Tracey G Simon1, Mi Na Kim2, Xiao Luo3, Wanshui Yang4, Yanan Ma4, Dawn Q Chong5, Charles S Fuchs6, Jeffrey A Meyerhardt7, Kathleen E Corey1, Raymond T Chung8, Meir Stampfer9, Xuehong Zhang4, Edward L Giovannucci9, Andrew T Chan10. 1. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA. 2. Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA; Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea. 3. Harvard Medical School, Boston, MA; School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. 4. Harvard Medical School, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA. 5. National Cancer Centre Singapore, Singapore. 6. Yale University Cancer Center, New Haven, CT. 7. Harvard Medical School, Boston, MA; Dana-Farber Cancer Center, Boston, MA. 8. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA. 9. Harvard Medical School, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA. 10. Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA; Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, MA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA; Broad Institute, Boston, MA; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA. Electronic address: achan@mgh.harvard.edu.
Abstract
BACKGROUND & AIMS: Obesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within 2 nationwide populations. METHODS: We conducted a prospective cohort study of 77,238 women and 48,026 men, with detailed, validated assessments of weekly physical activity (metabolic equivalent task [MET]-hours]), adiposity (body mass index [BMI], waist circumference), and diet, alcohol use and clinical comorbidities, biennially from 1986 through 2012. Using Cox proportional hazards regression models, we calculated multivariable-adjusted hazard ratios (aHRs) and 95% CIs for liver-related mortality, including death from hepatocellular carcinoma (HCC) and other complications of cirrhosis. RESULTS: Over 1,856,226 person-years, we recorded 295 liver-related deaths (108 HCC; 187 cirrhosis). Risk of liver-related mortality increased monotonically with higher BMI during adulthood (ptrend<0.0001) and with weight gain during early adulthood (ptrend <0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (ptrend = 0.0003); the aHRs across increasing physical activity quintiles were: 1.0, 0.70 (95% CI 0.51-0.96), 0.59 (95% CI 0.42-0.84), 0.52 (95% CI 0.36-0.74) and 0.46 (95% CI 0.31-0.66). Compared to lean-active adults (BMI <25; ≥18 MET-hours/week), the aHRs for obese-active, lean-sedentary, and obese-sedentary adults were: 1.04 (95% CI 0.73-1.37), 2.08 (95% CI 1.21-3.33) and 3.40 (95% CI 2.06-5.56), respectively. Findings were similar for HCC-specific and cirrhosis-specific mortality. Overall, engaging in average-pace walking for >3 hours/week could have prevented 25% of liver-related deaths (95% CI 0.12-0.38). CONCLUSIONS: In 2 prospective, nationwide cohorts, both excess adiposity and reduced physical activity were significant predictors of liver-related mortality. Achieving higher physical activity levels counteracted the excess liver-related risks associated with obesity. LAY SUMMARY: This is the first large, prospective cohort study to simultaneously evaluate the impact of obesity and physical activity on the long-term risk of liver-related mortality in 2 nationwide populations of American men and women. The study demonstrated that obesity predicted significantly increased risk of liver-related mortality, while physical activity predicted significantly lower risk of liver-related mortality. Importantly, the excess risk of liver-related mortality observed with obesity was no longer statistically significant among adults who engaged in the equivalent of average-pace walking for 3 hours or more, per week.
BACKGROUND & AIMS:Obesity in adulthood has been associated with increased risk of liver-related mortality. Whether higher levels of physical activity counteract the excess risk conferred by obesity remains unknown. We simultaneously evaluated the long-term impact of physical activity and adiposity on liver-related mortality, within 2 nationwide populations. METHODS: We conducted a prospective cohort study of 77,238 women and 48,026 men, with detailed, validated assessments of weekly physical activity (metabolic equivalent task [MET]-hours]), adiposity (body mass index [BMI], waist circumference), and diet, alcohol use and clinical comorbidities, biennially from 1986 through 2012. Using Cox proportional hazards regression models, we calculated multivariable-adjusted hazard ratios (aHRs) and 95% CIs for liver-related mortality, including death from hepatocellular carcinoma (HCC) and other complications of cirrhosis. RESULTS: Over 1,856,226 person-years, we recorded 295 liver-related deaths (108 HCC; 187 cirrhosis). Risk of liver-related mortality increased monotonically with higher BMI during adulthood (ptrend<0.0001) and with weight gain during early adulthood (ptrend <0.0001). The risk of liver-related mortality also declined progressively, with increasing physical activity (ptrend = 0.0003); the aHRs across increasing physical activity quintiles were: 1.0, 0.70 (95% CI 0.51-0.96), 0.59 (95% CI 0.42-0.84), 0.52 (95% CI 0.36-0.74) and 0.46 (95% CI 0.31-0.66). Compared to lean-active adults (BMI <25; ≥18 MET-hours/week), the aHRs for obese-active, lean-sedentary, and obese-sedentary adults were: 1.04 (95% CI 0.73-1.37), 2.08 (95% CI 1.21-3.33) and 3.40 (95% CI 2.06-5.56), respectively. Findings were similar for HCC-specific and cirrhosis-specific mortality. Overall, engaging in average-pace walking for >3 hours/week could have prevented 25% of liver-related deaths (95% CI 0.12-0.38). CONCLUSIONS: In 2 prospective, nationwide cohorts, both excess adiposity and reduced physical activity were significant predictors of liver-related mortality. Achieving higher physical activity levels counteracted the excess liver-related risks associated with obesity. LAY SUMMARY: This is the first large, prospective cohort study to simultaneously evaluate the impact of obesity and physical activity on the long-term risk of liver-related mortality in 2 nationwide populations of American men and women. The study demonstrated that obesity predicted significantly increased risk of liver-related mortality, while physical activity predicted significantly lower risk of liver-related mortality. Importantly, the excess risk of liver-related mortality observed with obesity was no longer statistically significant among adults who engaged in the equivalent of average-pace walking for 3 hours or more, per week.
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Authors: Tracey G Simon; Mi Na Kim; Xiao Luo; Xing Liu; Wanshui Yang; Yanan Ma; Dawn Q Chong; Charles S Fuchs; Meir Stampfer; Edward L Giovannucci; Andrew T Chan; Xuehong Zhang Journal: Cancer Prev Res (Phila) Date: 2021-07-15