BP Measurement in Clinical Practice: Time to SPRINT to Guideline-Recommended Protocols

Abstract

Hypertension is the leading chronic disease risk factor in the world and is especially important in patients with CKD, nearly 90% of whom have hypertension. Recently, in the Systolic BP Intervention Trial (SPRINT), intensive lowering of clinic systolic BP to a target <120 mm Hg, compared with a standard BP target of <140 mm Hg, reduced risk for cardiovascular disease and all-cause mortality. However, because BP was measured unobserved using an automated device, some investigators have questioned the ability to translate SPRINT results into routine clinical practice, in which measurement of BP is typically less standardized. In this review, we discuss the BP measurement techniques used in major observational studies and clinical trials that form the evidence base for our current approach to treating hypertension, evaluate the effect of measurement technique on BP readings, and explore how ambulatory BP data from the SPRINT trial may inform this discussion. We conclude by arguing for implementation of guideline-recommended BP measurement techniques in routine clinical practice.

Recently, in the Systolic BP Intervention Trial (SPRINT), among hypertensive patients with and without CKD, intensive lowering of systolic BP to a target <120 mm Hg reduced risk for cardiovascular disease (CVD) and all-cause mortality compared with a standard BP target of <140 mm Hg. Results were similar in those with and without CKD.¹ Some have questioned the ability to translate the results into clinical practice because BP was measured with an automated monitor and a protocol on the basis of recommendations from the American Heart Association (AHA), which are not done routinely in many clinical practices.^2,3 The purpose of this review is to discuss the BP measurement techniques utilized in prior large observational studies and clinical trials that form the evidence base for our current approach to treating hypertension, to review the effect of nonstandardized BP measurement technique, and to describe ambulatory BP data from a subset of SPRINT participants which may inform this discussion and facilitate translation of SPRINT findings into clinical practice.

SPRINT randomly assigned 9261 patients at high cardiovascular risk to intensive treatment (systolic BP target <120 mm Hg) or standard treatment (<140 mm Hg).¹ SPRINT specifically oversampled persons with CKD—2646 (30%) participants had CKD at baseline. After a median follow-up of 3.3 years, the trial was stopped early. Intensive treatment was associated with a substantial reduction in the primary cardiovascular outcome (hazard ratio [HR], 0.75; 95% confidence interval [95% CI], 0.64 to 0.89) as well as all-cause mortality (HR, 0.73; 95% CI, 0.60 to 0.90). Importantly for nephrologists, results were similar in those with and without CKD; there was a similar effect size and direction for the effect of intensive BP treatment for the primary CVD outcome in the CKD and non-CKD subgroups (interaction P value was 0.36). Likely because of lower statistical power in the CKD subset, the association of randomization to intensive BP control with CVD did not reach statistical significance in the CKD subset alone (HR, 0.81; 95% CI, 0.63 to 1.05).⁴ On the other hand, even within the CKD subset, intensive BP control was associated with lower risk of all-cause mortality (HR, 0.72; 95% CI, 0.53 to 0.99).⁴ The two previous trials evaluating different BP targets in patients with CKD, the African American Study of Kidney Disease and Hypertension (AASK) and Modification of Diet in Renal Disease (MDRD), had renal outcomes as their primary end points, and did not examine CVD events.^5,6 It should be noted that SPRINT participants with CKD were at high cardiovascular risk but lower risk for progression of CKD with lower proteinuria and only mild-to-moderate decreased eGFR compared with AASK and MDRD participants. These aspects of the trial design are reflected in the low rates of renal events (decrease in eGFR of 50% or more or development of ESRD for patients with CKD at baseline) in SPRINT participants with CKD at baseline; only 29 of 2646 CKD participants experienced this composite end point and only 16 required dialysis.¹ As mentioned in the introduction, the BP measurement protocol outlined in the SPRINT Manual of Procedures was on the basis of recommendations from the AHA and included 5 minutes of quiet rest, average of three readings 1 minute apart, and appropriate patient positioning.² However, because of adherence to these recommendations, the use of automated devices, and measurement of BPs in the absence of an observer at some sites, some have questioned the ability to translate SPRINT results into routine clinical practice where measurement of BP is typically less standardized.³

Although numerous hypertension experts have argued that the BP measurement technique in SPRINT makes it an outlier, the SPRINT protocol is much more similar to nearly all prior clinical trials than the technique used in routine clinical practice. Early studies utilized manual BPs^7–10 whereas more recent studies have used automated monitors.^11–13 Regardless of the type of measurement device, nearly all of the studies that shape our understanding of the relationship between BP and adverse outcomes and guide antihypertensive therapy followed protocols that would be considered adherent to recommendations from the AHA (see Table 1). In addition to a period of quiet rest and multiple readings averaged to represent the clinic BP for that visit, the BP measurement protocols included the use of appropriate cuff size; proper patient positioning including back support, feet flat on floor, and arm supported at heart level; and cuff placed on a bare arm.²

Table 1.

Method/device, rest, and number of readings from BP protocols for prior large observational studies and clinical trials

Study	Year	Type of Study	Method/Device	Wait/Rest, min	# Readings
Framingham23	1970s	Observational	Manual	5	2
SHEP24	1991	Clinical trial	Manual	5	2
MDRD5	1994	Clinical trial	Manual	5	3
UKPDS7	1998	Clinical trial	Manual	5	3
ALLHAT8	2000	Clinical trial	Manual	5	2
HOPE9,10	2001	Clinical trial	Manual	15	2
HYVET25	2001	Clinical trial	Manual and automated	5	2
AASK6	2002	Clinical trial	Manual	5	3
ADVANCE11	2007	Clinical trial	Automated/Omron	5	2
CRIC26	2009	Observational study	Manual	5	3
ACCORD12	2010	Clinical trial	Automated/Omron	5	3
SPS327	2011	Clinical trial	Automated/Colin electronic device	15	3
ONTARGET13	2012	Clinical trial	Automated/Omron	3	2
CKD-JAC28	2013	Observational study	Manual	5	3

SHEP, Systolic Hypertension in the Elderly Program; UKPDS, UK Prospective Diabetes Study; ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; HOPE, Heart Outcomes Prevention Evaluation; HYVET, Hypertension in the Very Elderly Trial; ADVANCE, Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation; CRIC, Chronic Renal Insufficiency Cohort; ACCORD, Action to Control Cardiovascular Risk in Diabetes; SPS3, Secondary Prevention of Small Subcortical Strokes; ONTARGET, Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; CKD-JAC, Chronic Kidney Disease Japan Cohort.

Trained personnel left the room during automated BP measurement at some SPRINT centers. Notably, the AHA guidelines do not comment on the presence or absence of an observer during BP measurement. This is in part due to the fact that prior iterations of the guidelines were published when manual readings predominated because automated devices were just becoming available. The effect of an observer on automated BP readings is unknown. Whereas prior studies have compared manual BPs to unobserved automated BPs,¹⁴ to our knowledge, no study has compared BP results for observed versus unobserved measurement techniques using automated devices.

Studies have consistently found that nonadherence to specific components of the measurement protocol, such as cuff size, arm position, and rest, leads to higher readings (Table 2, top). Additionally, investigators have compared “routine” clinic BPs to those measured using appropriate protocols and found that routine BPs are typically 5–10 mm Hg higher (Table 2, middle). Unfortunately, the routine and AHA adherent BPs were not measured on the same day or in random order in the majority of these studies. Furthermore, the routine BPs were often obtained retrospectively from the clinic visits at which the patients were referred for ambulatory BP or to a hypertension specialist.¹⁵ The type of measurement device, manual versus automated, can also affect BP readings. Given that automated BP measurement in SPRINT may have been unobserved, this last issue has been the subject of much consternation by some, when considering the clinical ramifications of the SPRINT trial results. Regardless, the BP measurement techniques in SPRINT and prior observational studies and randomized trials more closely adhere to AHA recommendations than the technique utilized in routine clinical practice.

Table 2.

Studies evaluating effect of different BP measurement protocols

Author	Population	Protocol 1		Protocol 2		Notes
		Method	BP	Method	BP
A. Studies comparing specific components of BP measurement protocols
Mourad et al.29	Normotensive	Arm dependent	113/72	Arm horizontal	103/62	Similar results observed for ambulatory BP monitoring
	Hypertensive	Arm dependent	163/88	Arm horizontal	145/79
Webster et al.30	Hypertensive	Arm dependent	158/104	Arm horizontal	140/90
Adiyaman et al.31	Hypertensive	Legs crossed	147/88	Legs uncrossed	140/86
	Patients with diabetes	Legs crossed	138/76	Legs uncrossed	130/74
Fonseca-Reyes et al.32	Large arm circumference	Standard cuff	125/80	Large cuff	118/74	Prevalence of large arm circumference >40% in family medicine and hypertension clinics
B. Studies comparing “routine” and guideline-adherent BP measurement protocols
Myers et al.33	Hypertensive	“Routine” office	146/87	“Research RN”	137/78	Routine office BP was average over prior 3 mo
Graves et al.34	Hypertensive	“Routine” office	152/84	AHA method	138/74	Routine office BP at time of referral for ABPM
Brown et al.35	Hypertensive	“Routine” office	161/95	Formally trained RNs	152/85	Routine office BP at time of referral for ABPM
Ray et al.36	Hypertensive	“Routine” office	133/78	AHA method	134/80	Random order; 93% of patients results differed by ≥5 mm Hg SBP or ≥2 mm Hg DBP
C. Studies comparing manual and automated BP measurement protocols
Campbell et al.37	Firefighters	BpTRU	120/76	Standardized	122/78	Random order of measurement
Edwards et al.38	Hypertensive	BpTRU	136/74	Standardized	144/77	Retrospective; standardized BP before BpTRU in all patients
Myers et al.39	Adults	BpTRU	115/71	Standardized	118/74	Random order of measurement
Filipovský et al.40	Hypertensive	BpTRU	131/78	Physician	147/86	BpTRU first in all patients; no standard protocol for physician BPs

RN, registered nurse; ABPM, ambulatory blood pressure monitor; SBP, systolic blood pressure; DBP, diastolic blood pressure.

Ambulatory BP was measured in a subset of SPRINT participants during the treat-to-target phase of the trial. Results from this ancillary study provide new insights on the relationship of BP measured using the SPRINT protocol to ambulatory BP and allow for a comparison with BPs measured in other trials and settings. Twenty-four-hour ambulatory BP was measured during follow-up visits in 897 SPRINT participants at 15 clinical sites.¹⁶ Among these participants, daytime ambulatory systolic BP was 7 mm Hg higher than the corresponding SPRINT clinic BP in the intensive treatment group and 3 mm Hg higher than clinic BP in the standard treatment group (corresponding numbers were 6 and 5 mm Hg for diastolic BP). Observational studies have demonstrated that this type of masked effect, with higher ambulatory than clinic BPs, is associated with increased risk for CVD and all-cause mortality.¹⁷ On the other hand, white-coat hypertension (elevated clinic BP and normal ambulatory BP) is associated with lower risk for adverse outcomes. This is increasingly important because guidelines, including from the AHA and the US Preventative Services Task Force, recommend out-of-office BPs in the diagnosis and management of hypertension.^2,18 Despite these recommendations, the BPs used to define eligibility and BP targets in all major hypertension trials have been office based; whether targeting ambulatory versus clinic BP reduces risk for adverse outcomes is unknown, and represents an important research need in future studies.

In clinical practice, daytime ambulatory BPs are often lower than clinic BPs. Interestingly, this observation is not seen in clinical trials, where daytime ambulatory BPs have been found to be higher than clinic BPs. This finding may be due, in part, to the use of protocolized clinic BP measurement in clinical trials. Examples include the Heart Outcomes Prevention Evaluation and AASK trials as well as the Chronic Renal Insufficiency Cohort observational cohort study (Table 3).^19–21 Additional factors that may have contributed to lower daytime ambulatory relative to clinic BP in SPRINT include: (1) participants had attended at least 13 prior SPRINT visits which may reduce any potential white-coat effect and (2) the potential, albeit unknown, effect of the unobserved automated measurement technique. Although direct comparisons to BPs in routine clinical practice aren’t available in SPRINT, it is likely that the protocolized research clinic BPs were lower. This leads to an inevitable question: what systolic BP shall one target if one wants to use the evidence from SPRINT in clinical practice?

Table 3.

“Clinic” versus ambulatory BP in prior clinical trials and observational studies

Study	Clinic SBP	Daytime Ambulatory SBP	∆ Systolic BP
SPRINT <140 mm Hg group	135.5±14	138.8±13	+3.3
SPRINT <120 mm Hg group16	119.7±13	126.5±12	+6.8
AASK cohort20	133.6±17	137.6±17	+4.0
CRIC21	126.4±20	132.3±16	+5.9
HOPE10	151±20	156±20	+5.0

Values presented are mean ± SD. CRIC, Chronic Renal Insufficiency Cohort; HOPE, Heart Outcomes Prevention Evaluation.

The SPRINT results have at least two important implications for clinical practice. First and foremost, providers caring for patients at high risk for CVD should consider targeting a more intensive systolic BP goal, with a target of <120 mm Hg. Second, targeting a lower clinic BP necessitates adherence to clinic BP measurement techniques used in trials for measuring BP. At lower BPs, the importance of accurate measurement may be particularly important. For example, patients with a systolic BP just above 120 mm Hg using routine clinic BPs may have a systolic BP <110 mm Hg when measured appropriately. Such a patient would not actually need increased dosing or additional antihypertensive medications. Similarly, a patient with a systolic BP of approximately 110 mm Hg using routine clinic BPs who may be considered below goal may actually have a systolic BP of <100 mm Hg and should be more carefully screened for symptoms of hypotension. On the other end, higher systolic BPs obtained by non-AHA techniques likely lead to over-diagnosis and over-treatment of hypertension. Last, aggressive BP lowering may increase the likelihood of harm, such as hypotension, syncope, and AKI. When implementing SPRINT results into clinical practice, it seems prudent to consider close follow-up, orthostatic BP checks, and laboratory studies to assess safety as was done during SPRINT.

The 5 minutes of rest and three BP measurements 1 minute apart mean that measurement using the AHA protocol typically takes 8–10 minutes. Clinic space, staffing, and organizational inertia may be considered potential obstacles to implementing such protocols in clinical practice. Fortunately, newer BP monitors allow for unobserved BP measurement as was suggested in SPRINT. During the 8–10 minutes protocol, clinic staff can begin rooming other patients, document in the medical record, and perform other tasks. The time that patients wait, either before getting roomed or after the rooming process before being seen by a provider, should be seen as an opportunity to implement such protocols. Indeed, the average time that a patient waits to see their provider in the United States was recently reported to be >18 minutes.²²

As nephrologists, we are frequently asked to provide opinions on patients with resistant hypertension and hypertensive emergencies. It is time for us, as hypertension specialists, to push our colleagues, clinics, organizations, and health systems to stop treating measurement of BP as an obstacle to rapid patient flow in clinic, but rather as one of the most important aspects of each visit. At a minimum, BP measurement protocols should include a 3–5 minutes period of quiet rest, measurement of 2–3 BPs which are averaged, use of an appropriately sized cuff placed on a bare arm, and proper patient positioning including back support and arm supported at heart level. This recommendation applies to all patients, irrespective of CKD status. Nonprotocolized, routine clinic BP measurement almost certainly leads to over-diagnosis and over-treatment of hypertension. The response to the SPRINT trial results should not be to discount the findings as irrelevant or too challenging to be translated to clinical care. BP is a vital sign, after all, and should be measured as in the clinical trials so that we can provide evidence-based care to our patients, prevent harm, and improve quality and length of life.

Disclosures

None.