Effects of the circadian time of antihypertensive treatment on the ambulatory blood pressure pattern of elderly patients with essential hypertension

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Recent results indicate that non-dipping in hypertensive patients treated with single morning doses is markedly related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097–1104]. In the elderly, as compared to younger patients, the day/night ratio of blood pressure (BP) (calculated as the nocturnal decline of BP relative to the diurnal mean) is diminished due to a progressive increase in nocturnal BP with aging. Accordingly, we studied the impact of antihypertensive treatment and the time of therapy on the circadian pattern of BP in elderly patients with essential hypertension. We studied 1286 elderly patients with grade 1–2 essential hypertension (573 men), 68.4±5.6 years of age. Among them, 352 patients were untreated at the time of the study, 547 patients were receiving all their antihypertensive medication upon awakening, and 387 were taken one antihypertensive drug at 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 to accurately calculate the diurnal and nocturnal means of BP on a per subject basis. Among untreated patients, 62.5% were non-dippers. In treated patients, BP was highly reduced during diurnally active hours, but not during nocturnal sleep, as compared to untreated patients. The percentage of non-dippers among treated patients was increased up to 66.3%. As a function of the circadian time of treatment, 75.2% of the patients with all drugs on awakening were non-dippers. This percentage was significantly reduced to just 53.7% in patients who received one antihypertensive drug at bedtime (P<0.001). Antihypertensive therapy, mostly given exclusively upon awakening, significantly modifies the circadian pattern of BP. In the elderly, 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 chronotherapeutic approach allows reducing the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk.