24-HOUR Blood Pressure Profile in Centenarians

Original article 1765 24-hour blood pressure profile in centenarians Giovanni Bertinieria,b , Guido Grassia,d,e , Paolo Rossic , Anna Melonia , Maria Ciampaa , Giorgio Annonic , Carlo Verganic and Giuseppe Manciaa,d,e Objective Ambulatory blood pressure in the elderly has been studied in the past, the age range most frequently examined being 65 to 80 years. The present study was aimed at determining 24-h blood pressure means and profile in centennial human beings. Patients and methods Sphygmomanometric blood pressure (average of three values) and 24-h ambulatory blood pressure measurements were performed in 16 centennial subjects (age 101.7 6 0.4 years, mean 6 SEM) and in 20 healthy normotensives aged 80.7 6 1.1 years. All subjects were in good clinical and mental conditions for their age. They had no history, signs or symptoms of cardiovascular or non-cardiovascular diseases and were under no drug treatment. sphygmomanometric and 24-h blood pressure averages were 146.6 6 4.4/82.8 6 2.2 and 131.8 6 2.5/ 75.3 6 1.6 mmHg, respectively, with a clearcut reduction in night-time as well as in post-prandial values. Conclusions In centenarians 24-h blood pressure values are: (1) lower than sphygmomanometric blood pressures and (2) slightly less than in subjects aged 80 years. At variance with these subjects, however, in centenarians nocturnal hypotension and bradycardia are abolished, presumably because of a derangement in the central sleep influences on the cardiovascular system. J Hypertens 20:1765–1769 & 2002 Lippincott Williams & Wilkins. Journal of Hypertension 2002, 20:1765–1769 Results In the centennial group sphygmomanometric blood pressure amounted to 131.2 6 3.0/70.7 6 2.2 mmHg (systolic/diastolic) and 24-h blood pressure and heart rate average values to 125.6 6 3.4/64.8 6 2.0 mmHg and 77.5 6 4.3 bpm, respectively. Blood pressure and heart rate showed no difference between daytime and night-time values, i.e. night-time was accompanied by no blood pressure and heart rate fall. In contrast, in all subjects, a significant reduction in blood pressure was observed during the post-prandial period, with no significant heart rate changes. In the octogenarian group, Keywords: ageing, blood pressure, circadian rhythm, monitoring ambulatory blood pressure a Centro Interuniversitario di Fisiologia Clinica ed Ipertensione, b Istituto di Clinica Medica, c Divisione di Geriatria, Ospedale Maggiore IRCCS-Milano, d Istituto di Clinica Medica, Università Milano-Bicocca, Ospedale S.Gerardo, Monza (MI) and e Istituto Auxologico Italiano, Milano, Italy. Correspondence and requests for reprints to Giuseppe Mancia, Clinica Medica, Ospedale S.Gerardo dei Tintori, Via Donizetti 106, 20052 Monza (MI), Italy. Tel: +39 039 2333357; fax: +39 039 322274; e-mail: [email protected] Received 14 March 2002 Revised 8 May 2002 Accepted 14 May 2002 Introduction Methods Several studies have shown that 24-h average systolic and diastolic blood pressures (BP) change with ageing in a less steep fashion than the corresponding office values [1–3]. They have also shown that the physiological hypotension that occurs at night is largely present up to 74 years, but it shows some attenuation at 80 years of age leading to an abnormality of the circadian BP profile [4]. The population of our study consisted of 36 normal weight subjects, whose age ranged from 80 to 106 years. A total of 16 subjects (13 females) were selected as being centenarians from the list of the general practitioners in Milan area and the surrounding area. (1) They had an age ranging from 100 to 106 years (mean  SEM: 101.7  0.4 years) and a body mass index [body weight (BW) in kg divided by the height in m2 ], ranging from 19 to 22.5 kg/m2 ; (2) they lived at home and displayed a satisfactory degree of personal and motor autonomy, including performance of the usual daily activities of elderly people, and (3) did not take drugs on a continuous basis and did not assume any occasional drug in the week immediately preceding the ambulatory BP monitoring (see below). In all subjects the authors obtained routine laboratory examinations in the 3–4 weeks preceding the study. No subject had any evident deterioration of cognitive Little information is available on ambulatory BP at a very advanced age [5] and whether under this circumstance the circadian BP profile is even more markedly altered, is thus unknown. We have addressed this issue by performing ambulatory BP monitoring in centennial individuals and by comparing the data with those obtained in octogenarians. The subjects were all selected if devoid of diseases, to allow the results to reflect ‘physiological’ alterations in circadian BP profile. 0263-6352 & 2002 Lippincott Williams & Wilkins 1766 Journal of Hypertension 2002, Vol 20 No 9 functions and all were capable of holding a simple conversation. A total of 20 normotensive less aged subjects (age range: 80 to 85 years, mean age: 80.7  1.1 years; 13 females; body mass index ranging from 20 to 23.3 kg/ m2 ) were studied as a comparative group. They were referred to the Outpatient Clinic of the Geriatric Unit of our hospital for routine laboratory examinations and for cognitive function assessment, in the absence of specific symptoms. They also (1) did not assume drugs on a continuous basis, (2) were instructed not to take any occasional drugs before the study, (3) were clinically defined as normotensives on the basis of repeated office BP measurements, and (4) did not show any evidence of cognitive function impairment. All individuals were in sinus rhythm (ECG assessment) and none displayed clinical or laboratory evidence of coronary heart disease, congestive heart failure, diabetes, renal disease, liver disease or metabolic and hematologic abnormalities. This was confirmed also by the anamnestic check performed on the subjects as well as on the medical records of their general practitioners. All subjects gave written informed consent to the study, whose protocol was approved by the Ethics Committee of our Institution. In each subject, BP was measured by a doctor during a home visit. Three sphygmomanometric BP measurements were obtained in the sitting position, taking the first and fifth Korotkoff sounds to identify systolic and diastolic values, respectively. The first BP measurement was collected approximately 5 min from the beginning of the visit, the second measurement approximately 10 min from the beginning, and the final one at the end of the visit. Heart rate (HR) was measured after BP measurements by the palpatory method (30 s). After the third measurement, every subject was fitted with an ambulatory BP monitoring device (Spacelabs 90207, Milan, Italy) programmed to perform automatic readings at 20 min intervals during the daytime (0700–2300 h) and at 30 min intervals during the night-time (2300–0700 h). Each subject was asked to carry out the usual daily activities during the monitoring period and to report in a diary meal times, sleep times and unusual events during both the day and night. Night-time sleep was reported as uneventful with the exception of a micturition episode in some individuals of either group. The recording device was removed 24 h later. BP monitorings were performed in both groups in the same seasonal period, i.e. between October and February. In each subject, the validity of individual BP readings was checked by the criteria previously reported [6,7]. Valid ambulatory systolic and diastolic readings in the two groups (respectively 92 and 90% of the 64 readings planned for the 24 h) were averaged for each hour of the monitoring period, the daytime (0700–2300 h), the night-time (2300–0700 h) and the whole 24 h. Similar calculations were performed for pulse pressure and HR. Data from each subject were separately averaged for the two groups and expressed as mean  SEM. Comparisons between data obtained in centennial and octogenarian subjects were made by two-way analysis of variance (ANOVA). The two-tailed t-test for unpaired observations was used to locate between-group differences. A probability value (P) of less than 0.05 was considered to be statistically significant. Results As shown in Figure 1 sphygmomanometric systolic and diastolic BP values were lower in the centenarians than in octogenarians. In both groups, 24-h average BPs were less than the sphygmomanometric ones, again with lower values in centenarian than in octogenarian individuals. The 24-h average HR was similar to clinic HR in both groups and slightly less in octogenarians than in centenarians. Calculated pulse pressure values were superimposable in the two groups (centenarians: office 60.5  4.3 mmHg and 24-h average 60.9  2.7 mmHg; octogenarians: 63.8  3.4 mmHg and 24-h average 56.4  1.9 mmHg). Figure 1 also shows day and night BP and HR values, whereas circadian BP and HR profiles are shown in Figure 2. In octogenarians night-time was accompanied by a clearcut reduction in systolic BP ( 8.7  0.6 mmHg), diastolic BP ( 9.7  0.8 mmHg) and HR ( 8.7  0.9 bpm). Nocturnal bradycardia was absent (HR: 0.2  0.1 bpm) in centenarians, in whom there was virtually no nocturnal hypotension (systolic BP: 1.6  0.9 mmHg; diastolic BP: 0.2  0.1 mmHg) making day and night BP values almost superimposable. The post-prandial time was accompanied by a significant systolic and diastolic BP fall in both groups (Fig. 3), without significant HR changes in either group (data not shown). Discussion The main new finding of the present study is that subjects aged 100 years or more did not show any reduction in BP and HR during the night-time. Because the individuals selected (1) did not have any major clinical problem, (2) were not under any type of medical treatment, and (3) did not report any alteration in ordinary night-time sleep during the 24-h BP monitoring time, the conclusion can be drawn that this group of selected centenarians is characterized by a profound alteration in circadian BP and HR profiles, which consist of the virtual disappearance of the physiological fall in these two variables occurring during night-time sleep. This alteration may originate BP profile in centenarians Bertinieri et al. 1767 Fig. 1 (a) * * * ** 160 * S mmHg 130 100 70 D ** ** * ** 40 ** BP (b) * 90 * * b/min 80 ** 70 60 50 Octogenarians Centenarians HR The 24-h average, daytime, night-time and sphygmomanometric systolic (S) and diastolic (D) (a) blood pressure (BP) and (b) heart rate (HR), in octogenarians (left) and centenarians (right). Data are mean  SEM.  P , 0.05 and  P , 0.01 refer to the level of statistical significance between groups or between values in each groups. White bars, 24-h average BP and HR values; hatched bars, daytime values; black bars, night-time values; grey bars, sphygmomanometric values. 1768 Journal of Hypertension 2002, Vol 20 No 9 Fig. 2 (a) BP (b) 120 120 mmHg 150 mmHg 150 90 BP S 90 60 D 60 0 7 9 11 13 15 17 19 21 23 1 3 5 0 h 7 9 11 13 15 17 19 21 23 1 h 5 HR HR 90 90 80 80 b/min b/min 3 70 60 70 60 7 9 11 13 15 17 19 21 23 1 3 5 h 7 9 11 13 15 17 19 21 23 1 3 5 h The 24 h systolic blood pressure, the diastolic blood pressure (BP), and heart rate (HR) profiles in (a) octogenarians and (b) centenarians. Data are shown as mean ( SEM) hourly values. Fig. 3 20 0 40 60 80 100 120 min 5 0 20 40 60 80 100 120 min 4 * * * * * 10 * * * * * * * * * * * * * * * * * * * * ⫺12 ∆ DBP (mmHg) * * * * * * 8 * * ⫺15 ∆ SBP (mmHg) * * * * * * * * * * * Time course of the systolic and diastolic blood pressure (BP) post-prandial reductions (˜ SBP and ˜ DBP) collected every 20 min for a 2-h period in octogenarians (white bars) and centenarians (grey bars). Data are shown as mean  SEM taking as baseline the 2-h BP values preceding a meal.  P , 0.05 and  P , 0.01 refer to the level of statistical significance between baseline and post-prandial values in each group. from the loss of the sleep-dependent ability to increase the vagal drive or to reduce the cardiac sympathetic one [8]. It may additionally originate from the loss of the sleep-dependent ability to reduce sympathetic vascular tone [8–10] and/or from the inability of resistance vessels to respond with a dilatation to a reduction in autonomic tone, because of vascular hypertrophy and stiffness [11]. Several other results of our study provide new information and deserve to be mentioned. First, centenarians showed a post-prandial BP fall similar to the one seen in octogenarians. This suggests that in centenarians mesenteric vessels can dilate during the digestive phase [12], thereby speaking against vascular unresponsiveness as the main cause of the loss of nocturnal hypotension (see above). Second, in both octogenarians and BP profile in centenarians Bertinieri et al. centenarians, post-prandial BP fall was accompanied by little increase in HR. This confirms that at an advanced age, the baroreflex ability to modulate the heart is compromised [13,14], the impairment, however, being already expressed in the ninth decade of life. Third, octogenarians showed a clearcut reduction in BP and HR during the night-time, which suggests that, at variance from reflex mechanisms, central sleep influences on the cardiovascular system are still largely preserved at that age and only undergo a compromisation later. Fourth, in the young, middle-age and elderly fractions of the population, 24-h average systolic and diastolic BPs have been reported to be lower than office BPs [1,6]. This appears to be the case also in centenarians, in whom however, the two sets of values were also lower than in octogenarians. Thus the progressive BP increase that occurs with ageing is likely not to continue beyond the eighth or ninth decade of life. Indeed, subjects living beyond this age may be characterized by low BP values, both when measured by a doctor and in daily life, which may represent one of the factors responsible for preservation of vascular integrity and for allowing the centennial status to be reached [15,16]. The present study has some limitations. (1) The measurements did not include night-time electroencephalographic, oculographic and electromyographic recordings, thus preventing comparison of BP and HR changes seen in the two age groups for matched sleep patterns to be performed [17]. (2) To limit patients’ discomfort, we measured night-time BP at 30 min intervals. This is unlikely to have introduced some bias in the assessment of night-time average BP values [18]. It also made calculation of 24-h day or night standard deviations of BP and HR of limited relevance, because these values reflect the real BP standard deviations in an accurate fashion only if readings are not spaced by more than 15 min [18]. 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