Sex Differences in the Pulmonary Artery Wedge Pressure Response to Exercise in Healthy Older Adults

Background Dyspnea with physical exertion is an important limitation in the aging population. A proportion of affected patients demonstrate marked increases in the pulmonary artery wedge pressure (PAWP) during exercise, which is thought to reflect latent abnormalities of left ventricular diastolic function or early Heart Failure with preserved ejection fraction (HFpEF). This condition demonstrates a clear female disposition. Although hemodynamic exercise testing is a promising means to identify this patient population, it is limited by lack of normal reference ranges. Our objectives were to 1) describe the PAWP response to exercise in healthy, community‐dwelling older adults and 2) examine whether there were sex differences with respect to this physiology. We hypothesized that compared to similarly aged men, post‐menopausal women would demonstrate an elevated PAWP in response to submaximal exercise. Methods Thirty‐six healthy volunteers [18 men (54 ± 7 years)/ 18 women (58 ± 6 years)] were studied at rest (control) and during two consecutive stages of semi‐upright cycle‐ergometry designed to elicit heart rates of approximately 100 bpm (Light Exercise) and 120 bpm (Moderate Exercise). Right heart catheterization was performed to measure pulmonary pressures, with simultaneous echocardiography. At each exercise intensity, pulmonary artery systolic, diastolic, mean, and wedge pressures were manually analyzed offline, beat‐by‐beat. Cardiac output (CO) and stroke volume (SV) were derived from thermodilution (n = 28) or Doppler echocardiography (n = 8). Results Exercise hemodynamic data are presented in Table 1. At control, PAWP was similar between men and women, while CO and SV tended to be lower in women even when indexed to body size. To achieve the same target HR at light and moderate exercise, workrates (WR) were smaller in women. At both light and moderate exercise, CO and SV increased, although they remained lower in women. Despite lower WR, CO, and SV in women, the pattern of the PAWP response was similar between sexes across both exercise intensities. PAWP increased at light exercise (17 ± 5 mmHg), with no further increase and a slight decline at moderate exercise (15 ± 5 mmHg). This occurred despite significantly elevated heart rate and CO throughout exercise. When indexed to exercise workrate (PAWR) or when adjusted as the ratio of PAWP to workload/body weight (PAWL), the PAWP response at light exercise was significantly higher in women compared to men. Although PAWR and PAWL then decreased from light to moderate exercise, they remained significantly elevated in women compared to men. Conclusion In healthy older adults, the PAWP response to submaximal exercise is complex, increasing during exercise then remaining stable or even declining as exercise intensity increases. Although the rise in the PAWP response to submaximal exercise appears similar in men and women, the increase in PAWP occurs despite lower CO and WR in women, even when adjusted for smaller body size. Women may be predisposed to effort‐related dyspnea based on relative pulmonary venous hypertension at lower exercise workload. Support or Funding Information This study was supported by the Heart & Stroke Foundation of Ontario. 1 Exercise Hemodynamic DataControl Light ModerateWR (W) Men ‐ 49 ± 16 82 ± 21 †Women ‐ 31 ± 18 * 53 ± 23 *, †HR(bpm) Men 62 ± 7 102 ± 2 # 121 ± 2 #, †Women 64 ± 8 104 ± 3 # 122 ± 3 #, †CI (L/min/m 2 ) Men 2.8 ± 1 5.7 ± 1 # 6.6 ± 2 #, †Women 2.5 ± 0.4 5.0 ± 1 # 5.7 ± 2 #SVI (mL/m 1 ) Men 45 ± 11 56 ± 15 # 55 ± 16 #Women 39 ± 8 48 ± 12 # 47 ± 10 #PASP (mmHg) Men 25 ± 5 39 ± 9 # 37 ± 7 #Women 25 ± 3 39 ± 7 # 37 ± 8 #PADP (mmHg) Men 10 ± 3 16 ± 4 # 15 ± 4 #Women 11 ± 3 17 ± 4 # 16 ± 5 #mPAP (mmHg) Men 17 ± 3 27 ± 5 # 25 ± 6 #, †Women 18 ± 2 27 ± 5 # 26 ± 6 #, †PAWP (mmHg) Men 11 ± 3 17 ± 5 # 15 ± 5 #Women 12 ± 2 17 ± 5 # 15 ± 5 #, †WL (W/kg) Men ‐ 0.60 ± 0.22 * 0.97 ± 0.29 †Women ‐ 0.40 ± 0.29 * 0.64 ± 0.41 *, †PAWR (mmHg/W) Men ‐ 0.36 ± 0.10 0.19 ± 0.05 †Women ‐ 0.70 ± 0.45 * 0.25 ± 0.14 *, †PAWL (mmHg/W/kg) Men ‐ 32 ± 14 17 ± 8 †Women ‐ 67 ± 64 * 30 ± 25 *, †* P < 0.05 vs. Men; # P < 0.05 vs. Control; † P < 0.05 vs. Light WR, workrate; HR, heart rate; CI, cardiac index; SVI, stroke volume index; PASP, pulmonary artery systolic pressure; PADP, pulmonary artery diastolic pressure; mPAP, mean pulmonary artery pressure; PAWP, pulmonary artery wedge pressure; WL, workrate adjusted for body weight; PAWR. pulmonary artery wedge pressure indexed to exercise workrate; PAWL. The ratio of pulmonary artery wedge pressure to workload/body weight.