Biomedical subjects

Diana E Ayala

Publications and source records attributed to Diana E Ayala.

At least 19 recordsLinked to original sources

PubMed2006

[Chronotherapy with torasemide in hypertensive patients: increased efficacy and therapeutic coverage with bedtime administration].

BACKGROUND AND OBJECTIVE: Torasemide is a high ceiling loop diuretic frequently used for treatment of heart failure, renal failure and hypertension, according to results mainly based on clinic blood pressure measurements, without proper evaluation of the 24-hour efficacy of the drug. Accordingly, we investigated the time-dependent antihypertensive efficacy of torasemide in hypertensive patients. PATIENTS AND METHOD: We studied 58 patients with grade 1-2 essential hypertension (25 men and 33 women), 48.7 (11.9) years of age, randomly assigned to receive torasemide (5 mg/day) either upon awakening or at bedtime. Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 6 weeks of therapy. RESULTS: Efficacy of torasemide was significantly higher with bedtime dosing (11.2 and 8.0 mmHg reduction in the 24-hour mean of systolic and diastolic blood pressure, respectively) as compared to the administration of the drug on awakening (6.2 and 3.7 mmHg reduction in systolic and diastolic blood pressure). The percentage of patients with controlled ambulatory blood pressure after treatment was also higher after bedtime treatment (54% versus 27%). The time-response curves indicate a full 24-hour therapeutic duration only when torasemide was administered before bedtime. With regard to the safety profile, 2 patients presented secondary effects (abdominal pain, diarrhea) in morning dose, and 4 patients taking the drug at bedtime reported nicturia. CONCLUSIONS: A dose of 5 mg/day torasemide is effective for blood pressure reduction after bedtime administration. The differences in efficacy and therapeutic duration as a function of the circadian time of treatment with torasemide here documented should be taken into account when prescribing this loop diuretic for treatment of patients with essential hypertension.

Blood Pressure↗

PubMed2006

[Effects of time-dependent administration of antihypertensive treatment in patients with resistant hypertension].

BACKGROUND AND OBJECTIVE: Patients with resistant hypertension represent an important clinical problem due to their poor control, high prevalence of target organ damage, and the associated increase in cardiovascular risk. Therapeutic strategies in resistant hypertension currently include a sequential change of drugs or the synergic combination of new drugs. Most patients, however, receive all their drugs in a single morning dose. We have evaluated the impact on the circadian pattern of blood pressure (BP) of modifying the time of treatment without increasing the number of prescribed drugs. PATIENTS AND METHOD: We studied 123 patients with resistant hypertension (73 men and 50 women), 59.9 (11.9) years of age, who were receiving 3 antihypertensive drugs in a single morning dose. Patients were randomly assigned to one of two groups according to the modification in their treatment strategy: a) Changing one of the drugs, but keeping all 3 in the morning. b) The same approach but prescribing one of the drugs to be taken at bedtime. Blood pressure was measured at 20-minute intervals from 07:00 to 23:00 hours and at 30-minute intervals at night for 48 consecutive hours at baseline and after 3 months of treatment with the new therapeutic scheme. RESULTS: There was a small and non-significant BP reduction when all drugs were still taken on awakening (p > 0.374). On baseline, only 22% of the patients in this group were dippers, and this percentage was further reduced to 15% after 3 months of therapy with all drugs on awakening. The blood pressure reduction was statistically significant (8.6 and 5.9 mmHg for systolic and diastolic blood pressure; p < 0.001) with one drug at bedtime. This effect was markedly larger in the nocturnal mean of blood pressure. Thus, while only 13% of the patients in this group were dippers at baseline, 53% were already dippers after 3 months of therapy. CONCLUSIONS: Results from this prospective trial indicate that, in patients with resistant hypertension, time of treatment may be more important for patient control and for the proper modeling of the circadian blood pressure pattern than just changing the drug combination.

Aged↗

PubMed2005

Aspirin administered at bedtime, but not on awakening, has an effect on ambulatory blood pressure in hypertensive patients.

OBJECTIVES: The purpose of this research was to investigate in untreated hypertensive patients the effects on ambulatory blood pressure (BP) of aspirin (ASA) administered at different times of the day. BACKGROUND: Previous studies have shown that ASA produces an administration time-dependent inhibition of angiotensin II. Low-dose ASA has also been shown to reduce BP when administered before bedtime, as opposed to upon awakening, in normotensive and hypertensive volunteers, and in pregnant women at high risk for preeclampsia. METHODS: We studied 328 untreated patients with grade 1 hypertension, 44.0 +/- 12.6 years of age, randomly divided into three groups: nonpharmacological hygienic-dietary recommendations, the same recommendations and ASA (100 mg/day) on awakening, or the same recommendations and ASA before bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive h before and after 3 months of intervention. RESULTS: After three months of nonpharmacological intervention, there was a small and nonsignificant reduction of BP (<0.2 mm Hg; p = 0.648). Blood pressure was slightly elevated after aspirin on awakening (2.6/1.6 mm Hg in the 24-h mean of systolic/diastolic BP; p = 0.002). A significant BP reduction, however, was observed in the patients who received aspirin before bedtime (6.8/4.6 mm Hg in systolic/diastolic BP; p < 0.001). CONCLUSIONS: This prospective trial documents a significant administration time-dependent effect of low-dose ASA on BP in untreated hypertensive patients. The timed administration of low-dose ASA could provide a valuable approach, beyond the secondary prevention of cardiovascular disease, in the added BP control of patients with mild essential hypertension.

Adult↗

PubMed2005

Decrease in urinary albumin excretion associated with the normalization of nocturnal blood pressure in hypertensive subjects.

Previous results have indicated that valsartan administration at bedtime as opposed to on wakening improves the diurnal/nocturnal ratio of blood pressure without loss in efficacy and therapeutic coverage. We hypothesized that increasing this ratio could reduce microalbuminuria. We conducted a prospective, randomized, open-label, blinded endpoint trial on 200 previously untreated nonproteinuric patients with grade 1 to 2 essential hypertension, assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The significant blood pressure reduction after 3 months of therapy was similar for both treatment times. The diurnal/nocturnal blood pressure ratio was unchanged after valsartan on awakening, but significantly increased from 7.5 to 12.2 (P<0.001) when valsartan was administered at bedtime. Urinary albumin excretion was significantly reduced by 41% after bedtime treatment. This reduction was independent of the 24-hour blood pressure decrease but highly correlated with the decrease in nocturnal blood pressure and mainly with the increase in diurnal/nocturnal ratio (P<0.001). Bedtime valsartan administration improves the diurnal/nocturnal blood pressure ratio to a more dipper profile. This normalization of the circadian blood pressure pattern is associated with a significant decrease in urinary albumin excretion and plasma fibrinogen, and could thus reduce the increased cardiovascular risk in nondipper hypertensive patients.

Adult↗

PubMed2005

Differing administration time-dependent effects of aspirin on blood pressure in dipper and non-dipper hypertensives.

Aspirin is a potent antioxidative agent that reduces vascular production of superoxide, prevents angiotensin II-induced hypertension, and induces NO release. Low-dose aspirin administered at bedtime, but not on awakening, has also been shown to reduce blood pressure, possibly enhancing the nocturnal trough in NO production. Because endothelium-dependent vasodilation is blunted through a decrease in NO release in non-dipper compared with dipper patients, we compared the administration time-dependent influence of aspirin on ambulatory blood pressure in dipper and non-dipper hypertensive subjects. We studied 257 patients with mild hypertension (98 men and 159 women), 44.6+/-12.5 years of age, randomly assigned to receive 100 mg per day of aspirin either on awakening or at bedtime. Ambulatory blood pressure was measured for 48 hours at baseline and after 3 months of intervention. Blood pressure was slightly elevated after aspirin on awakening (increase of 1.5/1.0 mm Hg in the 24-hour mean of systolic/diastolic blood pressure; P<0.028). A highly significant blood pressure reduction was observed in patients who received aspirin at bedtime (decrease of 7.2/4.9 mm Hg in systolic/diastolic blood pressure; P<0.001). The reduction in nocturnal blood pressure mean was double in non-dippers (11.0/7.1 mm Hg) compared with dippers (5.5/3.3 mm Hg; P<0.001). This prospective trial corroborates the significant administration time-dependent effect of low-dose aspirin on blood pressure, mainly in non-dipper hypertensive patients. The timed administration of low-dose aspirin could thus provide a valuable approach, beyond prevention of cardiovascular disease, in the blood pressure control of patients with mild hypertension.

Adult↗

PubMed2005

Effects of time of day of treatment on ambulatory blood pressure pattern of patients with resistant hypertension.

Patients with resistant hypertension present high prevalence of a non-dipper blood pressure pattern. Recent results indicate that non-dipping is related partly to the absence of 24-hour therapeutic coverage in patients treated with single morning doses. Accordingly, we investigated the impact of treatment time on the blood pressure pattern in 700 patients with resistant hypertension on the basis of clinic measurements who were studied by 48-hour ambulatory monitoring. Among them, 299 patients received all their medication on awakening, and 401 were taking > or =1 antihypertensive drug at bedtime. The percentage of patients with controlled ambulatory blood pressure was double in patients taking 1 drug at bedtime (P=0.008). Among the 578 patients with true resistant hypertension, subjects receiving 1 drug at bedtime showed a significant reduction in the 24-hour mean of systolic and diastolic blood pressure (3.1 and 1.6 mm Hg, respectively; P<0.011). This reduction was much more prominent during nighttime (5.1 and 3.0 mm Hg; P<0.001). Accordingly, the diurnal/nocturnal blood pressure ratio was significantly increased by 2.7 and the prevalence on non-dipping reduced (56.9 versus 81.9%; P<0.001) in patients taking 1 drug at bedtime. Compared with patients receiving all drugs on awakening, subjects with 1 drug at bedtime also showed significant reductions in the average values of glucose, cholesterol, fibrinogen, and urinary albumin excretion (P<0.011). In patients with resistant hypertension, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient to improve control and to avoid the non-dipper pattern associated to higher cardiovascular risk.

Activity Cycles↗

PubMed2005

Administration time-dependent effects of valsartan on ambulatory blood pressure in elderly hypertensive subjects.

Previous results have indicated that valsartan administration at bed-time, as opposed to upon wakening, improves the diurnal/nocturnal ratio of blood pressure (BP) toward a normal dipping pattern, without loss of 24 h efficacy. This ratio is characterized by a progressive decrease with aging. Accordingly, we investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin blocking agent, in elderly hypertensive patients. We studied 100 elderly patients with grade 1-2 essential hypertension (34 men and 66 women), 68.2+/-4.9 years of age, randomly assigned to receive valsartan (160 mg/d) as a monotherapy either upon awakening or at bed-time. BP was measured for 48 h by ambulatory monitoring, at 20 min intervals between 07:00 to 23:00 h and at 30 min intervals at night, before and after 3 months of therapy. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately determine the duration of sleep and wake spans to enable the accurate calculation of the diurnal and nocturnal means of BP for each subject. There was a highly significant BP reduction after 3 months of valsartan treatment (p < 0.001). The reduction was slightly larger with bed-time dosing (15.3 and 9.2 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively) than with morning dosing (12.3 and 6.3 mm Hg reduction in the 24 h mean of systolic and diastolic BP, respectively). The diurnal/nocturnal ratio, measured as the nocturnal decline of BP relative to the diurnal mean, was unchanged in the group ingesting valsartan upon awakening (-1.0 and -0.3 for systolic and diastolic BP; p > 0.195). This ratio was significantly increased (6.6 and 5.4 for systolic and diastolic BP; p < 0.001) when valsartan was ingested at bed-time. The reduction of the nocturnal mean was doubled in the group ingesting valsartan at bed-time, as compared to the group ingesting it in the morning (p < 0.001). In elderly hypertensive patients, mainly characterized by a diminished nocturnal decline in BP, bed-time valsartan dosing is better than morning dosing since it improves efficacy during the nighttime sleep span, with the potential reduction in cardiovascular risk that has been associated with a normalized diurnal/nocturnal BP ratio.

Antihypertensive Agents↗

PubMed2005

Circadian blood pressure variability in normotensive pregnant women as a function of parity, maternal age, and stage of gestation.

Studies based on conventional office blood pressure (BP) measurements concluded that both maternal age and parity have significant effects on BP during pregnancy. Previous results have also indicated predictable trends of BP variability with gestational age. Accordingly, we have evaluated possible differences in the circadian pattern of ambulatory BP as a function of parity, maternal age, and stage of gestation in normotensive women who were systematically studied by ambulatory BP monitoring during their pregnancies. We analyzed 1408 BP profiles obtained from 126 nulliparous and 109 multiparous pregnant women sampled for 48 consecutive h every 4 weeks from the first obstetric visit (usually within the first trimester of pregnancy) until delivery. Data were divided for comparative analysis according to parity (nulliparous versus multiparous), age (< or = 25, 26-30, 31-35, and > or = 36 yrs), and trimester of gestation. Circadian BP parameters established by population multiple-components analysis were compared between groups using a nonparametric test. A highly statistically significant circadian pattern described by a model that includes components with periods of 24 and 12h is demonstrated for systolic and diastolic BP for all groups of pregnant women in all trimesters (always p < 0.001). There was no significant difference in the 24h mean among groups divided by parity at any age or stage of pregnancy. A trend of increasing BP with age was found for diastolic but not for systolic BP. Although statistically significant, differences in the 24h mean of diastolic BP among groups divided by age were always less than 2 mm Hg. Data obtained from systematic ambulatory monitoring in normotensive pregnant women indicate the lack of differences in BP according to parity. The small, although significant, increase in diastolic BP with age may have scarce influence in the proper identification of women with gestational hypertension. Reference thresholds for BP to be used in the early identification of hypertensive complications in pregnancy could thus be developed as a function of the rest-activity cycle and gestational age only, and independently of parity or maternal age.

Adult↗

PubMed2005

Reference thresholds for 24-h, diurnal, and nocturnal ambulatory blood pressure mean values in pregnancy.

OBJECTIVES: Several studies have indicated that the use of the 24-h mean of blood pressure, mainly using reference thresholds derived from the general non-pregnancy practice, does not provide a proper test for diagnosis of hypertension in pregnancy. This prospective study examines previously derived reference thresholds for the 24-h, diurnal, and nocturnal mean of blood pressure as potential screening tests for the diagnosis of hypertension in pregnancy. METHODS: We studied 235 normotensive and 168 hypertensive pregnant women, who provided 2430 blood pressure series sampled every 20 min during the day and every 30 min at night for 48 consecutive hours once every 4 weeks from the first obstetric visit until delivery. Sensitivity and specificity for each parameter are based on the comparison of the distributions of mean blood pressure values with reference thresholds previously established from an independent population of 113 pregnant women also evaluated monthly by 48-h ambulatory monitoring throughout gestation. RESULTS: Sensitivity of mean blood pressure values, above 70% at all stages of pregnancy, was higher than that obtained from clinic blood pressure measurements, which were always below 14%. The poorest results were consistently obtained for the nocturnal mean. Sensitivity was similar for the 24-h and the diurnal mean, with values ranging from 71% for diastolic blood pressure in the first trimester of pregnancy to 93% for systolic blood pressure in the third trimester. Systolic blood pressure consistently provided better sensitivity than diastolic blood pressure at all gestational ages. CONCLUSIONS: This prospective study on women systematically studied by 48-h ambulatory monitoring throughout gestation indicates that mean ambulatory blood pressure values provide higher sensitivity and specificity than conventional measurements. Moreover, results indicate that diagnosis of hypertension in pregnancy based on ambulatory blood pressure should be established from thresholds much lower than those currently used in clinical practice.

Adult↗

PubMed2005

Treatment of non-dipper hypertension with bedtime administration of valsartan.

BACKGROUND: Previous results have indicated that valsartan administration at bedtime, as opposed to upon wakening, may improve the diurnal: nocturnal ratio of blood pressure without loss in 24-h coverage and efficacy. OBJECTIVES: To investigate the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients. METHODS: We studied 148 non-dipper patients with grade 1-2 essential hypertension, aged 53.0+/-12.6 years, who were randomly assigned to receive valsartan (160 mg/day) as a monotherapy either on awakening or at bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per subject basis. RESULTS: The significant blood pressure reduction after 3 months of valsartan (P<0.001) was similar for both treatment times (13.1 and 8.5 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 14.7 and 10.3 mmHg with bedtime administration; P>0.126 for treatment-time effect). The diurnal: nocturnal ratio of blood pressure was significantly increased only when valsartan was administered before bedtime, which resulted in 75% of the patients in this group reverting to dippers, a significant increase in the percentage of patients with controlled blood pressure over 24 h, and a reduction in urinary albumin excretion. CONCLUSIONS: In non-dipper hypertensive patients, dosing time with valsartan should be chosen at bedtime, for improved efficacy during the nocturnal resting hours, as well as the potential associated reduction in cardiovascular risk.

Adult↗

PubMed2005

Administration-time-dependent effects of antihypertensive treatment on the circadian pattern of blood pressure.

PURPOSE OF REVIEW: Many studies show that the extent of the nocturnal blood-pressure decline is deterministic of cardiovascular injury and risk. Accordingly, there is growing interest in how to tailor the treatment of hypertensive patients according to their circadian blood-pressure pattern. RECENT FINDINGS: Differences in efficacy depending on the time of day of drug administration lead to differences in effects of antihypertensive drugs on the nocturnal decline relative to the diurnal mean of blood pressure. Thus, bedtime dosing with nifedipine gastrointestinal therapeutic system (GITS) is more effective than morning dosing, while also reducing significantly secondary effects. Bedtime administration of trandolapril results in a safe and effective means of controlling morning blood pressure without inducing excessive reduction nocturnally. The dose-response curve, therapeutic coverage, and efficacy of doxazosin GITS are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime as opposed to upon wakening results in improved day/night blood-pressure ratio, a significant increase in the percentage of controlled patients after treatment, and a significant reduction in urinary albumin excretion. SUMMARY: Nocturnal hypertension increases one's risk of cardiovascular and cerebrovascular events, nephrosclerosis, and progression to end-stage kidney failure in renal patients. Normalization of the circadian blood-pressure pattern is considered an important clinical goal of pharmacotherapy because it may slow the advance of renal injury. Chronotherapy provides a means of individualizing treatment of hypertension according to the circadian blood-pressure profile of each patient, and constitutes a new option in optimizing blood-pressure control and reducing risk.

Adrenergic alpha-Antagonists↗

PubMed2004

Differences in circadian pattern of ambulatory pulse pressure between healthy and complicated pregnancies.

With the use of ambulatory monitoring, a circadian blood pressure pattern has been shown to characterize normotensive as well as hypertensive pregnant women. However, the potential differences between healthy and complicated pregnancies in pulse pressure, an independent marker of cardiovascular risk in the general population, have not yet been investigated. We analyzed 2523 blood pressure series sampled for 48 hours once every 4 weeks from the first obstetric visit until delivery in 245 women with uncomplicated pregnancies, 140 with gestational hypertension, and 49 who developed preeclampsia. Compared with uncomplicated pregnancies, a statistically significant elevation in the 24-hour mean of pulse pressure is found in complicated pregnancies in all trimesters (P<0.001). Results further indicate similar 24-hour mean of pulse pressure between gestational hypertension and preeclampsia in the first trimester of pregnancy (P=0.158). The increase in pulse pressure among women who developed preeclampsia compared with women with gestational hypertension, although small, was statistically significant in the second trimester (1.4 mm Hg; P=0.010) and, to a larger extent, in the third trimester of pregnancy (1.8 mm Hg; P<0.001). The differences in pulse pressure between healthy and complicated pregnancies, observed already in the first trimester of gestation, are found when systolic and diastolic blood pressure for women with a later diagnosis of gestational hypertension or preeclampsia are within the accepted range of normotension. Moreover, ambulatory pulse pressure provides higher sensitivity than clinic measurements for the diagnosis of hypertension in pregnancy.

Adult↗

PubMed2004

[Prospective evaluation of the hyperbaric-tolerance test for the diagnosis of gestational hypertension and preeclampsia].

BACKGROUND AND OBJECTIVE: Recent studies have tried to overcome poor results from isolated blood pressure values in detecting hypertension in pregnancy by relying on ambulatory monitoring. Low sensitivity of the 24-hour mean has led many authors to conclude that ambulatory monitoring is not a valid approach in pregnancy. Against this background, we have evaluated prospectively the sensitivity and specificity in the diagnosis of gestational hypertension of the tolerance-hyperbaric test. This is a combined approach consisting of establishing tolerance intervals for the circadian variability of blood pressure as a function of gestational age, and then computing the hyperbaric index (area of blood pressure excess above the upper limit of the interval) by comparison of any patient's blood pressure profile with those limits. PATIENTS AND METHOD: We studied 328 women who provided a 2014 blood pressure series. They were sampled for 48 hours once every 4 weeks from the first obstetric visit (mostly within the first trimester of gestation) until delivery. The hyperbaric index of each blood pressure series was calculated by taking into account the reference circadian tolerance limits established from a 497 series previously sampled from an independent reference group of 189 normotensive pregnant women. RESULTS: Sensitivity of the tolerance-hyperbaric test was 91% for women sampled during the first trimester of gestation, and increased up to 99% in the third trimester. Specificity was above 99% in all trimesters. Positive and negative predictive values were above 96% in all trimesters. Moreover, the hyperbaric index provided an early identification of subsequent gestational hypertension and preeclampsia, on the average of 23 weeks prior to the clinical confirmation of the disease. CONCLUSIONS: The tolerance-hyperbaric test represents a reproducible, stable, noninvasive, and high sensitivity test for the very early identification of subsequent gestational hypertension and preeclampsia, which can also be used as a guide for establishing prophylactic or therapeutic interventions.

Adult↗

PubMed2004

Circadian time-qualified tolerance intervals for ambulatory blood pressure monitoring in the diagnosis of hypertension.

The large-amplitude circadian pattern in blood pressure of healthy subjects of both genders suggests that the constant threshold currently used to diagnose hypertension should be replaced by a time-specified reference limit reflecting the mostly predictable blood pressure variability during the 24 h. Accordingly, we derived circadian time-specified reference standards for blood pressure as a function of gender. We studied 743 normotensive Caucasian volunteers (400 men and 343 women), 45.7 +/- 16.5 (mean +/- SD) years of age. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours. Data from each blood pressure series were synchronized according to the rest-activity cycle of each individual in order to avoid differences among subjects in actual times of daily activity. Data were then used to compute 90% circadian tolerance intervals for each gender separately. The method, derived on the basis of bootstrap techniques, does not need to assume normality or symmetry in the data and, therefore, it is highly appropriate to describe the circadian pattern of blood pressure variability. Results reflect expected changes in the tolerance limits as a function of gender and circadian sampling time, as well as upper blood pressure limits below the thresholds currently used for diagnosing hypertension, especially for women. The use of these time-dependent tolerance limits for the computation of a hyperbaric index as a measure of blood pressure excess has already been shown to provide a reproducible and high-sensitivity test for the diagnosis of hypertension, which can also be used to evaluate treatment efficacy.

Adult↗

PubMed2004

Administration-time-dependent effects of doxazosin GITS on ambulatory blood pressure of hypertensive subjects.

Previous studies have shown that a single nighttime dose of standard doxazosin, an alpha-adrenergic antagonist, reduces blood pressure (BP) throughout the 24 h. We investigated the administration-time-dependent effects of the new doxazosin gastrointestinal therapeutic system (GITS) formulation. We studied 91 subjects (49 men and 42 women), 56.7+/-11.2 (mean+/-SD) yrs of age with grade 1-2 essential hypertension; 39 patients had been previously untreated, and the remaining 52 had been treated with two antihypertensive medications with inadequate control of their hypertension. The subjects of the two groups, the monotherapy and polytherapy groups, respectively, were randomly assigned to receive the single daily dose of doxazosin GITS (4 mg/day) either upon awakening or at bedtime. BP was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours just before and after 3 months of treatment. After 3 months of doxazosin GITS therapy upon awakening, there was a small and nonstatistically significant reduction in BP (1.8 and 3.2mm Hg in the 24 h mean of systolic and diastolic BP in monotherapy; 2.2 and 1.9mm Hg in polytherapy), mainly because of absence of any effect on nocturnal BP. The 24 h mean BP reduction was larger and statistically significant (6.9 and 5.9 mm for systolic and diastolic BP, respectively, in monotherapy; 5.3 and 4.5 mm Hg in polytherapy) when doxazosin GITS was scheduled at bedtime. This BP-lowering effect was similar during both the day and nighttime hours. Doxazosin GITS ingested daily on awakening failed to provide full 24h therapeutic coverage. Bedtime dosing with doxazosin GITS, however, significantly reduced BP throughout the 24h both when used as a monotherapy and when used in combination with other antihypertensive pharmacotherapy. Knowledge of the chronopharmacology of doxazosin GITS is key to optimizing the efficiency of its BP-lowering effect, and this must be taken into consideration when prescribing this medication to patients.

Adrenergic alpha-Antagonists↗

PubMed2004

Reproducibility of the tolerance-hyperbaric test for diagnosing hypertension in pregnancy.

BACKGROUND: The tolerance-hyperbaric test has been shown to provide a valuable approach for the prediction of the outcome of pregnancy. In this test, diagnosis of hypertension is based on the hyperbaric index (area of blood pressure excess above the upper limit of a reference threshold) calculated by comparison with a time-specified tolerance interval for the circadian variability of blood pressure. OBJECTIVE: To evaluate prospectively the stability and reproducibility of the tolerance-hyperbaric test. METHODS: We studied 403 women who provided 2430 blood pressure series sampled for 48 consecutive hours once every 4 weeks from the first obstetric visit (mostly within the first trimester of gestation) until delivery. Circadian 90% tolerance limits for blood pressure were established as a function of trimester of gestation from 497 series previously sampled from an independent reference group of 189 normotensive pregnant women. Diagnosis of hypertension was established in this trial for each woman in the validation sample on the highly restricted basis of presenting at least one blood pressure profile with a hyperbaric index above the threshold for diagnosis after 20 weeks of gestation. RESULTS: Sensitivity of the tolerance-hyperbaric test was 93% for women sampled during the first trimester of gestation, and increased to 99% by the third trimester. Specificity was more than 99% in all trimesters. The positive and negative predictive values were greater than 96% in all trimesters. CONCLUSIONS: The tolerance-hyperbaric test represents a reproducible, stable, non-invasive and high-sensitivity test for the very early identification of subsequent hypertension in pregnancy.

Adult↗

PubMed2004

Effects of telmisartan 80 mg and valsartan 160 mg on ambulatory blood pressure in patients with essential hypertension.

OBJECTIVES: This trial investigated and compared the antihypertensive efficacy of telmisartan and valsartan, two angiotensin II receptor blockers, used in monotherapy at their maximum recommended dose in hypertensive patients. METHODS: We studied 70 subjects (32 men and 38 women) aged 47.6 +/- 12.2 (mean +/- SD) years, with mild to moderate essential hypertension; they were randomly assigned to receive monotherapy with either telmisartan (80 mg) or valsartan (160 mg), in the form of a single daily tablet upon awakening. Blood pressure was measured by ambulatory monitoring every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to calculate accurately the diurnal and nocturnal means of blood pressure on a per subject basis. RESULTS: There was a highly significant blood pressure reduction during the 24 h with both drugs. The blood pressure reduction in the 24-h mean was significantly larger for valsartan 160 mg (18.6 and 12.1 mmHg for systolic and diastolic blood pressure, respectively) than for telmisartan 80 mg (10.8 and 8.4 mmHg; P < 0.001 between treatment-groups). There was also a highly significant reduction (P < 0.001) of 6.5 mmHg in the 24-h mean of pulse pressure after valsartan administration only. The trough : peak ratio and the smoothness index were slightly higher in systolic, but similar in diastolic blood pressure, for telmisartan as compared to valsartan. CONCLUSIONS: Despite a shorter half-life, 160 mg/day valsartan was more effective in lowering blood pressure over 24 h than 80 mg/day telmisartan. Furthermore, valsartan was also more effective in lowering arterial pulse pressure, an observation that may have important therapeutic implications, given the mounting evidence that pulse pressure may be a risk factor for future cardiovascular events.

Administration, Oral↗

PubMed2004

Effect of continuous positive airway pressure on ambulatory blood pressure in patients with obstructive sleep apnoea.

OBJECTIVES: Previous reports on the effects of continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) on blood pressure has shown contradictory results. Accordingly, we have investigated the effects of CPAP on blood pressure and on the potential reversal of the diagnosis of hypertension in patients with OSA evaluated repeatedly by ambulatory blood pressure monitoring. METHODS: We studied 122 patients (104 men and 18 women), 55.1+/-10.5 years of age, with diagnosis of OSA corroborated by overnight polysomnography at the clinic. Among those patients, 83 were treated with CPAP after their first evaluation, while 39 remained without CPAP for the duration of the trial. Blood pressure was measured by ambulatory monitoring at 20-min intervals during the day and at 30-min intervals at night for 48 consecutive hours, at baseline and after 2 and 4 months of intervention. RESULTS: There was a small, but not statistically significant, reduction in ambulatory blood pressure in patients treated with CPAP (0.7 and 1.5 mmHg in 24-h mean of systolic and diastolic blood pressure after 2 months of therapy; 2.0 and 2.3 mmHg after 4 months; P>0.239). The blood pressure reduction was very similar in patients with OSA followed for 4 months without CPAP (1.9 and 2.2 mmHg in 24-h mean of systolic and diastolic blood pressure, respectively; P=0.543). We found a high (77%) prevalence of hypertension among the patients participating in this study, although only 37% were receiving antihypertensive medication at the time of recruitment. The prevalence of hypertension was slightly but not significantly reduced to just 74% after 4 months of treatment with CPAP. CONCLUSIONS: The small reduction in blood pressure for consecutive profiles of ambulatory monitoring can probably be explained by the documented 'ABPM pressor effect' on patients using the ambulatory device for the first time. The high prevalence of hypertension among patients with OSA is not significantly reduced by treatment with CPAP. These results suggest that patients with OSA should always be properly evaluated for diagnosis of hypertension, and provided, if needed, with antihypertensive treatment apart from the recommended CPAP.

Blood Pressure↗