative plasma (46 vs. 38 ml/kg), red cell (30 vs. 26 ml/kg), and total blood volumes (76 vs. 64 ml/kg) (all P < 0.05). Athletes had larger peak cycle ergometer exercise stroke volume indexes (75 vs. 57 ml/m2, P < 0.05) and 17% larger end-diastolic volume indexes. In the total group, VO2 max correlated with plasma, red cell, and total blood volumes (r = 0.61-0.70, P < 0.01). Peak exercise stroke volume was correlated directly with the blood volume variables (r = 0.59-0.67, P < 0.01). Multiple regression analyses showed that fat-free mass and plasma or total blood volume, but not red cell volume, were independent determinants of VO2 max and peak exercise stroke volume. Plasma and total blood volumes correlated with the stroke volume and end-diastolic volume changes from rest to peak exercise. This suggests that expanded intravascular volumes, particularly plasma and total blood volumes, contribute to the higher peak exercise left ventricular end-diastolic volume, stroke volume, and cardiac output and hence the higher VO2 max in master athletes by eliciting both chronic volume overload and increased utilization of the Frank-Starling effect during exercise.

Independent prognostic significance of ischemic ST-segment response limited to recovery from treadmill exercise in asymptomatic subjects.

BACKGROUND: Although exercise-induced ST depression is an independent predictor of future coronary events in asymptomatic populations, the predictive value of ST depression beginning after exercise cessation is unknown. METHODS AND RESULTS: We analyzed the treadmill exercise tests of 825 healthy volunteers who were 22 to 89 years of age from the Baltimore Longitudinal Study of Aging. All subjects were free from coronary heart disease by history, physical examination, and resting ECG. From 825 participants, 611 (group 0) had no ischemic ST-segment changes during or after treadmill exercise, while 214 subjects developed > or = 1-mm flat or downsloping ST depression: 151 (group 1) had ST changes starting during exercise, and 63 (group 2) had changes limited to recovery. Groups 1 and 2 were similar in age, sex, smoking status, hypertension prevalence, fasting plasma glucose, and serum cholesterol (CHOL). However, both groups were older and had higher CHOL and prevalence of hypertension than group 0. Treadmill exercise duration, peak oxygen consumption, and maximal heart rate were similar between groups 1 and 2 but were lower than in group 0 (each P < 0.05). During a mean follow-up time of 9 years, 55 subjects developed coronary events (angina pectoris, myocardial infarction, or coronary death): 21 of 611 (3.4%) in group 0, 22 of 151 (14.6%) in group 1, and 12 of 63 (19%) in group 2 (P = 0.001). By survival analysis, the risk of coronary events was similar in groups 1 and 2 but significantly higher than in group 0 (P < 0.0001). Multiple logistic regression showed that age (odds ratio [OR] = 1.07 per year, P = 0.00001), CHOL (OR = 1.02 per 1 mg, P = 0.0001), and presence of ST-segment depression (OR = 2.59, P = 0.007 and OR = 2.38, P = 0.04 for groups 1 and 2, respectively) were independent predictors of events. CONCLUSIONS: Thus, ischemic ST-segment changes developing during recovery from treadmill exercise in apparently healthy individuals have adverse prognostic significance similar to those appearing during exercise.

Do echocardiographic changes explain the age-associated increase in exercise-induced supraventricular arrhythmias?

Although exercise-induced supraventricular arrhythmias (EISVA) increase with advancing age, it is unclear whether age-associated changes in cardiac structure or function play a major role in this increase. To address this question, we examined the relationship between M-mode echocardiographic variables and EISVA occurring during maximal treadmill exercise in 366 healthy volunteers aged 20 to 90 years from the Baltimore Longitudinal Study of Aging. Simple (i.e., isolated) EISVA were detected in 69 subjects (19%), and complex EISVA (i.e., comprising > 10% of beats in any minute or occurring in runs) in another 29 subjects (8%). Univariate predictors of any EISVA, whether simple or complex, were older age (p < 0.0001), male gender (p < 0.05), greater left atrial size (p < 0.01), left ventricular mass index (p < 0.0001), interventricular septal thickness (p < 0.001), isovolumic relaxation time (p < 0.01), atrial filling fraction (p < 0.01), reduced mitral E-F closure slope (p < 0.001), peak E velocity (p < 0.02), and peak E/A ratio (p < 0.0001). Lesser exercise duration (p < 0.01), lower maximal heart rate (p < 0.0001), and higher peak systolic and diastolic blood pressures (p < 0.001) were also associated with EISVA. However, by multiple logistic regression analysis, age (p < 0.0001) was the only independent predictor of any EISVA. Univariate predictors of complex EISVA were greater age (p < 0.0001), and atrial filling fraction (p < 0.001), diastolic blood pressure (p < 0.05), lesser mitral E-F slope (p < 0.004), exercise duration (p < 0.005) and maximal heart rate (p < 0.01). However, only age (p < 0.0001) independently predicted complex EISVA. Thus, in healthy volunteers undergoing maximal treadmill exercise. EISVA are associated with greater left ventricular wall thickness, reduced early diastolic performance, diminished exercise capacity and elevated exercise blood pressure. However, none of these variables are independent predictors of EISVA over and above the powerful effect of age.

Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men.

BACKGROUND: Although it has become clear that habitual exercise in older individuals can partially offset age-associated cardiovascular declines, it is not known whether the beneficial effects of exercise training in older individuals depend on their prior fitness level. METHODS AND RESULTS: Ten sedentary men (S), age 60.0 +/- 1.6 years (mean +/- SEM), who were carefully screened to exclude cardiac disease underwent exercise training for 24 to 32 weeks, and eight age-matched endurance-trained men (ET) stopped their exercise training for 12 weeks. All underwent treadmill exercise and rest and maximal cycle exercise upright gated blood pool scans at baseline and after the lifestyle intervention. Before the intervention, the treadmill maximum rate of oxygen consumption (Vo2max) was 49.9 +/- 1.9 and 32.1 +/- 1.4 mL.kg-1.min-1 in ET and S, respectively. During upright cycle exercise at exhaustion, although heart rate did not differ between groups, cardiac index, stroke volume index, ejection fraction, and left ventricular contractility index (systolic blood pressure/end-systolic volume index) all were significantly higher, and end-systolic volume index, diastolic blood pressure, and total systemic vascular resistance all were significantly lower in ET versus S. After the partial deconditioning of ET men, Vo2max fell to 42 +/- 2.2 mL.kg-1.min-1, and training of S increased Vo2max to 36.2 +/- 1.6 mL.kg-1.min-1. Training of S had effects on cardiovascular function that were similar in magnitude but directionally opposite those of detraining ET. All initial differences in cardiovascular performance at peak work rate between S and ET were abolished with the intervention. Across the broad range of fitness levels encountered before and after change in training status (Vo2max of 26 to 58 mL.kg-1.min-1), cardiac index, stroke volume index, end-systolic volume index, ejection fraction, and the left ventricular contractility index were all linearly correlated with Vo2max. CONCLUSIONS: Exercise training or detraining of older men results in changes in left ventricular performance that are qualitatively and quantitatively similar, regardless of the initial level of fitness before the intervention.

Why do exercise-induced ventricular arrhythmias increase with age? Role of M-mode echocardiographic aging changes.

BACKGROUND: Although advancing age is associated with a higher prevalence and complexity of exercise-induced ventricular arrhythmias (EIVA), the role of age-associated cardiac anatomic and functional characteristics in this relationship has not been explored. METHODS: We performed both M-mode echocardiography and maximal treadmill exercise testing within two consecutive visits in 366 healthy volunteers ages 20 to 90 years from the Baltimore Longitudinal Study of Aging. RESULTS: Simple (i.e., isolated) EIVA were detected in 79 subjects (21%) and complex EIVA (i.e., EIVA comprising > or = 10% of beats in any minute or occurring in runs) in another 17 (5%). Univariate predictors of any EIVA, whether simple or complex, were older age (p < .0001), greater LV mass index (p < .0001), male gender (p < .001), higher peak exercise systolic blood pressure (p = .003), and larger body surface area (p = .005). By multiple logistic regression analysis, only age (p = .0001) independently predicted the occurrence of EIVA. For complex EIVA alone, the strongest univariate predictors were age (p = .004), male gender (p = .008), lower maximal heart rate (p = .01), greater left atrial size (p = .03), and larger LV posterior wall thickness (p = .04); on multiple logistic regression, only older age (p = .03) and larger left atrial size (p = .04) independently predicted the presence of complex EIVA. CONCLUSION: In healthy volunteers undergoing maximal treadmill exercise, greater LV wall thickness and mass are associated with the development of EIVA but they do not independently predict EIVA once the powerful effect of age is considered. The association between complex EIVA and left atrial dilatation may be mediated by higher LV end diastolic pressure and volume during exercise in subjects with larger left atria.

Cardiovascular responses to exhaustive upright cycle exercise in highly trained older men.

It is unclear whether the markedly enhanced aerobic exercise capacity of older endurance-trained men relative to their sedentary age peers is mediated primarily by central or peripheral cardiovascular mechanisms. To address this question, we performed radionuclide ventriculography with respiratory gas exchange measurements during exhaustive upright cycle ergometry in 16 endurance-trained men aged 63 +/- 7 yr and in 35 untrained men of similar age. As expected, maximal O2 consumption during treadmill exercise was much higher in athletes than in controls. At rest and during fixed submaximal cycle work rates through 100 W, athletes demonstrated lower heart rates and greater stroke volume indexes than controls while maintaining similar cardiac indexes and O2 uptake (VO2). At exhaustion, athletes achieved 53% higher work rates and peak VO2 per kilogram body weight than the sedentary men. The higher peak VO2 in athletes was achieved by a 22.5% larger cardiac index and a 15.6% greater arteriovenous O2 difference. The larger peak cardiac index in the athletes than in sedentary controls was mediated entirely by a greater stroke volume index; peak heart rates were virtually identical. The athletes' greater stroke volume index was achieved through an 11% larger end-diastolic volume index and a 7% higher ejection fraction, both of borderline significance. At exhaustion, athletes demonstrated a lower systemic vascular resistance than controls, despite a higher value at rest. Athletes also showed greater exercise-induced increments in heart rate, stroke volume index, and cardiac index and a greater reduction in systemic vascular resistance from rest to maximal workload.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age and aerobic capacity on arterial stiffness in healthy adults.

BACKGROUND: It has been well established that arterial stiffness, manifest as an increase in arterial pulse wave velocity or late systolic amplification of the carotid artery pressure pulse, increases with age. However, the populations studied in prior investigations were not rigorously screened to exclude clinical hypertension, occult coronary disease, or diabetes. Furthermore, it is unknown whether exercise capacity or chronic physical endurance training affects the age-associated increase in arterial stiffness. METHODS AND RESULTS: Carotid arterial pressure pulse augmentation index (AGI), using applanation tonometry, and aortic pulse wave velocity (APWV) were measured in 146 male and female volunteers 21 to 96 years old from the Baltimore Longitudinal Study of Aging, who were rigorously screened to exclude clinical and occult cardiovascular disease. Aerobic capacity was determined in all individuals by measurement of maximal oxygen consumption (VO2max) during treadmill exercise. In this healthy, largely sedentary cohort, the arterial stiffness indexes AGI and APWV increased approximately fivefold and twofold, respectively, across the age span in both men and women, despite only a 14% increase in systolic blood pressure (SBP). These age-associated increases in AGI and APWV were of a similar magnitude to those in prior studies of less rigorously screened populations. Both AGI and APWV varied inversely with VO2max, and this relationship, at least for AGI, was independent of age. In endurance trained male athletes, 54 to 75 years old (VO2max = 44 +/- 3 mL.kg-1.min-1), the arterial stiffness indexes were significantly reduced relative to their sedentary age peers (AGI, 36% lower; APWV, 26% lower) despite similar blood pressures. CONCLUSIONS: Even in normotensive, rigorously screened volunteers in whom SBP increased an average of only 14% between ages 20 and 90 years, major age-associated increases of arterial stiffness occur. Higher physical conditioning status, indexed by VO2max, was associated with reduced arterial stiffness, both within this predominantly sedentary population and in endurance trained older men relative to their less active age peers. These findings suggest that interventions to improve aerobic capacity may mitigate the stiffening of the arterial tree that accompanies normative aging.

Additive effects of age and silent myocardial ischemia on the left ventricular response to upright cycle exercise.

To separate the independent effects of age and silent myocardial ischemia on the left ventricular response to aerobic exercise, maximal upright cycle ergometry was performed in three groups: 8 clinically healthy older men [76 +/- 3 (SE) yr] with ischemic electrocardiogram (ECG) and Tl scan responses to prior maximal treadmill exercise (old silent ischemic subjects), 16 age-matched men with normal ECG and Tl scan responses (old controls), and 21 healthy young (33 +/- 1 yr) men (young controls). Although the left ventricular ejection fraction, end-diastolic volume index, and end-systolic volume index were similar in the three groups at rest, with increasing work loads there was a progressive increase in the end-diastolic volume index and a blunted decline in end-systolic volume index in the two older groups, which was most apparent in the old silent ischemic subjects. Thus, at peak effort, end-diastolic volume index was largest in old silent ischemic subjects (101 +/- 6 ml/m2), intermediate in old controls (85 +/- 6 ml/m2), and smallest in young controls (67 +/- 3 ml/m2) (P < 0.002); conversely, left ventricular ejection fraction was highest in young controls (85 +/- 2), intermediate in old controls (76 +/- 3), and lowest in the old silent ischemic group (66 +/- 2) (P < 0.001). At exhaustion the peak systolic pressure-end-systolic volume index was significantly lower in the silent ischemic group than in young controls (6 +/- 1 vs. 25 +/- 4 mmHg.ml-1 x m-2, respectively; P < 0.001) with the old controls in between (16 +/- 5 mmHg.ml-1 x m-2).(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency and importance of postprandial blood pressure reduction in elderly nursing-home patients.

OBJECTIVE: To determine the frequency and importance of postprandial reductions in systolic blood pressure in debilitated, elderly patients receiving nursing home care. DESIGN: Cohort study. SETTING: Community-based, university-affiliated, teaching nursing home. PATIENTS: A total of 113 volunteer nursing-home residents with a mean (+/- SD) age of 78 +/- 9 years; seven residents who refused the test meal served as controls. INTERVENTION: Participants had sequential blood pressure measurements for 90 minutes after the administration of a standardized meal. MEASUREMENTS AND MAIN RESULTS: Of 113 patients, 109 (96%) showed a postprandial reduction in systolic blood pressure (mean reduction, 17.9 +/- 15.5 mm Hg) within 75 minutes; 41 patients (36%) had a reduction in systolic blood pressure of more than 20 mm Hg. Twelve patients (11%) had a reduction in systolic blood pressure to less than 100 mm Hg (mean systolic blood pressure, 88 +/- 6.4 mm Hg); two of these patients became acutely symptomatic. Multiple regression analysis showed that higher premeal systolic blood pressure, a history of syncope, treatment with vasodilators, and dependent posture of the lower extremities during the postprandial period were all associated with a more severe postprandial decline in systolic blood pressure. Systolic blood pressure in noneating control subjects did not change during the same observation period. No significant differences in the mean systolic blood pressure nadir were found between the 14 patients who died during the follow-up period (mean follow-up, 6.1 +/- 3.8 months) and those who survived. CONCLUSION: Postprandial reductions in systolic blood pressure among elderly nursing-home patients are common, often large, and potentially symptomatic, but they do not generally presage subsequent intermediate-term mortality.