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Inverse Association Between Variety of Proteins With Appropriate Quantity From Different Food Sources and New-Onset Hypertension

Originally publishedhttps://doi.org/10.1161/HYPERTENSIONAHA.121.18222Hypertension. 2022;79:1017–1027

Abstract

The relationships of the variety and quantity of different sources of dietary proteins with hypertension remain uncertain. We aimed to investigate associations between the variety and quantity of proteins intake from 8 major food sources and new-onset hypertension among 12 177 participants from the China Health and Nutrition Survey. Dietary intake was measured by 3 consecutive 24-hour dietary recalls combined with a household food inventory. The variety score of protein sources was defined as the number of protein sources consumed at the appropriate level, accounting for types and quantity of proteins. New-onset hypertension was defined as systolic blood pressure ≥140 mm Hg and diastolic blood pressure ≥90 mm Hg, or physician-diagnosed hypertension or receiving antihypertensive treatment, during the follow-up. During a median follow-up of 6.1 years, there were U-shaped associations of percentages energy from total, unprocessed or processed red meat-derived, whole grain-derived, and poultry-derived proteins with new-onset hypertension; an reverse J-shaped association of fish-derived protein with new-onset hypertension; L-shaped associations of eggs-derived and legumes-derived proteins with new-onset hypertension; and an reverse L-shaped association of refined grain-derived protein with new-onset hypertension (all P values for nonlinearity <0.001). That is, for each protein, there is a window of consumption (appropriate level) where the risk of hypertension is lower. Moreover, a significantly lower risk of new-onset hypertension was found in those with higher variety score of protein sources (per score increment, hazard ratio, 0.74 [95% CI, 0.72–0.76]). In summary, there was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset hypertension.

Novelty and Significance

What Is New?

  • The relationships of the variety and quantity of different sources of dietary protein intake with hypertension risk remains uncertain. We aimed to investigate the prospective associations between the variety and quantity of proteins intake from 8 major food sources and new-onset hypertension among 12 177 participants without hypertension at baseline from the China Health and Nutrition Survey.

What Is Relevant?

  • There were U-shaped associations of percentages energy from total, unprocessed or processed red meat-derived, whole grain-derived and poultry-derived proteins with new-onset hypertension; an reverse J-shaped association of fish-derived protein with new-onset hypertension; L-shaped associations of eggs-derived and legumes-derived proteins with new-onset hypertension; and an reverse L-shaped association of refined grain-derived protein with new-onset hypertension. Moreover, a significantly lower risk of new-onset hypertension was found in those with higher variety score of protein sources.

Summary

There was an inverse association between the variety of proteins with appropriate quantity from different food sources and new-onset hypertension in general Chinese adults.

Hypertension has become an emergent challenge for global public health, because of its remarkably high prevalence, detrimental effects on cardiovascular disease and premature death.1,2 In this context, modified preventive strategies for hypertension are urgently needed.

Recently, nutrition has been suggested as a possible measure to fight against the hypertension epidemic.3,4 Along with fat and carbohydrate, protein is one of the 3 basic macronutrients. A previous meta-analysis (including 3277 participants in total) of randomized controlled trials with 3 to 52 weeks duration has showed that dietary protein intake was associated with reduced blood pressure (BP) levels.5 However, a recent randomized trial6 found that protein supplementation for 2 years did not significantly affect BP levels. Consistently, several long-term prospective studies about dietary protein intake and hypertension also reported inconsistent findings, including nonsignificant,7 inverse,8 and positive associations.9 Of note, previous studies only focused on the intake of total protein, total animal protein, and total plant protein. In fact, it has been reported that protein intake is a rather heterogeneous exposure and proteins from specific food sources may differentially affect BP. However, only a few attempts with relatively small sample sizes (n<3600)10,11 have been made to examine the association between proteins intake from specific food sources and the risk of hypertension and have reported inconsistent results. Moreover, most previous studies about protein intake and hypertension association regarded protein intake as a categorical variable, and the continuous relationship of protein intake with hypertension risk has not been well characterized. Therefore, to date, the prospective association between protein intake, especially proteins from different food sources, and new-onset hypertension remains uncertain.

In addition, although some studies in cross-sectional design have suggested that dietary variety had an inverse association with elevated BP,12,13 the relationship between the variety of protein sources and incident hypertension has not yet been examined in the prospective design.

To address the essential knowledge gaps, based on data from the China Health and Nutrition Survey (CHNS), we aimed to evaluate the prospective associations between the variety and quantity of protein intake from 8 major food sources (whole and refined grain, processed and unprocessed red meat, poultry, fish, egg, and legumes) and new-onset hypertension in general Chinese adults. CHNS is an ongoing open cohort, international collaborative project between the Carolina Population Center at the University of North Carolina at Chapel Hill and the National Institute for Nutrition and Health at the Chinese Center for Disease Control and Prevention, which was designed to determine changes of economic, sociological, demographic, lifestyle, nutritional, and health status in China.

Methods

Study Design and Participants

Our article adheres to the American Heart Association Journals’ implementation of the Transparency and Openness Promotion Guidelines. The data and study materials that support the findings of this study can be found from the CHNS official website (http://www.cpc.unc.edu/projects/china). The study was approved by the institutional review boards of the University of North Carolina at Chapel Hill and the National Institute of Nutrition and Food Safety, and Chinese Center for Disease Control and Prevention. Each participant provided the written informed consent.

The CHNS was conducted by an international team of researchers whose backgrounds include nutrition, public health, economics, sociology, Chinese studies, and demography. Using a multistage random clustering design, initiated in 1989, and followed up every 2 to 4 years, CHNS has completed 10 rounds (1989, 1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, and 2015) and included >47% of Chinese population.14 In the 2009 wave of CHNS, blood samples were collected and analyzed in a national central lab in Beijing (medical laboratory accreditation certificate ISO 15189:2007) with strict quality control.15 Details of the study design and some major results of the CHNS were available elsewhere.14–18

The present study was a prospective cohort based on 7 rounds of CHNS data from 1997 to 2015 (1997, 2000, 2004, 2006, 2009, 2011, and 2015). First, we excluded participants who were pregnant, <18 years old, or with missing data on BP. Remaining participants who were surveyed at least 2 rounds were included, and the first round is termed as baseline. Then, participants with hypertension (systolic BP [SBP] ≥140 mm Hg or diastolic BP [DBP] ≥90 mm Hg, or diagnosed by a physician or receiving antihypertensive treatment) at baseline, were excluded. Furthermore, participants with missing dietary protein data or with extreme dietary energy data (male: >4200 or <600 kcal/d; female: >3600 or <500 kcal/d) were also excluded.19 Finally, a total of 12 117 participants were included in the final analysis (Figure S1).

Dietary Nutrient Intakes

Both individual and household level dietary data in the CHNS were collected by trained nutritionists through face-to-face interview in each survey round. The dietary intake was recorded by 3 consecutive 24-hour recalls in individual level, in combination with using a 3-day food-weighed method to assess cooking oil and condiment consumption at the household level. For the 24-hour recall, a trained interviewer recorded all the food consumption during a face-to-face interview by combining the individuals’ self-reporting with the total household consumption.14 The 3 consecutive days were randomly allocated in a week. The nutrient intake and total energy were calculated using the China food composition tables. The accuracy of 24-hour dietary recall designed to assess energy and nutrient intake has been validated.20

In the analyses, 3-day average intakes of dietary macronutrients and micronutrients in each round were calculated. In our analysis, cumulative average intake levels of each nutrient from baseline to the last visit before the date of new-onset hypertension, or the end of follow-up were further calculated and used to minimize within-person variation and make better estimates of long-term dietary intake status.21,22

Furthermore, in the present study, total protein was divided into specific-sourced proteins. Food sources constituting these subtypes are shown in Table S1.23,24 Of those, whole and refined grain, processed and unprocessed red meat, poultry, fish, egg, and legumes were the 8 major sources of protein in this population.

The variety score of protein sources was calculated as the sum of total numbers of 8 major food sources of proteins consumed at the appropriate quantities during the study period. The appropriate quantity for each major food source of protein means a window of consumption level (% of energy, shown in the results section) where the risk of new-onset hypertension is relatively lowest. The appropriate quantity for each major food source of protein was determined by assessing different sources of protein intakes (% of energy) as categorical variables (quartiles or quintiles), and choosing the corresponding protein categories with relatively lowest risk of new-onset hypertension. In other words, if participants consumed one of 8 major food sources of proteins at an appropriate quantity during the entire study period, they will get one point, with a maximal score of 8. The variety score of protein sources may account for both types and quantity of proteins intake.

Assessment of BP and Other Covariates

After the participants had seated for 5 minutes, BP was measured by trained research staff using a standard mercury manometer for 3 times. Triplicate measurements on the same arm were taken in a quiet and bright room. The mean of the 3 measurements were used in the analysis.

Information on age, sex, urban or rural residents, region, education level, occupation, physical activity, smoking, and drinking status were obtained from the questionnaires at each follow-up survey. Height and weight were measured following a standard procedure with calibrated equipment. Body mass index was calculated as weight (kg) by height squared (m2). The level of physical activity was defined as the self-reported time spent in each activity multiplied by specific metabolic equivalent values.25

Study Outcome

The study outcome was new-onset hypertension. Answering “yes” to the question “Has a doctor ever told you that you suffer from high blood pressure” was defined as self-reported physician-diagnosed hypertension. Therefore, new-onset hypertension was defined as SBP/DBP ≥140/90 mm Hg, or physician-diagnosed hypertension, or using antihypertensive drugs during the follow-up.

When a participant was first identified with new-onset hypertension in a following survey, the midpoint between this and the nearest previous survey was used to calculate the follow-up time. For those free of hypertension in all following surveys, the last survey date was used to calculate the follow-up time.

Statistical Analysis

Population characteristics are presented as mean±SDs and proportions for continuous and categorical variables, respectively. Differences in population characteristics by dietary total protein intake quintiles (% of energy, <10.6, 10.6–<11.6, 11.6–<12.5, 12.5–<14.0, and ≥14.0) were compared using ANOVA tests, Kruskal-Wallis test, or χ2 tests, accordingly.

Cox proportional hazards models were used to assess the relationship of variety score of protein sources, energy from total protein and proteins from different food sources (whole and refined grain, processed and unprocessed red meat, poultry, fish, egg, and legumes) with new-onset hypertension, with and without adjustments for age, sex, body mass index, occupations, education level, region, smoking status, alcohol drinking status, SBP, urban or rural residents, physical activity (low, moderate, and high), as well as total energy intake, fiber intake, sodium intake, potassium intake, and fat intake (% of energy), in addition to mutual adjustments for percentages of energy intake from other sources of dietary protein. Restricted cubic splines with 4 knots (20%, 40%, 60%, and 80% of energy from proteins) were also used to explore the potentially nonlinear relationship of energy from total protein and proteins from different food sources with new-onset hypertension.

Moreover, possible modifications of the association between total protein intake, variety score of protein source and new-onset hypertension were evaluated by stratified analyses and interaction testing.

The 2-side P<0.05 was deemed as statistically significant in all analysis. All statistical analyses were conducted using R version 4.0.1.

Results

Baseline Characteristics of Study Participants

The flow chart of the study participants was shown in Figure S1, the final analytic cohort included a total of 12 177 participants. Mean percentages of energy intake from total protein was 12.4% (SD: 2.4), and mean variety score of protein sources was 3.0 (SD: 1.3). Grains followed by red meat, legumes, fish, egg, and poultry are the major sources of protein, accounting for >80% of dietary protein intake (Table S1).

Table 1 showed characteristics of the study participants according to total protein intake quintiles. Among the study participants, 46.8% were males, and the mean age was 41.2±14.2 years. Those with higher total dietary protein intake were more likely to be males, alcohol drinkers, urban residents, and unemployed, and less likely to be farmer; had higher SBP, DBP, body mass index and education levels, higher intake of potassium, lower intake of carbohydrate, and lower physically active levels.

Table 1. Participants Characteristics by Quintiles of Energy From Total Protein Intake (% of Energy)*

CharacteristicsQuintiles of protein intake, % of energyP value
Q1 (<10.6)Q2 (10.6–<11.6)Q3 (11.6–<12.5)Q4 (12.5–<14.0)Q5 (≥14.0)
N24362435243524352436
Male, N (%)1063 (43.6)1099 (45.1)1153 (47.4)1211 (49.7)1172 (48.1)<0.001
Age, y42.2±14.840.7±13.740.3±13.739.9±13.942.9±14.6<0.001
Systolic blood pressure, mm Hg113.1±12.0113.1±11.2113.6±11.1113.9±11.4115.8±11.1<0.001
Diastolic blood pressure, mm Hg73.5±8.273.7±8.074.2±7.774.1±7.875.4±7.4<0.001
Body mass index, kg/m221.9±3.022.2±3.022.3±2.922.6±3.123.0±3.2<0.001
Smoking, N (%)703 (29.0)744 (30.7)778 (32.2)713 (29.4)750 (30.8)0.111
Alcohol drinking, N (%)725 (30.1)782 (32.5)825 (34.5)894 (37.1)912 (37.6)<0.001
Urban residents, N (%)502 (20.6)632 (26.0)767 (31.5)1050 (43.1)1454 (59.7)<0.001
Regions, N (%)<0.001
 Central896 (36.8)953 (39.1)1148 (47.1)1240 (50.9)1345 (55.2)
 North528 (21.7)499 (20.5)427 (17.5)432 (17.7)598 (24.5)
 South1012 (41.5)983 (40.4)860 (35.3)763 (31.3)493 (20.2)
Physical activity, N (%)<0.001
 Low711 (29.4)718 (29.8)775 (32.3)859 (35.6)944 (39.0)
 Moderate674 (27.9)719 (29.8)792 (33.0)897 (37.1)955 (39.4)
 High1032 (42.7)974 (40.4)835 (34.8)660 (27.3)522 (21.6)
Occupation, N (%)<0.001
 Farmer1290 (53.8)1215 (50.4)1002 (41.5)614 (25.5)227 (9.4)
 Worker191 (8.0)221 (9.2)312 (12.9)392 (16.3)341 (14.1)
 Unemployed511 (21.3)498 (20.6)551 (22.8)629 (26.1)848 (35.1)
 Other404 (16.9)478 (19.8)547 (22.7)777 (32.2)999 (41.4)
Education, N (%)<0.001
 Illiteracy659 (27.7)516 (21.6)470 (19.7)334 (14.0)226 (9.4)
 Primary school606 (25.5)592 (24.8)478 (20.0)373 (15.6)278 (11.5)
 Middle school746 (31.3)796 (33.4)853 (35.7)871 (36.5)725 (30.1)
 High school or above369 (15.5)481 (20.2)586 (24.5)806 (33.8)1179 (49.0)
Dietary intake
 Variety score of protein2.7±1.33.0±1.43.0±1.43.2±1.33.0±1.3<0.001
 Energy, Kcal/d2241.4±534.32247.7±483.32221.6±480.22173.1±509.82006.8±537.6<0.001
 Fat, % of energy31.3±12.029.2±9.529.2±9.631.2±9.733.9±9.2<0.001
 Carbohydrate, % of energy59.1±11.759.7±9.558.8±9.655.6±9.750.1±9.6<0.001
 Protein, g/d53.9±13.962.3±13.566.8±14.571.5±16.879.8±22.6<0.001
 Fiber, g/d9.9±5.610.9±5.511.3±6.011.2±6.510.6±7.9<0.001
 Sodium intake, g/d5.1±3.15.0±2.75.1±3.15.0±2.84.9±3.30.162
 Potassium intake, g/d1.5±0.51.6±0.51.7±0.61.7±0.61.9±0.7<0.001

* Variables are presented as mean±SDs or N (%).

Relationships of Dietary Total Protein and Proteins From Different Food Sources (% of Energy) With New-Onset Hypertension

During a median follow-up duration of 6.1 years, a total of 4269 participants (35.1%) were identified with new-onset hypertension. Of these, 826 were those with physician-diagnosed hypertension, 525 reported with the use of antihypertensive treatment during follow-up, and 3923 had a new-onset mean SBP ≥140 mm Hg and mean DBP of ≥90 mm Hg during follow-up. Some of the patients met at least 2 of the above 3 criteria. Of note, although the mean of the 3 BP measurements were used in the analysis, the usage of only the last 2 values of BP measurements did not obviously change the incidence of new-onset hypertension (35.3%) during the follow-up.

Overall, there was a U-shaped relationship of the percentage energy from dietary total protein intake with the risk of new-onset hypertension (P for nonlinearity <0.001, Figure S2). Accordingly, after assessing total protein intake in quintiles, participants in the first quintile (<10.6% of energy from total protein, adjusted hazard ratio, 1.30 [95% CI, 1.20–1.41]) and the fifth quintile (≥14.0% of energy from total protein, adjusted hazard ratio, 1.26 [95% CI, 1.15–1.38]) had significantly higher risks of new-onset hypertension, when compared with those in the 2 to 4 quintiles (10.6%–<14.0% of energy from total protein; Table 2). Similar trends were observed for the association between the average level of total protein intake on the first 2 surveys and the subsequent new-onset hypertension after the second survey (Table S2). Further adjustment for blood urea nitrogen among participants with blood samples measurements; excluding participants with physician-diagnosed hypertension, but with a normal BP level and without antihypertensive drugs treatment (n=205); calculating the follow-up person-time for new-onset hypertension as from baseline until the first hypertension diagnosis; or setting the most recent survey round to the event or censoring as baseline, also did not significantly alter the findings (Table S2).

Table 2. The Relationship of Total Protein Intake (% of Energy) With New-Onset Hypertension

Protein intake, % of energyCasesPerson-yearsUnadjusted modelP valueModel 1P value
HR (95% CI)HR (95% CI)
Quintile
 Q1 (<10.6)97718 9591.30 (1.18–1.42)<0.0011.32 (1.20–1.45)<0.001
 Q2 (10.6–<11.6)86821 725ReferenceReference
 Q3 (11.6–<12.5)86221 1061.03 (0.93–1.13)0.5981.00 (0.90–1.10)0.957
 Q4 (12.5–<14.0)81019 2971.06 (0.96–1.17)0.2261.07 (0.97–1.19)0.194
 Q5 (≥14.0)75214 0701.38 (1.25–1.53)<0.0011.29 (1.15–1.45)<0.001
Category
 Q1 (<10.6)97718 9591.26 (1.17–1.36)<0.0011.30 (1.20–1.41)<0.001
 Q2–4 (10.6–<14.0)254062 128ReferenceReference
 Q5 (≥14.0)75214 0701.35 (1.24–1.46)<0.0011.26 (1.15–1.38)<0.001

Model 1: Adjusted for age, sex, BMI, occupations, education level, region, smoking status, alcohol drinking status, systolic blood pressure (SBP), urban or rural residents, physical activity (low, moderate, and high), as well as total energy intake, fiber intake, sodium intake, potassium intake, and fat intake (% of energy). BMI indicates body mass index; HR, hazard ratio; SBP, systolic blood pressure.

In the stratified analyses, the P value of the interaction for total carbohydrate intake was <0.05. However, because of multiple testing and similar directionality of the associations in subgroups with different carbohydrate intake levels, the clinical implications of the interaction still should be further investigated. Other variables, including age, sex, body mass index, abdominal obesity, BP status (optimal: SBP <120 and DBP <80, normal: 120≤SBP<130 and 80≤DBP<85, high normal: 130≤SBP<140 and 85≤DBP<90 mm Hg), energy intake, total fat intake (% of energy), variety score of protein sources, fiber intake, sodium intake, and potassium intake, did not significantly modify the association between the percentage energy from total protein intake and new-onset hypertension (All P values of the interactions >0.05; Table S3). That is, there were similar U-shaped relations of total protein intake with new-onset hypertension in all the subgroups.

For specific protein sources, there were U-shaped associations of the percentages energy from unprocessed red meat-derived (Figure 1A) or processed red meat-derived (Figure 2A), poultry-derived (Figure 2B), and whole grain-derived (Figure 2C) proteins with new-onset hypertension; an reverse J-shaped association of fish-derived protein (Figure 2D) with new-onset hypertension; L-shaped associations of eggs-derived (Figure 2E) and legumes-derived (Figure 2F) proteins with new-onset hypertension; and an reverse L-shaped association of refined grain-derived protein (Figure 1B) with new-onset hypertension (all P values for nonlinearity <0.001). That is, when the percentages energy from these foods-derived protein intakes were relatively low, there were negative correlations or no correlations between intake of foods-derived proteins and hypertension risk, however, when intake exceeded certain thresholds, the risks of new-onset hypertension will increase or reach a plateau.

Figure 1.

Figure 1. The relations of unprocessed red meat-derived protein, refined grain-derived protein with new-onset hypertension*.

*Adjusted for age, sex, body mass index (BMI), occupations, education level, region, smoking status, alcohol drinking status, systolic blood pressure (SBP), urban or rural residents, physical activity (low, moderate, and high), as well as total energy intake, fiber intake, sodium intake, potassium intake, and fat intake (% of energy), and mutual adjustments for percentages of energy intake from other specific dietary protein source. (A, unprocessed red meat-derived protein; B, refined grain-derived protein.) HR indicates hazard ratio.

Figure 2.

Figure 2. The relations of other specific-sourced proteins intake with new-onset hypertension*.

*Adjusted for age, sex, body mass index (BMI), occupations, education level, region, smoking status, alcohol drinking status, systolic blood pressure (SBP), urban or rural residents, physical activity (low, moderate, and high), as well as total energy intake, fiber intake, sodium intake, potassium intake, and fat intake (% of energy), and mutual adjustments for percentages of energy intake from other specific dietary protein source. (A, processed-derived protein; B, poultry-derived protein; C, whole grain-derived protein; D, fish-derived protein; E, egg-derived protein; and F, legumes-derived protein.) HR indicates hazard ratio.

Similar trends were found when assessing different sources of protein intakes (% of energy) as categorical variables. In detail, the appropriate levels (% of energy) of specific-sourced proteins associated with lowest risk of new-onset hypertension were 0.5 to <3.1 (the 2–4 quintiles) for unprocessed red meat protein, 0 to <0.8 (the 1–3 quartiles among consumers) for processed red meat protein, 0 to <1.3 (the 1–3 quartiles among consumers) for poultry protein, 0 to <0.8 (the 1–3 quartiles among consumers) for whole grain protein, 0 to <1.4 (the 1–3 quartiles among consumers) for fish protein, >0 (consumers) for eggs protein, ≥0.3 (the 2–5 quintiles) for legumes protein and <3.8 (the first quintile) for refined grain protein (Figure S3). Similar results for the associations between different sources of protein intakes (% of energy) and new-onset hypertension were observed when the follow-up person-time for new-onset hypertension was calculated as from baseline until the first hypertension diagnosis (Figure S3).

Relationship of Variety Score of Protein Sources With New-Onset Hypertension

Overall, there was an inverse association between the variety score of protein sources and new-onset hypertension (per score increment, hazard ratio, 0.74 [95% CI, 0.72–0.76]; Table 3). The Kaplan-Meier curves of the cumulative event rate of new-onset hypertension by quartiles of the variety score of protein sources are shown in Figure S4A. Compared with those in the first quartile (protein variety score <2), participant in the fourth quartile (protein variety score ≥4; hazard ratio, 0.34 [95% CI, 0.31–0.38]) had a significantly lower risk of new-onset hypertension (Table 3). Similar trends were observed when the follow-up person-time for new-onset hypertension was calculated as from baseline until the first hypertension diagnosis (Table S4, Figure S4B), or after the removal of any one kind of protein from the protein variety score (Table S5).

Table 3. The Association Between Variety Score of Protein Sources and New-Onset Hypertension

Protein variety scoreCasesPerson-yearsUnadjusted modelP valueModel 1P value
HR (95% CI)HR (95% CI)
Continuous426995 1570.72 (0.71–0.74)<0.0010.74 (0.72–0.76)<0.001
Quartile
 Q1 (<2)7909545ReferenceReference
 Q2 (2)123520 0280.73 (0.67–0.80)<0.0010.78 (0.71–0.85)<0.001
 Q3 (3)118626 1740.53 (0.49–0.58)<0.0010.57 (0.51–0.62)<0.001
 Q4 (≥4)105839 4110.31 (0.28–0.34)<0.0010.34 (0.31–0.38)<0.001
P for trend<0.001<0.001

Model 1: Adjusted for age, sex, BMI, occupations, education level, region, smoking status, alcohol drinking status, SBP, urban or rural residents, physical activity (low, moderate, and high), as well as total energy intake, fiber intake, sodium intake, potassium intake, and fat intake (% of energy), in addition to total protein intake (% of energy). BMI indicates body mass index; HR, hazard ratio; and SBP, systolic blood pressure.

We performed the stratified analyses to further assess the association between variety score of protein sources (continuous, per score increment) and new-onset hypertension. Overall, the inverse associations between variety score of protein sources and risk of new-onset hypertension were indicated in all the subgroups. Although P values of the interactions for energy intake, total carbohydrate intake, and fiber intake were <0.05, because of multiple testing and similar directionality of the associations in different subgroups, the clinical implications of the interactions still should be further investigated (Table S6).

Discussion

In this prospective cohort with a relatively large sample size, we first found that there were U-shaped, reverse J-shaped, L-shaped, or reverse L-shaped associations between proteins from different food sources and new-onset hypertension. That is, for each protein, there is a window of consumption (appropriate level) where the risk of hypertension is lower. Moreover, there was an inverse association between variety score of protein sources and new-onset hypertension.

In fact, Schwingshackl et al3 have conducted a high-quality, dose-response meta-analysis and showed nonlinear relations of the intakes of whole grains, fruits, fish, and processed meats with the risk of hypertension. However, this study took focus on the relation of the intakes of 12 major food groups, but not the specific nutrients, with the risk of hypertension. Moreover, meta-analysis usually could not have comprehensive adjustments for the related covariates. Furthermore, a previous meta-analysis (including 3277 participants in total) of randomized controlled trials with small sample sizes (a median of 61 participants) and relatively short-term trial durations (1–52 weeks, median: 8 weeks) found that dietary protein intake was associated with a slight and significant reduction of SBP (mean: 1.76 mm Hg) and DBP (mean: 1.76 mm Hg).5 However, a recent randomized trial6 suggested that protein supplementation for 2 years did not significantly affect BP levels. Of note, most of the previous supplementation studies examined the effects of additional high protein supplementation on BP without considering the possible effect of baseline protein intake. Moreover, findings from prospective cohort studies with rather longer follow-up duration ranging from 2 to 7 years, also have indicated inconsistent findings, including nonsignificant,7 inverse,8 or positive relations9 of dietary protein intake with hypertension. Of note, these previous studies mainly evaluated protein intake in aspects of total protein, total animal protein, and total plant protein, which were rough. More importantly, most of the previous studies only focused on the BP difference among 2 or several categories of the proteins’ intake. Few previous studies have been conducted using the dietary protein intake data continuously, which may allow for the possibility of nonlinear association between protein intake and the risk of hypertension, and provide more granular information. Our current study examined the prospective associations between the variety and quantity of proteins intake from 8 major food sources and new-onset hypertension and provided some new insights in the following aspects:

Animal Proteins (Red Meat, Poultry, Fish, and Eggs) and Hypertension Risk

So far, 2 previous studies,10,11 both only enrolled Dutch general population, have been designed to investigate the relationships of specific protein sources with incidence of hypertension. However, maybe because of relatively limited sample size (N=2241,10 N=358811) or just linear hypothesis, neither found possible associations of proteins from animal products, such as dairy and meat, with the risk of new-onset hypertension.

Our study, featured by a relatively larger sample size, continuous and categorical assessments for dietary data, and more specific sources of proteins, demonstrated that there were U-shaped associations of unprocessed or processed red meat-derived and poultry-derived proteins with new-onset hypertension. That is, for each protein, there is a window of consumption (appropriate level) where the risk of hypertension is lower. The potential detrimental effects on BP of meat proteins might due to their metabolites, such as branched chain amino acids and aromatic amino acids, which increased the production of reactive oxygen species and activated NF-κB (nuclear factor-κB) pathway, resulted in the promotion of oxidative stress and inflammation.26,27 Furthermore, these amino acids can interfere the relaxation of endothelium through tetrahydrobiopterin production28,29 or affect central BP regulation via decreasing serotonin and catecholamine synthesis.30,31 Consistently, the AHS-2 (Adventist Health Study 2), a large North American cohort, had reported that vegetarian diets were associated with lower all-cause mortality.32 In addition, a recent systematic review also revealed that higher consumption of fruits, vegetables, nuts, legumes, whole grains, unsaturated vegetable oils, fish, and lean meat or poultry were related to a decreased risk of all-cause mortality.33 In another aspect, overall, the Chinese had lower consumption levels of unprocessed or processed red meat and poultry. With the role as one major energy supplier and the BP lowering effects of its metabolic products, for example, peptides,34 appropriate consumption level of meat proteins may possibly have some beneficial role in the control of BP levels. However, other studies are required to further validate these findings.

Moreover, higher intake of fish-derived protein showed no benefits on new-onset hypertension in our study. It has been reported that fish-derived proteins are able to reduce appetite and food intake and improve insulin sensitivity,35,36 thus decreasing the hypertension risk that is associated with insulin resistance.37 However, any extra servings provided no further beneficial effects on BP, this is similar to the findings from Del Brutto et al.38

Furthermore, we observed that higher intake of egg-derived protein intake was associated with lower incident risk of hypertension. It seemed that the protective effects of proteins from egg against hypertension were credit to their antihypertensive peptides, such as ovokinin, YAEERYPIL (the sequence Tyr-Arg-Glu-GluArg-Tyr-Pro-Ile-Leu), oligopeptides, and RADHPFL (the sequence Arg-Ala-Asp-His-Pro-PheLeu). Through stimulating release of nitric oxide and prostacyclin, these bioactive peptides can inhibit angiotensin-converting enzyme activity and endothelium-dependent vasodilatory activity and have some beneficial effects on BP.39–42

Plant Proteins (Grain and Legumes) and Hypertension Risk

For specific sources of plant proteins, only Doetinchem cohort study reported a marginally inverse association between grain protein and hypertension risk.11 In our study, both high and low intakes of whole grain-derived protein or refined grain-derived protein were related to higher hypertension risk. That might be reasonable, compared with the relatively limited level of grain protein intake in Dutch population (average level of 16 g/d),11 the larger range of grain-derived protein intake level (average level of 30 g/d, which was mainly based on refined grains) in the present population provided us an opportunity to give more information on their associations. In one aspect, our study confirmed the beneficial impacts for moderate intake of grain-derived proteins on BP. In the other aspect, not the same to Western residents who consumed less protein from grain and lacked of evidence between grain-derived protein and hypertension, we further discovered that excessively higher intake of grain-derived protein, especially refined grain-derived protein, might do harm on BP levels.

We also found lower risk of hypertension among Chinese population who consumed more legumes-derived protein. Several potential mechanisms have suggested benefits from legumes sourced protein. Arginine contained in legume protein has the vasodilatory effects via converting into nitric oxide.43 Besides, legume protein also increased insulin sensitivity and glucose tolerance, control the subsequent hyperinsulinemia and hypertension risk.37,44

Variety of Protein Sources and Hypertension Risk

More importantly, to simultaneously evaluated the role of appropriate amount and diversity of specific-sourced protein, we developed variety score of protein source based on whether specific-sourced protein consumption was in the range of lower hypertension risk. Our present study first observed that there was a significant inverse linear association between the variety score of protein sources and new-onset hypertension. Moreover, removal of any one kind of protein from the protein variety score could not materially change our findings. The possible interpretation is that consuming greater variety of proteins in proper quantity may guarantee the intake of different essential amino acids, correlate with better nutritional status, microbiota richness and diversity.45,46 A recent meta-analysis of prospective studies3 also considered both types and quantity of food groups and reported that optimal consumption of 5 hypertension risk-decreasing foods, including whole grains, fruits, nuts, legumes, and dairy, was related to a 44% reduction of hypertension, when compared with nonconsumption of these foods. However, a risk reduction by 44% would be achieved by not consuming hypertension risk-increasing foods, including red meat, processed meat, fish, and sugar-sweetened beverages. Our present study expanded from these food groups in the meta-analysis3 to 8 specific-sourced proteins and assessed the variety score of protein sources as both continuous and categorizable variable, which further emphasized the beneficial effect of the increment of each kind of protein on the new-onset hypertension. Moreover, our study had comprehensive adjustments and a series of subgroup analysis to examine the robustness of the findings. However, more studies are needed to further examine the underlying mechanisms.

Limitations of our study also need consideration. First, residual confounding effects from unmeasured or unknown covariates cannot be completely ruled out, although many confounders have been included in our adjustments. Second, the present study could not determine a causation due to the observational design. Third, the recall bias in the process of self-reported dietary 24-hour recalls was unavoidable, although it is a common survey method for dietary assessment in some important cohorts,13,47,48 and its accuracy for nutrition intake has been validated.14,49 Fourth, our study only included proteins from 8 major food sources of protein in Chinese adults. Fifth, proteinuria and sodium excretion were not measured in the CHNS, therefore, we could not evaluate the modifying effect of these factors on the findings. Sixth, due to the relatively low consumption levels, we cannot evaluate the association between excessive intakes of eggs and processed red meat intake and new-onset hypertension. Finally, the CHNS only included Chinese general population, it is unsure about the generalization of our findings. Therefore, the results need further confirmation.

Perspectives

In summary, our findings suggested that there was an inverse association between the variety of proteins with appropriate quantity from different food sources (whole and refined grain, processed and unprocessed red meat, poultry, fish, egg, and legumes) and new-onset hypertension in general Chinese adults. If further confirmed, these findings encourage the consumption of a balanced diet and emphasized the particularly important role of moderate quantity of proteins from diverse food sources for the primary prevention of hypertension.

Article Information

Acknowledgments

This research uses data from China Health and Nutrition Survey (CHNS). We thank the National Institute for Nutrition and Health, China Center for Disease Control and Prevention, Carolina Population Center (P2C HD050924 and T32 HD007168), the University of North Carolina at Chapel Hill, the NIH (R01-HD30880, DK056350, R24 HD050924, and R01-HD38700) and the NIH Fogarty International Center (D43 TW009077 and D43 TW007709) for financial support for the CHNS data collection and analysis files from 1989 to 2015 and future surveys, and the China-Japan Friendship Hospital, Ministry of Health for support for CHNS 2009, Chinese National Human Genome Center at Shanghai since 2009, and Beijing Municipal Center for Disease Prevention and Control since 2011. C. Zhou and X. Qin designed the research. C. Zhou, Z. Zhang, M. Liu, C. Liu, and X. Qin conducted the research. C. Zhou and C. Liu performed the data management and statistical analyses. C. Zhou and X. Qin wrote the article. All authors revised and approved the final article.

Nonstandard Abbreviations and Acronyms

AHS-2

Adventist Health Study 2

BP

blood pressure

CHNS

China Health and Nutrition Survey

DBP

diastolic blood pressure

NF-κB

nuclear factor-κB

SBP

systolic blood pressure

Disclosures None.

Footnotes

Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/HYPERTENSIONAHA.121.18222.

For Sources of Funding and Disclosures, see page 1026.

Correspondence to: Xianhui Qin, National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Email

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