ORIGINAL ARTICLE

Association Between Metabolic Syndrome and

Helicobacter pylori Infection Diagnosed by Histologic
Status and Serological Status
Dong Wook Shin, MD, MBA,* Hyuk Tae Kwon, MD, MPH,w Jung Min Kang, MD,*
Jin Ho Park, MD, MPH, PhD,*w Ho Chun Choi, MD,* Min Seon Park, MD, PhD,*
Sang Min Park, MD, MPH, PhD,* Ki Young Son, MD, MPH,*
and BeLong Cho, MD, MPH, PhD*w

Goals: We aimed to simultaneously evaluate the association between metabolic syndrome and Helicobacter pylori (HP) infection
diagnosed histologically and serologically in a large number of
healthy Korean adults.
Background: Serological positivity for HP does not necessarily indicate current infection. No study to date has compared the association between metabolic syndrome and HP infection diagnosed
by histologic and serological status.
Study: HP status was ascertained histologically and serologically in
healthy Korean adults who underwent comprehensive health
screening in a private health screening center in Korea. Metabolic
syndrome was dened according to the International Diabetes
Federation denition. Multivariate logistic analyses were performed, after adjusting for potential confounders, including age,
sex, smoking, alcohol consumption, and income level.
Results: A total of 5889 subjects were included in the analysis. The
metabolic syndrome was more strongly associated with histologic
positivity for HP [adjusted odds ratio (aOR) = 1.26; 95% condence interval (CI), 1.08-1.48] than serologic positivity (aOR =
1.12, 95% CI, 0.95-1.32), after adjusting for age, sex, smoking
status, alcohol consumption, and economic status.
Conclusions: The stronger association between metabolic syndrome
and histologic positivity than serological positivity suggests that the
eects of HP infection on the pathogenesis of cardiometabolic
outcomes may be reversible. Further prospective studies are
needed.
Key Words: Helicobacter pylori, metabolic syndrome, serology,
histology

(J Clin Gastroenterol 2012;46:840845)

elicobacter pylori (HP) infection may have a pathogenic

role in the development of metabolic syndrome, atherosclerosis, and cardiovascular disease. A series of case-control17
Received for publication September 29, 2011; accepted February 24,
2012.
From the *Department of Family Medicine, Health Promotion Center;
and wHealthcare System Gangnam Center, Seoul National University Hospital, Seoul, South Korea.
Partly supported by Grant No. 04-2010-0420100960 from the Seoul
National University Hospital Research Fund.
The authors declare that they have nothing to disclose.
Reprints: BeLong Cho, MD, MPH, PhD, Department of Family
Medicine, Health Promotion Center, Seoul National University
Hospital, 101 Daehak-ro, Jongno-Gu, Seoul 110-744, South Korea
(e-mail: belong@snu.ac.kr).
Copyright r 2012 by Lippincott Williams & Wilkins

840 | www.jcge.com

and cross-sectional816 studies have suggested that chronic HP

infection is associated with cardiometabolic risks of metabolic
syndrome,4,5,7,1113,15,16 atherosclerosis,13,14 and coronary13,8,9
and cerebrovascular disease.6 In addition, several prospective
cohort studies have indicated that HP has a pathogenic role in
adverse cardiovascular outcomes,17 and that antibiotic therapy
may reduce cardiometabolic risks and vascular events.1821
Among the many potential mechanisms are proinammatory
eects,3,6,9,11,14,1820 oxidative stress,12 immunologic crossreactivity,22 hypercoagulation,3,79,13,18 platelet aggregation,23
endothelial dysfunction,14 increased blood pressure (BP),13,15,21
modications of atherogenic lipoprotein,3,4,7,8,10,11,13,15,1820
and impaired insulin secretion7 or insulin resistance.5,12,16,19
Other case-control and cross-sectional studies, however, did
not support this possible link2428; several prospective cohort
studies reported that HP infection did not predict cardiovascular outcomes29,30; and several interventional studies
reported no benecial eect of antibiotic treatment on cardiovascular outcomes.31
These discrepancies may be because of dierences in
study subjects; for example, patients with established coronary or cerebral artery disease,1,3,4,6,7,13,24,2628 patients
with diabetes or hypertension,8,21 patients with dyspepsia
or peptic ulcer,12,18,19,31 elderly individuals,29,30 and healthy
subjects or general populations.911,1417,20,25 Other dierences among studies include the degree of adjustment for
potential confounders, including no adjustment,7,8,12,13,20,21
adjustment for age and/or sex,10,30 and adjustment further
for various health, behavioral, clinical, and socioeconomic
variables.1,3,4,6,9,1417,2429 Most importantly, these discrepancies among studies may be because of dierences in the
methods used to diagnose HP infection, which have included serology,1,3,610,1317,20,2430 histology and/or rapid
urease tests,12,18,19,31 urea breath tests,4,21,24 and stool antigen tests.20
The observation that benecial metabolic eects can
occur as soon as 6 weeks after HP eradication19 suggested
that current, not previous, HP infection is responsible for
the causal link. Most studies, however, determined HP
status by serological positivity alone. Serological positivity
does not necessarily indicate current infection15,29 (sensitivity, 85%; specicity, 79%32), suggesting that this diagnostic inaccuracy may yield false-positive results. Other
studies, however, have used diagnostic methods more
suitable for detecting current HP infection, including histology, rapid urease tests,12,18,19,31 urea breath tests,4,21,24
and stool antigen tests.20 One case-control study used
13
C-urea and serological tests to simultaneously estimate

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Helicobacter pylori and Metabolic Syndrome

the association between HP status and coronary heart

disease,24 but did not assess the dierences between these
diagnostic methods and did not explore the discordance of
these techniques. To our knowledge, no study to date has
compared the association between metabolic syndrome and
HP infection diagnosed by histologic and serological status.
We therefore simultaneously evaluated the association of
helicobacter infection with metabolic syndrome and its individual components by serological and histologic status in
a large number of healthy Korean adults.

METHODS
Study Subjects
From October 2004 to April 2010, 70,226 subjects
visited the Seoul National University Hospital Healthcare
System Gangnam Center for routine health check-ups.
As screening esophagogastroduodenoscopy (EGD) and serological tests for HP are included in the basic screening
program, most of the subjects underwent EGD, unless they
had undergone previous EGD for other reasons or preferred
an upper gastrointestinal series. The study was approved by
the institutional review board of Seoul National University
Hospital. Individual patient consents were not obtained, as
this study was an analysis of data that was collected as part of
routine clinical practice. Patient anonymity was secured.
Of the 70,226 subjects, 20,501 subjects were excluded
as they had been diagnosed with diabetes mellitus, dyslipidemia, or hypertension (n = 12,137), had history of established myocardial infarction/angina, stroke, chronic
kidney disease, malignancy (including gastric cancer) or use
of steroids (n = 2184), or lacked detailed history of diabetes
mellitus, dyslipidemia, or hypertension (n = 6180). Of the
remaining 49,725 individuals, 44,600 (89.7%) underwent
screening EGD with biopsies taken from 7702 (17.2%) for
suspicious gastric mucosal lesions. We excluded individuals
with gastric or duodenal ulcers or submucosal tumors, as
conrmed by EGD (n = 933), individuals with pathology
other than chronic gastritis (eg, adenocarcinoma, MALToma)
(n = 175), those with inadequate biopsy specimens (n = 2),
and those who were not tested serologically for HP (n = 703).
Thus, 5889 subjects were included in the analyses (Fig. 1).

Data Collection
Helicobacter Status
The diagnosis of HP infection was based on (1) the
detection of HP-specic antibody in serum; and (2) detection
of HP by histologic analysis. Anti-HP immunoglobulin G
(IgG) antibody titers were measured using enzyme-linked
immunosorbent assay kit (ELISA, Radim diagnostics, Rome,
Italy), and antibody titers of Z30 U/mL were considered
positive, according to the manufacturers instruction. ELISA
was validated in the Korean population with high sensitivity
and specicity.33
Subjects underwent EGDs, performed by well-trained
gastroenterologists, after an overnight fast. Biopsy samples
were taken from any suspicious regions of the stomach and
sent to the pathology laboratory, where they were stained
with hematoxylin and eosin and examined by experienced
pathologists who were blinded to all clinical information.
Although rapid urease tests were occasionally performed at
the request of the patient, these results were not considered
in our analysis.
r

2012 Lippincott Williams & Wilkins

FIGURE 1. Subjects of the study. EGD indicates esophagogastroduodenoscopy.

Anthropometric and Laboratory Data

Metabolic syndrome was dened according to the International Diabetes Federation (IDF), modied specically for Koreans.34 Individuals must have (1) central
obesity, dened as a waist circumference of Z90 cm for
men and Z80 cm for women, plus any 2 of the following 4
factors: (2) serum triglyceride (TG) > 150 mg/dL (> 1.7 mmol/
L); (3) high-density lipoprotein cholesterol (HDL-C) < 40 mg/
dL (< 1.0 mmol/L) for men and <50 mg/dL (< 1.3 mmol/L)
for women; (4) systolic BP > 130 mm Hg or diastolic BP >
85 mm Hg; and 5) fasting plasma glucose (FPG) > 100 mg/dL
(> 5.6 mmol/L).35 To conrm the robustness of our analysis,
we also utilized the National Cholesterol Education Program
(NCEP) denition of metabolic syndrome (ie, any 3 or more
of the above 3 factors).36
All subjects underwent physical examinations by
trained personnel who used a written, systematic protocol
with standardized instruments. Waist circumference was
measured at the middle level between the lowest rib margin
and the iliac crest. Body mass index was calculated from
measured height and weight (kg/m2). BP was measured
with an automated machine. Blood samples collected from
each subject after overnight fasting were assayed for cardiometabolic markers such as FPG, total cholesterol, TG,
HDL-C, and low-density lipoprotein cholesterol (LDL-C).

Behavioral Factors and Previous Medical History

At the time of health check-up, all subjects completed
a self-administered questionnaire, which included questions
about smoking status, alcohol consumption, and medical
history. Smoking status was categorized as nonsmoker,
past smoker, and current smoker. Total amount of alcohol
consumed per week was calculated in grams on the basis of
frequency, amount, and kind of alcohol, and then categorized into 3 groups: non, low to moderate (r119 g/wk,
corresponding to 14 drinks/wk), and heavy (> 119 g/wk).
Self-reported eradication history was also obtained.

Statistical Analysis
Continuous variables were expressed as means and SD
and compared using Student t tests and analysis of covariance. Categorical variables were compared by the
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Shin et al

w2 test and logistic regression. Three sequential multivariate

analyses were performed to assess the correlation between
HP status and metabolic syndrome. Results were sequentially adjusted for age and sex (model 1), for smoking and
alcohol consumption (model 2), and nally for income level
(model 3). Potential interactions between independent
variables were tested and included in the model if statistically signicant. Analyses were performed using STATA
software (version 10.1; STATA Corp, Houston, TX). For
each variable, the odds ratio (OR) and 95% condence
interval (95% CI) were calculated. All statistical tests
were 2-sided, and P < 0.05 was considered statistically
signicant.

RESULTS
Subject Characteristics
Of the 5889 included subjects, 3297 (56.0%) were male
and 2592 (44.0%) were female; their mean age was
48.0 10.7 years. We found that 3591 (61.0%) were HPpositive by serology, whereas 3082 (52%) were HP-positive
by histology. A total of 15.5% reported a history of HP
eradication, 11.6% were not sure, and 66.3% were not
treated for HP eradication (Table 1).

Concordance Between Serological and

Histologic Status of HP Infection
Among those who were HP-positive by serology,
19.7% were negative by histology. Among those who were
HP-negative by serology, 8.8% were positive by histology.
Concordance between serologic and histologic diagnosis
was moderate, with a k coecient of 0.69. When stratied
by self-reported HP eradication history, the concordance
was higher in those with no eradication history (k = 0.73)
than in those with an uncertain (k = 0.63) or positive
(k = 0.53) eradication history (Table 2).

Volume 46, Number 10, November/December 2012

Associations of HP Infection and Metabolic

Syndrome by Serological and Histologic Status
When subjects were assessed relative to their serological HP status in the fully adjusted model, there was no
signicant dierence in the prevalence of central obesity
[adjusted odds ratio (aOR) = 1.10; 95% CI, 0.96-1.25),
high TG (aOR = 1.04; 95% CI, 0.90-1.22), low HDL-C
(aOR = 1.06; 95% CI, 0.91-1.23), high BP (aOR = 1.12;
95% CI, 0.98-1.30), impaired fasting glucose (aOR = 1.05;
95% CI, 0.91-1.20), or metabolic syndrome by either the
IDF (aOR = 1.11; 95% CI, 0.93-1.33) or NCEP (aOR =
1.12; 95% CI, 0.95-1.32) denition. When subjects were
assessed relative to their histologic status, the HP-positive
group showed a higher prevalence of central obesity
(aOR = 1.20; 95% CI, 1.06-1.36), low HDL-C (aOR =
1.17; 95% CI, 1.02-1.36), and high BP (aOR = 1.19; 95%
CI, 1.04-1.36), but no dierence in high TG (aOR = 1.07;
95% CI, 0.92-1.24) or impaired fasting glucose (aOR =
1.04; 95% CI, 0.91-1.19) concentration. Histologically, HPpositive subjects had a higher prevalence of metabolic
syndrome, both by the IDF (aOR = 1.23; 95% CI, 1.041.46) and NCEP (aOR = 1.26; 95% CI, 1.08-1.48) denitions (Table 3).

Comparison of Cardiometabolic and

Inflammatory Parameters by Serological and
Histologic Status
Cardiometabolic parameters, including body mass index, systolic and diastolic BP, total cholesterol, and leukocyte count were signicantly higher, and HDL-C was
signicantly lower, in the HP-positive than in the HP-negative group by both histologic and serological status
(P < 0.05). In contrast, there were no signicant between
group dierences in TG, LDL-C, and FPG concentrations.
Waist circumference was signicantly higher in HP-positive
group by histologic status, whereas there was no signicant
dierence by serological status (Table 4).

DISCUSSION
TABLE 1. Characteristics of Study Subjects (n = 5889)

Characteristics
Age (mean SD)
< 40
40-49
50-59
Z60
Sex, female
Smoking
Nonsmoker
Past smoker
Current smoker
Missing
Alcohol consumption
None
Low to moderate (14 drinks/wk)
Heavy (Z14 drinks/wk)
Missing
Self-reported history of helicobacter eradication
No
Not sure
Yes
Missing
Helicobacter status
Serology, positive
Histology, positive

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N (%)
48.0 10.7
1341 (22.8)
1873 (31.8)
1846 (31.3)
829 (14.1)
2592 (44.0)
2820
1368
1361
340

(47.9)
(23.2)
(23.1)
(5.8)

2106
2154
1250
379

(35.8)
(36.5)
(21.2)
(6.4)

3907
684
911
387

(66.3)
(11.6)
(15.5)
(6.6)

3591 (61.0)
3082 (52.3)

To our knowledge, this is the rst study to compare

the serologic and histologic association of HP status with
metabolic syndrome in a large population. We found that
TABLE 2. Concordance Between Serological and Histologic HP
Status

Histologic Status
Serological
Status

Histology
( )

All patients
Serology ( )
2099 (91.3)
Serology (+)
708 (19.7)
By self-reported HP eradication
No
Serology ( ) 1329 (91.6)
Serology (+) 381 (15.5)
Not sure
Serology ( ) 236 (89.7)
Serology (+) 98 (23.3)
Yes
Serology ( ) 417 (92.7)
Serology (+) 178 (38.6)

Histology
(+)

Concordance
Agreement

84.6

0.69

122 (8.4)
2075 (84.5)

87.1

0.73

27 (10.3)
323 (76.7)

81.7

0.63

33 (6.33)
283 (61.4)

76.8

0.53

199 (8.7)
2883 (80.3)
history

HP indicates Helicobacter pylori.

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Helicobacter pylori and Metabolic Syndrome

TABLE 3. Associations of Helicobacter pylori Infection and Metabolic Syndrome by Serological and Histologic Status

Positive, n (%)
By serological status
Central obesity
High triglyceride
Low HDL
High blood pressure
Impaired fasting glucose
Metabolic syndrome (by
Metabolic syndrome (by
By histologic status
Central obesity
High triglyceride
Low HDL
High blood pressure
Impaired fasting glucose
Metabolic syndrome (by
Metabolic syndrome (by

Unadjusted

Model 1

Model 2

Model 3

Crude OR (95% CI)

aOR (95% CI)

aOR (95% CI)

aOR (95% CI)

1.10
1.04
1.06
1.12
1.05
1.11
1.12

IDF)
NCEP)

1245
779
720
1063
1087
538
678

(34.7)
(21.7)
(20.1)
(29.6)
(30.3)
(15.0)
(18.9)

1.23
1.20
1.05
1.33
1.23
1.29
1.30

(1.10-1.38)
(1.05-1.37)
(0.92-1.20)
(1.18-1.50)
(1.10-1.39)
(1.10-1.50)
(1.13-1.50)

1.15
1.04
1.07
1.15
1.04
1.14
1.14

(1.02-1.28)
(0.91-1.20)
(0.94-1.23)
(1.01-1.30)
(0.92-1.18)
(0.97-1.33)
(0.99-1.32)

1.14
1.06
1.08
1.14
1.05
1.13
1.13

(1.01-1.29)
(0.91-1.23)
(0.93-1.24)
(1.00-1.31)
(0.92-1.20)
(0.95-1.34)
(0.97-1.33)

IDF)
NCEP)

1076
674
630
918
920
471
594

(34.9)
(21.9)
(20.4)
(29.8)
(29.9)
(15.3)
(19.3)

1.21
1.19
1.10
1.28
1.14
1.29
1.31

(1.08-1.35)
(1.04-1.37)
(0.97-1.25)
(1.14-1.44)
(1.02-1.27)
(1.11-1.50)
(1.15-1.50)

1.18
1.05
1.14
1.21
1.04
1.20
1.22

(1.06-1.32)
(0.92-1.19)
(1.00-1.30)
(1.07-1.36)
(0.93-1.18)
(1.03-1.40)
(1.06-1.40)

1.22 (1.09-1.39)
1.09 (0.95-1.26)
1.21 (1.05-1.39)
1.20 (1.06-1.37)
1.06 (0.93-1.20)
1.25 (1.06-1.47)
1.28 (1.11-1.49)

(0.96-1.25)
(0.90-1.22)
(0.91-1.23)
(0.98-1.30)
(0.91-1.20)
(0.93-1.33)
(0.95-1.32)

1.20 (1.06-1.36)
1.07 (0.92-1.24)
1.17 (1.02-1.36)
1.19 (1.04-1.36)
1.04 (0.91-1.19)
1.23 (1.04-1.46)
1.26 (1.08-1.48)

Model 1: adjusted for age, sex.

Model 2: adjusted for age, sex, smoking, and alcohol.
Model 3: adjusted for age, sex, smoking, alcohol, and income level.
aOR indicates adjusted odds ratio; CI, condence interval; HDL, high-density lipoprotein; IDF, International Diabetes Foundation; NCEP, National
Cholesterol Education Program; OR, odds ratio.

the metabolic syndrome was more strongly associated with

histologic positivity for HP than serologic positivity, after
adjusting for age, sex, smoking status, alcohol consumption,
and economic status. The strengths of our study include
a large sample population and statistical robustness from
the use of several dierent multivariate models.
There was considerable discordance between serological and histologic HP status in our study population.
When histology is taken as the gold standard, serology had
a sensitivity of 93.5% and a specicity of 74.8% and most
discordances occurred in subjects who were serologically
positive and histologically negative.37 This was likely due to
the slow decline in IgG antibody titer, which remains elevated for months to years after HP eradication.13,37 Indeed,
increased discordance was observed in those who reported
HP eradication history. We think such discordance may

explain the attenuation of association between metabolic

syndrome and HP infection when using serology.
The association between histologic positivity for HP
and metabolic syndrome was signicant even after adjusting for potential confounders in a hierarchical manner.
Although it is presently unclear how HP infection could
cause metabolic syndrome and vascular diseases, it likely
involves many interrelated mechanisms. We found that
between group dierences in waist circumference,13
HDL-C,4,7,8,10,11,13,18,20 BP,21 TG,8,10,13 and FPG7,13 were
in the expected direction, although the absolute dierences
were slight and those of the latter 2 were not statistically
signicant after adjustment. These ndings suggest that
insulin resistance is involved in the HP-associated pathogenesis of metabolic syndrome.38 In addition, we observed
signicant dierences in leukocyte9,11 and neutrophil

TABLE 4. Comparison of Cardiometabolic and Inflammatory Parameters by Serological and Histologic Status

By Serological Status
Crude Mean (Unadjusted)
HP( ) HP(+)
Body mass index
Weight (kg)
Waist circumference(cm)
Systolic BP (mm Hg)
Diastolic BP (mm Hg)
Total cholesterol (mg/dL)
Triglyceride (mg/dL)
HDL cholesterol (mg/dL)
LDL cholesterol (mg/dL)
FPG (mg/dL)
Leukocyte count (/mm3)
Neutrophil count (/mm3)

23.2
63.1
83.7
115.2
73.7
194
111.4
55.8
119.6
94.7
5.64
3.18

23.8
65.3
85.2
117.3
76.0
197.9
116.8
54.0
124.6
96.2
5.92
3.35

P
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
0.009
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001

By Histologic Status

Adjusted Mean
HP( ) HP(+)
23.4
64.2
84.3
116.0
74.6
194.8
114.9
54.9
121.1
95.6
5.71
3.21

23.6
64.9
84.8
116.9
75.8
197.0
114.9
54.1
123.3
95.9
5.89
3.34

P
0.004
0.009
0.063
0.032
< 0.001
0.030
0.996
0.028
0.07
0.53
< 0.001
0.002

Crude Mean (Unadjusted)

HP( ) HP(+)
23.2
63.2
83.9
115.6
74.0
194.9
111.1
55.6
121.0
95.1
5.66
3.19

23.8
65.5
85.2
117.2
76.1
197.8
118.0
53.9
124.0
96.1
5.95
3.37

P
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
< 0.001
0.006
0.014
< 0.001
< 0.001

Adjusted Mean
P

HP( ) HP(+)
23.4
64.2
84.2
116.0
74.6
195.0
113.3
54.9
121.7
95.6
5.71
3.22

23.7
65.1
84.9
117.0
76.0
197.2
116.3
53.9
123.0
95.9
5.92
3.35

< 0.001
< 0.001
< 0.001
0.018
< 0.001
0.022
0.158
0.005
0.281
0.489
< 0.001
0.001

Adjusted for age, sex, smoking, alcohol, and income level

BP indicates blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoprotein; HP, Helicobacter pylori; LDL, low-density lipoprotein.

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counts, suggesting the involvement of inammation. Lowgrade chronic inammation was recently proposed to be a
critical factor underlying the metabolic syndrome,39 with
proinammatory cytokines such as tumor necrosis factor-a
and interluekin-6 playing a key role in the common
pathogenesis of HP infection and metabolic syndrome.40
Although the nonsignicant dierences in fasting TG and
FPG were not expected, they may be due to insulin resistance in healthy subjects with HP infection may not be severe enough to cause a signicant increase in TG and FPG
or that these parameters are less sensitive measures of insulin resistance than postprandial TG41 or postprandial
glucose.42 Our nding, that LDL-C did not increase, may
be because of atherogenic lipidemia in metabolic syndrome
involving an increase in smaller and denser LDL-C particles, rather than absolute amount of LDL-C.38 However,
previous studies have suggested that LDL-C is increased in
HP-infected individuals.10
Consistent with previous studies,10,15 the association
between metabolic syndrome and HP infection in our study
was only mild to moderate, suggesting that it accounted for
only a minor portion of total risk. However, the positive
change of cardiometabolic proles after HP eradication19
suggested that adverse cardiometabolic eect of HP infection is at least partially reversible. Although unlikely to
be a strong risk factor, the high prevalence of HP and the
limited eect of current prevention approaches suggest that
this association merits further investigation.
Our study had several limitations. First, because of the
cross-sectional design of this study, our results do not
necessarily imply causation. However, as HP infection
usually occurs during childhood, it is more likely that HP
preceded the development of metabolic syndrome.15 Second, as a retrospective analysis of clinical data, there is a
potential risk of selection bias because many subjects were
excluded as they had neither undergone EGD nor biopsied.
Prospective study that collects both histologic and serological data for the study purpose would be necessary.
Third, histologic diagnosis of HP infection might not be
optimal, as this was performed primarily in a clinical context, rather than for research per se. Multiple biopsies of
normal stomach mucosa (antrum19,37,43 and/or corpus19,43)
and several staining techniques (eg, hematoxylin and
eosin,37 Warthin-Starry silver,37 Giemsa,19,44 McMullen,44
and immunostaining44) have been utilized in studies evaluating several diagnostic methods. However, HP is more
likely to be detected in lesions than in normal mucosa,43
and careful examination almost always detects the microorganism, regardless of the staining technique.44 Thus, any
bias from a failure of histologic identication is not likely to
be considerable, and if present, should not aect our conclusions. Fourth, we did not include dietary habits and
physical activity as covariates15,16 in our analysis, as these
variables were not uniformly available. Although several
studies have suggested a link between HP infection and
diet, the relationship is far from established showing conicting results.45 Moreover, level of physical activity is
likely not associated with HP status, suggesting that omitting these variables would not inuence our conclusions.
In conclusion, our ndings provide further evidence of
a small to moderate association between metabolic syndrome and HP infection, which cannot be fully accounted
for by other risk factors. The stronger association between
metabolic syndrome and histologic positivity than serological positivity suggests that the eects of HP infection on

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Volume 46, Number 10, November/December 2012

the pathogenesis of cardiometabolic outcomes may be

reversible, and that the latter may be reduced by HP
eradication. Future studies on the eects of HP on cardiometabolic outcomes should consider assessment of HP
status by diagnostic methods other than serology to ensure
the identication of current infectious status. Large, prospective studies are warranted to examine how current HP
status aects metabolic syndrome and subsequent vascular
disease, and how eradication reverses the cardiometabolic
eect of HP.
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