THE INFLUENCE OF AMBULATORY BLOOD-PRESSURE MONITORING ON THE DESIGN AND INTERPRETATION OF TRIALS IN HYPERTENSION

Objective: To describe the reproducibility of diastolic blood pressure (DBP) measurement by clinic and ambulatory monitoring and to evaluate the effects of this reproducibility on the design and interpretation of clinical trials in hypertension research. Design: Prospective single-blind study of repeat measurement reproducibility of blood pressure recording. Setting: Tertiary referral hospital hypertension clinic. Patients: One hundred untreated mild-to-moderate hypertensive subjects taking 1 month of single-blind placebo. Main outcome measures: A single clinic measurement of DBP was poorly reproducible and the results for single DBP estimates taken out of a daytime ambulatory recording were similar. Average ambulatory DBP was much more reproducible, although this improvement depended upon the averaging of many measurements taken throughout the day. Conclusions: Ambulatory monitoring would decrease antihypertensive trial size by a factor of four or halve the size of a detectable DBP difference between treatments. The use of poorly reproducible DBP measurements such as single clinic readings may have led to an underestimation of the risks of minor degrees of blood pressure elevation because of a 'regression dilution' bias. For single clinic DBP readings, we calculate this underestimation to be as much as 69%, and for average ambulatory DBP approximately 20%.