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Original Investigation | Cardiology
Evaluation of Dietary Niacin and New-Onset Hypertension Among Chinese Adults
Zhuxian Zhang, MD; Mengyi Liu, MD; Chun Zhou, MD; Panpan He, MD; Yuanyuan Zhang, MD; Huan Li, MD; Qinqin Li, MD; Chengzhang Liu, MS; Xianhui Qin, MD
Abstract
IMPORTANCE The relationship of dietary niacin intake with the risk of hypertension
remains unknown.
OBJECTIVE To determine the prospective association between dietary niacin intake and new-onset
hypertension, and examine factors that may modify the association among Chinese adults.
DESIGN, SETTING, AND PARTICIPANTS This nationwide cohort study of 12 243 Chinese adults
used dietary intake data from 7 rounds of the China Health and Nutrition Survey. Dietary intake was
measured by 3 consecutive 24-hour dietary recalls from participants in combination with a weighing
inventory taken over the same 3 days at the household level. Statistical analysis was conducted from
May 2020 to August 2020.
EXPOSURES Dietary intake.
MAIN OUTCOMES AND MEASURES The study outcome was new-onset hypertension, defined as
systolic blood pressure 140 mm Hg or greater and/or diastolic blood pressure 90 mm Hg or greater,
diagnosis by physician, or current antihypertensive treatment during the follow-up.
RESULTS The mean (SD) age of the study population was 41.2 (14.2) years, and 5728 (46.8%) of
participants were men. The mean (SD) dietary niacin intake level was 14.8 (4.1) mg/d. A total of 4306
participants developed new-onset hypertension during a median (interquartile range) follow-up
duration of 6.1 (3.6-11.3) years. When dietary niacin was assessed in quartiles, the lowest risk of
new-onset hypertension was found in participants in quartile 3 (14.3 to <16.7 mg/d; adjusted hazard
ratio, 0.83; 95% CI, 0.75-0.90) compared with those in quartile 1 (<12.4 mg/d). Consistently in the
threshold analysis, for every 1 mg/d increase in dietary niacin, there was a 2% decrease in new-onset
hypertension (adjusted HR, 0.98; 95% CI, 0.96-1.00) in those with dietary niacin intake less than
15.6 mg/d, and a 3% increase in new-onset hypertension (adjusted HR, 1.03; 95% CI, 1.02-1.04) in
participants with dietary niacin 15.6 mg/d or greater. Based on these results, there was a J-shaped
association between dietary niacin intake and new-onset hypertension in the general population of
Chinese adults, with an inflection point at 15.6 mg/d and a minimal risk at 14.3 to 16.7 mg/d (quartile
3) of dietary niacin intake.
CONCLUSIONS AND RELEVANCE The results of this study provide some evidence for maintaining
the optimal dietary niacin intake levels for the primary prevention of hypertension.
JAMA Network Open. 2021;4(1):e2031669. doi:10.1001/jamanetworkopen.2020.31669
Key Points
Question Is there an association
between dietary niacin intake and the
risk of new-onset hypertension?
Findings In this nationwide cohort
study, a J-shaped association was found
between dietary niacin intake and
new-onset hypertension in Chinese
adults, with an inflection point at about
15.6 mg/d and minimal risk between
14.3 and 16.7 mg/d of dietary
niacin intake.
Meaning The results of this study
provide evidence that maintaining
optimal dietary niacin intake levels may
support the primary prevention of
hypertension.
+Supplemental content
Author affiliations and article information are
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Open Access. This is an open access article distributed under the terms of the CC-BY License.
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Introduction
Hypertension is a leading cause of noncommunicable diseases, mortality, and disability worldwide.
1-3
Approximately one-third of the adult population, or more than 300 million people, had hypertension
in China between 2014 and 2015.
4,5
Therefore, there is an urgent need to identify high-risk
individuals and develop effective primary prevention strategies to reverse the rapidly rising trend of
hypertension.
Niacin, also known as nicotinic acid or vitamin B
3
, is a vitamin precursor of nicotinamide adenine
dinucleotide and is therefore essential for energy metabolism and redox reactions.
6
Studies have
shown that niacin supplementation may regulate abnormal lipid metabolism, improve endothelial
function, and have antioxidant and anti-inflammatory properties.
7
Nevertheless, excessive niacin is
also engaged in numerous pathologies, including insulin resistance and elevated homocysteine (HCY)
levels.
8,9
Several randomized clinical trials have assessed the effect of niacin supplementation on
blood pressure (BP), but the results were inconsistent.
10-15
Of note, these trials mainly examined the
effects of relatively high niacin supplementation in high-risk populations rather than the effects of
dietary niacin derived from foods in general populations. The dietary sources of niacin mainly include
cereals and cereal products, meat and meat products, and vegetables.
16
However, to date, research
on the association between dietary niacin intake and hypertension is limited, and the prospective
association between dietary niacin intake and incident hypertension risk remains unknown in the
general population.
To address these knowledge gaps, our present study aimed to investigate the prospective
association between dietary niacin intake and the risk of new-onset hypertension and to examine
factors that may modify the association in the general population using data from the nationwide
China Health and Nutrition Survey (CHNS).
Methods
Study Design and Population
Details on the study design and major results of the CHNS have been described previously.
17-19
In
brief, the CHNS is an ongoing multipurpose longitudinal open cohort study established in 1989, with
follow up scheduled for every 2 to 4 years. A multistage, random cluster approach was used to
sample the study population from 9 provinces (Heilongjiang [enrolled in 1997], Liaoning, Shandong,
Henan, Jiangsu, Hubei, Hunan, Guizhou, and Guangxi) and 3 of China’s largest autonomous cities
(Beijing, Shanghai, and Chongqing [all enrolled in 2011]). The CHNS rounds were conducted in 1989,
1991, 1993, 1997, 2000, 2004, 2006, 2009, 2011, and 2015. By 2011, the CHNS included 12 provinces
and autonomous cities and 288 communities; the provinces included in the CHNS constituted 47%
of China’s population.
20
We conducted a prospective cohort study based on 7 rounds of the CHNS data from 1997 to
2015. We first excluded participants who were pregnant, younger than 18 years, or with missing BP
data. Among the remaining participants, those who were surveyed in at least 2 study rounds (15 774
participants; 61 612 person-waves) were included, and the first survey round was considered as
baseline. The included population did not differ in most of the baseline characteristics from those not
included (14 888 person-waves) (eFigure 1, eTable 1 in the Supplement). Of the 15 774 participants,
we further excluded participants with hypertension (defined as having systolic blood pressure [SBP]
ⱖ140 mm Hg and/or diastolic blood pressure [DBP] ⱖ90 mm Hg, previous diagnosis by physician,
or currently receiving antihypertensive treatment) at the time of the first survey. Furthermore,
participants with missing dietary niacin data or with extreme dietary energy data (for men, >8000 or
<800 kcal/d; women, >6000 or <600 kcal/d) were also excluded. Overall, a total of 12 243
participants were enrolled in the final analysis (eFigure 1 in the Supplement).
The institutional review boards of the University of North Carolina at Chapel Hill, the National
Institute of Nutrition and Food Safety, and the Chinese Center for Disease Control and Prevention
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approved the study. Each CHNS participant provided their written informed consent. The data, as
well as study materials that support the findings of this study, are available at the CHNS website.
21
This study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
reporting guideline.
Dietary Nutrient Intakes
Both individual and household-level dietary data in the CHNS were collected by trained nutritionists
through face-to-face interviews in each survey round. Individual diet was repeatedly assessed by 3
consecutive 24-hour dietary recalls at the individual level in combination with a weighing inventory
over the same 3 days at the household level.
22
The 3 consecutive days were randomly allocated from
Monday to Sunday and are almost equally balanced across the 7 days of the week for each sampling
unit. Nutrient intakes were calculated using the China food composition tables. Specifically, our
analysis did not include the dietary data from the 1989, 1991, or 1993 waves because the food codes
in those data sets did not match the food codes in the composition tables (the matching codes were
not publicly released). The accuracy of 24-hour dietary recall designed to assess energy and nutrient
intake has been validated.
22
In the analyses, 3-day average intakes of dietary macronutrients and
micronutrients in each round were calculated.
In this study, we evaluated the energy-adjusted nutrient intake for dietary niacin using residual
method.
23
Cumulative intake values of each nutrient were calculated for each participant using all
results up to the last visit prior to the date of new-onset hypertension (or all results for participants
without new-onset hypertension) to represent long-term dietary intake and minimize within-person
variation.
Blood Pressure Measurements
Seated blood pressure measurements were obtained by trained research staff after the patients had
rested for 5 minutes using a mercury manometer, following the standard method and with
appropriately sized cuffs at each follow-up survey. Triplicate measurements on the same arm were
taken in a quiet and bright room. The mean SBP and DBP of the 3 independent measures were used
in analysis.
Assessment of Covariates
Information on age, sex, urban or rural residence, region, education level (eg, illiteracy, primary
school, middle school, and ⱖhigh school), occupation (eg, farmer, worker, unemployed, and others),
and smoking and drinking status were obtained from the questionnaires at each follow-up survey.
Smoking was defined by whether participants had ever smoked cigarettes (including hand-rolled or
device-rolled), and drinking was defined by whether participants had ever drunk beer or any other
alcoholic beverage. Height, weight, and waist and hip circumference were measured following a
standard procedure with calibrated equipment. Body mass index (BMI) was calculated as weight in
kilograms divided by height in meters squared.
The questionnaire on physician-diagnosed hypertension and antihypertensive treatment
included the following questions: “(1) Has a doctor ever told you that you suffer from high blood
pressure? If yes, (2) for how many years have you had it? and (3) are you currently taking anti-
hypertension drugs?” In China, the clinical diagnosis and treatment of hypertension were mainly
according to the Chinese Guidelines for Prevention and Treatment of Hypertension (1999, 2005,
2010, and 2018 versions). In all versions, hypertension was defined as a clinical SBP of 140 mm Hg or
greater and/or DBP 90 mm Hg or greater without the use of antihypertensive medications. Overall,
all the physicians used the same criteria for the clinical diagnosis and treatment of hypertension
during the follow-up period.
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Study Outcome
The study outcome was new-onset hypertension, defined as mean SBPⱖ140 mm Hg and/or mean
DBPⱖ90 mm Hg, diagnosis by physician, or current antihypertensive treatment during the
follow-up. When a participant was first identified with new-onset hypertension in a follow-up survey,
the middle date between this and the nearest survey before was used to calculate the follow-up time.
For those free of hypertension in all follow-up surveys, the last survey date wasused to calculate the
follow-up time.
Statistical Analysis
We assumed that the annual incident hypertension rate of Chinese adults with low dietary niacin was
about 6% (with a type I error rate of .05), and so an enrollment of approximately 3000 participants
in each group stratified by dietary niacin intake (eg, low, medium, high) would be necessary to
provide more than 80% power to observe hazard ratios (HRs) of 1.2 or more for the comparison
between low and high vs medium dietary niacin group during a follow-up period of about 6 years.
Thus, a sample size of about 10 000 would be required.
Statistical analysis was conducted from May 25, 2020, to August 6, 2020. The population
characteristics are presented as mean (SD) for continuous variables and proportions for categorical
variables by quartiles of dietary niacin. The differences in population characteristics were compared
using ANOVA tests or χ
2
tests.
The association of dietary niacin intake with new-onset hypertension were estimated using Cox
proportional hazards models before and after adjustments for age, sex, BMI, smoking status, SBP,
DBP, region, education, and occupation, as well as energy intake and sodium to potassium (Na/K)
intake ratio. Threshold analysis in the association of dietary niacin intake with the study outcome was
conducted with a 2-piecewise Cox regression model using a smoothing function. The threshold level
(ie, inflection point) was determined using a likelihood-ratio test and bootstrap resampling methods.
Furthermore, possible modifications of the association between dietary niacin and new-onset
hypertension were evaluated for the following variables: age (<40 [median] vs ⱖ40 years), sex, BMI
(<25 vs ⱖ25), waist to hip ratio (<0.85 [median] vs ⱖ0.85), smoking status, drinking status, SBP
(<120 vs ⱖ120 mm Hg), sodium to potassium intake ratio (<2.8 [median] vs ⱖ2.8), potassium (<1.4
[tertile 1] vs ⱖ1.4 g/d), sodium (<3.7 [tertile 1] vs ⱖ3.7 g/d), fat (<70.9 [median] vs ⱖ70.9 g/d),
protein (<65.4 [median] vs ⱖ65.4 g/d), carbohydrate (<305.9 [median] vs ⱖ305.9 g/d), energy
(<2162.0 [median] vs ⱖ2162.0 Kcal/d), fruit intake (0 vs >0 g/d) and vegetable intake (<356.4
[median] vs ⱖ356.4 g/d), residence (urban vs rural), and education level (ⱕprimary school vs
ⱖmiddle school). Heterogeneity across subgroups was assessed by Cox proportional hazards
models, and interactions between subgroups and dietary niacin intake were examined by likelihood
ratio testing.
A 2-tailed P< .05 was considered to be statistically significant in all analyses. R software, version
3.6.1 (R Project for Statistical Computing) was used for all data analyses.
Results
Study Participants and Baseline Characteristics
Our study included 12 243 participants with complete dietary niacin intake measurements from the
CHNS (eFigure 1 in the Supplement). The mean (SD) age of the study population was 41.2 (14.2) years,
and 5728 (46.8%) of the participants were men. The mean (SD) and median (interquartile range
[IQR]) of dietary niacin intake were 14.8 (4.1) and 14.3 (12.4-16.7) mg/d (to convert niacin to μmol/d,
multiply by 8.123), respectively. Baseline characteristics of study participants are presented by
quartiles of dietary niacin in Table 1. Participants with higher dietary niacin intake had lower BMI, SBP,
and DBP; lower percentages of residence in east and central regions; higher percentages of urban
residence, higher education levels, and higher intake of fat, protein, potassium, and fruit and
vegetables; lower intake of energy, carbohydrates, and sodium; and a lower sodium to potassium
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intake ratio. They were also younger and more likely to be men, smokers, and drinkers and less likely
to be farmers (Table 1).
Association Between Dietary Niacin Intake and New-Onset Hypertension
During a median (IQR) follow-up of 6.1 years (3.6-11.3 years), 4306 (45.0 per 1000 person-years)
participants developed new-onset hypertension. Of these, 834 (19.4%) were diagnosed with
hypertension by a physician, 533 (12.4%) reported use of antihypertensive treatment during
follow-up, and 3955 (91.8%) had a new-onset mean SBP of 140 mm Hg or greater and/or a mean DBP
of 90 mm Hg or greater during follow-up. Some of the patients met at least 2 of the 3 criteria.
Overall, the association between dietary niacin and new-onset hypertension followed a J-shape
(Figure 1). Accordingly, when dietary niacin intake was assessed in quartiles and compared with
Table 1. PopulationCharacteristics by Quartiles of Die tary Niacin Intake
Variable
Participants, No. (%)
Pvalue
Q1 (<12.4
mg/d)
(n = 3061)
Q2 (12.4 to
<14.3 mg/d)
(n = 3060)
Q3 (14.3 to
<16.7 mg/d)
(n = 3061)
Q4 (≥16.7
mg/d)
(n = 3061)
Men 1340 (43.8) 1317 (43.0) 1399 (45.7) 1672 (54.6) <.001
Age, mean (SD), y 41.5 (14.6) 42.0 (14.3) 40.7 (14.0) 40.5 (13.7) <.001
Blood pressure, mean (SD),
mm Hg
Systolic 114.5 (11.3) 113.8 (11.5) 113.1 (11.5) 114.2 (11.4) <.001
Diastolic 74.3 (7.9) 74.3 (7.9) 73.6 (7.8) 74.4 (7.8) <.001
BMI, mean (SD) 22.7 (3.1) 22.2 (3.0) 22.2 (3.0) 22.5 (3.1) <.001
Waist to hip ratio,
mean (SD)
0.9 (0.1) 0.8 (0.1) 0.8 (0.1) 0.9 (0.1) <.001
Smoking status 882 (28.9) 853 (28.1) 920 (30.2) 1053 (34.5) <.001
Drinking status 972 (32.1) 931 (30.9) 1019 (33.7) 1242 (40.9) <.001
Urban residence 926 (30.3) 940 (30.7) 1170 (38.2) 1379 (45.1) <.001
Region
East and central 2187 (71.4) 1505 (49.2) 1398 (45.7) 1421 (46.4)
<.001
Northeast and north 525 (17.2) 779 (25.5) 614 (20.1) 571 (18.7)
Southwest and south 349 (11.4) 776 (25.4) 1049 (34.3) 1069 (34.9)
Occupation
Farmer 1231 (40.8) 1328 (44.0) 1097 (36.0) 728 (24.0)
<.001
Worker 333 (11.0) 304 (10.1) 382 (12.6) 441 (14.5)
Unemployed 819 (27.2) 721 (23.9) 719 (23.6) 790 (26.0)
Other 631 (20.9) 668 (22.1) 845 (27.8) 1076 (35.5)
Education
Illiteracy 684 (22.8) 644 (21.6) 517 (17.2) 369 (12.2)
<.001
Primary school 604 (20.2) 637 (21.4) 599 (19.9) 503 (16.6)
Middle school 1021 (34.1) 995 (33.4) 992 (33.0) 1008 (33.3)
≥High school 685 (22.9) 705 (23.6) 902 (30.0) 1143 (37.8)
Self-report diabetes 35 (1.2) 35 (1.2) 37 (1.2) 47 (1.6) .47
Dietary intake
Energy, mean (SD), Kcal/d 2276.2 (578.7) 2162.7 (519.8) 2120.6 (485.7) 2207.0 (566.2) <.001
Fat, mean (SD), g/d 75.6 (32.6) 69.5 (28.7) 72.7 (27.1) 80.9 (30.4) <.001
Carbohydrate, mean (SD),
g/d
334.9 (110.4) 321.8 (101.3) 301.1 (94.4) 292.7 (100.7) <.001
Protein, mean (SD), g/d 64.1 (18.7) 62.6 (17.1) 65.4 (15.8) 77.0 (24.5) <.001
Sodium, mean (SD), g/d 5.5 (3.3) 5.0 (3.1) 4.7 (2.6) 4.9 (3.0) <.001
Potassium, mean (SD), g/d 1.6 (0.5) 1.6 (0.5) 1.7 (0.5) 1.9 (1.0) <.001
Na:K ratio 3.8 (2.5) 3.3 (2.1) 3.0 (1.7) 2.7 (1.8) <.001
Vegetables, mean (SD), g/d 329.0 (138.1) 361.3 (138.4) 385.9 (144.4) 418.9 (185.3) <.001
Fruit intake 1201 (39.2) 1354 (44.2) 1510 (49.3) 1543 (50.4) <.001
Abbreviations: BMI, body mass index (calculated as
weight in kilograms divided by height in meters
squared); Na:K, sodium to potassium.
SI conversion factor: Toconvert niacin to μmol/d,
multiply by 8.123.
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quartile 1 (<12.4 mg/d), the risk of new-onset hypertension was lower for quartile 2 (12.4 to <14.3
mg/d: HR, 0.90; 95% CI, 0.83-0.97; P= .01), quartile 3 (14.3 to <16.7 mg/d: HR, 0.70; 95% CI, 0.64-
0.76; P< .001), and quartile 4 (ⱖ16.7 mg/d: HR, 0.92; 95% CI, 0.85-1.00; P= .05) (Table 2). The
lowest risk of new-onset hypertension was found in those in quartile 3. When combining quartiles in
further exploratory analysis, a significantly higher risk of new-onset hypertension was found among
participants in quartiles 1 and 2 (<14.3 mg/d: adjusted HR, 1.18; 95% CI, 1.09-1.28; P< .001) and in
quartile 4 (ⱖ16.7 mg/d: adjusted HR, 1.31; 95% CI, 1.20-1.44) compared with those in quartile 3 (14.3
to <16.7 mg/d) (Table 2).
Consistently in the threshold analysis, for every 1 mg/d increase in dietary niacin there was a 2%
decrease in new-onset hypertension (adjusted HR, 0.98; 95% CI, 0.96-1.00) in participants with
dietary niacin less than 15.6 mg/d, and a 3% increase in new-onset hypertension (adjusted HR, 1.03;
95% CI, 1.02-1.04) in participants with dietary niacin 15.6 mg/d or greater (Table 3).
Moreover, further adjustments for waist to hip ratio, drinking status, sodium, and fruit and
vegetable intake (eTable 2 in the Supplement), or excluding participants from the 3 autonomous
cities (eTable 3 in the Supplement) did not substantially alter the association between dietary niacin
and new-onset hypertension. Similar trends were also found for different components of new-onset
hypertension, including hypertension diagnosed by a physician and participants who were using
antihypertensive treatment during follow-up, and participants with mean SBP 140 mm Hg or greater
and/or mean DBP of 90 mm Hg or greater during follow-up (eTable 4 in the Supplement).
Figure 1. Dietary Niacin Intake and the Risk of New-Onset Hypertension
2.0
1.8
1.6
1.4
1.2
1.0
0.8
New-onset hypertension, adjusted HR
Dietary niacin intake, mg/d
305 10 15 20 25 35
The shaded area indicates 95% confidence intervals
for adjusted hazard ratios (HR). The model was
adjusted for age, sex, body mass index, smoking
status, systolic blood pressure, diastolic blood
pressure, region, education, and occupation, as well as
energy intake and sodium to potassium intake ratio.
Table 2. Dietary Niacin Intake and the Risk of New-OnsetHyper tension Stratified byQuar tiles and Combined Quartiles
Niacin intake, mg/d Participants, No. Events, No. (rate)
a
Crude model Adjusted model
b
HR (95% CI) Pvalue HR (95% CI) Pvalue
Quartiles
Q1 (<12.4) 3061 1188 (51.7) 1 [Reference] 1 [Reference]
Q2 (12.4 to <14.3) 3060 1166 (46.6) 0.90 (0.83-0.97) .009 0.95 (0.87-1.04) .27
Q3 (14.3 to <16.7) 3061 952 (36.2) 0.70 (0.64-0.76) <.001 0.83 (0.75-0.90) <.001
Q4 (≥16.7) 3061 998 (47.0) 0.92 (0.85-1.00) .05 1.08 (0.99-1.19) .09
Categories
Q1-2 (<14.3) 6121 2354 (49.0) 1.36 (1.26-1.47) <.001 1.18 (1.09-1.28) <.001
Q3 (14.3 to <16.7) 3061 952 (36.2) 1 [Reference] 1 [Reference]
Q4 (≥16.7) 3061 998 (47.0) 1.32 (1.21-1.44) <.001 1.31 (1.20-1.44) <.001
Abbreviations: HR, hazard ratio; Q, quartile.
SI conversion factor: Toconvert niacin to μmol/d, multiply by 8.123.
a
Incident rate is presented per 1000 person-years of follow-up.
b
Adjusted for age, sex, body mass index, smoking status, systolic blood pressure,
diastolic blood pressure, region, education, and occupation, as well as energy intake
and sodium to potassium intake ratio.
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Stratified Analyses by Additional Factors
We performed further stratified analyses to assess the association between dietary niacin (quartile
1-2 vs quartile 3 vs quartile 4) and the risk of new-onset hypertension in various subgroups (Figure 2;
eFigure 2 in the Supplement). Overall, the J-shaped association between dietary niacin intake and
new-onset hypertension was observed in all subgroups.
None of the variables, including age, sex, BMI, waist/hip ratio, smoking status, drinking status,
SBP, sodium to potassium intake ratio, potassium, sodium, fat, protein, carbohydrate, energy, fruit
and vegetable intake, residence, and education level significantly modified the association between
dietary niacin and new-onset hypertension (Figure 2; eFigure 2 in the Supplement). Although the P
values for interactions for sex, drinking status, and vegetable intake were lower than .05, these
results may not have significant clinical implications given multiple testing and similar directionality
of the associations (Figure 2; eFigure 2 in the Supplement).
Discussion
In this large, national, longitudinal cohort study among general Chinese adults, we found a J-shaped
association between dietary niacin intake and new-onset hypertension, with an inflection point at
approximately 15.6 mg/d and minimal risk at 14.3 to 16.7 mg/d of dietary niacin.
The acute and chronic effects of niacin on blood pressure have been evaluated in several
previous trials, which have reported inconsistent results.
10-15
The original Coronary Drug Project
revealed that no significant changes in BP were found in men with previous myocardial infarction
over 5 to 8.5 years of niacin treatment (3.0 g/d).
10
However, a post hoc analysis of the data in patients
with metabolic syndrome found that treatment with niacin was associated with a reduction in BP of
approximately 2 to 3 mm Hg compared with placebo at treatment year 1.
11
At the same time, Kelly
et al
14
found that short-term niacin treatment (ie, 500 mg daily for 7 days, then 1 g daily for a further
7 days) did not significantly affect SBP or DBP. An 8-week niacin titration (1 g/d for 4 weeks, 2g/d for
the remaining 4 weeks) study of 412 dyslipidemic patients also showed no significant change in BP
from baseline.
12
Nevertheless, Gadegbeku et al
15
reported that acute niacin administration (1.4 g
infusion for 60 min) may lower BP in patients with hypertension, but not in normotensive patients.
Data from a longer and larger (ie, 24 wk with 1613 participants) study suggested that, compared with
placebo, niacin therapy (1 g/d for 4 weeks, then 2 g/d for 20 weeks) in patients with dyslipidemia
significantly decreased BP at both 4 and 24 weeks.
13
Overall, these studies indicated that the
association between niacin supplementation and BP remains uncertain. Of note, all of these studies
focused on relatively high levels of niacin supplementation and did not have detailed information
about dietary niacin intake. Although it is reported that nutrients obtained from foods and
supplements may confer different health effects,
24
to date the association between dietary niacin
intake and hypertension has not been thoroughly investigated. The CHNS study provides an
opportunity to evaluate the dose-response association between dietary niacin intake and the risk of
new-onset hypertension in the general population, with comprehensive adjustments for a number
of known covariables and a series of subgroup analyses.
Table 3. ThresholdAnalyses of Die tary Niacin Intakeon New-Onset Hypertension Using 2-Piecewise
Regression Models
Niacin intake, mg/d
Crude model
Niacin intake, mg/d
Adjusted model
a
HR (95% CI) Pvalue HR (95% CI) Pvalue
<16.0 0.95 (0.93-0.96) <.001 <15.6 0.98 (0.96-1.00) .04
≥16.0 1.04 (1.03-1.05) <.001 ≥15.6 1.03 (1.02-1.04) <.001
Abbreviation: HR, hazard ratio.
SI conversion factor: Toconvert niacin to μmol/d, multiply by 8.123.
a
Adjusted for age, sex, body mass index, smoking status, systolic blood pressure, diastolicblood pre ssure,region,
education, and occupation, as well as energy intake and sodium to potassium intake ratio.
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Our study provides some new insights. First, among participants with dietary niacin of less than
15.6 mg/d, the risk of new-onset hypertension significantly decreased with the increment of dietary
niacin intake. Niacin has been widely used clinically to regulate abnormalities in lipid/lipoprotein
metabolism. Some studies have found that niacin alone or in combination can slow or reverse the
progression of atherosclerosis in patients with hypercholesterolemia.
25,26
Endothelial dysfunction is
considered to be the initial phase in the development of arterial hypertension and atherosclerosis.
27
Niacin has been shown to promote the production of endothelial nitric oxide, increase vasodilation,
Figure 2. Stratified Analyses by Potential Modifiers of the Association Between Dietary Niacin Intake and New-Onset Hypertension
Subgroup
category
Age, y
Adjusted HR
(95% CI)
Events
(ratea)
<40
743 (29.7)Q1-2 1.30 (1.14-1.49)
Q3 1.00 [Reference]310 (20.9)
Q4 1.42 (1.21-1.66)364 (29.2)
Sex
Men
1131 (56.9)Q1-2 1.19 (1.07-1.33)
Q3 1.00 [Reference]492 (41.5)
Q4 1.21 (1.07-1.37)580 (49.7)
Drinking status
No
1487 (45.2)Q1-2 1.18 (1.07-1.31)
Q3 1.00 [Reference]580 (33.5)
Q4 1.44 (1.28-1.62)568 (46.6)
Waist to hip ratio
<0.85
966 (38.7)Q1-2 1.13 (1.01-1.28)
Q3 1.00 [Reference]421 (29.4)
Q4 1.27 (1.10-1.47)380 (34.9)
Systolic blood pressure, mm Hg
<120
1138 (35.4)Q1-2 1.17 (1.05-1.30)
Q3 1.00 [Reference]500 (26.5)
Q4 1.40 (1.23-1.59)507 (34.8)
Sodium intake, g/d
<3.7
737 (60.5)Q1-2 1.27 (1.11-1.45)
Q3 1.00 [Reference]342 (40.3)
Q4 1.27 (1.09-1.47)354 (49.6)
Fat intake, g/d
<70.9
1372 (53.4)Q1-2 1.16 (1.04-1.29)
Q3 1.00 [Reference]533 (39.7)
Q4 1.39 (1.22-1.58)426 (52.2)
Protein intake, g/d
<65.4
1353 (49.3)Q1-2 1.14 (1.02-1.27)
Q3 1.00 [Reference]474 (35.8)
Q4 1.44 (1.24-1.68)296 (51.3)
Carbohydrate intake, g/d
<305.9
891 (48.1)Q1-2 1.15 (1.03-1.30)
Q3 1.00 [Reference]438 (34.4)
Q4 1.31 (1.15-1.49)501 (44.6)
210.8
Adjusted HR (95% CI)
P for
interaction
Subgroup
category
Age, y
Adjusted HR
(95% CI)
Events
(ratea)
≥40
1611 (70.2)
.30
Q1-2 1.15 (1.05-1.27)
Q3 1.00 [Reference]642 (56.0)
Q4 1.24 (1.11-1.39)634 (72.4)
Sex
Women
1223 (43.4)
.02
Q1-2 1.17 (1.05-1.31)
Q3 1.00 [Reference]460 (31.8)
Q4 1.47 (1.28-1.69)418 (43.8)
Drinking status
Yes
830 (57.4)
.02
Q1-2 1.16 (1.02-1.32)
Q3 1.00 [Reference]359 (41.8)
Q4 1.16 (1.00-1.33)425 (48.5)
Waist to hip ratio
≥0.85
1309 (60.3)
.76
Q1-2 1.20 (1.08-1.34)
Q3 1.00 [Reference]502 (45.0)
Q4 1.34 (1.18-1.51)590 (60.6)
Systolic blood pressure, mm Hg
≥120
1216 (76.8)
.18
Q1-2 1.17 (1.04-1.31)
Q3 1.00 [Reference]452 (60.4)
Q4 1.22 (1.07-1.39)491 (74.0)
Sodium intake, g/d
≥3.7
1617 (45.1)
.12
Q1-2 1.14 (1.04-1.25)
Q3 1.00 [Reference]610 (34.2)
Q4 1.33 (1.19-1.49)644 (45.7)
Fat intake, g/d
≥70.9
982 (44.0)
.74
Q1-2 1.15 (1.02-1.29)
Q3 1.00 [Reference]419 (32.5)
Q4 1.30 (1.14-1.48)572 (43.8)
Protein intake, g/d
≥65.4
1001 (48.7)
.27
Q1-2 1.17 (1.05-1.31)
Q3 1.00 [Reference]478 (36.5)
Q4 1.30 (1.15-1.46)702 (45.5)
Carbohydrate intake, g/d
≥305.9
1463 (49.6)
.89
Q1-2 1.18 (1.07-1.31)
Q3 1.00 [Reference]514 (37.8)
Q4 1.37 (1.20-1.55)497 (49.8)
210.8
Adjusted HR (95% CI)
a
Incident rate is presented per 1000 person-years of follow-up.
The model was adjusted, if not stratified, for age, sex, body mass index, smoking status,systolic blood pressure, diastolic blood pressure, region, education, and occupation, as well
as energy intake and sodium to potassium intake ratio.
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and improve endothelial dysfunction.
28,29
Moreover, niacin also reduces endothelial oxidative stress
via increasing the cellular content of nicotinamide adenine dinucleotide phosphate, reducing
glutathione, and inhibiting reactive oxygen species generation in endothelial cells.
30,31
Additionally,
niacin can reduce the release of inflammatory markers such as lipoprotein-associated phospholipase
A2 and high sensitivity C-reactive protein.
32,33
Taken together, a plausible biological explanation for
the niacin-hypertension association we observed may be that niacin can regulate abnormal lipid
metabolism, improve endothelial function, and has potentially antioxidant and anti-inflammatory
properties.
7
However, further research on this mechanism is needed.
Second, the risk of new-onset hypertension significantly increased with the increment of
dietary niacin intake in participants with dietary niacin of 15.6 mg/d or greater. Elevated HCY and
insulin resistance may impair endothelial function and are identified as important risk factors for
hypertension.
34,35
It was reported that an increased nicotinamide load resulted in a significant
increase in pulse pressure, which might be related to the fact that high niacin intake depletes the
methyl pool, increases HCY generation and betaine consumption, and inhibits catecholamine
degradation.
9,36
In addition, a previous study found that treatment with niacin was related to
increased insulin resistance as well.
14
Of note, Table 1 shows that participants with lower dietary niacin (quartile 1 and 2) were older
and had higher SBP and DBP levels, lower percentages of residence in urban and southern regions,
and a higher sodium to potassium intake ratio. All these variables may partly explain the increased
hypertension risk in participants with lower dietary niacin in the crude model in Table 2. As expected,
with the increase of these variables in the adjusted models, the HR (ie, quartile 1-2 vs quartile 3)
decreased gradually. We speculated that the change between the crude and adjusted models may be
in part accounted for by the joint effect of these baseline characteristics. However, our results should
be further confirmed in more studies.
Limitations
Our study had several limitations. First, because this is an observational analysis, residual
confounding cannot be completely eliminated, although data were adjusted for a series of
confounders. Second, the biosynthesis of niacin from tryptophan was not included in our analysis. In
general, 60 mg of tryptophan is equivalent to 1 mg of niacin through de novo synthesis.
37
Nevertheless, this biosynthesis process does not occur in all tissues.
38
In our stratified analysis,
protein intake did not significantly modify the association between dietary niacin intake and
new-onset hypertension. Third, we have no detailed information on dietary supplement use.
However, data from the 2010–2012 China Nutrition and Health Surveillance study, a nationally
representative cross-sectional study covering all 31 provinces, autonomous regions, and
municipalities, showed that only 0.71%, 0.06%, and 0.2% of the Chinese population reported using
nutrient supplements, multivitamins, and vitamin B supplements, respectively.
39
Because of the low
proportion of nutrient supplementation, especially vitamin B, we speculate that our findings may
not be substantially changed by dietary supplement use. Fourth, because only 53 participants
reported the use of special dietary patterns for the treatment of diabetes, and we lack information on
circulating cholesterol levels in the present study, we could not examine the modifying effect of
different dietary patterns and hypercholesterolemia. Other information was limited in our data
source; the CHNS did not include clinic-based blood pressure measurements, and although the CHNS
took place in different provinces and municipal cities that vary substantially in geography, economic
development, public resources, and health indicators, the study participants could not represent the
population of provinces or cities that were not included in the survey. Fifth, compared with those
not included in the analysis, participants included seemed to be older and have a lower education
level. However, all these variables were included in the regression models, and the stratified analysis
further showed that age and education level did not materially modify the results. Sixth, our study
was conducted among Chinese living in China—whether the observed findings can be extrapolated to
JAMA Network Open | Cardiology Evaluation of Dietary Niacin and New-Onset Hypertension Among Chinese Adults
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other populations needs further investigation. Therefore, our results should be regarded as
hypothesis generating. Further confirmation of our findings in more studies is essential.
Conclusions
In summary, our study found a J-shaped association between dietary niacin intake and new-onset
hypertension in the general population of Chinese adults, with an inflection point at about 15.6 mg/d
and minimal risk observed at 14.3 to 16.7 mg/d of dietary niacin. If further confirmed, our data provide
evidence for maintaining the optimal dietary niacin intake levels for the primary prevention of
hypertension.
ARTICLE INFORMATION
Accepted for Publication: November 5, 2020.
Published: January 6, 2021. doi:10.1001/jamanetworkopen.2020.31669
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Zhang Z et al.
JAMA Network Open.
Corresponding Authors: Xianhui Qin, MD (pharmaqin@126.com),and Chengzhang Liu, MS (lczbruce@sina.com),
Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Author Affiliations: National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure
Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou, China (Z. Zhang,
M. Liu, Zhou, He, Y. Zhang, H. Li, C. Liu, Qin); Guangdong Provincial Key Laboratory of Renal Failure Research,
Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, China (Z. Zhang, M. Liu, Zhou,
He, Y.Zhang, H. Li); Institute of Biomedicine, Anhui Medical University, Hefei, China (Q. Li, C. Liu).
Author Contributions: Dr Qin had full access to all of the data in the study and takes responsibility for the integrity
of the data and the accuracy of the data analysis.
Concept and design: Z. Zhang, Zhou, Q. Li, C. Liu, Qin.
Acquisition, analysis, or interpretation of data: Z. Zhang, M. Liu, He, Y. Zhang, H. Li, C. Liu, Qin.
Drafting of the manuscript: Z. Zhang, Q. Li, Qin.
Critical revision of the manuscript for important intellectual content: Z. Zhang,M. Liu, Zhou, He, Y. Zhang, H. Li, C.
Liu, Qin.
Statistical analysis: Z. Zhang, He, H. Li, Q. Li, C. Liu, Qin.
Obtained funding: Qin.
Administrative, technical, or material support: C. Liu.
Supervision: Zhou.
Conflict of Interest Disclosures: None reported.
Funding/Support: This study was supported by the National Natural Science Foundation of China (grant Nos.
81973133, 81730019). This research uses data from the China Health and Nutrition Survey (CHNS). Wethank the
National Institute for Nutrition and Health, China Center for Disease Control and Prevention, Carolina Population
Center (grant Nos. P2C HD050924, T32 HD007168), the University of North Carolina at Chapel Hill, the National
Institutes of Health (grant Nos. R01-HD30880, DK056350, R24 HD050924, and R01-HD38700), and the
National Institutes of Health Fogarty International Center (grant Nos. D43 TW009077, D43 TW007709) for
financial support for the CHNS data collection and analysis files from 1989 to 2015 and future surveys. The China-
Japan Friendship Hospital, Ministry of Health provided support for CHNS 2009; the Chinese National Human
Genome Center at Shanghai provided support for CHNS analysis after 2009; and the Beijing Municipal Center for
Disease Prevention and Control provided support for CHNS surveys since 2011.
Role of the Funder/Sponsor:The funders had no role in the design and conduc t of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approvalof the manuscript; and
decision to submit the manuscript for publication.
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REFERENCES
1. GBD 2017 Risk Factor Collaborators. Global, regional, and national comparativerisk asse ssment of 84
behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and
territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392
(10159):1923-1994. doi:10.1016/S0140-6736(18)32225-6
2. Li Y, Zhou H, Liu M, et al. Association of visit-to-visit variability in blood pressure and first stroke risk in
hypertensive patients with chronic kidney disease. J Hypertens. 2020;38(4):610-617.
3. Qin X, Huo Y. H-Type hypertension, stroke and diabetes in China: opportunities for primary prevention.
J Diabetes. 2016;8(1):38-40. doi:10.1111/1753-0407.12333
4. Lewington S, Lacey B, Clarke R, et al; China Kadoorie Biobank Consortium. The burden of hypertension and
associated risk for cardiovascular mortality in China. JAMA Intern Med. 2016;176(4):524-532. doi:10.1001/
jamainternmed.2016.0190
5. Li Y, Yang L, Wang L, et al. Burden of hypertension in China: a nationally representative survey of 174 621 adults.
Int J Cardiol. 2017;227:516-523. doi:10.1016/j.ijcard.2016.10.110
6. Kirkland JB. Niacin status, NAD distribution and ADP-ribose metabolism. Curr Pharm Des. 2009;15(1):3-11. doi:
10.2174/138161209787185823
7. Zeman M, Vecka M, Perlík F, et al. Pleiotropic effects of niacin: current possibilities for its clinical use. Acta
Pharm. 2016;66(4):449-469. doi:10.1515/acph-2016-0043
8. Poynten AM, Gan SK, Kriketos AD, et al. Nicotinic acid-induced insulin resistance is related to increased
circulating fatty acids and fat oxidation but not muscle lipid content. Metabolism. 2003;52(6):699-704. doi:10.
1016/S0026-0495(03)00030-1
9. Sun WP, Li D, Lun YZ, et al. Excess nicotinamide inhibits methylation-mediated degradationof catecholamine s
in normotensives and hypertensives. Hypertens Res. 2012;35(2):180-185. doi:10.1038/hr.2011.151
10. Coronary Drug Project Research Group. Clofibrate and niacin in coronary heart disease. JAMA. 1975;231(4):
360-381. doi:10.1001/jama.1975.03240160024021
11. Canner PL, Furberg CD, McGovern ME. Benefits of niacin in patients with versus without the metabolic
syndrome and healed myocardial infarction (from the Coronary Drug Project). Am J Cardiol. 2006;97(4):477-479.
doi:10.1016/j.amjcard.2005.08.070
12. Paolini JF, Mitchel YB, Reyes R, et al. Effects of laropiprant on nicotinic acid-induced flushing in patients with
dyslipidemia. Am J Cardiol. 2008;101(5):625-630. doi:10.1016/j.amjcard.2007.10.023
13. Bays HE, Maccubbin D, Meehan AG, Kuznetsova O, Mitchel YB, Paolini JF. Blood pressure-lowering effects of
extended-release niacin alone and extended-release niacin/laropiprant combination: a post hoc analysis of a
24-week, placebo-controlled trial in dyslipidemic patients. Clin Ther. 2009;31(1):115-122. doi:10.1016/j.clinthera.
2009.01.010
14. Kelly JJ, Lawson JA, Campbell LV, et al. Effects of nicotinic acid on insulin sensitivity and blood pressure in
healthy subjects. J Hum Hypertens. 2000;14(9):567-572. doi:10.1038/sj.jhh.1001099
15. Gadegbeku CA, Dhandayuthapani A, Shrayyef MZ, Egan BM. Hemodynamic effects of nicotinic acid infusion in
normotensive and hypertensive subjects. Am J Hypertens. 2003;16(1):67-71. doi:10.1016/S0895-7061(02)
03196-5
16. Li L, Zhang B, Wang HJ, et al. Sociodemographic factors associated with dietary intake of thiamine, riboflavin,
and niacin among Chinese adults in 2015. Biomed Environ Sci. 2020;33(9):660-669.
17. Popkin BM, Du S, Zhai F, Zhang B. Cohort profile: the China Health and Nutrition Survey—monitoring and
understanding socioeconomic and health change in China, 1989-2011. IntJ Epidemiol. 2010;39(6):1435-1440. doi:
10.1093/ije/dyp322
18. Li Y, Wang DD, Ley SH, et al. Time trends of dietary and lifestyle factors and their potential impact on diabetes
burden in China. Diabetes Care. 2017;40(12):1685-1694. doi:10.2337/dc17-0571
19. Qin B, Viera AJ, Muntner P, et al. Visit-to-visitvariability in blood pressure is related to late-life cognitive
decline. Hypertension. 2016;68(1):106-113. doi:10.1161/HYPERTENSIONAHA.116.07494
20. Zhang B, Zhai FY,Du SF, Popkin BM. The China Health and Nutrition Survey, 1989-2011. Obes Rev. 2014;
15(suppl 1):2-7. doi:10.1111/obr.12119
21. China Health and Nutrition Survey.UNC Carolina Population project . Accessed November 25, 2020. https://
www.cpc.unc.edu/projects/china
22. Zhai F,Guo X, Popkin B, et al Evaluation of the 24-hour individual recall method in China. Food Nutr Bull.
1996;17 (2): 1-7. doi:10.1177/156482659601700209
JAMA Network Open | Cardiology Evaluation of Dietary Niacin and New-Onset Hypertension Among Chinese Adults
JAMA Network Open. 2021;4(1):e2031669. doi:10.1001/jamanetworkopen.2020.31669 (Reprinted) January 6, 2021 11/12
Downloaded From: https://jamanetwork.com/ on 01/10/2021
23. Willett W, Stampfer MJ. Total energy intake: implications forepidemiologic analyse s. Am J Epidemiol. 1986;
124(1):17-27. doi:10.1093/oxfordjournals.aje.a114366
24. Zhang FF, Barr SI, McNultyH, Li D, Blumberg JB. Health effects of vitamin and mineral supplements. BMJ.
2020;369:m2511. doi:10.1136/bmj.m2511
25. Meyers CD, Kamanna VS, Kashyap ML. Niacin therapy in atherosclerosis. Curr Opin Lipidol. 2004;15(6):
659-665. doi:10.1097/00041433-200412000-00006
26. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the
prevention of coronary disease. N Engl J Med. 2001;345(22):1583-1592. doi:10.1056/NEJMoa011090
27. Chen B, Lu Y, Chen Y, Cheng J. The role of Nrf2 in oxidative stress-induced endothelial injuries. J Endocrinol.
2015;225(3):R83-R99. doi:10.1530/JOE-14-0662
28. Sahebkar A. Effect of niacin on endothelial function: a systematic review and meta-analysis of randomized
controlled trials. Vasc Med. 2014;19(1):54-66. doi:10.1177/1358863X13515766
29. Wu BJ, Yan L, Charlton F,Witting P, Barter PJ, Rye KA. Evidence that niacin inhibits acute vascularinf lammation
and improves endothelial dysfunction independent of changes in plasma lipids. Arterioscler Thromb Vasc Biol.
2010;30(5):968-975. doi:10.1161/ATVBAHA.109.201129
30. Ganji SH, Qin S, Zhang L, Kamanna VS, Kashyap ML. Niacin inhibits vascular oxidative stress, redox-sensitive
genes, and monocyte adhesion to human aortic endothelial cells. Atherosclerosis. 2009;202(1):68-75. doi:10.
1016/j.atherosclerosis.2008.04.044
31. Hamoud S, Kaplan M, Meilin E, et al. Niacin administration significantly reduces oxidative stress in patients with
hypercholesterolemia and low levels of high-density lipoprotein cholesterol. Am J Med Sci. 2013;345(3):195-199.
doi:10.1097/MAJ.0b013e3182548c28
32. Thoenes M, Oguchi A, Nagamia S, et al. The effects of extended-release niacin on carotid intimal media
thickness, endothelial function and inflammatory markers in patients with the metabolic syndrome. Int J Clin
Pract. 2007;61(11):1942-1948. doi:10.1111/j.1742-1241.2007.01597.x
33. Kuvin JT, Dave DM, Sliney KA, et al. Effects of extended-release niacin on lipoprotein particle size, distribution,
and inflammatory markers in patients with coronary artery disease. Am J Cardiol. 2006;98(6):743-745. doi:10.
1016/j.amjcard.2006.04.011
34. Zhao M, Wang X, He M, et al. Homocysteine and stroke risk: modifying effect of methylenetetrahydrofolate
reductase C677T polymorphism and folic acid intervention. Stroke. 2017;48(5):1183-1190. doi:10.1161/
STROKEAHA.116.015324
35. Perticone F,Sciacqua A , Maio R, et al. Endothelial dysfunction, ADMA and insulin resistance in essential
hypertension. Int J Cardiol. 2010;142(3):236-241. doi:10.1016/j.ijcard.2008.12.131
36. Sun WP, Zhai MZ, Li D, et al. Comparison of the effects of nicotinic acid and nicotinamide degradation on
plasma betaine and choline levels. Clin Nutr. 2017;36(4):1136-1142. doi:10.1016/j.clnu.2016.07.016
37. Deen CPJ, van der Veen A, van Faassen M, et al. Urinary excretion of N
1
-methylnicotinamide, as a biomarker of
niacin status, and mortality in renal transplant recipients. J Clin Med. 2019;8(11):1948. doi:10.3390/jcm8111948
38. Bogan KL, Brenner C. Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+
precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-130. doi:10.1146/annurev.nutr.28.061807.
155443
39. Gong W, Liu A, Yao Y, et al Nutrient supplement use among the Chinese population: a cross-sectional study of
the 2010-2012 China Nutrition and Health Surveillance. Nutrients. 2018; 10: 1733. doi:10.3390/nu10111733
SUPPLEMENT.
eFigure 1. Flow Chart of the Participants
eFigure 2. Stratified Analyses by Potential Effect Modifiers for the Association Between Dietary Niacin Intake
(Quartile 1-2 vs. Quartile 3 vs. Quartile 4) and New-Onset Hypertension
eTable 1. Characteristics of the Included and ExcludedParticipants
eTable 2. The Association Between Dietary Niacin Intake and the Risk of New-Onset Hypertension With Further
Adjustment for Waist/Hip Ratio, Drinking Status, Sodium, Fruitsand Vegetables Intake
eTable 3. The Association Between Dietary Niacin Intake and the Risk of New-Onset Hypertension With Exclusion
of Participants From the Three Autonomous Cities
eTable 4. The Association Between Dietary Niacin Intake and Different Components of New-Onset Hypertension
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