Chinese Heart Healthy Diet for People With High Cardiovascular Risk in China (DECIDE-Diet)

The Chinese Heart Healthy Diet (CHH-diet) is a study in the DECIDE project (Diet, ExerCIse and carDiovascular hEalth), which includes five studies. The others are DECIDE - Exercise, DECIDE - Salt in Elderly, DECIDE - Obesity in Children, and DECIDE - Smart Living. The primary aim of this study is to evaluate the effects of CHH-diet in reducing blood pressure in Chinese adults with high cardiovascular risk. The corresponding null hypothesis is the mean systolic blood pressure of participants in CHH-diet group is equal to the mean systolic blood pressure of those in usual diet group. The secondary aims of this study are: 1) to evaluate the effect of CHH-diet on reducing the blood lipid, blood glucose and overall risk of cardiovascular and cerebrovascular diseases; 2) the influence of different cuisines on the intervention effect; 3) the influence of baseline blood pressure, blood glucose and lipid levels on the intervention effect; 4) the difference of the food preference between the two groups; 5) the effect of CHH-diet on intestinal flora, and the influence of intestinal flora on the effect of CHH-diet on blood pressure, fasting blood glucose and blood lipids.

Potential participants will be evaluated for eligibility at each center located in cities accordance with the four cuisines: Qingdao and Beijing (Shandong cuisine), Shanghai (Huaiyang cuisine), Guangzhou (Cantonese cuisine), and Chengdu (Szechuan cuisine). Two screening visits will be performed to identify eligible participants. At the first visit, participants will be asked several key questions about inclusion and exclusion criteria. At the second visit, a full questionnaire and measurement will be conducted to screen eligible participants. All eligible participants will participate in a 1-week run-in phase in which they will be fed with the usual diet in urban China. A participant will be excluded if failing to consume more than three meals for any reason. Participants who pass the run-in phase will be re-check the inclusion and exclusion criteria and then assigned 1:1 to receive CHH-diet or usual diet with the use of a central concealed randomization procedure (simple randomization), stratified by center and batch after the each baseline survey completed. At each center, participants will enter the randomization phase through 3-4 batches according to the feeding capacity of each center.

Four different recipes of CHH-diet have been developed according to four local cuisines: Shandong cuisine (Qingdao and Beijing), Huaiyang cuisine (Shanghai), Cantonese cuisine (Guangzhou), and Chengdu (Szechuan cuisine), but the four different healthy recipes share the same nutrients targets. The control group will receive local usual diet with the similar 4-week menus as CHH-diet group, but their nutrients targets will be the same as run-in period. We will measure the actual intake of every meal for all participants during the whole study period to better estimate their nutrients intakes. All subjects will be advised to avoid outside food during the study period, and the information outside food should be reported if they eat.

Intake of foods and nutrients measurement: First, for each food/dish, raw food materials will be weighted after cleaning and before cooking. Then before the food served to the study participants it will also be weighted and recorded. After each meal, the leftover food from each participant will be measured and recorded as well. The average daily energy and dietary nutrient intake by each participants will be calculated using the China Food Composition (2nd Edition, volume 1).

The baseline data collection should be performed on the last two days of the run-in phase, which includes a questionnaire interview on demography, lifestyle and health behaviors, history of diseases, medication use (antihypertensive drugs, antidiabetic drugs, and lipid-lowering drugs), food preference; physical examinations (blood pressure, body weight \& height, pulse rate); fasting blood tests (fasting glucose [FBG], total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides, and serum potassium); spot urine tests (sodium, potassium, creatinine excretion); and fecal sample tests on gut microbial community. The same physical examinations, medication use, food preference, fasting blood tests, spot urine tests, physical examinations and fecal sample tests on microbiome will be repeated at the end of the trial with the same methods by staffs blinded to the intervention. In addition, blood pressure, body weight, medication use, food preference assessment will be assessed weekly during the trial.

Power analysis: According to the findings from the DASH diet that successfully reduced SBP by 5.5 mmHg in 8 weeks, we conservatively assumed that CHH diet will reduce SBP by 3.0 mm Hg in comparison with the control diet in 4 weeks. And we further assumed the standard deviation of SBP change will be 8 mmHg in the control group according to our previous studies. To have 90% power with a type I error rate of 5% to detect the assumed effect size, we would need 165 participants in each arm. Assuming that 10% of study participants will be lost by the end of the study, we will recruit a total of 360 participants (90 from each center).

Statistical analysis: The primary analyses will follow the intention-to-treat principle and will be conducted among participants who have been randomized and the primary outcome are collected. The linear regression will be used to estimate the absolute differences between two groups in both primary and secondary outcomes, reported as least squared means after adjusting for centers. The differences in pre-set confounders between groups will be calculated by using a t-test, Wilcoxon rank test, or chi-square test. Sensitivity analyses will be performed to adjust for the imbalanced pre-set confounders if existed and to repeat the analyses with imputed missing values due to the lost to follow ups if the missing rates of outcomes higher than 5%. Per-protocol analyses will be conducted among population including those who consume more than 80% of study meals and completed the final follow up, with body weight change within 2kg and as well as the medications and dosages unchanged throughout study period. Subgroup analyses will be performed to identify potential modifiers of the intervention effect, including type of Chinese cuisine (center), gender, age, baseline multi-morbidity, medications use, blood pressure, glucose, total cholesterol, and estimated 10-year risk of ischemic cardiovascular disease.

Date management: a Web-based Data Management System (Redcap) will be used to facilitate data collection and central management during the whole process of the trial. Access to stored information is restricted to authorized personnel only. Paper forms with participant-identifiable information are held in secure, locked in file cabinets within a restricted area of each site.

Quality control: quality control team was established before the initiation of this study. All the researchers participating in this study must attend the technical training and pass the examination organized by the coordinating center, including study protocol, informed consent, case report form, standard operating procedures of participants' data collections, collection and preservation methods of biological samples. All biological samples will be tested in our central laboratory located in Beijing. The biochemist who performs the assessment will be blinded to allocation. In addition, 10% of urine and blood samples will be taken as split samples to control the quality of laboratory test results. On-site and on-line monitoring for data verification will be used. Each site will have at least two on-site monitoring visits, one at the beginning of the trial and one at the end of the trial. Quality control team will convene executive committee teleconferencing for quality control if necessary.

Data sharing plan: Data are available upon reasonable request (Yanfang Wang, pucri_wangyf1225@bjmu.edu.cn).