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Home and clinic blood pressure responses in elderly individuals with systolic hypertension
Journal of the American Society of Hypertension 6(3) (2012) 210–218
Research Article
Home and clinic blood pressure responses in elderly individuals with systolic hypertension William C. Cushman, MDa,*, Daniel A. Duprez, MD, PhDb, Howard S. Weintraub, MDc, Das Purkayastha, PhDd, Dion Zappe, PhD, MScd, Rita Samuel, MDd, and Joseph L. Izzo Jr., MDe a
University of Tennessee and the VA Medical Center, Memphis, TN, USA; b University of Minnesota, Minneapolis, MN, USA; c New York University School of Medicine, New York, NY, USA; d Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; and e State University of New York at Buffalo, Buffalo, NY, USA Manuscript received January 4, 2012 and accepted March 12, 2012
Abstract Home blood pressure (BP) monitoring may enhance assessment of BP control. In this 16-week study, men and women 70 years or older with systolic BP between 150 and 200 mm Hg were randomized to receive valsartan/hydrochlorothiazide (V/HCTZ) 160/12.5 mg (n ¼ 128), HCTZ 12.5 mg (n ¼ 128), or V 160 mg (n ¼ 128) for 4 weeks. Participants whose BP was 140/90 mm Hg or higher at weeks 4, 8, or 12 were uptitrated to a maximum of V/HCTZ 320/25 mg. Participants were evaluated by home BP monitoring using an automated device weekly before taking daily study medication (n ¼ 301). Baseline BP SD for clinic (165.5 11.8/85.1 9.5 mm Hg) was approximately 3/1 mm Hg greater than home readings (162.5 15.8/84.3 10.2 mm Hg). Reductions in BP SEM at week 4 were similar for clinic (12.6 1.0/4.7 0.5 mm Hg) and home (10.9 1.1/3.8 0.5 mm Hg) readings (P ¼ .25/P ¼ .23; clinic versus home); differences between V/HCTZ and HCTZ or V were also similar for both home and clinic readings and results by either technique correlated significantly (P < .0001). Home BP measurements confirm that treatment initiated with V/HCTZ versus monotherapy resulted in greater antihypertensive efficacy. Home BP monitoring, if done with proper technique, provides a reliable indicator of BP control in elderly patients and may help guide drug dosing and titration. J Am Soc Hypertens 2012;6(3):210–218. Ó 2012 American Society of Hypertension. All rights reserved. Keywords: Hydrochlorothiazide; valsartan; randomized controlled trial; blood pressures monitoring technique.
Funding/support: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. Editorial assistance from Oxford PharmaGenesis was funded by Novartis Pharmaceuticals Corporation. The authors express their appreciation to Colleen Faller of Novartis Pharmaceuticals Corporation for expert assistance in project management (ClinicalTrials.gov identifier: NCT00698646). Conflict of interest: W.C.C.: Consultancies at Takeda, Merck, Daiichi-Sankyo, Omron; grant support from Merck; stock ownership/ financial interests: none. D.A.D.: Speakers’ Bureau at Novartis Pharmaceuticals Corporation, Forest, Pfizer, Merck; advisory boards at Novartis Pharmaceuticals Corporation, Pfizer, Abbott; grant support from Novartis Pharmaceuticals Corporation, Roche; stock
ownership/financial interests: none. H.S.W.: consultancies at Gilead; Speakers’ Bureau at Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda, AstraZeneca, Gilead, Abbott, Kowa; grant support: none; stock ownership/financial interests: none. D.P., D.Z., and R.S. are employees of Novartis Pharmaceuticals Corporation. J.L.I.: Consultancies at Boehringer-Ingelheim, Forest Laboratories, Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda; grant support from GlaxoSmithKline, Novartis Pharmaceuticals Corporation; stock ownership/financial interests: none. *Corresponding author: William C. Cushman, MD, 127 Harbor Town Boulevard, Memphis, TN 38103. Tel/Fax: 1-901-522-3016. E-mail: [email protected]
1933-1711/$ - see front matter Ó 2012 American Society of Hypertension. All rights reserved. doi:10.1016/j.jash.2012.03.001
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Introduction Some of the benefits of home blood pressure (HBP) monitoring (HBPM) over conventional clinic blood pressure (BP) measurement include (1) measurement of BP in familiar surroundings, thus minimizing white-coat effect; (2) ability to take multiple readings over long periods of time; (3) increased adherence to medication; and (4) easy availability.1 In addition, use of HBP may reduce the need for antihypertensive medication.2 Compared with standard clinic BP measurements, HBP readings have been shown to better predict cardiovascular mortality3,4 and target-organ damage, such as left ventricular hypertrophy and atherosclerosis.5–8 HBPM is also recommended for the identification of white-coat and masked hypertension, to evaluate resistant hypertension, and has been used in high-risk patients and pregnancy.9 National and international hypertension guidelines, including those from the American Society of Hypertension10; the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7)11; the European Society of Hypertension1; the British Hypertension Society12; and the British National Institute for Health and Clinical Excellence (NICE),13 have recommended the use of HBPM in addition to clinic BP monitoring for the diagnosis or management of hypertension. Overall, HBPM tends to provide more consistent BP readings8 with resultant values often lower than clinic BP values on average1; some of the differences in home versus clinic BP are potentially attributable to lack of consistency in time of day BP is measured or lack of proper measurement technique (eg, seated in chair with back supported, posture, arm position, or cuff size and placement).10 A segment of the population that might benefit from the increased use of HBPM is the elderly.14 This population may have challenges getting to a health care provider’s office for regular BP assessments and is more prone to white-coat hypertension15,16 and to variability in BP,17,18 which is associated with increased cardiovascular risk.19,20 In addition, older individuals are more likely to record HBP than younger
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individuals, supporting improved adherence to use of HBPM in the elderly population.21 Previously, we reported from the Valsartan Very Elderly Trial (ValVET)22 that initial use of combination therapy with the angiotensin receptor blocker valsartan (V) and the diuretic hydrochlorothiazide (HCTZ) results in significantly greater reductions in BP and increased BP control compared with Vor HCTZ monotherapy in the elderly (age 70 years) with systolic BP 150 to 200 mm Hg. In the analysis reported here, we compared the HBP measurements with clinic BP measurements from this study.
Methods Methods for ValVET have been previously described in detail22 and are briefly summarized here.
Subjects Eligible participants were older men and women (aged 70 years) with primary systolic hypertension (mean sitting systolic blood pressure [MSSBP] between 150 mm Hg and 200 mm Hg).
Study Design The ValVET study was a 16-week, multicenter, randomized, double-blind, prompted-titration trial conducted at 80 centers in the United States and Canada. After screening and after a 3- to 14-day washout, eligible subjects were randomized (1:1:1) to 1 of the following 3 treatment groups: V/HCTZ 160/12.5 mg combination therapy (V/HCTZ group), HCTZ 12.5 mg monotherapy (HCTZ group), or valsartan 160 mg monotherapy (V group). Uptitration was based on clinic BP readings and was prompted via an Interactive Voice Response System (IVRS). Following 4 weeks of treatment, subjects not at the BP goal of less than 140/90 mm Hg were prompted to uptitrate their doses to V/HCTZ 320/12.5 mg in the initial combination therapy arm or to V/HCTZ 160/12.5 mg in either of the initial monotherapy arms. After
Table 1 Baseline clinic versus home blood pressure measures (intent-to-treat population) Parameter
V/HCTZ (n ¼ 103)
Mean SD clinic SBP, mm Hg Mean SD home SBP, mm Hg Difference in means Median (range) clinic SBP, mm Hg Median (range) home SBP, mm Hg Mean SD clinic DBP, mm Hg Mean SD home DBP, mm Hg Difference in means Median (range) clinic DBP, mm Hg Median (range) home DBP, mm Hg
163.8 161.3 2.5 162.0 160.0 84.2 83.6 0.6 85.0 85.0
11.6 15.1 (P ¼ .19) (119–198) (119–197) 9.6 9.5 (P ¼ .62) (59–107) (61–106)
HCTZ (n ¼ 100) 165.4 162.7 2.7 162.5 163.0 86.2 86.1 0.1 86.5 86.0
12.2 15.5 (P ¼ .18) (147–199) (123–198) 8.9 10.2 (P ¼ .90) (64–117) (61–109)
V (n ¼ 98) 167.3 163.6 3.7 166.0 164.0 85.0 83.2 1.8 85.5 83.5
11.6 16.8 (P ¼ .07) (145–195) (122–208) 9.9 10.7 (P ¼ .24) (66–104) (54–112)
Overall (n ¼ 301) 165.5 162.5 3.0 163.0 163.0 85.1 84.3 0.8 86.0 85.0
11.8 15.8 (P ¼ .01) (119–199) (119–208) 9.5 10.2 (P ¼ .29) (59–117) (54–112)
DBP, diastolic blood pressure; HCTZ, hydrochlorothiazide; SBP, systolic blood pressure; SD, standard deviation; V, valsartan.
77.1 10.4 7.5
8 weeks, there was additional prompted uptitration for subjects not at BP goal to V/HCTZ 320/25 mg in the initial combination therapy arm or to V/HCTZ 320/12.5 mg in either of the initial monotherapy arms. After 12 weeks, any subject not at BP goal and not taking the maximum dose of V/HCTZ (320/25 mg), was prompted to be uptitrated to the maximum dose level for the remaining 4 weeks of the study. All treatments were administered once daily.
78.5 11.3 7.6 75.7 8.9 7.8 Hg
Blood Pressure Determination
DBP, diastolic blood pressure; HCTZ, hydrochlorothiazide; SBP, systolic blood pressure; SD, standard deviation; V, valsartan. Changes and differences shown in the table are least-square mean values.
76.8 10.6 7.2
146.3 19.6 18.5 0.5 (P ¼ .72) 77.7 9.7 7.3 0.2 (P ¼ .75) 146.1 19.7 19.0
150.2 20.1 16.3 2.7 (P ¼ .34) 78.2 10.1 6.4 0.8 (P ¼ .57) 144.9 20.1 18.6
145.1 18.9 19.6 1.0 (P ¼ .69) 78.5 10.7 7.7 0.1 (P ¼ .95) 142.2 19.0 19.7
143.7 19.5 19.5 0.2 (P ¼ .94) 76.3 8.3 7.7 0.2 (P ¼ .88)
83.2 10.6 3.0 77.1 9.7 6.3 Hg
Hg
81.6 10.8 2.2
80.7 10.7 3.8
152.3 19.9 10.9
152.4 19.1 12.6 1.7 (P ¼ .25) 80.3 10.2 4.7 0.9 (P ¼ .23) 153.0 18.1 10.3
Week 4 Mean SD SBP, mm Hg Change from baseline, mm Difference, mm Hg Mean SD DBP, mm Hg Change from baseline, mm Difference, mm Hg Week 16 Mean SD SBP, mm Hg Change from baseline, mm Difference, mm Hg Mean SD DBP, mm Hg Change from baseline, mm Difference, mm Hg
Hg
147.2 18.7 16.1 0.5 (P ¼ .84) 77.0 9.6 7.0 0.7 (P ¼ .53)
146.0 19.8 15.6
151.0 17.2 13.9 3.6 (P ¼ .10) 82.5 10.5 3.7 0.8 (P ¼ .55)
159.2 19.6 7.3 0.5 (P ¼ .84) 81.5 9.7 3.1 0.9 (P ¼ .48)
157.8 20.3 6.8
Home Clinic Home Clinic Home Clinic
Clinic
Home
Overall (n ¼ 301) V (n ¼ 98) HCTZ (n ¼ 100) V/HCTZ (n ¼ 103) Parameter
Table 2 Clinic and home blood pressure measures at week 4 and week 16 (intent-to-treat population)
144.4 19.6 19.0
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Clinic BP measurements were performed at each clinic visit (at baseline and at weeks 2, 4, 8, 12, and 16) using an Omron automated BP monitor (Model #HEM-705 CP, Omron Healthcare Inc, Bannockburn, Illinois, which has been validated23). After subjects relaxed in a sitting position for 5 minutes, systolic and diastolic BP were determined 3 times at 1- to 2-minute intervals, and the mean of these values was used. Home BP devices were given to all patients for weekly monitoring of BP. The analyses reported here focus on those assessments performed at home during the morning of the scheduled office visit, before coming into the clinic. The subjects were instructed to measure their BP using the Omron automated BP monitor (Model #HEM-705 CP) device, 3 times in a row in the morning in a relaxed state before taking medication. They were instructed to bring the printouts and/or the BP machine with them to their scheduled office visit.
Statistical Analysis Within-treatment least-square mean (LSM) changes in MSSBP (and mean home systolic blood pressure [MHSBP]) and mean sitting diastolic blood pressure (MSDBP) (and mean home diastolic blood pressure [MHDBP]) from baseline were analyzed using a paired t test. A post hoc analysis was performed to compare clinic BP and HBP values at baseline within each treatment group and overall using a 1-way analysis of variance; clinic BP and HBP LSM changes from baseline were compared within each treatment group and overall using an analysis of covariance model. The proportions of subjects achieving BP lower than 140/90 mm Hg and lower than 135/85 mm Hg, based on clinic BP versus HBP assessments, were compared using the Cochran-Mantel-Haenszel chi-squared test. In addition, to compare the correlation between HBPM measures and clinic measures, Spearman’s coefficient was used. All analyses were carried out using a last observation carried forward (LOCF) and observed cases (OC) approach.
Results Subjects In the study, 384 randomized subjects (n ¼ 128 in each treatment group) were provided with an electronic HBPM
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Figure 1. LSM reductions from baseline in (A) SBP and (B) DBP using clinic and home measures at weeks 4 and 16.
device. HBPM data were available for 304 subjects: 104 in the V/HCTZ, 102 in the HCTZ, and 98 in the V group. Baseline demographic and clinical characteristics were well matched and similar to those reported for the overall population,22 with no statistically significant differences observed across the treatment groups. Overall, subjects with HBPM data had a mean age of 77.3 years, 53.9% were female, and 83.2% were white. Most subjects were overweight, with a mean body mass index of 28.7 kg/m2. About 21.4% of subjects were diabetic.
Baseline BP Measurements Overall, the baseline BP standard deviation (SD) values for MSSBP/MSDBP and MHSBP/MHDBP were 165.5 11.8/85.1 9.5 mm Hg and 162.5 15.8/84.3 10.2 mm Hg, respectively. Thus, clinic BP was approximately 3/1 mm Hg greater than HBP. Based on SD, more variability was observed with HBP measurement than
with clinic BP at baseline (Table 1). Within each treatment group, no significant differences were observed between clinic BP and HBP readings. Overall, a significant difference was observed between MSSBP versus MHSBP (P ¼ .01), but not between MSDBP versus MHDBP (P ¼ .29) (Table 1).
Dosing By week 8, 32.8% of subjects in the initial combinationtherapy group (V/HCTZ group) were titrated to the next highest dose (320/12.5 mg). Among subjects randomized to initial monotherapy groups, 48.4% in the HCTZ group and 57.0% in the V group were switched to combination therapy. By week 16, the number of subjects receiving combination therapy had increased. In the HCTZ and V groups, 57.8% and 60.2%, respectively, switched to combination therapy, whereas 43.0% of subjects in the V/HCTZ group were titrated to higher dose levels.
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and HBP measurements with respect to reductions from baseline in systolic or diastolic BP. Overall, at week 8, reductions in BP SEM were 17.2 1.1/6.7 0.5 mm Hg based on clinic readings versus 14.7 1.1/6.0 0.5 mm Hg based on home readings (P ¼ .10/P ¼ .38). Corresponding reductions at week 12 were 19.0 1.1/7.7 0.5 mm Hg versus 18.0 1.1/7.4 0.5 mm Hg (P ¼ .52/P ¼ .68). At week 16, all treatments produced significant reductions from baseline in clinic as well as home systolic and diastolic BP (P < .001). As observed at the earlier time points, within each treatment group and overall, no significant differences were observed between clinic BP and HBP measurements with respect to reductions from baseline in systolic or diastolic BP at week 16. Overall, reductions in BP SEM over this time period were 18.5 1.1/ 7.3 0.5 mm Hg based on clinic readings versus 19.0 1.1/7.5 0.5 mm Hg based on home readings (P ¼ .72/ P ¼ .75).
Figure 2. Home SBP and DBP over time by treatment group. All 3 treatments significantly (P < .01) reduced SBP and DBP from baseline at all time points (except for DBP reduction at week 4 in V group).
Changes from Baseline in Clinic BP versus HBP Comparisons of changes from baseline in clinic BP versus HBP are summarized within each treatment group and overall in Table 2 and Figure 1A and 1B. HBP is shown over time in Figure 2. In each treatment group, the pattern of HBP reduction over time was similar to the clinic findings reported previously for the overall population.22 At week 4, all treatments produced significant reductions from baseline in systolic and diastolic BP with clinic as well as HBP measurements (P < .01). The only exception was a nonsignificant reduction of 2.2 0.9 mm Hg in diastolic BP, based on HBP readings, in the V group. Within each treatment group and overall, no significant differences were observed between clinic BP and HBP measurements with respect to reductions from baseline in systolic or diastolic BP at week 4. Overall, reductions in BP standard error of the mean (SEM) over this time period were 12.6 1.0/4.7 0.5 mm Hg based on clinic readings versus 10.9 1.1/3.8 0.5 mm Hg based on home readings (P ¼ .25/P ¼ .23). At weeks 8 and 12, all treatments produced significant reductions from baseline in systolic and diastolic BP regardless of whether clinic or HBP measurements were used (P < .001). Within each treatment group and overall, no significant differences were observed between clinic BP
BP Lower than 140/90 mm Hg and Lower than 135/85 mm Hg as Measured by Clinic BP versus HBP Measures Within each treatment group and overall, no significant differences were observed between clinic BP and HBP measurements with respect to the percentage of patients achieving BP lower than 140/90 mm Hg (Figure 3A) or lower than 135/85 mm Hg (Figure 3B) at weeks 4 or 16. Overall, at the end of the study, BP lower than 140/90 mm Hg was achieved by 45.5% of patients based on clinic readings and 51.9% based on home readings (P ¼ .22). Corresponding results for attainment of BP lower than 135/85 mm Hg were 30.8% versus 36.8% (P ¼ .21).
Correlation Between Clinic BP and HBP Measures Using estimated Spearman correlation coefficients, a significant correlation was observed between the clinic and home measures of BP. At baseline, the Spearman correlation coefficient between clinic and home systolic BP (SBP) measures (r ¼ 0.48, P ¼ .007) and between clinic and home diastolic BP (DBP) measures (r ¼ 0.53, P < .0001) were highly significant. Similar significant correlations were also obtained for the estimated change from baseline between clinic versus home SBP (r ¼ 0.42, P < .0001) and DBP (r ¼ 0.43, P < .0001) measures. Fitted regression lines for change in MHSBP on change in MSSBP and for change in MHDBP on change in MSDBP at week 16 are shown in Figure 4A and 4B. Across all treatment groups, the r value was 0.47 for SBP and 0.40 for DBP (both P < .0001), indicating a strong correlation between home and clinic BP measures.
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Figure 3. Percentage of subjects achieving BP (A) <140/90 mm Hg and (B) <135/85 mm Hg using clinic and home measures at weeks 4 and 16.
Variability Based on SDs, the variability in both clinic BP and HBP assessments for week 4 and week 16 was similar for all treatment groups (Table 2). Of interest to note was that, although SDs at baseline for HBP measures were higher compared with clinic BP measures, over time (from week 4 to week 16) the SDs for HBP measures were similar to the SDs for clinic BP measures.
Discussion In our study, use of the same model automated BP monitor at home as in the clinic resulted in similar BP measurements. The responsiveness to antihypertensive treatments observed with clinic measures were confirmed with HBPM. Both clinic BP and HBP measures showed
that initiation of treatment with combination V/HCTZ in elderly hypertensive subjects lowered BP more effectively than initiation of monotherapy with V or HCTZ. Thus, HBPM proved to be a reliable measure of BP in this population. Clinic BP has often been reported to be 5 to 10 mm Hg higher than HBP. One review reported clinic BP as 8.1/5.6 mm Hg greater than HBP,24 with BP thresholds for defining hypertension reflecting this disparity; many have suggested that for a clinic threshold of 140/90 mm Hg, the threshold for HBP should be 130 to 135/85 mm Hg.10,24,25 Some of the difference between clinic BP and HBP can be attributed to a white-coat effect; however, measurement of BP in the clinic by auscultation using mercury or aneroid sphygmomanometers is also subject to a number of potential inaccuracies (eg, variation in interpretation of Korotkoff sounds among different observers).26,27 In addition, with
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Figure 4. Fitted regression line for change in (A) MSSBP on change in MHSBP for overall treatment group (ITT population) and (B) MSDBP on change in MHDBP for overall treatment group (ITT population).
either a manual or an automated manometer, clinic BP measurements are often overestimated because of methodologic errors, primarily not using the proper cuff size, not sitting the patient in a chair, not waiting 5 minutes while the patient rests without talking, and not taking multiple readings11,28,29 (although many of these errors can also affect the accuracy of HBP measurements). In our study, differences between clinic BP and HBP measured at baseline or postbaseline were much smaller than those previously reported in most studies; at baseline, clinic BP was only approximately 3/1 mm Hg greater than HBP. We attribute this, in part, to the use of the same Omron automated BP device in both environments, and to the careful attention
paid to standardize BP measurement procedures in both locations. The fact that HBP tends to decrease as the number of measurements increase may also have played a role in the small differences between clinic BP and HBP at baseline.30 Our results are comparable to those reported by Giles and colleagues,31 who used the same Omron automated BP device and procedure to monitor clinic BP and HBP in their study, where baseline clinic BP was approximately 3/2 mm Hg greater than baseline HBP (164.5/94.6 vs 161.6/92.8 mm Hg). Use of the same automated BP device also likely contributed to the highly significant correlations we, and others,32 have observed between home and clinic BP measures.
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An interesting observation in our study was that the SDs were higher at baseline for HBP compared with clinic BP but were similar at weeks 4 and 16 between the 2 BP measures. A possible explanation for the difference in variability at baseline might be that some subjects initially were unfamiliar with, and had more anxiety related to, using the BP monitor properly in the home environment. Possibly more important, as baseline clinic BP was an entry criterion for eligibility, this may have truncated the range of clinic BPs at baseline, but because HBPs were not used for eligibility, they encompassed a broader range. In our study, BP control based on similar arbitrary thresholds was generally numerically greater with home measures than with clinic measures. This finding mimics previously reported findings from a meta-analysis of 18 randomized controlled trials in which the proportion of subjects achieving target increased with use of HBP compared with clinic BP.33 This may have clinical implications, particularly in the elderly, in that the use of HBP to adjust the dose of antihypertensive treatment can result in avoiding overdosing and increased adverse events, and lower costs of therapy. However, using a lower criterion for HBP may also result in overtreatment if titration of medications is based on a 5 to 10 mm Hg lower goal for HBP than clinic BP, which overestimates the difference in clinic and HBP measurements. HBPM has several advantages over clinic BP monitoring and may be particularly useful in the elderly. Importantly, HBPM allows the health care professional to capture daily and weekly BP measurements from patients without such frequent visits to the clinic, with the potential to curtail the escalating costs of health care and help guide treatment decisions. Currently, HBP measurements can be transmitted by telephone line to clinical settings, but in the near future, wireless transmission of BP recordings directly from the home to the clinic will become more readily available, adding even greater convenience.34
Study Limitations Statistical comparisons between clinic BP versus HBP measures within each treatment group were done post hoc. Because the 2 BP measures were done within the same population, however, comparisons are justifiable. The HBP measures used in our analysis were obtained on days when the subject had a clinic visit. On these days, study medication was given to the subject after clinic procedures were completed. Because the recordings reflect the end of the dosing period, hypotensive episodes were less likely to have been identified by the HBP measurements.
Conclusion In conclusion, our findings show that HBPM is a reliable indicator of BP control in this population and may help guide drug dosing and titration. Our data support greater
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use of HBPM in clinical practice, especially in the older hypertensive population.
References 1. Parati G, Stergiou GS, Asmar R, Bilo G, de Leeuw P, Imai Y, et al. European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring. J Hypertens 2008;26: 1505–26. 2. Verberk WJ, Kroon AA, Lenders JW, Kessels AG, van Montfrans GA, Smit AJ, et al. Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized, controlled trial. Hypertension 2007;50:1019–25. 3. Ohkubo T, Imai Y, Tsuji I, Nagai K, Kato J, Kikuchi N, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens 1998;16:971–5. 4. Mancia G, Facchetti R, Bombelli M, Grassi G, Sega R. Long-term risk of mortality associated with selective and combined elevation in office, home, and ambulatory blood pressure. Hypertension 2006;47:846–53. 5. Stergiou GS, Argyraki KK, Moyssakis I, Mastorantonakis SE, Achimastos AD, Karamanos VG, et al. Home blood pressure is as reliable as ambulatory blood pressure in predicting target-organ damage in hypertension. Am J Hypertens 2007;20:616–21. 6. Niiranen T, Jula A, Kantola I, Moilanen L, K€ah€onen M, Kes€aniemi YA, et al. Home-measured blood pressure is more strongly associated with atherosclerosis than clinic blood pressure: the Finn-HOME Study. J Hypertens 2007;25:1225–31. 7. Niiranen TJ, Jula AM, Kantola IM, Karanko H, Reunanen A. Home-measured blood pressure is more strongly associated with electrocardiographic left ventricular hypertrophy than is clinic blood pressure: the FinnHOME study. J Hum Hypertens 2007;21:788–94. 8. Bobrie G, Chatellier G, Genes N, Clerson P, Vaur L, Vaisse B, et al. Cardiovascular prognosis of ‘‘masked hypertension’’ detected by blood pressure selfmeasurement in elderly treated hypertensive patients. JAMA 2004;291:1342–9. 9. Parati G, Stergiou GS, Asmar R, Bilo G, de Leeuw P, Imai Y, et al. European Society of Hypertension practice guidelines for home blood pressure monitoring. J Hum Hypertens 2010;24:779–85. 10. Pickering TG, Miller NH, Ogedegbe G, Krakoff LR, Artinian NT, Goff D. Call to action on use and reimbursement for home blood pressure monitoring: a joint scientific statement from the American Heart Association, American Society Of Hypertension, and
218
11.
12.
13.
14.
15.
16.
17.
18. 19.
20.
21.
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Preventive Cardiovascular Nurses Association. Hypertension 2008;52:10–29. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52. Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ 2004;328:634–40. National Institute of Health and Clinical Excellence (NICE). Hypertension. Clinical management of primary hypertension in adults. NICE clinical guideline 127. August 2011. Available at: http://www.nice.org.uk/ nicemedia/live/13561/56008/56008.pdf. Accessed March 28, 2012. Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, et al. ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol 2011;57:2037–114. Staessen JA, O’Brien ET, Amery AK, Atkins N, Baumgart P, De Cort P, et al. Ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database. J Hypertens Suppl 1994;12:S1–12. Verberk WJ, Kroon AA, Kessels AG, de Leeuw PW. Home blood pressure measurement: a systematic review. J Am Coll Cardiol 2005;46:743–51. Giannattasio C, Ferrari AU, Mancia G. Alterations in neural cardiovascular control mechanisms with ageing. J Hypertens Suppl 1994;12:S13–7. Sowers JR, Lester M. Hypertension, hormones, and aging. J Lab Clin Med 2000;135:379–86. Mancia G, Ferrari A, Gregorini L, Parati G, Pomidossi G, Bertinieri G, et al. Blood pressure and heart rate variabilities in normotensive and hypertensive human beings. Circ Res 1983;53:96–104. Pringle E, Phillips C, Thijs L, Davidson C, Staessen JA, de Leeuw PW, et al. Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population. J Hypertens 2003;21:2251–7. Kramer MH, Breydo E, Shubina M, Babcock K, Einbinder JS, Turchin A. Prevalence and factors affecting home blood pressure documentation in routine clinical care: a retrospective study. BMC Health Serv Res 2010; 10:139.
22. Izzo JL Jr, Weintraub HS, Duprez DA, Purkayastha D, Zappe D, Samuel R, et al. Treating systolic hypertension in the very elderly with valsartan-hydrochlorothiazide vs either monotherapy: ValVET primary results. J Clin Hypertens 2011;13:722–30. 23. O’Brien E, Mee F, Atkins N, Thomas M. Evaluation of three devices for self-measurement of blood pressure according to the revised British Hypertension Society Protocol: the Omron HEM-705CP, Philips HP5332, and Nissei DS-175. Blood Press Monit 1996;1:55–61. 24. Yarows SA, Julius S, Pickering TG. Home blood pressure monitoring. Arch Intern Med 2000;160:1251–7. 25. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007;25: 1105–87. 26. Staessen JA, O’Brien ET, Thijs L, Fagard RH. Modern approaches to blood pressure measurement. Occup Environ Med 2000;57:510–20. 27. Vidt DG, Lang RS, Seballos RJ, Misra-Hebert A, Campbell J, Bena JF. Taking blood pressure: too important to trust to humans? Cleve Clin J Med 2010;77:683–8. 28. Cushman WC, Cooper KM, Horne RA, Meydrech EF. Effect of back support and stethoscope head on seated blood pressure determinations. Am J Hypertens 1990;3: 240–1. 29. Kim JW, Bosworth HB, Voils CI, Olsen M, Dudley T, Gribbin M, et al. How well do clinic-based blood pressure measurements agree with the mercury standard? J Gen Intern Med 2005;20:647–9. 30. Niiranen TJ, Jula AM, Kantola IM, Reunanen A. Comparison of agreement between clinic and homemeasured blood pressure in the Finnish population: the Finn-HOME Study. J Hypertens 2006;24:1549–55. 31. Giles TD, Oparil S, Ofili EO, Pitt B, Purkayastha D, Hilkert R, et al. The role of ambulatory blood pressure monitoring compared with clinic and home blood pressure measures in evaluating moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy. Blood Press Monit 2011;16:87–95. 32. Eguchi K, Kuruvilla S, Ishikawa J, Ogedegbe G, Gerin W, Schwartz JE, et al. Correlations between different measures of clinic, home, and ambulatory blood pressure in hypertensive patients. Blood Press Monit 2011;16:142–8. 33. Cappuccio FP, Kerry SM, Forbes L, Donald A. Blood pressure control by home monitoring: meta-analysis of randomised trials. BMJ 2004;329:145. 34. Omre AH. Bluetooth low energy: wireless connectivity for medical monitoring. J Diabetes Sci Technol 2010;4: 457–63.
Research Article
Home and clinic blood pressure responses in elderly individuals with systolic hypertension William C. Cushman, MDa,*, Daniel A. Duprez, MD, PhDb, Howard S. Weintraub, MDc, Das Purkayastha, PhDd, Dion Zappe, PhD, MScd, Rita Samuel, MDd, and Joseph L. Izzo Jr., MDe a
University of Tennessee and the VA Medical Center, Memphis, TN, USA; b University of Minnesota, Minneapolis, MN, USA; c New York University School of Medicine, New York, NY, USA; d Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; and e State University of New York at Buffalo, Buffalo, NY, USA Manuscript received January 4, 2012 and accepted March 12, 2012
Abstract Home blood pressure (BP) monitoring may enhance assessment of BP control. In this 16-week study, men and women 70 years or older with systolic BP between 150 and 200 mm Hg were randomized to receive valsartan/hydrochlorothiazide (V/HCTZ) 160/12.5 mg (n ¼ 128), HCTZ 12.5 mg (n ¼ 128), or V 160 mg (n ¼ 128) for 4 weeks. Participants whose BP was 140/90 mm Hg or higher at weeks 4, 8, or 12 were uptitrated to a maximum of V/HCTZ 320/25 mg. Participants were evaluated by home BP monitoring using an automated device weekly before taking daily study medication (n ¼ 301). Baseline BP SD for clinic (165.5 11.8/85.1 9.5 mm Hg) was approximately 3/1 mm Hg greater than home readings (162.5 15.8/84.3 10.2 mm Hg). Reductions in BP SEM at week 4 were similar for clinic (12.6 1.0/4.7 0.5 mm Hg) and home (10.9 1.1/3.8 0.5 mm Hg) readings (P ¼ .25/P ¼ .23; clinic versus home); differences between V/HCTZ and HCTZ or V were also similar for both home and clinic readings and results by either technique correlated significantly (P < .0001). Home BP measurements confirm that treatment initiated with V/HCTZ versus monotherapy resulted in greater antihypertensive efficacy. Home BP monitoring, if done with proper technique, provides a reliable indicator of BP control in elderly patients and may help guide drug dosing and titration. J Am Soc Hypertens 2012;6(3):210–218. Ó 2012 American Society of Hypertension. All rights reserved. Keywords: Hydrochlorothiazide; valsartan; randomized controlled trial; blood pressures monitoring technique.
Funding/support: This study was funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. Editorial assistance from Oxford PharmaGenesis was funded by Novartis Pharmaceuticals Corporation. The authors express their appreciation to Colleen Faller of Novartis Pharmaceuticals Corporation for expert assistance in project management (ClinicalTrials.gov identifier: NCT00698646). Conflict of interest: W.C.C.: Consultancies at Takeda, Merck, Daiichi-Sankyo, Omron; grant support from Merck; stock ownership/ financial interests: none. D.A.D.: Speakers’ Bureau at Novartis Pharmaceuticals Corporation, Forest, Pfizer, Merck; advisory boards at Novartis Pharmaceuticals Corporation, Pfizer, Abbott; grant support from Novartis Pharmaceuticals Corporation, Roche; stock
ownership/financial interests: none. H.S.W.: consultancies at Gilead; Speakers’ Bureau at Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda, AstraZeneca, Gilead, Abbott, Kowa; grant support: none; stock ownership/financial interests: none. D.P., D.Z., and R.S. are employees of Novartis Pharmaceuticals Corporation. J.L.I.: Consultancies at Boehringer-Ingelheim, Forest Laboratories, Novartis Pharmaceuticals Corporation, Daiichi-Sankyo, Takeda; grant support from GlaxoSmithKline, Novartis Pharmaceuticals Corporation; stock ownership/financial interests: none. *Corresponding author: William C. Cushman, MD, 127 Harbor Town Boulevard, Memphis, TN 38103. Tel/Fax: 1-901-522-3016. E-mail: [email protected]
1933-1711/$ - see front matter Ó 2012 American Society of Hypertension. All rights reserved. doi:10.1016/j.jash.2012.03.001
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Introduction Some of the benefits of home blood pressure (HBP) monitoring (HBPM) over conventional clinic blood pressure (BP) measurement include (1) measurement of BP in familiar surroundings, thus minimizing white-coat effect; (2) ability to take multiple readings over long periods of time; (3) increased adherence to medication; and (4) easy availability.1 In addition, use of HBP may reduce the need for antihypertensive medication.2 Compared with standard clinic BP measurements, HBP readings have been shown to better predict cardiovascular mortality3,4 and target-organ damage, such as left ventricular hypertrophy and atherosclerosis.5–8 HBPM is also recommended for the identification of white-coat and masked hypertension, to evaluate resistant hypertension, and has been used in high-risk patients and pregnancy.9 National and international hypertension guidelines, including those from the American Society of Hypertension10; the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7)11; the European Society of Hypertension1; the British Hypertension Society12; and the British National Institute for Health and Clinical Excellence (NICE),13 have recommended the use of HBPM in addition to clinic BP monitoring for the diagnosis or management of hypertension. Overall, HBPM tends to provide more consistent BP readings8 with resultant values often lower than clinic BP values on average1; some of the differences in home versus clinic BP are potentially attributable to lack of consistency in time of day BP is measured or lack of proper measurement technique (eg, seated in chair with back supported, posture, arm position, or cuff size and placement).10 A segment of the population that might benefit from the increased use of HBPM is the elderly.14 This population may have challenges getting to a health care provider’s office for regular BP assessments and is more prone to white-coat hypertension15,16 and to variability in BP,17,18 which is associated with increased cardiovascular risk.19,20 In addition, older individuals are more likely to record HBP than younger
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individuals, supporting improved adherence to use of HBPM in the elderly population.21 Previously, we reported from the Valsartan Very Elderly Trial (ValVET)22 that initial use of combination therapy with the angiotensin receptor blocker valsartan (V) and the diuretic hydrochlorothiazide (HCTZ) results in significantly greater reductions in BP and increased BP control compared with Vor HCTZ monotherapy in the elderly (age 70 years) with systolic BP 150 to 200 mm Hg. In the analysis reported here, we compared the HBP measurements with clinic BP measurements from this study.
Methods Methods for ValVET have been previously described in detail22 and are briefly summarized here.
Subjects Eligible participants were older men and women (aged 70 years) with primary systolic hypertension (mean sitting systolic blood pressure [MSSBP] between 150 mm Hg and 200 mm Hg).
Study Design The ValVET study was a 16-week, multicenter, randomized, double-blind, prompted-titration trial conducted at 80 centers in the United States and Canada. After screening and after a 3- to 14-day washout, eligible subjects were randomized (1:1:1) to 1 of the following 3 treatment groups: V/HCTZ 160/12.5 mg combination therapy (V/HCTZ group), HCTZ 12.5 mg monotherapy (HCTZ group), or valsartan 160 mg monotherapy (V group). Uptitration was based on clinic BP readings and was prompted via an Interactive Voice Response System (IVRS). Following 4 weeks of treatment, subjects not at the BP goal of less than 140/90 mm Hg were prompted to uptitrate their doses to V/HCTZ 320/12.5 mg in the initial combination therapy arm or to V/HCTZ 160/12.5 mg in either of the initial monotherapy arms. After
Table 1 Baseline clinic versus home blood pressure measures (intent-to-treat population) Parameter
V/HCTZ (n ¼ 103)
Mean SD clinic SBP, mm Hg Mean SD home SBP, mm Hg Difference in means Median (range) clinic SBP, mm Hg Median (range) home SBP, mm Hg Mean SD clinic DBP, mm Hg Mean SD home DBP, mm Hg Difference in means Median (range) clinic DBP, mm Hg Median (range) home DBP, mm Hg
163.8 161.3 2.5 162.0 160.0 84.2 83.6 0.6 85.0 85.0
11.6 15.1 (P ¼ .19) (119–198) (119–197) 9.6 9.5 (P ¼ .62) (59–107) (61–106)
HCTZ (n ¼ 100) 165.4 162.7 2.7 162.5 163.0 86.2 86.1 0.1 86.5 86.0
12.2 15.5 (P ¼ .18) (147–199) (123–198) 8.9 10.2 (P ¼ .90) (64–117) (61–109)
V (n ¼ 98) 167.3 163.6 3.7 166.0 164.0 85.0 83.2 1.8 85.5 83.5
11.6 16.8 (P ¼ .07) (145–195) (122–208) 9.9 10.7 (P ¼ .24) (66–104) (54–112)
Overall (n ¼ 301) 165.5 162.5 3.0 163.0 163.0 85.1 84.3 0.8 86.0 85.0
11.8 15.8 (P ¼ .01) (119–199) (119–208) 9.5 10.2 (P ¼ .29) (59–117) (54–112)
DBP, diastolic blood pressure; HCTZ, hydrochlorothiazide; SBP, systolic blood pressure; SD, standard deviation; V, valsartan.
77.1 10.4 7.5
8 weeks, there was additional prompted uptitration for subjects not at BP goal to V/HCTZ 320/25 mg in the initial combination therapy arm or to V/HCTZ 320/12.5 mg in either of the initial monotherapy arms. After 12 weeks, any subject not at BP goal and not taking the maximum dose of V/HCTZ (320/25 mg), was prompted to be uptitrated to the maximum dose level for the remaining 4 weeks of the study. All treatments were administered once daily.
78.5 11.3 7.6 75.7 8.9 7.8 Hg
Blood Pressure Determination
DBP, diastolic blood pressure; HCTZ, hydrochlorothiazide; SBP, systolic blood pressure; SD, standard deviation; V, valsartan. Changes and differences shown in the table are least-square mean values.
76.8 10.6 7.2
146.3 19.6 18.5 0.5 (P ¼ .72) 77.7 9.7 7.3 0.2 (P ¼ .75) 146.1 19.7 19.0
150.2 20.1 16.3 2.7 (P ¼ .34) 78.2 10.1 6.4 0.8 (P ¼ .57) 144.9 20.1 18.6
145.1 18.9 19.6 1.0 (P ¼ .69) 78.5 10.7 7.7 0.1 (P ¼ .95) 142.2 19.0 19.7
143.7 19.5 19.5 0.2 (P ¼ .94) 76.3 8.3 7.7 0.2 (P ¼ .88)
83.2 10.6 3.0 77.1 9.7 6.3 Hg
Hg
81.6 10.8 2.2
80.7 10.7 3.8
152.3 19.9 10.9
152.4 19.1 12.6 1.7 (P ¼ .25) 80.3 10.2 4.7 0.9 (P ¼ .23) 153.0 18.1 10.3
Week 4 Mean SD SBP, mm Hg Change from baseline, mm Difference, mm Hg Mean SD DBP, mm Hg Change from baseline, mm Difference, mm Hg Week 16 Mean SD SBP, mm Hg Change from baseline, mm Difference, mm Hg Mean SD DBP, mm Hg Change from baseline, mm Difference, mm Hg
Hg
147.2 18.7 16.1 0.5 (P ¼ .84) 77.0 9.6 7.0 0.7 (P ¼ .53)
146.0 19.8 15.6
151.0 17.2 13.9 3.6 (P ¼ .10) 82.5 10.5 3.7 0.8 (P ¼ .55)
159.2 19.6 7.3 0.5 (P ¼ .84) 81.5 9.7 3.1 0.9 (P ¼ .48)
157.8 20.3 6.8
Home Clinic Home Clinic Home Clinic
Clinic
Home
Overall (n ¼ 301) V (n ¼ 98) HCTZ (n ¼ 100) V/HCTZ (n ¼ 103) Parameter
Table 2 Clinic and home blood pressure measures at week 4 and week 16 (intent-to-treat population)
144.4 19.6 19.0
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Clinic BP measurements were performed at each clinic visit (at baseline and at weeks 2, 4, 8, 12, and 16) using an Omron automated BP monitor (Model #HEM-705 CP, Omron Healthcare Inc, Bannockburn, Illinois, which has been validated23). After subjects relaxed in a sitting position for 5 minutes, systolic and diastolic BP were determined 3 times at 1- to 2-minute intervals, and the mean of these values was used. Home BP devices were given to all patients for weekly monitoring of BP. The analyses reported here focus on those assessments performed at home during the morning of the scheduled office visit, before coming into the clinic. The subjects were instructed to measure their BP using the Omron automated BP monitor (Model #HEM-705 CP) device, 3 times in a row in the morning in a relaxed state before taking medication. They were instructed to bring the printouts and/or the BP machine with them to their scheduled office visit.
Statistical Analysis Within-treatment least-square mean (LSM) changes in MSSBP (and mean home systolic blood pressure [MHSBP]) and mean sitting diastolic blood pressure (MSDBP) (and mean home diastolic blood pressure [MHDBP]) from baseline were analyzed using a paired t test. A post hoc analysis was performed to compare clinic BP and HBP values at baseline within each treatment group and overall using a 1-way analysis of variance; clinic BP and HBP LSM changes from baseline were compared within each treatment group and overall using an analysis of covariance model. The proportions of subjects achieving BP lower than 140/90 mm Hg and lower than 135/85 mm Hg, based on clinic BP versus HBP assessments, were compared using the Cochran-Mantel-Haenszel chi-squared test. In addition, to compare the correlation between HBPM measures and clinic measures, Spearman’s coefficient was used. All analyses were carried out using a last observation carried forward (LOCF) and observed cases (OC) approach.
Results Subjects In the study, 384 randomized subjects (n ¼ 128 in each treatment group) were provided with an electronic HBPM
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Figure 1. LSM reductions from baseline in (A) SBP and (B) DBP using clinic and home measures at weeks 4 and 16.
device. HBPM data were available for 304 subjects: 104 in the V/HCTZ, 102 in the HCTZ, and 98 in the V group. Baseline demographic and clinical characteristics were well matched and similar to those reported for the overall population,22 with no statistically significant differences observed across the treatment groups. Overall, subjects with HBPM data had a mean age of 77.3 years, 53.9% were female, and 83.2% were white. Most subjects were overweight, with a mean body mass index of 28.7 kg/m2. About 21.4% of subjects were diabetic.
Baseline BP Measurements Overall, the baseline BP standard deviation (SD) values for MSSBP/MSDBP and MHSBP/MHDBP were 165.5 11.8/85.1 9.5 mm Hg and 162.5 15.8/84.3 10.2 mm Hg, respectively. Thus, clinic BP was approximately 3/1 mm Hg greater than HBP. Based on SD, more variability was observed with HBP measurement than
with clinic BP at baseline (Table 1). Within each treatment group, no significant differences were observed between clinic BP and HBP readings. Overall, a significant difference was observed between MSSBP versus MHSBP (P ¼ .01), but not between MSDBP versus MHDBP (P ¼ .29) (Table 1).
Dosing By week 8, 32.8% of subjects in the initial combinationtherapy group (V/HCTZ group) were titrated to the next highest dose (320/12.5 mg). Among subjects randomized to initial monotherapy groups, 48.4% in the HCTZ group and 57.0% in the V group were switched to combination therapy. By week 16, the number of subjects receiving combination therapy had increased. In the HCTZ and V groups, 57.8% and 60.2%, respectively, switched to combination therapy, whereas 43.0% of subjects in the V/HCTZ group were titrated to higher dose levels.
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and HBP measurements with respect to reductions from baseline in systolic or diastolic BP. Overall, at week 8, reductions in BP SEM were 17.2 1.1/6.7 0.5 mm Hg based on clinic readings versus 14.7 1.1/6.0 0.5 mm Hg based on home readings (P ¼ .10/P ¼ .38). Corresponding reductions at week 12 were 19.0 1.1/7.7 0.5 mm Hg versus 18.0 1.1/7.4 0.5 mm Hg (P ¼ .52/P ¼ .68). At week 16, all treatments produced significant reductions from baseline in clinic as well as home systolic and diastolic BP (P < .001). As observed at the earlier time points, within each treatment group and overall, no significant differences were observed between clinic BP and HBP measurements with respect to reductions from baseline in systolic or diastolic BP at week 16. Overall, reductions in BP SEM over this time period were 18.5 1.1/ 7.3 0.5 mm Hg based on clinic readings versus 19.0 1.1/7.5 0.5 mm Hg based on home readings (P ¼ .72/ P ¼ .75).
Figure 2. Home SBP and DBP over time by treatment group. All 3 treatments significantly (P < .01) reduced SBP and DBP from baseline at all time points (except for DBP reduction at week 4 in V group).
Changes from Baseline in Clinic BP versus HBP Comparisons of changes from baseline in clinic BP versus HBP are summarized within each treatment group and overall in Table 2 and Figure 1A and 1B. HBP is shown over time in Figure 2. In each treatment group, the pattern of HBP reduction over time was similar to the clinic findings reported previously for the overall population.22 At week 4, all treatments produced significant reductions from baseline in systolic and diastolic BP with clinic as well as HBP measurements (P < .01). The only exception was a nonsignificant reduction of 2.2 0.9 mm Hg in diastolic BP, based on HBP readings, in the V group. Within each treatment group and overall, no significant differences were observed between clinic BP and HBP measurements with respect to reductions from baseline in systolic or diastolic BP at week 4. Overall, reductions in BP standard error of the mean (SEM) over this time period were 12.6 1.0/4.7 0.5 mm Hg based on clinic readings versus 10.9 1.1/3.8 0.5 mm Hg based on home readings (P ¼ .25/P ¼ .23). At weeks 8 and 12, all treatments produced significant reductions from baseline in systolic and diastolic BP regardless of whether clinic or HBP measurements were used (P < .001). Within each treatment group and overall, no significant differences were observed between clinic BP
BP Lower than 140/90 mm Hg and Lower than 135/85 mm Hg as Measured by Clinic BP versus HBP Measures Within each treatment group and overall, no significant differences were observed between clinic BP and HBP measurements with respect to the percentage of patients achieving BP lower than 140/90 mm Hg (Figure 3A) or lower than 135/85 mm Hg (Figure 3B) at weeks 4 or 16. Overall, at the end of the study, BP lower than 140/90 mm Hg was achieved by 45.5% of patients based on clinic readings and 51.9% based on home readings (P ¼ .22). Corresponding results for attainment of BP lower than 135/85 mm Hg were 30.8% versus 36.8% (P ¼ .21).
Correlation Between Clinic BP and HBP Measures Using estimated Spearman correlation coefficients, a significant correlation was observed between the clinic and home measures of BP. At baseline, the Spearman correlation coefficient between clinic and home systolic BP (SBP) measures (r ¼ 0.48, P ¼ .007) and between clinic and home diastolic BP (DBP) measures (r ¼ 0.53, P < .0001) were highly significant. Similar significant correlations were also obtained for the estimated change from baseline between clinic versus home SBP (r ¼ 0.42, P < .0001) and DBP (r ¼ 0.43, P < .0001) measures. Fitted regression lines for change in MHSBP on change in MSSBP and for change in MHDBP on change in MSDBP at week 16 are shown in Figure 4A and 4B. Across all treatment groups, the r value was 0.47 for SBP and 0.40 for DBP (both P < .0001), indicating a strong correlation between home and clinic BP measures.
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Figure 3. Percentage of subjects achieving BP (A) <140/90 mm Hg and (B) <135/85 mm Hg using clinic and home measures at weeks 4 and 16.
Variability Based on SDs, the variability in both clinic BP and HBP assessments for week 4 and week 16 was similar for all treatment groups (Table 2). Of interest to note was that, although SDs at baseline for HBP measures were higher compared with clinic BP measures, over time (from week 4 to week 16) the SDs for HBP measures were similar to the SDs for clinic BP measures.
Discussion In our study, use of the same model automated BP monitor at home as in the clinic resulted in similar BP measurements. The responsiveness to antihypertensive treatments observed with clinic measures were confirmed with HBPM. Both clinic BP and HBP measures showed
that initiation of treatment with combination V/HCTZ in elderly hypertensive subjects lowered BP more effectively than initiation of monotherapy with V or HCTZ. Thus, HBPM proved to be a reliable measure of BP in this population. Clinic BP has often been reported to be 5 to 10 mm Hg higher than HBP. One review reported clinic BP as 8.1/5.6 mm Hg greater than HBP,24 with BP thresholds for defining hypertension reflecting this disparity; many have suggested that for a clinic threshold of 140/90 mm Hg, the threshold for HBP should be 130 to 135/85 mm Hg.10,24,25 Some of the difference between clinic BP and HBP can be attributed to a white-coat effect; however, measurement of BP in the clinic by auscultation using mercury or aneroid sphygmomanometers is also subject to a number of potential inaccuracies (eg, variation in interpretation of Korotkoff sounds among different observers).26,27 In addition, with
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Figure 4. Fitted regression line for change in (A) MSSBP on change in MHSBP for overall treatment group (ITT population) and (B) MSDBP on change in MHDBP for overall treatment group (ITT population).
either a manual or an automated manometer, clinic BP measurements are often overestimated because of methodologic errors, primarily not using the proper cuff size, not sitting the patient in a chair, not waiting 5 minutes while the patient rests without talking, and not taking multiple readings11,28,29 (although many of these errors can also affect the accuracy of HBP measurements). In our study, differences between clinic BP and HBP measured at baseline or postbaseline were much smaller than those previously reported in most studies; at baseline, clinic BP was only approximately 3/1 mm Hg greater than HBP. We attribute this, in part, to the use of the same Omron automated BP device in both environments, and to the careful attention
paid to standardize BP measurement procedures in both locations. The fact that HBP tends to decrease as the number of measurements increase may also have played a role in the small differences between clinic BP and HBP at baseline.30 Our results are comparable to those reported by Giles and colleagues,31 who used the same Omron automated BP device and procedure to monitor clinic BP and HBP in their study, where baseline clinic BP was approximately 3/2 mm Hg greater than baseline HBP (164.5/94.6 vs 161.6/92.8 mm Hg). Use of the same automated BP device also likely contributed to the highly significant correlations we, and others,32 have observed between home and clinic BP measures.
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An interesting observation in our study was that the SDs were higher at baseline for HBP compared with clinic BP but were similar at weeks 4 and 16 between the 2 BP measures. A possible explanation for the difference in variability at baseline might be that some subjects initially were unfamiliar with, and had more anxiety related to, using the BP monitor properly in the home environment. Possibly more important, as baseline clinic BP was an entry criterion for eligibility, this may have truncated the range of clinic BPs at baseline, but because HBPs were not used for eligibility, they encompassed a broader range. In our study, BP control based on similar arbitrary thresholds was generally numerically greater with home measures than with clinic measures. This finding mimics previously reported findings from a meta-analysis of 18 randomized controlled trials in which the proportion of subjects achieving target increased with use of HBP compared with clinic BP.33 This may have clinical implications, particularly in the elderly, in that the use of HBP to adjust the dose of antihypertensive treatment can result in avoiding overdosing and increased adverse events, and lower costs of therapy. However, using a lower criterion for HBP may also result in overtreatment if titration of medications is based on a 5 to 10 mm Hg lower goal for HBP than clinic BP, which overestimates the difference in clinic and HBP measurements. HBPM has several advantages over clinic BP monitoring and may be particularly useful in the elderly. Importantly, HBPM allows the health care professional to capture daily and weekly BP measurements from patients without such frequent visits to the clinic, with the potential to curtail the escalating costs of health care and help guide treatment decisions. Currently, HBP measurements can be transmitted by telephone line to clinical settings, but in the near future, wireless transmission of BP recordings directly from the home to the clinic will become more readily available, adding even greater convenience.34
Study Limitations Statistical comparisons between clinic BP versus HBP measures within each treatment group were done post hoc. Because the 2 BP measures were done within the same population, however, comparisons are justifiable. The HBP measures used in our analysis were obtained on days when the subject had a clinic visit. On these days, study medication was given to the subject after clinic procedures were completed. Because the recordings reflect the end of the dosing period, hypotensive episodes were less likely to have been identified by the HBP measurements.
Conclusion In conclusion, our findings show that HBPM is a reliable indicator of BP control in this population and may help guide drug dosing and titration. Our data support greater
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use of HBPM in clinical practice, especially in the older hypertensive population.
References 1. Parati G, Stergiou GS, Asmar R, Bilo G, de Leeuw P, Imai Y, et al. European Society of Hypertension guidelines for blood pressure monitoring at home: a summary report of the Second International Consensus Conference on Home Blood Pressure Monitoring. J Hypertens 2008;26: 1505–26. 2. Verberk WJ, Kroon AA, Lenders JW, Kessels AG, van Montfrans GA, Smit AJ, et al. Self-measurement of blood pressure at home reduces the need for antihypertensive drugs: a randomized, controlled trial. Hypertension 2007;50:1019–25. 3. Ohkubo T, Imai Y, Tsuji I, Nagai K, Kato J, Kikuchi N, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens 1998;16:971–5. 4. Mancia G, Facchetti R, Bombelli M, Grassi G, Sega R. Long-term risk of mortality associated with selective and combined elevation in office, home, and ambulatory blood pressure. Hypertension 2006;47:846–53. 5. Stergiou GS, Argyraki KK, Moyssakis I, Mastorantonakis SE, Achimastos AD, Karamanos VG, et al. Home blood pressure is as reliable as ambulatory blood pressure in predicting target-organ damage in hypertension. Am J Hypertens 2007;20:616–21. 6. Niiranen T, Jula A, Kantola I, Moilanen L, K€ah€onen M, Kes€aniemi YA, et al. Home-measured blood pressure is more strongly associated with atherosclerosis than clinic blood pressure: the Finn-HOME Study. J Hypertens 2007;25:1225–31. 7. Niiranen TJ, Jula AM, Kantola IM, Karanko H, Reunanen A. Home-measured blood pressure is more strongly associated with electrocardiographic left ventricular hypertrophy than is clinic blood pressure: the FinnHOME study. J Hum Hypertens 2007;21:788–94. 8. Bobrie G, Chatellier G, Genes N, Clerson P, Vaur L, Vaisse B, et al. Cardiovascular prognosis of ‘‘masked hypertension’’ detected by blood pressure selfmeasurement in elderly treated hypertensive patients. JAMA 2004;291:1342–9. 9. Parati G, Stergiou GS, Asmar R, Bilo G, de Leeuw P, Imai Y, et al. European Society of Hypertension practice guidelines for home blood pressure monitoring. J Hum Hypertens 2010;24:779–85. 10. Pickering TG, Miller NH, Ogedegbe G, Krakoff LR, Artinian NT, Goff D. Call to action on use and reimbursement for home blood pressure monitoring: a joint scientific statement from the American Heart Association, American Society Of Hypertension, and
218
11.
12.
13.
14.
15.
16.
17.
18. 19.
20.
21.
W.C. Cushman et al. / Journal of the American Society of Hypertension 6(3) (2012) 210–218
Preventive Cardiovascular Nurses Association. Hypertension 2008;52:10–29. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 2003;42:1206–52. Williams B, Poulter NR, Brown MJ, Davis M, McInnes GT, Potter JF, et al. British Hypertension Society guidelines for hypertension management 2004 (BHS-IV): summary. BMJ 2004;328:634–40. National Institute of Health and Clinical Excellence (NICE). Hypertension. Clinical management of primary hypertension in adults. NICE clinical guideline 127. August 2011. Available at: http://www.nice.org.uk/ nicemedia/live/13561/56008/56008.pdf. Accessed March 28, 2012. Aronow WS, Fleg JL, Pepine CJ, Artinian NT, Bakris G, Brown AS, et al. ACCF/AHA 2011 Expert Consensus Document on Hypertension in the Elderly. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents developed in collaboration with the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol 2011;57:2037–114. Staessen JA, O’Brien ET, Amery AK, Atkins N, Baumgart P, De Cort P, et al. Ambulatory blood pressure in normotensive and hypertensive subjects: results from an international database. J Hypertens Suppl 1994;12:S1–12. Verberk WJ, Kroon AA, Kessels AG, de Leeuw PW. Home blood pressure measurement: a systematic review. J Am Coll Cardiol 2005;46:743–51. Giannattasio C, Ferrari AU, Mancia G. Alterations in neural cardiovascular control mechanisms with ageing. J Hypertens Suppl 1994;12:S13–7. Sowers JR, Lester M. Hypertension, hormones, and aging. J Lab Clin Med 2000;135:379–86. Mancia G, Ferrari A, Gregorini L, Parati G, Pomidossi G, Bertinieri G, et al. Blood pressure and heart rate variabilities in normotensive and hypertensive human beings. Circ Res 1983;53:96–104. Pringle E, Phillips C, Thijs L, Davidson C, Staessen JA, de Leeuw PW, et al. Systolic blood pressure variability as a risk factor for stroke and cardiovascular mortality in the elderly hypertensive population. J Hypertens 2003;21:2251–7. Kramer MH, Breydo E, Shubina M, Babcock K, Einbinder JS, Turchin A. Prevalence and factors affecting home blood pressure documentation in routine clinical care: a retrospective study. BMC Health Serv Res 2010; 10:139.
22. Izzo JL Jr, Weintraub HS, Duprez DA, Purkayastha D, Zappe D, Samuel R, et al. Treating systolic hypertension in the very elderly with valsartan-hydrochlorothiazide vs either monotherapy: ValVET primary results. J Clin Hypertens 2011;13:722–30. 23. O’Brien E, Mee F, Atkins N, Thomas M. Evaluation of three devices for self-measurement of blood pressure according to the revised British Hypertension Society Protocol: the Omron HEM-705CP, Philips HP5332, and Nissei DS-175. Blood Press Monit 1996;1:55–61. 24. Yarows SA, Julius S, Pickering TG. Home blood pressure monitoring. Arch Intern Med 2000;160:1251–7. 25. Mancia G, De Backer G, Dominiczak A, Cifkova R, Fagard R, Germano G, et al. 2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 2007;25: 1105–87. 26. Staessen JA, O’Brien ET, Thijs L, Fagard RH. Modern approaches to blood pressure measurement. Occup Environ Med 2000;57:510–20. 27. Vidt DG, Lang RS, Seballos RJ, Misra-Hebert A, Campbell J, Bena JF. Taking blood pressure: too important to trust to humans? Cleve Clin J Med 2010;77:683–8. 28. Cushman WC, Cooper KM, Horne RA, Meydrech EF. Effect of back support and stethoscope head on seated blood pressure determinations. Am J Hypertens 1990;3: 240–1. 29. Kim JW, Bosworth HB, Voils CI, Olsen M, Dudley T, Gribbin M, et al. How well do clinic-based blood pressure measurements agree with the mercury standard? J Gen Intern Med 2005;20:647–9. 30. Niiranen TJ, Jula AM, Kantola IM, Reunanen A. Comparison of agreement between clinic and homemeasured blood pressure in the Finnish population: the Finn-HOME Study. J Hypertens 2006;24:1549–55. 31. Giles TD, Oparil S, Ofili EO, Pitt B, Purkayastha D, Hilkert R, et al. The role of ambulatory blood pressure monitoring compared with clinic and home blood pressure measures in evaluating moderate versus intensive treatment of hypertension with amlodipine/valsartan for patients uncontrolled on angiotensin receptor blocker monotherapy. Blood Press Monit 2011;16:87–95. 32. Eguchi K, Kuruvilla S, Ishikawa J, Ogedegbe G, Gerin W, Schwartz JE, et al. Correlations between different measures of clinic, home, and ambulatory blood pressure in hypertensive patients. Blood Press Monit 2011;16:142–8. 33. Cappuccio FP, Kerry SM, Forbes L, Donald A. Blood pressure control by home monitoring: meta-analysis of randomised trials. BMJ 2004;329:145. 34. Omre AH. Bluetooth low energy: wireless connectivity for medical monitoring. J Diabetes Sci Technol 2010;4: 457–63.