Abstract
Guidelines recommend using out of office blood pressure (BP) measurements to confirm the diagnoses of hypertension and in the titration of antihypertensive medication. The prevalence of out-of-office BP phenotypes for an office systolic/diastolic BP goal < 140/90 mmHg has been reported. However, the prevalence of these phenotypes when targeting an office systolic/diastolic BP goal < 120/80 is unknown. The Systolic Blood Pressure Intervention Trial Ambulatory BP Ancillary study evaluated out-of-office BP using ambulatory BP monitoring (ABPM) in 897 participants 27 months after randomization to intensive vs. standard BP targets (office systolic BP <120 mmHg vs. <140 mmHg). We used office and daytime BP to assess the proportion of participants with white coat effect (WCE) [standard target: office BP ≥140/90 mmHg and daytime BP <135/85 mmHg vs. intensive target: office BP ≥120/80 mmHg and daytime BP <120/80 mmHg] and masked uncontrolled hypertension (MUCH) [standard target: office BP <140/90 mmHg and daytime BP ≥135/85 mmHg vs. intensive target: office BP <120/80 mmHg and daytime BP ≥120/80 mmHg] in each treatment arm. The prevalence of WCE and MUCH was 9% and 34%, in both treatment groups. Among participants with uncontrolled office BP, WCE was present in 20% and 23% in the intensive and standard groups, respectively. Among participants with controlled office BP, MUCH was present in 62% and 56% in the intensive and standard groups, respectively. In conclusion, a more intensive BP target resulted in a similar proportion of patients with WCE and MUCH compared to a standard target.
Keywords: Hypertension, ambulatory blood pressure, blood pressure goal
Guidelines and scientific statements recommend measuring office blood pressure (BP) to identify the presence of hypertension and to monitor the response to antihypertensive medication.1 However, for many adults, BP is different outside versus inside the office. Many guidelines recommend measuring BP outside of the office setting to confirm the diagnosis of hypertension and evaluate whether BP is controlled among individuals taking antihypertensive medication.2–4 In meta-analyses of population-based studies, about 13% of adults taking antihypertensive medication have white coat effect and 31% have masked uncontrolled hypertension when defined using an office systolic BP/diastolic BP of 140/90 mm Hg to define high BP.2, 5 The Systolic Blood Pressure Intervention Trial (SPRINT) demonstrated that targeting office systolic BP <120 compared to <140 mm Hg was associated with lower risk of cardiovascular disease (CVD) and mortality.6 The prevalence of white coat effect and masked uncontrolled hypertension when treating to an office systolic/diastolic BP target of <120/80 mm Hg is unknown. Estimating the prevalence of these phenotypes when using a lower BP treatment target may help guide whether out-of-office BP measurements are needed.
The aim of the current study was to estimate the prevalence of white coat effect and masked uncontrolled hypertension when targeting an office systolic/diastolic BP <120/80 mm Hg compared to <140/90 mm Hg. To accomplish this aim, we analyzed data from the SPRINT Ambulatory BP ancillary study.
Methods
Data Availability
Some anonymized data and materials have been made publicly available through the National Heart, Lung, and Blood Institute at https://biolincc.nhlbi.nih.gov/studies/sprint/ for reproducing/replicating the results of this analysis. The Statistical Analysis section provides details of analytical methods.
Study Participants
The study design and methods of SPRINT have been previously published.6, 7 Briefly, SPRINT is a multicenter, randomized controlled trial that assigned 9,361 participants to an intensive (<120 mm Hg) or standard (<140 mm Hg) office BP-based strategy. Eligible participants were at least 50 years old with an office systolic BP between 130 and 180 mm Hg, depending on the number of classes of antihypertensive medication they were taking during the screening process. Participants had at least one or more CVD risk factor: the presence of clinical or subclinical CVD other than stroke, an estimated glomerular filtration rate (eGFR) [based on the Modification of Diet in Renal Disease study equation] of 20–59 ml/min per 1.73 m2, a Framingham 10-year risk score ≥15%, or age ≥75 years. Exclusion criteria included diabetes mellitus, previous stroke, polycystic kidney disease, symptomatic heart failure in the past 6 months, left ventricular ejection fraction <35%, a known cause of secondary hypertension, any organ transplant, severe chronic kidney disease (CKD) (eGFR <20 mL/min per 1.73 m2), dialysis, proteinuria >1 g/d, dementia, and systolic BP <110 mm Hg after 1 minute of standing.
The present study was an analysis based on a subgroup of SPRINT participants who were recruited at 15 sites to participate in an ambulatory blood pressure monitoring (ABPM) ancillary study at the 27‐month follow‐up visit. Each site’s institutional review board approved the ancillary study. Participants were excluded from the ABPM ancillary study for the following reasons: their arm circumference was >50 cm, they were a shift worker or worked regularly at night, they had a history of breast cancer requiring mastectomy or radiation on the non-dominant arm and needed to avoid frequent BP measurements due to lymphedema, or they had end‐stage renal disease. Across the 15 sites, 1,003 participants consented to participate in the ABPM ancillary study. Of these, 925 participants were eligible and underwent ABPM; 28 participants were excluded due to an incomplete ABPM recording as defined below. The 897 participants included 453 participants in the intensive office BP-based strategy group and 444 participants in the standard office BP-based strategy group.
For the current study, clinical and laboratory data from the 24 and 27-month study visits and office BP at the 27-month study visit were used for the analysis. CKD was defined as having an eGFR <60 mL/min per 1.73 m2 or urine albumin to creatinine ratio [UACR] ≥ 30mg/g.
Blood Pressure Measurement
Office BP was measured using a validated automated oscillometric measurement device (HEM‐907XL, Omron Healthcare, Lake Forest, IL) and standardized procedures.7–9 Clinic staff was instructed to measure BP early in the visit, before any potentially stressful exam components such as blood draws. After properly positioning participants in a chair with back support and determining the appropriate BP cuff size for the right arm, clinic staff were instructed to set the device to automatically wait 5 minutes and then obtain 3 measurements at 1 minute intervals.10 A participant’s left arm was used for BP measurement if BP was higher in that arm or if there was an anomaly in the right arm.
ABPM was conducted over a 24-hour period within 3 weeks of the 27-month study visit using a validated device, SpaceLabs 90207 (Snoqualmie, WA).11 The median number of days between the 27-month study visit and initiation of ABPM was 0 (25–75th percentiles 0–6 days). The monitor was placed on the participants’ non-dominant arm and configured to measure BP every 30 minutes. An ABPM recording was deemed to be complete if there were at least 14 readings between 6:00 AM and midnight and at least 6 readings between midnight and 6:00 AM.12–14 As recommended by the European Society of Hypertension, daytime systolic BP and daytime diastolic BP were defined as the mean of all systolic BP readings and diastolic BP readings, respectively, during the 9:00 AM to 9:00 PM window; nighttime systolic BP and nighttime diastolic BP were defined as the average of all systolic BP readings and diastolic BP readings, respectively, during the 1:00 AM to 6:00 AM window.15 Twenty-four hour systolic BP and diastolic BP was defined as the mean of all systolic BP readings and diastolic BP readings, respectively, over the entire monitoring period.
Phenotypes Based on Office BP and ABPM
In primary analyses, we used office and daytime systolic/diastolic BP to define the following BP phenotypes: white coat effect, masked uncontrolled hypertension, sustained uncontrolled hypertension, and sustained controlled hypertension. Two approaches were undertaken to define these BP phenotypes. The first approach was to use the daytime systolic/diastolic BP thresholds recommended by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) high BP guideline that correspond to the office systolic systolic/diastolic BP of 120/80 mmHg in the intensive strategy group (daytime systolic/diastolic BP of 120/80 mmHg) and 140/90 mmHg in the standard strategy group (daytime systolic/diastolic BP of 135/85 mmHg) (Table S1).2, 16 The second approach was to use the same office and daytime systolic/diastolic BP goal for both groups: office systolic systolic/diastolic BP and daytime systolic/diastolic BP of 130/80 mmHg (Table S2). This is the threshold used to define uncontrolled BP in the 2017 ACC/AHA high BP guideline.2
Statistical Analyses
We compared characteristics of patients randomized to the intensive vs. standard treatment groups. Continuous variables are presented as mean (SD), and categorical variables as n (%). The statistical significance of differences across treatment groups were calculated using chi‐squared (χ2) tests for categorical variables and t tests for continuous variables. Within each group, intensive strategy group and standard strategy group, the proportion of participants with each BP phenotype (white coat effect, masked uncontrolled hypertension, sustained uncontrolled hypertension, and sustained controlled hypertension) was calculated with their corresponding 95% confidence intervals (CI) using the Wilson score method. The difference in proportions of BP phenotypes between participants randomized to the intensive versus standard treatment group for each hypertension phenotype and overall was determined by χ2 test. Further, within each treatment group, the proportion of participants with white coat effect was calculated among participants with uncontrolled office systolic/diastolic BP (≥120/80 mmHg for the intensive strategy group and ≥140/90 mmHg for the standard strategy group) and the proportion with masked uncontrolled hypertension was calculated among participants with controlled office systolic/diastolic BP (<120/80 mmHg for the intensive strategy group and <140/90 mmHg for the standard strategy group), respectively.
In sensitivity analyses we defined BP phenotypes using only systolic BP rather than systolic/diastolic BP, because only office systolic BP was targeted in SPRINT. In a second sensitivity analysis, we used 24 hour systolic/diastolic BP instead of daytime systolic/diastolic BP to define out-of-office BP (Table S3 and S4). In addition to doing analyses for the overall population, we assessed the proportion of participants with each BP phenotype within subgroups defined by age (<65 and ≥ 65 years), race (black and white), sex (female and male), and chronic kidney disease (CKD). Statistical analyses were conducted using RStudio (RStudio: Integrated Development for R. RStudio, Inc., Boston, MA, Version 3.0).
Results
Clinical characteristics
Among the intensive and strategy groups, participants had a median of 34 daytime systolic and diastolic BP readings and 12 nighttime systolic and diastolic BP. The characteristics of participants in each treatment group are shown in Table 1. There were no statistically significant differences in age, sex, race/ethnicity, body mass index, smoking status, and alcohol use between the intensive strategy group versus standard strategy group. The percentage of participants with reduced eGFR was higher and with albuminuria was lower in the intensive strategy group compared with the standard strategy group at the 24-month study visit. Participants in the intensive strategy group were taking more classes of antihypertensive medication than participants in the standard strategy group at the 27-month study visit. Office, daytime, 24-hour systolic, and nighttime systolic BP and diastolic BP were lower in participants in the intensive strategy group versus participants in the standard strategy group.
Table 1.
Characteristics of SPRINT participants in the ambulatory blood pressure monitoring ancillary study
| Characteristics | Intensive strategy group (N=453) | Standard strategy group (N=444) | P-value |
|---|---|---|---|
| Age, years; 27 month | 71.5 ± 9.3 | 71.5 ± 9.7 | 0.90 |
| Female sex | 132 (29%) | 125 (28%) | 0.80 |
| Race/ethnicity | 0.50 | ||
| White | 300 (66%) | 304 (69%) | |
| Black | 127 (28%) | 124 (28%) | |
| Hispanic | 13 (3%) | 8 (2%) | |
| Other | 13 (3%) | 8 (2%) | |
| Body mass index, kg/m2; 24 month | 29.6 ± 5.7 | 29.4 ± 5.5 | 0.57 |
| Smoking status; 24 month | 0.60 | ||
| Never | 210 (47%) | 204 (46%) | |
| Former | 192 (43%) | 199 (45%) | |
| Current | 50 (11%) | 41 (9%) | |
| Alcohol use, baseline | 0.10 | ||
| Non-drinker | 171 (38%) | 178 (40%) | |
| Light drinker | 91 (20%) | 89 (20%) | |
| Moderate drinker | 117 (26%) | 99 (22%) | |
| Heavy drinker | 43 (10%) | 60 (14%) | |
| Unknown | 31 (7%) | 18 (4%) | |
| History of CVD, baseline | 94 (21%) | 101 (23%) | 0.52 |
| Experienced CVD event before ABPM | 15 (3%) | 14 (3%) | >0.999 |
| Reduced eGFR1 < 60 ml/min/1.73m2; 24 month | 107 (24%) | 65 (15%) | 0.001 |
| Albuminuria1; 24 month | 59 (14%) | 99 (24%) | <0.001 |
| Total cholesterol, mg/dL; 24 month | 183.4 ± 39.9 | 178.4 ± 38.6 | 0.06 |
| HDL cholesterol, mg/dL; 24 month | 52.7 ± 17.2 | 53.5 ± 16.7 | 0.46 |
| LDL cholesterol, mg/dL; 24 month | 107.9 ± 34.6 | 101.9 ± 32.6 | 0.01 |
| Total triglycerides, mg/dL; 24 month | 100 [70.8, 142] | 93 [63, 145] | 0.8 |
| Number of antihypertensive medication classes; 27 month | 2.9 ± 1.2 | 1.8 ± 1.1 | <0.001 |
| Diuretics | 342 (76%) | 188 (42%) | <0.001 |
| B-blockers | 182 (40%) | 125 (28%) | <0.001 |
| Calcium channel blockers | 271 (60%) | 145 (33%) | <0.001 |
| ACE inhibitors | 163 (36%) | 128 (29%) | 0.03 |
| Angiotensin receptor blockers | 190 (42%) | 141 (32%) | 0.002 |
| Vasodilators | 26 (6%) | 10 (2%) | 0.01 |
| Alpha-blockers | 47 (10%) | 33 (7%) | 0.16 |
| Systolic BP, mmHg | |||
| Office systolic BP, mmHg; 27 month | 119.9 ± 13.3 | 135.5 ± 13.7 | <0.001 |
| Daytime systolic BP, mmHg | 126.5 ± 12.3 | 138.8 ± 12.6 | <0.001 |
| 24-hour systolic BP, mmHg | 122.7 ± 12.0 | 134.0 ± 11.8 | <0.001 |
| Nighttime systolic BP, mmHg | 115.7 ± 14.6 | 125.5 ± 14.6 | <0.001 |
| Diastolic BP, mmHg | |||
| Office diastolic BP, mmHg; 27 month | 65.9 ± 10.5 | 73.6 ± 12.2 | <0.001 |
| Daytime diastolic BP, mmHg | 72.0 ± 8.5 | 78.6 ± 10.7 | <0.001 |
| 24-hour diastolic BP, mmHg | 68.8 ± 8.0 | 74.7 ± 10.0 | <0.001 |
| Nighttime diastolic BP, mmHg | 63.4 ± 9.5 | 68.5 ± 10.8 | <0.001 |
CVD: cardiovascular disease, eGFR: estimated glomerular filtration rate, BP: blood pressure
Values are n(%), mean ± standard deviation, or median (25th percentile, 75th percentile). Baseline data (sex, race, alcohol use, and history of CVD) are collected at randomization visit. 24-month data (body mass index, smoking status, reduced eGFR, albuminuria, total cholesterol, HDL cholesterol, LDL cholesterol, and total triglycerides) are collected at 24-month annual visit. 27-month data (age, experienced CVD event before ABPM, antihypertensive mediactions, and ambulatory BPs) is collected at 27 month study visit.
eGFR: based on MDRD study equation;
Urine albumin-to-creatinine ratio ≥30 mg/g
BP phenotypes
Using office and daytime systolic/diastolic thresholds of 120/80 mmHg in the intensive strategy group, and an office systolic/diastolic BP threshold of 140/90 mmHg and daytime systolic/diastolic BP threshold of 135/85 mmHg in standard strategy group, the proportion of participants with white coat effect was 9% in each treatment group and the proportion of participants with masked uncontrolled hypertension was 34% in each group (Figure 1, Table 2). Compared to the standard strategy group, the proportion of participants with sustained uncontrolled hypertension was higher among the intensive compared to the standard strategy group (30% versus 37%, p-value=0.03) and the proportion of participants with sustained controlled systolic hypertension was lower among the intensive strategy group (27% versus 20%, p-value=0.02). Among participants with uncontrolled office systolic/diastolic BP, white coat effect was present in 20% (95%CI: 14.8%, 25.5%) and 23% (95%CI: 17.6%, 30.1%) in the intensive and standard groups, respectively. The proportion of participants with masked uncontrolled hypertension among participants with controlled office systolic/diastolic BP was 62% (95%CI: 56.1%, 68.1%) and 56% (95%CI: 49.8%, 61.5%) in intensive and standard groups, respectively.
Figure 1. Distribution of blood pressure phenotypes based on office and daytime systolic/diastolic blood pressure using thresholds specific to the intensive and standard strategy group.
• Threshold for intensive group: office systolic/diastolic blood pressure of 120/80 mm Hg and daytime systolic/diastolic blood pressure of 120/80 mm Hg
• Threshold for standard strategy group: office systolic/diastolic blood pressure of 140/80 mm Hg and daytime systolic/diastolic blood pressure of 135/85 mm Hg
Table 2.
Distribution of blood pressure phenotypes based on office and daytime systolic/diastolic blood pressure using thresholds specific to the intensive and standard strategy group
| BP phenotype | Intensive strategy group (N=453) | Standard strategy group (N=444) | P-value* | Overall X2 P-value** |
|---|---|---|---|---|
| White coat effect | 9% [7%, 12%] | 9% [7%, 12%] | 0.99 | 0.048 |
| Masked uncontrolled hypertension | 34% [29%, 38%] | 34% [30%, 39%] | 0.92 | |
| Sustained uncontrolled hypertension | 37% [33%, 42%] | 30% [26%, 34%] | 0.03 | |
| Sustained controlled hypertension | 20% [17%, 24%] | 27% [23%, 31%] | 0.02 |
Data are expressed as percentages with 95% confidence interval (CI) within arm.
p-value for the difference in proportions of BP phenotypes between participants randomized to the intensive versus standard treatment group for each hypertension phenotype
X2 = 7.9, df=3
• Threshold for intensive group: office systolic/diastolic blood pressure of 120/80 mm Hg and daytime systolic/diastolic blood pressure of 120/80 mm Hg
• Threshold for standard strategy group: office systolic/diastolic blood pressure of 140/80 mm Hg and daytime systolic/diastolic blood pressure of 135/85 mm Hg
Using an office systolic/diastolic BP threshold of 130/80 mmHg and daytime systolic/diastolic threshold of 130/80 mmHg in both the intensive strategy and standard strategy groups, a lower proportion of participants in the intensive strategy group had sustained uncontrolled hypertension (15% versus 82%, p-value<0.001) and a higher proportion of participants had sustained controlled hypertension (54% versus 11%, p-value<0.001) compared to the standard strategy group (Figure S1, Table S3). Among participants with uncontrolled office systolic/diastolic BP, white coat effect was present in 38% (95%CI: 29.4%, 47.1%) and 13% (95%CI: 10.0%, 17.7%) in the intensive and standard group, respectively. The proportion of participants with masked uncontrolled hypertension among participants with controlled office systolic/diastolic BP was 29% (95%CI: 24.1%, 33.7%) and 62% (95%CI: 53.3%, 70.1%) in intensive and standard group, respectively.
Sensitivity and subgroup analyses
The proportion of participants with each BP phenotype in the intensive versus standard groups using daytime systolic BP only and using 24-hour systolic/diastolic BP instead of daytime systolic/diastolic BP are shown in Tables S6 to S9. The percentage of participants with white coat hypertension in the intensive and standard treatment arms was between 6% and 9% within all subgroups defined by age, race, sex and CKD status compared to 9% in the overall cohort (Tables S10 to S13), respectively. Between 25% and 41% of participants in all subgroups had masked uncontrolled hypertension compared to 34% in the main results. For all subgroups except female participants with masked uncontrolled hypertension, there was no statistically significant difference in the proportion of patients with white coat effect and masked uncontrolled hypertension between treatment groups. Among female participants, the percentage of patients with masked uncontrolled hypertension in the intensive and standard group was 39% and 36% respectively (p=0.01).
Discussion
There are several important findings from the current study when using treatment arm specific cutoff thresholds to determine BP phenotypes. First, a similar proportion of patients had white coat effect and masked uncontrolled hypertension when randomized to an intensive versus a standard BP lowering treatment strategy. However, intensive treatment was associated with a larger proportion of individuals with sustained uncontrolled hypertension and a smaller proportion with sustained controlled hypertension, when using BP thresholds specific for treatment group. The results were similar when using daytime systolic BP only and 24-hour systolic/diastolic BP to define BP phenotypes. The prevalence of masked uncontrolled hypertension was higher than the prevalence of white coat effect in both treatment arms. White coat effect was present in approximately 20% of participants with uncontrolled office BP in both arms and masked uncontrolled hypertension was present in approximately 60% of participants with controlled office BP in both arms, when using treatment specific BP thresholds. Since the prevalence of white coat effect and masked uncontrolled hypertension were high when using a standard and intensive BP target, recommendations for obtaining ABPM apply regardless of treatment intensity.
When using the same BP thresholds (130/80 mmHg) for office BP and daytime BP, an intensive versus standard treatment strategy led to a smaller proportion with sustained uncontrolled hypertension and a larger proportion with sustained controlled hypertension. Compared to the standard treatment strategy, intensive treatment resulted in a higher proportion of participants with white coat effect among those with uncontrolled office BP and a smaller proportion of participants with masked uncontrolled hypertension among those with controlled office BP. These results should be interpreted with caution as the systolic BP targets used in SPRINT were 120 and 140 mm Hg for the intensive and standard treatment group, respectively, rather than 130mm Hg. Given the high prevalence of white coat effect and masked uncontrolled hypertension, the results from the current study suggest that out of office BP measurements are still useful to characterize BP phenotypes even with an intensive systolic treatment goal (<120 mmHg).
A few prior studies have examined the effects of antihypertensive medication treatment on both office and ambulatory BP. Along with the current study, these studies provide an estimate of the effect of antihypertensive medication on white-coat effect and masked uncontrolled hypertension. In a substudy (n=695) of the Systolic Hypertension in Europe (Syst-Eur) Trial, a randomized double-blind placebo controlled trial of antihypertensive medication treatment in older individuals with isolated systolic hypertension (office BP of 160–219/<95 mmHg), Fagard et. al., found that among those with white coat effect at baseline (daytime systolic BP < 140 mmHg), antihypertensive medication treatment led to a larger reduction in office BP compared to placebo.17 In contrast, there were no reductions in daytime or nighttime BP with antihypertensive medication. Further, antihypertensive medication versus placebo led to larger reductions of office, daytime and nighttime BP among those with mild sustained uncontrolled hypertension (daytime systolic BP 140–159 mmHg) and moderate sustained uncontrolled hypertension (daytime systolic BP ≥ 160 mmHg). In the European Lacidipine Study on Atherosclerosis (ELSA), a randomized double-blind controlled trial comparing atenolol and lacidipine, office BP was measured at 6-month intervals and ABPM was performed at 12-month intervals.18 In an analysis that pooled the individuals who were treated with atenolol and lacidipine (n=1,921), Mancia et. al., found that among those with white coat hypertension at baseline, defined as having high office BP (≥150/95 mmHg) with 24-hour BP <130/80 mmHg, antihypertensive medication treatment was associated with a reduction in office BP but not a reduction in 24-hour BP.19 In contrast, antihypertensive medication treatment was associated with a reduction in office, daytime, nighttime and 24-hour systolic and diastolic BP among individuals with sustained uncontrolled hypertension, defined as having high office BP (≥ 150/95 mmHg) and 24-hour systolic BP/diastolic BP ≥ 130/80 mmHg. The findings from the Sys-Eur and ELSA trials suggest that using antihypertensive medication to lower office BP may only reduce office BP among individuals with white coat effect. Furthermore, antihypertensive medication resulted in a decrease in both office BP and ambulatory BP among individuals with sustained uncontrolled hypertension. In the current study, reducing office BP to <120 mmHg or <140 mmHg resulted in a similar prevalence of white coat effect.
In the current study, the prevalence of masked uncontrolled hypertension was also not different between the intensive versus standard treatment groups. It has been proposed that intensifying antihypertensive medication to target office BP may inadvertently increase the likelihood of having masked uncontrolled hypertension.5, 20 Individuals with sustained uncontrolled hypertension may be converted to having masked uncontrolled hypertension as ambulatory BP, which is not targeted, may not be reduced.21
There are several strengths of the study. The study was part of SPRINT, a large randomized controlled trial that tested intensive versus standard treatment strategies. Further, the study sample was multi-ethnic which increases the generalizability of the study findings. The study also included the analyses of several subgroups. There are several potential limitations. ABPM was not performed at baseline. Therefore, the study was unable to determine within-person changes in BP phenotypes. ABPM was conducted in only a subset of SPRINT participants; however, the participants who did and did not participate in the ABPM ancillary study had similar baseline characteristics.14 Office BP was based on a single visit and ABPM was done only once. Office BP and ambulatory BP do not have perfect short-term reproducibility.1 We relied on ABPM times to determine daytime/nighttime readings as we did not have patient diaries. As per protocol ABPM was measured in the non-dominant arm and office BP was measured in the right arm unless BP was higher in the left arm. The data on the percentage of participants that had ABPM measured in the right arm were not available. In the US, ABPM is not widely available in primary care settings but is only available in specialty centers or practices. Another form of out-of-office monitoring is home BP monitoring.1 In contrast to ABPM, home BP monitoring devices are more widely available in the US.1 Home BP monitoring was not conducted in SPRINT. Future studies should assess the impact of intensive BP control on white coat effect and masked uncontrolled hypertension. Moreover, the current results are based on research grade office BP measurements and ABPM readings. In routine clinical practice, the quality of BP measurements greatly varies whether obtained inside or outside the office setting.22 Further, for some SPRINT participants, office BP readings were obtained in an unattended manner (i.e., without a staff member being present). It is unclear whether the current findings are generalizable to BP measurements taken in clinical practice or whether the findings would differ between unattended and attended measurements. Also, we were not able to evaluate the prognostic significance of the different BP phenotypes. Finally, the study was comprised of older adults who were at high baseline CVD risk. It is unclear if the study findings can be extrapolated to younger adults who are low CVD risk.
Perspectives
In the current study, the proportion of participants with white coat effect and masked uncontrolled hypertension were similar with an intensive versus standard office BP-based hypertension treatment strategy. The prevalence of masked uncontrolled hypertension was high, even among participants with a systolic BP target of <120 mm Hg. Recent guidelines recommend out-of-office BP monitoring to detect white coat effect and masked uncontrolled hypertension among adults taking antihypertensive medication with and without high office BP, respectively.2, 3 The current findings suggest that ABPM should still be recommended to detect white coat effect and masked uncontrolled hypertension even with a systolic BP goal of 120 mm Hg. This is in concordance with the 2017 ACC/AHA BP guideline, which recommend obtaining out of office BP measurements to confirm the diagnosis of hypertension and screen for white coat effect and masked uncontrolled hypertension among patients taking antihypertensive medication.2
Supplementary Material
Table 3.
Distribution of blood pressure phenotypes based on office and daytime systolic/diastolic blood pressure using the same thresholds in the intensive strategy and standard strategy groups
| BP phenotype | Intensive strategy group (N=453) | Standard strategy group (N=444) | P-value* | Overall X2 P-value** |
|---|---|---|---|---|
| White coat effect | 9% [7%, 12%] | 10% [7%, 13%] | 0.75 | <0.001 |
| Masked uncontrolled hypertension | 22% [18%, 26%] | 17% [14%, 21%] | 0.13 | |
| Sustained uncontrolled hypertension | 15% [12%, 19%] | 62% [58%, 67%] | <0.001 | |
| Sustained controlled hypertension | 54% [49%, 58%] | 11% [8%, 14%] | <0.001 |
Data are expressed as percentages with 95% confidence interval (CI) within arm.
p-value for the difference in proportions of BP phenotypes between participants randomized to the intensive versus standard treatment group for each hypertension phenotype
X2 = 260.0, df=3
• Threshold for intensive and standard strategy group: office systolic/diastolic blood pressure of 130/80 mm Hg and daytime systolic/diastolic blood pressure of 130/80 mm Hg
Novelty and Significance.
What is New?
An intensive vs. standard treatment strategy (office systolic BP< 120 mmHg vs < 140 mmHg) resulted in: 1) no change in percentage of white coat effect and masked uncontrolled hypertension; 2) larger proportions of participants with masked uncontrolled hypertension among those with controlled clinic BP
What is Relevant?
Our findings demonstrate that even with an intensive BP goal, ABPM is needed to screen for white coat effect and masked uncontrolled hypertension.
Summary
An intensive BP lowering strategy does not affect the prevalence white coat effect or masked uncontrolled hypertension.
Acknowledgements
We thank the study participants, with whom this trial would not have been possible.
Sources of Funding
The SPRINT ambulatory blood pressure ancillary study was supported by grants R03DK100530 (P.E. Drawz). The SPRINT (Systolic Blood Pressure Intervention Trial) is funded with Federal funds from the NIH, including the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), and the National Institute of Neurological Disorders and Stroke (NINDS), under Contract Numbers HHSN268200900040C, HHSN268200900046C, HHSN268200900047C, HHSN268200900048C, HHSN2682009 00049C, and Inter-Agency Agreement Number A-HL-13–002-001. It was also supported in part with resources and use of facilities through the Department of Veterans Affairs. The SPRINT investigators acknowledge the contribution of study medications (azilsartan and azilsartan combined with chlorthalidone) from Takeda Pharmaceuticals International, Inc. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, NHLBI, the US Department of Veterans Affairs, the US Department of Health and Human Services, the University of Minnesota, or the United States Government. We also acknowledge the support from the following: Clinical and Translational Science Awards funded by National Center for Advancing Translational Sciences (NCATS)—Case Western Reserve University: UL1TR000439; Ohio State University: UL1RR025755; University of Pennsylvania: UL1RR024134 and UL1TR000003; Boston: UL1RR025771; Stanford: UL1TR000093; Tufts: UL1RR025752, UL1TR000073, and UL1TR001064; University of Illinois: UL1TR000050; University of Pittsburgh: UL1TR000005; University of Texas Southwestern: 9U54TR000017–06; University of Utah: UL1TR000105–05; Vanderbilt University: UL1TR000445; George Washington University: UL1TR000075; University of CA, Davis: UL1TR000002; University of Florida: UL1TR000064; University of Michigan: UL1TR000433; and Tulane University: P30GM103337 Center of Biomedical Research Excellence Award, National Institute of General Medical Sciences. All components of the SPRINT study protocol were designed and implemented by the investigators. The investigative team collected, analyzed, and interpreted the data. All aspects of article writing and revision were performed by the coauthors. Scientists at the National Institutes of Health participated in the design of SPRINT and as a group had 1 vote on the steering committee of the trial.
Footnotes
Disclosures
The authors have no disclosures to report.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
Some anonymized data and materials have been made publicly available through the National Heart, Lung, and Blood Institute at https://biolincc.nhlbi.nih.gov/studies/sprint/ for reproducing/replicating the results of this analysis. The Statistical Analysis section provides details of analytical methods.