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Administration time-dependent effects of low-dose aspirin on ambulatory blood pressure in grade 1 hypertensive patients
40A
POSTERS: Blood Pressure Measurement/Monitoring
24 hours. Sensitivity andspecificity of the HBI were similar for the values calculated from the original series and those obtained from shorter series up to data obtained at 2-hour intervals. Sensitivity, however, was reduced by 9%, and specificity by a very high 44%, when diagnosis was based on data sampled at 20 –30 min intervals for the first 24 hours. This prospective study demonstrates that sampling for just 24 hours is insufficient for a proper diagnosis of hypertension based on the highly reproducible tolerance-hyperbaric test. Moreover, sampling rate can be greatly reduced, for increased patient compliance, by expanding the monitoring span for at least 2 consecutive days. Results also corroborate that the proper estimation of any parameter derived from a BP series (such as the HBI) is markedly dependent on duration of sampling, but not on sampling rate. Key Words: Ambulatory Monitoring, Sampling Requirements, Hyperbaric Index
P-20 EFFECTS OF HYGIENIC-DIETARY RECOMMENDATIONS ON AMBULATORY BLOOD PRESSURE IN UNTREATED PATIENTS WITH GRADE 1 HYPERTENSION Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Maria J Fontao, Rita Soler, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, ETSI Telecomunicacion, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. International guidelines for the prevention and treatment of hypertension recommended hygienic-dietary intervention (including sodium restriction, weight loss, the DASH diet, limit alcohol intake, and regular aerobic exercise) as the starting non-pharmacological treatment of patients with grade-1 hypertension. A recent trial on a very small number of patients already under pharmacological antihypertensive treatment and who were required to eat once daily at the clinic, has shown the expected significant blood pressure (BP) reduction after 9 weeks of intervention with all those recommendations [Hypertension. 2002;40:612– 618]. Accordingly, we have evaluated the efficacy of hygienic-dietary recommendations (HDR) in unrestricted patients with untreated hypertension. We studied 218 patients with grade 1 essential hypertension (117 men), 47.3⫾14.0 years of age. BP was measured by ambulatory monitoring (ABPM) at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours at baseline and after 3 months of HDR without pharmacological treatment. A complete clinical evaluation was also performed in all patients following the standardized protocol at the Hypertension Unit, including blood and urine tests, both before and after HDR. Results indicate the lack of statistically significant changes after 3 months of intervention in weight (mean loss of 0.2 Kg), body mass index, or waist and hip perimeters (always P⬎0.208). The average of six conventional BP measurements taken at the clinic was unchanged after 3 months of HDR (average reduction of 2.2 and 1.3 mm Hg for systolic and diastolic BP, respectively; P⬎0.122). Serum values of glucose, creatinine, cholesterol and triglycerides also remained unchanged. With regard to ABPM, results indicate a small and not statistically significant BP reduction after 3 months of HDR (0.1 and 0.3 mm Hg in the 24-hour mean of systolic and diastolic BP, respectively; P⬎0.608). While the beneficial effects of HDR on BP under full compliance seem unquestionable, results from this trial indicate that in real-life conditions these non-pharmacological recommendations are very poorly followed by patients with mild hypertension, thus limiting the practical use of HDR for BP control in those patients. Key Words: Mild Hypertension, Hygienic-Dietary Intervention, BP Control
AJH–May 2004 –VOL. 17, NO. 5, PART 2
P-21 DIFFERENCES IN THE SEASONAL VARIATION OF PLASMA GLUCOSE BETWEEN DIPPER AND NONDIPPER HYPERTENSIVE PATIENTS Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Maria J Fontao, Rita Soler, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. Previous results have indicated that nondipper hypertensives (patients with ⬍10% decline in the nocturnal relative to the diurnal blood pressure (BP) mean) are more glucose intolerant than dippers. The lack of nocturnal decline in BP seems to be associated with an increase in cardiovascular events. Moreover, several investigators have reported a seasonal variation in the incidence of onset of acute myocardial infarction with a peak in winter. Accordingly, we have quantified and compared a possible yearly variation of plasma glucose in dipper and nondipper hypertensive patients. We studied 2443 patients with grade 1–2 hypertension (1193 men), 52.7⫾13.6 years of age. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. The circannual variation of plasma glucose was established for all patients as well as for subgroups of dippers (n⫽1216) and nondippers (n⫽1227) by multiple-component analysis. For the whole sample, plasma glucose is characterized by a significant seasonal variation (P⫽0.009) with a mean value of 105 mg/dl, double circannual amplitude (extent of predictable change along the year) of 8 mg/dL and time of peak value on March, with a secondary peak on September. A similar pattern of seasonal variation also characterizes dippers and nondippers analyzed separately. Throughout the year, nondippers showed significantly higher plasma glucose levels than did the dippers (difference in yearly mean of 7.5 mg/dL, P⬍0.001). The circannual variation in glucose here demonstrated is timely correlated with the reported yearly variation in coronary events, as well as with the seasonal variation of fibrinogen, an independent marker of myocardial infarction and stroke [Circulation. 2003;108:1101–1106]. The elevation of plasma glucose in nondippers as compared to dippers supports the tendency to nondipping among hypertensive patients with diabetes. Results could also support the association between nondipping BP and an increased risk of cardiovascular events, more prominent during the late winter months. Key Words: Glucose, Yearly Rhythm, Nondippers
P-22 ADMINISTRATION TIME-DEPENDENT EFFECTS OF LOW-DOSE ASPIRIN ON AMBULATORY BLOOD PRESSURE IN GRADE 1 HYPERTENSIVE PATIENTS Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Maria J Fontao, Rita Soler, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. Previous studies have shown statistically significant circadian rhythms in thromboxane and prostacyclin production, platelet aggregation, clotting and fibrinolytic inhibitors, and the inhibition of platelet aggregation produced by aspirin (ASA). ASA has also been shown to produce a dose and administration time-dependent inhibition of angiotensin II. Moreover, an administration time-dependent effect of low-dose ASA on blood pressure (BP) has been previously documented in normotensive volunteers, patients with mild hypertension, and pregnant women at high risk for preeclampsia [Hypertension. 2003;41:651– 6; 2003;41:1259 – 67]. We
41A
AJH–May 2004 –VOL. 17, NO. 5, PART 2
POSTERS: Blood Pressure Measurement/Monitoring
have extended these results by investigating the potential influence of ASA on BP in previously untreated hypertensive patients who received ASA at different times of the day according to their rest-activity cycle. We studied 287 untreated patients with grade 1 hypertension (110 men), 43.8⫾12.8 years of age, randomly divided in 3 groups: non-pharmacological hygienic-dietary recommendations (HDR); the same HDR and ASA (100 mg/day) on awakening; or HDR and ASA (100 mg/day) before bedtime. BP and heart rate (HR) were measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours at baseline and after 3 months of intervention. After 3 months of HDR, there was a small and nonsignificant reduction of BP (0.4 and 0.5 mm Hg for systolic and diastolic BP; P⬎0.244). BP was slightly elevated after ASA on awakening, mainly during nocturnal hours (increase of 2.3 and 1.4 mm Hg in the 24-hour mean of systolic and diastolic BP; P⬍0.029). A highly significant BP reduction was, however, observed in the patients who received ASA before bedtime (decrease of 6.6 and 4.4 mm Hg in systolic and diastolic BP, respectively; P⬍0.001). This prospective trial corroborates the highly significant administration time-dependent effect of low-dose ASA on BP in untreated patients with grade 1 hypertension. Results indicate that the timed administration of low-dose ASA with respect to the rest-activity cycle of each patient could provide a valuable approach not just for the secondary prevention of cardiovascular disease, but also in the added BP control of patients with mild hypertension and poor compliance with HDR.
times. ABPM for 48 consecutive hours reveals a statistically significant pressor response that remains significant even when the same patients are evaluated repeatedly every few months. This effect has marked implications in both research and clinical daily practice for a proper diagnosis of hypertension and evaluation of treatment efficacy by the use of ABPM.
Key Words: Aspirin, Chronopharmacology, Circadian
P-23 THE PRESSOR EFFECT DUE TO AMBULATORY BLOOD PRESSURE MONITORING PERSISTS IN HYPERTENSIVE PATIENTS REPEATEDLY EVALUATED THREE OR MORE TIMES Carlos Calvo, Ramon C Hermida, Diana E Ayala, Jose E Lopez, Maria J Dominguez, Manuel Covelo, Maria J Fontao, Rita Soler, Artemio Mojon, Jose R Fernandez. Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain; Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain. While a “white-coat” pressor effect on clinic blood pressure (BP) measurements has been defined and used for the improved evaluation of hypertensive patients, there is limited indication that ambulatory BP monitoring (ABPM) could also influence BP. Previous results have indicated that ABPM provides a pressor effect on patients using the device for the first time [JACC. 2002;40:710 –717]. Our objective was to test and quantify the extent and duration of this pressor effect due to ABPM in hypertensive patients repeatedly evaluated every few months. We studied 446 patients with grade 1–2 essential hypertension (226 men and 220 women), 52.0⫾13.4 years of age. BP and heart rate (HR) were measured by ABPM at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours, every 3 months and at least 3 times in each patient. Physical activity was simultaneously monitored every minute by wrist actigraphy. The total number of BP profiles obtained in this study was 1,518. Circadian parameters obtained for each of the two consecutive days of monitoring by population multiple-components analysis were compared with a paired nonparametric test. In hypertensive patients evaluated for the first time, results indicate a highly statistically significant (P⬍0.001) reduction during the second day of monitoring as compared to the first in the diurnal mean of systolic and diastolic BP, but not in HR or physical activity. This pressor effect increases BP on the average by a significant 6 and 4 mm Hg for systolic and diastolic BP for the first 4 hours of measurement, and it remains statistically significant for the first 7 hours of monitoring. This presor effect is slightly diminished in extent and duration for successive sessions of ABPM on the same patients, but still remains significant for the first 2 hours of measurement even in patients evaluated 4 or more
Key Words: ABPM Effect, Mild Hypertension, Treatment Efficacy
P-24 AMBULATORY BLOOD PRESSURE PATTERN IN PATIENTS WITH RESISTANT HYPERTENSION AS A FUNCTION OF THE CIRCADIAN TIME OF ANTIHYPERTENSIVE THERAPY Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. Hypertensive patients with high blood pressure (BP) after treatment with 3 or more antihypertensive drugs present elevated cardiovascular risk, and high prevalence of a non-dipper BP pattern (⬍10% decline in the nocturnal relative to the diurnal BP mean). Recent results indicate that non-dipping in treated patients may be related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. Accordingly, we studied the impact of the time of treatment on the circadian pattern of BP in patients with resistant hypertension. We studied 444 patients with resistant hypertension (228 men), 58.9⫾11.0 years of age. Among them, 210 patients received all their medication upon awakening. In the remaining 234 patients, one drug was prescribed to be taken before bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. In comparison with patients who received all their antihypertensive medication upon awakening, subjects with one drug before bedtime were characterized by a significant reduction in the 24-hour mean of systolic BP (4.9 mm Hg, P⬍0.001). This reduction was much more prominent during nocturnal resting hours (7.5 mm Hg, P⬍0.001). The reduction in nocturnal mean was also significant in diastolic BP (2.3 mm Hg, P⫽0.011). Patients receiving one drug before bedtime also showed a significant reduction in the 24-hour mean of pulse pressure (4.3 mm Hg, P⬍0.001). A very high 82.9% of the patients with all drugs on awakening were non-dippers. This percentage was significantly reduced to just 51.7% in patients who received one antihypertensive drug before bedtime (P⬍0.001). In patients with resistant hypertension, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient, as a function of the therapeutic coverage of the drugs and the baseline circadian BP profile of the patient. This chronopharmacology therapeutic approach allows to reduce the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk. Key Words: Resistant Hypertension, Chronotherapy, Non-Dipper
P-25 SIGNIFICANT INCREASE OF AMBULATORY PULSE PRESSURE IN SUBJECTS WITH WHITE COAT HYPERTENSION Ramon C Hermida, Carlos Calvo, Diana E Ayala, Manuel Covelo, Maria J Dominguez, Artemio Mojon, Jose R Fernandez, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. The clinical prognostic significance of white coat hypertension (WCH) is still controversial. Although recent longitudinal studies have provided
POSTERS: Blood Pressure Measurement/Monitoring
24 hours. Sensitivity andspecificity of the HBI were similar for the values calculated from the original series and those obtained from shorter series up to data obtained at 2-hour intervals. Sensitivity, however, was reduced by 9%, and specificity by a very high 44%, when diagnosis was based on data sampled at 20 –30 min intervals for the first 24 hours. This prospective study demonstrates that sampling for just 24 hours is insufficient for a proper diagnosis of hypertension based on the highly reproducible tolerance-hyperbaric test. Moreover, sampling rate can be greatly reduced, for increased patient compliance, by expanding the monitoring span for at least 2 consecutive days. Results also corroborate that the proper estimation of any parameter derived from a BP series (such as the HBI) is markedly dependent on duration of sampling, but not on sampling rate. Key Words: Ambulatory Monitoring, Sampling Requirements, Hyperbaric Index
P-20 EFFECTS OF HYGIENIC-DIETARY RECOMMENDATIONS ON AMBULATORY BLOOD PRESSURE IN UNTREATED PATIENTS WITH GRADE 1 HYPERTENSION Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Maria J Fontao, Rita Soler, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, ETSI Telecomunicacion, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. International guidelines for the prevention and treatment of hypertension recommended hygienic-dietary intervention (including sodium restriction, weight loss, the DASH diet, limit alcohol intake, and regular aerobic exercise) as the starting non-pharmacological treatment of patients with grade-1 hypertension. A recent trial on a very small number of patients already under pharmacological antihypertensive treatment and who were required to eat once daily at the clinic, has shown the expected significant blood pressure (BP) reduction after 9 weeks of intervention with all those recommendations [Hypertension. 2002;40:612– 618]. Accordingly, we have evaluated the efficacy of hygienic-dietary recommendations (HDR) in unrestricted patients with untreated hypertension. We studied 218 patients with grade 1 essential hypertension (117 men), 47.3⫾14.0 years of age. BP was measured by ambulatory monitoring (ABPM) at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours at baseline and after 3 months of HDR without pharmacological treatment. A complete clinical evaluation was also performed in all patients following the standardized protocol at the Hypertension Unit, including blood and urine tests, both before and after HDR. Results indicate the lack of statistically significant changes after 3 months of intervention in weight (mean loss of 0.2 Kg), body mass index, or waist and hip perimeters (always P⬎0.208). The average of six conventional BP measurements taken at the clinic was unchanged after 3 months of HDR (average reduction of 2.2 and 1.3 mm Hg for systolic and diastolic BP, respectively; P⬎0.122). Serum values of glucose, creatinine, cholesterol and triglycerides also remained unchanged. With regard to ABPM, results indicate a small and not statistically significant BP reduction after 3 months of HDR (0.1 and 0.3 mm Hg in the 24-hour mean of systolic and diastolic BP, respectively; P⬎0.608). While the beneficial effects of HDR on BP under full compliance seem unquestionable, results from this trial indicate that in real-life conditions these non-pharmacological recommendations are very poorly followed by patients with mild hypertension, thus limiting the practical use of HDR for BP control in those patients. Key Words: Mild Hypertension, Hygienic-Dietary Intervention, BP Control
AJH–May 2004 –VOL. 17, NO. 5, PART 2
P-21 DIFFERENCES IN THE SEASONAL VARIATION OF PLASMA GLUCOSE BETWEEN DIPPER AND NONDIPPER HYPERTENSIVE PATIENTS Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Maria J Fontao, Rita Soler, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. Previous results have indicated that nondipper hypertensives (patients with ⬍10% decline in the nocturnal relative to the diurnal blood pressure (BP) mean) are more glucose intolerant than dippers. The lack of nocturnal decline in BP seems to be associated with an increase in cardiovascular events. Moreover, several investigators have reported a seasonal variation in the incidence of onset of acute myocardial infarction with a peak in winter. Accordingly, we have quantified and compared a possible yearly variation of plasma glucose in dipper and nondipper hypertensive patients. We studied 2443 patients with grade 1–2 hypertension (1193 men), 52.7⫾13.6 years of age. BP was measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. The circannual variation of plasma glucose was established for all patients as well as for subgroups of dippers (n⫽1216) and nondippers (n⫽1227) by multiple-component analysis. For the whole sample, plasma glucose is characterized by a significant seasonal variation (P⫽0.009) with a mean value of 105 mg/dl, double circannual amplitude (extent of predictable change along the year) of 8 mg/dL and time of peak value on March, with a secondary peak on September. A similar pattern of seasonal variation also characterizes dippers and nondippers analyzed separately. Throughout the year, nondippers showed significantly higher plasma glucose levels than did the dippers (difference in yearly mean of 7.5 mg/dL, P⬍0.001). The circannual variation in glucose here demonstrated is timely correlated with the reported yearly variation in coronary events, as well as with the seasonal variation of fibrinogen, an independent marker of myocardial infarction and stroke [Circulation. 2003;108:1101–1106]. The elevation of plasma glucose in nondippers as compared to dippers supports the tendency to nondipping among hypertensive patients with diabetes. Results could also support the association between nondipping BP and an increased risk of cardiovascular events, more prominent during the late winter months. Key Words: Glucose, Yearly Rhythm, Nondippers
P-22 ADMINISTRATION TIME-DEPENDENT EFFECTS OF LOW-DOSE ASPIRIN ON AMBULATORY BLOOD PRESSURE IN GRADE 1 HYPERTENSIVE PATIENTS Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Maria J Fontao, Rita Soler, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. Previous studies have shown statistically significant circadian rhythms in thromboxane and prostacyclin production, platelet aggregation, clotting and fibrinolytic inhibitors, and the inhibition of platelet aggregation produced by aspirin (ASA). ASA has also been shown to produce a dose and administration time-dependent inhibition of angiotensin II. Moreover, an administration time-dependent effect of low-dose ASA on blood pressure (BP) has been previously documented in normotensive volunteers, patients with mild hypertension, and pregnant women at high risk for preeclampsia [Hypertension. 2003;41:651– 6; 2003;41:1259 – 67]. We
41A
AJH–May 2004 –VOL. 17, NO. 5, PART 2
POSTERS: Blood Pressure Measurement/Monitoring
have extended these results by investigating the potential influence of ASA on BP in previously untreated hypertensive patients who received ASA at different times of the day according to their rest-activity cycle. We studied 287 untreated patients with grade 1 hypertension (110 men), 43.8⫾12.8 years of age, randomly divided in 3 groups: non-pharmacological hygienic-dietary recommendations (HDR); the same HDR and ASA (100 mg/day) on awakening; or HDR and ASA (100 mg/day) before bedtime. BP and heart rate (HR) were measured by ambulatory monitoring at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours at baseline and after 3 months of intervention. After 3 months of HDR, there was a small and nonsignificant reduction of BP (0.4 and 0.5 mm Hg for systolic and diastolic BP; P⬎0.244). BP was slightly elevated after ASA on awakening, mainly during nocturnal hours (increase of 2.3 and 1.4 mm Hg in the 24-hour mean of systolic and diastolic BP; P⬍0.029). A highly significant BP reduction was, however, observed in the patients who received ASA before bedtime (decrease of 6.6 and 4.4 mm Hg in systolic and diastolic BP, respectively; P⬍0.001). This prospective trial corroborates the highly significant administration time-dependent effect of low-dose ASA on BP in untreated patients with grade 1 hypertension. Results indicate that the timed administration of low-dose ASA with respect to the rest-activity cycle of each patient could provide a valuable approach not just for the secondary prevention of cardiovascular disease, but also in the added BP control of patients with mild hypertension and poor compliance with HDR.
times. ABPM for 48 consecutive hours reveals a statistically significant pressor response that remains significant even when the same patients are evaluated repeatedly every few months. This effect has marked implications in both research and clinical daily practice for a proper diagnosis of hypertension and evaluation of treatment efficacy by the use of ABPM.
Key Words: Aspirin, Chronopharmacology, Circadian
P-23 THE PRESSOR EFFECT DUE TO AMBULATORY BLOOD PRESSURE MONITORING PERSISTS IN HYPERTENSIVE PATIENTS REPEATEDLY EVALUATED THREE OR MORE TIMES Carlos Calvo, Ramon C Hermida, Diana E Ayala, Jose E Lopez, Maria J Dominguez, Manuel Covelo, Maria J Fontao, Rita Soler, Artemio Mojon, Jose R Fernandez. Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain; Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain. While a “white-coat” pressor effect on clinic blood pressure (BP) measurements has been defined and used for the improved evaluation of hypertensive patients, there is limited indication that ambulatory BP monitoring (ABPM) could also influence BP. Previous results have indicated that ABPM provides a pressor effect on patients using the device for the first time [JACC. 2002;40:710 –717]. Our objective was to test and quantify the extent and duration of this pressor effect due to ABPM in hypertensive patients repeatedly evaluated every few months. We studied 446 patients with grade 1–2 essential hypertension (226 men and 220 women), 52.0⫾13.4 years of age. BP and heart rate (HR) were measured by ABPM at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours, every 3 months and at least 3 times in each patient. Physical activity was simultaneously monitored every minute by wrist actigraphy. The total number of BP profiles obtained in this study was 1,518. Circadian parameters obtained for each of the two consecutive days of monitoring by population multiple-components analysis were compared with a paired nonparametric test. In hypertensive patients evaluated for the first time, results indicate a highly statistically significant (P⬍0.001) reduction during the second day of monitoring as compared to the first in the diurnal mean of systolic and diastolic BP, but not in HR or physical activity. This pressor effect increases BP on the average by a significant 6 and 4 mm Hg for systolic and diastolic BP for the first 4 hours of measurement, and it remains statistically significant for the first 7 hours of monitoring. This presor effect is slightly diminished in extent and duration for successive sessions of ABPM on the same patients, but still remains significant for the first 2 hours of measurement even in patients evaluated 4 or more
Key Words: ABPM Effect, Mild Hypertension, Treatment Efficacy
P-24 AMBULATORY BLOOD PRESSURE PATTERN IN PATIENTS WITH RESISTANT HYPERTENSION AS A FUNCTION OF THE CIRCADIAN TIME OF ANTIHYPERTENSIVE THERAPY Ramon C Hermida, Diana E Ayala, Carlos Calvo, Maria J Dominguez, Manuel Covelo, Artemio Mojon, Jose R Fernandez, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. Hypertensive patients with high blood pressure (BP) after treatment with 3 or more antihypertensive drugs present elevated cardiovascular risk, and high prevalence of a non-dipper BP pattern (⬍10% decline in the nocturnal relative to the diurnal BP mean). Recent results indicate that non-dipping in treated patients may be related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. Accordingly, we studied the impact of the time of treatment on the circadian pattern of BP in patients with resistant hypertension. We studied 444 patients with resistant hypertension (228 men), 58.9⫾11.0 years of age. Among them, 210 patients received all their medication upon awakening. In the remaining 234 patients, one drug was prescribed to be taken before bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. In comparison with patients who received all their antihypertensive medication upon awakening, subjects with one drug before bedtime were characterized by a significant reduction in the 24-hour mean of systolic BP (4.9 mm Hg, P⬍0.001). This reduction was much more prominent during nocturnal resting hours (7.5 mm Hg, P⬍0.001). The reduction in nocturnal mean was also significant in diastolic BP (2.3 mm Hg, P⫽0.011). Patients receiving one drug before bedtime also showed a significant reduction in the 24-hour mean of pulse pressure (4.3 mm Hg, P⬍0.001). A very high 82.9% of the patients with all drugs on awakening were non-dippers. This percentage was significantly reduced to just 51.7% in patients who received one antihypertensive drug before bedtime (P⬍0.001). In patients with resistant hypertension, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient, as a function of the therapeutic coverage of the drugs and the baseline circadian BP profile of the patient. This chronopharmacology therapeutic approach allows to reduce the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk. Key Words: Resistant Hypertension, Chronotherapy, Non-Dipper
P-25 SIGNIFICANT INCREASE OF AMBULATORY PULSE PRESSURE IN SUBJECTS WITH WHITE COAT HYPERTENSION Ramon C Hermida, Carlos Calvo, Diana E Ayala, Manuel Covelo, Maria J Dominguez, Artemio Mojon, Jose R Fernandez, Jose E Lopez. Bioengineering and Chronobiology Labs., University of Vigo, Vigo, Spain; Hypertension and Vascular Risk Unit, Hospital Clinico Universitario, Santiago de Compostela, Spain. The clinical prognostic significance of white coat hypertension (WCH) is still controversial. Although recent longitudinal studies have provided