Lack of effect of percutaneous transluminal renal angioplasty on nocturnal hypotension in renovascular hypertensive patients.

OBJECTIVE: To investigate whether nocturnal blood pressure fall is blunted in renovascular hypertension and can therefore be used as a diagnostic criterion for this condition. METHODS: In 14 renovascular hypertensive patients (age 43.8+/-2.1 years, mean+/-SEM, clinic blood pressure 173.6+/-3.7 mmHg systolic and 109.0+/-2.0 mmHg diastolic) and in 14 age- and blood pressure-matched essential hypertensive controls 24 h ambulatory blood pressure was measured after washout from drug treatment, during angiotensin converting enzyme inhibitor treatment and, in renovascular hypertension, also after percutaneous transluminal renal angioplasty. RESULTS: The 24 h average systolic and diastolic blood pressures were 146.4+/-5.7 and 97.5+/-3.6 mmHg in renovascular and 144.3+/-1.2 and 98.0+/-2.2 mmHg in essential hypertensive patients. The angiotensin converting enzyme inhibitor treatment reduced 24 h average systolic and diastolic blood pressures by 8.5% and 9.7% in the renovascular and by 8.3% and 10.8% in the essential hypertensive group. Greater systolic and diastolic blood pressure reductions (-18.2% and -18.1%) were observed in renovascular hypertensive patients after percutaneous transluminal renal angioplasty. Blood pressure fell by about 10% during the night and the fall was similar in renovascular and in essential hypertensive patients. In the former group, nocturnal hypotension was similar after washout, during angiotensin converting enzyme inhibitor treatment and after percutaneous transluminal renal angioplasty. Similar results were obtained for nocturnal bradycardia. CONCLUSIONS: Nocturnal blood pressure fall is equally manifest in renovascular and essential hypertension. The removal of the renal artery stenosis and blood pressure normalization do not enhance this phenomenon. Nocturnal hypotension seems therefore to be unaffected by renovascular hypertension.

Ambulatory blood pressure monitoring in the evaluation of antihypertensive drugs.

CLINIC VERSUS AMBULATORY BLOOD PRESSURE MEASUREMENT: Clinic blood pressure measurements do not give the best estimate of the efficacy of antihypertensive drugs because (1) they provide readings for one time-point only, (2) they are subject to a 'white-coat' effect and also show a significant placebo effect and (3) they are poorly reproducible. Ambulatory blood pressure monitoring overcomes these problems and offers the possibility of obtaining reliable, reproducible and detailed information on the time-course and magnitude of the effect of antihypertensive treatment on blood pressure over 24 h. MEAN 24-H VERSUS MEAN HOURLY AMBULATORY BLOOD PRESSURE VALUES: Compared with mean 24-h values, reproducibility is poorer for mean hourly ambulatory values, which show greater variability when tested under different conditions. Thus, caution must be exercised when the effects of antihypertensive drugs on hourly blood pressure profiles are analysed and the trough:peak ratio is calculated. FURTHER PROBLEMS WITH AMBULATORY MONITORING: There are further reasons for caution: (1) ambulatory blood pressure readings can be inaccurate, (2) there is only preliminary information on normal reference values and (3) there have been no longitudinal studies demonstrating the prognostic value of ambulatory blood pressure monitoring, which introduces uncertainty into attempts to evaluate the optimal effect of antihypertensive treatment by this method. CONCLUSIONS: These limitations do not detract from the use of ambulatory blood pressure monitoring in drug studies, but they do suggest that this measurement technique should not be used routinely for assessing antihypertensive treatment in clinical practice.

Beta-adrenergic blocking treatment and 24-hour baroreflex sensitivity in essential hypertensive patients.

We dynamically evaluated the effects of beta-blockade on the sensitivity of arterial baroreflex control of heart rate in 10 mild or moderate essential hypertensive patients in whom blood pressure was recorded intra-arterially for 24 hours in ambulatory conditions. Twenty-four-hour baroreflex sensitivity was assessed by both (1) a time-domain approach based on the calculation of the slope of the regression line between linearly related progressive increases in systolic blood pressure and pulse interval (+PI/+SBP sequences) and decreases in systolic blood pressure and pulse interval (-PI/-SBP sequences) and (2) a frequency-domain approach, ie, the ratio between the spectral powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha coefficient). Data were obtained before and after 1 month of administration of either acebutolol (n = 5) or labetalol (n = 5). Before treatment, the 24-hour average slopes of the +PI/+SBP and -PI/-SBP sequences were 4.36 +/- 0.32 and 4.05 +/- 0.27 ms/mm Hg, respectively, while the alpha coefficient was 7.78 +/- 0.7 ms/mm Hg. After beta-blockade, these values were increased by 25.3 +/- 6.8%, 25.0 +/- 8.0%, and 32.1 +/- 9.3%, respectively (P < .01 for all values). Thus, beta-blockers potentiate baroreflex sensitivity in daily life. Time-domain and frequency-domain methods yielded superimposable results in dynamically evaluating 24-hour baroreflex sensitivity and its changes after beta-blockade.

Spectral and sequence analysis of finger blood pressure variability. Comparison with analysis of intra-arterial recordings.

The aim of our study was to assess whether the Finapres device is able to accurately monitor not only average blood pressure values but also blood pressure variability. To examine this issue, we analyzed 30-minute recordings of finger and intra-arterial pressure simultaneously obtained at rest in 14 patients. We compared systolic blood pressure, diastolic blood pressure, mean arterial pressure, pulse interval (the reciprocal of heart rate), overall variability (standard deviation), and specific time-domain and frequency-domain components. Systolic blood pressure, diastolic blood pressure, mean arterial pressure, and pulse interval spectral powers were computed by fast Fourier transform over three frequency bands: low frequency (0.025 to 0.07 Hz), midfrequency (0.07 to 0.14 Hz), and high frequency (0.14 to 0.35 Hz). The coherence, ie, the degree of association between blood pressure and pulse interval powers obtained by the two techniques, was also assessed. Standard deviations of diastolic blood pressure, mean arterial pressure, and pulse interval were similar when assessed from the two recordings, whereas standard deviation of systolic blood pressure was overestimated by analysis of finger pressure recordings. All powers of diastolic blood pressure and mean arterial pressure and high-frequency powers of systolic blood pressure estimated from analysis of finger blood pressure tracings were superimposable to those obtained by analyzing invasive recordings. Low-frequency and midfrequency powers of intra-arterial systolic blood pressure were significantly overestimated by the analysis of finger blood pressure tracings (+13.7 +/- 4.4 mm Hg2, P < .01, and +2.3 +/- 0.9 mm Hg2, P < .05).(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.

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 physician's 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.

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 doctor's 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.

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)

Advantages and disadvantages of non-invasive ambulatory blood pressure monitoring.

Our studies have shown that (1) automatic blood pressure readings obtained from portable monitors do not induce any alerting reaction or pressor response in the patient; (2) although the measurements are intermittent, non-invasive ambulatory blood pressure monitoring is able to provide a true estimate of 24-h blood pressure and heart rate mean values (the assessment of 24-h blood pressure and heart rate variabilities is less accurate); (3) the nocturnal fall in blood pressure is not altered by the possible disturbance to the patient's sleep induced by repeated cuff inflations; and (4) even when the automatic blood pressure readings obtained are similar to simultaneous readings obtained by a sphygmomanometer, the accuracy of the values provided by portable monitors used in truly ambulatory conditions cannot be taken for granted. These findings have particular implications for the cost: benefit ratio if ambulatory blood pressure monitoring is to be used in the routine evaluation of hypertensive patients.

Early 24-hour blood pressure elevation in normotensive subjects with parental hypertension.

Subjects with a family history of parental hypertension are reported to have a slightly higher office blood pressure in the prehypertensive stage. Whether this reflects a hyperreactivity to blood pressure measurement or a more permanent blood pressure elevation, however, is not known. In the present study, blood pressure was measured in 15 normotensive subjects whose parents are both hypertensive (FH++), 15 normotensive subjects with one hypertensive parent (FH(+)-), and 15 normotensive subjects whose parents are not hypertensive (FH--); among the three groups, subjects were matched for age, sex, and body mass index. The measurements were made in the office during a variety of laboratory stressors and during a prolonged resting period, and for a 24-hour period (ambulatory blood pressure monitoring). Office blood pressure was higher in the FH++ group than in the FH-- group (p less than 0.05). The pressor responses to laboratory stressors were similar in the two groups, but the FH++ group had higher prolonged resting and 24-hour blood pressure than the FH-- group; the difference was always significant (p less than 0.05) for systolic blood pressure. The FH++ group also had a greater left ventricular mass index (on echocardiographic examination) than the FH-- group (p less than 0.01). The blood pressure values and echocardiographic values of the FH(+)- group tended to be between those of the other two groups. Thus, the higher blood pressure shown by individuals in the prehypertensive stage with a family history of parental hypertension does not reflect a hyperreactivity to stress but an early permanent blood pressure elevation.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of smoking.

Coronary heart disease (CHD) increases with smoking and this factor interacts with hypercholesterolemia and hypertension in raising the incidence of this condition in a greater than linear fashion. This can be explained by the adverse effect of smoking on plasma fibrogen, platelet turnover and lipid profile. It may also be accounted for, however, by the acute bradycardia, increase in blood pressure and generalized vasoconstriction accompanying smoking, due to a nicotine-dependent activation of the sympathetic nervous system. These effects (which in heavy smokers can raise blood pressure permanently) are only partly offset by beta-blockers and can only be abolished by opposing the cardiac and vascular sympathetic influences by alpha and beta-blockade combined.

Early twenty-four-hour blood pressure elevation in subjects with parental hypertension.

We studied 15 normotensive offspring of hypertensive parents, comparing them with 15 normotensive controls matched for sex, body mass index and age. In the offspring, both parents were hypertensive, while in the controls, neither parent was hypertensive. Blood pressure was measured at rest, during a variety of laboratory stressors (mental arithmetic, mirror drawing test, hand grip and cold pressor test), and was also monitored for 24 h in ambulatory conditions (Spacelabs 5300 M, Richmond, Washington, USA). Resting mean and diastolic blood pressures were higher (P less than 0.05) in the subjects with parental hypertension than in those without. The mean blood pressure rise induced by the laboratory stressors was not significantly greater at any time in the subjects with hypertensive parents compared with controls. Twenty-four-hour systolic and mean blood pressures, however, were significantly higher (P less than 0.05) in the subjects with hypertensive parents than in the controls. Thus the higher office blood pressure shown in the prehypertensive stage by subjects with parental hypertension is not due to hypersensitivity to stress, but represents an early and permanent blood pressure elevation.

Ambulatory blood pressure monitoring in the evaluation of antihypertensive treatment.

Cuff blood pressure measurements by doctors and self blood pressure measurements by patients reflect imprecisely 24-hour or daytime mean blood pressure values. This limits the physician's ability to diagnose the absence or presence of hypertension. It also limits his ability to evaluate the response to non-pharmacologic interventions or antihypertensive drugs. This is a major disadvantage because the prognosis of hypertensive persons depends to a large extent on the blood pressure attained during treatment. Ambulatory blood pressure monitoring is a valid method for assessing the effectiveness of antihypertensive treatment because it allows the physician: (1) to determine whether the initially elevated blood pressure is reduced under the various circumstances of the patient's lifetime; and (2) to exclude that this reduction is associated with hypotensive events that might interfere with organ nutrition and function during the day and night. However, this approach has a cost that makes its use impractical in clinical practice, except in cases in which there are reasons to suspect very low or excessively high blood pressures in conditions that are out of the reach of sphygmomanometry. Furthermore, the prognostic value of on-treatment ambulatory blood pressures is still unknown. On the other hand, studies on new antihypertensive agents derive great benefits from the use of ambulatory blood pressure monitoring. This is emphasized by the fact that the ambulatory blood pressure values are more reproducible than isolated cuff blood pressure values, allowing the number of patients necessary to establish an antihypertensive effect to be reduced. Furthermore, these values are little affected by placebo influences thus permitting simplification of the study design. Finally, sequential analysis of the data obtained provides accurate information on the duration of the antihypertensive effect, and thus on the optimal posology to be adopted. However, ambulatory blood pressure monitoring does have technical problems. In the case of non-invasive monitoring, the ability to measure blood pressure phasic events and variability is limited. Another problem, which is of greater importance, is that non-invasive blood pressure monitoring devices generate a number of artifactual and imprecise readings. These problems cannot be entirely eliminated by editing the blood pressure tracing.

Clinical and hemodynamic effects of celiprolol in essential hypertension.

The antihypertensive effect of celiprolol, a selective beta-adrenoceptor blocker with ancillary partial beta 2-agonist, vasodilator, and bronchosparing properties, has been evaluated in open and placebo-controlled trials. Celiprolol (200-600 mg once daily) has been reported to reduce blood pressure significantly in 60-80% of patients with side effects which are mild and low in frequency. The antihypertensive efficacy of celiprolol has been found comparable with that of propranolol, atenolol, metoprolol and nadolol, but celiprolol does not cause the same degree of bradycardia as these other drugs. By means of ambulatory blood pressure monitoring we have demonstrated that celiprolol, administered to 10 essential hypertensive patients (aged 20-64 years) as a single daily dose (200-400 mg), can induce a significant and sustained reduction in 24-h systolic and diastolic blood pressure, with no effects on 24-h heart rate. Similar results have been obtained in elderly patients (aged 65-74 years) responsive to this drug. Both in young and elderly patients treatment was well tolerated. Available evidence therefore suggests that celiprolol is an effective and safe antihypertensive drug, the favorable ancillary properties of which are likely to make its administration feasible in a broad range of patients.

24-h ambulatory non-invasive blood pressure monitoring in the assessment of the antihypertensive action of celiprolol.

The well-known limitations of traditional sphygmomanometer blood pressure measurements have led to the development of a number of invasive and non-invasive 24-h blood pressure monitoring techniques which provide information on blood pressure in daily life. A non-invasive portable blood pressure monitor (IRC Spacelab S5300 monitor) was used to assess the antihypertensive action of celiprolol, 400 mg once daily, in a randomized, double-blind, crossover, placebo-controlled study. After a washout period of 7 days, 15 patients with mild or moderate essential hypertension were subjected to three 24-h blood pressure recordings: at the end of washout, and after 1 month of placebo and celiprolol treatment. In the 10 responsive patients, celiprolol reduced 24-h systolic blood pressure, diastolic blood pressure and heart rate by 6.8%, 8.1% and 2.7%, respectively, when compared with placebo. The reduction in blood pressure was also evident during the night and the antihypertensive action of celiprolol was maintained 24-h after administration. Celiprolol had no effect on 24-h blood pressure or heart rate variability and, therefore, did not produce any alteration in cardiovascular homeostasis. These results demonstrate that celiprolol is an effective once daily treatment for hypertension.