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Increased Mortality with Gallstone Disease: Results of a 20-Year Population-Based Survey in Pima Indians

Charles H. Grimaldi, MD; Robert G. Nelson, MD, MPH; David J. Pettitt, MD; Richard E. Sampliner, MD; Peter H. Bennett, MB; and William C. Knowler, MD, DrPH
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From the Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona; the Hopital de Cimiez, Nice, France; The Cleveland Clinic Foundation, Phoenix, Arizona; the Veterans Affairs Medical Center and University of Arizona, Tucson, Arizona. Acknowledgments: The authors thank the members of the Gila River Indian Community for their participation; the staff of the Diabetes and Arthritis Epidemiology Section, National Institute of Diabetes and Digestive and Kidney Diseases for conducting examinations and processing data; and the State of Arizona Department of Vital Statistics for providing death certificates.

Copyright ©2004 by the American College of Physicians

Ann Intern Med. 1993;118(3):185-190. doi:10.7326/0003-4819-118-3-199302010-00005
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Objective: To determine if gallstone disease is associated with an increased risk for malignancy and higher total mortality in Pima Indians.

Design: Inception cohort.

Setting: American Indian community.

Participants: Age- and sex-stratified random population-based sample.

Measurements: Between 1966 and 1969, an age- and sex-stratified random sample of Pima Indians from the Gila River Indian Community in Arizona was examined to identify evidence of gallstone disease defined as either gallstones (oral cholecystography) or previous cholecystectomy. During 20 years of follow-up, deaths were recorded and underlying causes of death, according to death certificates, were determined.

Results: Among 383 persons with known gallbladder status, 186 (49%) died: 133 among the 222 persons with gallstone disease and 53 among the 161 without. The overall death rate was higher in persons with gallstone disease than in those with normal gallbladders. The age-and sex-adjusted death rate ratio was 1.9 (95% CI, 1.3 to 2.7). Furthermore, the death rate attributed to malignancies was 6.6 times (CI, 1.3 to 33.1) as high in persons with gallstone disease as in those with normal gallbladders. Of the 20 fatal malignancies in persons with gallstone disease, 11 occurred in the digestive tract, of which six involved the gallbladder or bile ducts.

Conclusions: Increased cancer mortality and total mortality were found in Pima Indians with gallstone disease. Although plausible explanations exist for the increased cancer mortality, the increased death rates due to other causes are unexplained. Whether cholecystectomy would change this risk is unknown.


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Figure 1.
Survival according to presence or absence of gallstone disease at entry.

Survival probability was computed from a proportional hazards model of survival time as a function of gallbladder disease, age, sex, and age-sex interaction. To construct the figure, the model was evaluated for each sex at an entry age of 35 years (top panel) and 55 years (bottom panel).

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Figure 2.
Effect on death rate ratios of gallstone disease and diabetes.

Death rates for persons with these diseases were examined relative to persons with neither condition at entry into the study (for whom a ratio of 1.0 was assigned). The ratios were derived from a proportional hazards model of survival time as a function of gallstone disease, diabetes, age, and sex and evaluated for each sex at the mean age (48 years) of all persons. D = diabetes; GS = gallstone disease.

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