Abstract
Objectives
The objective of this cohort study was to determine whether subjects with gallstone disease identified by screening of a general population had increased overall mortality when compared to gallstone-free participants and to explore causes of death.
Methods
The study population (N = 5928) was examined 1982–1992 and included an abdominal ultrasound examination to assess gallstone status, a physical examination, blood samples, and a questionnaire about medical history. Participants were followed up through national registers until 2015. Multiple adjusted Cox regression models were built.
Results
Gallstone disease was present in 10%. Mortality was 46% during median 24.7 years of follow-up with 1% lost. Overall mortality and death from cardiovascular diseases were significantly associated to gallstone disease. Death from unknown causes was significantly associated to gallstone disease and death from cancer and gastrointestinal disease was not associated. No differences in mortality for ultrasound-proven gallstones or cholecystectomy were identified.
Conclusions
Gallstone disease is associated with increased overall mortality and to death from cardiovascular disease. Gallstones may be considered a possible cardiometabolic risk factor. Other unknown factors also seem to play a role.
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References
Bender AM, Jorgensen T, Pisinger C (2015) Is self-selection the main driver of positive interpretations of general health checks? The Inter99 randomized trial. Prev Med 81:42–48. doi:10.1016/j.ypmed.2015.07.004
Bennet AM et al (2007) Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 298(11):1300–1311. doi:10.1001/jama.298.11.1300
Biddinger SB et al (2008) Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nat Med 14(7):778–782. doi:10.1038/nm1785
Bortnichak EA et al (1985) The association between cholesterol cholelithiasis and coronary heart disease in Framingham, Massachusetts. Am J Epidemiol 121(1):19–30
Diehl AK (2000) Cholelithiasis and the insulin resistance syndrome. Hepatology 31(2):528–530. doi:10.1002/hep.510310238
Everhart JE, Ruhl CE (2009) Burden of digestive diseases in the United States Part III: liver, biliary tract, and pancreas. Gastroenterology 136(4):1134–1144. doi:10.1053/j.gastro.2009.02.038
Friedman G (1968) The relationship between coronary heart disease and gallbladder disease. A critical review. Ann Intern Med 68:222–235
Friedman GD, Kannel WB, Dawber TR (1966) The epidemiology of gallbladder disease: observations in the Framingham Study. J Chronic Dis 19(3):273–292
Goldacre MJ, Wotton CJ, Abisgold J, Yeates DG, Collins J (2012) Association between cholecystectomy and intestinal cancer: a national record linkage study. Ann Surg 256(6):1068–1072. doi:10.1097/SLA.0b013e3182759efb
Grimaldi CH, Nelson RG, Pettitt DJ, Sampliner RE, Bennett PH, Knowler WC (1993) Increased mortality with gallstone disease: results of a 20-year population-based survey in Pima Indians. Ann Intern Med 118(3):185–190
Grundy SM (2004) Cholesterol gallstones: a fellow traveler with metabolic syndrome? Am J Clin Nutr 80(1):1–2
Hatters DM, Peters-Libeu CA, Weisgraber KH (2006) Apolipoprotein E structure: insights into function. Trends Biochem Sci 31(8):445–454. doi:10.1016/j.tibs.2006.06.008
Helweg-Larsen K (2011) The Danish register of causes of death. Scand J Public Health 39(7 Suppl):26–29. doi:10.1177/1403494811399958
Hirschfield GM, Chapman RW, Karlsen TH, Lammert F, Lazaridis KN, Mason AL (2013) The genetics of complex cholestatic disorders. Gastroenterology 144(7):1357–1374. doi:10.1053/j.gastro.2013.03.053
Janssen F, Kunst AE (2004) ICD coding changes and discontinuities in trends in cause-specific mortality in six European countries, 1950–99. Bull World Health Organ 82(12):904–913. doi:10.1590/S0042-96862004001200006
Jensen KH, Jorgensen T (1991) Incidence of gallstones in a Danish population. Gastroenterology 100(3):790–794
Jiang ZY, Cai Q, Chen EZ (2014) Association of three common single nucleotide polymorphisms of ATP binding cassette G8 gene with gallstone disease: a meta-analysis. PLoS One 9(1):e87200. doi:10.1371/journal.pone.0087200
Johansen C, Chow WH, Jorgensen T, Mellemkjaer L, Engholm G, Olsen JH (1996) Risk of colorectal cancer and other cancers in patients with gall stones. Gut 39(3):439–443
Jorgensen T (1987) Prevalence of gallstones in a Danish population. Am J Epidemiol 126(5):912–921
Jorgensen T (1988) Gallstones in a Danish population: familial occurrence and social factors. J Biosoc Sci 20(1):111–120
Jorgensen T (2007) Gallstones. In: Talley N, Loke III R, Saito Y (eds) GI epidemiology. Blackwell Publishing, pp 215–220
Kaye MD, Kern F (1971) Clinical relationships of gallstones. Lancet 1(7711):1228–1230
Li Q et al (2011) History of cholelithiasis and the risk of prostate cancer: the Ohsaki Cohort Study. Int J Cancer (Journal international du cancer) 128(1):185–191. doi:10.1002/ijc.25303
Lv J et al (2015) Gallstone disease and the risk of ischemic heart disease. Arterioscler Thromb Vasc Biol 35(10):2232–2237. doi:10.1161/ATVBAHA.115.306043
Mahley RW (1988) Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science 240(4852):622–630
Olaiya MT, Chiou HY, Jeng JS, Lien LM, Hsieh FI (2013) Significantly increased risk of cardiovascular disease among patients with gallstone disease: a population-based cohort study. PLoS One 8(10):e76448. doi:10.1371/journal.pone.0076448
Patterson HA (1954) The association of gallstones and heart disease. Ann Surg 139(5):683–689
Paul O et al (1963) A longitudinal study of coronary heart disease. Circulation 28:20–31
Ruhl CE, Everhart JE (2011) Gallstone disease is associated with increased mortality in the United States. Gastroenterology 140(2):508–516. doi:10.1053/j.gastro.2010.10.060
Schmidt M, Smastuen MC, Sondenaa K (2012) Increased cancer incidence in some gallstone diseases, and equivocal effect of cholecystectomy: a long-term analysis of cancer and mortality. Scand J Gastroenterol 47(12):1467–1474. doi:10.3109/00365521.2012.719928
Schmidt M, Pedersen L, Sorensen HT (2014) The Danish civil registration system as a tool in epidemiology. Eur J Epidemiol 29(8):541–549. doi:10.1007/s10654-014-9930-3
Shabanzadeh D, Sørensen L, Jørgensen T (2016a) Determinants for clinical events in gallstone carriers unaware of their gallstones. J Gastroenterol Hepatol (accepted for publication)
Shabanzadeh DM, Sorensen LT, Jorgensen T (2016b) Determinants for gallstone formation—a new data cohort study and a systematic review with meta-analysis. Scand J Gastroenterol 51(10):1239–1248. doi:10.1080/00365521.2016.1182583
Shabanzadeh DM, Sorensen LT, Jorgensen T (2016c) A prediction rule for risk stratification of incidentally discovered gallstones: results from a large cohort study. Gastroenterology 150(1):156–167 e1 doi:10.1053/j.gastro.2015.09.002
von Elm E et al (2007) The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet 370(9596):1453–1457. doi:10.1016/S0140-6736(07)61602-X
Wei CY et al (2014) Gallstone disease and the risk of stroke: a nationwide population-based study. J Stroke Cerebrovasc Dis Off J Natl Stroke Assoc 23(7):1813–1820. doi:10.1016/j.jstrokecerebrovasdis.2014.04.024
Wirth J et al (2015) Presence of gallstones and the risk of cardiovascular diseases: the EPIC-Germany cohort study. Eur J Prev Cardiol 22(3):326–334. doi:10.1177/2047487313512218
Xue P, Niu WQ, Jiang ZY, Zheng MH, Fei J (2012) A meta-analysis of apolipoprotein E gene ε2/ε3/ε4 polymorphism for gallbladder stone disease. PLoS One 7(9):e45849. doi:10.1371/journal.pone.0045849
Acknowledgements
We would like to thank Rikke Kart Jacobsen for statistical supervision and Anja Lykke Madsen for data management.
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Shabanzadeh, D.M., Sørensen, L.T. & Jørgensen, T. Gallstone disease and mortality: a cohort study. Int J Public Health 62, 353–360 (2017). https://doi.org/10.1007/s00038-016-0916-7
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DOI: https://doi.org/10.1007/s00038-016-0916-7