gastroesophageal reflux disease ( gerd ) is characterized by symptoms and complications such as esophagitis , esophageal stricture , barrett esophagus , and esophageal adenocarcinoma , and is caused by the reflux of gastric contents . previous studies have reported the prevalence of gerd ( as defined by experiencing heartburn or acid regurgitation at least once per week ) was 14% to 24% in adults in western countries , and 3% to 10.5% in asian populations . the manifestations of gerd include esophageal syndromes , such as erosive esophagitis and nonerosive reflux disease ( nerd ) , and extra - esophageal syndromes such as reflux - associated cough , asthma , laryngitis , and dental erosion . the features of gerd - induced chest pain are similar to those of cardiac pain , and thus the 2 types of pain can be confused . in addition , gerd and coronary heart disease ( chd ) can interact with each other to produce chest pain . studies have shown that esophageal stimulation can cause cardiac pain by inducing cardiac dysrhythmia or coronary spasm to compromise coronary blood flow . studies have also shown that myocardial ischemia can worsen gerd by causing esophageal dysmotility or relaxation of the lower esophageal sphincter . a coexisting relationship between gerd and chd has been widely accepted , though the mechanism underlying the relationship is complex . previous studies have shown that male sex , obesity , diabetes , hypertension , smoking , and alcohol drinking are associated with gerd , and that metabolic risk factors can influence the severity of symptoms or esophageal erosion in gerd patients . hyperlipidemia , hypertension , diabetes , alcoholism , and smoking are well - known risk factors for chd . however , the existence of an association between gerd and subsequent development of chd remains under debate . moreover , it has been reported that proton pump inhibitors ( ppis ) can reduce cardiac contractility and raise the risk of atherosclerosis by increasing the serum levels of homocysteine . we hypothesized that gerd might be related to an increased risk of the subsequent chd development . in this nationwide population - based cohort study , we analyzed the data from the national health insurance research database ( nhird ) to evaluate the relationship between gerd and subsequent chd development and to determine whether the risk of chd increases after longer use of ppis . the taiwan government has operated the national health insurance ( nhi ) since 1995 . furthermore , this compulsory single - payer healthcare system covers more than 99% of the 23 million taiwan residents and has contracts with > 97% of medical care facilities nationwide ( http://www.nhi.gov.tw/english/index.aspx ) . the government conducts a peer review system by appointing several medical specialists to audit the accuracy of all insurance claims . the national health research institutes ( nhri ) ( http://nhird.nhri.org.tw ) is in charge of maintaining the data security obtained from the nhird ( http://w3.nhri.org.tw/nhird//date_01.html ) and all data were deposited in a public repository . each encrypted patient 's unique personal identification number was crossly linked in the datasets of nhird to obtain each patient 's longitudinal medical history , and the researchers can access the database after approval for research purpose . all the data relevant to ambulatory care , inpatient care , prescriptions , and medications of 1,000,000 patients randomly sampled from the 2000 registry of beneficiaries in the nhird are included in the longitudinal health insurance database 2000 ( lhid 2000 ) , which has been widely used for research in taiwan . furthermore , the nhri has validated that the lhid 2000 is representative of the general taiwan population . the international classification of diseases , ninth revision , clinical modification ( icd-9-cm ) was used for coding the diagnosis in the nhird database . we conducted this study under approval by the research ethics committee of china medical university ( cmuh-104-rec2 - 115 ) . patients age 20 years who were newly diagnosed with gerd ( icd-9-cm codes 530.11 and 530.81 ) between 2000 and 2011 were identified from the lhid 2000 . to increase the validity of gerd diagnoses , we only included patients diagnosed using endoscopy or 24-h ph monitoring who subsequently received ppi treatment . the date of gerd diagnosis was set as the index date . patients with chd ( icd-9-cm codes 410414 ) before the index date and those without complete information in the lhid 2000 were excluded . furthermore , the patients with chd were classified into subgroups , namely those with acute coronary syndrome ( acs ; icd-9-cm codes 410 , 411.1 , and 411.8 ) , old myocardial infarction ( icd-9-cm code 412 ) , angina pectoris ( icd-9-cm code 413 ) , and chronic ischemic heart disease ( icd-9-cm code 414 ) . patients without a history of gerd or chd were randomly selected from the same database as the comparison cohort . the comparison cohort was frequency - matched with the study cohort by sex , age ( every 5 years ) , and index year of gerd diagnosis from 2000 to 2011 at a ratio of 4:1 . all the patients were followed up from the index date until the date of chd diagnosis . the patients were censored at death , loss to follow - up , withdrawal from the insurance program , or the end of 2011 , whichever came first . the baseline comorbidity history was determined for each patient , including hypertension ( icd-9-cm codes 401405 ) , diabetes ( icd-9-cm code 250 ) , hyperlipidemia ( icd-9-cm code 272 ) , alcohol - related illness ( icd-9-cm codes 291 , 303 , 305 , 571.0 , 571.1 , 571.2 , 571.3 , 790.3 , a215 , and v11.3 ) , stroke ( icd-9-cm codes 430438 ) , obesity ( icd-9-cm code 278 ) , chronic obstructive pulmonary disease ( copd ) ( icd-9-cm codes 491 , 492 , and 496 ) , asthma ( icd-9-cm code 493 ) , biliary stone ( icd-9-cm code 574 ) , anxiety ( icd-9-cm code 300 ) , depression ( icd-9-cm codes 296.2296.3 , 300.4 , and 311 ) , thyroid disease ( icd-9-cm codes 240242 and 244246 ) , chronic kidney disease ( icd-9-cm codes 580589 ) , and cirrhosis ( icd-9-cm code 571 ) . the demographic characteristics , including age , sex , and comorbidities , of the gerd cohort were compared with those of the comparison cohort by using a chi - squared test for categorical variables and student t tests for continuous variables . to estimate the probability of chd - free events in the gerd and comparison cohorts , a survival analysis was performed using the kaplan  meier method , with significance based on the log - rank test . the incidence densities of chd ( per 1000 person - years ) were calculated for both cohorts . univariable and multivariable cox proportion hazards regression models were used to determine the relative risk of chd in the study cohort compared with the comparison cohort , shown as a hazard ratio ( hr ) and 95% confidence interval ( ci ) . when the patients were stratified according to sex , age , and comorbidities , the relative risk of chd in the gerd cohort compared with the comparison cohort was also analyzed by using cox models . the proportionality assumption was violated since there was a significant relationship between schoenfeld residuals for gerd and follow - up time ( p value = 0.002 ) . therefore , the follow - up duration was then stratified to address the violation of the proportional hazard assumption . the multivariable cox models included age , sex , and comorbidities of gerd , hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , copd , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis . among the comorbidities , only gerd , hypertension , hyperlipidemia , and anxiety exhibited a significant association with the development of chd in the multivariable cox models . further data analysis was performed to evaluate the joint effect of gerd with comorbidities of hypertension , hyperlipidemia , and anxiety . on the basis of propensity score matching , a cox proportional hazards model was used to estimate the hr and 95% ci of the risk of chd associated with gerd . all statistical analyses were performed using the sas package ( version 9.3 for windows ; sas institute , inc , cary , nc ) . the taiwan government has operated the national health insurance ( nhi ) since 1995 . furthermore , this compulsory single - payer healthcare system covers more than 99% of the 23 million taiwan residents and has contracts with > 97% of medical care facilities nationwide ( http://www.nhi.gov.tw/english/index.aspx ) . the government conducts a peer review system by appointing several medical specialists to audit the accuracy of all insurance claims . the national health research institutes ( nhri ) ( http://nhird.nhri.org.tw ) is in charge of maintaining the data security obtained from the nhird ( http://w3.nhri.org.tw/nhird//date_01.html ) and all data were deposited in a public repository . each encrypted patient 's unique personal identification number was crossly linked in the datasets of nhird to obtain each patient 's longitudinal medical history , and the researchers can access the database after approval for research purpose . all the data relevant to ambulatory care , inpatient care , prescriptions , and medications of 1,000,000 patients randomly sampled from the 2000 registry of beneficiaries in the nhird are included in the longitudinal health insurance database 2000 ( lhid 2000 ) , which has been widely used for research in taiwan . furthermore , the nhri has validated that the lhid 2000 is representative of the general taiwan population . the international classification of diseases , ninth revision , clinical modification ( icd-9-cm ) was used for coding the diagnosis in the nhird database . we conducted this study under approval by the research ethics committee of china medical university ( cmuh-104-rec2 - 115 ) . patients age 20 years who were newly diagnosed with gerd ( icd-9-cm codes 530.11 and 530.81 ) between 2000 and 2011 were identified from the lhid 2000 . to increase the validity of gerd diagnoses , we only included patients diagnosed using endoscopy or 24-h ph monitoring who subsequently received ppi treatment . patients with chd ( icd-9-cm codes 410414 ) before the index date and those without complete information in the lhid 2000 were excluded . furthermore , the patients with chd were classified into subgroups , namely those with acute coronary syndrome ( acs ; icd-9-cm codes 410 , 411.1 , and 411.8 ) , old myocardial infarction ( icd-9-cm code 412 ) , angina pectoris ( icd-9-cm code 413 ) , and chronic ischemic heart disease ( icd-9-cm code 414 ) . patients without a history of gerd or chd were randomly selected from the same database as the comparison cohort . the comparison cohort was frequency - matched with the study cohort by sex , age ( every 5 years ) , and index year of gerd diagnosis from 2000 to 2011 at a ratio of 4:1 . all the patients were followed up from the index date until the date of chd diagnosis . the patients were censored at death , loss to follow - up , withdrawal from the insurance program , or the end of 2011 , whichever came first . the baseline comorbidity history was determined for each patient , including hypertension ( icd-9-cm codes 401405 ) , diabetes ( icd-9-cm code 250 ) , hyperlipidemia ( icd-9-cm code 272 ) , alcohol - related illness ( icd-9-cm codes 291 , 303 , 305 , 571.0 , 571.1 , 571.2 , 571.3 , 790.3 , a215 , and v11.3 ) , stroke ( icd-9-cm codes 430438 ) , obesity ( icd-9-cm code 278 ) , chronic obstructive pulmonary disease ( copd ) ( icd-9-cm codes 491 , 492 , and 496 ) , asthma ( icd-9-cm code 493 ) , biliary stone ( icd-9-cm code 574 ) , anxiety ( icd-9-cm code 300 ) , depression ( icd-9-cm codes 296.2296.3 , 300.4 , and 311 ) , thyroid disease ( icd-9-cm codes 240242 and 244246 ) , chronic kidney disease ( icd-9-cm codes 580589 ) , and cirrhosis ( icd-9-cm code 571 ) . the demographic characteristics , including age , sex , and comorbidities , of the gerd cohort were compared with those of the comparison cohort by using a chi - squared test for categorical variables and student t tests for continuous variables . to estimate the probability of chd - free events in the gerd and comparison cohorts , a survival analysis was performed using the kaplan  meier method , with significance based on the log - rank test . the incidence densities of chd ( per 1000 person - years ) were calculated for both cohorts . univariable and multivariable cox proportion hazards regression models were used to determine the relative risk of chd in the study cohort compared with the comparison cohort , shown as a hazard ratio ( hr ) and 95% confidence interval ( ci ) . when the patients were stratified according to sex , age , and comorbidities , the relative risk of chd in the gerd cohort compared with the comparison cohort was also analyzed by using cox models . the proportionality assumption was violated since there was a significant relationship between schoenfeld residuals for gerd and follow - up time ( p value = 0.002 ) . therefore , the follow - up duration was then stratified to address the violation of the proportional hazard assumption . the multivariable cox models included age , sex , and comorbidities of gerd , hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , copd , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis . among the comorbidities , only gerd , hypertension , hyperlipidemia , and anxiety exhibited a significant association with the development of chd in the multivariable cox models . further data analysis was performed to evaluate the joint effect of gerd with comorbidities of hypertension , hyperlipidemia , and anxiety . on the basis of propensity score matching , a cox proportional hazards model was used to estimate the hr and 95% ci of the risk of chd associated with gerd . all statistical analyses were performed using the sas package ( version 9.3 for windows ; sas institute , inc , cary , nc ) . table 1 shows the demographic characteristics and comorbidities of the gerd and comparison cohorts . in both cohorts , most of the patients were men ( 50.8% ) and the mean age was 49 years . the gerd cohort was significantly more likely than the comparison cohort to have comorbidities of hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , obesity , copd , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis ( all p  <  0.001 ) . table 2 shows the incidences and hrs of chd stratified by sex , age , comorbidities , and duration of gerd follow - up in the patients with and without gerd . the mean duration of follow - up was 3.60    1.95 years in the gerd cohort and 3.65    1.95 years in the comparison cohort . the overall incidence of chd was 82% higher in the gerd cohort than in the comparison cohort ( 11.8 vs 6.50 per 1000 person - years ) , with an adjusted hr ( ahr ) of 1.49 ( 95% ci = 1.341.66 ) . the risks of acs , angina pectoris , and chronic ischemic heart disease were higher in the gerd cohort than in the comparison cohort . the age - specific relative risk of chd in the gerd cohort was lowest in the 65 years age group than in the comparison cohort . compared with the non - gerd cohort , the gerd cohort had a greater risk of chd among women and men ( ahr = 1.33 , 95% ci = 1.131.57 for women ; ahr = 1.62 , 95% ci = 1.411.87 for men ) , patients age 35 to 49 and 50 to 64 years ( ahr = 1.75 , 95% ci = 1.412.19 for patients age 3549 years ; ahr = 1.55 , 95% ci = 1.321.82 for patients age 5064 years ) , and patients with or without comorbidity ( ahr = 2.39 , 95% ci = 1.813.16 for patients without comorbidity ; ahr = 1.39 , 95% ci = 1.241.55 for patients with comorbidity ) . the relative risk of chd contributed by gerd was greater in the patients without comorbidity than in those with comorbidity . 1 , the probability of chd was significantly higher in the gerd cohort than in the comparison cohort ( log - rank test , p  <  0.001 ) . however , the incidence of chd was not correlated with the total duration of gerd ( table 2 ) and a significant relationship existed between schoenfeld residuals for gerd and follow - up time ( p value = 0.002 ) . the ahr was greatest during the first 2 years follow - up after gerd diagnosis , even though the risk of chd remained correlated with gerd within the first 5 years after gerd diagnosis . comparison of incidence and hazard ratio of coronary heart disease stratified by sex , age , comorbidity , and follow - up years between those subjects with and without gerd . table 3 shows the hrs of chd associated with age , sex , and comorbidities in univariable and multivariable cox regression models . the ahr of chd development increased with every 1-year increment in age ( ahr = 1.03 , 95% ci = 1.031.04 ) , and was higher among men than women ( ahr = 1.30 , 95% ci = 1.181.43 ) . the risk of developing chd was higher in patients with comorbidities of hypertension ( ahr = 2.30 , 95% ci = 2.062.58 ) , hyperlipidemia ( ahr = 1.39 , 95% ci = 1.251.56 ) , and anxiety ( ahr = 1.44 , 95% ci = 1.281.62 ) than in those without the comorbidities . furthermore , the gerd cohort was associated with a higher risk of chd than was the comparison cohort ( ahr = 1.49 , 95% ci = 1.341.66 ) after adjustment for age , sex , hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , copd , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis . hazard ratios of coronary heart disease in association with age , sex , and comorbidities in univariable and multivariable cox regression models . table 4 shows the results of a cox proportional hazard regression analysis of the combined effects of gerd and comorbidities on the risk of chd . compared with the patients without gerd or hypertension , those with gerd and hypertension exhibited an increased risk of chd ( ahr = 3.26 ; 95% ci = 2.773.84 ) . compared with the patients without gerd or hyperlipidemia , those with gerd and hyperlipidemia had an increased risk of chd ( ahr = 2.01 ; 95% ci = 1.712.36 ) . similarly , compared with the patients without gerd and anxiety , those with gerd and anxiety displayed an increased risk of chd ( ahr = 1.98 , 95% ci = 1.692.33 ) . cox proportional hazard regression analysis for the risk of gerd with joint effect of gerd and comorbidity . the risk of chd was higher among the gerd cohort patients who were treated with ppis for < 1 year ( ahr = 1.56 , 95% ci = 1.391.74 ) and more than 1 year ( ahr = 1.67 , 95% ci = 1.342.08 ) than among the control cohort patients . moreover , the relative risk of chd contributed by ppi use was greater for more than 1 year of treatment than for < 1 year of treatment . the second set of cohorts revealed a higher incidence of chd among the patients with gerd than among the propensity score - matched controls ( 11.6 and 8.00 per 1000 person - years , respectively ) ( table 6 ) . the gerd patients had a hr of 1.46 ( 95% ci = 1.281.67 ) for developing chd relative to patients without gerd . incidence ( per 1000 person - years ) and hazard ratio of coronary heart disease in propensity score - matched between those subjects with and without gerd . consistent with the results from previous studies , our study results show that gerd is more common in men than in women ( 50.8% vs 49.2% ) . we identified 12,960 gerd patients , diagnosed through endoscopy or 24-h ph monitoring , from a population of 1,000,000 , indicating a prevalence of approximately 1.3% . in previous population - based studies on gerd in chinese ethnic populations , the prevalence of gerd , diagnosed through direct interviews , was highly variable , with 0.8% identified in singapore , 2.5% in hong kong , and 6.2% in south china . the reason for higher incidence of gerd in men than in women has yet to be fully elucidated , though the relatively low parietal cell mass in women , relatively poor lower esophageal function in men , and higher body mass index or number of gerd - related comorbidities in men might contribute to the trend . our study results indicate that the age - specific relative risk of chd in the gerd cohort decreased with increasing age , but no difference was observed in the risk of chd between patients age 65 years with and without gerd . it is possible that increased prevalence of other chd - associated risk factors in patients age  65 years could have reduced the relative influence of gerd on chd risk . moreover , it has been reported that older patients tend to be insensitive to acid reflux and might become asymptomatic . our study results indicate that gerd patients have a greater number of comorbidities than do non - gerd patients , and indicate that gerd is associated with hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , obesity , copd , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis . according to our analyses , risk of chd is increased in gerd patients who are older , male , or have hypertension , hyperlipidemia , or anxiety . our results indicate that gerd is associated with subsequent chd development after adjustment for age , sex , hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , copd , asthma , biliary stones , anxiety , depression , chronic kidney disease , and cirrhosis . however , further investigation is required to determine whether gerd is a risk factor or epiphenomenon for chd development . previous studies have suggested that shared pathophysiological mechanisms might underlie the association between gerd and chd . first , in linked angina , exposure of the esophageal mucosa to acid and reduced lower esophageal sphincter pressure might compromise myocardial perfusion resulting from coronary spasm and cause arrhythmia through sympathetic activation . in addition , myocardial ischemia can induce esophageal dysmotility or relaxation of the lower esophageal sphincter . second , many visceral pain receptors are polymodal and sensitive to acid , mechanical distension , and changes in temperature . cardiac and esophageal afferent sensory innervations entering the spinal cord can overlap , and thus stimulation of the esophagus or heart might be perceived and summed up over the dermatomes corresponding to either organ . third , the relationship between gerd and sleep disturbances is bidirectional and interactive , and it is well established that sleep apnea increases the risk of a cardiovascular event . finally , ppi use can reduce the cardioprotective effects of certain therapies by reducing the metabolism of antiplatelet agents to their active form . ppis might also reduce the contractility of myocardial tissue and increase homocysteine by impairing the absorption of vitamin b12 . moreover , our results suggest that ppi use might have a detrimental effect on chd , because the risk of chd among the patients treated for more than 1 year was greater than that of patients treated for < 1 year . the increased prevalence of other chd - associated risk factors in older patients might attenuate the effects of gerd on chd risk with increasing age . the risk of developing chd was consistently increased after we have controlled the confounding risk factors as possible as we could , even though the association might be caused by their shared risk factors . however , we still could not ascertain whether there is a causal relationship between gerd and chd or whether the duration of ppi use imposes the deteriorating defect on chd development in a dose johansson et al reported that the incidence of chd significantly differed between patients with and without gerd within 1 month of gerd diagnosis , and the authors suggested that the misinterpretation of prodromal ischemic symptoms as reflux symptoms could have caused this finding . similarly , our results suggest that the risk of chd is greatest in the first 2 years after gerd diagnosis rather than increasing incrementally with follow - up duration after gerd diagnosis ( table 2 ) . the possible reasons for the discordance between the incidence of chd and the total duration of gerd follow - up may include the delayed diagnosis of gerd for the patients with gerd symptoms , the early compromise of myocardial perfusion after gerd diagnosis , and misinterpretation because of overlapping sensory innervation of the esophagus and the heart . however , our results consistently indicate a close association between gerd and chd , and suggest that gerd with ppi treatment for more than 1 year might increase the risk of chd development . according to our research , our study is the largest population - based study to examine the association between gerd and subsequent development of chd . the national database we used contains a representative cohort of 1,000,000 people covered by the taiwan nhi program , and the 12-year observation period ensured the power of our statistical analyses . the evaluated patients were sampled from a stable population and represent approximately 99% of the residents of taiwan . our study also used a longitudinal rather than cross - sectional approach to evaluate the temporal and casual associations between gerd and chd . this is the first population - based study to suggest that gerd is associated with an increased risk of chd development , though some risk factors for gerd are associated with the development of chd . first , we may have overlooked some potential confounding factors because the nhird does not include detailed information on the chd - related lifestyle factors , socioeconomic status , and family history of patients . however , we controlled for a number of potential chd - associated comorbidities and gerd was consistently associated with chd development . third , the proportionality assumption was violated because a significant relationship existed between the schoenfeld residuals for gerd and follow - up time . moreover , the association between gerd severity and chd severity could not be assessed in our study . the casual relationship between gerd and chd may remain debated , but our results support the association between gerd and chd . fourth , the pathophysiological mechanisms of acs and others are quite different . acs might be caused by plaque rupture and arterial thrombosis , whereas mechanisms of coronary artery disease might be related to the progression of atherosclerosis . it might be difficult to validate the date of old myocardial infarction , the beginning of stable angina pectoris , and other forms of chronic ischemic heart disease . nonetheless , gerd was consistently associated in our study with acs and other forms of stable coronary artery disease , particularly angina pectoris and chronic ischemic heart disease ( table 2 ) . however , our study also has strengths such as its longitudinal population - based design and use of nhird records with a large sample size and low loss to follow - up . in addition , the reimbursement policy is universal and operated by a single payer , namely the taiwan government . all insurance claims are scrutinized by medical reimbursement specialists and peer reviewed according to standard diagnosed criteria . doctors or hospitals are heavily penalized if they make incorrect diagnoses or provide incorrect codes . therefore , the chd diagnoses based on icd-9 codes in this study were highly reliable . in addition , related studies have used the same diagnosis method and criteria with icd-9 coding . furthermore , patients with chd diagnosed before the index date and those without complete information in the lhid 2000 were excluded in our study . the inclusion of all chd diagnoses in our end - point data would have reduced the lost recruitment of patients with asymptomatic coronary artery disease because silent myocardial infarction is reported to account for 9% to 37% of all nonfatal myocardial infarction events . in addition , the association between gerd and chd , rather than the casual relationship , can still be supported by our study . finally , the asymptomatic gerd patients might be included in the control patients ; likewise , some patients with asymptomatic chd might be misclassified . however , this misclassification would overestimate the risk of chd in the comparison cohort rather than in the gerd cohort ; therefore , the relative risk of chd contributed by gerd night be greater than that in our study . in conclusion , the results from our population - based cohort study indicate that gerd was associated with an increased risk of developing chd , and ppi usage for more than 1 year might increase the risk of chd .
abstractin this study , we aimed to determine the association between gastroesophageal reflux disease ( gerd ) and subsequent coronary heart disease ( chd ) development , if any , and to evaluate whether longer use of proton pump inhibitors ( ppis ) increases the risk of chd.patients diagnosed with gerd between 2000 and 2011 were identified as the study cohort ( n = 12,960 ) . 
 patients without gerd were randomly selected from the general population , frequency - matched with the study group according to age , sex , and index year , and evaluated as the comparison cohort ( n = 51,840 ) . 
 both cohorts were followed up until the end of 2011 to determine the incidence of chd . 
 the risk of chd was evaluated in both groups by using cox proportional hazards regression models.the gerd patients had a greater probability of chd than the cohort without gerd did ( log - rank test , p  <  0.001 and 11.8 vs 6.5 per 1000 person - years ) . 
 the gerd cohort had a higher risk of chd than the comparison cohort did after adjustment for age , sex , hypertension , diabetes , hyperlipidemia , alcohol - related illness , stroke , chronic obstructive pulmonary disease , asthma , biliary stone , anxiety , depression , chronic kidney disease , and cirrhosis ( adjusted hazard ratio [ ahr ] : 1.49 , 95% confidence interval [ ci ] : 1.341.66 ) . 
 the risk of chd was greater for the patients treated with ppis for more than 1 year ( ahr = 1.67 , 95% ci = 1.342.08 ) than for those treated with ppis for < 1 year ( ahr = 1.56 , 95% ci = 1.391.74).our population - based cohort study results indicate that gerd was associated with an increased risk of developing chd , and that ppi use for more than 1 year might increase the risk of chd .