Rita Soler

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 ≥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.

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.

Association of Metabolic Syndrome and Blood Pressure Nondipping Profile in Untreated Hypertension

BACKGROUND There is a marked association between metabolic syndrome (MS) and increased cardiovascular risk. Moreover, nondipping (patients with <10% decline in the asleep relative to the awake blood pressure (BP) mean) has also been associated with increased cardiovascular morbidity and mortality. METHODS We investigated the association between MS and impaired nocturnal BP decline in 1,770 nondiabetic, untreated hypertensive patients (824 men and 946 women), 48.7 +/- 13.2 years of age. BP was measured by ambulatory monitoring for 48 h to increase reproducibility of the dipping pattern. Physical activity was simultaneously monitored every minute by wrist actigraphy. RESULTS MS was present in 42.4% of the patients. The prevalence of a nondipper BP profile was significantly higher in patients with MS (46.1% vs. 37.5% in patients without MS, P < 0.001). Patients with MS were characterized by significant elevations in uric acid (5.9 mg/dl vs. 5.2 mg/dl, P < 0.001), fibrinogen (314 mg/dl vs. 304 mg/dl, P = 0.021), and globular sedimentation rate (13.8 mm vs. 11.6 mm, P < 0.001). Nondipping was significantly associated to the presence of MS in a multiple logistic regression model adjusted by other significant confounding factors, including age, serum creatinine, and cigarette smoking. The single most relevant factor in the definition of MS associated to nondipping was elevated waist perimeter. CONCLUSIONS This study documents a significant increase of a blunted nocturnal BP decline in patients with MS. Patients with MS were also characterized by elevated values of relevant markers of cardiovascular risk, including fibrinogen and globular sedimentation rate.

Cronoterapia con torasemida en pacientes hipertensos: aumento de la duración y la eficacia terapéuticas con su administración a la hora de acostarse☆

Fundamento y objetivo La torasemida es un diuretico de asa utilizado con frecuencia en el tratamiento de la insuficiencia cardiaca, la insuficiencia renal y la hipertension, en funcion de resultados basados, sobre todo, en la medida clinica de la presion arterial, sin que se haya valorado la eficacia y la duracion del farmaco durante las 24 h. Por ello, hemos investigado la eficacia antihipertensiva y los efectos de la torasemida en el perfil circadiano de la presion arterial, administrada a distintas horas en funcion del ciclo de actividad y descanso. Pacientes y metodo Estudiamos a 58 pacientes hipertensos (25 varones y 33 mujeres) con una media (DE) de edad de 48,7 (11,9) anos, asignados aleatoriamente a 2 grupos de tratamiento en funcion del momento de tomar una dosis de 5 mg/dia de torasemida: a la hora de levantarse o a la hora de acostarse. La presion arterial se determino ambulatoriamente durante 48 h consecutivas antes y despues de 6 semanas de intervencion terapeutica. Resultados La eficacia de la torasemida fue mayor con la dosis nocturna (11,2 y 8,0 mmHg en la media de 24 h de la presion arterial sistolica y diastolica, respectivamente) que con la matutina (6,2 y 3,7 mmHg de presion sistolica y diastolica). El porcentaje de pacientes con presion arterial ambulatoria controlada fue el doble cuando se administro la torasemida a la hora de acostarse (54%) que cuando se la administro a la hora de levantarse (27%). La duracion de la eficacia terapeutica se mantuvo a lo largo de las 24 h solo cuando se administro la torasemida a la hora de acostarse. Con respecto al perfil de seguridad, 2 pacientes presentaron efectos secundarios (dolor abdominal, diarrea) con la toma matutina y 4 con la nocturna (nicturia). Conclusiones Una dosis de 5 mg/dia de torasemida en monoterapia reduce de forma eficaz la presion arterial cuando se administra el farmaco a la hora de acostarse. Se debe tener en cuenta las diferencias en la eficacia antihipertensiva, la duracion del efecto terapeutico y el grado de control en funcion de la hora de tomar la torasemida cuando se prescriba este diuretico de asa en el tratamiento de pacientes con hipertension arterial esencial.

P-20: Effects of hygienic-dietary recommendations on ambulatory blood pressure in untreated patients with grade 1 hypertension

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.