Does Antihypertensive Drug Class Affect Day-to-Day Variability of Self-Measured Home Blood Pressure? The HOMED-BP Study

Abstract

Background: Recent literature suggests that blood pressure variability (BPV) predicts outcome beyond blood pressure level (BPL) and that antihypertensive drug classes differentially influence BPV. We compared calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockade for effects on changes in self-measured home BPL and BPV and for their prognostic significance in newly treated hypertensive patients.

Methods and results: We enrolled 2484 patients randomly allocated to first-line treatment with a calcium channel blocker (n=833), an angiotensin-converting enzyme inhibitor (n=821), or angiotensin receptor blockade (n=830). Home blood pressures in the morning and evening were measured for 5 days off treatment before randomization and for 5 days after 2 to 4 weeks of randomized drug treatment. We assessed BPL and BPV changes as estimated by variability independent of the mean and compared cardiovascular outcomes. Home BPL response in each group was significant (P≤0.0001) but small in the angiotensin-converting enzyme inhibitor group (systolic/diastolic: 4.6/2.8 mm Hg) compared with the groups treated with a calcium channel blocker (systolic/diastolic: 8.3/3.9 mm Hg) and angiotensin receptor blockade (systolic/diastolic: 8.2/4.5 mm Hg). In multivariable adjusted analyses, changes in home variability independent of the mean did not differ among the 3 drug classes (P≥0.054). Evening variability independent of the mean before treatment significantly predicted hard cardiovascular events independent of the corresponding home BPL (P≤0.022), whereas BPV did not predict any cardiovascular outcome based on the morning measurement (P≥0.056). Home BPV captured after monotherapy had no predictive power for cardiovascular outcome (P≥0.22).

Conclusions: Self-measured home evening BPV estimated by variability independent of the mean had prognostic significance, whereas antihypertensive drug classes had no significant impact on BPV changes. Home BPL should remain the primary focus for risk stratification and treatment.

Clinical trial registration: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: C000000137.

Keywords: antihypertensive drugs; blood pressure variability; cardiovascular outcomes; home blood pressure; morning and evening self‐measurement.

Figure 1

Time course of home blood pressure measurement before and after randomization. During the study period, morning blood pressure was measured in a sitting position once every morning after ≥2 minutes of rest and within 1 hour of awakening, before breakfast, and before taking antihypertensive medication, if patients were taking antihypertensive medication. Evening blood pressure was measured in a sitting position once every evening just before going to bed and after ≥2 minutes of rest. Data on home blood pressure values for, in principle, 5 days before randomization and for 5 days after 10 to 28 days of randomized drug treatment were used for the calculation; patients with 3 to 4 days of home blood pressure data in each interval were also included. ACEI indicates angiotensin‐converting enzyme inhibitor; ARB, angiotensin receptor blockade; CCB, calcium channel blocker.

Figure 2

The 10‐year estimated absolute risk of hard cardiovascular events associated with the mean level of systolic home blood pressure and VIM in the morning (A) or the evening (B), measured at baseline. The risk functions were standardized to the distribution (mean or ratio) of sex, age, body mass index, corresponding heart rate, current smoking and drinking, hypercholesterolemia, diabetes mellitus, history of cardiovascular disease, and antihypertensive drug classes. Among 2484 patients, 43 hard cardiovascular events occurred. Mean systolic blood pressure along the horizontal axis covers 135 to 170 mm Hg. Four continuous lines represent the risk independently associated with VIM equal to 5, 8, 11, and 14 U. P values are for the independent effect of systolic blood pressure (P_SBP) and VIM (P_VIM). VIM indicates variability independent of the mean.

Figure 3

The 10‐year estimated absolute risk of hard cardiovascular events associated with the mean level of systolic home blood pressure and VIM in the morning (A) or the evening (B), measured after monotherapy. The risk functions were standardized to the distribution (mean or ratio) of sex, age, body mass index, corresponding heart rate, current smoking and drinking, hypercholesterolemia, diabetes mellitus, history of cardiovascular disease, and antihypertensive drug classes. Among 2484 patients, 43 hard cardiovascular events occurred. Mean systolic blood pressure along the horizontal axis covers 125 to 160 mm Hg. Four continuous lines represent the risk independently associated with VIM equal to 5, 8, 11, and 14 U. P values are for the independent effect of systolic blood pressure (P_SBP) and VIM (P_VIM). VIM indicates variability independent of the mean.

Figure 4

The 10‐year estimated absolute risk of hard cardiovascular events associated with the mean level of systolic home blood pressure and ARV in the morning (A) or the evening (B), measured at baseline. The risk functions were standardized to the distribution (mean or ratio) of sex, age, body mass index, corresponding heart rate, current smoking and drinking, hypercholesterolemia, diabetes mellitus, history of cardiovascular disease, and antihypertensive drug classes. Among 2484 patients, 43 hard cardiovascular events occurred. Mean systolic blood pressure along the horizontal axis covers 135 to 170 mm Hg. Four continuous lines represent the risk independently associated with ARV equal to 6, 9, 12, and 15 mm Hg. P values are for the independent effect of systolic blood pressure (P_SBP) and ARV (P_ARV). ARV indicates average real variability.

Figure 5

The 10‐year estimated absolute risk of hard cardiovascular events associated with the mean level of systolic home blood pressure and ARV in the morning (A) or the evening (B), measured after monotherapy. The risk functions were standardized to the distribution (mean or ratio) of sex, age, body mass index, corresponding heart rate, current smoking and drinking, hypercholesterolemia, diabetes mellitus, history of cardiovascular disease, and antihypertensive drug classes. Among 2484 patients, 43 hard cardiovascular events occurred. Mean systolic blood pressure along the horizontal axis covers 125 to 160 mm Hg. Four continuous lines represent the risk independently associated with ARV equal to 6, 9, 12, and 15 mm Hg. P values are for the independent effect of systolic blood pressure (P_SBP) and ARV (P_ARV). ARV indicates average real variability.