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 approximately 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 alpha 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.

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. DESIGN: Cross-sectional analysis for FDS and QOL; 10-year prospective study for mortality. SETTING: The historical and central district of the city of Brescia, northern Italy. PARTICIPANTS: The entire cohort of 70 to 75-year-old people living in the above-mentioned district (n = 1303): 1201 subjects were eligible for interview at baseline; 11 refused the physical examination; 52 were lost to follow-up; data are presented for the remaining sample of 1137 subjects. MEASUREMENTS: FDS examination was used to classify the subjects into three groups: naturally adequate (ADS) (25.2%), naturally inadequate (IDS) (14.3%) dental status, and denture wearers (DW) (60.4%). Various QOL domains were assessed: mood level, cognitive status, instrumental activities of daily living (IADL), social relationships, indexes of somatic health, and health behaviors. The demographic and socioeconomic parameters were used as covariates. RESULTS: Univariate analysis showed that both the ADS and the DW groups had a better QOL profile than the IDS group. Multiple logistic regression indicated that ADS and DW conditions were predicted independently by better educational and financial conditions, higher social relationships and a better IADL level in comparison with IDS. Moreover, compared with IDS, DS was a significant predictor of a better level at the SELF, IADL, and HCU scales whereas DW predicted only a better IADL level. Crude survival analysis showed that ADS was associated with a lower mortality risk compared with both DW and IDS, which did not differ from each other. FDS also remained a significant and independent predictor of mortality in a more general Cox's regression model. CONCLUSIONS: Within this cohort of 70 to 75-year-old urban residents, FDS is associated with several QOL domains and with long-term survival. A hierarchy of reciprocal relationships exists among these parameters. The present study provides a basis for encouraging more extensive use of dentures. Longitudinal studies using oral health outcomes are warranted before clinical recommendations can be made.

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.

Blood pressures other than the one at the clinic.

While assessing the cardiovascular risk of hypertensive patients, different types of blood pressure measurements can be regarded as suitable surrogate endpoints. In this context the possible role of clinic, stress, exercise, basal, home and ambulatory blood pressures is briefly discussed. The clinical value of night-time blood pressure, of the clinic-daytime blood pressure difference and of blood pressure variability is also addressed.

Influence of dental status on dietary intake and survival in community-dwelling elderly subjects.

OBJECTIVE: to evaluate the relationships between a functional measure of dental status (FDS), the nutrients intake profile (NIP) and mortality in a community elderly population. DESIGN: cross-sectional analysis for FDS and NIP and a prospective study for mortality. SETTING: the central district of Brescia, northern Italy. PARTICIPANTS: of the entire cohort of 70-75-year-old elderly subjects living in the district (n = 1303), 1189 subjects were interviewed and examined at baseline. Fifty-two of these were lost to follow-up; data are presented for the remaining 1137 subjects. MEASUREMENTS: baseline data were collected by a door-to-door interview using a standardized questionnaire which included a section about the dietary intake in the 24 h preceding the interview. The 24-h NIP was calculated and compared with the US Food and Drug Administration's 1980 Recommended Dietary Allowances to obtain a percentage value of each nutrient for each respondent. The dental examination considered the direct assessment of the number and position of residual teeth as well as the use of dentures; subjects were classified into three groups: naturally adequate or naturally inadequate dentition and denture wearers. Association of NIP with FDS was computed using ANCOVA and multiple logistic regression models. Mortality data were collected over a 78-month follow-up period. Association of survival with FDS was estimated by Kaplan-Meier analysis and multivariate Cox proportional hazard models. RESULTS: multiple logistic regression showed a significant and independent association between the dental status and the intake of micronutrients, but not of macronutrients. Moreover, denture wearers had a dietary intake very similar to adequate dentition and substantially better than inadequate dentition. Inadequate dentition in women was associated with higher mortality than adequate dentition. In elderly women, both inadequate dental status and folate intake were significant and independent predictors of mortality in a multivariate analysis based on nutritional parameters. However, inadequate dentition did not remain an independent predictor of mortality in a general multivariate model. CONCLUSION: in this cohort of urban elderly people, FDS is significantly associated with the NIP and indirectly with mortality.

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

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.

Effects of aging on 24-h dynamic baroreceptor control of heart rate in ambulant subjects.

The effects of aging on the dynamic modulation of baroreflex sensitivity over 24 h was assessed in eight elderly (mean age +/- SD, 63.9 +/- 3.2 yr) and in eight young (23.9 +/- 6.1 yr) mild or moderate essential hypertensive patients, who were subject to a 24-h intra-arterial (Oxford technique) blood pressure recording in ambulatory conditions. The sensitivity of baroreflex control of the heart rate was dynamically assessed by quantifying 1) the slope of the regression line between pulse interval (the reciprocal of heart rate) and systolic blood pressure changes over spontaneously occurring hypertension-bradycardia or hypotension-tachycardia sequences (time domain analysis) and 2) the ratio between spectral-powers of pulse interval and systolic blood pressure around 0.1 Hz (alpha-coefficient: frequency domain analysis). The 24-h average sequence slope was lower in old than in young individuals (4.4 +/- 0.5 vs. 9.9 +/- 1.3 and 4.8 +/- 0.7 vs. 8.4 +/- 1.4 ms/mmHg for hypertension-bradycardia and hypotension-tachycardia sequences, respectively; P < 0.05 for both). Similar results were obtained by using the alpha-coefficient approach. The marked nighttime increase in baroreflex sensitivity observed in young individuals was much less evident in the elderly. Thus 24-h baroreflex sensitivity is markedly impaired by aging. The impairment becomes manifest also as an inability to increase baroreflex sensitivity at night.

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.

Blood pressure variability: clinical implications and effects of antihypertensive treatment.

HYPOTHESIS ON RELATIONSHIP BETWEEN BLOOD PRESSURE VARIABILITY AND END-ORGAN DAMAGE: Several studies have shown that the cardiovascular complications of hypertension are more closely related to ambulatory 24-h or daytime average blood pressure than to office readings. A few studies have also provided evidence that in hypertensive patients, not only average ambulatory blood pressure but also the degree of blood pressure variability is significantly and independently related to the end-organ damage associated with hypertension. LIMITATIONS OF PREVIOUS STUDIES: A common limitation of previous studies is that they were based on cross-sectional or retrospective observations, so that the correlative evidence they provide does not allow the relationship between blood pressure variability and end-organ damage to be interpreted causally. EVIDENCE FROM RECENT STUDIES: Recent evidence from follow-up observations has strongly supported the hypothesis that blood pressure variability is prognostically important in hypertensive patients. These findings suggest that optimal antihypertensive treatment should aim not only to reduce mean blood pressure levels, but also to reduce the degree of blood pressure fluctuation. EFFECTS OF ANTIHYPERTENSIVE DRUGS: Unfortunately, while most new antihypertensive drugs seem to be effective in reducing 24-h mean blood pressure levels, they are frequently unable to reduce 24-h blood pressure variability, which is often increased during treatment when expressed in normalized units. The development of drugs that guarantee a constant and uniform reduction in blood pressure over 24 h may, in principle, offer a further advantage by preventing the increase in 24-h blood pressure fluctuations that may follow the administration of short-acting antihypertensive agents. TROUGH: PEAK MEASUREMENTS OF BLOOD PRESSURE: The trough: peak ratio, proposed as an arithmetic indicator of the duration of the antihypertensive effect of a drug, may be a useful measure of the occurrence of a smooth reduction in blood pressure over 24 h. The possibility of obtaining an additional reduction in cardiovascular risk for hypertensive patients by minimizing the net trough: peak effect of antihypertensive drugs is thus an important issue for future studies.

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.

Blood pressure variability and organ damage.

Several studies have now shown that hypertension-induced end-organ damage is more closely related to 24-h average blood pressure than to clinic measurements. Furthermore, the degree of variability of blood pressure during a 24-h period bears a relation to organ damage that is independent of average blood pressure value. The measurement of blood pressure variability is a complex task, however, because data from automatic ambulatory blood pressure monitoring should be interpreted with caution, especially if the interval between blood pressure measurements is more than 15 min, and different types of blood pressure variability (e.g., short-term and long-term) can make calculation of variability by standard deviation of 24-h blood pressure values difficult, which further complicates measurement procedures and interpretation. Evidence is growing to suggest that blood pressure variability in hypertension is clinically significant. We have recently shown that over a 7.5-year period, end-organ damage is independently related to the initial blood pressure variability. Although information on the effect of antihypertensive treatment on 24-h blood pressure variability is limited, the available data suggest more of an effect on 24-h average blood pressure levels than on 24-h blood pressure changes. Further studies should investigate treatment effects on different types of blood pressure variability and the impact of treatment on patient protection and prognosis.

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) 1-13 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)

Spectral analysis of 24 h blood pressure recordings.

Spectral analysis of blood pressure and heart rate signals allows overall blood pressure and heart rate variabilities to be split into their different frequency components. When used to analyze 24 h discontinuous blood pressure recordings, the low sampling frequency that characterizes these devices allows only the slow fluctuations in day and night blood pressure to be adequately described by the spectral approach. Conversely, spectral analysis of continuous blood pressure recordings provides information both on fast and slow changes in blood pressure and heart rate. Because blood pressure and heart rate powers are characterized by a 1/f distribution over the 24 h, slow fluctuations in blood pressure and heart rate contribute most importantly to 24 h variance, while faster components provide only a minor contribution. However, spectral analysis of the latter has raised considerable interest due to the possible association of these components with cardiovascular regulatory mechanisms. It is now possible to perform 24 h dynamic spectral analysis of blood pressure and heart rate on continuous blood pressure recordings obtained noninvasively by a finger pressure device.

Clinical value of blood pressure measurements: focus on ambulatory blood pressures.

Because clinic blood pressure values are compromised by 2 major limitations--the alerting reaction to clinic measurements and the spontaneous blood pressure variability--they have only a limited correlation with average 24-hour blood pressure values. Whether the latter should be employed routinely in substitution for, or in addition to, traditional blood pressure measurements has not yet been determined, however. To date, average 24-hour blood pressure values have been shown to correlate more closely than clinic blood pressure values with the organ damage of hypertension. A correlation with organ damage has been shown also for a number of blood pressure values within the 24 hours. Nevertheless, the clinical importance of 24-hour blood pressure and blood pressure variability has never been confirmed by prospective controlled studies. This information needs to be obtained before this approach is routinely employed in the clinical practice.

Twenty-four hour blood pressure variability: clinical implications.

Ambulatory blood pressure monitoring techniques have allowed quantification of blood pressure variations occurring over a 24 hour time. The evaluation of these phenomena has not only allowed us to investigate the mechanisms responsible for cardiovascular regulation, but it has also provided information of clinical value. In particular there is evidence that blood pressure variations are significantly related to cardiovascular complications of hypertension. Progress in technology may allow us to extend these observations by means of non-invasive continuous blood pressure recordings to all those conditions where intra-arterial methods are not allowed.

Ambulatory blood pressure monitoring.

This paper reviews the evidence that, in patients with hypertension, end-organ damage correlates more closely with blood pressure values obtained by ambulatory blood pressure monitoring than with those obtained by conventional sphygmomanometry. However, ambulatory blood pressure monitoring is not suitable for routine use in the clinical setting because of a lack of standard reference values and data regarding the prognostic significance of this method. Ambulatory blood pressure values are reproducible and this method avoids the so-called placebo effect; thus, this method is useful in clinical studies investigating the efficacy and duration of action of antihypertensive drugs. Data from 1 study in which hypertensive patients were treated with slow release verapamil 240 mg, enalapril 20 mg, nitrendipine 20 mg and placebo, given once daily for 8 weeks according to a double-blind parallel group design, showed that mean 24-hour ambulatory blood pressure was reduced by all 3 drugs compared with placebo. Verapamil and enalapril showed similar antihypertensive efficacy and both drugs reduced night-time blood pressure more effectively than nitrendipine.

Twenty-four-hour blood pressure and antihypertensive treatment.

Normal values for 24-hour blood pressure (BP) have not been well characterized. However, it is believed that the maintenance of normal blood pressure control is a desirable feature of an antihypertensive agent. This is particularly important with respect to the drug's ability to (1) maintain circadian variation, albeit from a lower baseline, (2) lower BP throughout the 24 hours, (3) avoid the development of postural hypotension, (4) avoid decreases in BP sufficient to precipitate an ischemic event, (5) and to reduce BP variability toward the normal BP limits.