Cardiovascular Biomarkers: Research Article

Cardiology Received: January 8, 2019

Accepted after revision: March 22, 2019
DOI: 10.1159/000499867 Published online: July 12, 2019

Levels of Systolic and Diastolic Blood

Pressure and Their Relation to Incident
Metabolic Syndrome
Ju Young Jung a Chang-Mo Oh b Joong-Myung Choi b Jae-Hong Ryoo c
Pil-Wook Chung d Hyun Pyo Hong e Sung Keun Park f
a TotalHealthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul,
Republic of Korea; b Department of Preventive Medicine, School of Medicine, Kyung Hee University, Seoul,
Republic of Korea; c Department of Occupational and Environmental Medicine, College of Medicine, Kyung Hee
University, Seoul, Republic of Korea; d Department of Neurology, College of Medicine, Kangbuk Samsung Hospital,
Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; e Department of Radiology, College of
Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
f Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School

of Medicine, Seoul, Republic of Korea

Keywords HR for MetS, even after adjusting for covariates. Subgroup

Blood pressure · Hypertension · Metabolic syndrome ·
Cardiovascular risk
Abstract
Background: Elevated blood pressure (BP) is a component
of the metabolic syndrome (MetS), and one third of individu-
als with hypertension simultaneously have MetS. However,
the evidence is still unclear regarding the predictive ability
of BP for incident MetS. Methods: In total, 5,809 Koreans
without baseline MetS were grouped by baseline systolic
(SBP) and diastolic BP (DBP) and monitored for 10 years to
identify incident MetS. A Cox proportional hazards model
was used to evaluate the HR and 95% CI for MetS according
to SBP and DBP. Subgroup analysis was conducted in the
normotensive population based on a new guideline of the
American College of Cardiology and the American Heart As-
sociation. Results: High-BP groups tended to have worse
metabolic profiles than the lowest-BP group in both SBP and
DBP categories. In all of the participants, elevated SBP and
DBP levels were significantly associated with the increased
analysis for normotensive participants indicated that the HR
for MetS increased proportionally to both SBP (<110 mm Hg:
reference, 110–119 mm Hg: HR = 1.60 [95% CI 1.40–1.84],
and 120–129 mm Hg: HR = 2.12 [95% CI 1.82–2.48]) and DBP
levels (<70 mm Hg: reference, 71–74 mm Hg: HR = 1.31 [95%
CI 1.09–1.58], and 75–79 mm Hg: HR = 1.51 [95% CI 1.25–
1.81]). Conclusion: The risk of incident MetS increased pro-
portionally to baseline SBP and DBP, and this was identically
observed even in normotensive participants.
© 2019 S. Karger AG, Basel
Introduction
The metabolic syndrome (MetS) is defined by the si-
multaneous occurrence of at least 3 of the 5 metabolic ab-
normalities including abdominal obesity, high blood pres-
sure (BP), high blood glucose, high triglycerides (TG), and
low high-density lipoprotein (HDL) [1]. Prospective stud-
ies have suggested that the development of MetS may be
the result of a combined interaction including insulin re-
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sistance (IR), obesity, and health behaviors including de-
creased physical activity and a sedentary life style [2–4]. In
particular, the growing prevalence of obesity has contrib-
uted to the markedly increased prevalence of MetS [5], and
approximately 20–25% of adults globally are presumed to
have MetS [6]. This trend is also prominent in Korea,
where the age-adjusted prevalence of MetS had risen from
24.9% in 1998 to 31.3% in 2007, with an estimated annual
increase of 0.6% over 10 years [7].
MetS can result in increased cardiovascular morbidity
and mortality, which poses a substantial burden on public
health due to frequent healthcare utilization and rising
medical costs. Thus, public health efforts have focused on
early identification and management of the risk factors for
MetS to reduce the medical comorbidities and long-term
sequelae of MetS. In this context, identification of the pre-
dictors of MetS may be an important medical achievement
in terms of preventing MetS.
A high BP is a component of MetS, and MetS is present
in up to one third of hypertensive patients [8, 9]. Elevation
of BP relates to IR, visceral obesity, and dyslipidemia that
are the main pathophysiologic features underlying MetS
[10, 11]. In particular, IR is strongly associated with BP as
well as with MetS. IR leads to increased renal sodium reab-
sorption, increased sympathetic neural outflow, and an
impaired ability of insulin to dilate the peripheral vascula-
ture [12], which may be involved in the pathogenesis of
primary hypertension in up to 40–50% of cases [13]. There-
fore, it is postulated that BP itself may be a significant fac-
tor related to the increased risk for MetS with mediation of
IR. However, data is still insufficient on the predictive abil-
ity of BP for incident MetS. Additionally, there is only lim-
ited information regarding the influence of BP on the risk
of MetS in a normotensive population.
The aim of the present study is to examine the indepen-
dent role of BP on incident MetS. Using data from the Ko-
rean Genome and Epidemiology Study (KoGES), we eval-
uated the long-term risk of MetS according to BP levels.
Our analysis was conducted in a normotensive population
to identify whether an elevated BP, even within the normal
range, increases the risk of MetS.
Research Design and Methods
Study Population
All of the subjects were participants of the KoGES An-
san and Ansung study, which is a population-based, epi-
demiological study of rural and urban communities in
South Korea. The detailed methods and the study popula-
2 Cardiology
DOI: 10.1159/000499867
tion of the present study have been described in a previ-
ous study [14]. The baseline survey of the KoGES Ansan
and Ansung study was completed in 2001–2002, and fol-
low-up surveys were conducted every 2 years. Initially, a
total of 10,038 participants aged 40–69 years participated
in the study. A total of 5,018 participants were recruited
via the cluster-sampling method, stratified by age, sex,
and residential district in the Ansung community, and
5,020 subjects were selected via the random sampling
method in Ansan. Of those 10,038 participants, 629 had
missing values for important clinical and biochemical
characteristics such as BP, fasting glucose, lipid profile,
BMI, and waist circumference (WC), and 2,977 partici-
pants had baseline MetS. During a 10-year follow-up pe-
riod, 623 patients were further excluded due to loss to
follow-up or incomplete follow-up data. Finally, 5,809
participants were enrolled into the present study. All of
the subjects participated in this study voluntarily, and in-
formed consent was obtained in all cases.
Clinical and Biochemical Measurements
Study data included a medical history and sociodemo-
graphic information provided via a self-administered
questionnaire, anthropometric measurements, and lab­
oratory biochemical measurements. All of the study
participants were also asked to complete a health-relat-
ed behavior questionnaire, which included the topics
of alcohol consumption, smoking, and exercise. Physical
activity was divided into the following 2 categories: regu-
lar exercise (≥90 min of exercise per week, at least mod-
erate intensity) and inactivity. Questions about alcohol
intake included the frequency of alcohol consumption
on a weekly basis and the typical amount that was con-
sumed on a daily basis (g/day). Smoking status was di-
vided into the following 3 categories: never, former, and
current smoker. Diabetes mellitus was defined as a fast-
ing serum glucose level of at least 126 mg/dL, a serum
HbA1c level of at least 6.5%, or a 2-h glucose level of at
least 200 mg/dL, or ever having been diagnosed with di-
abetes [15]. Hypertension was defined as ever having
been diagnosed with hypertension with or without in-
take of antihypertensive medication, or as having a mea-
sured BP ≥130/80 mm Hg at the initial examination
based on a newly published guideline from the American
College of Cardiology and the American Heart Associa-
tion (ACC/AHA) [16]. BP was measured at both arms in
the sitting position after relaxation for at least 10 min.
BP measurement was conducted twice, with a 5-min re-
cess between each measurement. The arithmetic mean of
the BP was used to define the systolic (SBP) and the dia-
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Table 1. Main clinical characteristics of the study population according to SBP

SBP (mm Hg): <110 110–119 120–129 130–139 140–149 ≥150 p for
(n = 2,072) (n = 1,633) (n = 1,060) (n = 501) (n = 283) (n = 260) trend

Male sex 864 (41.7) 852 (52.2) 622 (58.7) 299 (59.7) 158 (55.8) 137 (52.7) <0.001
Age, years 48.1±7.5 50.0±8.2 52.5±8.8 54.6±9.3 56.6±8.7 57.9±8.1 <0.001
Fasting glucose, mg/dL 82.7±14.6 83.9±14.3 85.3±16.3 84.4±13.8 84.3±10.1 84.8±11.7 <0.001
Total cholesterol, mg/dL 184.7±32.8 188.6±34.0 190.9±35.4 187.7±37.2 193.0±39.9 192.1±35.7 <0.001
HDL cholesterol, mg/dL 45.8±9.7 46.5±10.2 47.4±9.7 49.3±10.1 50.9±10.4 51.5±11.6 <0.001
TG, mg/dL 128.0±78.8 138.0±84.6 139.2±87.1 123.4±49.0 128.8±53.7 127.7±60.4 0.923
Average alcohol intake, g/day 6.6±16.2 10.4±24.6 12.8±24.6 11.6±24.0 9.8±18.0 10.0±18.7 <0.001
Current smokers, % 26.1 27.5 28.1 27.1 26.5 24.6 0.903
Regular exercise, % 31.8 40.7 43.8 48.3 49.8 51.9 <0.001
BMI 23.5±2.7 24.0±2.8 23.9±2.9 23.4±2.9 23.6±2.6 23.8±3.2 0.247
WC, cm 78.1±7.7 80.2±7.4 81.2±7.5 79.9±7.0 80.2±7.1 80.7±7.4 <0.001
SBP, mm Hg 101.0±6.3 114.2±2.9 123.9±2.9 133.6±2.9 143.8±3.0 161.2±11.5 <0.001
DBP, mm Hg 68.8±6.6 76.7±5.6 81.6±6.5 87.8±7.3 92.2±8.4 98.1±9.4 <0.001
History of hypertension, % 0.8 2.7 7.0 17.6 29.0 48.5 <0.001
Diabetes mellitus, % 3.7 6.2 5.8 4.4 5.3 6.5 0.039
Incidence of MetS 387 (18.7) 511 (31.3) 408 (38.5) 182 (36.3) 129 (45.6) 112 (43.1) <0.001

Continuous variables are expressed as means ± SD, and categorical variables are expressed as numbers (%) unless otherwise stated.

stolic BP (DBP). The WC, height, and weight were also
measured and the BMI was calculated for all of the par-
ticipants.
After fasting overnight for 12 h, the plasma concentra-
tions of glucose, total cholesterol, TG, and HDL choles-
terol were measured enzymatically using a Hitachi Auto-
matic Analyzer 7600 (Hitachi, Tokyo, Japan). Fasting
plasma insulin concentrations were determined using a
radioimmunoassay kit (Linco Research, St. Charles, MO,
USA). HbA1C levels were measured via high-perfor-
mance liquid chromatography (VARIANT II; Bio-Rad
Laboratories, Hercules, CA, USA).
The presence of MetS was determined according to
the joint interim statement of the International Diabetes
Federation (IDF) Task Force on Epidemiology and Pre-
vention [1]. Elevated BP was defined as SBP or DBP
≥130/85 mm Hg, elevated fasting serum glucose was de-
fined as levels ≥100 mg/dL, high serum TG was defined
as levels ≥150 mg/dL, low HDL cholesterol was defined
as levels <40 mg/dL in men and <50 mg/dL in women.
The presence of visceral obesity was defined based on the
criteria of the Korean Society for the Study of Obesity
(i.e., WC ≥90 cm for men and ≥85 cm for women) [17].
MetS was defined as the presence of 3 or more of the
above components.
Statistical Analysis
The study participants were categorized according to
SBP and DBP, respectively. Data are presented as means
± SD within study groups for continuous variables and as
proportions for categorical variables. The linear trends of
variables between study groups were calculated using a
linear regression model for continuous variables and the
Cochran-Armitage trend test for categorical variables.
The baseline characteristics of the study population, in-
cluding participants with MetS, are also presented in the
online supplementary Tables 1 and 2 (for all online suppl.
material, see www.karger.com/doi/10.1159/000499867).
Crude and multivariate adjusted HR and their 95% CI
for MetS were obtained using the Cox proportional haz-
ards model. The covariates of the adjusted model were:
age, sex, area, regular exercise, WC, diabetes, smoking,
alcohol intake, and HDL cholesterol. The incidence cases
of MetS and the incidence density (incidence cases per
1,000 person-years) were also calculated in each SBP and
DBP group. In the analysis of all of the participants, SBP
and DBP were divided by a unit of 10 mm Hg, and the
group with the lowest BP level was used as the reference
group (i.e., SBP: <110, 110–119, 120–129, 130–139, 140–
149, and ≥150 mm Hg; DBP: <70, 70–79, 80–89, 90–99,
and ≥100 mm Hg). The subgroup analyses were per-
formed in normotensive participants (subjects with a BP
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Table 2. Main clinical characteristics of the study population according to DBP

DBP (mm Hg): <70 70–79 80–89 90–100 ≥100 p for trend
(n = 1,191) (n = 2,292) (n = 1,548) (n = 579) (n = 199)

Male sex 388 (32.6) 1,147 (50.0) 898 (58.0) 376 (64.9) 123 (61.8) <0.001
Age, years 48.3±7.7 50.2±8.4 52.2±8.9 54.2±9.0 53.4±8.6 <0.001
Fasting glucose, mg/dL 81.8±14.5 84.1±15.6 84.6±13.9 84.4±12.2 85.5±10.2 <0.001
Total cholesterol, mg/dL 183.3±32.1 186.5±33.9 190.8±35.1 191.5±37.2 200.1±39.8 <0.001
HDL cholesterol, mg/dL 46.3±9.8 46.1±9.9 47.6±10.3 49.7±9.7 51.3±11.6 <0.001
TG, mg/dL 124.5±71.8 133.0±79.2 137.8±81.1 132.8±84.1 132.4±65.8 0.003
Average alcohol intake, g/day 5.4±15.8 8.7±20.7 11.4±22.5 15.6±29.1 12.0±18.9 <0.001
Current smokers, % 20.7 27.6 29.7 30.6 24.1 <0.001
Regular exercise, % 29.0 40.2 43.4 48.4 43.7 <0.001
BMI 23.2±2.6 23.8±2.8 23.9±2.9 24.0±2.7 24.1±2.9 <0.001
WC, cm 76.9±7.5 79.7±7.5 80.7±7.5 81.5±6.9 81.1±7.0 <0.001
SBP, mm Hg 100.5±9.2 111.7±8.8 122.9±10.7 138.2±12.5 155.0±15.9 <0.001
DBP, mm Hg 63.9±4.4 74.2±3.1 83.3±2.9 93.2±2.9 104.8±5.7 <0.001
History of hypertension, % 0.8 2.6 8.7 24.4 43.7 <0.001
Diabetes mellitus, % 3.9 5.9 5.0 4.8 4.0 0.810
Incidence of MetS 192 (16.1) 636 (27.7) 575 (37.1) 237 (40.9) 89 (44.7) <0.001

Continuous variables are expressed as mean ± SD, and categorical variables are expressed as numbers (%) unless otherwise stated.

<140/90 mm Hg and without a history of hypertension).
The normotensive participants were grouped by a unit of
10 mm Hg in SBP and a unit of 5 mm Hg in DBP (i.e.,
SBP: <110, 110–119, and 120–129 mm Hg; DBP: <70, 70–
74, and 75–79 mm Hg). All statistical analyses were per-
formed using R 3.4.3 (R Foundation for Statistical Com-
puting, Vienna, Austria), p < 0.05 was considered statisti-
cally significant in all analyses.
Results
A total of 5,809 participants (2,932 men and 2,877
women, mean age 50.8 years) were enrolled into this
study. The overall incidence rate of MetS was 28.6% (n =
1,729), and incidence density was 40.8. The final follow-
up examination was done in 2011–2012.
Table 1 presents the baseline clinical and biochemical
characteristics of the study participants according to SBP.
Compared to the group with the lowest SBP level, the high-
er-SBP groups tended to have worse metabolic profiles in-
cluding age, fasting glucose, WC, DBP, prevalence of DM,
and incidence of MetS. The rates of male gender, HDL cho-
lesterol, and regular exercise were higher in the higher-SBP
groups than in the lowest-SBP group. However, statistical
significance was not identified for TG, BMI, and the pro-
portion of current smokers. These findings were similarly
observed in the DBP groups (Table 2). The higher-DBP
groups also had the more males and worse metabolic pro-
files than the lowest-DBP group, besides HDL cholesterol
and regular exercise. Statistical significance was identified
for all clinical and biochemical characteristics.
Table 3 shows the unadjusted and adjusted HR and
95% CI for MetS in the SBP and DBP groups. Even after
adjusting for the metabolic covariates, elevated SBP and
DBP levels were significantly associated with increased
HR for MetS. A clear dose-response relationship was ob-
served between DBP levels and HR for MetS (< 70 mm
Hg: reference, 70–79 mm Hg: HR = 1.46 [95% CI 1.24–
1.72], 80–89 mm Hg: HR = 2.10 [95% CI 1.77–2.49], 90–
99 mm Hg: HR = 2.63 [95% CI 2.16–3.21], and ≥100 mm
Hg: HR = 3.94 [95% CI 3.05–5.10]). The subgroup analy-
sis for normotensive participants also indicated increased
HR for MetS proportionally to SBP (<110 mm Hg: refer-
ence, 110–119 mm Hg: HR = 1.60 [95% CI 1.40–1.84],
and 120–129 mm Hg: HR = 2.12 [95% CI 1.82–2.48]) and
DBP levels (<70 mm Hg: reference, 71–74 mm Hg: HR =
1.31 [95% CI 1.09–1.58], and 75–79 mm Hg: HR = 1.51
[95% CI 1.25–1.81]) (Table 4).
Online supplementary Tables 1 and 2 present the as-
sociation between BP levels and the risk of incident MetS
based on the cut-off of WC from the IDF task force (WC
≥102 cm in men and ≥89 cm in women). Even after
adopting a cut-off for WC that was higher than the mod-
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 Table 3. HR and 95% CI for the incidence of MetS

Characteristics Unadjusted HR Adjusted HR Incidence Incidence

cases, n densitya

SBP (mm Hg)

<110 (n = 2,072) 1.00 (reference) 1.00 (reference) 387 23.9
110–119 (n = 1,633) 1.83 (1.61–2.09) 1.58 (1.38–1.81) 511 42.2
120–129 (n = 1,060) 2.51 (2.18–2.88) 2.11 (1.83–2.44) 408 55.9
130–139 (n = 501) 2.36 (1.98–2.81) 2.31 (1.92–2.77) 182 52.7
140–149 (n = 283) 3.30 (2.70–4.02) 3.57 (2.90–4.39) 129 70.7
≥150 (n = 260) 3.51 (2.85–4.34) 3.52 (2.82–4.38) 112 72.2
DBP (mm Hg)
<70 (n = 1,191) 1.00 (reference) 1.00 (reference) 192 20.5
70–79 (n = 2,292) 1.85 (1.58–2.18) 1.46 (1.24–1.72) 636 37.1
80–89 (n = 1,548) 2.74 (2.33–3.22) 2.10 (1.77–2.49) 575 52.8
90–99 (n = 579) 3.35 (2.77–4.05) 2.63 (2.16–3.21) 237 62.5
≥100 (n = 199) 4.09 (3.18–5.26) 3.94 (3.05–5.10) 89 74.1

Values were adjusted for age, sex, area, regular exercise, WC, smoking, HDL cholesterol, diabetes mellitus,
and alcohol intake. a Incidence cases per 1,000 person-years.

Table 4. HR and 95% CI for the incidence of MetS in subjects without hypertension

Characteristic Unadjusted HR Adjusted HR Incidence Incidence

cases, n densitya

SBP (mm Hg)

<110 (n = 2,055) 1.00 (reference) 1.00 (reference) 381 23.7
110–119 (n = 1,575) 1.86 (1.63–2.13) 1.60 (1.40–1.84) 495 42.4
120–129 (n = 862) 2.49 (2.15–2.89) 2.12 (1.82–2.48) 327 54.7
DBP (mm Hg)
<70 (n = 1,180) 1.00 (reference) 1.00 (reference) 190 20.5
70–74 (n = 1,143) 1.64 (1.37–1.97) 1.31 (1.09–1.58) 286 32.9
75–79 (n = 1,078) 2.06 (1.72–2.46) 1.51 (1.25–1.81) 324 40.7

Adjusted for age, sex, area, regular exercise, WC, smoking, HDL cholesterol, diabetes mellitus, and alcohol
intake. a Incidence cases per 1,000 person-years.

ified cut-off in Koreans, the risk of MetS significantly in-
creased proportionally to the levels of baseline SBP and
DBP in both all and the normotensive participants.
Discussion
Obesity has a great influence on the pathogenesis of
both MetS and hypertension. However, it is evident that
Asians have a higher metabolic risk despite a lower degree
of obesity compared to Caucasians [18]. Our study also
yielded a mean BMI of less than 25 and a mean WC of 85
cm. Additionally, none of the groups had a mean BMI
≥25 or a WC ≥85 cm. These findings show the need to
assess other predictors of MetS besides obesity in Asians.
We grouped the study participants by stratification of
SBP and DBP and evaluated the risk of incident MetS ac-
cording to BP strata. Our results, despite the generally
nonobese figures of the subjects, showed a proportional
relationship between the risk of MetS and SBP and DBP.
In the SBP groups, compared to the group with a SBP
<110 mm Hg, the risk of MetS significantly increased up
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to 3.57-fold proportionally to SBP levels within strata.
This trend was identically observed in the DBP groups, in
which subjects with a DBP ≥100 mm Hg had a 3.94 times
higher risk of MetS than subjects with a DBP <70 mm Hg.
Despite the close association between BP and MetS, no
study has shown the predictive potential of BP for inci-
dent MetS. Palaniappan et al. [19] assessed the predictive
ability of the risk factors for the MetS in 714 nondiabetic
subjects without MetS in the Insulin Resistance Athero-
sclerosis Study, but their analysis did not show a statisti-
cally significant association between elevated BP (≥130
mm Hg systolic or ≥85 mm Hg diastolic) and incident
MetS with an OR of 1.1 (95% CI 0.7–1.6). However, our
results clearly show a stepwise increase in the risk of MetS
proportionally to the levels of SBP and DBP, which indi-
cates a close link between elevated BP and incident MetS
as well as hypertension. In individuals with hypertension,
incident MetS may have a synergistic effect with high BP,
resulting in a poor cardiovascular prognosis. Previous
studies have also demonstrated the graded associations
between higher SBP and DBP and an increased risk of
cardiovascular disease (CVD). A meta-analysis of 61 pro-
spective studies indicated that the risk of CVD gradually
increased in a log-linear fashion from SBP <115 mm Hg
and DBP <75 mm Hg to SBP >180 mm Hg and DBP >105
mm Hg, respectively [20]. Additionally, in an observa-
tional study including >1 million adults aged ≥30 years,
higher SBP and DBP were significantly associated with an
increased risk of CVD including angina, myocardial in-
farction, HF, stroke, peripheral artery disease, and ab-
dominal aortic aneurysm [21]. Thus, it is inferred that
lifestyle modifications and educational interventions for
MetS should be conducted in individuals with an elevated
BP even in a nonhypertensive state to reduce the cardio-
vascular risk related to MetS.
Our results may provide a clue to verify the validity of
newly established guidelines for hypertension in predict-
ing the cardiovascular risk. Currently, the cut-off for hy-
pertension is not agreed upon globally, showing subtle dif-
ference across committees and regions. In particular, the
ACC/AHA published an updated guideline including a
new BP classification in November 2017 [16]. In the new
guideline, although the cut-off of for normal BP remained
the same as that in the 7th report of the joint national com-
mittee (JNC 7) [22], the cut-off for hypertension was low-
ered from 140 mm Hg in SBP and 90 mm Hg in DBP to
130 mm Hg in SBP and 80 mm Hg in DBP. This disagree-
ment may arise from the heterogeneous opinions regard-
ing the anticipated cardiovascular risk derived from spe-
cific BP categories determined by the BP cut-off. Our
6 Cardiology
DOI: 10.1159/000499867
study demonstrated a gradual increase in the risk of MetS
from SBP ≥110 mm Hg and DBP ≥70 mm Hg, which sup-
ports the benefit of lowering the cut-off for hypertension
in terms of reducing the cardiovascular risk. In particular,
it is of note that this association was identically identified
even in the normotensive population. The current guide-
line has a wide range of BP within a specific BP category,
and thus individuals even within the same BP category can
have diverse BP levels. Our results indicate an increased
risk for MetS proportionally to BP levels even within a
normal BP category, which suggests the clinical impor-
tance of suppressing BP elevation and maintaining an op-
timal BP for reduction of the cardiometabolic risk.
Our study was based on a hypothesis that BP elevation
is a signal of derangement not only of circulatory stability
but also metabolic homeostasis. In our study, BP elevation
was potentially linked to the increased cardiometabolic
risk reflected by MetS. Even allowing for the adverse effect
of a high BP directly on the cardiovascular system, our re-
sults suggest that MetS may play the significant role in
mediation of the causative relationship between a high BP
and CVD. Probably, the condition of BP elevation may be
a result of the comprehensive function of unfavorable
conditions including structural instability in the vascula-
ture, cardiac dysfunction, circulatory disturbance, and
impaired metabolic homeostasis. These unfavorable con-
ditions may be driven from the interaction of pathophys-
iologic mechanisms like increased secretion of proinflam-
matory cytokines [23], oxidative stress and endothelial
dysfunction by chronic systemic inflammation [24], over-
production of adipocytokine from adipose tissue, and ad-
verse effects of IR including an activated rennin angioten-
sin system, sodium retention, and sympathetic overactiv-
ity [25–27]. Their interrelated functions may lead to BP
elevation and, coincidentally, increase the risk of MetS
with insidious aggravation of metabolic conditions.
We longitudinally evaluated the risk of MetS accord-
ing to BP levels in both normotensive and hypertensive
populations and expanded the clinical implication of BP
to a metabolic risk factor. Nonetheless, the limitations
of our study should be acknowledged.
First, in the present study, the ACC/AHA guideline
was used to establish the definition of hypertension, but
global agreement has yet to be reached regarding this
point. The ACC/AHA guideline presents a cut-off for hy-
pertension of 130/80 mm Hg, which is lower than the cur-
rently used cut-off (140/90 mm Hg) in Korea. Thus, it is
recognized that adopting the ACC/AHA guideline might
have led to an overestimated prevalence of hypertension
in our study participants.
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 Second, we could not identify detailed information on
antihypertensive medication during the follow-up. Ran-
domized clinical trials have shown that antihypertensive
therapies with thiazide diuretics and β-blockers are asso-
ciated with an increased incidence of new onset diabetes
and other metabolic abnormalities [28, 29]. Thus, it is in-
ferred that types of antihypertensive medications might
have an impact on incident MetS during follow-up. How-
ever, it was hard to confirm the types and kinds of anti-
hypertensive medications during follow-up. This limita-
tion arose from our dependency on a self-report ques-
tionnaire for identification of a history of antihypertensive
medications. Thus, the absence of detailed information
on antihypertensive medications should be recognized as
a limitation.
Third, our study participants were comprised of Ko-
reans only. Since the cardiometabolic risk can vary
among ethnicities and regions at given metabolic condi-
tions, it is unlikely that our findings can be extrapolated
to other ethnic and regional groups.
In conclusion, our study presented that an elevated BP
was significantly associated with an increased risk of in-
cident MetS in a Korean population. The incidence and
HR of MetS increased proportionally to the BP level, and
this was identically observed even in the normotensive
population. These findings indicate the clinical signifi-
cance of BP as a metabolic risk factor.
Acknowledgement
Data in this study were from the KoGES (4851–302), National
Research Institute of Health, Centers for Disease Control and Pre-
vention, Ministry for Health and Welfare, Korea.
Statement of Ethics
Ethical approval for the study protocol and analysis of the data
was obtained from the institutional review board of the Kangbuk
Samsung Hospital.
Author Contributions
Ju Young Jung coordinated this study, analyzed the data, and
wrote this paper as first author. Chang-Mo Oh played a role in
analysis of the data and verification of the results. Joong-Myung
Choi participated in English editing and review of this paper. Jae-
Hong Ryoo and Pil-Wook Chung participated in the conduction
of this study and the writing of this paper. Hyun Pyo Hong con-
ducted additional statistical analysis and writing of this paper in
the process of revision of this work.
Sung Keun Park is the guarantor of this work and, as such, had
full access to all of the data in this study and takes responsibility
for the integrity of the data and the accuracy of the data analysis.
All of the authors had access to the data used in this study and
participated in the writing of this paper.

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