Luisa Ulian

Limitations of the difference between clinic and daytime blood pressure as a surrogate measure of the 'white-coat' effect

Background The difference between clinic and ambulatory average daytime blood pressures is frequently taken as a surrogate measure of the ‘white-coat effect’ (i.e. the pressor reaction triggered in the patient by the physicians visit). Objective To assess the reproducibility of this difference and its relationship with clinic and average ambulatory daytime blood pressure levels. Design and methods These issues were addressed with two large groups of subjects in whom both clinic and ambulatory blood pressures were measured, namely 783 outpatients with systolic and diastolic essential hypertension [Group 1, aged 50.8 ± 9.4 years (mean ± SD)], participating in standardized Italian trials of antihypertensive drugs, and 506 elderly patients (group 2, age 71 ± 7 years) with isolated systolic hypertension, participating in the European Syst-Eur trial. Results The clinic-daytime blood pressure difference for the essential systolic and diastolic hypertensive patients (group 1) was 13.6 ± 14.3 mmHg for systolic and 9.1 ± 8.6 mmHg for diastolic blood pressure (P always < 0.01). This difference for the elderly patients with isolated systolic hypertension (group 2) was 21.2 ± 16.0 mmHg for systolic and only 1.3 ± 10.2 mmHg for diastolic blood pressure (P < 0.01 and P < 0.05, respectively). In both studies little or no systematic clinic-daytime difference could be observed for heart rate. The reproducibility of the clinic-daytime blood pressure difference, tested for 108 essential systolic and diastolic hypertensive patients from group 1 and 128 isolated systolic hypertensives from group 2, was invariably lower than that both of daytime and of clinic blood pressure values. Finally, the clinic-daytime blood pressure difference was progressively higher for increasing levels of clinic blood pressure and progressively lower for higher levels of ambulatory daytime blood pressure. Conclusions Thus, the clinic-daytime blood pressure difference has a limited reproducibility; depends not only on clinic but also on daytime average blood pressure, which means that its size is a function of the blood pressure criteria employed for selection of the patients in a trial; and is never associated with a systematic clinic-daytime difference in heart rate, which further questions its use as a reliable surrogate measure of the true pressor response induced in the patient by the doctors visit.

Increase in blood pressure reproducibility by repeated semi-automatic blood pressure measurements in the clinic environment.

Objective To evaluate whether increasing the number of blood pressure readings obtained in the clinic environment increases the blood pressure reproducibility Patients: Thirteen mild essential hypertensive patients studied in the outpatient clinics, following withdrawal of antihypertensive treatment for 4 weeks Methods The systolic and diastolic blood pressures were measured three times, using a mercury sphygmomanometer, with the patient in the sitting position. Measurements were then performed with the patient in the lying position using an oscillometric device (SpaceLabs 90202 or 90207). The device was operated semi-automatically at 3-min intervals until 25 readings had been collected. The same procedure was repeated 4 weeks later. The systolic blood pressure, diastolic blood pressure and heart rate were averaged by considering a progressively greater number of readings, from 1 to 25. The reciprocal of the standard deviation (1/SD) of the mean difference after 4 weeks was taken as the measure of reproducibility Results 1/SD increased progressively as the number of semi-automatic blood pressure readings from which the average was calculated increased. For a similar number of blood pressure readings the reproducibility was similar for semi-automatic readings to that for automatic readings obtained by 24-h ambulatory blood pressure monitoring Conclusion Multiple blood pressure readings obtained semi-automatically in the outpatient clinics increase blood pressure reproducibility and make the value similar to that obtained by ambulatory blood pressure monitoring. The advantage of an increase in reproducibility for studies on antihypertensive drugs thus depends on the number of readings, and can also be obtained by semi-automatic measurements in the clinic environment

Blood pressure variability, cardiovascular risk and antihypertensive treatment

Twenty-four hour blood pressure parameters: The use of ambulatory blood pressure monitoring techniques has shown clearly that 24-h average blood pressure is more closely related to the end-organ damage of hypertension than isolated office blood pressure readings. It has also provided evidence that the degree of blood pressure variability over a 24-h period may be independently related to the cardiovascular complications of hypertension. However, all the available data on this issue come from cross-sectional studies, and prospective evidence on the actual prognostic value of 24-h blood pressure parameters has only recently been provided for daytime blood pressure variability. There is still no prospective evidence concerning overall 24-h blood pressure variability. Antihypertensive agents and blood pressure variability: Available antihypertensive agents are unable to effectively buffer blood pressure variability. However, drugs with a long-lasting antihypertensive effect and an optimal trough: peak ratio may at least prevent further iatrogenic increases in the amplitude of blood pressure fluctuations. Beat-to-beat blood pressure monitoring: The ability of antihypertensive agents to actually reduce 24-h blood pressure variability needs to be demonstrated in future studies, using beat-to-beat blood pressure monitoring which is now possible by means of non-invasive techniques.

Hemodilution Reduces Clinic and Ambulatory Blood Pressure in Polycythemic Patients

Limited information is available for humans on whether blood viscosity affects total peripheral resistance and, hence, blood pressure. Our study was aimed at assessing the effects of acute changes in blood viscosity on both clinic and 24-hour ambulatory blood pressure (BP) values. In 22 normotensive and hypertensive patients with polycythemia, clinic and 24-hour ambulatory BPs were measured before and 7 to 10 days after isovolumic hemodilution; this was performed through the withdrawal of 400 to 700 mL of blood, with concomitant infusion of an equivalent volume of saline-albumin solution. Hematocrit, plasma renin activity, plasma endothelin-1, right atrial diameter (echocardiography), and blood viscosity were measured under both conditions. Plasma renin activity and right atrial diameter were used as indirect markers of blood volume changes. Plasma endothelin-1 was used to obtain information on a vasomotor substance possibly stimulated by our intervention, which could counteract vasomotor effects. Isovolumic hemodilution reduced hematocrit from 0.53+/-0.05 to 0.49+/-0.05 (P<.01). Plasma renin activity, plasma endothelin-1 and right atrial diameter were unchanged. Clinic blood pressure was reduced by hemodilution (systolic, 144.3+/-5.4 to 136.0+/-3.9 mm Hg[mean+/-SEM]; diastolic, 87.0+/-2.8 to 82.1+/-2.6 mm Hg, P<.05 for both) and a reduction was observed also for 24-hour average ABP (systolic, 133.6+/-2.9 to 129.5+/-2.7 mm Hg; diastolic, 80.0+/-2.0 to 77.3+/-1.7 mm Hg, P<.05 for both). The reduction was consistent in hypertensive patients (n = 12), whereas in normotensive patients (n = 10) it was small and not significant. Both clinic and 24-hour average heart rates were unaffected by the hemodilution. Thus, in polycythemia, reduction in blood viscosity without changing blood volume causes a significant fall in both clinic and 24-hour ambulatory BPs; this is particularly true when, as can often happen, blood pressure is elevated. This emphasizes the importance this variable may have in the determination of blood pressure and the potential therapeutic value of its correction when altered.

Lacidipine and blood pressure variability in diabetic hypertensive patients.

The aim of our study was to assess the effects of lacidipine, a long-acting calcium antagonist, on 24-hour average blood pressure, blood pressure variability, and baroreflex sensitivity. In 10 mildly to moderately hypertensive patients with type II diabetes mellitus (aged 18 to 65 years), 24-hour ambulatory blood pressure was continuously monitored noninvasively (Portapres device) after a 3-week pretreatment with placebo and a subsequent 4-week once daily lacidipine (4 mg) or placebo treatment (double-blind crossover design). Systolic blood pressure, diastolic blood pressure, and heart rate means were computed each hour for 24 hours (day and night) at the end of each treatment period. Similar assessments were also made for blood pressure and heart rate variability (standard deviation and variation coefficient) and for 24-hour baroreflex sensitivity, which was quantified (1) in the time domain by the slope of the spontaneous sequences characterized by progressive increases or reductions of systolic blood pressure and RR interval and (2) in the frequency domain by the squared ratio of RR interval and systolic blood pressure spectral power ≈0.1 and 0.3 Hz over the 24 hours. Compared with placebo, lacidipine reduced the 24-hour, daytime, and nighttime systolic and diastolic blood pressure (P <0.05) with no significant change in heart rate. It also reduced 24-hour, daytime, and nighttime standard deviation (−19.6%, −14.4%, and −24.0%, respectively;P <0.05) and their variation coefficient. The 24-hour average slope of all sequences (7.7±1.7 ms/mm Hg) seen during placebo was significantly increased by lacidipine (8.7±1.8 ms/mm Hg, P <0.01), with a significant increase being obtained also for the 24-hour average &agr; coefficient at 0.1 Hz (from 5.7±1.5 to 6.4±1.3 ms/mm Hg, P <0.01). Thus, in diabetic hypertensive patients, lacidipine reduced not only 24-hour blood pressure means but also blood pressure variability. This reduction was accompanied by an improvement of baroreflex sensitivity. Computer analysis of beat-to-beat 24-hour noninvasive blood pressure monitoring may offer valuable information about the effects of antihypertensive drugs on hemodynamic and autonomic parameters in daily life.

Blood pressure reduction and end-organ damage in hypertension

Value of ambulatory blood pressure monitoring: Studies that have used ambulatory blood pressure monitoring techniques have shown that the average 24-h or daytime blood pressure values are more closely related to the end-organ damage associated with hypertension than are isolated office readings. Importance of blood pressure variability in prognosis: More recently, blood pressure variability, measured as the overall 24-h blood pressure standard deviation, has been shown to have a significant relationship to end-organ damage in hypertensive patients. The potential clinical relevance of blood pressure variability has been strengthened in a recent prospective study. The possible prognostic value of blood pressure variability has practical implications for antihypertensive treatment; it may mean, for example, that the optimal antihypertensive drug should reduce not only the mean 24-h values but also the degree of fluctuation in blood pressure. This is more likely to occur with long-acting drugs, which induce a more balanced reduction in blood pressure throughout the 24 h. Use of the trough: peak ratio: A proposed measure of a balanced 24-h blood pressure effect is the trough: peak ratio of the blood pressure fall. This ratio can be obtained by clinic blood pressure measurements but ambulatory blood pressure monitoring offers some distinct advantages. One of these advantages is that by revealing the possibility of an excessive fall in blood pressure at the time of the peak effect or an uncontrolled rise at the trough, ambulatory monitoring can also reveal the possible impact of pharmacological treatment on 24-h blood pressure variability.

Clinical value of ambulatory blood pressure monitoring

&NA; This report reviews the evidence for and against clinical use of ambulatory blood pressure monitoring (ABPM) on a large scale. Such monitoring is supported by a number of data, among which is that the end‐organ damage associated with hypertension correlates more with 24‐h average blood pressure than with clinic blood pressure, the correlation becoming even closer with addition of blood pressure variability values. However, the evidence thus far collected is largely cross‐sectional. Furthermore, ABPM devices have limited accuracy and the procedure has a high cost. Therefore, while prospective studies on the prognostic value of ambulatory blood pressure are awaited, use of this approach should be restricted to a limited number of clinical circumstances (e.g., identification of white‐coat hypertension) and used only in specialized centers.

Cardiovascular regulation and analysis of blood pressure‐heart rate variability interactions

Introduction Over the last 30-40 years, a great number of papers have shown that the quantitative assessment of blood pressure (BP) or heart rate (HR) variability (V) can provide relevant information on the mechanisms involved in cardiovascular regulation as well as on their derangement in a number of pathological conditions (1 -5) . More recently, however, evidence has been provided that the simultaneous assessment of both BPV and HRV and the analysis of their interaction can provide a more comprehensive insight into the features of cardiovascular regulation in different clinical conditions (1,2,5). Aim of this paper is to briefly review some evidence obtained in this field both through laboratory studies and by means of ambulatory monitoring techniques. In particular, we will address the interactions between BPV and HRV after having roughly classified them in two large groups: the situations where these variables display concordant changes, i.e. where both BP and HR increase or fall, and the conditions where BP and HR display discordant changes, i.e. where BP increases and HR falls or, conversely, where BP falls and HR increases.