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.

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.

Radial artery compliance in essential hypertension: effects of antihypertensive therapy with lacidipine.

OBJECTIVE: To evaluate the effects of antihypertensive therapy with lacidipine on the increase in radial artery compliance observed in mild essential hypertensive patients. METHODS: The study was performed in eight mild to moderate essential hypertensive patients in whom clinic blood pressure, radial artery diameter and radial artery compliance were evaluated before and after 3 months' administration of lacidipine, at a single daily dose of 4 mg. Radial artery diameter and compliance were evaluated by means of a high precision echo-tracking device able to assess arterial compliance over the blood pressure oscillations that characterize the cardiac cycle. RESULTS: Lacidipine treatment caused a significant reduction in clinic systolic and diastolic blood pressure, while the heart rate was not modified by the drug. Radial artery diameter and compliance were both reduced by lacidipine over the entire systolodiastolic blood pressure range. CONCLUSIONS: Chronic administration of lacidipine seems to reverse the increase in compliance observed in essential hypertension at the radial artery level. We suggest that lacidipine treatment can reverse an increase in the smooth muscle component in the arterial wall induced by hypertension.

Ambulatory blood pressure monitoring in the design of studies on antihypertensive drug efficacy.

Ambulatory blood pressure monitoring (ABPM) provides advantages for studies of the efficacy of antihypertensive drugs in addition to demonstrating antihypertensive effects in daily life conditions. For example, ABPM is devoid of the "white coat" effect and can thus more precisely estimate the relative proportion of responders and nonresponders to treatment. It also may reduce the study size because of the greater reproducibility of 24 h average blood pressure (BP) (as compared to clinic BP) and the lack of a substantial placebo effect, which eliminates the need for a placebo group. Some disadvantages exist, including the inability of automatic ABPM to consistently provide accurate BP readings and to estimate BP variability. Finally, hourly average BPs are less reproducible than their average 24 h counterpart, which may make it more difficult to statistically demonstrate an antihypertensive effect throughout the 24 h. Some of these disadvantages, however, may be reduced in the near future by new ABPM devices.

Clinical value of ambulatory blood pressure monitoring.

Although office blood pressure measurement may be predictive of cardiovascular complications, it still has several limitations: first, the accuracy of its predictions is limited; second, the stress reaction it causes may lead to an overestimation of the need for treatment and to an underestimation of the therapeutic response in some patients; and third, because of this 'white-coat' reaction and the wide variation in blood pressure over 24 h, office blood pressure can only be an approximate reflection of 24-h average blood pressure values both during and in the absence of treatment. The alternative method of ambulatory blood pressure monitoring may represent a valuable approach in the clinical management of hypertension. Values derived by this method are largely devoid of the consequences of the 'white-coat' reaction and are more closely correlated to the organ damage associated with hypertension than those derived from office blood pressure measurement. However, longitudinal studies are needed to demonstrate whether ambulatory blood pressure monitoring is truly prognostically superior to the traditional method, and to determine precisely which are the blood pressure values within the 24-h period on which to base the diagnosis of hypertension to assess more accurately the efficacy of antihypertensive treatment. However, there is the suggestion that optimal blood pressure control probably consists of an even reduction of both daytime and night-time values, and that the wide variations in blood pressure that occur throughout 24 h should probably also be reduced and maintained on a long-term basis.

Vascular effects of lacidipine: a review of animal and human data.

AIM: To compare the vascular effects of lacidipine with those of other calcium antagonists. METHODS: A review of published studies. RESULTS: Experimental studies have shown that for a similar fall in blood pressure, lacidipine increased cardiac contractility while verapamil decreased cardiac contractility. In the rat aorta, the dose of lacidipine required to reduce a calcium-induced contraction by 50% was lower than that of all other calcium antagonists tested except nisoldipine. In human studies, especially, there are inherent limitations in the techniques available to measure regional blood flows under physiological conditions, making it difficult to compare the effects of different antihypertensive drugs. A recent study showed that renal blood flow was increased by lacidipine without any reduction in renal function. As in animals, vital organ perfusion was either preserved or increased. Further, maximal coronary vasodilation was associated with lower coronary resistance values during lacidipine treatment compared with pretreatment values. Another lacidipine study showed increased brachial artery compliance, while a study on the radial artery showed that lacidipine increased the compliance of this artery also. CONCLUSIONS: Lacidipine has vascular selectivity. Although regional blood flows are difficult to measure, due to inherent limitations in the techniques available, the evidence suggests that lacidipine produces vasodilation in essential hypertensive subjects while maintaining or even increasing vital organ perfusion. This appears to be due to a regression of the structural changes that characterize hypertension.

Isobaric compliance of the radial artery is increased in patients with essential hypertension.

OBJECTIVES: Hypertension is known to decrease arterial elasticity and systemic compliance. However, the arterial tree is not a homogeneous system, and whether a distal medium-sized artery such as the radial artery behaves like proximal arteries has not been determined. The aims of the present study were, first, to characterize non-invasively the mechanical properties of the radial artery through the determination of the pressure-diameter curve, the distensibility-pressure curve and the compliance-pressure curve, and, secondly, to compare untreated hypertensive patients with normotensive subjects. METHODS: A new high-precision echo-tracking device was developed which allows the diameter of peripheral arteries to be measured continuously. By relating the changes in internal diameter (cross-sectional changes) to those in blood pressure, the cross-sectional arterial compliance could be determined. PARTICIPANTS: Seventy-eight untreated mild or moderate essential hypertensive patients aged 24-78 years were compared with 44 normotensive subjects aged 22-81 years. In order to increase the database and provide independent assessments of the variables examined, the cross-sectional study was performed independently using a standardized procedure in three different research centres. RESULTS: The major finding was that diameter, distensibility and compliance of the radial artery of hypertensive patients were not significantly different from those of normotensive controls when the two populations were studied at their mean arterial pressure. Furthermore, when the two populations were compared for the same level of blood pressure, using distensibility--and compliance--pressure curves, it was clear that isobaric distensibility and compliance of hypertensives were not significantly lower than those of normotensives, being either unchanged or higher. CONCLUSIONS: These findings are in contrast with the well-known decrease in compliance of proximal large arteries due to hypertension. Whether such a difference between proximal large arteries and distal medium-sized arteries may be related to the structural vascular changes observed with long-standing hypertension is still difficult to analyse in humans, and requires further investigation.

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.

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 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.

Twenty-four hour blood pressure monitoring and end-organ damage.

Ambulatory blood pressure monitoring (ABPM) over 24 hours has become quite common. Evidence suggests that the mean 24-hour measurement is more closely associated with end organ damage, including end-points such as left ventricular hypertrophy (LVH), than is a single blood pressure measurement taken in the doctor's office. Clinicians disagree about the particular significance of blood pressure measurements obtained during exercise, blood pressure variability, and blood pressure load (a measurement above 140/90 over 24 hours). However, the morning peak in blood pressure appears to be associated with the highest incidence of coronary events, and end organ damage may be greater in subjects in whom nocturnal blood pressure falls only slightly from a diurnal baseline (non-dippers). From now, ABPM serves mainly as a research tool. Longitudinal controlled studies are needed to compare the value of ABPM to office blood pressure readings in terms of how these measurements can predict cardiovascular end-points or, more realistically, surrogate end-points, such as the development or regression of LVH.

Testing the accuracy of blood pressure monitoring devices in ambulatory conditions.

In recent years technological progress has improved the construction of ambulatory blood pressure monitoring devices. This has resulted in devices able to measure blood pressure continuously and non-invasively, and also in lighter, less noisy and more accurate intermittent blood pressure monitors. The accuracy of monitors, however, is still tested by taking blood pressure measurements at rest, and testing against intra-arterial blood pressure values, in true ambulatory conditions, is very seldom used. When evaluated by the latter approach, devices such as SpaceLabs 5300 and the Sandoz SPS 1558 recorders can be substantially inaccurate. Newer devices such as the SpaceLabs 90202 and 90207 are also somewhat inaccurate, particularly when diastolic blood pressure is considered. However, hour-to-hour changes in blood pressure obtained by the SpaceLabs 90202 and 90207 monitors are qualitatively and quantitatively similar to those obtained by invasive methods. This makes it possible to describe the 24-h blood pressure profile more accurately.

Methodological problems in evaluation of cardiovascular effects of stress in humans.

Cardiovascular effects of stress in humans are often assessed by application of physical or emotional stimuli in a laboratory environment. Although this method provides important information, these procedures have several limitations. First, blood pressure and heart rate responses to laboratory stressors are characterized by a limited within-subject reproducibility. Second, there is poor correlation between blood pressure and heart rate responses to different stressors, which implies that individual reaction to stress may be estimated differently according to the test used. Finally, these responses bear only a limited relation to 24-hour or daytime blood pressure variability, that is, they reflect to only a limited extent the tendency of blood pressure to vary during daily activities. If assessed by techniques that allow blood pressure to be continuously recorded for 24 hours in ambulatory subjects, blood pressure variability represents a possible approach to observation of cardiovascular reactivity away from an artificial laboratory environment. However, whether blood pressure variability should be expressed as a percentage or in absolute values is controversial. Furthermore, although naturally occurring stress may markedly increase blood pressure, 24-hour blood pressure variations also depend on factors that are not related to emotional stimuli. Thus, the study of cardiovascular responses to stress in humans encounters several problems, regardless of the method used.

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)

24-hour blood pressure monitoring in hypertension.

It has been recognized for some time that blood pressure is highly variable over a 24-h period. A number of studies have demonstrated that the extent and severity of target-organ damage associated with hypertension can be correlated more closely with blood pressure values monitored continuously for 24 h than with individual values recorded sphygmomanometrically. A great deal of interest is focused on whether absolute values of diastolic or systolic blood pressure, values during the day or night, or the rate of change of blood pressure such as the rapid increase that occurs in the early morning are more or less important factors contributing to the mortality and morbidity associated with hypertension. Work from our own unit provides evidence of the importance of two features in the variability of blood pressure. Blood pressure decreases during the night, but remains higher in hypertensive patients than in normotensive subjects. The mean nighttime blood pressure was shown to correlate with hypertension-related target-organ damage almost as closely as the mean daytime blood pressure. Using 24-h blood pressure monitoring, we have shown that the higher the mean 24-h blood pressure, the greater the extent and severity of target-organ involvement. In addition, for patients with comparable mean 24-h blood pressure values, larger degrees of blood pressure variability throughout the monitoring period were associated with more target-organ damage. Taking the available evidence into account, it is probably important that treatments used for hypertension should provide control of blood pressure for a full 24-h period confirmed by ambulatory blood pressure monitoring.

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)