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BOSTON, May 31 — Symptoms of gastroesophageal reflux disease (GERD) increase progressively with increasing weight, even among normal-weight women, according to data from the Nurses' Health Study.

The risk of GERD symptoms rose across all categories of increasing body mass index (BMI) from normal weight to obese, Brian Jacobson, M.D., of Boston University, and colleagues, in the June 1 issue of the New England Journal of Medicine.

Even moderate weight gain among normal-weight persons may be associated with symptoms of reflux, they said. By contrast, weight loss was linked to a decrease in symptoms, These findings held for all degrees of severity and duration, as well as for nocturnal symptoms.

In 2000, the researchers used a supplemental questionnaire to determine the frequency, severity, and duration of GERD symptoms among randomly selected participants in the Nurses Health Study. BMI had been measured in 1998.

Of 10,545 women who completed the questionnaire, 2,310 (10%) reported having symptoms at least once a week, while 3,419 (55%) of those who had any symptoms described their symptoms as moderate in severity. Symptoms were defined as heartburn, acid regurgitation, or both.

After controlling for smoking, alcohol use, sphincter-pressure medications, and dietary habits, the researchers observed a dose-dependent relationship between increasing BMI and the frequency of reflux symptoms (multivariate P for trend
Compared with women with a BMI of 20.0 to 22.4, the multivariate odds ratios for frequent symptoms were:

• BMI of less than 20.0, OR 0.67 (95% CI, 0.48 to 0.93);
• BMI 22.5 to 24.9, OR 1.38 (CI, 1. 13 to 1.67);
• BMI 25.0 to 27.4, OR 2.20 (CI, 1.81 to 2.66);
• BMI 27.5 to 29.9, OR 2.43 (CI, 1.96 to 3.01);
• BMI 30.0 to 34.9, OR 2.92 (CI 2.35 to 3.62);
• BMI 35.0 or more, OR 2.93 (CI 2.24 to 3.85).

Even among women with a normal baseline BMI, an increase in BMI of more than 3.5, compared with no weight changes, was associated with an increased risk of frequent reflux symptoms, the researchers reported (OR, 2.80; CI, 1.63 to 4.82).

Summarizing the findings, the team wrote that women with a BMI of 22.5 to 24.9 were approximately 40% more likely to report frequent GERD symptoms than women with a BMI of 20.0 to 22.4, whereas overweight women (BMI, 25.0 to 30.0) and obese women (BMI ≥ 30.0) were two or three times as likely to report frequent symptoms.

This trend held throughout the entire population regardless of severity or frequency of symptoms, and also among individuals with nocturnal symptoms (P for trend
GERD risks also decreased significantly among women who lost weight during the period of the study, Dr. Jacobson and colleagues wrote. The risk of frequent symptoms decreased nearly 40% among women with a decrease in BMI of more than 3.5 compared with women whose BMI remained unchanged (OR 0.64; CI 0.42 to 0.97).

These findings augment a growing body of literature addressing the association between GERD symptoms and BMI, but the present study extends those findings by showing that the risk of symptoms appears to be directly linked to BMI regardless of the individual's weight. Thus moderate amounts of weight gain may lead to the development or exacerbation of reflux disease, they said.

Among the study's limitations is that the data cannot provide a causative mechanism for the association, the researchers said. It is possible, they suggested, that a hormonal factor related to adiposity is more important in the development of GERD than are mechanical factors, "although probably multiple factors are responsible," they said.

Also, the investigators noted that because the study was limited to women, it was not possible to comment on the weight-reflux association in men.

The findings of this study, Dr. Jacobson and colleagues concluded, are of particular concern given recent U.S. trends of growing obesity in among both adults and children.

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