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Biomedical subjects

J L Fleg

Publications and source records attributed to J L Fleg.

At least 55 records · Page 3Linked to original sources

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.

Aged↗

The relationship of obesity and the development of coronary heart disease to longitudinal changes in systolic blood pressure.

In an investigation of the relationship of obesity and the development of coronary heart disease (CHD) to longitudinal changes in systolic blood pressure (SBP), a sample of 1029 male participants from the Baltimore Longitudinal Study of Baltimore (BLSA), who were free of CHD at the beginning of the study, were examined with a total of 4111 examinations (mean of four examinations per person) conducted during the study period. The mean follow-up time was 8.1 years with a maximum of 16 examinations and 30.9 years of follow-up. During the follow-up period, 192 participants developed CHD, and these participants' data collected after the CHD event were excluded from the analysis. A proportional hazards regression model was used to calculate the relative risk of developing CHD for several CHD risk factors. Both simple and multiple proportional hazards regression models indicate a strong association between body mass index (BMI), cholesterol, cigarette smoking, and systolic blood pressure (SBP) with the risk of developing CHD. In addition, a linear mixed-effects model was used to examine changes in SBP measurements over time and to identify factors, including the age at first examination and time in study, that are related to that change. The results from the linear mixed-effects model analysis indicate that those in the obese group (BMI > or = 30 kg/m2) have SBP measurements that are on average 9.0 mm Hg higher than those in the normal group (20 < or = BMI < 25). Also, SPB measurements were on average 6.6 mm Hg higher in those who developed CHD during the study period than those who remained free of disease. In addition, SPB showed a quadratic relationship with time, and its patterns of change with time were different among the different age groups. Also, the relationship between changes in SBP with respect to cholesterol was dependent on time in the study as well.

Adult↗

Age-associated changes in blood pressure in a longitudinal study of healthy men and women.

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.

Adolescent↗

Abnormal exercise electrocardiograms in master athletes after three months of deconditioning.

OBJECTIVE: To determine the effects of 3 months of voluntary deconditioning on cardiac function in master athletes. DESIGN: A prospective study. SETTING: Research participants at the University of Maryland School of Medicine and Johns Hopkins Bayview Medical Center. PARTICIPANTS: Ten older (59 +/- 8 years, mean +/- SD), highly conditioned (maximal aerobic capacity VO2 max 50 +/- 5 mL/kg/min), aerobically trained athletes. MEASUREMENTS AND RESULTS: Three months after the cessation of training, three of the 10 athletes had unexpected, new, markedly asymptomatic, ischemic-appearing, exercise-induced ST-segment depression on their maximal exercise tests. After retraining, the ST-segment changes disappeared in two of the subjects, but it persisted, although at a higher work load, in one of the athletes. CONCLUSION: In three master athletes, voluntary cardiopulmonary deconditioning was associated with the development of new, asymptomatic, exercise-induced ST-segment depression on exercise ECG. The mechanisms underlying these new ischemic-appearing ST-segment changes accompanying detraining and their clinical significance are not known and warrant further investigation.

Adult↗

Age and gender comparisons of muscle strength in 654 women and men aged 20-93 yr.

To assess age and gender differences in muscle strength, isometric, concentric (Con), and eccentric (Ecc) peak torque was measured in the knee extensors at a slow (0.52 rad/s) and fast (3.14 rad/s) velocity in 654 subjects (346 men and 308 women, aged 20-93 yr) from the Baltimore Longitudinal Study of Aging. Regression analysis revealed significant (P < 0.001) age-related reductions in Con and Ecc peak torque for men and women at both velocities, but no differences were observed between the gender groups or velocities. Age explained losses in Con better than Ecc peak torque, accounting for 30% (Con) vs. 19% (Ecc) of the variance in men and 28% (Con) vs. 11% (Ecc) in women. To assess age and gender differences in the ability to store and utilize elastic energy, the stretch-shortening cycle was determined in a subset of subjects (n = 47). The older women (mean age = 70 yr) showed a significantly greater enhancement in the stretch-shortening cycle, compared with men of similar age (P < 0.01) and compared with younger men and women (each P < 0.05). Both men and women showed significant declines in muscle quality for Con peak torque (P < 0.01), but no gender differences were observed. Only the men showed a significant decline in muscle quality (P < 0.001) for Ecc peak torque. Thus both men and women experience age-related losses in isometric, Con, and Ecc knee extensor peak torque; however, age accounted for less of the variance in Ecc peak torque in women, and women tend to better preserve muscle quality with age for Ecc peak torque. In addition, older women have an enhanced capacity to store and utilize elastic energy compared with similarly aged men as well as with younger women and men.

Adult↗

Intravascular magnetic resonance imaging of aortic atherosclerotic plaque composition.

Magnetic resonance imaging (MRI) may be an excellent tool to define atherosclerotic plaque composition, but surface MRI (SMRI) suffers from a low signal-to-noise ratio and low resolution of arterial images. Intravascular MRI (IVMRI) represents a potential solution for acquiring high-quality in vivo images of atherosclerotic plaques. Isolated segments of 11 thoracic human aortas obtained at autopsy were imaged by IVMRI using an intravascular receiver catheter coil designed and built at our institution. Images obtained by IVMRI were compared with corresponding images obtained by SMRI and with histopathological aortic cross sections. The intensity of intimal thickness and plaque components was graded by IVMRI and histopathology using a score of 1 for mild, 2 for moderate, and 3 for severe intensity. IVMRI had an agreement of 75% with histopathology in fibrous cap grading (37.5% expected, kappa = 0.60, P < 0.001) and of 74% in necrotic core grading (39% expected, kappa = 0.57, P < 0.001). Intraplaque calcification was correctly graded by IVMRI in six of the eight plaques in which histopathology recognized calcium. The analysis of intimal thickness showed 80% agreement between IVMRI and histopathology (52% expected, kappa = 0.59, P < 0.001). IVMRI image features were similar to those of SMRI. In addition, IVMRI accurately determined atherosclerotic plaque size in comparison with histopathology and SMRI (slope = 1.25 cm2, r = 0.99, P < 0.001 for luminal area by IVMRI vs histopathology; slope = 0.97 cm2, r = 0.996, P < 0.001 for luminal area by IVMRI vs SMRI). IVMRI has the potential to provide important prognostic information in patients with atherosclerosis because of its ability to accurately assess both plaque composition and size.

Adult↗

Age-associated changes in left ventricular outflow tract geometry in normal subjects.

This study examined age-associated changes in the geometry of the left ventricular outflow tract in normal subjects using Doppler echocardiography. With advancing age, the angle between the interventricular septum and the aortic root became more acute and a discrete bulging of the proximal septum was more common, but neither finding appeared to affect resting outflow tract velocity or left ventricular mass significantly.

Adult↗

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.

Aging↗

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.

Adult↗

Role of aerobic capacity and body mass index in the age-associated decline in heart rate variability.

The extent to which age-associated changes in aerobic capacity and body composition modulate the age-associated decline in heart rate variability (HRV) is unknown. We therefore measured HRV, peak O2 consumption (VO2peak) during treadmill testing, and relative weight (body mass index; BMI) in 164 healthy normotensive adults (75 men, age 20-87 yr) from the Baltimore Longitudinal Study on Aging. Two components of HRV, respiratory sinus arrhythmia (RSA; 0.12-0.40 Hz) and 0.10-Hz variability (0.06-0.10 Hz), were extracted from 8-min electrocardiogram recordings in the supine, seated, and standing postures. RSA, 0.10-Hz variability, and VO2peak varied inversely with age; BMI was unrelated to age. Age contributed 15.5-21.1% independent variance to RSA and 13.2-17.3% independent variance to 0.10-Hz HRV. VO2peak did not contribute significantly to RSA or 0.10-Hz HRV beyond the effect of age in any posture. There were no consistent independent contributions of BMI to HRV. Thus, in this population-based sample, age-associated changes in aerobic capacity and relative body weight do not provide the primary explanation for the decline in HRV observed with advancing age.

Adult↗

Stress testing for coronary artery disease in the elderly.

The elderly constitute an increasing percentage of patients evaluated and treated for coronary artery disease. Clinical and noninvasive evaluation are important in both the diagnosis and prognosis of coronary disease in the elderly, and stress testing is an important part of that evaluation. For older individuals capable of vigorous treadmill or cycle exercise, the exercise electrocardiogram, either alone or combined with radionuclide or echocardiographic imaging, remains an excellent diagnostic and prognostic tool. For the large percentage of elderly patients unable to perform adequate exercise, pharmacologic stress testing with dipyridamole, adenosine, or dobutamine is a valuable alternative. The clinician's challenge is to choose the most appropriate cardiac stress test for his or her patient from among the many alternatives available. Future studies comparing the accuracy and cost-to-benefit ratio of various stress tests with regard to the elderly will help achieve this goal.

Aged↗

Left ventricular diastolic filling performance in older male athletes.

OBJECTIVE: To determine whether older men who have undergone intensive endurance training over many years demonstrate less age-associated impairment of early diastolic left ventricular (LV) filling performance than their sedentary peers. DESIGN: Cross-sectional prospective study. SETTING: Community-dwelling research volunteers. PARTICIPANTS: Sixteen older competitive male endurance athletes aged 52 through 76 years and 17 young (< 40 years) and 23 older (52 through 76 years) sedentary control subjects from the Baltimore Longitudinal Study of Aging. INTERVENTION: All subjects underwent resting Doppler echocardiography and determination of maximal aerobic capacity (VO2max) during graded treadmill exercise. Doppler echocardiographic studies were interpreted without knowledge of the subject's age or exercise habits. MAIN OUTCOME MEASURES: Doppler-derived measures of LV diastolic filling performance: peak early (E) filling velocity, peak late (A) filling velocity, ratio of peak E to peak A velocities (E/A), and atrial filling fraction. RESULTS: Older athletes demonstrated higher VO2max (47 +/- 6 mL/kg per minute [mean +/- SD]) than either the young controls (41 +/- 7 mL/kg per minute) or older controls (30 +/- 7 mL/kg per minute) (P < .05) as evidence of their superior conditioning status. However, peak E diastolic LV filling velocity was higher in young controls (79 +/- 17 cm/s) than in older athletes (56 +/- 15 cm/s) or older controls (68 +/- 18 cm/s) (P < .001). This age difference persisted after normalizing peak E velocity for mitral stroke volume. Peak E/A ratio and atrial filling fraction were also similar in older athletes (1.2 +/- 0.5 and 0.41 +/- 0.1, respectively) and older controls (1.1 +/- 0.4 and 0.41 +/- 0.1, respectively), and differed significantly from corresponding values of 1.7 +/- 0.4 and 0.33 +/- 0.1 in young controls (P < .001 and P < .05, respectively). By multiple regression analysis, age but not treadmill VO2max was a significant predictor of peak E velocity, peak A velocity, peak E/A ratio, and atrial filling fraction. CONCLUSION: Older men with a long history of intensive endurance training demonstrate impaired early diastolic LV filling similar to that of their sedentary peers. Thus, impairment of early diastolic filling appears to be intrinsic to normative aging and not secondary to the reduction in aerobic capacity that accompanies the aging process.

Adult↗

Prevalence and prognostic significance of exercise-induced supraventricular tachycardia in apparently healthy volunteers.

The prevalence, characteristics, and prognostic significance of supraventricular tachycardia (SVT) occurring during maximal treadmill exercise testing were examined in 843 male and 540 female asymptomatic volunteers aged 20 to 94 years from the Baltimore Longitudinal Study of Aging who underwent exercise testing a mean of 2.3 times between 1977 and 1991. Exercise-induced SVT occurred during at least 1 test in 51 men (6.0%) and 34 women (6.3%), p = NS for gender. The 85 subjects with exercise-induced SVT were significantly older than the 1,298 free from this arrhythmia (66.0 +/- 13.5 vs 49.7 +/- 18.0 years, respectively, p < 0.001). The prevalence of SVT increased with age in men (p < 0.001) but not in women. Ninety-eight percent of the 141 discrete episodes of exercise-induced SVT were paroxysmal SVT, with heart rates varying from 105 to 290 beats/min (mean 186.3 +/- 43.3); only 16% were > 10 beats in duration and only 4% of subjects were symptomatic. Nearly half (44%) of SVT episodes occurred at peak effort. Coronary risk factors, echocardiographic left atrial size (3.3 +/- 6.7 vs 3.3 +/- 0.6 cm), and the prevalence of exercise-induced ischemic ST-segment depression (11% vs 13%) were similar in 85 subjects with SVT and 170 control subjects matched for age and sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Diagnostic and prognostic value of stress testing in older persons.

OBJECTIVE: To review the diagnostic and prognostic utility of exercise and pharmacologic stress testing in older individuals. DATA SOURCE: A computer-assisted search of the literature, followed by a manual reference review of pertinent articles. STUDY SELECTION: Studies addressing the use of exercise and pharmacologic stress testing for coronary artery disease (CAD) detection and prognosis were reviewed. Emphasis was placed on those studies applying these procedures to older populations. DATA EXTRACTION: Pertinent data were extracted regarding the diagnostic and prognostic accuracy and safety of exercise and nonexercise stress testing techniques in older patients. DATA SYNTHESIS: Available data from relevant articles were summarized and the merits and limitations of the available techniques discussed. CONCLUSIONS: Numerous studies over the past 2 decades support the usefulness of the exercise ECG and exercise thallium-201 perfusion scan for detecting CAD in older populations. Although exercise echocardiography generally appears to have diagnostic and prognostic accuracy similar to thallium-201 imaging, greater technical difficulty with this technique is frequently encountered in older patients. Non-exercise forms of stress testing, particularly those employing pharmacologic agents such as dipyridamole, adenosine, or dobutamine, combined with either thallium-201 scintigraphy or echocardiography, allow accurate CAD diagnostic and prognostic assessment in even very frail older patients. Additional studies are needed to compare the accuracy and cost-benefit ratio of the many stress testing modalities now available for older patients.

Adenosine↗

Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women.

To examine whether age differentially modifies the physiological response to exercise in men and women, we performed gated radionuclide ventriculography with measurement of left ventricular volumes at rest and during peak upright cycle exercise in 200 rigorously screened healthy sedentary volunteers (121 men and 79 women) aged 22-86 yr from the Baltimore Longitudinal Study of Aging. At rest in the sitting position, age-associated declines in heart rate (HR) and increases in systolic blood pressure occurred in both sexes. Whereas resting cardiac index (CI) and total systemic vascular resistance (TSVR) in men did not vary with age, in women resting CI decreased 16% and TSVR increased 46% over the six-decade age span. Men, but not women, demonstrated an age-associated increase of approximately 20% in sitting end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and stroke volume index over this age span. Peak cycle work rate declined with age approximately 40% in both sexes, but at any age it was greater in men than in women even after normalization for body weight. At peak effort, ejection fraction (EF), HR, and CI were reduced similarly with age while ESVI and TSVR were increased in both sexes; EDVI increased 35% with age and stroke work index (SWI) rose 19% in men, but neither was related to age in women; and stroke volume index did not vary with age in either sex. When hemodynamics were expressed as the change from rest to peak effort as an index of cardiovascular reserve function, both sexes demonstrated age-associated increases in EDVI and ESVI and reductions in EF, HR, and CI. However, the exercise-induced reduction in ESVI and the increases in EF, CI, and SWI from rest were greater in men than in women. Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise.

Adult↗

Rapid decline in FEV1. A new risk factor for coronary heart disease mortality.

Coronary heart disease (CHD) is the leading cause of mortality in the United States. The present cohort study was conducted to determine whether rate of FEV1 loss independently predicts CHD mortality in apparently healthy men. White male Baltimore Longitudinal Study of Aging (BLSA) participants without CHD underwent clinical evaluation at 2-yr intervals; 883 had satisfactory pulmonary and lipid studies and returned for a least one visit. Cases were BLSA subjects without CHD on entry who died a "coronary death" (death from acute myocardial infarction, sudden death, or congestive heart failure in the presence of coronary artery disease). Forced expiratory maneuvers followed American Thoracic Society guidelines. Serum cholesterol, blood pressure, cigarette smoking, and body mass index were obtained from the BLSA database. There were 79 CHD deaths and 804 survivors during an average follow-up of 17.4 yr. After adjustment for age, initial FEV1% predicted, smoking status, hypertension, and cholesterol, a time-dependent proportional hazards model showed that cardiac mortality, but not all causes of mortality, generally increased with increasing quintile of FEV1 decline for the entire cohort (relative risk [RR] 2.92-5.13) and separately for the subset of never-smokers. Thus, excess CHD mortality follows a large decline in FEV1, independent of the initial FEV1% predicted, cigarette smoking, and other common CHD risk factors.

Adolescent↗

Risk factors for exercise-induced silent myocardial ischemia in healthy volunteers.

This study determined the risk factors for exercise-induced silent ischemia (SI) in 281 apparently healthy volunteers aged 40 to 87 years and compared their risk factor profiles with those of 132 patients with overt coronary artery disease (CAD). SI (concordant exercise-induced asymptomatic ST-segment depression on electrocardiography and perfusion defects on tomographic thallium-201 scintigraphy) was detected in 37 of 225 men (16%), versus 2 of 56 women (4%, p < 0.05). The prevalence of SI increased with age from 6% in men aged < 55 years to 18% in men aged 55 to 70 years, and to 25% in men aged > 70 years (p < 0.001). Compared with the 118 men with concordant normal exercise electrocardiogram and thallium scan (normals), men with SI were older (p < 0.001), and had a higher waist-to-hip ratio (p < 0.005), higher plasma triglyceride levels (p < 0.001), and lower high-density lipoprotein (HDL) cholesterol levels (p < 0.001). In stepwise logistic regression analysis, age, waist-to-hip ratio, and HDL levels were independent predictors of SI in men. Compared with 108 men with overt CAD, men with SI were younger (67 +/- 2 vs 73 +/- 1 years, p < 0.001) but had similar plasma lipids and waist-to-hip ratio. Thus, older age, male gender, abdominal obesity, and reduced HDL levels--all well-established risk factors for overt CAD--were risk factors for exercise-induced SI in these asymptomatic volunteers.

Age Factors↗