Influence of aging on pulmonary hemodynamics in a population free of coronary artery disease

MISCELLANEOUS

Influence of Aging on Pulmonary in a Population Free of Coronary

Hemodynamics Artery Disease

William R. Davidson, Jr., MD, and Eric C. Fee, MD

Previaus studies showing an increase in pulmonary and vascuiar resistance with artery PA) m aging be not syrtemaiccllly excluded subjects withcoromwyarterydisease!oriefiventricuiarsystoiic dysfunctien. To better determine tile influeme ofagingonPAhemodynamicsintheabsenceof disease, we idedfbd 47 nomud subjects angiocoronary artery disease (18 wclphkellyfreeof men, 29 women) with normal iefi ventrichr systoik function (ejection fraction SO% and iefi ventricuim ed-diastoiic pressure <14 mm Hg) from S,SO8 ctonmdve ptients undergoing cardiac catilet~tionand -waw!d@mwY between September lo,1982 and March 9,1987. Ail subjectsmetasetofctinkaiandiaboratorycriteria nermai. In group I (age 260 idenwyrngth@!myears) mean PA pressure was 16 f 3 mm Hg, pul-

monaryvascdarresistancewas124f32dyness vascuiar resircan-’ and the puhomtyhystemic tame ratio was 0.099 f 0.046. in contrast, in group ii (age <60 years), these vaiues were lower at12f2mmHg,70f2Sdynesscm-5and 0.057 f 0.019, reqectheiy (ail p vaiues X0.01 to 0.001). All them parameters increased iineariy with age (r = 0.69, p
From the Division of Cardiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, Hershey, Pennsylvania. Manuscript received December 11, 1989; revised manuscript received and accepted February $1990. Address for reprints: William R. Davidson, Jr., MD, Division of Cardiology, The Milton S. Hershey Medical Center, The Pennsylvania State University, PO Box 850, Hershey, Pennsylvania 17033.

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here are fewer studies of the pulmonary circulation than of the systemic vasculature due to the relative inaccessibility of the pulmonary vessels. Those performed have shown an increase in pulmonary artery (PA) pressure and vascular resistance with aging.1-4 In these studies, coronary artery disease was excluded on clinical or noninvasive grounds; left-sided heart pressures were not measured nor was ventriculography performed. Most of these studies were performed before the era of coronary angiography.1-3 To establish the specific influence of aging on PA hemodynamics, subjects should have coronary artery disease and ventricular dysfunction excluded. Ethical constraints preclude prospective coronary angiographic evaluation of a large number of normal subjects. Therefore, we undertook a retrospective study to define the influence of aging on the pulmonary vasculature in a population with angiographically defined coronary anatomy and ventricular function.

T

METHODS

Each subject was included after evaluation of his or her medical record and cardiac catheterization data. All were 220 years of age and were identified from 5,508 consecutive cardiac catheterizations performed in the Division of Cardiology, University Hospital, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine from September 10, 1982, to March 9, 1987. The subjects were divided into the following 2 groups: group I was made up of subjects 160 years of age and group II was made up of subjects 120 but <60 years. All subjects with a final diagnosis of “normal” (no abnormalities found) were reviewed. Using the hospital record, the subjects’ medical history and physical examination at the time of cardiac catheterization were evaluated to exclude those with evidence of cardiac and/or pulmonary disease. The chest x-ray report was reviewed for clear lung fields, normal heart size and no evidence of active cardiac and/or pulmonary disease. Subjects with isolated pulmonary granulomata were not excluded from the study. Chest x-rays were reviewed by an investigator (WRD) if the report was unclear. The electrocardiogram was reviewed and subjects were excluded for rhythm disturbances and evidence for ischemia, infarction or hypertrophy. Those with a clinical history of systemic hypertension (by history in medical record, requiring drug therapy or blood pressures on the wards >140 mm Hg systolic or >90 mm Hg diastolic) were excluded. Those with abnormal pulmonary function tests (when performed) were excluded. A history of tobacco use without a history of

I Systemic Hemodynamics and Blood Gas Results

TABLE

Group Dependent

Variable

Age km) Body surface area (m2) Cardiac output (liters/min) Cardiac index (liters/min/m2) Ejection fraction Heart rate (beats/min) LVEDP (mm Hg) 02 sat. (%) Pa 02 (mm Hg) PCWP (mm Hg) Mean RAP (mm Hg) Systolic SAP (mm Hg) Diastolic SAP (mm Hg) Mean SAP (mm Hg) SVR (dynes s cm-5) SVRI (dynes cm-5 m2)

Group

I (n = 14)

Mean i SD 64*3 1.7710.17 5.6s 1.4 3.2 f 0.9

69f12 79f16 813 97f2 81 f 7f3 4f2 133f 69f9 94f 1355 f

14

18 13 342

2439*717

II (n = 33)

Mean f SD

Range

60to69 1.40t02.12 4.0 to 8.3

Range 24 to 55 1.37 to 2.30

42f8

1.84 f 0.23 6.3f 1.5 3.4 f 0.7 64fo9 77f13 9f3 97f2 84f8 7f3 4f2 128f 17 75fll

2.2 to 5.4 48to93

5Oto120 5to13 94to 100 71to108 3to 13 lto6 11oto 180 6oto90 72 to 125 704 to 1820 1304 to 3757

3.4 to 9.9 2.2 to 5.3

49to83 48to 112 4to13 91 to loo 71 to 100 2to13 lto8 100 to 160 5Oto100 75to115 711to2612 1208to4440

97flO 1252f363 2296 f 569

There were no significant dkrences between the groups for any variable listed other than age. LVEDP = left ventricular enddiistolic pressure: 02 sat = arterial oxygen saturation: PA 02 = artenal partal pressure of oxygen; PCWP = pulmonary capillary wedge pressure; RAP = right atrial pressure; SAP = systemic arterial pressure; SD = standard deviation; SVR = systemic vascular resistance: SVRI -systemic vascular resistance index.

TABLE

II Pulmonary Artery Pressure and Vascular Resistance Group

I (n = 14)

Mean f SD PA systolic (mm Hg) PA diastolic (mm Hg) Mean PA (mm Hg) Mean PA-PCWP (mm Hg) PVR (dynes s cm-5) PVRI (dynes s cm-5 m2) PVR/SVR X loo0

26f5* 11*3* 16f3* 9*3+

124*32+ 225 i 69+ 99*46+

Group Range

II (n = 33)

Mean f SD

16to35 8to18 11 to23 5to16 75 to 178

Range

13to28 6to14 8to 19 lto8 12to112 24 to 193 12to95

2of4

9f2 12f2 5h2 70f25 128i41

133 to 337 50 to 242

57f19

* p
pulmonary disease did not exclude subjects from the study. The subjects were categorized as nonsmokers, exsmokers and current smokers of l pack/day. All subjects underwent right- and left-sided heart catheterization with coronary arteriography and left ventriculography. A variety of fluid-filled catheters were used. Transducers are balanced routinely before each case and rechecked periodically before pressure recording in our laboratory, Each subject’s cardiac pressure tracings were reviewed. PA and other pressure values are reported as an average over the respiratory cycle. Hemodynamic inclusion criteria were the following: cardiac index 12.2 liters/*, left ventricular end-diastolic pressure I1 3 mm Hg; mean right atria1 pressure 18 mm Hg; and a mean PA wedge pressure I 13 mm Hg. Pressure decrease across the pulmonary vascular bed was calculated as PA mean - PA wedge pressure. Systemic and pulmonary vascular resistances (both measured in dynes s cmd5), systemic and pulmonary vascular resistance indexes (normalized by multiplying resistance values by the body surface area) and the ratio of pulmonary to systemic vascular resistance were calculated from the hemodynamic dataa Cases with poor quality hemodynamic tracings were excluded. Patients

with any occlusive or nonocclusive coronary disease were excluded. Patients with mitral regurgitation, mitral valve prolapse, ejection fraction GO% or regional wall motion abnormalities on ventriculography were excluded. The following were abstracted from the cardiac catheterization and medical records of each subject: age; gender; height; weight; body surface area; aortic mean, systolic and diastolic pressure; systemic arterial partial pressure of oxygen; arterial oxygen saturation; heart rate; cardiac output and index; and ventriculographic ejection fraction. All study population subjects had an arterial oxygen tension >70 mm Hg and an arterial oxygen saturation >90% at catheterization. The arterial oxygen saturation and oxygen tension determinations were performed with a Corning 168 pH blood gas system (Corning Medical) which was calibrated daily and used throughout the study. The data were expressed as the mean f standard deviation. An unpaired Student’s t test was used to compare means of the study groups and to examine gender differences. Univariate and multivariate linear regression analysis was used to evaluate the relation between age and the pulmonary variables. Data analysis was conducted on a Macintosh Plus computer using the THE AMERICAN

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statistical package, Statworks (Data Metrics). A p value <0.05 was accepted as statistically significant. RESULTS

Forty-seven adults (29 women, 18 men) aged 24 to 69 years (mean 48 f 13) were identified (Table I). The gender distribution did not differ between groups by cl&square analysis. Most had undergone coronary angiography for chest pain and/or suspected coronary disease. The study group comprised
25

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Age (years) THE AMERICAN

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This is the first study to document an increase in pulmonary vascular resistance and PA pressure with aging in a group of subjects in which coronary artery disease and left ventricular systolic dysfunction were excluded systematically. This increase was most striking for pressure decrease across the pulmonary vascular bed and indexes derived from it, which were pulmonary vascular resistance and resistance index and the pulmonary/systemic vascular resistance ratio. It was less strong for mean PA pressure. The smaller increase in mean PA pressure with age can be explained in part by the tendency for cardiac output to be lower in our older subjects, a finding described by some7.8 but not others.9 The increase in pressure and resistance with aging appeared continuous and linear without an apparent

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1

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DISCUSSION

.

I

I

area (r = 0.35, p <0.02) but this did not explain the variability due to age as the pulmonary vascular resistance index also increased significantly with age (r = 0.68, p
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FIGURE l.Relathofmeanpdmnary arterypmssuretoagein47mmml subjscts.y=O.12x+8.PA= p+nonuya~-.

“breakpoint,” as was suggested by Ehrsam4 (Figures 1, 2 and 3). Previous studies examining the influence of aging on pulmonary hemodynamics occurred before the era of modem stress testing or coronary arteriography. One third of Granath’s subjects had ST changes with exer-

200

tion and many had electrocardiographic abnormalities at restlJO Other studies used clinical criteria, stress testing or the resting electrocardiogram to screen for coronary disease.2-4 However, with the high prevalence of coronary disease in an older population, false negative exercise tests are more likely. In 1 study,4 most of

r = 0.69 p
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vasa~-

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dynes

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40

60

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Age (years) o (63, 24.2)

r = 0.50 p-eo.001

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iCVaSCllhldWUlW

nemd

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of Pmanayhystemretietoagein47 y = ‘G.Go14 x + 0.0027.

0

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20

40

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Age (years) THE AMERICAN

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the older subjects had undergone study for suspected pulmonary disease which raises other questions about the true “normality” of their subjects. The increase in coronary disease prevalence with aging” and the frequently silent nature of coronary artery disease are well known.12,13 In the elderly, the clinical incidence of coronary disease greatly underestimates the incidence of coronary atherosclerosis at autopsy.10,‘4 Doppler studies have documented the increasing frequency of mitral insufficiency with aging, which is frequently not clinically apparent.rj Because of our study design, clinically inapparent abnormalities of all these factors have been excluded as the cause of our findings. Fortuitously, 49% of the subjects also had an ergonovine challenge and all results were negative. Several mechanisms could explain the influence of age on pulmonary hemodynamics. A primary abnormality of the pulmonary vascular bed is likely as changes in the systemic circulation with aging are well described.7,16-17Such changes might influence the pulmonary circuit as well. Histopathologic changes in the pulmonary vasculature with aging are also well des~ribed.~*-~~However, the ratio of pulmonary to systemic vascular resistance also increased with age, suggesting that the effects of aging were proportionately greater in the pulmonary than in the systemic vascular bed. Left ventricular diastolic dysfunction may be responsible for the greater increase in the pulmonary bed as the wedge pressure increases more in older than younger subjects with exercise. 1+4,21 Abnormalities of left ventricular tilling and compliance and increased wall thickness are reported with aging.22-24 Higher systemic afterload may also cause higher pulmonary pressures with aging. However, in the current study, arterial pressure and systemic vascular resistance did not increase with aging. Limitations: A retrospective study limits the ability to control the quality of collected data or to obtain exercise pulmonary pressures. This was addressed by using stringent exclusion criteria. By this design, many clinically “normal” older subjects were excluded, thus we may have underestimated the degree of change in the pulmonary vascular bed associated with the aging process or the influence of ventricular diastolic function. Our younger subjects had hemodynamic findings similar to published normal subjects.5,25-27The identified trends with aging conform to published findings. Thus, a patient group was identified similar to those of previous studies.te4 Whether the observed changes continue further beyond the age of 70 cannot be addressed as our oldest patient was 69 years of age. Smokers were not excluded; however, smoking has not been found to be associated with the vascular intimal changes seen in the pulmonary circuit with aging in the absence of clinical pulmonary disease.‘* Clinical implkations There is a recognized need for better information concerning normal pulmonary hemodynamics and their relation to age.27 Pulmonary pressures are commonly used as an indicator of the severity

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of pulmonary and left-sided heart disease. Our results suggest that using such an approach in older subjects may overestimate the clinical severity of these disorders. Acknowledgment: We would like to thank Joseph A. Gascho, MD, for review of the manuscript and Gayle Herrin for patient typing.

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