K. O'malley

Digoxin in the elderly: Pharmacokinetic consequences of old age

A study of single‐dose digoxin kinetics was performed in 6 young and 7 elderly patients. The rate of absorption, determined by the time to peak concentration after an oral dose, was more rapid in the younger group. The extent of absorption, as measured by comparison of the area under the plasma concentration/time curve after oral and intravenous administration, was similar in both groups. Mean plasma half‐life was longer and individual values were more variable in the elderly patients. The absolute apparent volume of distribution was reduced in the older patients and correlated inversely with age. When corrected for weight, however, the difference in the apparent volume of distribution did not approach significance. Both absolute and weight‐corrected values for plasma clearance of digoxin were reduced in the elderly subjects.

A method of quantifying retinal microvascular alterations associated with blood pressure and age

Objective To find an objective, sensitive method for quantifying microvascular alterations associated with level of blood pressure and age. Design A prospective cross-sectional study. Subjects and methods Seventy-four previously untreated hypertensive patients, referred to a hospital outpatients department, and 26 normotensive volunteers participated. Twenty-four-hour ambulatory blood pressure monitoring and bilateral fundal photography were performed. The fundal photographs were projected on a screen such that the optic disc filled a circle of radius 5 cm. Microvessels crossing the border of a concentric circle of radius 20 cm were identified as arteriolar or venular, counted and their luminal diameters measured. Main outcome measures Arteriolar and venular numbers, mean diameters and vascularities (arteriolar and venular vascularities defined as the sum of arteriolar and venular diameters, respectively). Results The technique was reproducible. As blood pressure increased, arteriolar vascularity declined and venular vascularity increased. These associations resulted in a strong inverse correlation between blood pressure level and the ratio arteriolar vascularity: venular vascularity (r = 0.48, P<0.001). Arteriolar number declined with increasing diastolic blood pressure (r = 0.22, P<0.05). Mean arteriolar diameter appeared to have a U-shaped relationship with diastolic blood pressure levels (r = 0.27, P<0.05). Venular dilation was associated with increasing blood pressure levels (r = 0.22, P<0.05). Mean arteriolar and venular diameters declined significantly with age (r = 0.33 and 0.26, respectively; P<0.01) and there was no association between arteriolar vascularity: venular vascularity ratio and age. Conclusions The method detected disparate retinal microvascular alterations with age and blood pressure. The arteriolar vascularity: venular vascularity ratio shows promise as a non-invasive, prognostic and therapeutic guide in hypertension.

Ambulatory blood pressure monitoring in elderly patients with isolated systolic hypertension

Objectives: This study compared clinic and ambulatory blood pressure measurement and the reproducibility of these measurements in older patients with isolated systolic hypertension (ISH). Patients: Eighty-seven patients aged ≥60 years with ISH on clinic measurement were followed in the placebo run-in phase of the Syst-Eur trial. Methods: Clinic blood pressure was defined as the mean of two blood pressure readings on each of three clinic visits (six readings in total). Ambulatory blood pressure was measured over 24 h using non-invasive ambulatory blood pressure monitors. Results: Daytime ambulatory systolic pressure was, on average, 21 mmHg lower than the clinic blood pressure, whereas diastolic pressure was, on average, similar with both techniques of measurement. In the 42 patients who had repeat measurements, clinic blood pressure levels and the amplitude of the diurnal blood pressure profile (fitted by Fourier analysis) were equally reproducible. However, both were less reproducible than ambulatory blood pressure levels. The repeatability coefficients, expressed as per cent of near maximum variation (four times the standard deviation of a given measurement), were 52% and 45% for the clinic systolic and diastolic pressures, 56% and 42% for the amplitude of the diurnal profile, and 29% and 26% for mean 24-h pressures. Conclusions: In older patients with ISH, clinic and ambulatory systolic blood pressure measurements may differ largely: the prognostic significance of this difference remains to be elucidated. Furthermore, in these patients the level of pressure is more reproducible by daytime ambulatory blood pressure measurement than by clinic measurement.

Cumulative sums in quantifying circadian blood pressure patterns.

The plotting of cumulative sums (cusums), a technique of proven value in the detection of trends in data collected at intervals of time, may be modified to analyze circadian blood pressure patterns quantitatively. Mean 24-hour ambulatory blood pressure is taken as the reference value and is subtracted from each pressure value. The products of the remainders and the corresponding time intervals are summed in sequence and are plotted against time to form a modified cusum plot. The slope of the plot over any given time period equals the difference between mean blood pressure during that period and mean 24-hour blood pressure. Crest and trough blood pressures (the mean blood pressures of the 6-hour periods of highest and lowest pressures) may be identified as the 6-hour periods where plot slopes are most steeply ascending and descending, respectively. The magnitude of the circadian blood pressure change, defined as the difference between crest and trough blood pressure, is calculated from the difference between crest and trough plot slopes. The height of the cusum plot, which reflects pressure alteration extent and duration, may also be used as a measure of circadian pattern. The modified cusums technique and cusum-derived statistics are illustrated using ambulatory blood pressure profiles of hypothetical and actual hypertensive subjects. Independence from fixed time periods improves precision and reproducibility. Cusum-derived statistics are simply calculated from raw ambulatory data and should prove useful in the quantitative analysis of circadian blood pressure profiles.

Baroreflex function in elderly hypertensives.

Baroreflex function was assessed in elderly hypertensive patients and compared with that observed in young hypertensives and young normotensives. Mean arterial pressure was reduced by 20% using intravenous nitroprusside infusion in 10 elderly hypertensive patients (older than 65 years and diastolic pressures over 95 mm Hg), in 10 young hypertensives (under 60 years and diastolic pressures over 95 mm Hg), and in seven young normotensive subjects (under 60 years and diastolic pressures under 95 mm Hg). Elderly subjects demonstrated greater sensitivity (p less than 0.005) and greater variability of response (p less than 0.025) to nitroprusside than either young group. There was no significant difference between the slight heart rate increases observed in the supine position in the three groups. However, in the erect position, heart rate increases were significantly less in the elderly hypertensive group than in the young hypertensive group (p less than 0.01) or the young normotensive group (p less than 0.005). Furthermore, the slope of the regression line relating change in blood pressure with change in R-R interval was less for the elderly patients than for the young hypertensives (p less than 0.05) or the young normotensives (p less than 0.025). We conclude that the heart rate component of the baroreflex is impaired in elderly hypertensives, and anticipate that the clinical response to antihypertensive drugs will be altered.

Ambulatory blood pressure measurement in the evaluation of blood pressure lowering drugs.

Since the indirect m e h r e m e n t o f hlood pressure based o n the principle of arterial occlusion using a forearm cuff was introduced by Scipione Kiva-Rocci in 1896 111 and subsequently nlodifiecl t o incorporate auscultation by Nicolai Korotkolf in 1905 (21, this technique h:a been the universal method used in the assessment of blood pressure in medial practice. Most of the evidence showing that the antihypertensive drugs in everyday use lower blood pressure derives from studies of clinic blood pressure measured by this technique 13-51. However, it is well known that casual blood pressure measured in the clinic may be influenced by a number of factors and as long ago as 1904, Theodore Janeway, writing before Korotkoff had reported the now accepted auscultatory method of measuring blood pressure, showed that stress could raise blood pressure 161.

Accuracy of the SpaceLabs 90207 ambulatory blood pressure measuring system in normotensive pregnant women determined by the British Hypertension Society protocol.

The SpaceLabs 90207 monitor (Redmond, Washington, USA) for ambulatory blood pr-nue measurement u-as evaluated according to the protocol of the British Hypertension Society (BHS) 111 in normotmsive pregnant women. We have previously evaluated the SpaceLabs 90207 in nonnotmsive and hypertensive men and non-pregnant women according to the BHS protocol (21, In this evaluation the device achieved B gnding for systolic and diasoiic pressure and fulfilled the criteria of the Association for the Advancement of Medical Instrumentarion W) 131. three sequential measurements were performed in the same arm with the Spacehbs 90207 and a standard mercury sphvgmomanometer using Korotkoff phase v (disappearance of sounds) for diastolic pressure. The mean and standard deviation of the first mercury sphygmomanometer measurements were (systoliddiastolic) 1121 1/6&12 mrn~g. The SpaceLabs 90207 =as grad4 A for systolic and C for diastolic pressure according to the BHS protocol (Table 1). ~pplying the AMlI accuracy criteria 141, the SpaceLabs 90207 W e d the requirement for systolic but not diastolic p m , mean differences being 524 for systolic and mmHg for phase V diastolic pressurr.

Accuracy of the novacor DIASYS 200 determined by the British Hypertension Society protocol

criteria in that there were 3, rather than the permitted 2, failed days in 24 recording days. The main validation test was carried out on one device in 86 subjects with a wide range of pressures, the results being analysed according to a grading system from A to D. The DIASYS 200 achieved C rating for both systolic and diastolic pressures and also satisfied the criteria for accuracy of the Assocation for the Advancement of Medical lnstrumentation (AAMI), with an average difference (fs.d.) of - 1 f 8 and Of 8 mmHg for systolic and diastolic pressure, respectively. Subject acceptability was good. The manufacturers manual lacked much of the detail required by the BHS protocol. Conclusions: The DIASYS 200 ambulatory monitor achieved C rating for systolic and diastolic pressures according to the criteria of the BHS protocol and fulfilled the AAMI criteria of the protocol for both systolic and diastolic pressure. It just failed to satisfy the in-use criteria of the protocol. It can be recommended, therefore, for ambulatory measurment, especially in circumstances in which Korotkoff sound detection is preferred to oscillometry, with the proviso that the manufactures should improve the ambulatory performance of the device.

Relationship between blood pressure measured in the clinic and by ambulatory monitoring and left ventricular size as measured by electrocardiogram in elderly patients with isolated systolic hypertension

Objective: To assess the additional diagnostic precision conferred by ambulatory blood pressure monitoring on clinic blood pressure measurement in evaluating the severity of isolated systolic hypertension. Methods: The association between left ventricular size as determined by ECG voltages [R-wave voltages in lead V5 (RV5) and S-wave voltages in lead V1, (SV1,)] and blood pressure as assessed by clinic measurements and ambulatory blood pressure monitoring was studied in 97 elderly patients included in the placebo run-in phase of the Syst-Eur trial. The additional diagnostic precision conferred by ambulatory monitoring on clinic blood pressure measurements was assessed by relating the residual ambulatory blood pressure level to the ECG-left ventricular size. The residual ambulatory blood pressure level was calculated by subtracting the predicted ambulatory blood pressure level for each patient (using the linear regression equation relating both techniques for the group) from the observed ambulatory blood pressure. Results: Clinic systolic blood pressure was on average 20mmHg higher (P<0.001) than daytime ambulatory blood pressure while diastolic blood pressure was similar with both techniques. The sum of SV1 + RV5 was significantly related to clinic systolic pressure (r=0.25), and 24-h (systolic, r=0.37; diastolic, r=0.29), daytime (systolic, r=0.30; diastolic, r=0.19) and night-time (systolic, r=0.33; diastolic, r=0.28) ambulatory blood pressure levels. These findings were not affected by adjustment for gender, age and the body mass index. The sum of SV1 + RV5 was significantly related to the residual 24-h (systolic, r=0.30; diastolic, r=0.31), daytime systolic (r=0.20) and night-time (systolic, r=0.31; diastolic, r=0.29) ambulatory blood pressure monitoring levels. Conclusion: Ambulatory blood pressure monitoring adds to the diagnostic precision of clinic blood pressure measurement in assessing the severity of hypertension in this population. The ongoing side project on ambulatory blood pressure monitoring in the Syst-Eur study should establish whether these findings hold true for morbidity and mortality.

Accuracy of the Del Mar Avionics Pressurometer IV determined by the British Hypertension Society Protocol

Results: The three recorders passed the before-use interdevice variability assessment, after which 86% of inflations recorded with these devices during the in-use phase gave valid readings, and the three devices subsequently passed the after-use interdevice variability assessment. The main validation test was carried out in 86 subjects with a wide range of pressures, the results being analysed according to a grading system from A to D. The Pressurometer IV acheived C rating for systolic pressure and D rating for diastolic pressure. The first Pressurometer used in the main validation test failed to function after testing in 32 subjects and had to be replaced. The Pressurometer IV failed to satisfy the criteria for accuracy of the Association for the Advancement of Medical lnstrumentation (AAMI), with an average difference (f s.d.1 of - 2 f 11 and - 3 f 11 mmHg for systolic and diastolic pressure, respectively. Subject acceptability was poor, primarily because the monitor was cumbersome to wear and excessively noisy. The manufacturers manual was clear and reasonably comprehensive. Conclusions: The Pressurometer IV ambulatory monitor acheived C rating for systolic pressure and a D rating for diastolic pressure according to the criteria of the BHS protocol and failed to satisfy the AAMl criteria for both systolic and diastolic pressure. It also performed badly during the validation test and on the basis of these results cannot be recommended for ambulatory measurement in clinical practice.