Misclassification and discordance of measured blood pressure from patient’s true blood pressure in current clinical practice: a clinical trial simulation case study

Abstract

Treatment decisions for hypertension using sphygmomanometer based measurements and the current clinical practice paradigm do not account for the timing of blood pressure (BP) measurement. This study aimed to evaluate the clinical implications of discordance between measured and true BP, to quantify BP misclassification rate at a typical clinical visit in current clinical practice, and to propose a BP calibration system to decrease the impact of timing of BP measurement. A clinical trial simulation case study was performed using an in silico Monte Carlo Simulation approach. The time-courses of BPs with and without an antihypertensive treatment effect were simulated from a baseline BP model combined with an antihypertensive PK/PD model. Virtual subject characteristics were sampled from the FDA internal database. The baseline BP model was qualified using observed 24 h ambulatory BP monitoring (ABPM) data from 225 subjects by a visual predictive check as well as a global sensitivity analysis. First of all, our results showed that the measured cuff BP in current typical clinical practice deviated from the true values. (1) Cuff BP deviated from the true values by more than 5 mmHg in 57 % (95 % CI: 54-61 %) of patients and more than 10 mmHg in 26 % (95 % CI: 22-32 %) of patients respectively. (2) These discordances were reduced to 28 % (deviation ≥ 5 mmHg, 95 % CI: 18-40 %) and 9 % (deviation ≥ 10 mmHg, 95 % CI: 4-18%) of patients assuming perfect sphygmomanometer measurement and thus represent the contribution of ignoring the daily circadian rhythm of BP. Secondly, our results showed 23-32 % of patients were misclassified to an incorrect BP category for a casual clinical visit based on JNC 7 guideline. In addition, the accuracy of the measured cuff BP varied by time of clinic visit. Specifically, 11:00 AM to 3:00 PM was identified to be the better time frame, while times before 9:00 AM were the worst time frame. Therefore, clinic visit time may need to be adjusted accordingly. Finally, we proposed an easy BP calibration method for clinic use to adjust for time of day differences due to circadian variability in case that the desirable clinic visit time cannot be tailored for practical reasons.

Predicting Out-of-Office Blood Pressure in the Clinic (PROOF-BP)

“…Clinic blood pressure values are often different from out-of-office blood pressure and can lead to incorrect classification of blood pressure status and hence inappropriate management. 6 , 7 Patients with higher clinic blood pressure than the corresponding out-of-office pressure will have a negative home–clinic blood pressure difference (white coat effect) and are at risk of overtreatment (Figure S1 in the online-only Data Supplement). 8 Conversely, patients with higher out-of-office blood pressures than the corresponding clinic blood pressure would be expected to have a positive home–clinic blood pressure difference (masked effect), and often remain unrecognized and therefore potentially undertreated (Figure S1).…”

Scaling up the use of home blood pressure monitoring in the management of hypertension in low‐income countries: A step towards curbing the burden of hypertension

“…Even though CBPM is simple and convenient to use, it has some drawbacks including a high rate of patient misclassification attributed to masked or white‐coat hypertension (WCH), the inability to obtain serial measurements during a 24‐hour period, and a poor correlation with end‐organ damage and cardiovascular events . To get around the white‐coat effect in clinical practice, it had been suggested to measure BP using the validated automated devices in an isolated room, before the patient gets to the doctor's office .…”

Are Pain Ratings Irrelevant?

“…Even those considered “objective” such as blood pressure and heart rate recordings are plagued with issues of how to optimally measure them and capture their variability. However, it is very unlikely that those recordings will not be taken and noted as the starting point at any and all visits to the hypertension clinic . For pain medicine, it is important that we develop acceptable clinical tools that clinicians will find useful enough to record regularly as documentation in their care of pain patients.…”