Left Ventricular Hypertrophy

Angiology
2020, Vol. 71(1) 70-76
Development of Electrocardiographic ª The Author(s) 2019
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Left Ventricular Hypertrophy and Resting DOI: 10.1177/0003319719870950
journals.sagepub.com/home/ang
Heart Rate Over Time: Findings
From the OGHMA Study

Taku Inoue, MD, PhD1,2 , Hisatomi Arima, MD, PhD2,

Yuriko Katsuimata, PhD3, Chiho Iseki, BS4, Kozen Kinjo, MD5,
and Kunitoshi Iseki, MD, PhD4

Abstract
Both elevated resting heart rate (HR) and electrocardiographic left ventricular hypertrophy (ECG-LVH) are signs of a poor
prognosis. Although elevated resting HR is a known risk factor for cardiovascular disease and target organ damage, the association
between resting HR and the development of ECG-LVH is unclear. In the present study, 6860 subjects (4203 men, 2657 women,
19-89 years of age) without ECG-LVH at baseline were evaluated and followed for a mean duration of 3.7+1.4 years. During the
follow-up period, 484 (7.1%) subjects developed ECG-LVH. Cox regression analysis revealed that each 10 beats/min increase in
resting HR was associated with a 22% reduction in the development of ECG-LVH (95% confidence interval: 12%-30%, P < .0001) in
men. While an increase in HR tended to be associated with the development of ECG-LVH in women, the relationship was not
significant. In contrast to the concept that an elevated resting HR is a cardiovascular risk factor, these findings revealed that resting
HR was negatively associated with the development of ECG-LVH in men.

Keywords
resting heart rate, left ventricular hypertrophy, electrocardiogram, cohort study

Introduction mortality, and all-cause mortality within a wide range of sub-

Electrocardiographic left ventricular hypertrophy (ECG-LVH)
is associated with a significantly increased risk of cardiovas-
cular (CV) morbidity, mortality, and all-cause mortality among
the general population, hypertensive patients, and older
adults.1-7 Cohort studies of general populations and older adults
indicate that regression of ECG-LVH is associated with a
reduced CV risk and vice versa.3,8 Moreover, the results of
intervention studies for hypertensive patients indicate that
ECG-LVH regression reduces the risk of CV morbidity and
mortality.9,10 The LIFE (Losartan Intervention for Endpoint
Reduction in Hypertension) study9 revealed that regression of
ECG-LVH during antihypertensive therapy is associated with
reduced CV morbidity and mortality independent of blood
pressure lowering and treatment modality in patients with
essential hypertension. The HOPE (Heart Outcomes Preven-
tion Evaluation) study10 also demonstrated that the prevention
and regression of ECG-LVH is independently associated with a
reduced risk of CV events, death, and congestive heart failure
in hypertensive or high-risk hypertensive patients without
known heart failure.
Epidemiologic studies have consistently demonstrated
that resting heart rate (HR) is a predictor of CV morbidity,
jects.11,12 The clinical significance of resting HR relates to its
association with cardiometabolic risk accumulation11,13 and
target organ damage,14-17 which predispose to CV events.
Moreover, elevated on-treatment HR predicts a greater like-
lihood of subsequent all-cause and CV mortality, independent
of therapeutic drugs, blood pressure, and ECG-LVH regression
in hypertensive patients with ECG-LVH.18 These findings sup-
port the value of serial assessment of resting HR for improved
risk stratification.
Despite their role in CV risk, the association between resting
HR and ECG-LVH and/or newly diagnosed ECG-LVH has not
1
Cardiovascular Medicine, Nambu Hospital, Okinawa, Japan
2
Department of Preventive Medicine and Public Health, Fukuoka University,
Fukuoka, Japan
3
Department of Biostatistics, University of Kentucky, KY, USA
4
Okinawa Heart and Renal Association, Okinawa, Japan
5
Okinawa Health Promotion Foundation, Okinawa, Japan
Corresponding Author:
Taku Inoue, Cardiovascular Medicine, Nambu Hospital, 870 Maezato, Itoman
City, Okinawa, Japan.
Email: imtak-ryk@umin.ac.jp
Inoue et al
been analyzed. The present study evaluated the association
between resting HR and the development of ECG-LVH
over time.
Methods
Study Population and Data Collection
This was a retrospective cohort study based on the large
database of the OGHMA (Okinawa General Health Mainte-
nance Association), which is one of the largest health-care
screening centers in Okinawa, Japan. The subjects were parti-
cipants in a 1-day health evaluation program. This program
provides thorough anthropometric measurements, physical
examinations, laboratory tests, and electrocardiograms for
individuals, and health maintenance programs for companies
and public organizations.13 The population of this study was
recruited from among subjects who participated in this program
from April 1997 to March 2003.
Trained nurses measured systolic and diastolic blood
pressure twice using a standard sphygmomanometer with
an appropriately sized cuff after the subject sat quietly for
15 minutes. The lower of the 2 blood pressure values was
used in the analysis. Height and weight were recorded with
the participants wearing light clothes and no shoes. Body
mass index (BMI) was calculated as body weight (kg)
divided by the square of the height (m2). Current smoking
indicated those who currently have a smoking habit. Hyper-
tension was defined as systolic blood pressure 140 mm Hg
and/or diastolic blood pressure 90 mm Hg and/or blood
pressure-lowering drug use. Diabetes was defined as gly-
cated hemoglobin (HbA1c) values 6.5% (Japan Diabetes
Society [JDS]), fasting serum glucose 126 mg/dL
(6.9 mmol/L), or glucose-lowering drug use. Dyslipidemia
was defined as high-density lipoprotein cholesterol 40 mg/dL
(1.0 mmol/L), triglyceride 150 mg/dL (1.7 mmol/L), low-
density lipoprotein cholesterol 100 mg/dL (2.6 mmol/L) or
lipid-lowering drug use. Blood samples were obtained after
overnight fasting. Total cholesterol and triglyceride values
were measured using an enzymatic method, and high-density
lipoprotein cholesterol values were measured using a direct
method. Low-density lipoprotein cholesterol values were cal-
culated using the Friedewald equation.19 The HbA1c values
were measured using a latex coagulating method (HITACHI,
Tokyo, Japan). The HbA1c unit was converted from HbA1c
(JDS) to HbA1c (National Glycohemoglobin Standardization
Program [NGSP]) using the following equation: NGSP (%)
¼ 1.02  JDS (%) þ 0.25%.20
Electrocardiograms were recorded at each visit after the
subjects had been in the supine position for 2 minutes.
Using these data, we calculated the Sokolow-Lyon voltage
and resting HR. The endpoint of this analysis was the
development of ECG-LVH, which was defined as a
Sokolow-Lyon voltage (SV1 þ RV5/6) > 38 mm.21 Heart
rate was calculated from the mean RR interval of the
electrocardiogram.
71
Statistical Methods and Ethics
Baseline characteristics were classified into 4 HR levels as
mean (standard deviation [SD]) or median (interquartile range)
for continuous variables and number (proportion) for catego-
rical variables. The baseline characteristics among HR levels
were compared using the Kruskal-Wallis test or w2 test. To
analyze the effect of the resting HR, a time-varying variable,
on the development of ECG-LVH, we used a time-dependent
Cox proportional hazards model. In the multivariable adjusted
model, we adjusted for age, BMI, systolic blood pressure,
hemoglobin, HbA1c, low-density lipoprotein cholesterol, his-
tory of heart disease, and current smoking status. Hazard ratios
for developing ECG-LVH were calculated for subjects with the
lowest HR level as the reference. In addition, hazard ratios for
developing ECG-LVH with an HR change as a continuous
variable were estimated per 10 beats/min (bpm) increase.
Heart rate was considered as a time-dependent variable. To
analyze the effect of the resting HR on the development of
ECG-LVH, we used a time-dependent Cox proportional
hazards model. To elucidate the association between the base-
line Sokolow-Lyon voltage and the development of ECG-LV,
subjects were divided into 4 equal number groups based on the
sex-specific baseline Sokolow-Lyon voltage. We evaluated the
association between baseline Sokolow-Lyon voltage and inci-
dence of ECG-LVH over time and its future change. All anal-
yses were performed using SAS version 9.3 (SAS Institute,
Cary, North Carolina). All statistical tests were 2-sided, and
P <.05 was considered significant.
The present study was conducted in accordance with the
principles defined by the Declaration of Helsinki in 1975 and
revised in 1993. Data for this study were obtained from the
Okinawa General Health Maintenance Association upon
approval by their ethics committee. The subjects’ private infor-
mation was excluded from the original registry database. The
authors had full access to the data and took responsibility for its
integrity. All authors have read and agreed with the manuscript
as written.
Results
Of the 9706 subjects who participated in the health evaluation
program in 1997, 208 subjects without baseline ECG data,
1095 subjects with ECG-LVH at baseline, and 1751 subjects
without follow-up assessment were excluded from the study. A
total of 6860 subjects (4203 men, 2657 women, with a mean
age of 48.7 [SD: 9.8] years) were followed for a mean duration
of 3.7 (SD: 1.4) years. Clinical and demographic characteristics
of patients in relation to HR categories are shown in Table 1.
Subjects with a higher baseline resting HR were older, and men
were more likely to have elevated levels of cardiometabolic
risk factors. The Sokolow-Lyon voltage was negatively asso-
ciated with resting HR only in men. An HR-cardiometabolic
risk association was also found in women. Unlike in men,
resting HR was not associated with age or the Sokolow-Lyon
voltage in women. During the follow-up period, 484 subjects
72 Angiology 71(1)

Table 1. Clinical and Demographic Characteristics of 6860 Subjects Participating in a 1-Day Health Evaluation Program Held By Okinawa
General Health Maintenance Association According to Baseline Heart Rate Category.a

<60 bpm 60-64 bpm 65-69 bpm 70 bpm

Men n ¼ 1115 n ¼ 945 n ¼ 839 n ¼ 1304 P Value

Age, years 47.0 (9.7) 47.5 (10.0) 48.1 (9.2) 48.4 (9.8) .001
Body mass index, kg/m2 24.4 (2.8) 24.7 (2.8) 24.8 (3.0) 25.0 (3.2) <.0001
Systolic blood pressure, mm Hg 119 (15) 122 (16) 123 (15) 126 (17) <.0001
Diastolic blood pressure, mm Hg 74 (10) 76 (10) 78 (11) 79 (11) <.0001
Triglyceride, mmol/L 1.4 (1.0-2.0) 1.5 (1.1-2.2) 1.6 (1.1-2.2) 1.7 (1.2-2.5) <.0001
Total cholesterol, mmol/L 5.2 (0.9) 5.4 (0.9) 5.4 (1.0) 5.4 (0.9) <.0001
HDL cholesterol, mmol/L 1.4 (0.3) 1.3 (0.3) 1.3 (0.3) 1.3 (0.3) .001
LDL cholesterol, mmol/L 3.1 (0.7) 3.2 (0.8) 3.2 (0.8) 3.2 (0.8) .005
Serum blood glucose, mmol/L 5.6 (1.0) 5.8 (1.1) 5.8 (1.1) 6.1 (1.6) <.0001
HbA1c, % 5.3 (0.6) 5.3 (0.7) 5.4 (0.7) 5.5 (1.0) <.0001
Hemoglobin, g/L 152.8 (9.4) 154.5 (10.2) 154.4 (9.7) 156.0 (110.9) <.0001
Sokolow-Lyon voltage, mV 2.85 (0.53) 2.81 (0.55) 2.78 (0.54) 2.74 (0.57) <.0001
Hypertension 194 (17%) 217 (23%) 211 (25%) 409 (31%) <.0001
Diabetes 57 (5%) 65 (7%) 69 (8%) 153 (12%) <.0001
Dyslipidemia 614 (55%) 596 (63%) 515 (61%) 892 (68%) <.0001
History of heart disease 14 (1%) 23 (2%) 17 (2%) 24 (2%) .254
Current smoking 470 (42%) 403 (43%) 328 (39%) 564 (43%) .268
Blood pressure-lowering medication 75 (7%) 80 (8%) 65 (7%) 145 (11%) .00004
Glucose-lowering medication 15 (1%) 18 (2%) 16 (2%) 41 (3%) .017
Lipid-lowering medication 7 (1%) 6 (1%) 8 (1%) 18 (1%) .180

Women n ¼ 540 n ¼ 606 n ¼ 562 n ¼ 949 P Value

Age, years 49.9 (9.6) 50.2 (9.5) 50.5 (9.9) 50.3 (9.7) .971
Body mass index, kg/m2 23.2 (3) 23.5 (3.4) 23.3 (3) 23.7 (3.4) .050
Systolic blood pressure, mm Hg 114 (18) 116 (17) 118 (18) 122 (18) <.0001
Diastolic blood pressure, mm Hg 69 (11) 71 (10) 71 (10) 74 (11) <.0001
Triglyceride, mmol/L 0.9 (0.7-1.4) 1.0 (0.7-1.4) 1.0 (0.7-1.4) 1.0 (0.7-1.5) .005
Total cholesterol, mmol/L 5.4 (0.9) 5.5 (1.0) 5.4 (0.9) 5.5 (0.9) .037
HDL cholesterol, mmol/L 1.6 (0.4) 1.6 (0.4) 1.6 (0.4) 1.6 (0.4) .254
LDL cholesterol, mmol/L 3.2 (0.9) 3.3 (0.9) 3.3 (0.8) 3.3 (0.8) .272
Serum blood glucose, mmol/L 5.3 (0.7) 5.4 (0.8) 5.4 (0.7) 5.6 (1.0) <.0001
HbA1c, % 5.2 (0.5) 5.2 (0.6) 5.2 (0.6) 5.3 (0.7) <.0001
Hemoglobin, g/L 130 (12) 131 (12) 131 (12) 131 (14) .034
Sokolow-Lyon voltage, mV 2.54 (0.57) 2.55 (0.59) 2.55 (0.57) 2.57 (0.58) .891
Hypertension 80 (15%) 85 (14%) 102 (24%) 224 (24%) <.0001
Diabetes 15 (3%) 14 (2%) 16 (3%) 44 (5%) .049
Dyslipidemia 204 (38%) 250 (41%) 273 (42%) 433 (46%) .02879
History of heart disease 11 (2%) 5 (1%) 4 (1%) 17 (2%) .109
Current smoking 38 (7%) 29 (5%) 21 (4%) 39 (4%) .040
Blood pressure-lowering medication 51 (9%) 37 (6%) 46 (8%) 111 (12%) .002
Glucose-lowering medication 6 (1%) 4 (1%) 6 (1%) 11 (1%) .858
Lipid-lowering medication 3 (1%) 1 (0%) 7 (1%) 10 (1%) .1257
Abbreviations: HbA1c, glycated hemoglobin; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol.
a
Data are presented as mean (standard deviation) or median (interquartile range) for continuous variables and number (proportion) for categorical variables.

(352 men, 132 women) developed ECG-LVH. The incidence
of ECG-LVH in each HR category was from 1.8% to 2.1% in
men and from 0.9% to 1.4% in women. The incidence of ECG-
LVH in men was 1.5 to 2 times higher than that in women. A
nonadjusted Cox regression analysis revealed that the risk of
developing ECG-LVH was approximately 30% lower in men
with a resting HR of 70 bpm or more than in subjects with a
resting HR <60 bpm (hazard ratio: 0.71, 95% confidence inter-
val [CI]: 0.54-0.93; P ¼ .013; Table 2). In addition, every
10 bpm increase in resting HR was associated with a reduced
risk of developing ECG-LVH (hazard ratio: 0.88, 95% CI:
0.79-0.98; P ¼ .021; Table 2). This negative association
between resting HR and the development of ECG-LVH
remained significant in the multivariable adjusted model.
Every 10-bpm resting HR increase was associated with a
22% reduction in the risk of developing ECG-LVH. In women,
the association between HR and the development of ECG-LVH
was not significant (multivariable-adjusted hazard ratio: 0.85,
Inoue et al 73

Table 2. Time-Dependent. Time-Dependent Cox Regression Analyses to Assess the Predictive Value of Heart Rate for the Developing
Electrocardiographic Left Ventricular Hypertrophy.a

Crude Multivariable Adjustedb

Variables Hazard Ratio 95% Confidence Interval P Hazard Ratio 95% Confidence Interval P

Men
<60 bpm 1.00 Reference 1.00 Reference
60-64 bpm 0.72 0.53-0.96 .027 0.70 0.52-0.95 .021
65-69 bpm 0.82 0.61-1.10 .109 0.76 0.56-1.03 .079
70 bpm 0.71 0.54-0.93 .013 0.56 0.42-0.75 <.0001
P for trend .003 .0003
Every 10 bpm increase 0.88 0.79-0.98 .021 0.78 0.70-0.88 <.0001
Women
<60 bpm 1.00 Reference 1.00 Reference
60-64 bpm 0.69 0.41-1.14 .1503 0.68 0.40-1.13 .128
65-69 bpm 0.43 0.24-0.78 .005 0.36 0.20-0.67 .001
70 bpm 0.94 0.62-1.44 .775 0.74 0.48-1.15 .182
P for trend .854 .197
Every 10 bpm increase 0.96 0.80-1.14 .104 0.85 0.71-1.01 .072
a
Sex specific hazard ratios were calculated for both crude and multivariable adjusted models and heart rate change was evaluated for both categorical change and
every 10 beats/min (bpm) increase.
b
Adjusted for age, body mass index, systolic blood pressure, hemoglobin, HbA1c, low lipoprotein cholesterol, history of heart disease, and current smoking status.

Table 3. Incidence. Incidence of Developing Electrocardiographic Left Ventricular Hypertrophy and Sokolow-Lyon Voltage Change Over
Time Stratified By Quartile of Baseline Sokolow-Lyon Voltage.

Men Women

Sokolow-Lyon Voltage Events/Patient Sokolow-Lyon Voltage

Quartile of Baseline Change Over Time Year (Rate Per Change Over Time Events/Patient Year
Sokolow-Lyon Voltage (95% Confidence Interval) 1000 Patient Year) (95% Confidence Interval) (Rate Per 1000 Patient Year)

Q1 0.07 (0.04 to 0.10) 3/4693 (0.1%) 0.08 (0.04 to 0.11) 3/2929 (0.1%)
<2.4 mV for men
<2.2 mV for women
Q2 0.02 (0.01 to 0.05) 6/4858 (0.1%) 0.03 (0.00 to 0.07) 1/2912 (0.0%)
2.4-2.7 mV for men
2.2-2.4 mV for women
Q3 0.04 (0.07 to 0.01) 50/4526 (1.1%) 0.01 (0.05 to 0.02) 9/2943 (0.3%)
2.8-3.1 mV for men
2.5-2.9 mV for women
Q4 0.09 (0.12 to 0.06) 3/4112 (7.1%) 0.08 (0.11 to 0.04) 119/2641 (4.5%)
3.2 mV for men
3.0 mV for women
P for trend <.0001 <.0001 <.0001 <.0001

95% CI: 0.71-1.01; P ¼ .072; Table 2). The effects of HR on
the development of ECG-LVH did not clearly differ between
men and women even after adjusting for other confounders (P
heterogeneity ¼ .547).
Subjects were then quadrisected according to the baseline
Sokolow-Lyon voltage for subgroup analysis to elucidate the
association of the baseline Sokolow-Lyon voltage with the
development of ECG-LVH. Subjects with a lower baseline
Sokolow-Lyon voltage were likely to have a greater ECG vol-
tage change, and the incidence of ECG-LVH was significantly
higher in subjects with a higher baseline Sokolow-Lyon vol-
tage (Table 3). Evaluation of the association between the
baseline resting HR and the Sokolow-Lyon voltage change
revealed a weak but significant positive association (Figure 1).
Discussion
The findings of the present study revealed that subjects with
an elevated resting HR over time are less likely to develop
ECG-LVH. In other words, elevated resting HR is beneficial
for the suppression of ECG-LVH. To the best of our knowl-
edge, this is the first study demonstrating an association
between HR change over time and the development of
ECG-LVH.
74
Figure 1. Association between baseline resting heart rate and
Sokolow-Lyon voltage changes over time.
Resting HR as a CV Risk
Elevated resting HR is associated with all steps of the CV con-
tinuum,22,23 including cardiometabolic risk deterioration,11,13
target organ damage,14-17 and CV events and death.12,24 Not only
baseline resting HR but also in-treatment HR and/or HR change
worsen patients’ prognosis.18 According to studies evaluating
resting HR and target organ damage, elevated resting HR is
associated with higher frequencies of albuminuria,16 progression
to chronic kidney disease,15 accelerated arterial stiffness,14,25
and cognitive decline.26,27 On the basis of currently available
evidence, it is plausible that subjects with an elevated resting
HR would be more likely to develop ECG-LVH.
The results of the present study, however, demonstrated
that subjects with a lower resting HR were more likely to have
a higher baseline Sokolow-Lyon voltage and vice versa
(Table 1). Subjects with a higher baseline Sokolow-Lyon vol-
tage were more likely to develop ECG-LVH, but the change in
the Sokolow-Lyon voltage over time was significantly
smaller in subjects with a lower baseline Sokolow-Lyon vol-
tage (Table 3). Moreover, there was a weak but significant
association between baseline resting HR and ECG voltage
change during the follow-up period (Figure 1). Although sub-
jects with a lower baseline HR gain less Sokolow-Lyon vol-
tage over time, they have a higher baseline Sokolow-Lyon
voltage. Lower HR over time results in a greater risk of devel-
oping ECG-LVH (Table 2).
The association between HR-lowering and slow ECG-LVH
regression was suggested by the LIFE study.28 In this study,
patients treated with an atenolol-based antihypertensive strat-
egy had a lower Sokolow-Lyon voltage reduction than those
treated with a losartan-based antihypertensive strategy for any
Angiology 71(1)
level of change in systolic blood pressure. The greater
ECG-LVH reduction with losartan compared to atenolol-
based antihypertensive strategies in the setting of similar blood
pressure reductions suggests a potential antihypertrophic effect
of losartan, possibly mediated by direct blockade of the myo-
cardial effects of angiotensin II.29 In addition, b-adrenergic
blocking agent-derived HR-lowering might have an important
role in attenuating the Sokolow-Lyon voltage regression com-
pared to angiotensin receptor blocker-based antihypertensive
strategies. Considering these findings, lower HR and/or
HR-lowering and/or lower HR over time might be unfavorable
ECG-LVH regression in hypertensive patients. The results of
our study confirm the deleterious effects of a lower HR over
time on ECG-LVH progression.
The association found between resting HR and ECG-LVH
has also been suggested between resting HR and LV morphol-
ogy. Cross-sectional results elucidating the association
between resting HR and LV morphology demonstrated a neg-
ative association between resting HR and LV mass or chamber
size.30-35 This association was found in both hypertensive and
normotensive subjects and in any age-group. These findings
support our results.
Electrocardiographic left ventricular hypertrophy predicts
all-cause mortality and CV mortality independent of echocar-
diographic LV mass index and other CV risk factors.7,36 More-
over, ECG-LVH increases the risk of CV mortality even in
subjects without hypertension.5,37 On this basis, we should
recognize ECG-LVH as not a trivial ECG finding, but as an
electric risk marker for CV events independent of the classical
CV risk factors and LV morphology.
Clinical Implications
Our findings indicate that lower HR over time should be
considered as a potential risk factor for the development of
ECG-LVH in healthy subjects. In addition, the therapeutic strat-
egy must be reconsidered, especially for patients with hyperten-
sion, as antihypertensive drugs that lower HR might accelerate the
development of ECG-LVH. According to the results of a rando-
mized control trial, an HR lowering strategy, however, does not
worsen the patients’ prognosis in this spectrum of patients. The
Study Assessing the Morbidity–Mortality Benefits of the If Inhi-
bitor Ivabradine in Patients with Coronary Artery Disease
(SIGNIFY) study38 evaluated the prognostic significance of
HR-lowering using ivabradine in patients with stable coronary
artery disease, 90% of whom were hypertensive. Lowering HR
from 77 + 7 bpm at baseline to 61 + 9 bpm at the study end
during a mean follow-up of 27.8 months did not alter the prog-
nosis. Further studies are required to elucidate the clinical impli-
cations of lowering the HR in the development of ECG-LVH.
Study Limitations
This study has some limitations. First, the subjects of the
OGHMA database comprised a healthy population able to pay
the fee to participate in the screening program. Moreover, the
subjects were mainly employees of local companies and thus
Inoue et al
might not be representative of the general population. Second,
we did not have the information of the drugs prescribed for the
subjects who have HR-lowering effects, such as b-adrenergic
blockers and diltiazem. Lastly, this is a retrospective observa-
tional study with the inherent limitations and biases of such
studies. It is unclear whether the resting HR change over time
was the cause or the result of the development of ECG-LVH.
Most importantly, the clinical importance of ECG-LVH in a
healthy population like our cohort has not been established. A
prospective study for evaluating these issues is warranted.
Despite the same effect of HR on the development of
ECG-LVH among both sexes, the association between HR and
the development of ECG-LVH was not significant in women.
The smaller number of female subjects could be a reason for
the nonsignificant results in women.
Conclusions
In contrast to cardiometabolic risks, target organ damage, and
CV events, the risk of developing ECG-LVH in healthy men is
increased by lowering HR over time. The causal relationship
between HR change over time and the development of
ECG-LVH, however, remains to be determined.
Authors’ Note
This manuscript was presented orally on September 2, 2013 at
European Society of Cardiology 2013 Amsterdam, The Netherlands.
T.I. performed the study design and drafted the manuscript. H.A. and
Y.K. also performed the statistical analysis. C.I. and K.I. participated
in study design and data acquisition. K.K. participated in study
coordination. All authors read and approved the final manuscript.
Acknowledgments
The authors are grateful to the staff of the Okinawa General Health
Maintenance Association, and to Mr. M. Itokazu and Mr. K. Shiroma
for retrieving the data. The authors extend their sincere appreciation to
Mr. K. Nizato and Ms. K. Inoue for their dedicated assistance.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, author-
ship, and/or publication of this article.
ORCID iD
Taku Inoue https://orcid.org/0000-0002-2680-2509
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