Cardiovascular changes in dipper and nondipper hypertension in perimenopausal women ( time-dependent effects of antihypertensives)

Abstract

Background The lack of a decrease in nocturnal blood pressure to up to 10% of the daytime measure is termed as nondipper (ND) hypertension. It is a cardiovascular (CV) risk factor with increased CV morbidity and accelerated target organ damage especially in women. The beneficial effect of restoring the ND state by administering antihypertensives (chronotherapy) at bedtime rather than on awakening is still debated. Objectives The aim of this study was to determine the extent of ND hypertension and the magnitude of CV morbidities among perimenopausal women in comparison with an identical dipper group. The study also intended to determine the administration time-dependent effect on the ND state. Study designThe study included a cross-sectional part and a prospective randomized part. Patients and methods One hundred and thirty perimenopausal women who were not known to be hypertensive, with an office blood pressure repeatedly exceeding 140/90 mmHg were included. After obtaining informed consents, complete history was taken and clinical examination was carried out. The included patients underwent 12-lead ECG and echocardiography, and the carotid intima-media thickness was measured. Besides the routine urine and blood analysis, analyses to obtain levels of lipids, HbA1-c, serum thyroid stimulating hormone, coagulation factors (factor VIII, fibrinogen), urinary albumin excretion, and C reactive protein were also carried out. Ambulatory blood pressure of all patients on a nonworking day was monitored. The studied patients were classified as dippers and NDs. The ND patients were randomly assigned to treatment with angiotensin receptor blockers (ARBs). Half of the ND patients received their dosage at bedtime and the others received the same dosage on awakening for 6 months, after which the ambulatory blood pressure was remeasured. Results ND hypertension was detected in 61.5% of patients, its occurrence being significantly higher among women with hot flashes, those with postural hypotension, obese women, and among women with elevated HbA1-c, fibrinogen, cholesterol, C reactive protein and urinary albumin excretion levels. There was significant prolongation of the QTc interval and QT dispersion with a significant increase in the interventricular septal dimension and carotid artery intima-media thickness in the ND group. Disappearance of the ND phenomenon occurred in 80% of patients receiving therapy with ARBs at bedtime. Conclusion ND hypertension is common among perimenopausal women, especially those with hot flashes, postural hypotension, and higher BMIs and HbA1-c levels, and is associated with many CV risk factors. Chronotherapy with ARBs at bedtime is more efficient in restoring the circadian rhythm of blood pressure compared with that on awakening.

Keywords

• chronotherapy, dipper, nondipper