atrophic gastritis ( ag ) is a histopathologic entity characterized by chronic inflammation of the gastric mucosa with loss of gastric glandular cells and replacement by intestinal - type epithelium , pyloric - type glands , and fibrous tissue .
atrophy of the gastric mucosa is the endpoint of chronic processes , such as chronic gastritis associated with helicobacter pylori ( h. pylori ) infection , other unidentified environmental factors , and autoimmunity directed against gastric glandular cells .
pepsinogen ( pg ) is precursors of pepsin , and consists of two biochemically and immunologically distinct types , namely , pg i and pg ii .
serum pg levels are related to gastritis , gastric mucosal lesion , with a particular relationship to ag . decreased serum pg i levels and the pg i / ii ratio can be used to assess gastric atrophy .
miki et al . reported that the pg i / ii ratio of more than 3 has a sensitivity of 93.3% and specificity of 87.7% for the diagnosis of normal fundic gland mucosa .
h. pylori infection is the most common cause of ag , and at least 50% of the world s population is infected with h. pylori . 

h. pylori infection can lead to variety of upper gastrointestinal disorders , including peptic ulcer disease , gastric mucosa - associated lymphoid tissue lymphoma , and gastric cancer .
in addition , h. pylori infection has been linked to several extra - gastric disorders , such as atherosclerosis and coronary artery disease ( cad ) .
some studies have shown a positive association between h. pylori infection and cad , while others have shown no significant association .
recently , two studies have suggested that ag irrespective of h. pylori status was associated with atherosclerosis in general population . to the best of our knowledge
, however , no previous reports have investigated the effects of ag on the prevalence of cad in general population .
therefore , we investigated the relationship between ag , which is diagnosed based on serum pg levels , and cad in general japanese individuals .
the  human dry dock  , is one of the most popular medical services in japan , for the purpose of the medical health checkup promoting public health through early detection of chronic diseases and their risk factors .
a standard human dry dock features anamnesis and a survey of lifestyle , a physical examination , serum and urine examination , a chest x - ray , abdominal ultrasonography , and other tests .
the fee is paid by participants or supported ( fully or partially ) by their employers or medical insurers .
this study was designed to cross - sectionally evaluate the relationship between ag and cad in japanese population .
the study included 1,758 male and 875 female subjects , aged 2190 years , who attended the human dry dock of oike clinic in kyoto , japan in 2009 .
medical history and lifestyle factors were obtained from a self - administered questionnaire completed by all the subjects , which included medication use , family history of diseases , and habits of smoking and drinking .
in addition , all participants underwent physical examinations , routine biochemical screening tests obtained by venipuncture after an overnight fast .
all participants gave their informed consent , and the study was approved by the ethics committee of oike clinic .
body mass index ( bmi ) was calculated as body weight in kilogram divided by the square of the participant s height in meters .
systolic blood pressure and diastolic blood pressure were measured in the right upper arm of participants in a sedentary position using an automatic oscillometric blood pressure recorder .
hypertension was defined as systolic blood pressure / diastolic blood pressure  140/90 mmhg or pharmacological treatment for hypertension .
dyslipidemia was defined as total cholesterol  5.7  mmol / l , triglyceride  1.7 mmol / l , or pharmacological treatment for hyperlipidemia .
hyperuricemia was defined as serum uric acid  416.3  mol / l , or pharmacological treatment for hyperuricemia .
atrophic gastritis was defined as pg i  70  ng / ml and pg i / ii ratio  3.0 .
coronary artery disease was defined as a previous myocardial infarction based on the clinical history or electrocardiogram .
triglyceride value was presented as median ( interquartile range ) due to skewed distribution , and other continuous variables were presented as mean   standard deviation ( sd ) . unpaired student s t tests , mann - whitney s u test , or  test were conducted as appropriate to assess statistical significance of differences between groups , using stat view software ( ver . 5.0 ; sas institute , cary , nc ) .
multiple logistic regression analysis was performed to assess the combined influence of variables on the prevalence of cad . to examine the effects of various factors on the prevalence of cad
, the following factors were considered as independent variables : ag , age , sex , obesity , hypertension , diabetes mellitus , hyperlipidemia , hyperuricemia , and habits of smoking and drinking .
the  human dry dock  , is one of the most popular medical services in japan , for the purpose of the medical health checkup promoting public health through early detection of chronic diseases and their risk factors .
a standard human dry dock features anamnesis and a survey of lifestyle , a physical examination , serum and urine examination , a chest x - ray , abdominal ultrasonography , and other tests .
the fee is paid by participants or supported ( fully or partially ) by their employers or medical insurers .
this study was designed to cross - sectionally evaluate the relationship between ag and cad in japanese population .
the study included 1,758 male and 875 female subjects , aged 2190 years , who attended the human dry dock of oike clinic in kyoto , japan in 2009 .
medical history and lifestyle factors were obtained from a self - administered questionnaire completed by all the subjects , which included medication use , family history of diseases , and habits of smoking and drinking .
in addition , all participants underwent physical examinations , routine biochemical screening tests obtained by venipuncture after an overnight fast .
all participants gave their informed consent , and the study was approved by the ethics committee of oike clinic .
body mass index ( bmi ) was calculated as body weight in kilogram divided by the square of the participant s height in meters .
systolic blood pressure and diastolic blood pressure were measured in the right upper arm of participants in a sedentary position using an automatic oscillometric blood pressure recorder .
hypertension was defined as systolic blood pressure / diastolic blood pressure  140/90 mmhg or pharmacological treatment for hypertension .
diabetes mellitus was defined as fasting blood glucose  7.0  mmol / l or pharmacological treatment for diabetes mellitus .
dyslipidemia was defined as total cholesterol  5.7  mmol / l , triglyceride  1.7 mmol / l , or pharmacological treatment for hyperlipidemia .
hyperuricemia was defined as serum uric acid  416.3  mol / l , or pharmacological treatment for hyperuricemia .
atrophic gastritis was defined as pg i  70  ng / ml and pg i / ii ratio  3.0 .
coronary artery disease was defined as a previous myocardial infarction based on the clinical history or electrocardiogram .
triglyceride value was presented as median ( interquartile range ) due to skewed distribution , and other continuous variables were presented as mean   standard deviation ( sd ) .
unpaired student s t tests , mann - whitney s u test , or  test were conducted as appropriate to assess statistical significance of differences between groups , using stat view software ( ver .
multiple logistic regression analysis was performed to assess the combined influence of variables on the prevalence of cad . to examine the effects of various factors on the prevalence of cad ,
the following factors were considered as independent variables : ag , age , sex , obesity , hypertension , diabetes mellitus , hyperlipidemia , hyperuricemia , and habits of smoking and drinking .
characteristics of the 2,633 subjects enrolled in this study are shown in table  1 . among 2,633 study subjects , 531 subjects ( 20.2% )
mean age was significantly higher in the ag - positive group than that in the ag - negative group ( 64.5    9.4 vs 56.2    11.6 years , p<0.0001 ) .
serum uric acid concentration was lower in ag - positive group than that in ag - negative group ( 327.1    83.3 vs 345.0    83.3 
mol / l , p<0.0001 ) . proportions of drinker were significantly fewer in the ag - positive group than those in the ag - negative group ( 36.0% vs 40.9% , p<0.0001 ) .
the prevalence of hyperuricemia was significantly lower in the ag - positive group than that in the ag - negative group ( 19.2% vs 25.0% , p  =  0.0051 ) .
the prevalence of cad was significantly higher in the ag - positive group than that in the ag - negative group ( 5.8% vs 2.8% , p  =  0.0005 ) ( table  2 ) .
multiple logistic regression analysis demonstrated that age ( odds ratio [ or ] , 1.07 ; 95% confidence interval [ ci ] , 1.041.09 ) , hypertension ( or , 2.75 ; 95% ci , 1.674.53 ) , habits of smoking ( or , 2.53 ; 95% ci , 1.544.15 ) , and ag ( or , 1.67 ; 95% ci , 1.032.72 ) were significantly associated with cad ( table  3 ) .
we have shown that ag determined by serum pg levels is significantly associated with cad .
this significant association remained unchanged even after adjustment for age , sex , obesity , hypertension , diabetes mellitus , dyslipidemia , hyperuricemis , and habits of smoking and drinking .
atrophic gastritis represents the end stage of chronic inflammation of gastric mucosa , and h. pylori infection of the stomach is by far the most common cause of ag .
h. pylori infection can eventually lead to loss of the normal gastric mucosal architecture , with destruction of gastric glands and replacement by fibrosis and intestinal - type epithelium .
this process of ag and intestinal metaplasia are involved in the induction of an inflammatory response characterized by an influx of neutrophils , mononuclear cells , and t - helper 1 cells , typically aimed at clearing intracellular infections .
however , h. pylori is not an intracellular pathogen , and thus the t - helper 1 response results in epithelial cell damage rather than in the removal of h. pylori .
the ongoing infection with h. pylori thus causes a lifelong proinflammatory response coupled to cellular damage and initiates the cancer cascade .
the underlying hypothetical mechanisms include chronic low - grade activation of the coagulation cascade and accelerating atherosclerosis due to the vascular endothelial damage resembling the gastric epithelial damage through the induction of inflammatory response .
on the other hand , several studies demonstrated that h. pylori infection was associated with atherogenic lipid profiles including increased serum triglyceride and total cholesterol concentrations , and decreased hdl cholesterol concentrations .
however , some studies have shown no significant association between h. pylori infection and cad .
this issue is still controversial , thus further studies are needed to confirm the relationship between h. pylori infection and cad .
torisu et al . reported that pulse wave velocity , which is an early preclinical marker of atherosclerosis , was significantly higher in healthy subjects with ag diagnosed by serum pg test method than in those without ag .
they reported that serum ghrelin levels which might be protective against atherosclerosis , were significantly lower in ag - positive subjects than in ag - negative subjects .
reported that ag diagnosed by histologic method might cause hyperhomocysteinemia , which is an independent risk factor for atherosclerosis , in general population . in their report
, carotid intima - media thickness in subjects with ag was found to be thicker than that in controls , although it did not reach statistically significant levels .
those two reports have suggested that ag irrespective of h. pylori status was associated with atherosclerosis .
our study based on a large number of subjects suggested that ag was an independent risk factor for cad .
taken together these findings , it seems plausible that ag influences the development of atherosclerotic changes in coronary arteries .
second , it was not clear which extent of ag was related to h. pylori infection , because the serum immunoglobulin g antibody to h. pylori was not measured .
subjects with autoimmune gastritis and h. pylori - induced gastritis were included in ag - positive group .
however , the prevalence of autoimmune gastritis is low in japan , therefore the relationship between ag and cad could be regarded as the relationship between h. pylori - induced ag and cad .
third , we did not measure proinflammatory cytokines such as c - reactive protein , tumor necrosis factor - alpha , and interleukin-6 , although they might not be markedly increased in the end stage of chronic inflammation . finally , we did not measure homocysteine , ghrelin , and others , each of which has been reported to be related to atherosclerosis . in conclusion
 atrophic gastritis is characterized by chronic inflammation of gastric mucosa by helicobacter pylori infection and other factors . 
 helicobacter pylori infection has been linked to coronary artery disease . to our knowledge , however , no reports are available on the relationship between atrophic gastritis and coronary artery disease . in this study , we investigated the relationship between atrophic gastritis , which is diagnosed based on serum pepsinogen levels ( pepsinogen i   70  ng / ml and pepsinogen i / ii ratio   3.0 ) , and the prevalence of coronary artery disease in general japanese population . among 2,633 study subjects , 531 subjects ( 20.2% ) 
 were diagnosed as atrophic gastritis . 
 the prevalence of coronary artery disease was higher in the atrophic gastritis - positive group than that in the atrophic gastritis - negative group ( 5.8% vs 2.8% , p  =  0.0005 ) . 
 multiple logistic regression analysis demonstrated that atrophic gastritis was independently associated with coronary artery disease ( odds ratio , 1.67 ; 95% confidence interval , 1.032.72 ) , after adjustment for age , sex , obesity , hypertension , diabetes mellitus , dyslipidemia , hyperuricemia , and habits of smoking and drinking . 
 these results suggest that atrophic gastritis is an independent risk factor for coronary artery disease . 
 chronic inflammation of gastric mucosa may be associated with the prevalence of coronary artery disease . 
Introduction
Materials and Methods
Study subjects
Study measurements
Statistical analysis
Results
Discussion