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Biomedical subjects

E O'Brien

Publications and source records attributed to E O'Brien.

At least 19 recordsLinked to original sources

The increase in blood pressure with age and body mass index is overestimated by conventional sphygmomanometry.

This cross-sectional study investigated whether the technique of blood pressure measurement used (conventional sphygmomanometry vs. ambulatory monitoring) affects the relation between blood pressure and both age and body mass index. Two independent data sets were analyzed. The first comprised 328 subjects (48% men) drawn from the population of a small Belgian town, and the second comprised 776 Irish bank employees (51% men). Age ranged from 17 years to 81 years, and body mass index (weight (kg)/height (m)2) ranged from 16.6 to 40.2. Twenty-four-hour ambulatory blood pressure was lower than blood pressure measured by a nurse in both the Belgian population sample (118/71 mmHg vs. 122/73 mmHg) and the Irish employees (118/72 mmHg vs. 119/76 mmHg). When blood pressure was measured by an observer, the well-established relations between systolic and diastolic blood pressure and both age and body mass index were evident. When the analyses were repeated using 24-hour measurements, the increment (cross-sectionally assessed) in blood pressure with age was weaker, especially in young and middle-aged subjects (20-60 years), while the increase in blood pressure with body mass index was also reduced. The within-subject differences between the conventional and ambulatory blood pressure measurements increased with older age and greater body mass index. Several other relations with blood pressure as the response variable may require revision in light of the present findings.

Adult

Effects of aging and hypertension on plasma angiotensin II and platelet angiotensin II receptor density.

Plasma renin activity (PRA) declines with age in normal individuals, but the effect of age on plasma angiotensin II (ANG II) is less clear. A decline in plasma ANG II with age could result in altered platelet ANG II receptor density since plasma hormone levels influence their target organ receptors. To investigate this possibility, PRA, plasma ANG II, and platelet ANG II receptor density were examined in 17 young, 12 middle-aged, and 14 elderly healthy normotensive volunteers. To assess whether hypertension altered receptor density, these variables were also examined in 23 hypertensive patients. In normotensives, there was a negative correlation between age and PRA (r = -0.43, P < .05), no significant change in basal plasma ANG II with age, and a weak positive correlation between age and ANG II receptor density (r = 0.34, P < .05). Multiple regression analysis revealed that the relationship between age and ANG II receptor density was independent of the associated rise in mean arterial pressure with age (P < .05). Platelet ANG II receptor density was not significantly related to PRA or plasma ANG II. ANG II receptor affinity did not change with age. Neither PRA nor ANG II receptor density or affinity differed between hypertensives and normotensives of similar mean age, but plasma ANG II was significantly lower in hypertensives compared with normotensives. We concluded that aging is associated with a decline in supine PRA. The small decrease in plasma ANG II was not significant. Platelet ANG II receptor density increased with age primarily due to a small group of elderly subjects with elevated receptor density. There was no change in ANG II receptor density or affinity in hypertensives despite apparently lower plasma ANG II in these patients.

Adult

The diurnal blood pressure profile. A population study.

This population study included 399 subjects, of whom 370 (93%) showed a significant diurnal blood pressure (BP) rhythm. The nocturnal BP fall was normally distributed and averaged 16 +/- 9 mm Hg systolic and 14 +/- 7 mm Hg diastolic (mean +/- SD). The amplitude of the diurnal BP curve followed a positively skewed distribution, with a mean of 16 +/- 5 mm Hg for systolic BP and 14 +/- 4 mm Hg for diastolic BP. The daily BP maximum occurred at 15:54 +/- 4:47 for systolic BP and at 15:11 +/- 4:20 for diastolic BP. Thirty-four subjects were reexamined after a median interval of 350 days. The test for the presence of a significant diurnal rhythm was discordant in only two subjects. Repeatability (twice the standard deviation of the differences between paired recordings expressed as a percentage of the mean) varied from 11 to 25% for the 24 h, daytime, and overnight BP, and from 76 to 138% for the parameters describing the diurnal BP rhythm. In nine subjects with an initial night/day ratio of mean BP less than 0.78, the nighttime BP was significantly increased at the repeat examination, whereas the opposite tendency was observed in nine subjects with an initial ratio greater than 0.87. In conclusion, the distribution of the nocturnal BP fall is unimodal. The reproducibility of the ambulatory BP is satisfactory for the level of BP and for the presence of a diurnal BP rhythm, but not for the parameters of the diurnal BP curve. Thus, one 24 h recording is insufficient to fully characterize an individual's diurnal BP profile.

Adult

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.

Adult

The J-shaped curve in elderly hypertensives.

PURPOSE: To review the relationship between mortality and morbidity and achieved blood pressure, after drug treatment in elderly hypertensive patients. CONTENTS: Recent studies have suggested that a reduction in systolic blood pressure, with drug treatment, to levels below about 140 mmHg in elderly patients (greater than 60 years) may increase the risk of stroke. However, a J-shaped relationship between both mortality and morbidity and blood pressure has been reported in the untreated controls of the Hypertension in Elderly Patients in primary care (HEP) study. In the European Working Party on High Blood Pressure in the Elderly trial (EWPHE) there was a U-shaped relationship between total mortality and treated systolic pressure, but a similar U-shaped relationship was observed with diastolic pressure in patients on placebo. In addition, patients with the lowest pressure during treatment showed the greatest falls in body weight and haemoglobin concentrations, suggesting that the increased mortality seen with lower blood pressure levels may have been an expression of a deterioration in general health. Moreover, a U-shaped relationship between blood pressure and mortality has been observed in the very old (aged 80 + years). CONCLUSIONS: While it is premature to conclude, on the basis of present evidence, that reducing blood pressure to the lower part of the normal range is harmful in older patients, it appears prudent, nonetheless, not to lower blood pressure excessively with treatment in this age group.

Aged

Further learnings from the European Working Party on High Blood Pressure in the Elderly (EWPHE) study: focus on systolic hypertension.

Event rates in relation to the number of elderly hypertensives treated were calculated from randomized analysis data from the 840 patients who completed the European Working Party on High Blood Pressure in the Elderly (EWPHE) trial. In all, the actively treated group had 29 fewer cardiovascular events per 1000 patient years. Putting this another way, treating 34 patients for 1 year would prevent one cardiovascular event. Moreover, as there were 14 fewer cardiovascular deaths and 11 fewer nonfatal strokes per 1000 patient years in the actively treated groups, we calculated that treating 71 or 91 elderly patients for 1 year would prevent one cardiovascular death or nonfatal stroke, respectively. Because of the higher baseline incidence of cardiovascular events in this study, there were greater gains in terms of absolute reductions in mortality and morbidity in treated elderly hypertensive patients than in younger patients in similar studies. Of the 840 patients who participated in the trial, 247 had systolic blood pressure greater than or equal to 160 mmHg and diastolic blood pressure less than or equal to 95 mmHg. In this group, blood pressure was reduced by 13/8 mmHg after 3 years in those randomized to active treatment compared to placebo. While patient numbers were insufficient to draw firm conclusions, their outcome on treatment was similar to that for patients on active treatment in the overall study. These results high-light the need for a rigorous assessment of the value of treating isolated systolic hypertension in the elderly.

Aged

Ambulatory blood pressure monitoring in the evaluation of drug efficacy.

Conventional clinic measurement of blood pressure is influenced by many factors that make the technique unsuitable for the assessment of antihypertensive drug efficacy. The major drawback of conventional measurement is that it cannot indicate the duration of drug effect or the influence of antihypertensive drugs on nocturnal blood pressure. Noninvasive 24-hour ambulatory blood pressure measurement has a number of advantages over conventional measurement: it provides a profile of blood pressure over the 24-hour period; it detects white coat responders; it is free of regression to the mean and the placebo response, thereby making it possible to consider efficacy studies which need not have a placebo phase; it enables considerably more observations than is possible with clinic measurement by increasing the power of studies, which may reduce significantly the numbers of patients needed for antihypertensive drug studies. Twenty-four-hour ambulatory blood pressure measurement offers the opportunity to study antihypertensive drugs in fewer patients with greater accuracy than is possible with conventional clinic measurement and should be a mandatory requirement for such studies.

Ambulatory Care

Clinical benefits of structural and functional changes with calcium antagonists.

Calcium antagonists have a large variety of pharmacologic effects in addition to those exploited clinically. All drugs used in the management of hypertension, including calcium antagonists, are coming under increasing scrutiny for the possible beneficial and adverse effects they may have on the circulation and risk factor profile. This is particularly because of concern about the relative resistance of coronary heart disease to antihypertensive drug treatment and the increasing interest in evaluating the impact of blood pressure-lowering drugs on surrogate endpoints such as left ventricular hypertrophy. Given the pharmacokinetic and pharmacodynamic heterogeneity of calcium antagonists, it may be wise to keep in mind the subtypes as exemplified by the prototypes nifedipine, diltiazem, and verapamil and to extrapolate from one type to another with great caution. The increased understanding of the diversity among calcium antagonists as well as the pathophysiology of hypertension and other vascular diseases promises an exciting future for calcium antagonists in cardiovascular therapeutics.

Calcium Channel Blockers

Choice of drug treatment for elderly hypertensive patients.

It is generally agreed that moderate and severe hypertension in the elderly should be treated, but it is not clear which drug or drugs are most appropriate. Thiazide diuretics are inexpensive and effective, but they are associated with metabolic side effects that are becoming less acceptable as newer agents become available. Beta blockers are effective, but can be associated with central nervous system side effects and are often contraindicated by coexisting disease. Recently, attention has been focused on the newer agents, including calcium antagonists and angiotensin-converting enzyme inhibitors. The advantage of calcium antagonists is that they do not produce metabolic side effects. However, they are expensive and may cause vasodilatory side effects. The angiotensin-converting enzyme inhibitors are effective and relatively free of side effects and may be particularly useful for elderly hypertensive patients with congestive heart failure.

Aged

Plasma atrial natriuretic peptide concentration and platelet atrial natriuretic peptide binding site density in ageing and hypertension.

1. Ageing and hypertension are associated with changes in the way in which the body handles sodium. This may involve changes in plasma atrial natriuretic peptide concentration, since atrial natriuretic peptide is a regulator of sodium handling by the kidney and the plasma atrial natriuretic peptide concentration is increased in both ageing and hypertension. An increase in the plasma atrial natriuretic peptide concentration could also be associated with a change in atrial natriuretic peptide receptor density, possibly involving down-regulation. 2. To investigate these possibilities plasma atrial natriuretic peptide concentration and platelet atrial natriuretic peptide binding site density were measured in 18 young, 11 middle-aged and 12 elderly healthy subjects and in 23 patients with mild to moderate essential hypertension. 3. In normotensive subjects, the plasma atrial natriuretic peptide concentration increased with age (r = 0.49, P less than 0.01) and was significantly higher in elderly than young subjects (mean +/- SEM, 31.9 +/- 4.5 versus 18.3 +/- 2.0 pmol/l, P less than 0.05). The plasma atrial natriuretic peptide concentration increased with the mean arterial pressure in normotensive subjects (r = 0.47, P less than 0.01). Multiple regression analysis did not show independent relationships between the plasma atrial natriuretic peptide concentration and either age or mean arterial pressure in normotensive subjects alone. However, when normotensive subjects and hypertensive patients were considered together, multiple regression revealed both age and mean arterial pressure as independent predictors of the plasma atrial natriuretic peptide concentration (P less than 0.05, P less than 0.01, respectively). In normotensive subjects, the platelet atrial natriuretic peptide binding site density did not change with age (r = 0.19, P = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Twenty-four-hour ambulatory blood pressure in men and women aged 17 to 80 years: the Allied Irish Bank Study.

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).

Adult