Short summary

This quality assessment study will evaluate different blood pressure (BP) measurement techniques in the outpatient clinic of the Dept. of Medicine at Kolding Hospital. Specifically, the study will evaluate the quality of the usual BP-measurement routine (office blood pressure measurement (OBPM) or home blood pressure measurements (HBPM)) by comparison with a new alternative (automated office blood pressure measurement (AOBPM)) and gold standard approach (24 hour ambulatory blood pressure measurement (24hABPM)). As part of the study the treating physician will be asked whether treatment would have differed if AOBPM results were used for BP assessment rather than OBPM or HBPM.

Rationale

Hypertension is the strongest driver for cardiovascular (CV) disease in patients with type 2 diabetes (T2DM)1  and  progression of chronic kidney disease (CKD)2. More than two-thirds of patients with T2DM have hypertension3 and hypertension is one of the most frequent causes that lead to CKD4. Reliability of standard office blood pressure measurement (OBPM) in T2DM and CKD is modest,5,6 but remains the primary measurement technique in everyday clinical setting used for screening and diagnosis of hypertension. 

In patients with T2DM 24 hour ambulatory blood pressure measurement (24hABPM) is more closely associated with diabetes complications and hypertension mediated organ damage (HMOD)8 and the same is applicable for CKD. 24hABPM is a better predictor for CV disease and progression in CKD9,10  compared to OBPM. 24hABPM provides a comprehensive insight of blood pressure strain with estimation of white coat effect, masked hypertension, blood pressure variability and circadian variation. Routine use of 24hABPM may help identify patients with underestimated blood pressure allowing opportunity to lower CV risk (with therapeutics or lifestyle) and equally important; identifying patients with overestimated blood pressure thus preventing overmedication. However 24hABPM is not routinely used in everyday clinical practice due to unavailability, impracticalities and inconvenience for the patient. A possible alternative instead of 24hABPM is automated office blood pressure measurement (AOBPM). AOBPM eliminates the possibility for conversation during readings, terminal digit preference and reduces the risk for white-coat effect in numerous studies in primary care and hypertension clinic settings11-13.

The most recent European Guideline on hypertension (ESH Guideline 2018) advocates more use of out of office BP measurements using either 24hABPM or home blood pressure measurements (HBPM) for the diagnosis of hypertension. Given the limited access to 24hABPM, HBPM is a more widely available option and can be used to confirm the diagnosis of hypertension, detect white-coat hypertension, masked hypertension and in order to monitor BP control. HBPM is used in many patients attending the out-patient clinic instead of OBPM. However, use of HBPM requires either procurement of a BP-device by the patient or alternatively borrowing a device from either the local general practitioner (GP) or the outpatient clinic. Wider use of HBPM is therefore somewhat hampered by a financial burden in case of procurement or logistical difficulties in case of borrowing from the local GP or the outpatient clinic which especially eliminates frail and/or disabled patients. Use of a validated and frequently calibrated BP device is advocated regardless of the method used in order to obtain reliable BP measurements but for HBPM it is somewhat difficult to assure. Furthermore, the patient might not report correctly or simply forgets the recorded BP results at home, which also challenges the use of HBPM.

Blood pressure phenotypes in 12600 patients with diabetes and hypertension were evaluated from the Spanish Society of Hypertension ABPM Registry. Results indicate that about 38% of T2DM patients have disconcordant BP values when OBPM and 24hABPM are compared, primarily due to white coat effect14. 

To our knowledge comparison between OBPM, AOBPM, HBPM and 24hABPM have not been assessed in a dedicated cohort of patients with T2DM and CKD in a secondary care outpatient clinic. AOBPM may be a useful clinical tool for BP management for most patients with T2DM and CKD and provide a good alternative to 24hABPM.  

Study aim:

The primary aim of this study is to compare OBPM, AOBPM, HBPM and 24hABPM in patients with T2DM and CKD.

The secondary aim of this study is to identify variables that predict discrepancies between the different measurement techniques. 

Thirdly, the treating physician will be asked whether treatment (number of medications etc.) would have differed if AOBPM results were used for BP assessment rather than OBPM or HBPM.

Reference list:

1. Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NR. Cardiovascular outcomes in framingham participants with diabetes: The importance of blood pressure. Hypertension (Dallas, Tex. : 1979). 2011;57:891-897

2. Tozawa M, Iseki K, Iseki C, Kinjo K, Ikemiya Y, Takishita S.Blood pressure predicts risk of developing end-stage renal disease in men and women. Hypertension. 2003 Jun;41(6):1341-5. 

3. Ferrannini E, Cushman WC. Diabetes and hypertension: The bad companions. Lancet. 2012;380:601-610

4. Webster AC, Nagler EV, Morton RL, Masson P. Chronic Kidney Disease. Lancet. 2017 Mar 25;389(10075):1238-1252. 5. Gunawan F, Ng HY, Gilfillan C, Anpalahan M. Ambulatory blood pressure monitoring in type 2 diabetes mellitus: A cross-sectional study. Curr Hypertens Rev. 2018

6. Minutolo R, Agarwal R, Borrelli S, Chiodini P, Bellizzi V, Nappi F, Cianciaruso B, Zamboli P, Conte G, Gabbai FB, De Nicola L Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease.Arch Intern Med. 2011 Jun 27;171(12):

7. Leitao CB, Canani LH, Kramer CK, Boza JC, Pinotti AF, Gross JL. Masked hypertension, urinary albumin excretion rate, and echocardiographic parameters in putatively normotensive type 2 diabetic patients. Diabetes Care. 2007;30:1255-1260

8. Moran A, Palmas W, Pickering TG, Schwartz JE, Field L, Weinstock RS, Shea S. Office and ambulatory blood pressure are independently associated with albuminuria in older subjects with type 2 diabetes. Hypertension (Dallas, Tex. : 1979). 2006;47:955-961

9. Tozawa M, Iseki K, Iseki C, Kinjo K, Ikemiya Y, Takishita S. hypertension Prognostic importance of ambulatory blood pressure recordings in patients with chronic kidney disease. Agarwal R1, Andersen MJ.  Kidney Int. 2006 Apr;69(7):1175-80

 10. Tripepi G, Fagugli RM, Dattolo P, et al. Prognostic value of 24-hour ambulatory blood pressure monitoring and of night/day ratio in nondiabetic, cardiovascular  events-free hemodialysis patients. Kidney Int 2005; 68:1294-1302.

11. Jegatheswaran J, Ruzicka M, Hiremath S, Edwards C. Are automated blood pressure monitors comparable to ambulatory blood pressure monitors? A systematic review and meta-analysis. Can J Cardiol. 2017;33:644-652

12. Myers MG. Automated office blood pressure measurement. Korean Circ J. 2018;48:241-250

13. Cloutier L, Lamarre-Cliche M. Hypertension in adults with type 2 diabetes: A review of blood pressure measurement methods, targets and therapy. Can J Diabetes. 2018;42:188-195

14. Gorostidi M, de la Sierra A, Gonzalez-Albarran O, Segura J, de la Cruz JJ, Vinyoles E, Llisterri JL, Aranda P, Ruilope LM, Banegas JR, Spanish Society of Hypertension ARi. Abnormalities in ambulatory blood pressure monitoring in hypertensive patients with diabetes. Hypertens Res. 2011;34:1185-1189

Description of the cohort

Design:
Quality assessment study, cross-sectional design

We will enroll 50 patients with diabetes and 50 patients with CKD attending their routine evaluation at the outpatient clinic of Dept. of Medicine at Kolding Hospital.

Inclusion criteria:

• Age at screening ? 18 years

• Informed consent 

• Hypertension and either chronic kidney disease (stage 1-5) or diabetes attending routine evaluation at the outpatient clinic of Dept. of Medicine at Kolding Hospital

Exclusion criteria:

• Any medical condition that poses a safety risk or may interfere with the study objectives

• Chronic alcohol or drug abuse or any condition of an "unreliable" subject

• Pregnancy in women of childbearing potential  

• Cardiac arrhythmias causing unreliable BP-measurements 

In 2018 approximately 228 patients underwent 24hABPM via the outpatient clinic of the Dept. of Medicine in Kolding indicating a sufficient foundation for recruitment.

We expect that all measurements can be performed on the day of the planned routine evaluation. However, if 24hABPM was not already prescribed by the treating physician as part of the planned evaluation, the patient will have to accept an extra visit at the outpatient clinic on the following day in order to return the 24hABPM device for readout. 

Data and biological material

BP data:

OBPM 

AOBPM 

HBPM

24hABPM

Demographic and descriptive data used to characterize the participants are obtained from the routine diabetes and kidney examination.

No biological material is collected (e.g. blood and urine samples). 

The REDCap (Research Electronic Data Capture) system via the Odense Patient Explorative Network (OPEN) server will be used to send out an e-mail with a short questionnaire to the treating physician regarding whether treatment (number of medications etc.) would have differed if AOBPM results were used for BP assessment rather than OBPM or HBPM. 

Collaborating researchers and departments

Investigators

• Anne Daugaard Thuesen, Medical assistent nephrology, PhD
• Thomas Bastholm Olesen, MD

Department of Internal Medicine, Sygehus Lillebælt, Kolding Hospital

Department of Nephrology, Aarhus University Hospital

• Christian Daugaard Peters, Medical assistent nephrology, PhD