Out-of-Office Blood Pressure Measurements in Patients with Heart Failure Registry Study (OOBPM-HF study) in China: study protocol, rationale and design

Abstract

Background

The optimal blood pressure (BP) target for patients with heart failure (HF) remains a topic of debate. The relationship between out-of-office BP measurements and the prognosis of HF patients is still unclear. However, there is a lack of large-scale studies investigating out-of-office BP levels in Chinese populations with HF. This study aims to outline the rationale and design of the Out-of-Office Blood Pressure Measurements in Patients with Heart Failure registry (OOBPM-HF) study in China.

Methods

The OOBPM-HF study is a prospective, multicentre, observational cohort study involving participants recruited from 26 hospitals in China. Patents with relatively stable HF symptoms will undergo a screening process to determine their eligibility for study participation. Data from baseline clinical, laboratory and imaging examinations will be collected. BP parameters, including office BP, ambulatory BP and home BP, will be measured and documented. The primary endpoint of the study is the composite endpoint of death from cardiovascular causes and HF hospitalisation. Participants will be followed up for a duration of 18 months.

Conclusions

The study will establish a comprehensive understanding of the associations between out-of-office BP measurements and HF prognosis within the Chinese population. The findings of this study will provide valuable insights into the optimal BP range for patients with HF and will contribute to the management of BP in this patient group.

Trial registration number

ChiCTR2400090786; Result.

STRENGTHS AND LIMITATIONS OF THIS STUDY.

• The study employs a large registry design and standardised out-of-office blood pressure measurement protocols to investigate associations between blood pressure levels and heart failure prognoses in a Chinese patient cohort.

• As this study is a prospective observational study, it is crucial to acknowledge the possible presence of confounding factors.

• The types of devices used for ambulatory blood pressure monitoring and home blood pressure monitoring may vary among different sites, potentially introducing biases.

• The study’s participants are exclusively from China, which may restrict the generalisability of the findings.

Introduction

Recently, there has been a growing concern regarding the global burden of heart failure (HF), with over 64 million individuals affected by HF worldwide.¹ Moreover, the prevalence of HF has been consistently escalating.² HF is a clinical syndrome characterised by the presence of symptoms and signs indicating elevated ventricular filling pressure and/or impaired cardiac output, typically stemming from structural and/or functional abnormalities of the heart.^{3 4} It represents an advanced stage of various cardiovascular diseases (CVD), often linked with a high mortality rate and a poor prognosis.⁵ Based on the left ventricular ejection fraction, HF can be classified into three categories: HF with reduced EF (HFrEF), HF with mildly reduced EF (HFmrEF) and HF with preserved EF (HFpEF), with EF ranges of ≤40%, 41%–49% and ≥50%, respectively.^{3 4} Importantly, different types of HF exhibit significant variations in terms of aetiologies, treatment strategies and prognoses.⁴

Hypertension stands as one of the most prevalent comorbidities in HF.⁶ Blood pressure (BP) can vary significantly among different individuals with HF. The optimal BP range for patients with HF remains uncertain, posing a great challenge in optimising HF treatment. The adoption of out-of-office BP measurement techniques, such as ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM), has gained popularity among hypertensive patients.⁷ Furthermore, BP monitoring technology has gradually integrated into wearable devices.^{8 9} Out-of-office BP measurements exhibit high reproducibility and effectively reduce the white coat effect.^{10 11} HBPM enables daily BP monitoring, empowering patients to actively participate in self-management.⁷ Multiple studies have indicated that out-of-office BP measurements show stronger associations with cardiovascular events and have greater predictive value for cardiovascular outcomes in hypertensive patients compared with office BP measurements.^{12 13} However, there is limited evidence demonstrating the associations between out-of-office BP levels and the prognosis of HF patients.

In recent years, a global registry focused on ABPM in patients with HFpEF has been launched. The purpose of the study is to investigate the correlation between ABPM and outcomes in patients with HFpEF, while also exploring potential regional variations across different geographical areas.¹⁴ Given the scarcity of large registry studies on out-of-office BP measurements in Chinese HF patients, we have initiated a registry to investigate the associations between out-of-office BP levels and the prognoses of HF in China. The primary objective of the study is to explore the optimal BP range and promote effective BP management strategies in patients with HF.

Method

Study design and population

The study is a prospective, multicentre, observational cohort study involving participants recruited from 26 hospitals in China. These participating hospitals predominantly include tertiary hospitals situated in 12 provinces and 2 municipalities across mainland China. Outpatients with the diagnosis of HF will undergo screening to determine their eligibility for the study. All three inclusion criteria must be met for participation in the study: (1) patients with previous symptoms of HF, a history of hospitalisation due to HF and a confirmed diagnosis of chronic HF based on established HF guidelines^{3 4}; (2) patients with relatively stable symptoms within the past month and (3) individuals aged 18 years or older. Participants who meet the exclusion criteria outlined in table 1 will be excluded from the study. The study has been approved by the ethics committee of Fu Wai Hospital (approval number: 2024-2403). Each participating site will obtain independent ethics clearance from their respective ethics committees. Written informed consent will be obtained from the participants on their enrolment in the study. The participants will be followed up for 18 months. Data collected at baseline and during follow-up will be recorded using standardised case-report forms.

Table 1. Inclusion and exclusion criteria of the study.

Inclusion criteria

Exclusion criteria

Patients with previous symptoms of HF, a prior hospitalisation for HF and a confirmed diagnosis of chronic HF based on established HF guidelines. Patents with relatively stable symptoms in the past month. Age ≥18 years old.

Patients with a history of acute coronary syndrome, coronary artery revascularisation, acute myocarditis, cardiac surgery, or other cardiovascular surgeries within the past 3 months. Currently requiring treatment for acute decompensated HF. Recent adjustment in the type or dosage of antihypertensive medications within the past month. Relative contraindications to ABPM. Concurrently participating in other clinical trials. Pregnant women. Patients with chronic renal failure. Patients with malignant tumours. Patients with severe autoimmune diseases. Patients with severe cognitive impairments or psychiatric history. Patients with incomplete data.

ABPM, ambulatory blood pressure monitoring; HF, heart failure.

Study procedure

The study flow is illustrated in figure 1. On enrolment in the cohort, trained staff will collect demographic information and medical histories of the participants, including age, gender, ethnicity, marital status, education level, occupation, income level, medical insurance coverage, smoking and alcohol consumption habits, past medical conditions (such as hypertension, diabetes, hyperlipidaemia, chronic kidney disease, CVD, cerebrovascular disease, etc), New York Heart Association cardiac function classification and current medication status. Physical examination data will encompass height, weight, waist circumference, hip circumference and office BP. The following laboratory data will be collected and recorded: blood routine, liver function, renal function, electrolyte levels, blood glucose, blood lipid profile, uric acid, homocysteine, B type natriuretic peptide (BNP), N-terminal B type natriuretic peptide (NT-proBNP) and urinary microalbumin to creatinine ratio. ABPM will be conducted. Additionally, the participants will be instructed to perform HBPM for a minimum of 3 consecutive days.

Figure 1. Flow chart of the study. ABPM, ambulatory BP monitoring; BP, blood pressure; HBPM, home BP monitoring.

Throughout the 18-month follow-up period, participants will be mandated to document their home BP levels and office BP levels every 3 months. The recording can be conducted via telephone or through face-to-face interactions. In addition, ABPM, BNP (or NT-proBNP) and echocardiography will be performed every 6 months in the outpatient setting. No study-specific interventions will be implemented for BP values, and all clinical decisions will remain exclusively under the responsibility of the participants’ healthcare providers.

BP measurements

Office BP measurements will be conducted by trained staff using validated upper arm medical electronic sphygmomanometers, adhering to the standard measurement method recommended by the 2018 Chinese guidelines for hypertension.¹⁵ Patients will be instructed to rest for at least 5 min before the BP measurement. They should be seated and maintain their upper arm at the heart level during the BP measurement process. Two BP measurements will be conducted with an interval of 1–2 min and the average BP levels will be recorded. If there is a difference greater than 5 mm Hg between the two readings, a third measurement will be taken and the average BP levels from the three measurements will be recorded.

ABPM will be conducted using validated ABPM. BP measurements will be taken every 15 min during the daytime period and every 30 min during the nighttime period. The daytime period is defined from 6:00 to 21:59, while the night-time period is defined from 22:00 to 05:59. At least 20 daytime readings, 7 night-time readings and 70% of the expected valid BP readings should be included. To calculate the mean 24-hour, mean daytime and mean nighttime BP, the BP readings obtained during the corresponding periods will be averaged.

Before conducting HBPM, participants will be trained on the use of the devices. Only validated HBPM will be used in the study. Participants will be instructed to measure their home morning BP and evening BP for a duration of 7 consecutive days, with a minimum of 3 consecutive days.¹⁶ Morning BP should be measured in the seated position, after waking up and urination, and before taking antihypertensive drugs or breakfast. Evening BP should be measured in the seated position at bedtime.¹⁷ Each measurement session should consist of at least two readings taken with a 1 min interval, and the average BP levels should be documented.

Endpoints

The primary endpoint is the composite endpoint of death from cardiovascular causes and HF hospitalisation. Death from cardiovascular causes was defined as death attributed to ischaemic heart disease, arrhythmia, HF, stroke or other cardiovascular aetiologies. HF hospitalisation was defined as hospitalisation due to worsening HF. The secondary endpoints include death from any causes, death from cardiovascular causes, all-cause hospitalisation, HF hospitalisation and the change from baseline to 18 months in estimated glomerular filtration rate.

Sample size calculation

According to the findings of a prior study on HF by Komori et al,¹⁸ the incidence of the composite outcome (similar to the primary outcome in this study) was 45.4% in the morning BP surge group and 30.6% in the non-morning BP surge group. For a two-sided power calculation with 90% power and a significance level (α) of 0.05, 1301 participants are required to detect a difference in event rates between the groups. Assuming a 20% dropout rate, a total of 1627 participants will be enrolled in the study.

Statistical analysis

Continuous variables will be presented as mean±SD and compared using the independent sample t-test if they follow a normal distribution. In cases where the data deviates from normality, continuous variables will be presented as median and IQR and compared using the Mann-Whitney U test. Categorical variables will be expressed as percentages and compared by the χ² test. To estimate the associations of different out-of-office BP levels with the primary outcome in patients with HF, Kaplan-Meier analysis and log-rank statistics will be used. Univariate and multivariate Cox regression analysis will be applied to explore potential prognostic factors. A two-sided p <0.05 will be considered statistically significant in this study.

Patient and public involvement

Patients and the public were initially engaged in the research during the study design phase, where their insights were gathered through focus groups and interviews to elucidate their viewpoints on BP management in HF. Feedback from patient representatives and community members guided the selection of relevant outcomes. Furthermore, patient representatives played a crucial role in the recruitment process and study conduct, offering consultation on recruitment strategies, participant information materials and communication approaches. Moving forward, these representatives will be pivotal in shaping the dissemination strategy to ensure that the study findings are effectively communicated and meaningful to diverse audiences.

Discussion

To the best of our knowledge, this study represents the first prospective cohort study aimed at exploring the correlations between out-of-office BP measurements and prognosis in Chinese HF population. This study will involve the evaluation of both office BP measurements and out-of-office BP measurements, including ABPM and HBPM. Besides, this study will encompass three categories of HF patients: individuals with HFrEF, HFmrEF and HFpEF.

Hypertension stands as one of the most prevalent comorbidities and risk factors for HF.⁶ Despite this, the optimal BP target for HF patients remains uncertain. Several studies have suggested a BP target below 130/80 mm Hg for patients with HF and hypertension.^{7 19 20} However, other studies have reported that low BP might indicate a poor prognosis in patients with HF.^{21 22} To date, there is a scarcity of robust evidence regarding the specific BP target range for patients with HF. In this HF registry study, both office BP and out-of-office BP levels will be recorded, and cardiovascular outcomes will be evaluated over an 18-month follow-up period. The study will provide a more comprehensive understanding of the influence of BP on cardiovascular outcomes in HF patients.

ABPM and HBPM have been demonstrated to be associated with cardiovascular risk independent of office BP measurements in both general and hypertensive populations.^{23 24} These methods provide more comprehensive assessments of individuals’ BP profiles outside of the clinical setting. ABPM involves recording BP measurements over a 24-hour period, which enables the evaluation of BP fluctuations throughout the day and night, as well as BP variability. Based on the nocturnal decrease in BP compared with daytime levels, BP patterns can be categorised into dipper, non-dipper, riser and extreme dipper patterns. There are few studies exploring the prognostic value of ABPM and abnormal BP circadian patterns in HF. Ueda et al²⁵ analysed ABPM data in 325 patients with acute decompensated HF and found that the riser pattern was associated with an increased risk of all-cause and cardiovascular death specifically in patients with HFpEF. However, this association was not observed in patients with HFrEF or HFmrEF. Camafort et al²⁶ performed a prospective study involving 154 elderly patients with chronic HF who underwent ABPM. They demonstrated that the non-dipper BP pattern was associated with an increased risk of hospitalisation and death due to HF during a 1-year follow-up period. Furthermore, Komori et al¹⁸ revealed that morning BP surge was associated with a poorer prognosis in patients with HFrEF, but not in the HFpEF group. It is worth mentioning that the sample sizes in these studies were relatively small, and the conclusions drawn from them were inconsistent. Data from this study may offer valuable insights into the prognostic value of ABPM and HBPM in patients with HF.

The HF registry study has several limitations. First, as this study is a prospective observational study, it is crucial to recognise that potential confounding factors may exist. Therefore, the study’s findings can only offer indications or suggestions regarding the optimal BP value in patients with HF. It is imperative to interpret the findings while considering other relevant factors that may influence BP management in HF patients. Second, the types of devices used for ABPM and HBPM may vary across different sites, which can introduce potential biases. To mitigate measurement errors, only validated ABPM and HBPM devices will be permitted for use in this study. Third, it should be noted that the study participants are exclusively from China, which could restrict the generalisability of the findings to broader populations.

Conclusions

In conclusion, the study will provide a thorough comprehension of the relationships between out-of-office BP measurements and prognoses in HF within the Chinese population. The findings from this study are expected to provide valuable insights into establishing the optimal BP range for individuals with HF and enhancing their BP management strategies.

Ethical approval

Ethical approval for the study has been initially obtained from the Ethics Committee of Fu Wai Hospital, which serves as the coordinating center for this multicenter registry (Approval number: 2024-2403). To date, 12 participating centres have obtained ethical approval from their respective institutional review boards or ethics committees, including: Zibo Central Hospital (Approval number: 2024-238), the Second Hospital of Lanzhou University (Approval number: 2024A-1383), the Second Hospital of Tianjin Medical University (Approval number: KY2024K346), Nangong New Great Wall Hospital (Approval number: 25010301), Qingdao West Coast New Area Central Hospital (Approval number: 0005-25-1R0), Shenzhen Fuwai Hospital of Chinese Academy of Medical Sciences (Approval number: SP2025015), Fuwai Yunnan Cardiovascular Hospital (Approval number: 2025-006-01), Fu Xing Hospital of Capital Medical University (Approval number: 2025FXHEC-KSP006), Jinan Central Hospital (Approval number: 20250120003), Gongyi People's Hospital (Approval number: 2025KY-002), Qinghai University Affiliated Hospital (Approval number: 2025LLPJ-012) and the First Affiliated Hospital of Dalian Medical University (Approval number: PJ-KS-KY-2025-374).