A Blood Pressure-Lowering Diet for Preventing and Managing Hypertension

Detailed Description

Hypertension is a major public health challenge and an important risk factor for stroke, coronary heart disease, heart failure, chronic kidney disease, and premature death. The burden of hypertension is particularly substantial among working-age populations exposed to occupational stress, high-sodium dietary patterns, frequent consumption of refined or processed foods, insufficient physical activity, and irregular lifestyles. However, evidence-based dietary approaches for lowering blood pressure are not always readily transferable to workplace settings because of differences in food culture, meal preparation practices, individual energy requirements, and the organization of food services.

This study is a pragmatic, parallel-group, cluster-randomized controlled trial designed to evaluate the effectiveness, feasibility, and potential biological mechanisms of a culturally adapted blood pressure-lowering dietary pattern, referred to as the Eastern Blood Pressure-Lowering Diet, among employees with primary hypertension in Shengli Oilfield, China. The intervention is designed to be compatible with Chinese dietary habits and implemented through an established workplace food-service system.

The study will recruit approximately 800 participants from 16 workplace clusters. Eligible participants will be adults aged 18 to 60 years who have previously been diagnosed with primary hypertension by a medical institution or who meet the diagnostic criterion of systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg on three measurements obtained on different days. Participants are also required to regularly eat at the participating workplace canteens, generally on at least four working days per week, and to provide written informed consent.

Individuals will be excluded if they have secondary hypertension; are pregnant, breastfeeding, or planning pregnancy during the study; have a serious allergy or intolerance to major foods included in the intervention; have experienced a major cardiovascular or cerebrovascular event within the previous 6 months; have cancer, advanced kidney disease, severe liver disease, or another condition requiring a specialized therapeutic diet; have severe cardiopulmonary disease, serious psychiatric illness, major cognitive impairment, hearing impairment, or a physical disability that would substantially interfere with participation; or are otherwise considered unsuitable for participation by the investigators.

Cluster Randomization and Blinding

Randomization will be performed at the level of tertiary organizational units within Shengli Oilfield. Cluster randomization is used because the dietary intervention will be delivered through a centralized workplace catering system, and individual randomization within the same organizational unit or dining environment could lead to contamination between intervention groups.

After participant recruitment and baseline assessments have been completed for all clusters, an independent statistician who is not directly involved in intervention delivery will generate the random allocation sequence. The 16 clusters will be assigned in a 1:1 ratio to either the standard management group or the dietary intervention group, with approximately eight clusters and 400 participants in each group.

Because of the nature of the dietary intervention, participants, catering staff, and personnel responsible for intervention delivery cannot be blinded to group assignment. However, outcome assessors responsible for standardized blood pressure and anthropometric measurements, as well as investigators conducting the primary statistical analyses, will remain blinded to treatment allocation whenever feasible.

Standard Hypertension Management Group

Participants in the standard management group will continue to receive routine hypertension care from their designated hospitals or local medical institutions in accordance with current Chinese hypertension management guidelines.

Standard management may include lifestyle counseling, hypertension-related health education, clinical follow-up, and antihypertensive medication when medically indicated. Medication prescriptions and adjustments will remain under the authority of the participants' treating physicians, and the research team will not directly prescribe or modify antihypertensive treatment.

Participants will be encouraged to maintain stable medication types and dosages when clinically appropriate. Any changes in antihypertensive, lipid-lowering, glucose-lowering, or other relevant medications will be recorded and considered in the statistical analyses.

Participants will receive standardized educational materials concerning hypertension prevention and management, including written materials and health education videos. Educational topics may include sodium reduction, healthy food selection, physical activity, weight management, medication adherence, and other lifestyle measures relevant to blood pressure control.

Participants will also use the study application to complete questionnaires, record selected health behaviors, view health assessment results, and receive health education. Wearable devices may be used to passively record physical activity, heart rate, and sleep-related measures.

Dietary Intervention Group

Participants assigned to the dietary intervention group will receive the same standard hypertension management and health education as the control group, together with a structured dietary intervention.

The core intervention is the Eastern Blood Pressure-Lowering Diet, developed by the research team with reference to the Chinese Dietary Guidelines and national dietary guidance for adults with hypertension. The dietary pattern has been adapted to local dietary preferences and the operational conditions of workplace canteens in Shandong Province.

On working days, participants in the intervention group will receive a standardized blood pressure-lowering lunch prepared and distributed by the workplace food-service center. The meals will be produced according to standardized recipes, ingredient specifications, cooking procedures, and portion-control requirements.

The major principles of the dietary intervention include:

• Reducing sodium intake and increasing dietary potassium, including the use of potassium-enriched low-sodium salt and reduced-sodium condiments;
• Improving carbohydrate quality by reducing added sugars and refined carbohydrates and increasing the proportion of whole grains, mixed legumes, and tubers;
• Improving dietary fat quality by avoiding trans fatty acids, limiting saturated fat, and emphasizing unsaturated vegetable oils and fish;
• Increasing the intake of vegetables and high-quality protein sources, including fish, shrimp, soy products, and low-fat dairy products;
• Using cooking methods such as steaming, boiling, stewing, and cold mixing in place of deep-frying and other high-fat cooking methods; and
• Encouraging adequate water intake while limiting sugar-sweetened and high-caffeine beverages.

Each intervention lunch will generally include at least 200 g of fresh vegetables and an appropriate combination of staple foods and high-quality protein sources. Whole grains, mixed legumes, or tubers are intended to account for approximately 30% to 50% of the staple-food portion.

To address differences in individual energy requirements, three standardized lunch energy levels will be provided:

• Level S: approximately 550 to 600 kcal per meal;
• Level M: approximately 650 to 750 kcal per meal; and
• Level L: approximately 800 to 900 kcal per meal.

Energy-level assignment will be based on a standardized scoring approach incorporating sex, age, body mass index, occupational physical activity, and regular exercise. The overall dietary composition, sodium density, potassium density, and macronutrient distribution will remain broadly consistent across the three energy levels, with total energy adjusted primarily by changing the quantities of staple foods and high-quality protein foods.

A 1-week run-in period will be conducted before the formal 3-month intervention. During this period, participants will receive the intervention lunches so that the research team can assess meal acceptability, satiety, portion suitability, food tolerance, and initial adherence. Energy assignment or meal portions may be adjusted based on participant feedback and observed food intake.

Participants who consume fewer than 80% of the provided intervention meals during the run-in period, experience a serious food allergy or substantial gastrointestinal intolerance, withdraw consent, or are found not to meet the clinical eligibility requirements may not proceed to the formal intervention phase.

During the formal intervention period, participants will be asked to consume the designated lunch on working days at the participating canteen or meal-distribution site. They will use the study application to record meal consumption and may upload photographs of meal trays to support adherence assessment. Brief satisfaction surveys will be conducted periodically, and minor modifications to taste, preparation, or menu combinations may be made without changing the prespecified nutritional standards.

To extend sodium reduction beyond the workplace lunch, participants in the intervention group will also receive low-sodium salt, reduced-sodium condiments, and salt-measuring utensils for use at home. Educational and behavioral support will encourage healthier evening meals and weekend dietary practices.

Apart from the dietary components, hypertension treatment, health education, follow-up procedures, and other study-related activities will be kept as similar as possible between the two groups.

Intervention Duration and Follow-up

The formal dietary intervention will last 3 months following the run-in period. Participants will subsequently be followed for up to 24 months to assess maintenance of effects and longer-term health outcomes.

During the first 3 months, participants may record dietary intake and selected self-measured health indicators through the study application. They will be encouraged to wear a study-provided wearable device for the passive collection of step count, heart rate, and sleep-related data.

During the intervention period, participants may self-monitor body weight and blood pressure weekly. Standardized on-site assessments will be conducted at prespecified visits, including monthly measurements of blood pressure, body weight, waist and hip circumference, and body composition where applicable.

Comprehensive assessments will be conducted at baseline and at the end of the 3-month intervention. Key clinical and health assessments may also be repeated at months 12 and 24.

Blood Pressure Measurement

Resting blood pressure will be measured by trained physicians or nurses using a validated and regularly calibrated upper-arm electronic blood pressure monitor.

Measurements will be conducted in a quiet room at an appropriate temperature. Participants will be instructed to avoid smoking, caffeinated beverages, and strenuous physical activity for at least 30 minutes before measurement and to empty their bladder when necessary. After sitting quietly for at least 5 to 10 minutes, participants will be measured in a seated position with the back supported, feet placed flat on the floor, and the measured arm supported at heart level.

At least two measurements will be obtained, generally 30 to 60 seconds apart. If the two readings differ by no more than 10 mmHg, their mean will be used. If the difference exceeds 10 mmHg, an additional measurement will be obtained, and the mean of the three readings will be recorded.

Study Outcomes

The primary outcome is the between-group difference in change from baseline in resting systolic blood pressure at 3 months. Change in resting diastolic blood pressure will also be evaluated as a key blood pressure outcome.

Additional blood pressure outcomes include longitudinal changes in systolic and diastolic blood pressure and the proportion of participants achieving the prespecified blood pressure control target.

Secondary and exploratory outcomes include:

• Body weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio, body fat percentage, and other body-composition measures;
• Fasting blood glucose;
• Total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol;
• Homocysteine;
• Kidney function indicators;
• Estimated 24-hour urinary sodium and potassium excretion derived from spot or morning urine samples;
• Dietary intake and dietary quality;
• Physical activity assessed using the International Physical Activity -Questionnaire-Short Form;
• Psychological status assessed using the Depression Anxiety Stress Scales-21;
• Sleep quality assessed using the Pittsburgh Sleep Quality Index;
• Health-related quality of life assessed using the 12-Item Short Form Health -Survey;
• Intervention adherence, including workplace meal consumption and application-based dietary records;
• Wearable-device measures such as step count, heart rate, and sleep-related variables;
• Health care utilization, intervention costs, medical expenditures, work attendance, and work-related fatigue or burnout;
• Hypertension-related complications and cardiovascular or cerebrovascular events; and
• Estimated long-term cardiovascular risk based on an established Chinese cardiovascular risk prediction model.

Biological Samples and Mechanistic Analyses

Fasting blood, morning urine, and stool samples will be collected at baseline and after the 3-month intervention.

Approximately 15 mL of fasting venous blood will be collected after an overnight fast. Blood samples will be processed into components such as serum and plasma for routine biochemical testing and exploratory analyses.

Approximately 10 mL of clean-catch midstream morning urine will be collected for the assessment of urinary sodium, potassium, kidney function-related indicators, and metabolomic analyses.

Approximately 3 to 5 g of stool will be collected using standardized collection procedures and stored under low-temperature conditions before transfer to the designated biobank.

Samples will be labeled using unique coded identifiers and stored under controlled conditions. Direct personal identifiers will not appear on laboratory samples or analytical datasets. The linkage between participant identity and study code will be maintained separately and accessible only to authorized personnel.

Metagenomic analysis of stool samples will be used to characterize changes in gut microbial diversity, composition, and functional pathways. Blood- and urine-based metabolomic analyses will be conducted to identify changes in small-molecule metabolic profiles. These analyses are intended to explore biological pathways through which the dietary intervention may affect blood pressure and metabolic health.

Sample Size

The sample-size calculation is based on the expected between-group difference in change in systolic blood pressure at 3 months.

Assuming an expected difference of 5 mmHg, a standard deviation of 15 mmHg, a two-sided significance level of 0.05, and 80% statistical power, approximately 142 participants per group would be required under an individually randomized design.

To account for cluster randomization, an intracluster correlation coefficient of 0.02 and an average cluster size of 50 participants were assumed, resulting in a design effect of approximately 1.98. Additional allowance was made for potential cluster loss. The final planned sample consists of 16 clusters, with eight clusters per group and approximately 50 participants per cluster, for a total target enrollment of approximately 800 participants.

Statistical Analysis

The primary analysis will follow the intention-to-treat principle whenever possible and will account for the clustered study design.

Continuous outcomes, including changes in systolic and diastolic blood pressure, will be analyzed using linear mixed-effects models or generalized estimating equations, as appropriate. Models will include treatment group, assessment time, and relevant group-by-time terms and will account for clustering at the organizational-unit level.

The primary blood pressure models will adjust for the corresponding baseline blood pressure value and may additionally adjust for prespecified variables such as age and sex. Depending on the outcome, analyses may also account for baseline body mass index, medication use, smoking, alcohol consumption, occupational activity, and other clinically relevant covariates.

Binary outcomes, including achievement of blood pressure control, will be analyzed using mixed-effects logistic regression or other models appropriate for clustered binary data. Ordinal outcomes may be analyzed using mixed-effects ordinal logistic regression.

Cardiovascular and cerebrovascular events occurring during longer-term follow-up will be analyzed using Cox proportional hazards models with appropriate adjustment for clustering, provided that a sufficient number of events is observed. If event counts are too low for reliable time-to-event modeling, descriptive or exact statistical methods may be used.

Missing data will be assessed with respect to the likely missing-data mechanism. Multiple imputation by chained equations may be used as the primary approach for relevant missing participant-level data. Imputation models may include outcome measures, baseline characteristics, intervention-adherence indicators, wearable-device data, and workplace dining frequency. Results across imputed datasets will be combined using Rubin's rules.

Sensitivity analyses will include complete-case analyses and analyses based on alternative assumptions about outcomes among participants with missing follow-up data.

Prespecified subgroup analyses may examine whether the intervention effect differs according to duration of hypertension, baseline antihypertensive medication use, body mass index category, and age group. Interaction terms between intervention assignment and the subgroup variable will be used to evaluate statistical evidence of heterogeneity. These analyses will be considered exploratory unless otherwise specified.

Safety Monitoring and Participant Protection

The dietary intervention is considered to involve relatively low risk, but potential adverse events may include symptomatic hypotension, dizziness, falls, gastrointestinal discomfort, food intolerance, and allergic reactions.

Adverse events will be monitored from the time of informed consent through the end of follow-up. Clinically important changes in blood pressure or health status will be referred to the participant's treating physician. Clinical treatment, including medication adjustment, will take priority over adherence to the research intervention.

Serious adverse events, regardless of whether they are considered related to the intervention, will be documented and reported to the sponsor and/or the ethics committee in accordance with applicable requirements. Appropriate medical care and emergency procedures will be initiated when necessary.

All participants will provide written informed consent before study-specific procedures are conducted. Participants may withdraw from the study at any time without affecting their routine medical care or employment-related health services.

The study has been reviewed and approved by the Peking University Biomedical Ethics Committee. Participant information and biological samples will be managed using coded identifiers, access controls, encrypted data transmission, and secure storage procedures. Study findings will be reported in aggregate form without directly identifying individual participants.