Early-warning Intervention for Heat and Cold in Older Hypertensive Patients: Impact on Sleep Quality
Phase: NA
Conditions: Hypertension
Sponsor: Tiantian Li

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Trial Protocol
Early-warning
Intervention
for
Heat
Waves
and
Cold
Spells
in
Older
Hypertensive Patients: Impact on Sleep Quality
NCT Number: NCT06045403
Document Date: 2024-10-05
This protocol contains the following items:
1. Trial Protocol
2. Statistical Analysis Plan.
The trial protocol and statistical analysis plan have not changed throughout the trial.

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Protocol Synopsis
Title
Early-warning Intervention for Heat Waves and Cold Spells in
Older Hypertensive Patients
Intervention
A digital heat or cold health risk early warning tool intervention
combined with self-monitoring
Study Objectives
To assess the intervention's effectiveness in improving sleep quality
and its underlying biological mechanisms.
Study Design
The study is a cluster-randomized controlled trial of a digital heat
health
risk
early
warning
tool
intervention
combined
with
self-monitoring.
Primary Endpoint(s)
1. Change from Baseline in Sleeping Quality Assessment
Pittsburgh Sleep Quality Index (PSQI)
Secondary Endpoint(s)
1. Change from Baseline in Blood Pressure Measurement
1.1 Proportion of older individuals meeting the standard for blood
pressure control (SBP/DBP <140/90 mm Hg)
1.2 Proportion of older individuals meeting the standard for blood
pressure control (SBP/DBP <120/80 mm Hg)
1.3 Systolic Blood Pressure (SBP)
1.4 Diastolic Blood Pressure (DBP)
2.Change from Baseline in the Risk of Electrocardiogram (ECG)
Measurement
2.1 Overall warning level for abnormal ECG.
2.2 Left ventricular hypertrophy
2.3 Sinus arrhythmia
2.4 Sight bundle branch block
2.5 Ventricular premature beats
2.6 Atrial premature beats
2.7 Q waves
2.8 T-wave changes
2.9 ST changes
3.
Change
from
Baseline
in
Temperature
Exposure
Measurement
3.1 Temperature
3.2 Humidity
4. Change from Baseline in Heatwave Perception Assessment
4.1 Heatwave Awareness and Concern
5. Change from Baseline in Cold Spell Perception Assessment
5.1 Cold Spell Awareness and Concern
6. Change from Baseline in Cardiovascular and Cerebrovascular
Symptoms Assessment
7. Change from Baseline in Respiratory System Symptoms
Assessment
8. Change from Baseline in Generalized Anxiety Disorder

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Assessment
8.1 Generalized Anxiety Disorder Scale (GAD-7) score.
9. Change from Baseline in Cognitive Function Assessment
9.1 Mini-Mental State Examination (MMSE) score.
10. Change from Baseline in Depression Assessment
10.1 Patient Health Questionnaire-9 (PHQ-9) score
.11.Change
from
Baseline
in
Social
Support
Perception
Assessment
11.1 Perceived Social Support Scale (PSSS)
12.Change
from
Baseline
in
Time-Activity
Patterns
Measurement
12.1 Time-Activity Patterns
13.Change
from
Baseline
in
Medication
Adherence
Measurement
13.1 Self-management Behavior
13.2 Medication Adherence
14. Changes in liver function biomarkers (e.g., albumin (ALB),
alanine aminotransferase (ALT), aspartate aminotransferase
(AST), etc.) from baseline
15. Changes in kidney function biomarkers (e.g., uric acid (UA),
blood urea nitrogen (BUN), creatinine (CREA), etc.) from
baseline
16.
Changes
in
cardiovascular
biomarkers
(e.g.,
creatine
kinase-MB (CK-MB), creatine kinase (CK), etc.) from baseline
17. Changes in inflammatory biomarkers (e.g., interleukin-6
(IL-6), interleukin-1β (IL-1β), etc.) from baseline
18.
Changes
in
metabolic
biomarkers
(e.g.,
lactate
dehydrogenase
(LDH),
high-density
lipoprotein
(HDL),
low-density lipoprotein cholesterol (LDL) , etc.) from baseline
Accrual Objective
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Study Duration
6 months total duration covering two distinct periods which focuses
on heat wave and cold spell (From June 15th 2023 to August 31st
2023, and December 1st 2023 to February 28th 2024).
Treatment Description
This cluster-randomized trial will be conducted in various districts
across Tianjin, China. As part of the early warning interventions for
heat waves and cold spells, three communities from each of the two
selected districts will be randomly chosen and assigned to one of
three groups: the combined intervention group, the self-monitoring
group,
or
the
control
group.
Participants
in
the
combined
intervention group will receive health risk warnings for heat waves
and cold spells via digital tools, specifically through a WeChat
mini-program, which provides real-time updates on early warnings
and health advisories. Additionally, they will be instructed to

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perform daily self-monitoring of their blood pressure (BP) and
electrocardiogram
(ECG)
using
automated
home
devices.
Participants in the self-monitoring alone group will engage in daily
BP and ECG monitoring but not receive any health warnings. In
contrast, the control group will monitor their BP and ECG only
during baseline assessments and routine health check-ups (the day
after the first heat wave in July and August 2023, as well as
following the first cold spell in January and February 2024). All
participants will be required to record their daily time-activity
patterns. During the baseline and subsequent check-ups, data will be
collected on participants' demographics, medical history, lifestyle
factors
(e.g., diet, smoking,
physical
activity),
environmental
exposures, mental health status (including stress levels, emotional
stability, and psychological resilience), sleep quality, medication
adherence,
cardiovascular
and
cerebrovascular
symptoms,
respiratory system symptoms, and perceptions of heatwaves and
cold spells. In addition, blood, urine, and stool samples will be
gathered for further analysis.
Inclusion Criteria
(i) Individuals aged 60 to 65 years old; (ii) Individuals with a
diagnosis of hypertension; (iii) Individuals with untreated blood
pressure above 140/90 mmHg.
Exclusion Criteria
(i) Having a history of coronary heart disease, heart failure, or stroke

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Glossary of Abbreviations.................................................................................................................. 8
1.Background and Rationale...............................................................................................................9
2.Study Objectives..............................................................................................................................9
3.Study Design....................................................................................................................................9
3.1 Description of Study Design.........................................................................................................9
3.2 Primary and Secondary Outcomes............................................................................................. 10
3.2.1 Primary Outcomes................................................................................................................... 10
3.2.1.1 Change from Baseline in Sleeping Quality Assessment...................................................... 10
Pittsburgh Sleep Quality Index (PSQI)............................................................................................ 10
3.2.2 Secondary Outcomes............................................................................................................... 10
3.2.2.1 Change from Baseline inBlood Pressure Measurement.......................................................10
a. Proportion of older individuals meeting the standard for blood pressure control (SBP/DBP
<140/90 mm Hg)...............................................................................................................................10
b. Proportion of older individuals meeting the standard for blood pressure control (SBP/DBP
<120/80 mm Hg)...............................................................................................................................10
c. Systolic Blood Pressure (SBP)..................................................................................................... 10
d. Diastolic Blood Pressure (DBP)...................................................................................................10
3.2.2.2 Change from Baseline in the Risk of Electrocardiogram (ECG) Measurement..................10
a. Overall warning level for abnormal ECG.....................................................................................10
b. Left ventricular hypertrophy.........................................................................................................10
c. Sinus arrhythmia........................................................................................................................... 10
d. Right bundle branch block............................................................................................................10
e. Ventricular premature beats.......................................................................................................... 10
f. Atrial premature beats................................................................................................................... 10
g. Q waves.........................................................................................................................................10
h. T-wave changes.............................................................................................................................10
i. ST changes.....................................................................................................................................10
3.2.2.3 Change from Baseline in Temperature Exposure Measurement..........................................10
a. Temperature...................................................................................................................................10
b. Humidity.......................................................................................................................................10
3.2.2.4 Change from Baseline in Heatwave Perception Assessment...............................................10
Heatwave Awareness and Concern...................................................................................................10
3.2.2.5 Change from Baseline in Cold Spell Perception Assessment..............................................10
Cold Spell Awareness and Concern..................................................................................................10
3.2.2.6 Change from Baseline in Cardiovascular and Cerebrovascular Symptoms Assessment.... 10
3.2.2.7 Change from Baseline in Respiratory System Symptoms Assessment............................... 10
3.2.2.8 Change from Baseline in Generalized Anxiety Disorder Assessment.................................10
Generalized Anxiety Disorder Scale (GAD-7) score.......................................................................10
3.2.2.9 Change from Baseline in Cognitive Function Assessment..................................................10
Mini-Mental State Examination (MMSE) score.............................................................................. 10
3.2.2.10 Change from Baseline in Depression Assessment............................................................. 10
Patient Health Questionnaire-9 (PHQ-9) score................................................................................10
3.2.2.11 Change from Baseline in Social Support Perception Assessment..................................... 10

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Perceived Social Support Scale (PSSS)........................................................................................... 10
3.2.2.12 Change from Baseline in Time-Activity Patterns Measurement....................................... 10
Time-Activity Patterns......................................................................................................................10
3.2.2.13 Change from Baseline in Medication Adherence Measurement........................................10
a. Self-management Behavior...........................................................................................................11
b. Medication Adherence..................................................................................................................11
3.2.2.14. Changes in liver function biomarkers (e.g., albumin (ALB), alanine aminotransferase
(ALT), aspartate aminotransferase (AST), etc.) from baseline........................................................11
3.2.2.15. Changes in kidney function biomarkers (e.g., uric acid (UA), blood urea nitrogen (BUN),
creatinine (CREA), etc.) from baseline............................................................................................11
3.2.2.16. Changes in cardiovascular biomarkers (e.g., creatine kinase-MB (CK-MB), creatine
kinase (CK), etc.) from baseline.......................................................................................................11
3.2.2.17. Changes in inflammatory biomarkers (e.g., interleukin-6 (IL-6), interleukin-1β (IL-1β),
etc.) from baseline............................................................................................................................ 11
3.2.2.18. Changes in metabolic biomarkers (e.g., lactate dehydrogenase (LDH), high-density
lipoprotein (HDL), low-density lipoprotein cholesterol (LDL) , etc.) from baseline......................11
3.3 Randomization............................................................................................................................11
4.Participants.....................................................................................................................................11
4.1 Inclusion Criteria........................................................................................................................ 11
4.2 Exclusion Criteria.......................................................................................................................11
4.3 Sites.............................................................................................................................................11
5.Known and Potential Risks and Benefits to Participants..............................................................11
6.Intervention....................................................................................................................................12
6.1 Combined Intervention...............................................................................................................12
6.2 Self-Monitoring Alone................................................................................................................12
6.3 Criteria for Discontinuing or Modifying....................................................................................12
6.4 Strategies for Adherence.............................................................................................................12
7. Study Procedures.......................................................................................................................... 12
7.1 Enrollment.................................................................................................................................. 12
7.2 Randomization............................................................................................................................13
7.3 Sleeping Assessment Questionnaire...........................................................................................13
7.4 BP Measurement.........................................................................................................................13
7.6 Exposure Temperature Measurement.........................................................................................13
7.7 Heatwave Perception Questionnaire...........................................................................................13
7.8 Cold Spell Perception Questionnaire......................................................................................... 14
7.9 Cardiovascular and Cerebrovascular Symptoms Questionnaire................................................14
7.10 The Respiratory System Symptoms Questionnaire..................................................................14
7.11 Cognitive Assessment Scale..................................................................................................... 15
7.12 Generalized Anxiety Disorder Scale (GAD-7).........................................................................15
7.13 Depression Assessment Scale...................................................................................................15
7.14 Social Support Assessment Scale.............................................................................................15
7.15 Time-activity Patterns Measurement........................................................................................15
7.16 Medication Adherence Indicators Measurement......................................................................16
7.17 Cardiovascular Health Biomarkers Measurement....................................................................16

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7.18 Liver Function Health Biomarkers Measurement....................................................................16
7.19 Kidney Function Health Biomarkers Measurement.................................................................16
7.20 Inflammatory Indicators Measurement.................................................................................... 16
7.21 Metabolic Indicators Measurement..........................................................................................16
8. Statistical Considerations and Analytical Plan.............................................................................17
8.1 Sample Size Calculation.............................................................................................................17
8.2 Statistical Analysis......................................................................................................................17
8.3 Analytical Tools.......................................................................................................................... 18
9.Criteria for Participant and Study Completion and Premature Study Termination...................... 18
9.1 Participant Completion...............................................................................................................18
9.2 Participant Stopping Rules and Withdrawal Criteria................................................................. 18
10.Protocol Deviations..................................................................................................................... 18
11.Ethical Considerations.................................................................................................................18
12.Quality Control and Quality Assurance.......................................................................................18
13.References....................................................................................................................................19

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Glossary of Abbreviations
BP
Blood Pressure
SBP
Systolic Blood Pressure
DBP
Diastolic Blood Pressure
ECG
Electrocardiogram
MMSE
Mini-Mental State Examination
GAD-7
Generalized Anxiety Disorder-7
PSQI
Pittsburgh Sleep Quality Index
PHQ-9
Patient Health Questionnaire-9
PSSS
Perceived Social Support Scale
HPSMBRS
Hypertension Patient Self-Management Behavior
Rating Scale
HPMARS
Hypertension
Patient
Medication
Adherence
Rating Scale
CVD
Cardiovascular disease
LVH
Left ventricular hypertrophy
BMI
Body Mass Index
CK-MB
Creatine Kinase-MB
CK
Creatine Kinase
LDH
Lactate Dehydrogenase
CREA
Creatinine
UA
Uric Acid
BUN
Urea Nitrogen
PRA
Plasma Renin Activity
ALD
Aldosterone
ALT
Alanine Aminotransferase
AST
Aspartate Aminotransferase
ALB
Albumin
CRP
C-Reactive Protein
IL-6
Interleukin-6
PCT
Procalcitonin
LDH
Lactate Dehydrogenase
TRIGL
Triglycerides
HDL
High-Density Lipoprotein
LDL
Low-Density Lipoprotein Cholesterol
HCY
Homocysteine
RBBB
Right bundle branch block
VPBs
Ventricular premature beats
APBs
Atrial premature beats
MI
Myocardial infarction

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1.Background and Rationale
Hypertension is a significant public health issue, predominantly affecting older adults, who are notably
susceptible to the adverse effects of heat or cold exposure. In addition to the common cardiovascular
burden, decreased sleep quality is also one of the common complications of hypertension. Digital
technologies effectively support lifestyle changes, promote medication adherence, and offer timely
interventions to improve blood pressure management. However, they frequently fail to consider the
critical environmental impact of heat or cold. This study develops a digital tool that delivers heat or
cold health warnings, integrating it with traditional self-monitoring to provide a comprehensive
approach to managing hypertension that could further improve patients' sleep quality, especially in the
context of global climate change.
2.Study Objectives
The main objective of this study was to assess the effectiveness of interventions in improving sleep
quality and to understand the underlying biological mechanisms. In addition, the study was designed to
assess how the intervention affected other health-related factors, including blood pressure control,
electrocardiogram abnormalities, physical activity, environmental exposure, medication adherence, and
participants' perception of heat waves and cold periods. Finally, the impact of the intervention on
biological sample detection indicators will be analyzed to fully evaluate its impact on the overall health
of the participants.
3.Study Design
3.1 Description of Study Design
This cluster-randomized trial will be conducted in various districts across Tianjin, China. As part of the
early warning interventions for heat waves and cold spells, three communities from each of the two
selected districts will be randomly chosen and assigned to one of three groups: the combined
intervention group, the self-monitoring group, or the control group. The study will be divided into
pre-intervention and intervention phases. The pre-intervention period for the heat wave health
early-warning information intervention spans from July 1st, 2023, to July 7th, 2023, followed by the
intervention period from July 8th to September 9th, 2023. Similarly, during the cold spell health
early-warning information intervention, the pre-intervention phase occurs from December 1st, 2023, to
December 7th, 2023, and the intervention.
Participants in the combined intervention group will receive heat health risk warnings via digital tools,
specifically a WeChat mini-program, providing real-time updates on early warnings and health
advisories. Additionally, they will be instructed to perform daily self-monitoring of their blood pressure
(BP) and electrocardiogram (ECG) using automated home devices. Participants in the self-monitoring
alone group will engage in daily BP and ECG monitoring but not receive any health warnings. In
contrast, the control group will monitor their BP and ECG only during baseline assessments and routine
health check-ups (the day after the first heat wave in July and August 2023, as well as following the
first cold spell in January and February 2024).
All participants will be required to record their daily time-activity patterns. During the baseline and
subsequent check-ups, data will be collected on participants' demographics, medical history, lifestyle
factors (e.g., diet, smoking, physical activity), environmental exposures, sleep quality, mental health
status (including stress levels, emotional stability, and psychological resilience), medication adherence,
cardiovascular and cerebrovascular symptoms, respiratory system symptoms, and perceptions of
heatwaves and cold spells. In addition, blood, urine, and stool samples will be gathered for further
analysis.

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3.2 Primary and Secondary Outcomes
3.2.1 Primary Outcomes
3.2.1.1 Change from Baseline in Sleeping Quality Assessment
Pittsburgh Sleep Quality Index (PSQI)
3.2.2 Secondary Outcomes
3.2.2.1 Change from Baseline inBlood Pressure Measurement
a.
Proportion of older individuals meeting the standard for blood pressure control (SBP/DBP
<140/90 mm Hg)
b.
Proportion of older individuals meeting the standard for blood pressure control (SBP/DBP
<120/80 mm Hg)
c.
Systolic Blood Pressure (SBP)
d.
Diastolic Blood Pressure (DBP)
3.2.2.2 Change from Baseline in the Risk of Electrocardiogram (ECG) Measurement
a.
Overall warning level for abnormal ECG
b.
Left ventricular hypertrophy
c.
Sinus arrhythmia
d.
Right bundle branch block
e.
Ventricular premature beats
f.
Atrial premature beats
g.
Q waves
h.
T-wave changes
i.
ST changes
3.2.2.3 Change from Baseline in Temperature Exposure Measurement
a.
Temperature
b.
Humidity
3.2.2.4 Change from Baseline in Heatwave Perception Assessment
Heatwave Awareness and Concern
3.2.2.5 Change from Baseline in Cold Spell Perception Assessment
Cold Spell Awareness and Concern
3.2.2.6 Change from Baseline in Cardiovascular and Cerebrovascular Symptoms Assessment
3.2.2.7 Change from Baseline in Respiratory System Symptoms Assessment
3.2.2.8 Change from Baseline in Generalized Anxiety Disorder Assessment
Generalized Anxiety Disorder Scale (GAD-7) score.
3.2.2.9 Change from Baseline in Cognitive Function Assessment
Mini-Mental State Examination (MMSE) score.
3.2.2.10 Change from Baseline in Depression Assessment
Patient Health Questionnaire-9 (PHQ-9) score.
3.2.2.11 Change from Baseline in Social Support Perception Assessment
Perceived Social Support Scale (PSSS)
3.2.2.12 Change from Baseline in Time-Activity Patterns Measurement
Time-Activity Patterns
3.2.2.13 Change from Baseline in Medication Adherence Measurement

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a.
Self-management Behavior
b.
Medication Adherence
3.2.2.14. Changes in liver function biomarkers (e.g., albumin (ALB), alanine aminotransferase
(ALT), aspartate aminotransferase (AST), etc.) from baseline
3.2.2.15. Changes in kidney function biomarkers (e.g., uric acid (UA), blood urea nitrogen (BUN),
creatinine (CREA), etc.) from baseline
3.2.2.16. Changes in cardiovascular biomarkers (e.g., creatine kinase-MB (CK-MB), creatine
kinase (CK), etc.) from baseline
3.2.2.17. Changes in inflammatory biomarkers (e.g., interleukin-6 (IL-6), interleukin-1β (IL-1β),
etc.) from baseline
3.2.2.18. Changes in metabolic biomarkers (e.g., lactate dehydrogenase (LDH), high-density
lipoprotein (HDL), low-density lipoprotein cholesterol (LDL) , etc.) from baseline
3.3 Randomization
This cluster-randomized trial will be conducted in various districts across Tianjin, China. As part of the
early warning interventions for heat waves and cold spells, three communities from each of the two
selected districts will be randomly chosen and assigned to one of three groups: the combined
intervention group, the self-monitoring group, or the control group. Due to the cluster design and
intervention nature, the older individuals with hypertension, doctors in Community Health Planning
Services, and research staff collecting outcome data will be aware of the group assignments.
4.Participants
4.1 Inclusion Criteria
Inclusion rules for the study participants were:
4.1.1 individuals aged 60 to 65 years old
4.1.2 individuals with a diagnosis of hypertension
4.1.3 individuals with untreated blood pressure above 140/90 mmHg
4.2 Exclusion Criteria
Exclusion criteria were as follows:
4.2.1 having a history of coronary heart disease, heart failure, or stroke
4.3 Sites
In the summer of 2022, a global warming trend led to record-breaking temperatures across all
continents, the highest in over 100,000 years1,3. This summer, the Tianjin region has also experienced
an unprecedented heatwave, with a total of 27 days of high temperatures. Among them, the temperature
exceeded 40℃for 4 days4. Meanwhile, the winter of 2022 saw a severe cold spell affecting the region,
with temperatures plummeting to historic lows, reaching as low as -14°C5. These extreme conditions
significantly heightened the health risks associated with cold weather, especially for vulnerable
populations.
5.Known and Potential Risks and Benefits to Participants
The daily self-monitoring of BP and ECG will be trained by a professional, which will not cause health
risks and discomfort. All information and samples, including blood, urine, and stool, tested about the
subject will be kept strictly confidential and will only be used for this project. Participation in the
survey is voluntary, and the rights of respondents who do not agree to participate in this survey, or
withdraw at any time after the start of the survey, will not be affected in any way.

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Respondents will receive a feedback report on the results of the self-monitoring of BP, exposure to
temperature, time-activity patterns, and a small gift to thank to the respondents for participating.
6.Intervention
6.1 Combined Intervention
This study will utilize a digital heat or cold health risk early warning tool developed as a WeChat
mini-program in the combined intervention group. The tool features capabilities for disseminating early
heat or cold-health warning information.Throughout the intervention period, the heat or cold health risk
early warning model, established by the National Institute of Environmental Health at the Chinese
Center for Disease Control and Prevention, classified heat or cold-related health hazards into five levels:
"no warning," "concern level," "warning level one," "warning level two," and "warning level three."
Upon issuing a heat or cold health risk early warning, only the older individuals in the intervention
group rwill receive these early warnings and health advice through the digital tool.
Additionally, participants in the combined intervention group will be instructed to self-measure their
blood pressure (BP) three times each morning (from 6:00 a.m. to 8:00 a.m.) and evening (from 6:00
p.m. to 8:00 p.m.) at home, and to self-administer electrocardiogram (ECG) measurements twice
during the same morning and evening timeframes.
6.2 Self-Monitoring Alone
Participants in the self-monitoring alone groups will be instructed to self-measure their blood pressure
(BP) three times each morning (from 6:00 a.m. to 8:00 a.m.) and evening (from 6:00 p.m. to 8:00 p.m.)
at home, and to self-administer electrocardiogram (ECG) measurements twice during the same morning
and evening timeframes.
6.3 Criteria for Discontinuing or Modifying
The participation of subjects is voluntary and can be withdrawn at any time, and their rights will not be
affected in any way.
6.4 Strategies for Adherence
During the investigation, all tests will be conducted by professionally trained medical personnel and
will not cause any adverse effects. Participants will receive timely feedback on their blood pressure (BP)
and electrocardiogram (ECG) results. This real-time monitoring will allow them to manage their health
proactively, with immediate warnings and recommendations provided based on their health status and
exposure to temperature variations. Additionally, participants will be given feedback on their
questionnaire scores, including heat wave and cold spell perception scores, Pittsburgh Sleep Quality
Index (PSQI) score, Mini-Mental State Examination (MMSE) score, Generalized Anxiety Disorder-7
(GAD-7) scores, Patient Health Questionnaire-9 (PHQ-9) score, and Perceived Social Support Scale
(PSSS) score. These measures will provide insight into their psychological well-being and overall
quality of life. Biological monitoring indicators will be also assessed, with results including CK-MB,
CK, LDH, ALT, AST, ALB, CRP, CREA, UA, BUN, PRA, ALD, IL-6, PCT, TRIGL, HDL, LDL, and
HCY. These biomarkers will provide detailed information on participants' physiological responses and
health status.
6.4 Permitted or Prohibited Interventions
During the intervention study period, if the subject takes medication regularly, it can be carried out
normally according to the doctor's instructions.
7. Study Procedures
7.1 Enrollment

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The research subjects will be selected based on chronic disease management records, combined with
the above inclusion and exclusion criteria, and the research subjects with good compliance and willing
to complete the study according to the requirements of the project were selected.
7.2 Randomization
The process of conducting cluster randomization using a random number table starts with the random
selection of districts. Each district is assigned a unique numerical identifier, and the random number
table is then used to select the appropriate number of districts for inclusion in the study. After selecting
the districts, the next step involves randomly choosing communities within these selected districts.
Similar to the districts, each community is assigned a unique number, and the random number table is
again used to carry out the community selection process.
Once the communities are chosen, they are randomly assigned to one of three intervention groups: the
combined intervention group, the self-monitoring group, or the control group.
7.3 Sleeping Assessment Questionnaire
The Pittsburgh Sleep Quality Index (PSQI) is a widely used self-report questionnaire designed to
measure sleep quality and disturbances over a one-month period6. The PSQI consists of 19 individual
items that assess seven key components of sleep: subjective sleep quality, sleep latency (the time it
takes to fall asleep), sleep duration, habitual sleep efficiency (the ratio of total sleep time to time spent
in bed), sleep disturbances, use of sleep medication, and daytime dysfunction.Each of the seven
components is scored from 0 to 3, with the total PSQI score ranging from 0 to 21. A total score greater
than 5 indicates poor sleep quality, while a lower score suggests good sleep quality. The PSQI has been
validated in various populations and is frequently used to assess sleep problems in both clinical and
research settings.
7.4 BP Measurement
All participants will self-monitor their BP once during the pre-intervention phase and daily throughout
the intervention phase. Moreover, during the intervention period, participants in the intervention and
monitoring groups will measure their BP themselves three times each morning (6:00 a.m. to 8:00 a.m.)
and evening (6:00 p.m. to 8:00 p.m.) at home. BP measurements will be taken in a seated position after
5 minutes of quiet rest, using a self-monitored electronic sphygmomanometer (Model Maibobo,
Shenzhen Yike Network Technology Co., Ltd., China), following a standard protocol. The Global
System for Mobile Communication network can transmit these measurements to the digital health tool.
7.5 ECG Measurement
All participants will self-monitor their ECG once during the pre-intervention phase and daily
throughout the intervention phase. The handheld electrocardiographic recorder, CarePatch (ECG-H01,
Hangzhou Proton Technology Co., Ltd., China), will be used to monitor the electrocardiographic
conditions of the study participants, providing outputs such as normal status, overall ECG warning
level, Left ventricular hypertension, Sinus arrhythmia, Sinus tachycardia, Sinus bradycardia, Right
bundle branch block, Ventricular premature beats, Atrial premature beats, Abnormal Q waves, T-wave
changes and ST changes, which represent electrocardiographic abnormalities.
7.6 Exposure Temperature Measurement
Daily personal temperature exposure will be recorded using a portable temperature and humidity sensor
(Renke, COS-04) during two intervention periods. When participants are outdoors, the temperature and
humidity sensor will be worn on the upper chest and placed on the desk in the living room when
indoors.
7.7 Heatwave Perception Questionnaire

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The Heatwave Perception Questionnaire aims to assess individuals' awareness and concerns regarding
heatwaves, particularly their potential health impacts on people with hypertension. Given the frequent
occurrence of heatwaves in northern China during the summer, which poses significant health risks,
this questionnaire captures participants' perceptions of heatwave-related health risks and their level of
preparedness. Respondents rate their responses on a continuous scale from 0 to 100, with 0
representing "not at all" or "very low" and 100 representing "very much" or "very high," allowing them
to express the degree of their perception and concern. The questions include: how much attention they
pay to information about heatwaves and hypertension, how frequent they believe heatwaves occur in
their area, how much they know about the risks heatwaves pose to individuals with hypertension, how
concerned they are about these risks, how severe they believe the health impacts are, and how effective
they think protective measures like air conditioning can be in mitigating these impacts. This
questionnaire provides valuable insights into heatwave awareness, risk perception.
7.8 Cold Spell Perception Questionnaire
The Cold Spell Perception Questionnaire is designed to assess individuals' awareness and concerns
regarding cold spell events, particularly their potential health impacts on people with hypertension.
Given the frequent occurrence of cold spells in northern China during winter, which pose significant
health risks, this questionnaire captures participants' perceptions of cold spell-related health risks and
their level of preparedness. Respondents rate their responses on a continuous scale from 0 to 100, with
0 representing "not at all" or "very low" and 100 representing "very much" or "very high," allowing
them to express the degree of their perception and concern. The questions include: how much attention
they pay to information about cold spells and hypertension, how frequent they believe cold spells occur
in their area, how much they know about the risks cold spells pose to individuals with hypertension,
how concerned they are about these risks, how severe they believe the health impacts are, and how
effective they think protective measures (such as using heaters, dressing warmly, sealing windows,
resting, avoiding outdoor activities, eating warm foods, exercising moderately, and staying informed of
cold spell warnings) can be in mitigating these impacts. This questionnaire provides valuable insights
into cold spell awareness, risk perception.
7.9 Cardiovascular and Cerebrovascular Symptoms Questionnaire
The Cardiovascular and Cerebrovascular Symptoms Questionnaire assesses symptoms over the past
week. Participants are asked to indicate the frequency and characteristics of chest pain or discomfort,
including whether it occurs during physical exertion and how long it takes to relieve. They are also
asked about the duration of pain compared to usual, severe chest pain lasting more than 30 minutes,
and any numbness, tingling, or loss of sensation on one side of the body lasting more than 5 minutes.
Additionally, the questionnaire inquires about episodes of difficulty speaking or understanding others
and whether the participant sought medical attention for these symptoms. If medical attention was
sought, the main symptoms are identified. The medical history section includes questions on previous
diagnoses of angina, myocardial infarction, and stroke, with space for the dates of first diagnoses.
7.10 The Respiratory System Symptoms Questionnaire
The Respiratory System Symptoms Questionnaire evaluates symptoms experienced over the past week.
Participants are asked to indicate the frequency of various respiratory symptoms, including cough (≥4
times daily), sputum production (≥2 times daily, not just clearing the throat), cough with sputum,
wheezing, shortness of breath, dyspnea, chest tightness, fever, chest pain, and difficulty in breathing
not caused by medication. Additional symptoms assessed include wheezing sounds (e.g., "hehe"), nasal

15
symptoms (such as sneezing, runny nose, or nasal congestion), hemoptysis or blood-streaked sputum,
snoring, and daytime sleepiness. Each symptom is rated on a scale from 1 (all the time) to 5 (never).
7.11 Cognitive Assessment Scale
The Mini-Mental State Examination (MMSE) will be used to assess participants' cognitive function,
particularly focusing on memory, attention, language, and executive function in older adults7. The
MMSE evaluates five main areas: orientation (to time and place), memory (short-term and long-term),
attention and calculation (concentration and basic arithmetic), language (fluency and comprehension),
and executive function (complex task performance). Each area is scored on a scale from 0 to 5, with a
total score ranging from 0 to 30. Typically, a score above 24 indicates normal cognitive function, while
a score below 24 may suggest cognitive impairment.
7.12 Generalized Anxiety Disorder Scale (GAD-7)
The Generalized Anxiety Disorder Scale (GAD-7) will be used to assess the severity of generalized
anxiety disorder symptoms among participants8. The GAD-7 evaluates seven key symptoms of anxiety:
feeling nervous, anxious, or on edge; not being able to stop or control worrying; worrying too much
about different things; trouble relaxing; being so restless that it is hard to sit still; becoming easily
annoyed or irritable; and feeling afraid as if something awful might happen. Each symptom is rated on
a scale from 0 (not at all) to 3 (nearly every day), resulting in a total score ranging from 0 to 21. A score
of 5 or above indicates the presence of generalized anxiety disorder symptoms, with higher scores
reflecting greater symptom severity.
7.13 Depression Assessment Scale
The Patient Health Questionnaire-9 (PHQ-9) will be used to assess the severity of depressive
symptoms among participants9. This self-report tool evaluates nine key symptoms of depression
experienced over the past two weeks, including loss of interest or pleasure in activities, feeling down or
hopeless, trouble sleeping, fatigue, poor appetite or overeating, feelings of worthlessness or failure,
difficulty concentrating, physical agitation or slowing, and thoughts of self-harm or suicide. Each
symptom is rated on a scale from 0 (not at all) to 3 (nearly every day), with total scores ranging from 0
to 27. Scores of 5, 10, 15, and 20 indicate mild, moderate, moderately severe, and severe depression,
respectively.
7.14 Social Support Assessment Scale
The Perceived Social Support Scale (PSSS) will be utilized to assess participants' subjective perception
of the social support they receive10. The PSSS evaluates three key sources of support: family, friends,
and significant others. It consists of 12 items, with four items each related to family, friends, and
significant others. Participants rate their agreement with each statement on a scale from 1 (very
strongly disagree) to 7 (very strongly agree), resulting in a total score ranging from 12 to 84, where
higher scores indicate higher perceived social support.
7.15 Time-activity Patterns Measurement
All participants will complete self-reported time-activity diaries via the digital heat health risk early
warning tool during two intervention periods. The duration spent in various settings (such as outdoor
environments, workplaces, transportation, home, and other indoor areas) and at different intensity
levels of physical activity were recorded. Severe physical activities include shoveling, digging, plowing,
running, carpentry, construction, and carrying. Moderate activities comprise housework, walking, yard
work, light carpentry, and biking. Light activities are office work, driving, walking, and babysitting.
Sedentary activities include eating, reading, writing, watching TV, listening to the radio, and using the
computer.

16
7.16 Medication Adherence Indicators Measurement
The measurement of indicators of medication-taking behavior for hypertension is obtained through the
Hypertension Patient Self-Management Behavior Rating Scale (HPSMBRS) and the Hypertension
Patient Medication Adherence Rating Scale (HPMARS), yielding scores for self-management behavior
and medication adherence, respectively.
7.17 Cardiovascular Health Biomarkers Measurement
Cardiovascular indicators are crucial for assessing heart health and detecting potential damage to heart
muscle and other cardiovascular tissues. Creatine Kinase-MB (CK-MB) is an isoenzyme primarily
found in the heart muscle, and elevated levels in the blood can signal myocardial infarction or heart
damage. Creatine Kinase (CK) is an enzyme involved in energy production in muscles, and increased
levels may indicate muscle stress or damage. Lactate Dehydrogenase (LDH) is an enzyme that plays a
role in cellular energy production; elevated levels can suggest tissue damage, including from
cardiovascular events. These indicators are typically measured through blood tests that assess the
enzyme activity and concentration in the bloodstream.
7.18 Liver Function Health Biomarkers Measurement
Liver indicators help in evaluating liver function and detecting liver-related conditions. Alanine
Aminotransferase (ALT) is an enzyme predominantly found in the liver, with elevated levels often
indicating liver inflammation or damage. Aspartate Aminotransferase (AST) is another enzyme present
in the liver, heart, and muscles, with high levels potentially suggesting liver injury or other organ
damage. Albumin (ALB) is a protein synthesized by the liver, and its levels reflect liver function and
nutritional status; low levels can signal liver disease or malnutrition. C-Reactive Protein (CRP) is
produced by the liver in response to inflammation; increased CRP levels can indicate systemic
inflammation or infection. These indicators are assessed through blood tests that measure enzyme
activity, protein concentration, and inflammation markers.
7.19 Kidney Function Health Biomarkers Measurement
Kidney indicators are vital for monitoring kidney function and identifying potential renal issues. CREA
(Creatinine) is a waste product from muscle metabolism, and elevated levels can indicate impaired
kidney function. Uric Acid (UA) is produced from the breakdown of purines and high levels can be
associated with gout or renal problems. Urea Nitrogen (BUN) is a byproduct of protein metabolism,
and high levels can reflect kidney dysfunction. Plasma Renin Activity (PRA) is involved in regulating
blood pressure and electrolyte balance; abnormal levels can suggest kidney disease or hypertension.
Aldosterone (ALD) is a hormone that affects sodium and potassium levels and blood pressure; its
measurement can help diagnose adrenal or renal disorders. These indicators are evaluated through
blood tests that measure waste products, hormone levels, and other renal function markers.
7.20 Inflammatory Indicators Measurement
Inflammatory markers are essential for detecting and monitoring inflammatory conditions and
infections. Interleukin-6 (IL-6) and Interleukin-1β(IL-1β) are
cytokines that plays a role in immune
response and inflammation; elevated levels can indicate various inflammatory diseases. Procalcitonin
(PCT) is a protein that increases in response to bacterial infections and sepsis; high levels are used to
diagnose severe infections. Measurement of these markers is done through blood tests that detect
cytokine levels and protein concentrations, providing insights into the body's inflammatory and
immune responses.
7.21 Metabolic Indicators Measurement

17
Metabolic indicators assess metabolic health and risk factors for chronic diseases. Lactate
Dehydrogenase (LDH) also noted under cardiovascular indicators, is involved in energy metabolism
and its levels can indicate metabolic disturbances. Triglycerides (TRIGL) are a type of fat in the blood,
and elevated levels are linked to increased cardiovascular disease risk. High-Density Lipoprotein (HDL)
is beneficial for heart health, with higher levels associated with a lower risk of heart disease.
Low-Density Lipoprotein Cholesterol (LDL) can contribute to cardiovascular problems when elevated.
Homocysteine (HCY) is an amino acid whose high levels are associated with a greater risk of
cardiovascular disease. These indicators are typically measured through blood tests that analyze lipid
profiles and metabolic markers.
8. Statistical Considerations and Analytical Plan
8.1 Sample Size Calculation
In this study, the sample size is calculated according to the formula n=
2pαqβ(Zα+Zβ)2
(p1−p2)2
, assuming the
intervention’s effectiveness, a 3.2 difference of PQSI scores is anticipated in the combined intervention
group compared to the control group, and using the PASS15.0 software, where α=0.05 and β=0.211.
The sample size calculated for this study is 56, taking into account a 20% loss to follow-up rate, the
final sample size is determined to be 68. During two intervention periods, a total of 136 participants
will be enrolled in the study.
8.2 Statistical Analysis
For continuous variables such as age and BMI, data that follow a normal distribution will be described
using the mean and standard deviation (Mean ± SD). In cases where the data do not follow a normal
distribution, the median and interquartile range (Median, IQR) will be used instead. For categorical
variables, like gender and smoking status, percentages will be used to represent the distribution across
the groups. Group differences will be analyzed using one-way ANOVA for normally distributed data
and the Kruskal-Wallis test for non-normally distributed data.
The proportion of participants achieving a systolic blood pressure (SBP) below 140 mm Hg (or 120
mm Hg) and a diastolic blood pressure (DBP) below 90 mm Hg (or 80 mm Hg) each week or routine
health check-up is calculated by Control ratei =
Control numberi
Total numberi , where Control ratei
denotes the
proportion of participants who will achieve an SBP below 140 mm Hg (or 120 mm Hg) and a DBP
below 90 mm Hg (or 80 mm Hg) at each week or routine health check-up. Control numberi refers to
the count of participants who will meet the control criteria at the end of each week or routine health
check-up. The Total numberi indicates the participant count at the end of each week or routine health
check-up.
We will use a linear mixed-effects model to explore the effectiveness of combining this digital tool
with traditional self-monitoring in elderly patients with hypertension, comparing its impact on blood
pressure control to self-monitoring alone and the absence of any intervention.
Changes in BP, risks of ECG abnormalities, environmental exposures, mental health status (including
stress levels, emotional stability, and psychological resilience), medication adherence, perceptions of
heatwaves and cold spells, and indicators of biological sample testing compared with the
pre-intervention period in each group will be analyzed using a linear mixed-effects model, as shown in
Formula 1.

18
Yi = β0iperiod + βniXni + ZiΓi + εi (1)
where Yi represents the outcomes measured in both the pre-intervention and intervention periods. The
term period represents different intervention periods (pre-intervention and intervention period); Xni
represents matrixes of covariates (smoking and drinking status, and daily outdoor temperature).
βni
is
the
parameter
vector
of
covariates,
Γi
is
the
individual
random
effect, Zi is the parameter vector of the random effect, and εi is the residual.
The effect of the intervention will be assessed using a linear mixed-effects model, as indicated in
Formula 2.
��= �0������+ ������+ ����+ ��(2)
The term group denotes various interventions (the combined intervention, self-monitoring alone and
control groups); Xni represents matrixes of covariates (age, sex, BMI, age, education, smoking and
drinking status, baseline BP indicators, and daily outdoor temperature), Yiis the change in outcomes
for each group, compared to the baseline, and βni, Γi, Zi, and εi have equivalent meanings to those in
Formula 1.
8.3 Analytical Tools
All statistical analyses were carried out in R software version 4.1.1. Statistical tests were two-sided,
and p < 0.05 was considered statistically significant.
9.Criteria
for Participant
and
Study
Completion
and
Premature
Study
Termination
9.1 Participant Completion
Study participants who meet the inclusion exclusion criteria and complete all interventions during the
study.
9.2 Participant Stopping Rules and Withdrawal Criteria
Subjects may terminate the study early for the following reasons:
1. Study participants may voluntarily withdraw at any point in the course of the study.
2. Subject "lost to follow-up"
3. Participant died.
4. If any clinical adverse events, other medical conditions, or circumstances occur that make it not in
the best interest of the subject to continue participating in the study, the study subject will discontinue
further study intervention.
10.Protocol Deviations
The investigator will conduct the study in strict accordance with the protocol and will not allow
deviations from the protocol. In the event of any changes, disagreements, or deviations during the
course of the study, corrective actions will be developed by the site and implemented immediately.
11.Ethical Considerations
Participation in the trial is voluntary and the subject may withdraw from the study at any time for any
reason. Subjects (or their legal representatives) participating in the trial will be issued and read an
informed consent form, signed and dated informed consent form prior to any study procedures, and the
informed consent materials will be presented in the participant's primary language.
12.Quality Control and Quality Assurance
Before the investigation, each technical person responsible for BP, ECG, exposure monitoring,
questionnaire survey and computer testing should participate in technical training and pass the training
assessment; Each technical person should be familiar with the division of labor and tasks and

19
responsibilities. During the investigation, all technical personnel should carry out various tasks in strict
accordance with the investigation process and operating procedures; When you encounter a problem,
you should report it to the relevant person in charge and ask for help as soon as possible. The
replacement of research subjects and monitoring instruments should be recorded, and the monitoring
data obtained should be handed in in a timely manner, and the data collector should check the quality
of the monitoring data in a timely manner, and feedback to the investigator for correction if necessary.
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