Original Article
Optimal Target Blood Pressure and Risk of Cardiovascular
Disease in Low-Risk Younger Hypertensive Patients
Chang Hee Kwon,1 Jeonggyu Kang,2 Ara Cho,2 Yoosoo Chang,2 Seungho Ryu,2 and Ki-Chul Sung3
BACKGROUND
This study aimed to examine longitudinal associations between blood
pressure (BP) categories and incident cardiovascular disease (CVD) in
treated hypertensive patients without CVD.
METHODS
A cohort study was performed in Korean adults who underwent a com-
prehensive health examination from 1 January 2011 to 31 December
2016 and was followed for incident CVD via linkage to the Health
Insurance and Review Agency database until the end of 2016, with a
median follow-up of 4.3 years.
RESULTS
Among 263,532 participants, 8,418 treated hypertensive patients
free of CVD at baseline were included. The incident CVD end point
was defined as new hospitalization for CVD, including ischemic
heart disease, stroke, and transient ischemic attack. During 32,975.6
person-years of follow-up, 200 participants developed new-onset
CVD (incidence rate of 60.6 per 104 person-years). The multivariable-
adjusted hazard ratio (HR; 95% confidence intervals [CI]) for CVD
Hypertension has been defined as systolic blood pressure
(SBP) ≥ 140 mm Hg and/or diastolic blood pressure (DBP)
≥ 90  mm Hg since Joint National Committee IV report in
1988. However, the Systolic Blood Pressure Intervention Trial
(SPRINT) has reported that targeting SBP of less than 120 mm
Hg instead of less than 140 mm Hg can lower rates of major
cardiovascular disease (CVD) events (fatal and nonfatal) and
death from any cause among patients at high risk for CVD
events without diabetes.1 Since then, the 2017 American
College of Cardiology/American Heart Association guide-
line has lowered the threshold for the definition of hyperten-
sion to an SBP of ≥ 130 mm Hg and/or DBP ≥ 80 mm Hg.2
Most recently, the European Society of Cardiology/European
Society of Hypertension has maintained previous definition
of hypertension as office SBP ≥ 140  mm Hg and/or DBP ≥
90 mm Hg but recommended that treated BP values should
be 130/80 mm Hg or lower in most patients.3
Correspondence: Ki-Chul Sung (kcmd.sung@samsung.com).
Initially submitted February 19, 2019; date of first revision March 14,
2019; accepted for publication April 20, 2019; online publication May
02, 2019.
according to systolic blood pressure (SBP) levels (comparing SBP <
110, SBP = 120–129, SBP = 130–139, SBP = 140–149, SBP = 150–159,
and SBP ≥160 to SBP 110–119  mm Hg [reference]) were 0.83 (0.53–
1.30), 1.31 (0.91–1.89), 1.18 (0.74–1.87), 1.46 (0.79–2.72), 3.19 (1.25–
8.12), and 5.60 (2.00–15.70), respectively. In multivariable analysis for
CVD according to diastolic blood pressure (DBP) levels, HR (95% CI)
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of DBP < 60, DBP = 70–79, DBP = 80–89, DBP = 90–99, and DBP ≥100
compared to DBP = 60–69 mm Hg [reference]) were 0.51 (0.12–2.14),
1.13 (0.76–1.67), 1.26 (0.83–1.92), 1.62 (0.89–2.97), and 1.68 (0.51–
5.55), respectively.
CONCLUSIONS
In this large cohort of middle-aged treated hypertensive patients, SBP
< 120 mm Hg and/or DBP < 70 mm Hg were acceptable and showed a
trend of protection of incident CVD.
Keywords: blood pressure; cardiovascular disease; cohort study;
hypertension.
doi:10.1093/ajh/hpz067
Some new information on SBP and DBP targets for
drug treatment indicates that intensive BP lowering (SBP <
130  mm Hg or DBP < 80  mm Hg) can reduce the risk of
major CVD events including mortality.4,5 On the other hand,
other analyses have reported that lowering SBP to <130 mm
Hg in general has no further benefit on major CVD events
except that it may reduce the risk of stroke.6–8 Ironically,
although current guidelines define normal or optimal BP
level as SBP < 120 mm Hg and DBP < 80 mm Hg, but these
guidelines also recommend that treated SBP and DBP should
not be targeted to <120  mm Hg and <70  mm Hg, respec-
tively, because it has been consistently found that reducing
SBP to <120 mm Hg and DBP to <70 mm Hg can increase
the incidence of CVD events and death.2,3 These results have
emerged from post-hoc analyses of large outcome trials in
older patients at higher risk who often have comorbidities
and CVD.6–8
1Division of Cardiology, Department of Internal Medicine, Konkuk
University Medical Center, Konkuk University School of Medicine, Seoul,
Republic of Korea; 2Center for Cohort Studies, Total Healthcare Center,
Kangbuk Samsung Hospital, Sungkyunkwan University School of
Medicine, Seoul, Republic of Korea; 3Division of Cardiology, Department
of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan
University School of Medicine, Seoul, Republic of Korea.
© Crown copyright 2019.
American Journal of Hypertension  32(9)  September 2019  833
Kwon et al.
However, it is unknown whether these results of target
BP with lower safety boundaries from high-risk patients
are applicable to low-risk hypertensive patients without
CVD. Studies that evaluate the optimal target BP in rela-
tively young hypertensive patients with low risk are lacking.
Therefore, the objective of this study was to examine the as-
sociation between BP category and CVD in treated hyper-
tensive patients without CVD.
METHODS
Study population
The Kangbuk Samsung Health Study is a cohort study of
Korean men and women 18 years of age or older who have
undergone a comprehensive annual or biennial health ex-
amination at Kangbuk Samsung Hospital Total Healthcare
Centers in Seoul and Suwon, South Korea.9 Most examinees
(over 80%) are employees of various companies and local
governmental organizations and their spouses. In South
Korea, the Industrial Safety and Health Law requires annual
or biennial health screening examinations for all employees
free of charge. Other examinees voluntarily purchased a
health checkup at the center.
The Kangbuk Samsung Health Study participants who
underwent a comprehensive health examination from 1
January 2011 to 31 December 2016 and provided informed
consent for linkage to the Health Insurance Review and
Assessment Service (HIRA) database (n  =  263,532; Figure
1) were eligible for this study. In Korea, health care is or-
ganized under a mandatory single-payer nationwide insur-
ance system (National Health Insurance, NHI) that collects
all information on medical services utilization covering the
entire Korean population under a comprehensive database
operated by HIRA.10
Among these participants, 12,141 hypertensive subjects
with antihypertensive medication were selected from the
HIRA prescription database. Exclusion criteria were missing
data on BP or history of hypertension (n  =  70), history of
Figure 1.  Flow diagram showing the selection of the study population.
834  American Journal of Hypertension  32(9)  September 2019
malignancy (n = 546), or diagnosis of CVD (n = 3,289) be-
fore baseline visit. Because some participants met more than
one exclusion criterion, the final sample size included in the
analysis was 8,418 hypertensive patients, including 5,657
(67.2%) males. Written informed consent was obtained from
all participants. This study was approved by the institutional
review board of Kangbuk Samsung Hospital.
Measurements
Data on demographic characteristics, lifestyle factors,
medical history, and family history of CVD were collected
using standardized, self-administered questionnaires.11
Smoking status was categorized as never smoker, former
smoker, and current smoker. Alcohol intake was categorized
as <20 g/day and ≥20 g/day. Education level was categorized
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as less than college and college education or more. Physical
activity was assessed using validated Korean version of the
International Physical Activity Questionnaire short form.12
Participants were classified as inactive, minimally active,
and health-enhancing physically active (HEPA). HEPA was
defined as physical activity that met either of the following
2 criteria: (i) vigorous intensity activity on 3 or more days
per week accumulating ≥1,500 MET min/week; or (ii) 7 days
of any combination of walking, moderate intensity, or vig-
orous intensity activities achieving at least 3,000 MET min/
week.12 Usual dietary intake was assessed using a 103-item,
self-administered food frequency questionnaire designed
and validated for use in Korea.13
Height and weight were measured by trained nurses. Body
mass index (BMI) was calculated as weight in kilogram di-
vided by height in square meter. BP was measured using an
automated oscillometric device (53000, Welch Allyn, New
York, NY) by trained nurses while participant was in a sit-
ting position with the arm supported at the heart level after
a 5-minute rest. Three consecutive BP readings were re-
corded and the average of the 2nd and 3rd readings was used
in the analysis. For CVD risk stratification, Framingham
risk score (FRS) was calculated based on Pooled Cohorts
Equation.14 Risk scores were considered low if <10% and
high if ≥10%.2,14,15
Blood samples were drawn from the antecubital vein
after at least 10 hours of fasting. Blood tests included total
cholesterol, low-density lipoprotein cholesterol (LDL-C),
high-density lipoprotein cholesterol (HDL-C), triglycerides
(TG), glucose, uric acid, insulin, and high sensitivity
C-reactive protein. Insulin resistance was assessed with the
Homeostatic Model Assessment of Insulin Resistance equa-
tion as follows: fasting blood insulin (uU/ml) × fasting blood
glucose (mmol/l)/22.5. Diabetes was defined as a fasting
serum glucose level of ≥126 mg/dl, HbA1c level of ≥6.5%, or
current use of insulin or antidiabetic medications.
Antihypertensive and lipid-lowering medications
Information on antihypertensive and lipid-lowering
medications was obtained through linkage to the HIRA pre-
scription database.10 Antihypertensive medications were
defined as prescription of α-adrenergic blockers, angiotensin-
converting enzyme inhibitors, angiotensin II receptor

blockers, β-adrenergic blockers, calcium channel blockers
(CCB), or diuretics. For combination antihypertensive
medications, each active component was counted separately.
Outcomes
The primary outcome was incident CVD defined as the
first hospitalization for CVD including ischemic heart di-
sease International Classification of Diseases, Tenth Revision
(ICD-10, I20–I25), stroke (ICD-10, I60–I64), and transient
ischemic attack (ICD-10, G45) ascertained through linkage
to the HIRA database. As secondary outcomes, ischemic
heart disease, myocardial infarction (ICD-10 codes I21–
I24), stroke, ischemic stroke (ICD-10 code, I63), hemor-
rhagic stroke (ICD-10 code, I60–I62), and transient ischemic
attacks were also evaluated separately.16,17
Statistical analyses
Study participants were divided into 7 or 6 mutually ex-
clusive categories according to SBP or DBP. Each participant
was followed from the baseline examination until the devel-
opment of incident CVD or 31 December 2016, whichever
first. Hazard ratios (HRs) and 95% confidence intervals (CI)
for CVD were estimated using Cox-proportional hazards
regression analysis. Proportional hazards assumption was
assessed by examining graphs of estimated log (–log) sur-
vival curves.
Cox models were initially adjusted for age and sex. They
were then further adjusted for study center (Seoul, Suwon),
year of screening examination (1-year categories), BMI,
smoking (never, past, current, or unknown), alcohol intake
(0, <20, ≥20  g/day, or unknown), physical activity (inac-
tive, minimally active, HEPA, or unknown), education level
(<college education, ≥college education, or unknown), total
calorie intake, and history of diabetes (model 1). Model 2
was further adjusted for LDL-C, HDL-C, TG, and glucose.
We also examined the association between BP categories
and CVD in subgroups defined by FRS (<10 and ≥10%). All
statistical analyses were conducted with Statistical Analysis
Software (SAS) Enterprise Guide, Version 6.1 (SAS Institute,
Inc., Cary, NC). P values < 0.05 were considered statistically
significant.
RESULTS
Characteristics of the study population
The mean (SD) age of study participants was 51.1 (10.6)
years. Of 8,418 hypertensive patients, 5,657 (67.2%) were
males. Sixty-two percent participants had college education
or more. The prevalence of diabetes was 31.1%. Mean (SD)
BMI level was 25.3 (3.4) kg/m2. Mean (SD) systolic and di-
astolic BP were 118.3 (12.8) mm Hg and 76.2 (9.5) mm Hg,
respectively.
Tables 1 and 2 show baseline characteristics according
to SBP and DBP levels. Participants with SBP < 130  mm
Hg accounted for 81.7%. About half (54.1%) of them were
controlled with SBP < 120 mm Hg. Participants with DBP
Target BP and Risk of CVD
< 80 mm Hg accounted for 62.8%. About a quarter (23.4%)
of them had DBP < 70 mm Hg. Higher SBP and DBP levels
were positively associated with older age, male sex, alcohol
intake, family history of CVD, obesity, and higher levels of
uric acid, total cholesterol, LDL-C, and TG. They were in-
versely associated with HDL-C. Diabetes was significantly
associated with higher SBP levels, but not with DBP levels.
Baseline characteristics according to BP categories and
gender groups are shown in Supplementary Tables 1 and 2.
During 32,975.6 person-years of follow-up (median fol-
low-up: 4.3  years; interquartile range: 2.8–5.1  years), we
observed 200 incident cases of CVD (incidence rate: 60.6 per
10,000 person-years; Tables 3 and 4). In the fully adjusted
model, multivariable-adjusted HRs (95% CIs) for CVD ac-
cording to SBP levels (comparing SBP <110, SBP = 120–129,
SBP  =  130–139, SBP  =  140–149, SBP  =  150–159, and SBP
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≥160 to SBP  =  110–119  mm Hg [reference]) were 0.83
(0.53–1.30), 1.31 (0.91–1.89), 1.18 (0.74–1.87), 1.46 (0.79–
2.72), 3.19 (1.25–8.12), and 5.60 (2.00–15.70), respectively.
Multivariable-adjusted HRs (95% CIs) for CVD according to
DBP levels (comparing DBP <60, DBP = 70–79, DBP = 80–89,
DBP  =  90–99, and DBP ≥100 to DBP  =  60–69  mm Hg
[reference]) were 0.51 (0.12–2.14), 1.13 (0.76–1.67), 1.26
(0.83–1.92), 1.62 (0.89–2.97), and 1.68 (0.51–5.55), respec-
tively. Associations were particularly strong for cerebro-
vascular outcomes according to SBP and DBP categories.
Fully adjusted HRs (95% CIs) for stroke or transient is-
chemic attack (TIA) comparing SBP < 110, SBP = 120–129,
SBP  =  130–139, SBP  =  140–149, SBP  =  150–159, and SBP
≥160 to SBP = 110–119 mm Hg (reference) were 0.59 (0.24–
1.46), 1.54 (0.81–2.92), 1.02 (0.43–2.42), 0.72 (0.16–3.19),
5.94 (1.66–21.26), and 7.72 (1.70–35.08), respectively. Fully
adjusted HRs (95% CIs) for stroke or TIA comparing DBP
<60, DBP = 70–79, DBP = 80–89, DBP = 90–99, and DBP
≥100 to DBP  =  60–69  mm Hg (reference) were 1.7 (0.13–
8.56), 1.52 (0.71–3.29), 1.51 (0.65–3.48), 3.55 (1.32–9.57),
and 4.02 (0.84–19.27), respectively.
Supplementary Table 3 shows results of the associa-
tion between BP category and the development of CVD by
Framingham risk stratification. The association between BP
categories and incident CVD was stronger in those with FRS
< 10%. Especially, SBP categories showed a trend of having
positive association with the development of CVD in those
with FRS < 10%.
DISCUSSION
In this large cohort study of relatively low-risk, mid-
dle-aged hypertensive Korean adults with antihypertensive
medications, SBP > 120 mm Hg and DBP > 70 mm Hg showed
a trend of having increased CVD incidences compared to
SBP < 120 mm Hg and DBP category with <70 mm Hg. The
positive association between BP categories and risk of CVD
was stronger in low-risk participants with FRS ≤ 10%. Our
results showed that SBP < 120 mm Hg or DBP < 70 mm Hg
did not increase CVD in low-risk patients.
Although current guidelines define normal or optimal BP
level as SBP < 120 mm Hg and DBP < 80 mm Hg, there is
no conclusion for the optimal BP target in the treatment of
American Journal of Hypertension  32(9)  September 2019  835
 Table 1.  Baseline characteristics according to SBP category

P for
Characteristics SBP <110 SBP 110–119 SBP 120–129 SBP 130–139 SBP 140–149 SBP 150–159 SBP ≥160 trend
Kwon et al.

Number (%) 1,974 (23.4) 2,591 (30.7) 2,328 (27.6) 1,087 (12.9) 339 (4.0) 62 (0.7) 37 (0.4)
Age (years) 49.9 (10.5) 51.2 (10.3) 51.4 (10.6) 52.1 (11.0) 53.5 (11.9) 52.2 (10.2) 50.5 (12.8) <0.0001
Male (%) 55.2 70.1 72.4 70.2 67.6 77.4 75.7 <0.0001
Current smoker (%) 26.8 26.4 24.1 20.8 16.7 27.5 31.3 <0.0001
Alcohol intake (%)a 29.5 37.2 37.7 38.7 40.1 44.6 60.0 <0.0001
HEPA (%) 20.0 22.4 22.4 22.2 25.3 30.5 26.5 0.0114
High education level (%)b 62.5 61.3 63.1 59.1 57.4 55.2 61.1 0.0833
Diabetes (%) 28.3 31.8 30.3 32.5 40.4 38.7 32.4 0.0003
Family history of CVD (%) 20.5 21.0 21.9 17.6 22.1 16.1 16.2 0.3710
Obesity (%)c 38.8 49.4 56.9 57.1 60.2 69.4 56.8 <0.0001
Body mass index (kg/m2) 24.3 (3.2) 25.3 (3.2) 25.8 (3.4) 25.8 (3.4) 26.4 (3.8) 26.9 (3.9) 27.1 (5.3) <0.0001
Systolic BP (mm Hg)d 102.2 (5.7) 114.4 (2.9) 123.8 (2.9) 133.6 (2.8) 143.6 (2.8) 153.4 (2.9) 169.7 (9.5) <0.0001
Diastolic BP (mm Hg)d 66.7 (6.1) 74.3 (6.0) 79.8 (6.4) 84.2 (7.8) 88.6 (8.8) 95.5 (10.7) 107.0 (13.4) <0.0001
Total cholesterol (mg/dl)d 190.0 (35.7) 193.0 (36.1) 195.5 (35.8) 196.9 (34.1) 200.8 (33.6) 201.9 (38.7) 207.9 (37.9) <0.0001

836  American Journal of Hypertension  32(9)  September 2019

LDL-C (mg/dl)d 118.1 (32.3) 121.0 (33.0) 122.7 (32.7) 123.2 (32.7) 126.9 (31.0) 130.0 (33.2) 129.5 (36.4) <0.0001
HDL-C (mg/dl)d 54.6 (14.2) 53.6 (14.1) 52.6 (13.5) 54.2 (14.8) 52.6 (14.3) 52.4 (14.1) 53.8 (15.5) 0.0076
Glucose (mg/dl)d 102.7 (21.3) 105.1 (21.2) 107.3 (23.0) 110.3 (27.9) 111.5 (25.0) 129.1 (37.4) 120.7 (43.6) <0.0001
Uric acid (mg/dl)d 5.4 (1.4) 5.7 (1.5) 5.7 (1.5) 5.6 (1.5) 5.7 (1.5) 5.8 (1.6) 5.9 (1.9) <0.0001
Triglycerides (mg/dl)e 109 (77–155) 116 (83–167) 124 (87–180) 127 (89–179) 133 (96–197) 137 (94–186) 138 (90–182) <0.0001
AST (U/l)e 22 (18–28) 23 (19–30) 24 (19–31) 23 (19–30) 24 (19–30) 25 (18–33) 25 (20–30) <0.0001
ALT (U/l)e 21 (16–31) 24 (17–36) 25 (18–37) 24 (17–35) 25 (18–37) 27 (19–37) 24 (17–35) <0.0001
GGT (U/l)e 26 (16–44) 32 (20–53) 33 (21–56) 33 (21–60) 34 (21–59) 38 (21–58) 51 (21–89) <0.0001
HOMA-IRe 1.38 (0.89–2.19) 1.60 (1.02–2.48) 1.70 (1.09–2.63) 1.77 (1.12–2.76) 1.93 (1.31–3.15) 2.16 (1.22–2.73) 2.21 (1.38–3.58) <0.0001
hsCRP (mg/l)e 0.5 (0.3–1.1) 0.6 (0.3–1.3) 0.6 (0.4–1.3) 0.7 (0.4–1.5) 0.7 (0.4–1.6) 0.8 (0.4–1.5) 0.8 (0.4–1.6) <0.0001
Total energy intake 1,374.5 1,485.6 (1,109.7– 1,490.4 (1,071.0– 1,494.4 (1,118.9– 1,407.0 1,480.3 (1,058.9– 1,624.8 (1,241.5– 0.0554
(kcal/d)e (928.4–1,762.3) 1,848.6) 1,873.7) 1,883.8) (994.8–1,944.7) 1,964.0) 1,958.2)
FRSe 6 (3–12) 9 (6–15) 11 (7–19) 14 (8–22) 16 (9–30) 19 (13–32) 20 (12–36) <0.0001
FRS <5% (%) 50.6 33.9 27.1 25.6 24.8 17.7 18.9 <0.0001
FRS 5–10% (%) 23.6 27.0 25.4 20.9 18.3 11.3 8.1
FRS >10% (%) 25.8 39.1 47.5 53.5 56.9 71.0 73.0

Abbreviations: ALT, alanine aminotransferase; ASCVD, atherosclerotic cardiovascular disease; AST, aspartate aminotransferase; BP, blood pressure; CRS, cohort risk score; FRS,
Framingham risk score; GGT, gamma-glutamyl transferase; HDL-C, high-density lipoprotein-cholesterol; HEPA, health-enhancing physical activity; hsCRP, high sensitivity C-reactive pro-
tein; HOMA-IR, homeostasis model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure.
a≥20 g of ethanol per day; b≥college graduate; cBMI ≥ 25 kg/m2. Data are expressed as dmean (SD), emedian (interquartile range), or percentage.

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 Table 2.  Baseline characteristics according to DBP category

P for
Characteristics DBP <60 DBP 60–69 DBP 70–79 DBP 80–89 DBP 90–99 DBP ≥100 trend

Number (%) 235 (2.7) 1,747 (20.7) 3,323 (39.4) 2,473 (29.3) 536 (6.3) 104 (1.2)
Age (years) 49.3 (13.4) 52.0 (12.0) 52.0 (10.4) 50.2 (9.6) 48.8 (8.9) 46.5 (9.4) <0.0001
Male (%) 25.5 52.7 68.3 76.7 79.3 85.6 <0.0001
Current smoker (%) 14.4 25.0 25.0 24.8 24.4 37.4 0.0515
Alcohol intake (%)a 11.5 29.3 35.2 41.2 41.9 61.9 <0.0001
HEPA (%) 18.3 21.0 22.8 22.3 19.9 25.7 0.3782
High education level (%)b 58.4 56.6 60.4 65.0 69.0 74.0 <0.0001
Diabetes (%) 30.6 32.3 31.9 29.3 31.2 26.0 0.0574
Family history of CVD (%) 16.6 20.1 20.9 20.9 22.4 19.2 0.1739
Obesity (%)c 34.0 42.7 50.2 56.1 58.8 61.5 <0.0001
Body mass index (kg/m2) 23.6 (3.6) 24.7 (3.4) 25.3 (3.2) 25.7 (3.4) 26.0 (3.4) 26.5 (3.8) <0.0001
Systolic BP (mm Hg)d 96.9 (9.1) 107.8 (9.6) 116.2 (8.7) 125.4 (8.2) 136.0 (8.9) 151.4 (14.1) <0.0001
Diastolic BP (mm Hg)d 56.1 (2.8) 65.2 (2.9) 74.3 (2.9) 83.4 (2.8) 92.9 (2.7) 106.3 (7.8) <0.0001
Total cholesterol (mg/dl)d 182.6 (33.3) 189.5 (35.5) 192.7 (36.2) 197.4 (35.0) 201.9 (33.7) 208.8 (35.2) <0.0001
LDL-C (mg/dl)d 110.3 (29.1) 118.3 (32.5) 120.7 (33.0) 123.9 (32.5) 127.3 (31.3) 132.6 (34.1) <0.0001
HDL-C (mg/dl)d 58.6 (14.3) 54.4 (14.4) 53.4 (14.0) 53.0 (14.0) 52.8 (13.7) 53.1 (13.6) <0.0001
Glucose (mg/dl)d 99.9 (23.4) 104.1 (22.1) 105.7 (21.6) 107.7 (24.7) 111.5 (27.0) 112.6 (31.3) <0.0001
Uric acid (mg/dl)d 4.9 (1.3) 5.4 (1.4) 5.6 (1.5) 5.8 (1.5) 5.9 (1.5) 6.1 (1.6) <0.0001
Triglycerides (mg/dl)e 86 (66–124) 107 (76–153) 118 (84–167) 127 (89–185) 137 (97–196) 147 (110–197) <0.0001
AST (U/l)e 21 (17–26) 22 (19–28) 23 (19–30) 24 (19–30) 24 (19–31) 23 (19–30) <0.0001
ALT (U/l)e 19 (13–27) 22 (16–31) 24 (17–36) 25 (18–37) 27 (19–39) 27 (19–39) <0.0001
GGT (U/l)e 19 (13–30) 25 (17–45) 31 (19–51) 35 (22–60) 39 (24–72) 51 (31–73) <0.0001
HOMA-IRe 1.20 (0.79–2.03) 1.46 (0.91–1.20) 1.59 (1.03–2.49) 1.70 (1.10–2.60) 1.91 (1.24–2.96) 2.08 (1.27–3.11) <0.0001
hsCRP (mg/l)e 0.4 (0.2–0.9) 0.5 (0.3–1.2) 0.6 (0.3–1.3) 0.6 (0.4–1.3) 0.7 (0.4–1.5) 0.8 (0.4–1.9) <0.0001
Total energy intake (kcal/d)e 1,310.5 1,395.7 1,475.3 (1,056.1– 1,487.0 (1,115.7– 1,529.6 (1,102.3– 1,573.2 (1,058.9– <0.0001
(844.4–1,629.4) (949.9–1,767.3) 1,856.3) 1,879.3) 1,889.0) 1,916.6)
FRSe 3 (1–7) 7 (4–14) 10 (6–17) 11 (7–18) 13 (8–21) 14 (9–27) <0.0001
FRS <5% (%) 68.1 47.3 34.3 25.3 21.6 20.2 <0.0001
FRS 5–10% (%) 17.0 22.7 25.1 25.6 25.0 19.2
FRS >10% (%) 14.9 30.1 40.6 49.2 53.4 60.6

Abbreviations: ALT, alanine aminotransferase; ASCVD, atherosclerotic cardiovascular disease; AST, aspartate aminotransferase; BP, blood pressure; CRS, cohort risk score; FRS,
Framingham risk score; GGT, gamma-glutamyl transferase; HDL-C, high-density lipoprotein-cholesterol; HEPA, health-enhancing physical activity; hsCRP, high sensitivity C-reactive pro-
tein; HOMA-IR, homeostasis model assessment of insulin resistance; LDL-C, low-density lipoprotein cholesterol; SBP, systolic blood pressure.

American Journal of Hypertension  32(9)  September 2019  837

Target BP and Risk of CVD

a≥20 g of ethanol per day; b≥college graduate; cBMI ≥ 25 kg/m2. Data are expressed as dmean (standard deviation), emedian (interquartile range), or percentage.

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Kwon et al.

Table 3.  Development of cardiovascular disease by SBP category

Multivariable-adjusted HRa (95% CI)

Incident Incidence density Age–sex-adjusted HR
BP categories Person-years cases (per 10,000 person-years) (95% CI) Model 1 Model 2

Cardiovascular disease
  SBP <110 7,550.6 30 39.7 0.84 (0.54–1.32) 0.84 (0.53–1.32) 0.83 (0.53–1.30)
  SBP 110–119 9,900.3 51 51.5 1.00 (reference) 1.00 (reference) 1.00 (reference)
  SBP 120–129 9,350.5 67 71.7 1.33 (0.92–1.92) 1.35 (0.93–1.95) 1.31 (0.91–1.89)
  SBP 130–139 4,429.5 30 67.7 1.21 (0.77–1.91) 1.22 (0.77–1.92) 1.18 (0.74–1.87)
  SBP 140–149 1,355.1 13 95.9 1.47 (0.80–2.71) 1.54 (0.83–2.86) 1.46 (0.79–2.72)
  SBP 150–159 256.9 5 194.6 3.47 (1.39–8.71) 3.42 (1.35–8.68) 3.19 (1.25–8.12)
  SBP ≥160 132.7 4 301.5 5.97 (2.16–16.52) 5.93 (2.13–16.54) 5.60 (2.00–15.70)
  P for trend 0.0010 0.0013 0.0031

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Ischemic heart disease
  SBP <110 7,561.3 25 33.1 1.00 (0.60–1.67) 1.02 (0.61–1.71) 0.99 (0.59–1.66)
  SBP 110–119 9,931.2 36 36.2 1.00 (reference) 1.00 (reference) 1.00 (reference)
  SBP 120–129 9,391.3 43 45.8 1.21 (0.78–1.89) 1.20 (0.77–1.87) 1.17 (0.74–1.83)
  SBP 130–139 4,443.2 23 51.8 1.32 (0.78–2.23) 1.27 (0.76–2.19) 1.28 (0.75–2.18)
  SBP 140–149 1,358.5 11 81.0 1.75 (0.89–3.46) 1.79 (0.90–3.56) 1.69 (0.85–3.38)
  SBP 150–159 262.9 2 76.1 1.93 (0.46–8.00) 1.67 (0.40–7.02) 1.61 (0.38–6.76)
  SBP ≥160 142.3 2 140.6 3.65 (0.88–15.19) 3.77 (0.90–15.77) 3.65 (0.87–15.39)
  P for trend 0.3619 0.4004 0.4691
Stroke or TIA
  SBP <110 7,588.1 7 9.2 0.62 (0.25–1.51) 0.58 (0.23–1.41) 0.59 (0.24–1.46)
  SBP 110–119 9,976.4 16 16.0 1.00 (reference) 1.00 (reference) 1.00 (reference)
  SBP 120–129 9,439.9 24 25.4 1.51 (0.80–2.84) 1.58 (0.83–3.00) 1.54 (0.81–2.92)
  SBP 130–139 4,458.4 8 17.9 1.02 (0.44–2.38) 1.08 (0.45–2.54) 1.02 (0.43–2.42)
  SBP 140–149 1,388.4 2 14.4 0.70 (0.16–3.06) 0.77 (0.18–3.39) 0.72 (0.16–3.19)
  SBP 150–159 262.5 3 114.3 6.49 (1.89–22.29) 7.61 (2.17–26.77) 5.94 (1.66–21.26)
  SBP ≥160 139.1 2 143.7 9.00 (2.07–39.20) 8.02 (1.78–36.15) 7.72 (1.70–35.08)
  P for trend 0.0013 0.0011 0.0038

Abbreviations: BP, blood pressure; CI, confidence interval; DBP, diastolic blood pressure; HR, hazard ratio; SBP, systolic blood pressure.
aEstimated from Cox proportional hazard model. Multivariable model 1 was adjusted for age, sex, center, year of screening examination, body
mass index, smoking status, alcohol intake, physical activity, educational level, total calorie intake, and history of diabetes; model 2: model 1
plus adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, and glucose.

hypertension. A recent randomized clinical trial relevant to
the issue of target BP is SPRINT. It compared 2 different SBP
targets (<140 or <120 mm Hg) in more than 9,000 patients
aged at least 50 years with increased cardiovascular risk, ex-
cluding patients with diabetes or previous stroke.1 In this
trial, intensive treatment (achieved SBP 121 vs. 136 mm Hg)
was associated with a 25% reduction in major CVD events
and a 27% reduction in all-cause mortality.1 These results of
SPRINT provide substantial evidence to the benefit of inten-
sive BP-lowering treatment strategies in higher-risk patients.
However, SPRINT did not clarify the optimal BP target be-
cause its office BP measurement was made with automated
measurement system, which had not been used in any pre-
vious studies that provided evidence for the treatment of
hypertension.18 This is because unattended automated office
BP measurement can result in lower BP values compared
to conventional BP measurement due to the absence of
white-coat effect.19 Therefore, it was difficult to interpret the
lower safety limit of SBP 120 mm Hg with SPRINT data. One
large meta-analysis has reported that more vs. less intense BP
lowering can reduce not only stroke and coronary events but
also cardiovascular mortality in all SBP target ranges (149–
140, 139–130, and <130  mm Hg).4 Another meta-analysis
by Ettehad et  al.5 has shown that every 10  mm Hg reduc-
tion in SBP can significantly reduce the risk of major CVD
events and all-cause mortality across various baseline SBP
levels. Furthermore, a benefit of 10  mm Hg reduction was
also consistent in patients with baseline SBP < 130 mm Hg,
thereby achieving SBP < 120 mm Hg.5 However, there were
fewer patients in this subgroup. Results of this group might

838  American Journal of Hypertension  32(9)  September 2019

 Target BP and Risk of CVD

Table 4.  Development of cardiovascular disease by DBP category

Multivariable-adjusted HRa (95% CI)

Incident Incidence density Age-Sex adjusted HR
BP categories Person-years cases (per 10,000 person-years) (95% CI) Model 1 Model 2

Cardiovascular disease
  DBP <60 860.4 2 23.2 0.50 (0.12–2.06) 0.50 (0.12–2.06) 0.51 (0.12–2.14)
  DBP 60–69 6,617.9 38 57.4 1.00 (reference) 1.00 (reference) 1.00 (reference)
  DBP 70–79 12,820.0 78 60.8 1.12 (0.76–1.65) 1.13 (0.77–1.68) 1.13 (0.76–1.67)
  DBP 80–89 10,057.3 63 62.6 1.27 (0.84–1.91) 1.29 (0.85–1.96) 1.26 (0.83–1.92)
  DBP 90–99 2,188.3 16 73.1 1.65 (0.91–2.98) 1.70 (0.93–3.09) 1.62 (0.89–2.97)
  DBP ≥100 431.8 3 69.5 1.78 (0.55–5.81) 1.78 (0.54–5.85) 1.68 (0.51–5.55)
  P for trend 0.4047 0.3789 0.5009
Ischemic heart disease

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  DBP <60 863.5 1 11.6 0.30 (0.04–2.22) 1.30 (0.04–2.23) 0.31 (0.04–2.27)
  DBP 60–69 6,625.1 32 48.3 1.00 (reference) 1.00 (reference) 1.00 (reference)
  DBP 70–79 12,869.1 54 42.0 0.90 (0.58–1.40) 0.91 (0.59–1.42) 0.93 (0.59–1.44)
  DBP 80–89 10,085.5 46 45.6 1.07 (0.67–1.69) 1.06 (0.67–1.70) 1.06 (0.66–1.70)
  DBP 90–99 2,206.1 8 36.3 0.93 (0.43–2.05) 0.93 (0.42–2.04) 0.91 (0.41–2.03)
  DBP ≥100 441.4 1 22.7 0.64 (0.09–4.67) 0.65 (0.09–4.83) 0.65 (0.09–4.81)
  P for trend 0.8107 0.8329 0.8500
Stroke or TIA
  DBP <60 863.4 1 16.6 0.99 (0.13–7.89) 0.99 (0.12–7.91) 1.07 (0.13–8.56)
  DBP 60–69 666.2 9 13.5 1.00 (reference) 1.00 (reference) 1.00 (reference)
  DBP 70–79 12,921.7 25 19.3 1.56 (0.73–3.36) 1.57 (0.73–3.39) 1.52 (0.71–3.29)
  DBP 80–89 10,155.9 17 16.7 1.53 (0.67–3.47) 1.62 (0.70–3.72) 1.51 (0.65–3.48)
  DBP 90–99 2,213.3 8 36.1 3.70 (1.40–9.79) 3.98 (1.49–10.66) 3.55 (1.32–9.57)
  DBP ≥100 436.6 2 45.8 5.48 (1.16–25.85) 4.94 (1.04–23.5) 4.02 (0.84–19.27)
  P for trend 0.0681 0.0666 0.1426

Abbreviations: BP, blood pressure; CI, confidence interval; DBP, diastolic blood pressure; HR, hazard ratio; SBP, systolic blood pressure.
aEstimated from Cox proportional hazard model. Multivariable model 1 was adjusted for age, sex, center, year of screening examination, body

mass index, smoking status, alcohol intake, physical activity, educational level, total calorie intake, and history of diabetes; model 2: model 1
plus adjustment for low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, and glucose.

have been influenced by the unusually low BP values in the
SPRINT trial. In addition, post-hoc analysis of large Ongoing
Telmisartan Alone and in Combination with Ramipril
Global Endpoint and Telmisartan Randomized Assessment
Study in ACE Intolerant Subjects with Cardiovascular
Disease trials suggests that reduction of SBP to <120 mm Hg
or DBP to <70 mm Hg is associated with an increase in car-
diovascular death and all-cause death events without reduc-
tion in myocardial infarction or stroke.6 In this analysis for
high-risk patients, a target BP of 120–130  mm Hg systolic
and 70–80  mm Hg diastolic is associated with the lowest
rate of CVD events.6 Like this, no evidence was found that
below 120/70 mm Hg would have an incremental protection
for hypertensive patients. However, these results came from
high-risk patients. In low-risk hypertensive patients, evi-
dence on optimal target BP is insufficient.
Treatment of hypertensive patients with low risk has
been systematically understudied because lower-risk
groups would require prolonged follow-up to have a suffi-
cient number of clinical events to provide useful informa-
tion.2 The present cohort analyzed low-risk hypertensive
patients characterized by middle-age and highly educated
with antihypertensive medications but without previous
CVD. Although <50% of patients treated for hypertension
achieved a target office SBP <140 mm Hg,20,21 surprisingly,
more than 90% of participants had office BP <140/90  mm
Hg in this cohort. Moreover, >50% of participants achieved
office SBP <120 mm Hg and about 25% achieved office DBP
<70 mm Hg. In this cohort, a large number of participants
were categorized into groups of <120/70  mm Hg. It might
be explained that environment of health check-up place was
very calm and comfortable, and participants changed with
patient’s gown. So, it might reduce white-coat effect of office
BP in out-patient clinic. However, our study populations are
relatively young, highly educated, and high socioeconomic
group, suggesting good adherence of medical follow-up.

American Journal of Hypertension  32(9)  September 2019  839

Kwon et al.
So, we convince that our study populations are treated and
controlled hypertensive group. Actually, there was no in-
crease of CVD in patients with <120/70 mm Hg compared
to that in those ≥120/70 mm Hg in our study. Although fol-
low-up duration of this cohort was not prolonged (mean fol-
low-up duration of 3.9 years), our results provided evidence
for optimal BP target of treatment in low-risk hypertensive
patients. Our results support previous evidence that treat-
ment will interrupt the progressive course of hypertension.22
Considering that long-term exposure to elevated BP is as-
sociated with increased BP due to aging and a high lifetime
risk,23–25 our results may provide an evidence for the benefit
of BP control earlier in life. At present, a nationwide cohort
study was conducted in Korea to determine the association
of BP categories before age 40 years with risk of CVD later in
life. In this analysis, patients with stage 1 hypertension (SBP,
130–139  mm Hg and/or DBP, 80–89  mm Hg) not taking
antihypertensive medications had higher risk of CVD. On
the other hand, those who were prescribed antihypertensives
did not have increased CVD risk compared to their respec-
tive normal BP group.26 Results of that study suggest that
early BP treatment of stage 1 hypertension among young
adults may be associated with reduced CVD risk. Thus, strict
BP control may provide incremental protection of CVD
events in low-risk patients, like our results. However, future
prospective studies are needed to validate these findings.
At present, a longitudinal cohort study from England has
shown no evidence that antihypertensive treatment is associ-
ated with reduced mortality or rates of CVD among low-risk
patients with mild hypertension. It reported that treatment
was associated with an increased risk of adverse events, in-
cluding hypotension, syncope, electrolyte abnormalities, and
acute kidney injury.27 These adverse events are important
concerns. Thus, future study is needed to evaluate the weight
of adverse events related to lowering BP against the benefit
with respect to CVD events in intensive BP treatment.
Limitations
First, as with most previous studies, the determination
of BP was based on a single-day measurement instead of 24
hours ambulatory BP, although 3 readings were taken. This
approach might lead to misclassification of BP categories
and introduce dilution bias, possibly underestimating true
associations. Second, we did not incorporate duration of hy-
pertension, and changes in BP categories or other covariates
during follow-up. Third, health behaviors were assessed
via a self-administered structured questionnaire used in
health checkup programs in Korea as part of the NHI
plan.9 Measurement errors in these variables may intro-
duce some degree of residual confounding, similar to most
epidemiologic studies. Fourth, we did not evaluate total
number, doses or side effects of antihypertensive medications
and adherence to medication. Fifth, we had only baseline BP,
but not follow-up BP data. Thus, we evaluated the longitu-
dinal effect of baseline BP levels but could not evaluate the
effect of follow-up BP. Finally, our study was resulted from
single-center cohort, and the study population was relatively
highly educated, middle-aged Korean adults with high acces-
sibility to health care resources. Thus, further study should
840  American Journal of Hypertension  32(9)  September 2019
be needed including other ethnic groups or populations with
different demographics. Despite these limitations, results of
our study may have clinical significance because this study
also has strengths, including a large sample size, the use of
carefully standardized clinical procedures, and almost com-
plete follow-up for CVD events as NHI collects all medical
services utilization covering the entire Korean population.
In conclusion, among treated hypertensive Korean mid-
dle-aged patients at low CVD risk, SBP <120 mm Hg or DBP
<70 mm Hg were associated with a trend of decreased CVD
events compared to those with higher BP categories (SBP
≥120 mm Hg or DBP ≥70 mm Hg). Our study suggests that
strict BP control under optimal BP category may be required
to prevent adverse CVD outcomes in low-risk hypertensive
patients.
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SUPPLEMENTARY DATA
Supplementary data are available at American Journal of
Hypertension online.
ACKNOWLEDGMENT
We thank the efforts of the health screening group at
Kangbuk Samsung Hospital, Seoul, Korea.
DISCLOSURE
The authors have no conflicts of interest to disclose.
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