Silvia Trazzi

REPRODUCIBILITY OF NON-INVASIVE AND INTRA-ARTERIAL BLOOD PRESSURE MONITORING : IMPLICATIONS FOR STUDIES ON ANTIHYPERTENSIVE TREATMENT

Ambulatory blood pressure has been shown to be more reproducible than office blood pressure and thus to be more suited for studying the efficacy of antihypertensive drugs. In 34 untreated essential hypertensive subjects, we measured office and 24-h non-invasive or intra-arterial blood pressure twice over a 4-week interval; 24-h intra-arterial blood pressure was obtained by the Oxford method whereas 24-h non-invasive blood pressure was obtained by the automatic SpaceLabs 5300 device, with a 10 min (daytime) or 20 min (night-time) interval between measurements. The standard deviation of the mean difference (s.d.d.) between blood pressures obtained in each recording was taken as the reciprocal of blood pressure reproducibility. The s.d.d. was highest for office blood pressure and for single blood pressure readings taken from 24-h non-invasive recordings. The s.d.d. fell when the two 24-h average non-invasive blood pressures were considered. The fall was progressively greater as the number of ambulatory readings on which the average was calculated increased from two to 24, no further fall being observed when more than 24 values were considered. The maximal reduction in s.d.d. was 59% (systolic) and 42% (diastolic) as compared with the office s.d.d. The two 24-h mean values obtained by the intra-arterial approach were slightly more closely correlated than those obtained non-invasively. However, at comparable sampling rates, the s.d.d. was not substantially lower with 24-h intra-arterial blood pressure and including in the calculation the average of the thousand readings provided by this approach did not cause any further improvement.(ABSTRACT TRUNCATED AT 250 WORDS)

Limited reproducibility of hourly blood pressure values obtained by ambulatory blood pressure monitoring : implications for studies on antihypertensive drugs

Objective: To assess the reproducibility of average hourly blood pressure values obtained by 24‐h non‐invasive ambulatory monitoring. Patients: Fifteen outpatients with essential hypertension. In all subjects antihypertensive treatment was withdrawn for 4 weeks before and during the 4 weeks of the study. Methods: The 24‐h blood pressure was monitored by a SpaceLabs 5300 device (four readings per hour during the day and three readings per hour during the night) twice, at a 4‐week interval. Systolic (SBP) and diastolic blood pressure (DBP) were averaged for each hour and for the whole 24‐h period, and hourly and 24‐h reproducibility was quantified by the standard deviation of the mean difference (SDD) between the values obtained in the two recordings. Results: The SDD of hourly SBP and DBP was much greater than that of the 24‐h values and ranged widely between the hours of recording. The SDD of hourly SBP and DBP were also variably greater than the SDD of the 24‐h value in another 14 untreated essential hypertensives in whom 24‐h ambulatory blood pressure was monitored intra‐arterially twice at a 4‐week interval to calculate hourly average blood pressure on thousands rather than on three or four values per hour. Conclusion: Reproducibility is less for hourly than for 24‐h average blood pressure. This feature (which probably depends on behavioural differences between two recordings) suggests that ambulatory blood pressure measurement partly loses its advantages for reproducibility and reduction in trial size if the results are analysed over hourly periods.

24-Hour blood pressure monitoring: Evaluation of Spacelabs 5300 monitor by comparison with intra-arterial blood pressure recording in ambulant subjects

The accuracy of 24-h blood pressure values obtained by ambulatory monitoring via the Spacelabs 5300 device was evaluated by comparison with simultaneous 24-h intra-arterial blood pressure recording from the contralateral arm. The comparison was made in eight essential hypertensive subjects in whom non-invasive blood pressure was measured every 15 (day) or 30 min (night). The measurements were automatically and visually edited to eliminate artefactual readings and hourly and 24-h means were calculated separately for systolic and diastolic blood pressure. The corresponding intra-arterial blood pressure means were also calculated. In the group as a whole, hourly means obtained by the non-invasive device were similar or only slightly different from those recorded intra-arterially. The 24-h systolic blood pressure mean obtained non-invasively was not significantly different from that obtained intra-arterially (138.4 +/- 9.1 and 142.9 +/- 9.2 mmHg, respectively), nor were the corresponding 24-h diastolic blood pressure means significantly different (83.5 +/- 4.5 and 80.6 +/- 3.5 mmHg, respectively). However, in spite of these similarities, there were contrasting and often large discrepancies between non-invasive and intra-arterial values in individual subjects. For the 24-h systolic blood pressure mean the discrepancies ranged from 7.6 +/- 1.1 to 16.1 +/- 2.2 mmHg and for the 24-h diastolic blood pressure mean, from 3.5 to 13.2 mmHg. Thus, the Spacelabs 5300 device has a limited ability to correctly estimate ambulatory blood pressure in individual subjects. It may be better suited for the estimation of group blood pressures, but only because errors are smoothed by the summation of individual errors of opposing signs.

EFFECT OF PLACEBO ON 24-H NON-INVASIVE AMBULATORY BLOOD PRESSURE

Twenty-four-hour mean ambulatory blood pressure has been shown to be devoid of a placebo effect. However, whether this is the case for different periods within the 24 h has not been established. In 27 essential hypertensive outpatients, blood pressure was measured in the doctors office and by 24-h ambulatory blood pressure monitoring after a 3-week wash-out period from antihypertensive treatment (Control) and following 4 weeks of placebo administration. Office systolic and diastolic blood pressures were reduced by placebo (-9.6 +/- 2.6 and -3.1 +/- 1.7 mmHg, P less than 0.01, respectively), whereas 24-h mean blood pressure values did not show any significant change. This was not the case for all 24-h subperiods, however, because during the initial 8h, systolic and diastolic blood pressures were slightly (-4.1 +/- 9.2 and -2.5 +/- 6.4 mmHg) but significantly (P less than 0.05) lower during placebo than during control. Similar findings were obtained in 14 additional essential hypertensive patients in whom neither placebo nor any other treatment was employed between the two office and 24-h blood pressure measurements. Thus, placebo treatment is associated with a blood pressure reduction in the initial portion of the ambulatory blood pressure profile, probably because of an attenuation of an initial transient alerting response to the procedure. Although so small as to leave the 24-h blood pressure mean unaffected, this may lead to some overestimation of the antihypertensive effect of treatment during an appreciable portion of the circadian blood pressure tracing.

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

Role of heart rate variability in the production of blood pressure variability in man.

In both normotensive and hypertensive subjects blood pressure (BP) and heart rate (HR) show concordant changes over 24 h. This may depend on a central factor exerting influences of the same nature on cardiac and vascular targets. An alternative explanation, however, is that a cause-effect relationship links these variabilities, i.e. that HR variations induce BP changes [presumably via variations in cardiac output (CO)]. Blood pressure was recorded intra-arterially in five supine and five exercising (walking) essential hypertensive subjects during a control period of 1 h and during an additional hour in which atropine, 0.04 mg/kg body weight, was injected intravenously (i.v.). The same recordings were performed in seven other subjects, in which saline rather than atropine was employed. One-hour BP and HR variabilities (variation coefficients, VC) were computer analysed. In both the supine and the exercising subjects atropine caused a marked reduction in HR VC (-65.3 and -48.4%, respectively). In the supine subjects this reduction was accompanied by only a modest reduction in BP VC whereas in the exercising subjects the BP VC increased by 30.4%. In the seven subjects in which saline was injected no change in BP and HR VC occurred. Thus a marked reduction in HR variability is not accompanied by a comparable attenuation in BP variability, which rules out a cause-effect link between these two phenomena. Indeed, during physical exercise HR stabilization is followed by an increase rather than a reduction in BP variation, which supports the conclusion that under some circumstances HR plays an anti-oscillatory role.

Cardiac and vascular structural changes in normotensive subjects with parental hypertension

Objective To evaluate whether a predisposition to hypertension is associated with early cardiac and vascular alterations. Subjects Twenty-five normotensive subjects with both parents hypertensive (group 1) and 28 age- and sex-matched control subjects with both parents normotensive (group 2). Methods In the two groups the measurements included: clinic blood pressure; left ventricular end-diastolic diameter, septal wall thickness and posterior wall thickness (by echocardiography); minimal forearm and calf vascular resistances (i.e. resistance assessed immediately after prolonged ischaemia, which depends on arteriolar wall thickness); and baseline and postischaemic radial artery compliance-pressure curves over the systolodiastolic pressure range (by echotracking device and finger blood pressure). Results Group 1 had a slightly higher clinic blood pressure, and septal and posterior wall thickness, than group 2. Minimal forearm vascular resistance was clearly greater in group 1 than in group 2, whereas minimal calf vascular resistance was not significantly different in the two groups. Radial artery compliance was also similar in the two groups. Conclusions Parental predisposition to hypertension is accompanied by cardiac and arteriolar structural changes qualitatively similar to those found in hypertensive patients, although arteriolar structural changes do not involve all vascular beds. Arterial compliance is not altered in this condition. Vascular changes may be determined by mechanisms other than blood pressure elevation.

Evaluation of the antihypertensive effect of celiprolol by ambulatory blood pressure monitoring

The use of ambulatory blood pressure monitoring has gained popularity because it is not subject to those limitations associated with traditional sphygmomanometry (inaccuracy of blood pressure readings, low number of readings, and failure to represent daytime blood pressure readings). In the present study, we provide evidence that the 24-hour mean blood pressure obtained through intraarterial blood pressure measurements in ambulatory patients provides a more accurate diagnosis (and perhaps a prognosis) of hypertension than that provided by cuff-obtained casual blood pressure measurement. Furthermore, despite a reduction in the amount and in the accuracy of the information obtained, blood pressure data provided by noninvasive blood pressure monitoring are also more accurate diagnostically than cuff-obtained casual blood pressure measurements. In 15 essential hypertensive patients in whom celiprolol, 400 mg once daily, was compared with placebo in a randomized double-blind crossover study, the use of noninvasive 24-hour automatic blood pressure monitoring showed that in responsive patients, celiprolol induced a sustained reduction in systolic and diastolic blood pressure throughout the 24 hours. The blood pressure reduction was also apparent during the night, despite the concomitant occurrence of a slight tachycardia. These findings demonstrate that once-daily administration of celiprolol provides an effective lowering of the 24-hour blood pressure profile. This dosing schedule can therefore be regarded as appropriate for antihypertensive therapy.

Variability in arterial diameter and compliance: compliance modulation reserve.

Background Some antihypertensive drugs are known to increase arterial compliance in hypertensives; how far compliance can be increased is unknown. Design We studied eight mildly hypertensive patients to determine how far radial artery compliance can be acutely increased, i.e. the extent of the compliance modulation reserve. Methods We evaluated radial artery compliance by a new technique, assessing it throughout the cardiac cycle before and after the intra-arterial infusion of a vasodilator agent (papaverine). Results Before papaverine, compliance decreased progressively through diastolic to systolic blood pressure values. This was the case also during the papaverine infusion. However, over the full systolo-diastolic pressure range, compliance was increased by about 40% with papaverine. Conclusions In hypertensive subjects radial artery compliance can be markedly increased on a acute basis, indicating that those antihypertensive drugs that improve compliance have a considerable reserve to act upon.

Changes in 24 Hour Blood Pressure and in Cardiac and Vascular Structure in Normotensive Subjects with Parental Hypertension

Subjects with family history of hypertension represent a suitable model to investigate the mechanisms responsible for early cardiovascular structural and functional changes occurring in essential hypertension. In our study we have addressed the factors involved in determining the mild elevation in office blood pressure frequently observed in normotensive subjects with hypertensive parents. In 15 normotensive subjects with both parents hypertensive (FH++) and in 15 normotensive subjects with one parent hypertensive (FH(+)-) we found no evidence of a hyperreactivity to stress as compared to the responses of 15 normotensive subjects with no parental hypertension (FH--). On the contrary FH++ subjects were characterized by a significant although mild increase in their blood pressure values recorded either at rest and in ambulatory conditions over the 24 hours, including night sleep. FH++ and FH(+)- subjects also showed a greater left ventricular mass thickness and a greater minimal forearm vascular resistance than FH-- subjects. Thus, the elevation in blood pressure found in the pre-hypertensive stage in subjects with positive family history for hypertension does not reflect a hyperreactivity to the stress associated with physicians visit but indicates an early and persistent blood pressure elevation. This blood pressure elevation is accompanied by early cardiovascular structural changes which may indicate that these subjects are exposed to a higher risk even before developing overt hypertension.