Alessandra Frattola

Prognostic value of 24-hour blood pressure variability

Objectives: Evaluation of the prognostic value of 24-h blood pressure averages and 24-h blood pressure variability. Design: After an initial thorough clinical and laboratory evaluation which included 24-h continuous ambulatory blood pressure monitoring, a group of hypertensive patients were re-examined after an average of 7.4 years. End-organ damage at the follow-up visit was related to different measures of blood pressure levels and variability obtained at the initial or the follow-up visit or both. Methods: Seventy-three patients with essential hypertension of variable severity, in whom ambulatory blood pressure was monitored intra-arterially for 24 h (Oxford technique) were re-examined at a follow-up visit (including echocardiographic assessment of left ventricular mass index) 4-13 years later (mean 7.4 years). The severity of end-organ damage was quantified by a score and related to clinic blood pressure at follow-up and to (1) clinic blood pressure, (2) 24-h blood pressure mean, (3) 24-h short-term and long-term blood pressure variability, and (4) end-organ damage, all assessed at the initial visit (multiple regression analysis). Results: The set of independent variables considered was significantly related to end-organ damage at follow-up (R = 0.51). The individual variables most important in determining end-organ damage at follow-up were clinic blood pressure at the follow-up visit (P < 0.01), the initial level of end-organ damage (P < 0.05) and long-term blood pressure variability (among half-hour standard deviation of 24-h mean blood pressure) at the initial evaluation (P < 0.05). The prognostic individual weight of the other haemodynamic parameters considered was less and not statistically significant. Conclusions: The results confirm that the level of blood pressure achieved by treatment and the degree of end-organ damage at the time of initial evaluation are important determinants of future end-organ damage related to hypertension. They also constitute the first longitudinal evidence that the cardiovascular complications of hypertension may depend on the degree of 24-h blood pressure variability.

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)

Time and frequency domain estimates of spontaneous baroreflex sensitivity provide early detection of autonomic dysfunction in diabetes mellitus

Summary Diabetic autonomic dysfunction is associated with a high risk of mortality which makes its early identification clinically important. The aim of our study was to compare the detection of autonomic dysfunction provided by classical laboratory autonomic function tests with that obtained through computer assessment of the spontaneous sensitivity of the baroreceptor-heart rate reflex (BRS) by time domain and frequency domain techniques. In 20 normotensive diabetic patients (mean age ± SD 41.9 ± 8.1 years) with no evidence of autonomic dysfunction on laboratory autonomic testing (D0) blood pressure (BP) and ECG were continuously monitored over 15 min in the supine position. BRS was assessed as the slope of the regression line between spontaneous increases or reductions in systolic BP and linearly related lengthening or shortening in RR interval over sequences of at least 4 consecutive beats (sequence method), or as the squared ratio between RR interval and systolic BP spectral powers around 0.1 Hz. We compared the results with those of 32 age-matched normotensive diabetic patients with abnormal autonomic function tests (D1) and with those of 24 healthy age-matched control subjects with normal autonomic function tests (C). Compared to C, BRS was markedly less in D1 when assessed by both the slope of the two types of sequences (data pooled) and by the spectral method (–71.3 % and –60.2 % respectively, both p < 0.01). However, BRS was consistently although somewhat less markedly reduced in D0, the reduction being clearly evident for all the estimates (–57.0 % and –43.5 %, both p < 0.01). The effects were more evident than those obtained by the simple quantification of the RR interval variability. These data suggest that time and frequency domain estimates of spontaneous BRS allow earlier detection of diabetic autonomic dysfunction than classical laboratory autonomic tests. The estimates can be obtained by short non-invasive recording of the BP and RR interval signals in the supine patient, i. e. under conditions suitable for routine outpatient evaluation. [Diabetologia (1997) 40: 1470–1475]

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)

Dental Status, Quality of Life, and Mortality in an Older Community Population: A Multivariate Approach

OBJECTIVE: To evaluate the relationships between a functional measure of dental status (FDS), several variables belonging to a quality of life (QOL) profile, and mortality in an older community population.

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.

Broadband Spectral Analysis of Blood Pressure and Heart Rate Variability in Very Elderly Subjects

Systolic blood pressure (SBP) variability is increased and R-R interval variability is reduced in the elderly. Little is known, however, about how SBP and R-R interval variabilities change in the very elderly. More important, however, it is not known which frequency components of SBP and R-R interval variability are affected significantly. We addressed this issue in subjects older than 70 years by broadband spectral analysis, which allows all variability components from the lowest to the highest frequency to be considered. In 20 very elderly normotensive subjects (mean +/- SD age, 78.1 +/- 6.8 years) and 28 normotensive adult subjects (36.1 +/- 7.1 years), noninvasive finger blood pressure and R-R intervals were recorded continuously for 30 minutes in the supine position and 15 minutes in the upright position. SBP and R-R interval power spectral densities were computed over the entire frequency region between 0.005 Hz (0.007 Hz in the upright position) and 0.5 Hz. Overall SBP variability (SD) was greater and overall R-R interval variability was less in very old subjects than in adult subjects. All spectral R-R interval powers were reduced significantly in very elderly individuals. The spectral SBP powers were greater in the very elderly group than in the adult group only in the very-low-frequency range (<0.04 Hz). This was true in the supine and the standing positions. With subjects in the standing position, the shape of the broadband spectra differed in the very old and adult subjects because in the former group the increase in SBP and R-R interval power around 0.1 Hz that was seen in the latter was blunted. Therefore, in very elderly subjects a reduction in overall R-R interval variability is accounted for by a reduction in all of its frequency components. The accompanying increase in overall BP variability, however, results from a nonhomogeneous behavior of its frequency components, which consists of an increase in the very low frequency and a concomitant reduction in the higher frequency powers. The mechanisms responsible for these changes may be complex, but at least they may in part reflect the baroreflex impairment and autonomic dysfunction that characterize aging.

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.

1/f-Modelling of blood pressure and heart rate spectra: Relations to ageing

In this study a validation of the hypothesis that blood pressure (BP) and heart rate (HR) spectra are related to the frequency f according to the K/fα relation (briefly 1/f) was provided from the analysis of 24-h BP recordings. Frequency bands where the 1/f modelling correctly apply have been identified. Then the 1/f-models and the total power σ2 were computed in young and old subjects to quantify the effect of ageing on the BP and HR spectra. Significant differences between the groups were found indicating that physiological changes related to the age not only influence the overall variability but also the 1/f components of the BP and HR spectra.