Body-Mass Index and Symptoms of Gastroesophageal Reflux in Women 【关键词】 Symptoms, 关键词】 ABSTRACT Background Overweight and obese persons are at increased risk for gastroesophageal reflux disease. An association between body-mass index (BMI) ― the weight in kilograms divided by the square of the height in meters ― and symptoms of gastroesophageal reflux disease in persons of normal weight has not been demonstrated. Methods In 2000, we used a supplemental questionnaire to determine the frequency, severity, and duration of symptoms of gastroesophageal reflux disease among randomly selected participants in the Nurses' Health Study. After categorizing women according to BMI as measured in 1998, we used logistic-regression models to study the association between BMI and symptoms of gastroesophageal reflux disease. Results Of 10,545 women who completed the questionnaire (response rate, 86 percent), 2310 (22 percent) reported having symptoms at least once a week, and 3419 (55 percent of those who had any symptoms) described their symptoms as moderate in severity. We observed a dose-dependent relationship between increasing BMI and frequent reflux symptoms (multivariate P for trend <
  0.0
  01). As compared with women who had a BMI of
  20.0 to
  22.4, the multivariate odds ratios for frequent symptoms were
  0.67 (95 percent confidence interval,
  0.48 to
  0.
  93) for a BMI of less than
  20.0,
  1.38 (95 percent confidence interval,
  1.13 to
  1.
  67) for a BMI of
  22.5 to
  24.9,
  2.20 (95 percent confidence interval,
  1.81 to
  2.
  66) for a BMI of
  25.0 to
  27.4,
  2.43 (95 percent confidence interval,
  1.96 to
  3.
  01) for a BMI of
  27.5 to
  29.9,
  2.92 (95 percent confidence interval,
  2.35 to
  3.
  62) for a BMI of
  30.0 to
  34.9, and
  2.93 (95 percent confidence interval,
  2.24 to
  3.
  85) for a BMI of
  35.0 or more. Even in women with a normal baseline BMI, an increase in BMI of more than
  3.5, as compared with no weight changes, was associated with an increased risk of frequent symptoms of reflux (odds ratio,
  2.80; 95 percent confidence interval,
  1.63 to
  4.
  82). Conclusions BMI is associated with symptoms of gastroesophageal reflux disease in both normal-weight and overweight women. Even moderate weight gain among persons of normal weight may cause or exacerbate symptoms of reflux. Gastroesophageal reflux disease, with hallmark symptoms of heartburn and acid regurgitation,1 is a common disorder, affecting up to 60 percent of persons at some time during the course of a year and 20 to 30 percent of persons at least weekly.2,3 Gastroesophageal reflux disease accounts for at least 9 million office visits to physicians in the United States each year and costs approximately $10 billion annually.4 Frequent or severe symptoms of gastroesophageal reflux disease are associated with time lost from work,5 impaired health-related quality of life,6 and esophageal adenocarcinoma,7 further emphasizing the clinical significance of this entity. Several cross-sectional studies and one meta-analysis have demonstrated a positive association between elevated body-mass index (BMI) ― the weight in kilograms divided by the square of the height in meters ― and symptoms of gastroesophageal reflux disease.8,9,10,11,12,13,14,15,16 However, in these previous studies, analyses were restricted to overweight and obese subjects, with those who had a BMI of less than 24 or less than 25 serving as a reference group. We sought to explore more fully the association between BMI and symptoms of gastroesophageal reflux disease by determining the relative risks among a broader range of categories of BMI and among persons with various degrees of frequency, severity, and duration of symptoms. Methods
The cohort of the Nurses' Health Study was established in 1976, when 121,700 female registered nurses, 30 to 55 years of age, completed a mailed questionnaire about risk factors for cancer and cardiovascular disease. Participants have subsequently received follow-up questionnaires every two years. In 2000, a supplemental questionnaire about gastroesophageal reflux disease was sent to 11,080 participants with asthma and chronic obstructive pulmonary disease (COPD) and 11,080 randomly selected controls. For this analysis of BMI, the study population consisted of 11,080 control participants without asthma or COPD plus 1112 randomly selected women with airway disease (to represent the percentage of the entire Nurses' Health Study cohort with these conditions), for a total population of 12,192 women. The supplemental questionnaire inquired about the frequency, severity, and duration of heartburn and acid regurgitation. We defined symptoms of gastroesophageal reflux disease as the presence of heartburn, acid regurgitation, or both. Heartburn was defined as "a burning pain or discomfort behind the breast bone in your chest," and acid regurgitation as "a bitter or sour-tasting fluid coming into your throat or mouth," definitions that have been validated previously.17 The frequency of symptoms was reported as none in the past year, less than once a month, about once a month, about once a week, several times a week, and daily. We considered symptoms occurring once a week or more as frequent. Severity of symptoms was reported as mild ("can be ignored if I don't think about it"), moderate ("cannot be ignored but does not affect my lifestyle"), severe ("affects my lifestyle"), and very severe ("markedly affects my lifestyle"). Participants were also asked for the year when their symptoms began, whether they were awakened at night by symptoms, and whether they were taking antacid, antisecretory, or gastric-motility agents. We determined BMI from measurements of height provided by participants in the 1976 Nurses' Health Study questionnaire and from measurements of weight in the 1998 questionnaire. A 1980 questionnaire was used to obtain participants' weight at the age of 18 years. Waist and hip measurements were self-reported in 19
  86. The smoking status and history of diabetes mellitus were obtained in 1976 and updated every two years thereafter. Use of antihypertensive and asthma medication was assessed with the 1998 questionnaire. Menopausal status and use of postmenopausal hormones were determined in 1976 and updated every two years thereafter. Dietary information, including intake of coffee, tea, and alcohol, and information about physical activity were obtained in 19
  98. Each activity reported was measured in metabolic-equivalent (MET) hours per week. One MET represents the energy expended during one hour of rest. Self-reported BMI, waist and hip measurements, age at menopause, dietary information, and physical activity have been validated previously.18,19 Women were categorized according to BMI (<
  20.0,
  20.0 to
  22.4,
  22.5 to
  24.9,
  25.0 to
  27.4,
  27.5 to
  29.9,
  30.0 to
  34.9, and
  35.
  0). We used age- and multivariate-adjusted unconditional logistic regression to obtain odds ratios and 95 percent confidence intervals for the risk of reporting frequent symptoms of gastroesophageal reflux disease. For these analyses, women with a BMI of
  20.0 to
  22.4 served as the reference population. A test for trend across the categories of interest (e.g., BMI) was calculated by treating each category as an ordinal variable in the multivariate model. Potentially confounding variables included age; cigarette smoking (never smoked, former smoker, or current smoker); total daily activity in MET per week; total daily caloric intake; the number of drinks of alcohol, coffee, and tea per day; servings of chocolate per day; use of postmenopausal hormone therapy (premenopausal use, never any use, former use, current use of estrogen only, or current use of estrogen plus progesterone); use of antihypertensive or asthma medication; and presence or absence of a history of diabetes. To maximize the specificity of symptoms of gastroesophageal reflux disease for our primary analyses, we considered only participants with frequent symptoms and excluded women with symptoms less frequent than weekly. We analyzed the association between BMI and symptoms of gastroesophageal
reflux disease on the basis of severity and duration. We performed two analyses specifically to detect the presence of reverse causality between BMI and symptoms of gastroesophageal reflux disease (i.e., that reflux symptoms result in increased BMI). In one, we limited the analysis to women reporting symptoms for less than five years according to their BMI in 1994 (six years before the assessment of symptoms). In the second analysis, we studied women reporting at least 10 years of symptoms and used their 1984 BMI (16 years before the assessment of symptoms). Further analyses examined the associations between BMI and nocturnal symptoms of gastroesophageal reflux disease and between the waist-to-hip ratio and such symptoms. The attributable risks of symptoms of gastroesophageal reflux disease due to adiposity were calculated with multivariate relative risks (in this case, odds ratios) with the use of the formula (RR
  1)÷RR, where RR is the relative risk, and with a BMI of
  20.0 to
  22.4 as the referent. We evaluated the effect of weight change on symptoms by calculating the change in BMI between 1984 and 1998 and between age 18 and 19
  98. Women with missing BMI data were excluded from the analyses. We conducted all analyses with the use of SAS software (version
  8.
  2); two-sided P values of less than
  0.05 were considered to indicate statistical significance. The study was approved by the institutional review board of Brigham and Women's Hospital. Results A total of 10,545 participants returned the questionnaire about gastroesophageal reflux disease (response rate, 86 percent). Of these, 2497 (24 percent) reported having symptoms of gastroesophageal reflux disease less than once a month, 1302 (12 percent) once a month, 986 (9 percent) once a week, 1027 (10 percent) several times a week, and 297 (3 percent) daily. Frequency was missing for 106 women (2 percent). Therefore, 6215 women (59 percent) had symptoms and 2310 (22 percent) reported having symptoms at least once a week and were considered to have frequent episodes of gastroesophageal reflux disease. Of the women with symptoms, 3394 (55 percent) reported having both heartburn and acid regurgitation. No heartburn or acid regurgitation was reported in the previous year by 4330 women (41 percent), but 414 of these asymptomatic women reported taking medications often used for symptoms of gastroesophageal reflux disease, such as proton-pump inhibitors. To avoid potential misclassification, these women were excluded from the analysis, leaving 3916 women who were categorized as noncases. Of the women with symptoms of gastroesophageal reflux disease, 3419 (55 percent) described their symptoms as moderate in severity, 2396 (39 percent) as mild, 273 (4 percent) as severe, and 30 (<1 percent) as very severe. Data about severity were missing for 97 women (2 percent). Information about the year of onset of symptoms was available for only 2765 (44 percent) of the women. Among those who provided information about duration, 1180 (43 percent) had had symptoms of gastroesophageal reflux disease for less than 5 years, 400 (14 percent) had had symptoms for 5 to 9 years, and 1185 (43 percent) had had symptoms for at least 10 years. Characteristics of participants with frequent symptoms of gastroesophageal reflux disease and of those without symptoms are presented in Table
  1. Women with frequent symptoms were more likely than women without symptoms to have a higher BMI, to have used hormone therapy or asthma or antihypertensive medications, to have a greater daily caloric intake, and to be less active. At the time of the survey, women with gastroesophageal reflux disease were less likely to be current smokers but more likely to be former smokers than those without symptoms. Dietary factors such as the consumption of alcohol were similar between the two groups. Table
  1. Characteristics of Women with and Women without Symptoms of Gastroesophageal Reflux Disease.
A dose-dependent relationship was observed between increasing BMI and frequent reflux symptoms in both univariate and multivariate analyses (Figure
  1). This relationship continued across all categories of BMI, including those less than
  25.
  0. Women with a BMI of
  22.5 to
  24.9 were approximately 40 percent more likely to report frequent symptoms of gastroesophageal reflux disease than women with a BMI of
  20.0 to
  22.4, whereas overweight and obese women (BMI,
  25.0 to
  30.0 and
  30.0, respectively) were two to three times as likely to report frequent symptoms. Women in the lowest category of BMI (<
  20.
  0) had a lower risk of frequent symptoms of gastroesophageal reflux disease than did those with a BMI of
  20.0 to
  22.4 (multivariate odds ratio,
  0.67; 95 percent confidence interval,
  0.48 to
  0.
  93). Figure
  1. Association between Body-Mass Index and the Risk of Frequent Symptoms of Gastroesophageal Reflux Disease. Multivariate odds ratios are based on 2306 women who had symptoms (i.e., heartburn, acid regurgitation, or both) at least once a week and 3904 women who had no symptoms and have been adjusted for age; smoking status; total activity; daily caloric intake; intake of alcohol, coffee, tea, and chocolate; use of postmenopausal hormone therapy; use of antihypertensive or asthma medication; and presence or absence of diabetes mellitus. I bars denote 95 percent confidence intervals. This same trend was observed among the entire pop
 

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