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Biomedical subjects

Jerome L Fleg

Publications and source records attributed to Jerome L Fleg.

At least 19 recordsLinked to original sources
PubMed2007

Exercise therapy for elderly heart failure patients.

Exercise intolerance is one of the hallmark symptoms of heart failure (HF). Exercise training in this condition was not explored as a therapeutic modality until the past two decades. In fact, bed rest was promoted as a treatment for certain forms of HF in the 1970s. Over the past two decades, however, data have shown convincingly that exercise training can be implemented safely in patients who have HF, with significant improvement in functional capacity, various other physiologic variables, and quality of life. This article reviews the accumulated literature in this area, with specific emphasis on the effects of exercise training in older patients who have HF, a subset that may have the most to gain from such training.

Aged↗
PubMed2006

Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial.

BACKGROUND: About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published. METHODS AND RESULTS: Ambulatory chronic heart failure patients (n = 988) with normal sinus rhythm and ejection fraction > 45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n = 492) or placebo (n = 496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P = 0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04; P = 0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91; P = 0.061). CONCLUSIONS: In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations.

Aged↗
PubMed2006

Effects of normal aging on left ventricular lusitropic, inotropic, and chronotropic responses to dobutamine.

OBJECTIVES: The purpose of this study was to characterize how aging impacts the left ventricular (LV) functional reserve. BACKGROUND: Early diastolic LV filling slows markedly with advancing age, but the effects of beta-adrenergic stimulation on filling, and its major determinant, relaxation, have not been investigated in an aging population. Although the responses of contractility and heart rate to catecholamines reportedly diminish with age, the effect of age on the responses to steady-state dobutamine infusions is unclear. METHODS: Groups of younger (40 +/- 10 years, n = 26) and older (68 +/- 11 years, n = 24) normal adult patients were studied at baseline and at three progressive dobutamine infusion dosages (5, 10, and 20 mug/kg/min). The LV function was evaluated by two-dimensional and Doppler echocardiography. Myocardial relaxation was evaluated from cardiovascular magnetic resonance (CMR)-based rho, a preload-independent surrogate for tau . Effective LV pump-function index (PFi), defined as systolic blood pressure/end-systolic LV diameter, was measured. RESULTS: Both groups showed expected dose-dependent increases in heart rate and LV systolic function, diastolic function, and relaxation. Early LV filling reserve was much greater in younger than older patients (E-wave increase from baseline to highest dose, 24.0 vs. 9.5 cm/s, p < 0.004), although the dose responses of rho were indistinguishable (0.18% vs. 0.19%/ms, p = 0.22). Whereas dobutamine caused a significantly greater increase of PFi in younger than older patients (30.1 vs. 15.6 mm Hg/cm, p < 0.0001), there was no difference in heart rate augmentation (37 vs. 38 beats/min, p = 0.94). CONCLUSIONS: Aging is accompanied by a blunted inotropic but preserved chronotropic response to steady-state dobutamine infusion. Although LV filling reserve declines with age, relaxation reserve does not.

Adult↗
PubMed2006

Higher New York Heart Association classes and increased mortality and hospitalization in patients with heart failure and preserved left ventricular function.

BACKGROUND: The association between higher New York Heart Association (NYHA) class and outcomes in patients with heart failure and preserved systolic function is not well known. METHODS: We performed a retrospective follow-up study of 988 patients with heart failure with ejection fraction > 45% who participated in the DIG trial. Using Cox proportional hazard models, we estimated risks and all-cause mortality, heart failure mortality, all-cause hospitalization, and hospitalization due to worsening heart failure during a median follow-up of 38.5 months. RESULTS: Patients had a median age of 68 years; 41.2% were women and 13.9%, nonwhites. Overall, 23.4% of patients died, and 19.9% were hospitalized because of worsening heart failure. Proportion of patients with NYHA classes I, II, III, and IV were 19.9%, 58.0%, 20.9%, and 1.2%, respectively, and 14.7%, 21.1%, 35.9%, and 58.3%, respectively, died of all causes (P < .001 for trend). Respective rates for heart failure-related hospitalizations were 14.2%, 17.1%, 32.5%, and 33.3% (P < .001 for trend). Compared with NYHA class I patients, adjusted hazard ratios (HRs) for all-cause mortality for class II, III, and IV patients were 1.54 (95% CI 1.02-2.32, P = .042), 2.56 (95% CI 1.64-24.01, P < .001), and 8.46 (95% CI 3.57-20.03, P < .001), respectively. Respective adjusted HRs (95% CI) for hospitalization due to heart failure for class II, III, and IV patients were 1.16 (0.76-1.77) (P = .502), 2.27 (1.45-3.56) (P < .001), and 3.71 (1.25-11.02) (P = 018). New York Heart Association classes II through IV were also associated with higher risk of all-cause hospitalization. CONCLUSION: Higher NYHA classes were associated with poorer outcomes in patients with heart failure and preserved systolic function.

Aged↗
PubMed2006

Examination of lower targets for low-density lipoprotein cholesterol and blood pressure in diabetes--the Stop Atherosclerosis in Native Diabetics Study (SANDS).

Diabetes incidence is increasing rapidly in the United States. Diabetes increases the risk for cardiovascular disease, the major cause of death in diabetic individuals. The conventional cardiovascular risk factors of hyperlipidemia and hypertension worsen diabetic vascular disease. Treatment targets for low-density lipoprotein cholesterol (LDL-C) and blood pressure in diabetic individuals are being debated. The SANDS is a randomized, open-label, 3-year trial to examine the effects of aggressive LDL-C (goal <70 mg/dL) and blood pressure (BP) (goal <115/75 mm Hg) reduction versus the standard goals of <100 mg/dL for LDL-C and <130/85 mm Hg for BP. Five hundred forty-nine American-Indian men and women >40 years old with type 2 diabetes were randomized to 1 of 2 groups. Lipids and BP are managed using Food and Drug Administration-approved medications in an algorithmic approach. The presence and progression of atherosclerosis are evaluated by carotid ultrasonography; echocardiography assesses cardiac function. The primary end point is the composite outcome of change in carotid artery intimal medial thickness and fatal/nonfatal cardiovascular events. These outcomes are combined by using a ranked analysis for carotid thickness and assigning a "worst rank" for a cardiovascular event. Secondary end points include carotid plaque score, left ventricular geometry and function, serum C-reactive protein, and safety measures. Unique aspects of the study design and analysis plan involve the use of a composite outcome and changes during the trial of LDL-C treatment goals for participants with baseline or incident cardiovascular disease in the conventional group because of changes in the standard of care. Study results will further understanding of the effects of aggressive risk factor reduction on atherosclerosis burden and cardiac function in diabetic individuals in US populations and will help determine optimal LDL-C and BP treatment goals for diabetic patients.

Adult↗
PubMed2006

Outcomes in ambulatory chronic systolic and diastolic heart failure: a propensity score analysis.

BACKGROUND: Prior studies demonstrating significant difference in outcomes in systolic and diastolic heart failure (HF) are often limited to hospitalized acute HF patients, and may be confounded by residual bias. In this analysis, we examined long-term mortality and hospitalization in a propensity score matched cohort of ambulatory chronic systolic and diastolic HF patients. METHODS: Of the 7788 patients in the Digitalis Investigation Group trial, 6800 had systolic HF (ejection fraction >45%) and 988 had diastolic HF (ejection fraction >45%). We restricted our analysis to 7617 patients without valvular heart disease: 916 diastolic HF and 6701 systolic HF. Propensity scores for diastolic HF, calculated for each patient by a non-parsimonious multivariable logistic regression model, were used to match 697 diastolic HF with 2091 systolic HF patients. Matched Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for outcomes in diastolic (versus systolic) HF. RESULTS: During a median 38-month follow-up, compared with 32% mortality in systolic HF, 23% of diastolic HF patients died (HR=0.70; 95% CI=0.59-0.84; P<.0001). Respective HR (95%CI) for cardiovascular and HF mortality were 0.60 (0.48-0.74; P<.0001) and 0.56 (0.39-0.79; P=.001). All-cause hospitalizations occurred in 64% of systolic and 67% of diastolic HF patients (HR=0.99; 95% CI=0.87-1.11; P=0.801). Respective HR (95%CI) for cardiovascular and HF hospitalizations were 0.84 (0.73-0.96; P=.011) and 0.63 (0.51-0.77; P<.0001). CONCLUSIONS: Despite lower mortality and cardiovascular morbidity, diastolic HF patients had similar overall hospitalizations as in systolic HF. Ejection fraction should be assessed in all HF patients to guide therapy, with special attention to non-cardiovascular morbidity in diastolic HF.

Aged↗
PubMed2006

Estimating cardiorespiratory fitness in well-functioning older adults: treadmill validation of the long distance corridor walk.

OBJECTIVES: To determine criterion validity of the 400-m walk component of the Long Distance Corridor Walk (LDCW) and develop equations for estimating peak oxygen consumption (VO2) from 400-m time and factors intrinsic to test performance (e.g., heart rate (HR) and systolic blood pressure (SBP) response) in older adults. DESIGN: Cross-sectional validation study. SETTING: Gerontology Research Center, National Institute on Aging, Baltimore, Maryland. PARTICIPANTS: Healthy volunteers (56 men and 46 women) aged 60 to 91 participating in the Baltimore Longitudinal Study of Aging between August 1999 and July 2000. MEASUREMENTS: The LDCW, consisting of a 2-minute walk followed immediately by a 400-m walk "done as quickly as possible" over a 20-m course was administered the day after maximal treadmill testing. HR and SBP were measured before testing and at the end of the 400-m walk. Weight, height, activity level, perceived effort, and stride length were also acquired. RESULTS: Peak VO2 ranged from 12.2 to 31.1 mL oxygen/kg per minute, and 400-m time ranged from 2 minutes 52 seconds to 6 minutes 18 seconds. Correlation between 400-m time and peak VO2 was -0.79. The estimating equation from linear regression included 400-m time (partial coefficient of determination (R2)=0.625), long versus short stride (partial R2=0.090), ending SBP (partial R2=0.019), and a correction factor for fast 400-m time (<240 seconds; partial R2=0.020) and explained 75.5% of the variance in peak VO2 (correlation coefficient=0.87). CONCLUSION: A 400-m walk performed as part of the LDCW provides a valid estimate of peak VO2 in older adults. Incorporating low-cost, safe assessments of fitness in clinical and research settings can identify early evidence of physical decline and individuals who may benefit from therapeutic interventions.

Aged↗
PubMed2005

Serum digoxin concentration and outcomes in women with heart failure: A bi-directional effect and a possible effect modification by ejection fraction.

BACKGROUND: The association between serum digoxin concentration (SDC) and outcomes in women with heart failure (HF) has not been well studied. AIMS: To test the hypothesis that the effect of digoxin on outcomes in women with HF is bi-directional and dependent on SDC, as in men, and is modified by ejection fraction (EF). METHODS: We studied 1366 female participants of the Digitalis Investigation Group trial in whom data on SDC (ng/ml) were available. We calculated adjusted odds ratios (AOR) and Bonferroni-adjusted 97.5% confidence intervals (CI) for various outcomes at a median follow up of 41 months, in all women and stratified by EF 35%. RESULTS: Compared with placebo (26.9%), 40.3% with SDC> or =1.2 (AOR=1.80; CI=1.14-2.86; p=0.004) and 26.6% with SDC 0.5-1.1 (AOR=1.05; CI=0.73-1.51; p=0.762) died. Respective rates for HF-hospitalizations were: placebo (32.8%), SDC> or =1.2 (38.0%) and SDC 0.5-1.1 (25.5%). For women with EF<35% (N=677), SDC 0.5-1.1 lowered odds for HF-hospitalizations (AOR=0.63; CI=0.39-1.00; p=0.026) without increasing odds for death (AOR=0.77; CI=0.47-1.26; p=0.233). In women with EF> or =35% (N=689), SDC 0.5-1.1 had a borderline association with death (AOR=1.58; CI=0.92-2.72; p=0.058) but not with HF-hospitalization (AOR=0.95; CI=0.54-1.66; p=0.826). CONCLUSIONS: As in men, in women with HF, digoxin has a bi-directional effect based on SDC, and the beneficial effects were significant only among women with EF<35%.

Aged↗
PubMed2005

Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements.

Circulating testosterone levels (T) decrease with age in men. Low T has been associated with coronary disease and with risk factors for atherosclerosis. This study examines the relationship in men between androgenic hormones and arterial stiffness, a major risk factor for cardiovascular events. T, sex hormone-binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) were measured longitudinally over 33 yr (follow-up 11.8 +/- 8.3 yr) in 901 men from the Baltimore Longitudinal Study of Aging, of whom 206 (68.1 +/- 13.7 yr) underwent carotid duplex ultrasonography. The 901 men were used to characterize age-associated hormone levels by means of mixed-effects models. Hormone values were estimated for the 206 men at the time of ultrasonography. Free T index (FTI) was calculated by dividing T by SHBG. The arterial stiffness index was calculated from peak systolic and end diastolic diameters of the common carotid artery and simultaneous brachial artery blood pressure. T, FTI, and DHEAS were correlated negatively with age, pulse pressure (PP), and stiffness index (each P < 0.01), whereas SHBG was correlated positively with age and stiffness index (P < 0.01). However, T was the only hormone that predicted the stiffness index after adjustment for age, PP, fasting plasma glucose, body mass index, and total cholesterol. T values 5-10 yr before the carotid study also predicted the stiffness index (P < 0.05). Thus the adverse influence of low T on the cardiovascular system in men may be mediated in part via the effects of T on vascular structure and function.

Adult↗
PubMed2005

Accelerated longitudinal decline of aerobic capacity in healthy older adults.

BACKGROUND: The ability of older persons to function independently is dependent largely on the maintenance of sufficient aerobic capacity and strength to perform daily activities. Although peak aerobic capacity is widely recognized to decline with age, its rate of decline has been estimated primarily from cross-sectional studies that may provide misleading, overly optimistic estimates of aging changes. METHODS AND RESULTS: To determine longitudinal rate of change in aerobic capacity and the influence of age, gender, and physical activity on these changes, we performed serial measurements of peak treadmill oxygen consumption (peak VO2) in 375 women and 435 men ages 21 to 87 years from the Baltimore Longitudinal Study of Aging, a community-dwelling cohort free of clinical heart disease, over a median follow-up period of 7.9 years. A linear mixed-effects regression model was used to calculate the predicted longitudinal 10-year rate of change in peak VO2, expressed in milliliters per minute, for each age decade from the 20s through the 70s after adjustment for self-reported leisure-time physical activity. A longitudinal decline in peak VO2 was observed in each of the 6 age decades in both sexes; however, the rate of decline accelerated from 3% to 6% per 10 years in the 20s and 30s to >20% per 10 years in the 70s and beyond. The rate of decline for each decade was larger in men than in women from the 40s onward. Similar longitudinal rates of decline prevailed when peak VO2 was indexed per kilogram of body weight or per kilogram of fat-free mass and in all quartiles of self-reported leisure-time physical activity. When the components of peak VO2 were examined, the rate of longitudinal decline of the oxygen pulse (ie, the O2 utilization per heart beat) mirrored that of peak VO2, whereas the longitudinal rate of heart rate decline averaged only 4% to 6% per 10 years, and accelerated only minimally with age. CONCLUSIONS: The longitudinal rate of decline in peak VO2 in healthy adults is not constant across the age span in healthy persons, as assumed by cross-sectional studies, but accelerates markedly with each successive age decade, especially in men, regardless of physical activity habits. The accelerated rate of decline of peak aerobic capacity has substantial implications with regard to functional independence and quality of life, not only in healthy older persons, but particularly when disease-related deficits are superimposed.

Adult↗
PubMed2005

Effect of light-to-moderate alcohol consumption on age-associated arterial stiffening.

Increased thickness and stiffness of large arteries may contribute to why aging is the most important risk for cardiovascular diseases. Arterial stiffness, intimal medial thickness, and alcohol intake were measured in 563 subjects. A U-shaped relation was found between alcohol intake and a stiffness index, with the lowest index in moderate drinkers, which may partially explain the relation between alcohol and cardiovascular disease.

Adult↗
PubMed2005

Effect of exercise on blood pressure in older persons: a randomized controlled trial.

BACKGROUND: Because of age-related differences in the cause of hypertension, it is uncertain whether current exercise guidelines for reducing blood pressure (BP) are applicable to older persons. Few exercise studies in older persons have evaluated BP changes in relation to changes in body composition or fitness. METHODS: This was a 6-month randomized controlled trial of combined aerobic and resistance training; controls followed usual care physical activity and diet advice. Participants (aged 55-75 years) had untreated systolic BP (SBP) of 130 to 159 mm Hg or diastolic BP (DBP) of 85 to 99 mm Hg. RESULTS: Fifty-one exercisers and 53 controls completed the trial. Exercisers significantly improved aerobic and strength fitness, increased lean mass, and reduced general and abdominal obesity. Mean decreases in SBP and DBP, respectively, were 5.3 and 3.7 mm Hg among exercisers and 4.5 and 1.5 mm Hg among controls (P < .001 for all). There were no significant group differences in mean SBP change from baseline (-0.8 mm Hg; P=.67). The mean DBP reduction was greater among exercisers (-2.2 mm Hg; P=.02). Aortic stiffness, indexed by aortofemoral pulse-wave velocity, was unchanged in both groups. Body composition improvements explained 8% of the SBP reduction (P = .006) and 17% of the DBP reduction (P<.001). CONCLUSIONS: A 6-month program of aerobic and resistance training lowered DBP but not SBP in older adults with mild hypertension more than in controls. The concomitant lack of improvement in aortic stiffness in exercisers suggests that older persons may be resistant to exercise-induced reductions in SBP. Body composition improvements were associated with BP reductions and may be a pathway by which exercise training improves cardiovascular health in older men and women.

Aged↗
PubMed2005

Oxygen pulse during exercise is related to resting systolic and diastolic left ventricular function in older persons with mild hypertension.

BACKGROUND: The mechanisms responsible for impaired cardiovascular hemodynamics during exercise among persons with milder forms of hypertension are not well documented. We examined the relationship of oxygen pulse during exercise, a correlate of stroke volume, with echocardiographic indices of resting left ventricular function to determine whether abnormal contractility and relaxation are related to abnormal cardiovascular dynamics during exercise among such persons. METHODS: Subjects were 44 men and 55 women ages 55 to 75 years with mild hypertension but who were otherwise healthy. Resting left ventricular systolic and diastolic functions were assessed with 2-dimensional Doppler echocardiography and tissue Doppler imaging. Oxygen pulse (millimeters per beat) at rest and during multistage treadmill testing was derived from measurements of oxygen consumption and heart rate. The slope of oxygen pulse between successive exercise stages was calculated. RESULTS: After a steep rise in oxygen pulse from rest to stage 1 of exercise, a markedly diminished oxygen pulse slope was seen between subsequent exercise stages. In stepwise regression analysis, the increase in the slope of oxygen pulse from rest to stage 1 was explained by a greater lean body mass (57%, P < .001) and a larger left atrial size (2%, P < .001). After exercise stage 1, the increase in the slope of oxygen pulse was explained by sex (24%, P < .001), higher mitral E/A ratio (6%, P < .001), and higher mitral annular systolic velocity (6%, P < .001). CONCLUSIONS: These results suggest that a blunted oxygen pulse response to exercise among older persons with milder forms of hypertension may reflect impaired left ventricular stroke volume changes during exercise secondary to subtle abnormalities in both systolic and diastolic left ventricular functions.

Aged↗
PubMed2005

The combination of high fruit and vegetable and low saturated fat intakes is more protective against mortality in aging men than is either alone: the Baltimore Longitudinal Study of Aging.

Saturated fat (SF) intake contributes to the risk of coronary heart disease (CHD) mortality. Recently, the protective effects of fruit and vegetable (FV) intake on both CHD and all-cause mortality were documented. However, individuals consuming more FV may be displacing higher-fat foods. Therefore, we investigated the individual and combined effects of FV and SF consumption on total and CHD mortality among 501 initially healthy men in the Baltimore Longitudinal Study of Aging (BLSA). Over a mean 18 y of follow-up, 7-d diet records were taken at 1-7 visits. Cause of death was ascertained from death certificates, hospital records, and autopsy data. After adjustment for age, total energy intake, BMI, smoking, alcohol use, dietary supplements, and physical activity score, FV and SF intakes were individually associated with lower all-cause and CHD mortality (P < 0.05). When both FV and SF were included in the same model, associations of each were attenuated with CHD mortality, and no longer significant for all-cause mortality. Men consuming the combination of > or =5 servings of FV/d and < or =12% energy from SF were 31% less likely to die of any cause (P < 0.05), and 76% less likely to die from CHD (P < 0.001), relative to those consuming < 5 FV and >12% SF. Men consuming either low SF or high FV, but not both, did not have a significantly lower risk of total mortality; but did have 64-67% lower risk of CHD mortality (P < 0.05) relative to those doing neither. These results confirm the protective effects of low SF and high FV intake against CHD mortality. In addition, they extend these findings by demonstrating that the combination of both behaviors is more protective than either alone, suggesting that their beneficial effects are mediated by different mechanisms.

Adult↗
PubMed2005

The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature.

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.

Adolescent↗
PubMed2004

Age and gender affect ventricular-vascular coupling during aerobic exercise.

OBJECTIVES: The goal of this study was to examine the age-associated differences in ventricular-vascular coupling, defined by the ratio of arterial elastance (EaI) to left ventricular systolic elastance (E(LV)I), and its components, at rest and during exercise. BACKGROUND: Ejection fraction (EF) increases during exercise, but the EF reserve decreases with aging. Ejection fraction is inversely related to EaI/E(LV)I, an index of the interaction between arterial and ventricular properties, which is an important determinant of cardiac performance. Thus, age differences in EaI/E(LV)I during exercise, due to age differences in EaI, E(LV)I, or both, may help to explain the age deficit in EF reserve. METHODS: We noninvasively characterized EaI/E(LV)I = end-systolic volume index (ESVI)/stroke volume index (SVI) and its two determinants EaI = end-systolic pressure/SVI, and E(LV)I = end-systolic pressure/ESVI, at rest and during exercise in 239 healthy men and women (age range, 21 to 87 years). Blood pressures were assessed with cuff sphygomanometry, and cardiac volumes with gated blood pool scintingraphy. RESULTS: Resting EaI/E(LV)I was not age related in men or women. In both sexes, EaI/E(LV)I decreased during exercise and declined to a lesser extent in older subjects. There were gender differences in the components of EaI/E(LV)I during exercise: EaI was greater in older versus young women (p = 0.01) but was unaffected by age in men. Left ventricular systolic elastance increased to a greater extent in young versus older subjects (p = 0.0001 for men, p = 0.07 for women). CONCLUSIONS: Age-associated differences in EaI/E(LV)I occur in both genders during exercise. Sub-optimal ventricular-vascular coupling helps to explain the age-associated blunting of maximal exercise EF, and its underlying mechanisms appear to differ between men and women.

Adult↗