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Biomedical subjects

Carlos Calvo

Publications and source records attributed to Carlos Calvo.

At least 19 recordsLinked to original sources

[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↗

[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↗

Indapamide SR versus candesartan and amlodipine in hypertension: the X-CELLENT Study.

BACKGROUND: Reducing systolic blood pressure (BP) is of major benefit to patients with isolated systolic hypertension, but lowering normal diastolic BP may be harmful in terms of cardiovascular risk. Effects of different drugs on systolic BP, diastolic BP, and pulse pressure are therefore of interest. METHODS: The NatriliX SR versus CandEsartan and amLodipine in the reduction of systoLic blood prEssure in hyperteNsive patienTs study (X-CELLENT) was a randomized, double-blind, placebo-controlled study comparing the effects of three drugs on these BP components. Patients with systolic-diastolic or isolated systolic hypertension (n = 1758) received indapamide (1.5 mg) sustained release (SR), candesartan (8 mg), amlodipine (5 mg), or placebo once daily for 12 weeks. RESULTS: Compared to placebo all active treatments reduced all BP components significantly (P < .001). For the patients with isolated systolic hypertension (n = 388), the three treatments significantly reduced systolic BP, but only indapamide SR did not change diastolic BP and thus reduced pulse pressure significantly relative to placebo (P = .005). In an ancillary study using ambulatory BP monitoring (n = 576), all three treatments significantly reduced BP components during 24 h relative to placebo. Changes in systolic BP and pulse pressure were similar with the three treatments, but the reduction in diastolic BP was significantly smaller, and therefore more favorable, with indapamide SR compared with candesartan (P = .039). In patients with isolated systolic hypertension (n = 106), indapamide SR reduced 24-h systolic BP significantly more than amlodipine (P = .037), and only indapamide SR reduced 24-h pulse pressure significantly relative to placebo (P = .03). All three drugs were well tolerated. CONCLUSIONS: This distinctive BP-lowering profile of indapamide SR seems highly beneficial when compared to the either of candesartan or amlodipine.

Adult↗

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↗

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↗

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↗

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↗

Fluorescence, browning index, and color in infant formulas during storage.

Free and total fluorescent compounds, browning index, and color formation were measured in milk-based powdered infant formulas (IF) during 2 years of storage at 20 and 37 degrees C. The excitation spectra from 415 nm emission show three peaks (ex lambda1 = 270 nm, lambda2 = 325/315 nm, lambda3 = 350 nm) and from 347 nm excitation two emission peaks (415 and 520 nm), and no wavelength shifts were observed. Temperature and time of storage exert in general no significant effect on the development of fluorescence emission intensity and browning index. However, an important increase in pentodilysine was recorded-probably because of the iron and ascorbic acid contents of the samples-as well as in browning index in adapted IF. In both IF a color increase (deltaE) throughout storage was observed, this increase being greater in samples stored at 37 degrees C than in those stored at 20 degrees C. The increase in color with time fitted a linear regression model. Color appeared to be an indicator of sufficient sensitivity to measure the effect of temperature or storage time.

Color↗

Doxazosin GITS versus standard doxazosin in mild to moderate hypertension.

BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P < 0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.

Adolescent↗

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↗

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↗

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↗

Microalbuminuria in hypertensive patients: evaluation of one-year treatment with irbesartan.

BACKGROUND: Microalbuminuria is an important cardiovascular risk factor, and appears to be a marker of early arterial disease in patients with and without diabetes and/or hypertension. The aim of this study was to investigate prevalence of albuminuria in hypertensive patients in clinical settings, as well as to assess the efficacy of the angiotensin receptor blocker irbesartan on the evolution of this risk marker in habitual clinical practice. METHODS: KORAL-HT is a prospective, multicenter 1-year follow-up study in inadequately controlled hypertensive patients. Demographic data, major cardiovascular risk factors, albuminuria, and clinical parameters were recorded at baseline and at 6-month and 12-month visits. During the year of follow-up, the patients received antihypertensive therapy with irbesartan in addition to their usual antihypertensive regimen. RESULTS: A total of 1657 [802 diabetics (48.4%) and 855 nondiabetics (51.6%)] hypertensive patients were studied. The prevalence of microalbuminuria in this sample was 62.5%. After 1-year treatment with irbesartan, the percentage of patients with normoalbuminuria grew from 17.1% at baseline to 40.9% at 1-year follow-up. Blood pressure (BP) decreased from 157.3 +/- 13.7/93.6 +/- 9.2 mm Hg at baseline to 139.8 +/- 13.12 mm Hg and 136.1 +/- 11.6/80.1 +/- 8 mmHg at 6- and 12-month visits, respectively. The percentage of patients who achieved BP targets increased progressively, 57.2% at 6 months, and 70.1% at the study end. CONCLUSION: This study shows that the population attending Spanish HT centers have high prevalence of microalbuminuria. The addition of irbesartan to the usual treatment in poorly controlled hypertensive patients significantly improved BP control, and reduced microalbuminuria both in diabetic and nondiabetic patients. Our study confirms that similar results can be obtained in normal clinical practice as in controlled clinical trials.

Albuminuria↗

Lipoprotein composition in children and adolescents with type 1 diabetes mellitus.

Atherosclerotic cardiovascular diseases are the major causes of morbidity and mortality in patients with diabetes mellitus. Both quantitative and qualitative abnormalities of lipo-proteins are associated with the development of atherogenesis. In this study, the prevalence of dyslipidemia and the relative levels of glycosylated lipoproteins in 20 children and adolescents with type 1 diabetes mellitus were determined. Lipid profile, apolipoproteins A-I and B, Lp(a) and LpA-I in plasma were assayed. LpB and glycosylated HDL and LDL were evaluated by ELISA. Diabetic patients and controls had normal lipid profiles, but the diabetic group showed significantly higher LpA-I and lower LpA-I:A-II concentrations than controls. The diabetic group showed a significantly higher glycosylation level of HDL than controls and did not show a statistical difference for glycosylated LDL. No significant correlation between glycosylated lipoproteins, glycemia or HbA1c was found. In conclusion, these results suggest that type 1 diabetic patients develop important qualitative lipid abnormalities.

Adolescent↗

Erectile dysfunction in essential arterial hypertension and effects of sildenafil: results of a Spanish national study.

BACKGROUND: The aim of this study was to establish the prevalence of erectile dysfunction (ED) in hypertensive patients in specialized care hypertension units (SCHUs) and to assess the effectiveness and tolerability of sildenafil treatment. METHODS: This was a multicenter, prospective, open, observational pharmacoepidemiology study conducted in 25 Spanish SCHUs. A total of 2130 men with essential hypertension under treatment were recruited. In a second phase, 291 subjects with a score < or = 21 in the Sexual Health Inventory for Men (SHIM) received sildenafil (50 mg/day) as required 30 to 60 minutes before sexual activity, and were evaluated by the International Index of Erectile Function (IIEF). RESULTS: A total of 975 subjects (45.8%) had a score < or = 21 in the SHIM. In the second phase, sildenafil improved the score in the erectile function domain in 232 patients (83.2%). Severity of ED significantly improved (P <.001); severe (22.3% to 7.7%), moderate (23% to 5.6%), and mild impairment (36.3% to 44.8%). The IIEF was normalized in 39.1% of patients who completed post-treatment IIEF. In all, 33 subjects (11.8%) failed to complete the study: two (0.7%) because of lack of efficacy, two (0.7%) intercurrent disease, 10 (3.6%) failure to return to the visits, three (1.1%) fear of therapy, four (1.4%) adverse effects requiring treatment discontinuation, and 12 (4.3%) protocol violations. No statistically significant association was found between the prevalence of adverse effects and antihypertensive treatment with single drug or combination therapy. CONCLUSIONS: A high incidence of ED was found in hypertensive patients from Spanish SCHUs. Sildenafil showed an excellent response and safety profile.

3',5'-Cyclic-GMP Phosphodiesterases↗

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↗

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↗

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↗