Gallstone Disease and the Risk of Ischemic Heart Disease.
OBJECTIVE
Gallstone disease (GSD) is related to multiple cardiovascular risk factors; the present study was to prospectively examine the association between GSD and ischemic heart disease (IHD).


RESULTS
We examined the association of GSD with IHD among 199 292 men and 288 081 women aged 30-79 years in the China Kadoorie Biobank study. Participants with cancer, heart disease, and stroke at baseline were excluded. Cox proportional hazards regression model was used to estimate the association of GSD with IHD. The prevalence of self-reported GSD was 3.7% in men and 7.3% in women at baseline. During 3 431 124 person-years of follow-up between 2004 and 2013 (median, 7.2 years), we documented 10 245 incident IHD cases in men and 14 714 in women. As compared with men without GSD at baseline, the multivariate-adjusted hazard ratio for IHD was 1.11 (95% confidence interval, 1.02-1.22) for men with GSD; the respective hazard ratio was 1.27 (95% confidence interval, 1.20-1.34) in women and 1.23 (95% confidence interval, 1.17-1.28) in the whole cohort. The sex difference in IHD risk associated with GSD was statistically significant (P=0.009 for interaction with sex). In addition, we found that the association between GSD and IHD was stronger in nonhypertensive than in hypertensive women (P<0.001 for interaction).


CONCLUSIONS
In this large prospective study, the presence of GSD was associated with an increased risk of incident IHD, independent of other risk factors of cardiovascular disease. Our findings suggest novel prevention strategy to mitigate heart disease through improvement of gastrointestinal health.
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Jun
J
Lv
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.). lmlee@vip.163.com nhlqi@channing.harvard.edu.
Lu
L
Qi
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Canqing
C
Yu
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Yu
Y
Guo
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Zheng
Z
Bian
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Yiping
Y
Chen
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Ling
L
Yang
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Jie
J
Shen
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Shanqing
S
Wang
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Mingqiang
M
Li
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Yongmei
Y
Liu
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Libo
L
Zhang
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Junshi
J
Chen
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.).
Zhengming
Z
Chen
From the Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China (J.L., C.Y., L.L.); Department of Nutrition, Harvard School of Public Health, Boston, MA (L.Q.); Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (L.Q.); Chinese Academy of Medical Sciences, Beijing, China (Y.G., Z.B., L.L.); Clinical Trial Service Unit & Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, UK (Y.C., L.Y., Z.C.); Suzhou Sanitary Bureau, Suzhou, Jiangsu, China (J.S.); Hainan Center for Disease Control & Prevention, Haikou, Hainan, China (S.W.); Liuzhou Center for Disease Control & Prevention, Liuzhou, Guangxi, China (M.L.); Department of Non-communicable Disease Prevention & Control, Qingdao Center for Disease Control & Prevention, Qingdao, Shandong, China (Y.L.); Department of Non-communicable Disease Prevention & Control, Liuyang Center for Disease Control & Prevention, Changsha, Hunan, China (L.Z.); and China National Center for Food Safety Risk Assessment, Beijing, China (J.C.). lmlee@vip.163.com nhlqi@channing.harvard.edu.
Liming
L
Li
D000328:Adult; D017677:Age Distribution; D000368:Aged; D002681:China; D015897:Comorbidity; D016001:Confidence Intervals; D016208:Databases, Factual; D005260:Female; D042882:Gallstones / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000175:diagnosis* / Q000453:epidemiology* / Q000628:therapy; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D017678:Sex Distribution; D016019:Survival Analysis
Chinese; cardiovascular disease; ischemic heart diseases; longitudinal cohort study; risk factor