Roberto Casadei

Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing.

The accuracy of blood pressure values obtained by continuous noninvasive finger blood pressure recording via the FINAPRES device was evaluated by comparison with simultaneous intraarterial monitoring both at rest and during performance of tests known to induce fast and often marked changes in blood pressure. The comparison was performed in 24 normotensive or essential hypertensive subjects. The average discrepancy between finger and intra-arterial blood pressure recorded over a 30-minute rest period was 6.5±2.6 mm Hg and 5.4±2.9 mm Hg for systolic and diastoiic blood pressure, respectively; a close between-method correspondence was also demonstrated by linear regression analysis. The beat-to-beat changes in finger systolic and diastoiic blood pressure were on average similar to those measured intra-arterially during tests that induced a pressor or depressor response (hand-grip, cold pressor test, diving test, Valsalva maneuver, intravenous injections of phenylephrine and trinitroglycerine) as well as during tests that caused vasomotor changes without major variations in blood pressure (application of lower body negative pressure, passive leg raising). The average between-method discrepancy in the evaluation of blood pressure changes was never greater than 4.3 and 2.0 mm Hg for systolic and diastoiic blood pressure, respectively; the corresponding standard deviations ranged between 4.6 and 1.6 mm Hg. Beat-to-beat computer analysis of blood pressure variability over the 30-minute rest period provided standard deviations almost identical when calculated by separate consideration of intra-arterial and finger blood pressure tracings (3.7 and 3.8 mm Hg, respectively). The two methods of blood pressure recording also allowed similar assessments of the sensitivity of baroreceptor control of heart rate (vasoactive drug injections) and blood pressure (neck chamber technique) to be obtained. Thus, beat-to-beat blood pressure recording via FINAPRES provides an accurate estimate of means and variability of radial blood pressure in groups of subjects and represents in most cases an acceptable alternative to invasive blood pressure monitoring during laboratory studies.

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intraarterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats hi which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+ PI/ + SBP) or fell (− PI/ −SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and −PI/−SBP sequences of 3 beats were found whereas the number of sequences of 4,5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of plus; PI/ + SBP (7.6 ± 2.0 msec/mm Hg) and − PI/− SBP (6.4 ± 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 ± 4.7 and 62.6 ± 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (−33.2% for +PI/ + SBP and −31.7% for −PI/−SBP) and less steep in hypertensive subjects (−40.3 and −36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations hi sensitivity due in part to hemodynamic, temporal, and behavioral factors. All features of the baroreceptor-heart rate reflex are unpaired hi essential hypertension.

Alerting reaction and rise in blood pressure during measurement by physician and nurse

Blood pressure was monitored by a continuous intra-arterial recording in 46 subjects to investigate whether the alarm reaction and the blood pressure and heart rate increases that occur during cuff blood pressure measurement made by a physician 1) attenuate when the physicians visit is repeated several times and 2) are less pronounced if a nurse measures the blood pressure. In 16 subjects the peak mean blood pressure and heart rate rises that occurred in the early part of the physicians first visit (22.6 +/- 1.8 mm Hg and 17.7 +/- 1.7 beats/min) were virtually identical to those occurring during three subsequent visits by the same physician throughout a 2-day intra-arterial blood pressure monitoring. The less pronounced pressor and tachycardic responses observed in the last part of the physicians visit also were virtually identical among the four visits. In contrast, in 30 other subjects the blood pressure and heart rate rises that occurred during the nurses visit were 46.7% and 42.1% less (p less than 0.01) than those occurring during the physicians visit. The late and less pronounced pressor and tachycardic responses to the visit were also significantly less (p less than 0.01) in the former than in the latter condition. These results indicate that the error of overestimation of blood pressure inherent in cuff blood pressure measurement by a physician cannot be avoided by repeated visits by the physician over a short time span. It clearly can be reduced, however, if blood pressure measurements are performed by a nurse.

Arterial baroreflexes and blood pressure and heart rate variabilities in humans.

The factors responsible for 24-hour blood pressure and heart rate variabilities have never been clarified; however, studies performed in unanesthetized animals have shown an increase in blood pressure variability after sinoaortic denervation, and a negative relationship has been reported occasionally between blood pressure variability and baroreflex control of heart rate in humans. We have systematically investigated this issue in 82 ambulant hypertensive subjects using 24-hour intraarterial blood pressure recording (Oxford method) in which blood pressure and heart rate variabilities were measured by calculating the standard deviations of the values obtained throughout the 24 hours or during separate daytime and nighttime periods. Baroreflex sensitivity was assessed by the bradycardic or tachycardic responses to intravenous injections of phenylephrine or nitroglycerin and by the blood pressure response to changes in carotid transmural pressure obtained with a neck chamber. The sensitivity of the baroreceptor-heart rate reflex as Bssessed by the vasoactive drug technique showed a negative relationship with 24-hour blood pressure variability as well as with daytime and nighttime blood pressure variabilities measured separately (r = −0.28 to −0.50, p < 0.05). These Variabilities also correlated negatively with the sensitivity of the baroreceptor-blood pressure reflex as assessed by the neck chamber technique. By contrast, baroreflex sensitivity showed a positive correlation with heart rate variabilities (r = 0.32 to 0.47, p < 0.05). The relationship between baroreflex sensitivity and blood pressure and heart rate variabilities was confirmed when the data were analyzed by multiple regression to adjust for blood pressure and age differences among the 82 subjects. These results suggest that 1) arterial baroreflexes exert a buffering influence on the magnitude of daytime and nighttime blood pressure variabilities in humans; 2) these reflexes favor heart rate variability, which may represent one of the means by which baroreflex stabilization of blood pressure is accomplished; and 3) because of the low correlation indices between baroreflex sensitivity and blood pressure and heart rate variabilities, other factors (probably central in nature) are important in determining the size of these variations.

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.

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.

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.

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.

Calcium antagonists and neural control of circulation in essential hypertension.

Data from animals and from man suggest that calcium antagonists interfere with aadrenergic receptors and that this mechanism may be responsible for some of the vasodilation induced by these drugs. However, a-adrenergic receptors play a primary role in baroreceptor regulation of the cardiovascular system and blood pressure homeostasis, which might therefore be adversely affected by calcium antagonist treatment. We addressed this question in 14 essential hypertensives studied before treatment, 1 h after 20 mg oral nitrendipine and 5-7 days after daily administration of 20 mg oral nitrendipine. Blood pressure was measured by an intra-arterial catheter, heart rate by an electrocardiogram, cardiac output by thermodilution and forearm blood flow by venous occlusion plethysmography. Total peripheral and forearm vascular resistances were calculated by dividing mean blood pressure by blood flow values. Plasma norepinephrine was also measured (high performance liquid chromatography) in blood taken from the right atrium. Compared with the pretreatment values, acute nitrendipine administration caused a fall in resting blood pressure, an increase in the resting heart rate and cardiac output, and a fall in resting peripheral and forearm vascular resistance. The resting hypotension and vasodilation were also evident during the prolonged nitrendipine administration, which was, however, accompanied by much less resting cardiac stimulation than that observed in the acute condition. Baroreceptor control of the heart rate (vasoactive drug method) was similar before and after acute and prolonged nitrendipine treatment. This was also the case for carotid baroreceptor control of blood pressure (neck chamber technique) and for control of forearm vascular resistance as exerted by receptors in the cardiopulmonary region (lower-body negative- pressure and passive leg-raising techniques). The increases in blood pressure, cardiac output and total peripheral resistance induced by a cold pressor test and isometric exercise were also superimposable before and after the acute and more prolonged administration of nitrendipine. Even the cardiovascular adjustments to dynamic exercise (increase in blood pressure, heart rate and cardiac output, decrease in peripheral resistance) were superimposable before and after drug administration. These observations show that reflex control of circulation and blood pressure homeostasis are not adversely affected by acute and prolonged administration of nitrendipine at doses capable of exerting an antihypertensive effect. Although this does not exclude an a-blocking action by this drug, it indicates that any such action does not interfere with sympathetic cardiovascular control.

Twenty-four hour ambulatory intra-arterial blood pressure in normotensive and borderline hypertensive subjects

A number of studies have shown that blood pressure values obtained by ambulatory monitoring are lower than those obtained in the doctors office by cuff readings. However, there is still no suitable information on `normal‘ 24-h ambulatory blood pressure values. In 19 normotensive and 13 borderline hypertensive subjects, defined by repeated office blood pressure measurements, we recorded intra-arterial blood pressure under ambulatory conditions for 24 h (Oxford method) in order (1) to assess the 24-h blood pressure values of normal subjects, and (2) to compare their 24-h blood pressure values with those of borderline hypertensive patients. In the normotensive subjects systolic, diastolic and mean ambulatory blood pressure values over 24 h were significantly lower than the corresponding office values, the differences being −15.0, −22.1 and −17.9 mmHg, respectively. In the borderline hypertensives 24-h ambulatory blood pressure was significantly lower than office readings. On average, the 24-h mean blood pressure of normotensive subjects was significantly lower than that of borderline patients (P < 0.01). However, individual 24-h blood pressure values showed a considerable overlap. Thus, (1) ambulatory blood pressure values just below 140/90 mmHg do not necessarily mean that the blood pressure is in the normal range, the mean 24-h blood pressure of true normotensive subjects being much lower; (2) ambulatory blood pressure monitoring in patients with high office blood pressure readings may help to identify subjects whose 24-h mean values are indistinguishable from those of normotensives. However, the clinical relevance of these findings in the diagnosis of hypertension has to be validated by prospective clinical trials.