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White coat hypertension and target organ damage in Japanese: community-based Kinugawa study
152A
ASH
XIV
A021
A022
WHITE COAT HYPERTENSION AND TARGET ORGAN DAMAGE IN JAPANESE: COMMUNITY-BASED KINUGAWA STUDY Y.Sato. K.Kario, S.Hoshide, Y.Umeda, T.Hashimoto, R.Ohki, T.Ojima, O.Kunii, S.Kuroki, U.lkeda, K.Shimada Department of Cardiology, Jichi Medical School, Tochigi, Japan The degrees of target organ damage of white coat hypertension (WC-HT) have not yet been established. We investigated the relationship between blood pressure (BP) variability and target organ damage of WC-HT, using data obtained from 172 community dwelling subjects aged>40years (mean 61years) who underwent a cardiovascular examination. BP was measured in the sitting, supine and standing positions. Various stress tests (hand grip exercise; HG, cold presser test; CP) and 24-hour ambulatory BP monitoring were performed in all subjects. Target organ damage was assessed using the left ventricular mass index (LVMI) measured by echocardiography, infima-media thickness (IMT) measured by carotid ultrasonography and urinary albumin excretion (UAE). WC-HT was defined when mean BP in the siring position > 140/90mmHg and 24-hour mean BP value~135/85mmHg. The increase in systolic BP by standing in the WC-HT group (n=20) was greater than that in the normoteasion (biT) group (n=80) and of sustained hypertension (HT) group (n=72). There was no significant difference in the increase of systolic BP by other stress tests (HG and CP, respectively) among the three groups. The average LVMI of the WC-HT group was 13 lg/m-'. This was significantly higher than in the NT group (107g/m", P<0.01), but was not different from that of the HT group (135g/m~). The IMT of the WC-HT group (0.77mm) was not significantly different from that of the NT group (0.63mm). The IMT of the HT group was significantly higher than the other two groups(0.gSmm, P<0.05). Geometric means of UAE in the WC-HT group was significantly greater than that of the NT group (NT 4.9,a g/rain.; WC-HT 29.6,u g/min. :P<0.01; HT 32.2,u g/min. :P<0.01). There were no differences in LVMI or UAE between the WC-HT group and the HT group. The LVH was increased but the IMT was within the normal range in the WC-HT group. Since not IMT but LVMI was higher in the WC-HT group, as the cardiovascular overload of BP, cardiac remodeling may have preceded vascular remodeling. Considering the target organ damage and increased positional BP increase in WC-HT, not only high BP but also BP variability might cause target organ damage. Key Words:
A J H - A P R I L 1 9 9 9 - V O L . 12, NO. 4, P A R T 2
ABSTRACTS
PHYSICAL ACTIVITY RELATED EARLY MORNING RISE IN BLOOD PRESSURE MAY DETERMINE CARDIOVASCULAR REMODELING IN HYPERTENSIVE SUBJECTS R. Ohki. K. Katie, S. Hoshide, Y. Umeda, T. Hashimoto, Y. Sate, S. Kuroki, O. Kanii, T. Ojima. U. lkeda, K. Shimada
Department of Cardiology and Department of Public health, Jichi Medical School, Toehigi.Japan The early morning rise in blood pressure (BP) may be related to increased cardiovascular events in the early morning. We investigated the relationships among early morning rise in BP, physical activity and cardiovascular remodeling (left ventricular hypertrophy: LVH, intima media thickness: IMT) using ambulatory BP monitoring, actigraphy and cardiac and carotid ultrasooography, respectively. We analyzed data obtained from 121 community-dwelling subjects, aged > 40 years (mean, 61 years), who underwent a cardiovascular examination. We accurately determined the time of arising from bed by actigraphy. We defined the early morning rise in BP by the difference between the night minimum systolic BP and the maximum systolic BP within 2 hours alter the time of arising from bed. We also calculated the total activity for 2 hours after arising as morning activity. Moreover, we investigated BP changes by various stress tests [cold presser (CP) test, handgrip (HG) test and active standing test]. In untreated hypertensive patients (n=27), a significantly positive relationship was observed between the early morning BP rise and morning activity(r=0.525, p>0.01), while in anrmotansive patients (n=45) and treated hypertensive patients (n=53), no such relationship was found. When untreated hypertensive patients were divided into sustained hypertensive patients (SHT, n=15) and white coat hypertensive patients (WCHT, n=12), both subgroups showed positive relationships between morning BP rise and morning activity (SHT: r=0.509, p<0.1; WCHT: r=0.608, p<0.05). In oormotensive patients and untreated hypertensive patients (n=73), a relationship was found between the morning BP rise and BP increase by a CP test (r=-0.315, p<0.01), while no relationships were detected in the morning BP rise with changes in systolic BP by the HG test or with systolic BP changes by the standing test. In oormotensive and untreated hypertensive patients (n~70), a positive relationship was found between the morning BP rise and LVMI(r=0.297, p<0.05), but not with IMT. in conclusion, the early morning rise in BP is partly related to physical activity alter arising from bed in hypertensive patients and may promote more LVH than vascular remodeling. Restriction of physical activity early in the morning may suppress target organ damage in hypertensive subjects.
Key Words: morning BP rise, physical activity, cardiovascular remodeling
white coat hypertension, target organ damage, blood pressure variability
A023
A024
REALATIONSHIP O F SLEEP STATUS (QUALITY) AND DIPPING STATUS BLOOD PRESSURE: COMMUNITYBASED IN KINUGAWEA STUDY S.Hoshide. K.Kario, Y.Umeda, T.Hashimoto, Y.Sato, R.Ohki, T.Ojima, O.Kunii, S.Kuroki, U.Ikeda, JE.Schwartz, TG Pickering, K.Shimada. Department of Cardiology, Jichi Medical School, Japan and Cornell University Medical College, SUNY-Stony Brook, New York. Actigraphy is widely used to estimate sleep activity or disturbance. In hypertensive patients, the presence of target-organ damage is more advanced in patients with diminished diurnal blood pressure (BP) variation ("non-dippers") than in those with normal diurnal BP variation ("dippers"). The objective of the present study is to investigate the relationship of sleep status assessed by actigraphy to dipping status of blood pressure. The data come from a crosssectional study of community based subjects aged > 40 years (mean, 61 years). Screening BE ambulatory BP and actigraphy were obtained for 121 subjects. We investigated total sleep time, total activity level during sleep time (total ACT) and sleep activity level excluding exogenous activity due to nocturnal physical behaviors recorded in their daily diaries (sleep ACT). In normotensive patients (n=58), there was no relationship between 24-hour BP level and either total ACT or sleep ACT. In sustained hypertensive patients (24hour mean BP value > 135/85 mmHg; n=68) there was no relationship between total ACT and 24-hr BP level. However, there were significant positive relationships of sleep ACT with 24-hr BP level (r=0.32, p<0.05) and with nocturnal BP reduction (r=0.35, 13<0.05). When hypertensive patients were divided into quartiles by sleep ACT, those with diminished nocturnal BP reduction were more frequent in the highest quartile than the lowest quartile (Q1:28%, Q2:41%, Q3:41%, Q4:63%; Q I vs Q4: P<0.05). In conclusion, sleep status (quality) may contribute to diminished nocturnal BP reduction in hypertensive patients.
ROLE OF ABPM IN CLINICAL DEVELOPMENT OF ANTIHYPERTENSIVE DRUGS. RJ Lipicky and N Steckbridge for the ABPM Steering Committee. Division of Curdle-Renal Drug Products, FDA, Rockville, MD. The Division of Card in-Renal Drug Products of the FDA has been working with sponsors of antihypertensive drug trials and Medifacts, Ltd., a clinical research company performing ABPM studies, to perform recta-analyses of ABPM records obtained in such studies. The aim of this research has been to define the role of ABPM in antihypertensive drug development. Among the principal questions being asked are: • What sample size is necessary to demonstrate a statistically significant antihypertensive effect in a trial with or without a placebo group? • What is best way of analyzing ABPM data to characterize the time course of a drug effect on blood pressure? Sponsors of placebo-controlled studies were invited to submit their raw data for incorporation into an integrated FDA database. Analysis begins with firing to each ABPM record a collection of models-polynomial, sum-of-cosines, piecewise-linear-with various numbers of terms. FiRing uses both linear and non-linear least squares techniques and yields error estimates for each fired parameter. Goodness of fit is assessed within a model family or across families by comparison of mean square errors (sum-of-square error divided by the number of free parameters minus one), parameter error estimates, and visual inspection. Methods were validated with simulated ABPM data. To date, 6208 24-hour ABPM records from 2929 subjects in 31 placebo-controlled studies have passed quality-control checks and been entered into the main database. Another 4725 ABPM records are undergoing quality control checks. Preliminary results show: • There is a negligible treatment effect produced by placebo. • The sample size needed for an ABPM study is less than for conventional cuff measurements. • Many more model terms are necessary to characterize the time course of a treatment effect than simply to demonstrate the existence of a treatment effect.
Key Words:
Key Words:
hypertensive patients, sleep status, nocturnal BP reduction
ABPM,placebo,drug development.
ASH
XIV
A021
A022
WHITE COAT HYPERTENSION AND TARGET ORGAN DAMAGE IN JAPANESE: COMMUNITY-BASED KINUGAWA STUDY Y.Sato. K.Kario, S.Hoshide, Y.Umeda, T.Hashimoto, R.Ohki, T.Ojima, O.Kunii, S.Kuroki, U.lkeda, K.Shimada Department of Cardiology, Jichi Medical School, Tochigi, Japan The degrees of target organ damage of white coat hypertension (WC-HT) have not yet been established. We investigated the relationship between blood pressure (BP) variability and target organ damage of WC-HT, using data obtained from 172 community dwelling subjects aged>40years (mean 61years) who underwent a cardiovascular examination. BP was measured in the sitting, supine and standing positions. Various stress tests (hand grip exercise; HG, cold presser test; CP) and 24-hour ambulatory BP monitoring were performed in all subjects. Target organ damage was assessed using the left ventricular mass index (LVMI) measured by echocardiography, infima-media thickness (IMT) measured by carotid ultrasonography and urinary albumin excretion (UAE). WC-HT was defined when mean BP in the siring position > 140/90mmHg and 24-hour mean BP value~135/85mmHg. The increase in systolic BP by standing in the WC-HT group (n=20) was greater than that in the normoteasion (biT) group (n=80) and of sustained hypertension (HT) group (n=72). There was no significant difference in the increase of systolic BP by other stress tests (HG and CP, respectively) among the three groups. The average LVMI of the WC-HT group was 13 lg/m-'. This was significantly higher than in the NT group (107g/m", P<0.01), but was not different from that of the HT group (135g/m~). The IMT of the WC-HT group (0.77mm) was not significantly different from that of the NT group (0.63mm). The IMT of the HT group was significantly higher than the other two groups(0.gSmm, P<0.05). Geometric means of UAE in the WC-HT group was significantly greater than that of the NT group (NT 4.9,a g/rain.; WC-HT 29.6,u g/min. :P<0.01; HT 32.2,u g/min. :P<0.01). There were no differences in LVMI or UAE between the WC-HT group and the HT group. The LVH was increased but the IMT was within the normal range in the WC-HT group. Since not IMT but LVMI was higher in the WC-HT group, as the cardiovascular overload of BP, cardiac remodeling may have preceded vascular remodeling. Considering the target organ damage and increased positional BP increase in WC-HT, not only high BP but also BP variability might cause target organ damage. Key Words:
A J H - A P R I L 1 9 9 9 - V O L . 12, NO. 4, P A R T 2
ABSTRACTS
PHYSICAL ACTIVITY RELATED EARLY MORNING RISE IN BLOOD PRESSURE MAY DETERMINE CARDIOVASCULAR REMODELING IN HYPERTENSIVE SUBJECTS R. Ohki. K. Katie, S. Hoshide, Y. Umeda, T. Hashimoto, Y. Sate, S. Kuroki, O. Kanii, T. Ojima. U. lkeda, K. Shimada
Department of Cardiology and Department of Public health, Jichi Medical School, Toehigi.Japan The early morning rise in blood pressure (BP) may be related to increased cardiovascular events in the early morning. We investigated the relationships among early morning rise in BP, physical activity and cardiovascular remodeling (left ventricular hypertrophy: LVH, intima media thickness: IMT) using ambulatory BP monitoring, actigraphy and cardiac and carotid ultrasooography, respectively. We analyzed data obtained from 121 community-dwelling subjects, aged > 40 years (mean, 61 years), who underwent a cardiovascular examination. We accurately determined the time of arising from bed by actigraphy. We defined the early morning rise in BP by the difference between the night minimum systolic BP and the maximum systolic BP within 2 hours alter the time of arising from bed. We also calculated the total activity for 2 hours after arising as morning activity. Moreover, we investigated BP changes by various stress tests [cold presser (CP) test, handgrip (HG) test and active standing test]. In untreated hypertensive patients (n=27), a significantly positive relationship was observed between the early morning BP rise and morning activity(r=0.525, p>0.01), while in anrmotansive patients (n=45) and treated hypertensive patients (n=53), no such relationship was found. When untreated hypertensive patients were divided into sustained hypertensive patients (SHT, n=15) and white coat hypertensive patients (WCHT, n=12), both subgroups showed positive relationships between morning BP rise and morning activity (SHT: r=0.509, p<0.1; WCHT: r=0.608, p<0.05). In oormotensive patients and untreated hypertensive patients (n=73), a relationship was found between the morning BP rise and BP increase by a CP test (r=-0.315, p<0.01), while no relationships were detected in the morning BP rise with changes in systolic BP by the HG test or with systolic BP changes by the standing test. In oormotensive and untreated hypertensive patients (n~70), a positive relationship was found between the morning BP rise and LVMI(r=0.297, p<0.05), but not with IMT. in conclusion, the early morning rise in BP is partly related to physical activity alter arising from bed in hypertensive patients and may promote more LVH than vascular remodeling. Restriction of physical activity early in the morning may suppress target organ damage in hypertensive subjects.
Key Words: morning BP rise, physical activity, cardiovascular remodeling
white coat hypertension, target organ damage, blood pressure variability
A023
A024
REALATIONSHIP O F SLEEP STATUS (QUALITY) AND DIPPING STATUS BLOOD PRESSURE: COMMUNITYBASED IN KINUGAWEA STUDY S.Hoshide. K.Kario, Y.Umeda, T.Hashimoto, Y.Sato, R.Ohki, T.Ojima, O.Kunii, S.Kuroki, U.Ikeda, JE.Schwartz, TG Pickering, K.Shimada. Department of Cardiology, Jichi Medical School, Japan and Cornell University Medical College, SUNY-Stony Brook, New York. Actigraphy is widely used to estimate sleep activity or disturbance. In hypertensive patients, the presence of target-organ damage is more advanced in patients with diminished diurnal blood pressure (BP) variation ("non-dippers") than in those with normal diurnal BP variation ("dippers"). The objective of the present study is to investigate the relationship of sleep status assessed by actigraphy to dipping status of blood pressure. The data come from a crosssectional study of community based subjects aged > 40 years (mean, 61 years). Screening BE ambulatory BP and actigraphy were obtained for 121 subjects. We investigated total sleep time, total activity level during sleep time (total ACT) and sleep activity level excluding exogenous activity due to nocturnal physical behaviors recorded in their daily diaries (sleep ACT). In normotensive patients (n=58), there was no relationship between 24-hour BP level and either total ACT or sleep ACT. In sustained hypertensive patients (24hour mean BP value > 135/85 mmHg; n=68) there was no relationship between total ACT and 24-hr BP level. However, there were significant positive relationships of sleep ACT with 24-hr BP level (r=0.32, p<0.05) and with nocturnal BP reduction (r=0.35, 13<0.05). When hypertensive patients were divided into quartiles by sleep ACT, those with diminished nocturnal BP reduction were more frequent in the highest quartile than the lowest quartile (Q1:28%, Q2:41%, Q3:41%, Q4:63%; Q I vs Q4: P<0.05). In conclusion, sleep status (quality) may contribute to diminished nocturnal BP reduction in hypertensive patients.
ROLE OF ABPM IN CLINICAL DEVELOPMENT OF ANTIHYPERTENSIVE DRUGS. RJ Lipicky and N Steckbridge for the ABPM Steering Committee. Division of Curdle-Renal Drug Products, FDA, Rockville, MD. The Division of Card in-Renal Drug Products of the FDA has been working with sponsors of antihypertensive drug trials and Medifacts, Ltd., a clinical research company performing ABPM studies, to perform recta-analyses of ABPM records obtained in such studies. The aim of this research has been to define the role of ABPM in antihypertensive drug development. Among the principal questions being asked are: • What sample size is necessary to demonstrate a statistically significant antihypertensive effect in a trial with or without a placebo group? • What is best way of analyzing ABPM data to characterize the time course of a drug effect on blood pressure? Sponsors of placebo-controlled studies were invited to submit their raw data for incorporation into an integrated FDA database. Analysis begins with firing to each ABPM record a collection of models-polynomial, sum-of-cosines, piecewise-linear-with various numbers of terms. FiRing uses both linear and non-linear least squares techniques and yields error estimates for each fired parameter. Goodness of fit is assessed within a model family or across families by comparison of mean square errors (sum-of-square error divided by the number of free parameters minus one), parameter error estimates, and visual inspection. Methods were validated with simulated ABPM data. To date, 6208 24-hour ABPM records from 2929 subjects in 31 placebo-controlled studies have passed quality-control checks and been entered into the main database. Another 4725 ABPM records are undergoing quality control checks. Preliminary results show: • There is a negligible treatment effect produced by placebo. • The sample size needed for an ABPM study is less than for conventional cuff measurements. • Many more model terms are necessary to characterize the time course of a treatment effect than simply to demonstrate the existence of a treatment effect.
Key Words:
Key Words:
hypertensive patients, sleep status, nocturnal BP reduction
ABPM,placebo,drug development.