Aortic and large artery stiffness: current methodology and clinical correlations.

Current methodology for the in vitro determination of aortic and large artery stiffness is reviewed and involves three approaches: (1) the estimation of distensibility by pulse wave velocity measurement; (2) the estimation of distensibility from the fractional diameter change of a given arterial segment by imaging techniques (e.g., angiography, Doppler ultrasound) against pressure change; (3) the estimation of compliance by determining volume change against pressure change in the arterial system during diastolic runoff from the Windkessel model of the circulation. Clinical correlations may be summarized as follows: (1) age: a progressive stiffening on aging due to structural changes up to the seventh decade; (2) sex: a lower degree of stiffness in women until menopause, after which they show an accelerated stiffening, catching up with men by the seventh decade; (3) atherosclerosis: a dissociation between degree of stiffness and extent of atherosclerosis, with a suggestion that in advanced atherosclerosis the extensive calcification may lead to increased stiffness; (4) coronary disease: an inconsistent correlation by pulse wave velocity studies, but a strongly positive correlation by angiographic study of the aortic root; (5) diabetes mellitus: a significant correlation by pulse wave velocity study, particularly in the presence of advanced peripheral vascular disease; (6) hypertension (both essential and elderly patients with systolic): positive correlation but only referable to the stiffening effect of a higher mean arterial pressure (i.e., unrelated to structural changes), although an experimental study did show a loss of compliance unrelated to the mean arterial pressure level in baboons with chronic renovascular hypertension.

Aging increases adenosine and inosine release by human fibroblast cultures.

The effect of in vitro age and donor age on net release of adenosine and inosine was studied in cultures of normal human fibroblasts. Confluent cultures of low-(population doubling level [PDL] 23-25) and high- (PDL 43-45) passage human lung fibroblasts derived from a 16-week-old fetal donor (IMR-90) were incubated for 30 min in physiological saline and the release of adenosine and inosine into the saline was determined by HPLC. Release of adenosine and inosine into the saline bathing low-passage human skin fibroblasts derived from a 16-week-old fetal donor (GM6111) was also determined and compared with two strains of low-passage skin fibroblasts from aged (66-67 years) donors (GM3529 and GM3524). The release of adenosine and inosine by low-passage cultures of fetal lung fibroblasts was 911 and 225 pmol/30 min per mg protein, respectively. In high-passage cultures of lung fibroblasts, release of adenosine and inosine was significantly greater at 1403 and 351 pmol/30 min per mg protein, respectively. The release of adenosine and inosine by low-passage cultures of fetal skin fibroblasts was 250 and 179 pmol/30 min per mg protein, respectively. In low-passage skin fibroblasts from aged donors, release of adenosine and inosine was significantly greater at 583 and 652 pmol/30 min per mg protein, respectively. These results indicate that the net release of adenosine and inosine by cultured human fibroblasts into their extracellular environment is enhanced by in vitro aging of lung fibroblasts and is greater in skin fibroblast from aged donors.

Exercise testing and hemodynamic performance in healthy elderly persons.

To determine the effect of age on cardiovascular performance, 39 healthy elderly men and women, 70 to 83 years old, underwent treadmill thallium-201 exercise perfusion imaging and radionuclide equilibrium angiography at rest and during supine bicycle exercise. Five volunteers who had a positive exercise thallium test response were excluded from the study. Radionuclide left ventricular ejection fraction, regional wall abnormalities, relative cardiac output, stroke volume, end-diastolic volume and end-systolic volume were measured. Seventy-four percent of the subjects maintained or increased their ejection fraction with exercise. With peak exercise, mean end-diastolic volume did not change, end-systolic volume decreased and cardiac output and stroke volume increased. Moreover, in 35% of the subjects, minor regional wall motion abnormalities developed during exercise. There was no significant difference in the response of men and women with regard to these variables. However, more women than men had difficulty performing bicycle ergometry because they had never bicycled before. Subjects who walked daily performed the exercise tests with less anxiety and with a smaller increase in heart rate and systolic blood pressure.

Nutrition and the elderly.

As the size of the elderly population grows, nutrition for the elderly has assumed increasing significance. Osteoporosis is a prime example of a disease which is, at least partially, nutritionally related and of great importance in this population. Not only may essential nutrients be in short supply in the diet during later years, but impaired absorption and utilization may actually dictate increased amounts to prevent disease. The optimal amount of protein in the diet is not yet known, but a decrease in caloric intake as people age is probably desirable.

A geriatric special-care unit: experience in a university hospital.

Responding to a perceived need for specialized care for the acutely ill elderly, a 14-bed geriatric special-care unit was established in the University of Massachusetts Hospital in January 1980. Patients were selected for admission after assessment of their potential to benefit from restorative care. Most patients were admitted from the emergency room or outpatient clinics or were scheduled admissions; a few were in-hospital transfers. This report deals with a retrospective analysis of the first 514 admissions (431 patients) to the unit. Admissions by major service were: Medicine, 64 per cent; Surgery, 14 per cent; Neurology, 10 per cent; Orthopedics, 7 per cent; and other, 5 per cent. Approximately 64 per cent of patients were between the ages of 70 and 84. The overall average length of stay per admission was 11.5 days. Mortality rate of patients undergoing surgery (n = 125) was 4 per cent. The percentage of admissions that were discharged home was 78.7 per cent. Only 7.3 per cent of admissions were discharged to a nursing home, when those that were admitted to the unit from a nursing home are excluded. The authors conclude that a special nursing unit for acutely ill elderly patients may serve several purposes in a university hospital: overall patient care may be improved; length of hospital stay may be shortened; and medical students, housestaff, and attending physicians may gain an opportunity to learn the fundamentals of geriatric medicine as demonstrated by the staff of the unit.

Aging and hypertension: hemodynamic implications of systolic pressure trends.

The progressive rise in systolic pressure throughout life is accepted as a phenomenon of "normative aging," although elevated systolic pressure is established as an independent risk factor for untoward cardiovascular events. An analysis of published data for many thousands of individuals indicates comparable average systolic pressure increments of approximately 20 mm Hg between the ages of 40 and 65 years for both normotensives and hypertensives. In both groups there is a disproportionate rise in systolic pressure, that is, systolic increases more than mean and diastolic pressures. In a young person with a normally elastic arterial system an increase in total peripheral resistance (TPR) produces the same increments in systolic, diastolic, and mean arterial pressures; a decrease in arterial distensibility (AD), on the other hand, increases systolic pressure and decreases diastolic pressure to the same extent, leaving mean pressure unchanged. Thus, the proportion of the systolic pressure rise resulting from increased TPR is equal to the increase in the mean pressure (delta mean); the remainder of the increase (delta systolic minus delta mean) is caused by the only other variable that could account for an additional increase in systolic pressure with advancing age, a decrease in AD. Application of this formulation to published blood pressure data shows that in normotensives the ratio of the contribution toward rising systolic pressure of reduced AD to increased TPR is 1:1 between the ages of 40 and 65 years, whereas in hypertensives it is 2:1. Thus, the natural history of essential hypertension, once established, is one of accelerated arterial stiffening, a mechanism that would contribute importantly to the increasing prevalence of "systolic hypertension" with advancing age.

Cholesterol and cholesteryl ester concentration in different size classes of cultured human fibroblasts: effect of in vitro aging.

Early and late passage WI-38 fibroblasts were fractionated on the basis of cell size by gravity sedimentation, and free and esterified cholesterol concentrations were determined in each fraction. The cholesteryl ester concentration in all size classes of late passage cells was greater than that of all size classes of early passage cells; the average of all fractions of late passage cells was 2.5 times greater (pg/micrometers 3) and 1.7 times greater (micrograms/mg protein) than that of all fractions of early passage cells (p less than 0.001). The average free cholesterol concentration (micrograms/mg protein) in late passage cell fractions exhibited a consistent, but not statistically significant, increase over that in early passage cells. These results indicate that the increase in cholesteryl ester concentration in late passage WI-38 fibroblasts is not solely attributable to the large, non-dividing cells which accumulate in senescing cultures.

Renal vein renin activity and prostaglandins A and E in hypertension.

The relation between renal vein renin activity (RVRA) and renal vein-prostaglandin A (PGA) and prostaglandin E (PGE) concentrations was examined in 50 patients with hypertension who underwent renal vein catheterizations for suspected renovascular hypertension. In 14 patients wih unilateral renal artery stenosis, mean renal vein PGE concentrations were higher in the renal vein draining the nonischemic kidney, while RVRA was increased in the renal vein draining the ischemic kidney. PGE ratios from the two sides were inversely related to RVRA ratios in this group. In the other 36 patients with either bilateral renal artery stenosis, essential hypertension or nonrenovascular unilateral renal disease, RVRA and PGE concentrations were similar in both kidneys. No relation between RVRA and PGA could be established for any group.

Studies of the renin-renin substrate reaction in man; kinetic evidence for inhibition by serum.

Increasing evidence suggests that the renin-renin substrate reaction is regulated by factors other than the concentrations of enzyme and substrate. Partially purified human renin and renin substrate extracted from the plasma of each of eight human subjects were used to construct substrate-velocity curves comparing the rate of substrate cleavage in the whole serum of each individual with the rate in a corresponding system containing purified autologous substrate, or purified substrate plus a small amount of autologous serum. Linear regression analysis of the double reciprocal plots were used to compare the kinetic constants in paired experiments. Maximal reaction velocity (Vmax) was significantly lower (p greater than .05) when the reaction rate was measured in whole serum, in seven of the eight patients, while Km did not differ significantly, suggesting the presence of noncompetitive inhibition by human serum. The mean Michaelis constant in serum was 449 ng/ml while the average native substrate concentration of the five normal subjects was 629 ng/ml, an excess of less than twofold. The data suggest that plasma renin activity in man depends upon the concentrations of inhibitor and substrate, as well as upon the concentration of renin.

Plasma renin activity and cardiovascular disease.

1. A group of patients with essential hypertension was divided into three categories on the basis of the plasma renin activity. 2. There was no correlation between the plasma renin activity categorized as high, normal or low and the duration of hypertension, the incidence of left ventricular enlargement, the blood urea nitrogen, serum creatinine, cholesterol or uric acid respectively. 3. Analysis of data showed that the incidence of cardiovascular events in the hypertensive population correlated with the plasma renin activity only in combination with known risk factors.

Blood prostaglandin A (PGA) levels in normal human subjects.

PIP: Blood prostaglandin A levels were measured in 10 healthy subjects under different conditions of collection and storage. Plasma levels ranged from 1.20 to 1.81 ng/ml (M + or - SE=1.50 + or - 0.10) in 5 females, to 1.23 to 1.68 ng/ml (1.45 + or - 0.09) in 5 males, when centrifuged and frozen immediately after collection. Storage at 4 degrees Centigrade (C) for varying times up to 24 hours and at 22 degrees C (room temperature) up to 4 hours did not affect mean plasma concentrations significantly, but increased the range obtained to 1.00 to 2.47 ng/ml for both male and female groups. Serum concentrations differed in males and females and were lower than corresponding mean plasma values for males and higher for females. Mean serum concentrations were 1.77 + or - 0.08 ng/ml in females and 1.18 + or - 0.05 ng/ml in males and did not change significantly up to 24 hours of storage at 4 decrees C. These results suggest that prostaglandin A assayed in both plasma and serum under the conditions described is stable and should allow for greater flexibility in sampling under different experimental conditions.^ieng