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(Chest. 2005;127:1658-1666.)
© 2005 American College of Chest Physicians

Predictors of Heartburn During Sleep in a Large Prospective Cohort Study*

Ronnie Fass, MD; Stuart F. Quan, MD, FCCP; George T. O’Connor, MD, FCCP; Ann Ervin, MPH and Conrad Iber, MD, FCCP

* From the Sections of Gastroenterology (Dr. Fass), Department of Medicine, and Pulmonary and Critical Care Medicine (Dr. Quan), Department of Medicine, and the Arizona Respiratory Center, University of Arizona College of Medicine, Tucson, AZ; the Department of Medicine (Dr. O’Connor), Boston University, Boston, MA; the Johns Hopkins University (Ms. Ervin), Baltimore, MD; and the Department of Medicine (Dr. Iber), University of Minnesota, Minneapolis, MN.

Correspondence to: Ronnie Fass, MD, Southern Arizona VA Health Care System, Gastroenterology Section (1–111G-1), Tucson, AZ 85723-0001; e-mail: Ronnie.Fass{at}med.Va.gov


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Background and aims: Nocturnal gastroesophageal reflux, which may result in nocturnal heartburn, has been demonstrated to be associated with a more severe form of gastroesophageal reflux disease (GERD). The aim of this study was to determine the clinical predictors of heartburn during sleep in a large prospective cohort study.

Methods: Study subjects were members of the parent cohorts from which the Sleep Heart Health Study (SHHS) recruited participants. SHHS is a multicenter, longitudinal, cohort study of the cardiovascular consequences of sleep-disordered breathing. As part of the recruitment process, parent cohort members completed a questionnaire that permitted an assessment of the relationships between heartburn during sleep, and patient demographics, sleep abnormalities, medical history, and social habits in nine community-based parent cohorts across the United States. All variables, significant at the p < 0.05 level, were included as independent variables in multivariate logistic regression models with heartburn during sleep status included as the dependent variable

Results: A total of 15,314 subjects completed the questions about heartburn during sleep, and of these, 3,806 subjects (24.9%) reported having this symptom. In four increasingly comprehensive multivariate models, increased body mass index (BMI), carbonated soft drink consumption, snoring and daytime sleepiness (Epworth sleepiness scale score), insomnia, hypertension, asthma, and usage of benzodiazepines were strong predictors of heartburn during sleep. In contrast, college education decreased the risk of reporting heartburn during sleep.

Conclusions: Heartburn during sleep is very common in the general population. Reports of this type of symptom of GERD are strongly associated with increased BMI, carbonated soft drink consumption, snoring and daytime sleepiness, insomnia, hypertension, asthma, and usage of benzodiazepines. Overall, heartburn during sleep may be associated with sleep complaints and excessive daytime sleepiness.

Key Words: cohort studies • gastroesophageal reflux • heartburn • sleep


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Gastroesophageal reflux disease (GERD) is a very common disorder. Heartburn and acid regurgitation are the most common symptoms reported by patients with GERD.12 In the United States, 44% of the adult population has reported experiencing heartburn at least once a month, 14% have reported experiencing it weekly, and 7% have reported experiencing it daily,13 resulting in a significant adverse impact on quality of life.45 However, the relationship between GERD symptoms and gastroesophageal reflux is complex. GERD symptoms may be present in the absence of abnormal gastroesophageal reflux or absent in the presence of abnormal esophageal acid exposure.6

Nocturnal gastroesophageal reflux, which may result in heartburn during sleep, has been demonstrated to be associated with a more severe form of GERD. Unlike upright reflux (experienced while awake), which tends to be short and resolves quickly, supine reflux (experienced during sleep) tends to be longer and resolves slowly.78 Consequently, there is an association between nocturnal reflux, and more severe erosive esophagitis,9 Barrett’s esophagus,10 and greater risk for esophageal adenocarcinoma.11 Furthermore, nocturnal acidification of the esophagus has been associated with extraesophageal manifestations of GERD, perhaps because of the migration of minute volumes of acid to both the midesophagus and proximal esophagus during sleep.12 Laryngitis, pharyngitis, asthma, and aspiration pneumonia have been suggested to be more common in GERD patients who experience nocturnal gastroesophageal reflux than in those who do not.131415 Most importantly, the overall quality of life of patients with heartburn during sleep appears to be significantly worse than in patients with daytime heartburn only.5

The studies mentioned above have demonstrated the importance of nocturnal gastroesophageal reflux in promoting not only esophageal mucosal injury and the involvement of organs proximal to the esophagus, but also in altering patients’ perceptions of the severity of their disease. Unfortunately, although nighttime heartburn has been reported to affect 47 to 79% of GERD patients,116 many studies171819 have not included a definition of nocturnal or nighttime heartburn. Thus, factors associated with heartburn during sleep remain to be determined. Consequently, the aim of this study was to determine the demographic, social, and medical factors predictive of heartburn during sleep in a large prospective cohort study. In particular, we sought to determine whether heartburn during sleep was associated with various complaints of disrupted sleep.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Study Population
The Sleep Heart Health Study (SHHS) is a multicenter, prospective cohort study that is investigating the relationship between sleep-disordered breathing and cardiovascular diseases in the United States. Recruitment began in 1995, and, unlike most prospective population-based studies, SHHS did not enroll a new cohort. Rather, its participants were enlisted from existing cohorts of ongoing cardiovascular and respiratory disease research projects (parent cohorts),20 as follows: the Framingham Heart Study; the Hagerstown, MD, and Minneapolis, MN, sites of the Atherosclerosis Risk in Communities Study; the Hagerstown, MD, Pittsburgh, PA, and Sacramento, CA, sites of the Cardiovascular Health Study; the Strong Heart Study (SHS); two Tucson cohorts involved in a "Chronic Diseases of the Airways" Specialized Center of Research program (the Tucson Epidemiologic Study of Airways Obstructive Diseases and the Tucson Health and Environment Study; and three cohorts (Worksite, Hypertension Clinic, and Menopause) from New York City involved in a Cornell University program (now based at Mt. Sinai Hospital) project grant entitled "Psychosocial Factors and Cardiovascular Disease." The design, rationale, and methods of SHHS as well as a brief description of the parent cohorts have been previously published.20 As part of the SHHS recruitment process, all members of these parent cohorts were asked to complete the SHHS sleep habits questionnaire (SHQ [vide infra]), irrespective of whether they were ultimately recruited into the SHHS. From December 1995 to February 1998, a total of 15,699 individuals of 30,773 total members21 from these parent cohorts completed this questionnaire. The 51% completion rate of the SHQ by parent cohort members reflected differences among the parent cohort members in recruitment practices for SHHS21 and a refusal by some to complete the questionnaire. Subsequently, from those completing the SHQ, 6,441 subjects who were at least 40 years of age were enrolled into the SHHS. However, because of missing data on the SHQ, data from only 6,395 participants were used in these analyses. As previously described, emphasis was placed on the recruitment of snorers who were < 65 years of age and ethnic minorities.20 These participants completed additional questionnaires pertaining to their sleep and personal health, and underwent the collection of anthropometric data and home polysomnography.20 As previously reported,21 the characteristics of those eligible for recruitment and those actually enrolled in the SHHS differed minimally. In general, SHHS participants were slightly younger, had more years of education, were more likely to snore, had higher Epworth sleepiness scale (ESS) scores, and slightly higher BPs and body mass index (BMI).21

The SHHS was approved by the institutional review boards of the participating institutions. Appropriate informed consent was obtained, and procedures conformed to the Declaration of Helsinki on human research.

SHHS SHQ
This self-completion questionnaire includes 20 items about self-reported sleep habits, snoring, sleepiness, obstructive sleep apnea (OSA), and general symptoms related to sleep.20 The SHQ contains well-accepted items that have been used previously in several population-based studies, such as the Wisconsin Sleep Cohort22 and the Tucson Epidemiologic Study of Obstructive Airways Disease.23

The SHQ incorporates the ESS, a well-validated eight-item, self-completion questionnaire that asks the subject to rate his or her likelihood of falling asleep in a variety of commonly encountered situations.2425 Possible scores range from 0 (the least sleepy) to 24 (the most sleepy). The ESS score correlates with the severity of OSA and with an index of objectively measured sleepiness in patients with OSA.2627 An ESS score of ≥ 10 is indicative of significant sleepiness,24 and for this analysis, those subjects with an ESS score of > 10 were considered to be sleepy.

There were three items on the questionnaire pertaining to insomnia. Subjects were asked to "Please indicate how often you experience each of the following":

  1. Have trouble falling asleep;
  2. Wake up during the night and have difficulty getting back to sleep; and
  3. Wake up too early in the morning and are unable to get back to sleep.

For the purposes of this analysis, insomnia was defined as responding to any one of these three items five or more times per month.

Snoring was ascertained using responses to the following questions: "Have you ever snored?" and "How often do you snore?" Snoring was considered to be present if it occurred more frequently than three nights per week. For the purposes of this analysis, participants reporting snoring > 3 nights per week and feeling excessively sleepy during the day > 5 days per month were considered as having symptomatic OSA. The presence of both habitual snoring and daytime sleepiness has been used in many surveys2829 to identify individuals with symptomatic OSA.

Heartburn During Sleep
Although the design of the SHHS was primarily directed toward the assessment of sleep and sleep-disordered breathing, the SHQ also included response items pertaining to heartburn during sleep. Presently, there is no consensus definition for heartburn during sleep. Moreover, many therapeutic studies assessing the nocturnal effect of antireflux treatment on GERD symptoms have not included any definition of nocturnal/nighttime heartburn. Thus, it is possible that the interpretation of what is meant by heartburn during sleep varied considerably among participants in these studies. In contrast, on the SHQ, subjects were specifically asked "In the past year, how often, on average, have you been awakened during the night with heartburn or indigestion?" For the purpose of this study, heartburn during sleep was defined as heartburn that awakened the subject two or more times per month. Although this definition is more restrictive, we think that it was very clear to subjects and resulted in more consistent responses.

Anthropometric, Medical, and Social Information
The SHHS was designed to add an assessment of sleep and sleep-disordered breathing to the information already collected by parent cohorts pertaining to cardiovascular risk. Thus, the SHHS uses information already obtained from the parent cohorts in addition to its own data in its analyses. In the present study, data pertaining to age, race, gender, participant educational level, BMI, alcohol consumption, the presence of self-reported diabetes mellitus and hypertension, and spirometry were collected by the parent cohorts. However, information concerning a self-reported history of myocardial infarction, coronary artery bypass surgery, stroke, congestive heart failure, asthma, or COPD, the use of caffeinated beverages, and a detailed inventory of current medication usage was obtained at the time of SHHS data collection. The following drug classes were included in this analysis: nitrates; calcium channel blockers; antidepressants; and benzodiazepines (these drugs have been reported to increase the risk for gastroesophageal reflux).30

Statistical Analysis
Analyses were conducted using a statistical software package (SAS for Windows, version 8; SAS Institute; Cary, NC). Age categories represent decades of age. BMI categories were defined using established clinical guidelines for normal weight (≤ 24.9 kg/m2), overweight (25 to 29.9 kg/m2), and obesity (≥ 30 kg/m2).31 Spirometry categories were dichotomized as obstructive (FEV1/FVC ratio, < 0.7) or nonobstructive (FEV1/FVC ratio, ≥ 0.7).32 Participants who designated their ethnicity as "other" were excluded from race-specific analyses. The association of heartburn during sleep status with predictor variables of interest was assessed by {chi}2 tests. Bivariate logistic regression analysis provided odds ratios (ORs) and 95% confidence limits.

Variables with significant bivariate associations at the p < 0.05 level were considered for multivariate logistic regression. Among the significant factors, the following four covariate groups were identified: demographics (ie, gender, age, college education, ethnicity, and BMI); sleep factors (ie, sleepiness, snoring, and insomnia); medical conditions/medications (ie, use of antidepressants, calcium channel blockers, or benzodiazepines, hypertension, stroke, spirometry, and asthma); and social habits (ie, smoking, alcohol use, and carbonated soft drink intake). To determine the confounding effect of covariate groups, forward-selection regression procedures were employed to identify the most parsimonious model in the following four additive scenarios: (1) demographics only; (2) demographics and sleep factors; (3) demographics, sleep factors, and medical conditions/medications; and (4) demographics, sleep factors, medical conditions/medications, and social habits. The {chi}2 probability for entry into the model was set at p < 0.10. Multivariate models 1 and 2 were constructed from data collected from the SHQ (n = 15,699). Multivariate models 3 and 4, which included medical conditions/medications and/or social habits, utilized data only from the actual SHHS cohort (n = 6,396) because data concerning self-reported medical conditions and social habits were not available from those subjects completing only the SHQ.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
A total of 15,699 subjects were included in this study. Table 1 presents the demographic characteristics of this population. Consistent with the inclusion of the SHS as one of SHHS parent cohorts, the sample included a disproportionate number of American Indians relative to the general population of the United States and had a slight preponderance of female subjects. Of the 15,314 subjects who responded to the heartburn-during-sleep question, 3,806 subjects (24.9%) reported having heartburn during sleep. In comparison to the 11,508 individuals without nocturnal heartburn, the proportion of female subjects was the same (heartburn during sleep, 57.4%; no heartburn during sleep, 54.5%). However, those subjects who experienced heartburn during sleep were slightly younger (mean [± SD] age, 63.26 ± 10.0 years vs 63.68 ± 10.5 years, respectively; p = 0.039) and had a higher mean BMI (29.09 ± 5.5 vs 27.8 ± 5.2, respectively; p < 0.0001).


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  		Table 1.. Demographic Characteristics of Subjects*

 
As indicated previously, 6,441 of the 15,699 subjects who completed the SHQ eventually were recruited into the SHHS, of whom 6,396 subjects were used in these analyses. The demographic characteristics of these individuals are shown in Table 1. In comparison to the total sample, this subset of subjects was slightly younger and had a slightly lower percentage of female subjects. In addition, the percentages of African Americans and Hispanics were somewhat higher, and the percentage of American Indians was lower than in the larger sample. This was related in part to the ethnic recruitment targets used in the SHHS.

In Table 2 , the bivariate associations of the predictor variables used in this study with heartburn during sleep are shown. With respect to demographic characteristics, a significant positive association was observed for BMI. Male subjects were less likely to report heartburn than female subjects. College education also was associated with a lower risk of heartburn. In comparison to whites, American Indians were more likely to have heartburn during sleep. Strikingly, heartburn during sleep was strongly associated with all variables reflecting subjectively disturbed sleep. Unadjusted ORs for the following medical conditions and social habits also showed positive associations with heartburn during sleep: current smoking; hypertension; stroke; asthma; and carbonated soft drink use. In addition, heartburn during sleep was associated with the use of antidepressants, calcium channel blockers, and benzodiazepine medications. Surprisingly, reduced spirometry was associated with a lower risk of heartburn during sleep.


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  		Table 2.. Bivariate Associations With Nocturnal Heartburn*

 
As shown in Table 3 , an initial multivariate analysis was conducted using only demographic variables. We found that the top two quartiles of BMI were associated with heartburn during sleep with an adjusted OR in the top quartile (1.911). Age also was related to heartburn during sleep with men who were 64 to 71 years old having an adjusted OR of 1.2. However, this relationship was not apparent in those men who were > 71 years old. Furthermore, although gender no longer was associated with heartburn during sleep after controlling for age, BMI, education, and ethnicity, those with a college education continued to be less likely to report heartburn during sleep. Our initial bivariate analyses suggested that American Indians were more likely to have heartburn during sleep. However, these findings were no longer present after adjustment for BMI, age, and college education.


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  		Table 3.. Forward Stepwise Multivariate Models With Demographic Factors, Sleep Disturbances, Medical History, and Social Habits*

 
Also in Table 3, three additional multivariate models are shown that are characterized by successive additive adjustments for variables related to sleep disturbances, medical conditions including use of medications, and, finally, social habits. The latter two models (adding successively medical history and social factors) utilize data only from the actual SHHS cohort, because data concerning self-reported medical conditions and social habits were not available from those subjects completing only the SHQ. The model incorporating demographic and sleep variables used data from all SHHS parent cohort participants and demonstrated that the relationships between heartburn during sleep, and both BMI and college education remain. Similar to the bivariate analyses, all sleep variables including both snoring alone and symptomatic OSA were strongly associated with heartburn during sleep. However, age was no longer a factor in the model. The next model in which the effects of various medical conditions and medication use were added utilized data only from SHHS participants, and demonstrated that self-reported hypertension and asthma as well as the use of benzodiazepines are related to heartburn during sleep. College education, insomnia, snoring, and daytime sleepiness (ie, ESS score) remained in the model, but symptomatic OSA did not. The final model included the addition of various social habits and also utilized data only from SHHS participants. In this model, all previous variables remained significant. In addition, the use of carbonated soft drinks was entered into the model, but alcohol use and smoking were not.

In the four additive scenarios, the multivariate forward-selection regression eliminated the following variables from those found to be associated with heartburn during sleep using bivariate analyses: (1) demographic factors only (ie, gender, ethnicity, and age); (2) demographic and sleep factors (ie, gender and age); (3) demographic, sleep factors, and medical conditions/medications (ie, gender, age, OSA, stroke, and calcium channel blocker use); and (4) demographic, sleep factors, medical conditions/medications, and social habits (ie, gender, age, OSA, stroke, calcium channel blocker use, antidepressant use, spirometry, smoking, and alcohol use).


   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Very few epidemiologic studies have attempted to characterize the demographics of GERD patients who report heartburn during sleep. Farup et al5 evaluated 1,284 GERD patients using a national population-based telephone interview survey. Nocturnal GERD symptoms were defined as being awakened at night by GERD symptoms, being awakened at night by coughing or choking because of fluid, having an acid bitter taste or food in the throat, having GERD symptoms when lying down to sleep at night, and waking up in the morning with GERD symptoms. This is a more inclusive definition that may include GERD-related symptoms that are not necessarily affected by sleep physiology. Additionally, lying down to sleep or waking up in the morning may be interpreted by patients as different periods of times. In another telephone survey,16 which was sponsored by the American Gastroenterological Association, 1,000 GERD patients were evaluated for nighttime heartburn. However, this survey lacked any definition of nighttime heartburn.

Our study is the largest thus far to provide an epidemiologic analysis of heartburn during sleep. A total of 15,314 subjects from nine different centers around the country were evaluated. Additionally, a clear definition, albeit restrictive, of heartburn during sleep was used. This is also the first study to report the prevalence of heartburn during sleep in a large parent cohort, unlike the other two prevalence studies,1633 which were conducted in GERD patients only. Consequently, this study provided a unique opportunity to determine the factors associated with reports of heartburn during sleep in the general population.

Of the demographic parameters, using bivariate analysis, male gender and college education were found to decrease the risk of reporting heartburn during sleep. However, while male gender became a nonsignificant variable in the multivariate models, college education remained significant after adding multiple confounding factors. The protective effect of college education in relation to heartburn during sleep is difficult to explain but may be related to the level of understanding of surveys. Additionally, college education may be a surrogate for differences in lifestyle and diet, and a greater knowledge about the precipitating factors of GERD. The future assessment of the reasons for fewer reports of heartburn during sleep in subjects having a college education compared to those who lack a college education is vital and may reveal factors that should be recognized as having an impact on reports of GERD-related symptoms.

Not surprisingly, greater BMI (top two quartiles) was associated with increased reports of heartburn during sleep. Several studies3435 have reported a higher prevalence of GERD symptoms as well as increased esophageal acid exposure with greater BMI. Our study is the first to demonstrate an association between increased BMI and heartburn specifically during sleep. However, the mechanism by which increased BMI contributes to GERD remains an area of intense controversy.

Of the various social habits that have been suggested to promote gastroesophageal reflux (eg, smoking and alcohol use), only carbonated soft drink consumption was highly associated with reports of heartburn during sleep in this study. Lagergren et al11 also found that tobacco smoking and alcohol use were not strongly associated with gastroesophageal reflux symptoms. However, none of the studies assessed the intake of carbonated soft drinks as an important factor for GERD symptoms in general or specifically for heartburn during sleep. Thus, this study provides strong evidence that the use of carbonated beverages is an important underlying mechanism, not only for daytime reflux but also for nocturnal reflux. Feldman and Barnett36 compared the relationship between the acidity and osmolality of popular beverages, and reported postprandial heartburn. The authors36 found that carbonated beverages had the lowest pH values of any of the beverages studied and that reduced pH among carbonated beverages was correlated with heartburn scores. Further studies are needed in GERD subjects who consume carbonated beverages prior sleep to determine the mechanism and duration of the effect.

All factors associated with sleep and sleep-disordered breathing that we assessed were strongly associated with reports of heartburn during sleep in our multivariate models. Insomnia had the highest calculated OR (2.05) and may be the result rather than the cause of heartburn during sleep. Similarly, although sleepiness, as measured by the ESS score, was not a factor in our fully adjusted model, its presence in our less comprehensive models also suggests that it may be a consequence rather than cause of heartburn during sleep. The exact relationship between symptomatic OSA and GERD remains an area of intense research. We observed that a symptom complex of snoring and sleepiness, with the latter defined using either the ESS score or self-report, was associated with heartburn during sleep even in our most fully adjusted model. This symptom complex is a good, albeit not perfect, surrogate for OSA, and indicates that there is a link between OSA and GERD. Given that many of the known risk factors, such as obesity and alcohol use, for both conditions are the same, this observation is not surprising. However, the association may not just be limited to epidemiologic relationships because there are potential causal pathways. GERD has been proposed as a potential cause for symptomatic OSA, and several therapeutic studies3738 using antireflux treatment have demonstrated a decline in the mean apnea index and a reduction in the number of arousals. In contrast, other studies have claimed that GERD is a consequence of OSA pathophysiology. Those studies3940 have suggested that hyperinflation during apnea may interfere with the diaphragmatic augmentation of the lower esophageal sphincter (LES) and that apneic episodes may generate an increase in the transdiaphragmatic pressure gradient due to a more negative intrathoracic pressure. Irrespective of whether GERD contributes to OSA or OSA is a risk factor for GERD, the association between these two conditions is sufficiently robust to suggest that clinicians should be alert for the presence of both even if a patient presents with symptoms of only one.

Of the three types of medications (ie, antidepressants, calcium channel blockers, and benzodiazepines) known to precipitate gastroesophageal reflux due to their effect on lower esophageal resting pressure and/or esophageal motility, only the use of benzodiazepines was significantly associated with heartburn during sleep in all four multivariate models. Benzodiazepines have been demonstrated,4142 both in animal models and in humans, to decrease the basal LES pressure and to increase the number of gastroesophageal reflux events. However, it is not clear why benzodiazepines show a stronger relationship with heartburn during sleep compared to other types of medications that are also known to affect the basal LES pressure. Several benzodiazepines are commonly used hypnotics, and thus one potential explanation, albeit incomplete, is that there is greater consumption of these compounds at bedtime. Nevertheless, future studies are needed to determine the mechanism by which benzodiazepines appear to have a more symptomatic effect on heartburn at nighttime.

Hypertension was also strongly associated with heartburn during sleep, and that may be due to factors other than hypertension per se. Antihypertensive medications, comorbid factors, diet, and body habitus may all contribute to the occurrence of nocturnal heartburn, or only some may.

Previous studies4344 have demonstrated a strong association between asthma and gastroesophageal reflux, although the extent of causality remains unknown. Asthma may cause gastroesophageal reflux by increasing the pressure gradient between the thorax and abdomen.44 On the other hand, gastroesophageal reflux may result in asthma by small aspirations of acid or through the vagovagal reflex arc.45 Studies46 have shown that adult asthmatic patients are more prone to developing nocturnal bronchoconstriction due to gastroesophageal reflux. It is possible that these events are also associated with heartburn during sleep, explaining the significant association between the latter and asthma.

We acknowledge that, despite its large size, there are several drawbacks to the study that need to be considered in interpreting our findings. First, in any epidemiologic study there is the possibility of selection bias. In the case of the SHHS, because the cohort was selected from surviving participants of other population-based cohorts, estimates of the effects of the various factors identified as risks for heartburn during sleep in this study may be biased in relation to the parent cohorts or to the original source populations. However, although neither the SHHS nor its parent studies constitute random samples from any well-defined population, we have no a priori reason to suspect that selection bias affected the estimates of the relationship between various factors used in this analysis and heartburn during sleep. Second, the data used in this analysis were based on self-report. Thus, there is the possibility of error in the ascertainment of both heartburn and the various factors that we identified as being associated with it. However, we have no reason to believe that there was any systematic bias in the assessment of any of these factors. Third, the data in the SHHS were limited to those who were at least 40 years of age. Thus, our conclusions are not necessarily generalizable to younger individuals.

Gislason et al47 have assessed the association between reported symptoms of gastroesophageal reflux after bedtime, and sleep-disordered breathing, respiratory symptoms, and asthma. While the authors used a clear definition of heartburn during sleep (ie, heartburn after going to bed), it likely included GERD symptoms that were reported by subjects who were lying in bed awake. Regardless, the authors demonstrated that subjects with heartburn during sleep were more often overweight, had symptoms of sleep-disordered breathing, and had received a diagnosis of asthma, further supporting the results of our study.

In conclusion, this is the largest epidemiologic study to date to evaluate the clinical predictors for reports of heartburn during sleep in a large parent cohort. Due to the size of the sample, the ethnic and gender diversity, and the "tight" definition of heartburn during sleep, the results are likely to be more reliable. Some of the factors that were strongly associated with heartburn during sleep need to be further assessed for determination of the exact mechanism. Overall, increased BMI, carbonated soft drink consumption, snoring, daytime sleepiness, insomnia, hypertension, asthma, and the use of benzodiazepines were significant predictors for reports of heartburn during sleep, while college education was protective from reports of heartburn during sleep. Heartburn during sleep may represent a symptom of aggressive GERD, and thus further understanding of the predisposing factors for this complaint is strongly needed.


   Acknowledgements
 
The SHHS acknowledges the Atherosclerosis Risk in Communities Study, the Cardiovascular Health Study, the Framingham Heart Study, the Cornell/Mt. Sinai Worksite and Hypertension Studies, the SHS, the Tucson Epidemiologic Study of Airways Obstructive Diseases, and the Tucson Health and Environment Study for allowing their cohort members to be part of the SHHS, and for permitting the data acquired by them to be used in the study. The SHHS is particularly grateful to the members of these cohorts who agreed to participate in the SHHS as well. The SHHS further recognizes all of the investigators and staff who have contributed to its success. A list of SHHS investigators, staff, and their participants’ institutions is available on the SHHS web site (www.jhsph.edu/shhs).


   Footnotes
 
Abbreviations: BMI = body mass index; ESS = Epworth sleepiness scale; GERD = gastroesophageal reflux disease; LES = lower esophageal sphincter; OR = odds ratio; OSA = obstructive sleep apnea; SHHS = Sleep Heart Health Study; SHQ = sleep habits questionnaire; SHS = Strong Heart Study

This work was supported by National Heart, Lung and Blood Institute cooperative agreements U01HL53940 (University of Washington), U01HL53941 (Boston University), U01HL53938 (University of Arizona), U01HL53916 (University of California, Davis), U01HL53934 (University of Minnesota), U01HL53931 (New York University), U01HL53937 and U01HL64360 (Johns Hopkins University), U01HL63463 (Case Western Reserve University), and U01HL63429 (Missouri Breaks Research).

This study was presented in part during the annual meeting of the American Gastroenterological Association, San Francisco, CA, May 18–22, 2002.

The opinions expressed in this article are those of the authors who do not necessarily reflect the views of the Indian Health Service.

Received for publication May 6, 2004. Accepted for publication November 12, 2004.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

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