This study aimed to define the influence of healthy aging on the central hemodynamic response to exercise. Advancing age results in numerous alterations to the cardiovascular system and is a major risk factor to develop heart failure. In patients with suspected heart failure with preserved ejection fraction, there is an increasing interest in the incorporation of stress hemodynamic studies into the diagnostic evaluation pathway. However, many patients with suspected heart failure with preserved ejection fraction are older, and there are few data regarding the effect of aging on the normal central hemodynamic responses to exercise. Therefore, we examined 55 healthy patients using right-sided cardiac catheterization with exercise. Mean age was 49.6 years, with 36% older than 55 years. On exercise, the mean pulmonary artery pressure was higher with advancing age (r = 0.412, p = 0.002). Additionally, age was negatively associated with cardiac index (r = 0.407, p = 0.005). The exercise-induced rise in pulmonary capillary wedge pressure (r = 0.378, p = 0.004) was greater with advancing age. Pulse pressure measured during exercise (r = 0.541, p <0.01) increased with age, as did diastolic dysfunction assessed by E/A ratio (r = 0.569, p <0.001). In conclusion, aging was associated with decreased cardiac output and increased pulmonary artery pressure during exercise, which developed as the consequence of both increased pulmonary vasculature resistance and higher left ventricular filling pressures.
The effects of advancing age potentially confound the interpretation of exercise hemodynamic studies, particularly in heart failure with preserved ejection fraction (HFPEF), which typically occurs in older patients. For example, aging may be associated with increasing pulmonary artery pressures (PAPs) and systemic vascular stiffening. Echocardiographic studies suggest a relation between increased exercise PAP estimates and survival. To more formally incorporate exercise hemodynamics into the diagnostic evaluation, it is necessary to define the normal exercise response in the context of advancing age. The aim of the present study was to characterize the hemodynamic response to exercise in healthy subjects across a range of ages.
Methods
Data were extracted from the catheter laboratory records of all patients who underwent diagnostic right-sided cardiac catheterization at the Alfred Centre, Melbourne, Australia, and the Mayo Clinic, Rochester, Minnesota. We included healthy control patients from previous experimental studies as well as ongoing studies, and patients evaluated for unexplained exertional dyspnea, in the absence of any abnormalities on echocardiography or right-sided cardiac catheterization. We excluded patients with risk factors for pulmonary hypertension, such as history of thrombo-embolic pulmonary disease, connective tissue disease, or severe pulmonary disease. Research protocol was submitted and approved by the institutional ethics review board.
Right-sided cardiac catheterization was performed as described previously. Pulmonary vascular resistance (PVR) was calculated as (mean PAP [mPAP]–mean pulmonary capillary wedge pressure [PCWP])/cardiac output. Measurements were indexed to body surface area, as appropriate.
Subjects then exercised in the supine position on a cycle ergometer mounted to the catheter table. Exercise protocol in the Alfred Hospital (Melbourne, Australia)—subjects started at a work rate of 0.3 W/kg body weight for 3 minutes. The workload was increased to, respectively, 0.6, 1.0, and 1.5 W/kg for every 3 minutes or until exhaustion. Exercise protocol in the Mayo Clinic (Rochester, Minnesota)—subjects started at a workload of 20 W with 10 to 25 W increments at the discretion of the performing physician for every 3 minutes to maximum tolerated levels. PCWP and PAP were determined at baseline and at peak exercise. Peak exercise cardiac index was determined either by the Fick method (n = 31) or by the thermodilution (n = 24).
Standard M-mode, 2-dimensional, and Doppler blood flow recordings were performed using standardized instruments. Measurements were performed off-line. All parameters were measured in triplicate and averaged. Tissue Doppler images of the mitral annulus movement were obtained from the apical 4-chamber view. A sample volume was placed at the lateral and septal annular sites. Analysis was performed for the early (e′) and late (a′) diastolic peak velocities. The E/e′ ratio was calculated using the mean from the lateral and septal E/e′. Pulsed-wave Doppler echocardiography was used to assess peak early (E) and late (A) wave flow velocities.
Statistical analyses were performed using a commercially available software package (IBM SPSS Statistics version 20; SPSS Inc., Chicago, Illinois). Categorical data are given as counts and percentages. Continuous data are presented as mean ± SD or median (interquartile range). Groups were compared using chi-square test for categorical variables and t test for normally distributed continuous variables. Groups were compared using Mann-Whitney U test if variables were not normally distributed. Correlations were testing using Pearson’s correlation coefficient. Regression analyses were used for adjusted comparisons. A p value of <0.05 was considered to be statistically significant.
Results
Baseline characteristics of the study population (n = 55) are listed in Table 1 . Mean age was 49.6 years, with 36% older than 55 years. Clinical characteristics demonstrate a relatively healthy population with limited co-morbidities. When subjects were stratified into 2 groups according to age (>55 years), co-morbidities were evenly distributed between the 2 groups.
