Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect: evidence from the sample study.
The objectives of our study were to assess the reproducibility of the trough-to-peak ratio (T/P) and to see whether a high T/P is accompanied by more organ protection or vice versa. The study included 175 (mean+/-SD age, 51+/-9 years) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular (LV) hypertrophy taken from the SAMPLE study (Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation), an open-label multicenter study. The study included a 3-week washout pretreatment period, a 12-month treatment period with lisinopril (n=84) or lisinopril plus hydrochlorothiazide (n=91) once daily, and a 4-week placebo follow-up period. Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index (LVMI) were obtained before and after 3 and 12 months of treatment. T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough (changes in the last 2 hours of the monitoring period) by those at peak (average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake) after 3 and 12 months of treatment. Average 24-hour blood pressure was similarly reduced at 3 and 12 months. Trough blood pressure changes at 3 and 12 months were closely correlated, as were the corresponding peak blood pressure changes. However, the 3- and 12-month T/Ps correlated to a lesser degree (r<0.42). Furthermore, the reduction of LVMI induced by treatment was similarly correlated with the treatment-induced reduction in 24-hour average, trough, and peak blood pressures but not with the T/Ps. This was also evident when the contribution to LV hypertrophy regression by 24-hour blood pressure changes and T/Ps was assessed in a multivariate regression analysis. In patients with a T/P >/=0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment.
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From the Cattedra di Medicina Interna, Ospedale San Gerardo, Monza, Università di Milano, Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, and Istituto Scientifico Ospedale San Luca, Istituto Auxologico Italiano, Milano, Italy.
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D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D007558:Italy; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015203:Reproducibility of Results
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D017706:Lisinopril