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Biomedical subjects

J L Fleg

Publications and source records attributed to J L Fleg.

At least 91 records · Page 5Linked to original sources
PubMed1990

The age-associated decline in glomerular filtration in healthy normotensive volunteers. Lack of relationship to cardiovascular performance.

Whether the well-documented age-associated decline in the glomerular filtration rate, manifest as a decline in creatinine clearance, is secondary to an age-related change in cardiovascular performance is at present unknown. To answer this question, we measured arterial blood pressure, 24-hour creatinine clearance, and cardiac output determined from gated cardiac blood pool scans in the sitting position in healthy normotensive men (n = 75) and women (n = 42) (ages 25 to 82 years), from the Baltimore Longitudinal Study on Aging. These subjects were selected for the absence of cardiovascular disease, renal disease, and confounding medications. By linear regression analysis, creatinine clearance, expressed in mL/min/m2, declined cross-sectionally with age (creatinine clearance = 90 -0.33[age], r = .31, P less than .001), whereas systolic blood pressure in mm Hg increased with age (systolic blood pressure = 111 + 0.27[age], r = .30, P less than .001); cardiac output in L/min/m2 did not vary with age (r = .03, P = .74). In stepwise multiple regression analysis with age, cardiac index, and systolic blood pressure as independent variables and creatinine clearance as the dependent variable, only age was a significant predictor of creatinine clearance. (F = 11.31, DF + 116, r = .30, P less than .001). Thus, the age-associated decline in creatinine clearance is not modulated by changes in cardiac index or systolic blood pressure in healthy normotensive subjects.

Adult↗
PubMed1990

Interaction between left ventricular end-diastolic and end-systolic volumes in normal humans.

The extent to which the end-systolic volume (ESV) "follows" the end-diastolic volume (EDV) when the latter changes in response to various perturbations is a major determinant of the cardiac ejection fraction (EF) and has not been studied in humans. We measured EDV, ESV, and EF, determined by gated blood pool scans, during a change in posture from the supine to the upright seated position and during graded upright bicycle exercise. The experimental group consisted of 119 healthy individuals (79 males and 40 females) ranging in age from 21 to 81 yr and in physical-conditioning status (75-225 W maximum work load); rigorous screening excluded cardiac disease. Multiple regression analysis showed that the change in ESV (delta ESV) during a postural shift or during graded exercise was highly statistically correlated with the change in EDV (delta EDV) that occurred (r2 ranged from 0.34 to 0.49, correlation is positive) regardless of age, sex, or exercise work load. The correlation of delta ESV with delta EDV observed in this large sample, heterogeneous with respect to age, sex, and physical fitness, was also present in additional 31 subjects who exercised during beta-adrenergic blockade (propranolol 0.15 mg/kg). The delta EF with posture change and exercise in all subjects under all conditions was highly and inversely correlated with the delta ESV (r2 ranged from 0.38 to 0.81). Thus the delta ESV during the circulatory adaptive response to orthostatic and exercise stresses in humans is related to the delta EDV, and this relationship modulates the delta EF in response to these stresses.

Adult↗
PubMed1990

Can serial exercise testing improve the prediction of coronary events in asymptomatic individuals?

An abnormal ST segment response to treadmill exercise has a low predictive value for future coronary events (angina pectoris, nonfatal myocardial infarction, or cardiac death) in apparently healthy individuals. To determine whether the conversion from a normal to an abnormal ST segment response might identify individuals at high risk for a future coronary event, we analyzed the results of serial exercise tests performed at 2-4-year intervals in 726 male and female volunteers, aged 22-84 years (mean, 55.1 years), from the Baltimore Longitudinal Study of Aging (BLSA). All subjects were free of cardiovascular disease at entry by history, physical examination, and resting 12-lead electrocardiogram. Over a mean overall follow-up of 7.4 years, coronary events occurred in 34 of 178 (19.1%) of those with an abnormal ST response to exercise versus 30 of 548 (5.5%) in those with a normal response (p = 0.001). Angina pectoris was the most common presenting coronary event regardless of ST segment exercise response. Among individuals with an abnormal ST segment response, the incidence of events was virtually identical between those with an initially abnormal response (group 1) and those who converted from a normal to an abnormal response (group 2), 19.8% versus 18.5%. After adjustment for standard coronary risk factors by proportional hazards regression analysis, the risk of a coronary event relative to subjects with persistently normal ST segment responses (group 3) remained nearly identical in the two groups, 2.72 in group 1 (p less than 0.003) and 2.80 in group 2 (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Prevalence and prognostic significance of exercise-induced silent myocardial ischemia detected by thallium scintigraphy and electrocardiography in asymptomatic volunteers.

Although a silent ischemic electrocardiographic response to treadmill exercise in clinically healthy populations is associated with an increased likelihood of future coronary events (i.e., angina pectoris, myocardial infarction, or cardiac death), such a response has a low predictive value for future events because of the low prevalence of disease in asymptomatic populations. To examine whether detection of reduced regional perfusion by thallium scintigraphy improved the predictive value of exercise-induced ST segment depression, we performed maximal treadmill exercise electrocardiography (ECG) and thallium scintigraphy (201Tl) in 407 asymptomatic volunteers 40-96 years of age (mean = 60) from the Baltimore Longitudinal Study on Aging. The prevalence of exercise-induced silent ischemia, defined by concordant ST segment depression and a thallium perfusion defect, increased more than sevenfold from 2% in the fifth and sixth decades to 15% in the ninth decade. Over a mean follow-up period of 4.6 years, cardiac events developed in 9.8% of subjects and consisted of 20 cases of new angina pectoris, 13 myocardial infarctions, and seven deaths. Events occurred in 7% of individuals with both negative 201Tl and ECG, 8% of those with either test positive, and 48% of those in whom both tests were positive (p less than 0.001). By proportional hazards analysis, age, hypertension, exercise duration, and a concordant positive ECG and 201Tl result were independent predictors of coronary events. Furthermore, those with positive ECG and 201Tl had a 3.6-fold relative risk for subsequent coronary events, independent of conventional risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Prevalence and long-term significance of exercise-induced frequent or repetitive ventricular ectopic beats in apparently healthy volunteers.

Frequent or repetitive exercise-induced ventricular ectopic beats are often considered a marker for serious cardiac disease or sudden death, or both. However, the prognostic value of these arrhythmias in an unreferred asymptomatic community-dwelling population over a broad age range is unknown. Of 1,160 subjects aged 21 to 96 years who underwent maximal exercise treadmill testing an average of 2.4 times, 80 (6.9%) developed frequent (greater than or equal to 10% of beats in any 1 min) or repetitive (greater than or equal to 3 beats in a row) ventricular ectopic beats on at least one test. These 80 individuals were significantly older than the group without such arrhythmia (63.8 +/- 12.5 versus 50.0 +/- 16.1 years, p less than 0.0001). A striking age-related increase in the prevalence of frequent or repetitive exercise-induced ventricular ectopic beats was seen in men (p less than 0.0001) but not in women. The prevalence of electrocardiographic abnormalities at rest, exercise-induced ST segment depression and thallium perfusion defects, duration of treadmill exercise, maximal heart rate, systolic blood pressure and rate-pressure product did not differ between these 80 study subjects with frequent exercise-induced ventricular ectopic beats and a control group matched for age and gender. Furthermore, the incidence of cardiac events (angina pectoris, nonfatal myocardial infarction, cardiac syncope or cardiac death) (10% versus 12.5%) as well as noncardiac mortality (each 7.5%) was found to be similar for the study and control groups, respectively, over a mean follow-up period of 5.6 years. No study subjects required antiarrhythmic drugs over this time interval.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Physician utilization of laboratory procedures to monitor outpatients with congestive heart failure.

Little is known about how different types of physicians use laboratory procedures in the management of outpatients with congestive heart failure. We therefore analyzed data from a national survey of randomly selected general practitioners, internists, and cardiologists to assess their management of outpatients with New York Heart Association class II congestive heart failure. Most of the 2704 respondents (90%) scheduled office visits between two and four months apart. Body weight, serum electrolytes, and chest roentgenograms were followed regularly by 98% or more of respondents, at median intervals of one to two months, three to five months, and 12 to 17 months, respectively. Serum digoxin levels in patients taking digoxin were followed by 90% of respondents at a median interval of 12 months. Echocardiography, radionuclide ventriculography, and exercise testing were used by fewer respondents (81%, 61%, and 61%, respectively), each at a median interval of 18 months or longer. Cardiologists were significantly more likely to follow patients using either echocardiography, radionuclide ventriculography, or exercise testing. The estimated yearly cost of following a class II congestive heart failure outpatient varied nearly fourfold from the lowest quartile of physicians ($303) to the highest ($1167). Cardiologists were disproportionately represented among the high-cost users. In addition, physicians who were younger or who practiced in an urban setting were significantly more likely to be high-cost users. Thus, simple laboratory tests were used most frequently to follow patients with heart failure, but differences in use of more expensive tests led to large differences in cost. Test use for similar patients is affected by characteristics of both the physician and practice setting.

Ambulatory Care↗
PubMed1988

Role of muscle loss in the age-associated reduction in VO2 max.

A progressive decline in maximal O2 consumption (VO2max) expressed traditionally as per kilogram body weight generally occurs with advancing age. To investigate the extent to which this decline could be attributable to the age-associated loss of metabolically active tissue, i.e., muscle, we measured 24-h urinary creatinine excretion, an index of muscle mass, in 184 healthy nonobese volunteers, ages 22-87 yr, from the Baltimore Longitudinal Study of Aging who had achieved a true VO2max during graded treadmill exercise. A positive correlation was found between VO2max and creatinine excretion in both men (r = 0.64, P less than 0.001) and women (r = 0.47, P less than 0.001). As anticipated, VO2max showed a strong negative linear relationship with age in both men and women. Creatinine excretion also declined with age in men and women. When VO2max was normalized for creatinine excretion, the variance in the VO2max decline attributable to age declined from 60 to 14% in men and from 50 to 8% in women. Thus comparing the standard age regression of VO2max per kilogram body weight with that in which VO2max is normalized per milligram creatinine excretion, the decline in VO2max between a hypothetical 30 yr old and a 70 yr old was reduced from 39 to 18% in men and from 30 to 14% in women. We conclude that in both sexes, a large portion of the age-associated decline in VO2max in non-endurance-trained individuals is explicable by the loss of muscle mass, which is observed with advancing age.

Adult↗
PubMed1988

Ventricular arrhythmias in the elderly: prevalence, mechanisms, and therapeutic implications.

Aging is associated with an increase in both the prevalence and complexity of ventricular ectopic beats (VEB), whether detected by resting ECG, 24-hour ambulatory monitoring, or exercise testing. Frequent and/or multiform VEB, ventricular couplets, and short runs of ventricular tachycardia have been detected by these techniques in a sizeable percentage of apparently healthy subjects in the seventh decade and beyond. Although the mechanism for the increase in VEB with advancing age is uncertain, possibilities include latent coronary artery disease, left ventricular hypertrophy or dilatation, elevated plasma catecholamines, and a relative prolongation of the QT interval. Because the age-related increase in VEB does not appear to increase cardiac mortality in older subjects without demonstrable heart disease, and given the significant likelihood of adverse effects from antiarrhythmic drugs in their age group, these drugs should be reserved for elderly patients with organic heart disease and frequent or complex VEB.

Aged↗
PubMed1987

Exercise-induced arrhythmias in diuretic-treated patients with uncomplicated systemic hypertension.

Although hypertensive patients have been shown to have a higher prevalence of arrhythmias during ambulatory monitoring when treated with diuretic drugs than when untreated, the effects of maximal aerobic stress on arrhythmia frequency in such patients is unknown. The incidence of arrhythmias during graded maximal treadmill exercise in a group of 68 subjects with mild, clinically uncomplicated systemic hypertension treated chronically with diuretics alone for a median of 4.5 years was compared with that in an age-matched normotensive control group. The prevalence of exercise-induced arrhythmias was higher in the group treated with diuretics than in the control group, 57% vs 38% (p less than 0.05). This difference was entirely due to the higher incidence of isolated atrial or ventricular premature complexes in the diuretic-treated patients, 44% vs 26% (p less than 0.05). There was no difference in the incidence of frequent (more than 10% of beats) or complex supraventricular or ventricular premature complexes between the diuretic-treated and control groups. Within the diuretic group, no difference in the incidence of simple or complex arrhythmia was found between men and women, between those with and those without rest or exercise-induced electrocardiographic abnormalities or between those with a serum potassium level of less than 3.7 mEq/liter vs those with a level of 3.7 mEq/liter or greater. Thus, patients with uncomplicated hypertension treated with chronic diuretic monotherapy do not appear to be at increased risk for major arrhythmias during aerobic exercise.

Adult↗
PubMed1987

Prolonged decrease in cardiac volumes after maximal upright bicycle exercise.

Sequential exercise-gated cardiac blood pool scintigrams provide a noninvasive technique for evaluating the effect of therapeutic interventions on cardiac volumes and function only if both exercise periods are equivalent in the absence of an intervention. To assess whether they are indeed equivalent, 14 healthy subjects underwent gated blood pool scintigraphy during two maximal upright exercise periods separated by 60 min without changing position. Although resting cardiac output and blood pressure returned to base-line values 60 min after the first exercise period, mean resting heart rate was markedly higher (89.4 +/- 2.7 vs. 66.5 +/- 2.5 beats/min, P less than 0.001) and upright cardiac volumes lower [39.1 +/- 4.9 vs. 56.3 +/- 6.0 ml, P less than 0.001, for end-systolic volume (ESV) and 112.6 +/- 8.0 vs. 144.9 +/- 9.0 ml, P less than 0.001, for end-diastolic volume (EDV)] than before the first exercise period. These differences persisted during low levels of the subsequent exercise but not at high and maximum work loads. Cardiac volumes and heart rate 60 min after an identical exercise protocol in a second group of 22 subjects who received propranolol, 0.15 mg/kg iv, after their initial exercise, however, were the same as those preexercise. Thus higher sympathetic tone may be responsible for the persistently higher heart rate and decreased cardiac volumes after exercise, and the assumption that cardiac volumes and function are similar during two closely spaced sequential exercise studies is not always valid.

Adult↗
PubMed1986

Unexplained sinus bradycardia: clinical significance and long-term prognosis in apparently healthy persons older than 40 years.

The significance of sinus bradycardia (SB) in clinically healthy, non-endurance-trained, middle-aged and older persons is unknown. From 1,172 normal volunteers, aged 40 to 96 years, enrolled in the Baltimore Longitudinal Study of Aging, 47 subjects, aged 58 +/- 13 years, with SB (less than 50 beats/min) were identified by rest electrocardiography and were compared with a group of control subjects matched for age and sex. The prevalence of unexplained SB was approximately 4% and was nearly identical in men and women. At the latest follow-up examination, after a mean follow-up of 5.4 years, the SB group had a higher prevalence of associated conduction abnormalities (first-degree atrioventricular [AV] block, left-axis deviation, and complete or incomplete right bundle branch block) than the control group (43% vs 19%, p less than 0.05). On maximal treadmill exercise testing, performed in 44 patients within 1 visit of their most recent examination showing SB, maximal heart rate (157 +/- 18 beats/min) did not differ significantly from that of control subjects (163 +/- 19 beats/min); exercise duration, however, was greater in the former group, 11.0 +/- 2.8 vs 9.7 +/- 3.1 minutes (p less than 0.05). No patients with SB had syncope, high-degree AV block or other manifestation of sick sinus syndrome during follow-up. Angina pectoris, myocardial infarction, congestive heart failure or cardiac death occurred in 8% of patients with SB and 11% of control subjects over the observation period (difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Prevalence and significance of postexercise hypotension in apparently healthy subjects.

Although a decrease in systolic blood pressure (BP) occurring during treadmill exercise is often a sign of severe left ventricular dysfunction, the prevalence and significance of postexertional hypotension is unclear. The postexercise systolic BP response to maximal treadmill exercise was analyzed in 781 asymptomatic volunteers, aged 21 to 96 years (mean 51 +/- 16) from the Baltimore Longitudinal Study on Aging. Fifteen subjects (1.9%) had a postexercise decrease in systolic BP of at least 20 mm Hg from preexercise sitting values, to a level of 90 mm Hg or less. The prevalence of postexercise hypotension was 3.1% (14 of 449) in subjects younger than 55 years, but only 0.3% (1 of 332) in those older than 55 (p less than 0.01). Before exercise these 15 subjects demonstrated a slight orthostatic decrease in systolic BP of -1.7 +/- 4.8 mm Hg compared with an increase of 5.3 +/- 5.1 mm Hg in age-matched control subjects (p less than 0.001). The lowest systolic BP averaged 78 +/- 9 mm Hg (range 62 to 90) and occurred between 4 and 9 minutes after exercise in 80% of cases. All but 3 episodes were symptomatic, with dizziness dominant. In only 2 subjects was the hypotension associated with vagal symptoms and bradycardia. Compared with control subjects, subjects with postexercise hypotension had higher maximal heart rates (184 +/- 15 vs 173 +/- 11 beats/min, p less than 0.05), but showed no difference in exercise tolerance or systolic BP at submaximal or maximal effort. Postexercise ST-segment abnormalities suggesting ischemia occurred in one-third of the hypotensive subjects but none of the control subjects (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Alterations in cardiovascular structure and function with advancing age.

The greatest difficulty in studying the effects of aging on cardiovascular structure and function lies in separating the effects of aging itself from those of the inextricably entwined disease processes and life-style changes that accompany aging. Age-related stiffening of the arterial tree results in an increased systolic blood pressure, which appears to impose a greater load on the heart. Probably as an adaptive mechanism to maintain normal wall stress, a modest age-associated concentric left ventricular hypertrophy develops, which approximates 30% between ages 25 and 80. The decrease in mitral valve E-F slope and increase in the left atrial dimension, which are seen with advancing age, may be construed as the consequences of a thicker-walled, less compliant left ventricle. Systolic left ventricular function, measured at rest either by echocardiography or radionuclide techniques, is unaffected by aging. Aerobic exercise capacity, whether measured as total work performance or maximal oxygen consumption declines with age, although in subjects who maintain a high level of physical activity, the decline appears to be approximately half of the 10% per decade decrease seen in sedentary persons. An age-related decline in maximal exercise heart rate has been a universal finding. Although several studies over the past 4 decades have found cardiac output to decrease with age, both at rest and during exercise, a recent study of subjects carefully screened to exclude latent coronary artery disease found no such decline in cardiac output. In these subjects, the age-related decline in maximal heart rate and systolic emptying at peak exercise was offset by an increased utilization of the Frank-Starling mechanism. An attractive hypothesis for explaining the hemodynamic profile of a decreased maximum heart rate, increased preload and decrease in ejection fraction at maximal effort, despite elevated norepinephrine levels, is an age-associated, diminished end-organ responsiveness similar to beta-adrenergic blockade.

Adult↗
PubMed1986

Postural changes in cardiac volumes in men in relation to adult age.

Cardiac volumes by equilibrium gated cardiac blood pool scans and heart rate were measured in the supine and sitting positions in 64 male volunteer subjects (age 25-80 yrs) who had been rigorously screened to exclude cardiovascular disease. After the upright position was assumed, the average cardiac output of all subjects was unchanged but heart rate increased and stroke volume decreased due to a decrease in end diastolic volume. Neither the supine or sitting cardiac output nor the average postural change in cardiac output, cardiac volumes or heart rate was age-related. While the average cardiac output among the subjects was unaltered with a change in posture, in some individuals it increased slightly while in others it decreased. The postural change in cardiac output among the individuals correlated by linear regression analysis with a change in heart rate only in younger subjects and with a change in stroke volume in all age groups, but the slope of this relationship was greater in older than in younger subjects. The postural change in stroke volume was strongly correlated with a change in end diastolic volume and this relationship did not vary with age. Thus, although the average postural change in cardiac output among healthy subjects is not age-related, a given change in cardiac output with posture in an older individual depends more on a change in stroke volume and less on a heart rate change than in a younger one. This result, like the response to vigorous upright exercise previously demonstrated to occur with aging, indicates a greater reliance in the elderly on the Frank-Starling mechanism than on heart rate for a given change in cardiac output in response to perturbations from the basal supine state.

Adult↗
PubMed1986

Use of the Frank-Starling mechanism during submaximal versus maximal upright exercise.

To evaluate the extent to which the Frank-Starling mechanism is utilized during successive stages of vigorous upright exercise, absolute left ventricular end-diastolic volume and ejection fraction were determined by gated blood pool scintigraphy at rest and during multilevel maximal upright bicycle exercise in 30 normal males aged 26-50 yr, who were able to exercise to 125 W or greater. Left ventricular end-systolic volume, stroke volume, and cardiac output were calculated at rest and during each successive 3-min stage of exercise [25, 50, 75, 100, and 125-225 W (peak)]. During early exercise (25 W), end-diastolic and stroke volumes increased (+17 +/- 1 and +31 +/- 4%, respectively), with no change in end-systolic volume. With further exercise (50-75 W) end-diastolic volume remained unchanged as end-systolic volume decreased (-12 +/- 4 and -24 + 5%, respectively). At peak exercise end-diastolic volume decreased to resting level, stroke volume remained at a plateau, and end-systolic volume further decreased (-48 +/- 7%). Thus the Frank-Starling mechanism is used early in exercise, perhaps because of a delay in sympathetic mobilization, and does not appear to play a role in the later stages of vigorous exercise.

Adult↗
PubMed1986

CHF: reflections on current management of the older patient.

The deleterious effects of prolonged bedrest on aerobic capacity, mineral balance, and various metabolic processes have been amply demonstrated. Since these functions are already compromised by aging per se, complete or prolonged bedrest should be avoided in geriatric cardiac patients if at all possible, regardless of their specific diagnosis. Diuretics are still the mainstay therapy for CHF. For elderly patients with mild CHF and preserved renal function, a thiazide rather than a loop diuretic appears preferable, due to more gentle diuresis and lower frequency of side effects.

Aged↗