Zachary P Fricker1, Alison Pedley2, Joseph M Massaro3, Ramachandran S Vasan4, Udo Hoffmann5, Emelia J Benjamin6, Michelle T Long7. 1. Section of Gastroenterology, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts. 2. National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts. 3. Department of Mathematics and Statistics, Boston University School of Public Health, Boston, Massachusetts. 4. National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Section of Preventive Medicine and Epidemiology, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Whitaker Cardiovascular Institute and Cardiology Section, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts. 5. Radiology Department, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. 6. National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts; Whitaker Cardiovascular Institute and Cardiology Section, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts. 7. Section of Gastroenterology, Evans Department of Medicine, Boston University School of Medicine, Boston, Massachusetts; National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, Massachusetts. Electronic address: mtlong@bu.edu.
Abstract
BACKGROUND & AIMS: Nonalcoholic fatty liver disease is an inflammatory condition that results in progressive liver disease. It is unknown if individuals with hepatic steatosis, but not known to have liver disease, have higher serum concentrations of markers of systemic inflammation and oxidative stress. METHODS: We collected data from 2482 participants from the Framingham Heart Study (mean age, 51 ± 11 y; 51% women) who underwent computed tomography and measurement of 14 serum markers of systemic inflammation. Heavy alcohol users were excluded. The liver:phantom ratio (a continuous parameter of liver attenuation relative to a calibration phantom) was used to identify individuals with radiographic evidence of liver fat. Primary covariates included age, sex, smoking, alcohol, aspirin use, hypertension, dyslipidemia, diabetes, and cardiovascular disease. Body mass index and visceral fat were secondary covariates. We used multivariable linear regression models to assess the association between liver fat and systemic inflammatory markers. RESULTS: In multivariable-adjusted models, liver fat was associated with the following inflammatory markers: high-sensitivity C-reactive protein (P < .001), urinary isoprostanes (P < .001), interleukin 6 (P < .001), intercellular adhesion molecule 1 (P < .001), and P-selectin (P = .002). Additional adjustment for body mass index or visceral fat attenuated the results slightly, although all associations remained statistically significant (P for all ≤ .01). CONCLUSIONS: In a community-based cohort, individuals with hepatic steatosis without known liver disease had higher mean serum concentrations of systemic markers of inflammation. Studies are needed to determine whether treatment of hepatic steatosis reduces systemic inflammation.
BACKGROUND & AIMS:Nonalcoholic fatty liver disease is an inflammatory condition that results in progressive liver disease. It is unknown if individuals with hepatic steatosis, but not known to have liver disease, have higher serum concentrations of markers of systemic inflammation and oxidative stress. METHODS: We collected data from 2482 participants from the Framingham Heart Study (mean age, 51 ± 11 y; 51% women) who underwent computed tomography and measurement of 14 serum markers of systemic inflammation. Heavy alcohol users were excluded. The liver:phantom ratio (a continuous parameter of liver attenuation relative to a calibration phantom) was used to identify individuals with radiographic evidence of liver fat. Primary covariates included age, sex, smoking, alcohol, aspirin use, hypertension, dyslipidemia, diabetes, and cardiovascular disease. Body mass index and visceral fat were secondary covariates. We used multivariable linear regression models to assess the association between liver fat and systemic inflammatory markers. RESULTS: In multivariable-adjusted models, liver fat was associated with the following inflammatory markers: high-sensitivity C-reactive protein (P < .001), urinary isoprostanes (P < .001), interleukin 6 (P < .001), intercellular adhesion molecule 1 (P < .001), and P-selectin (P = .002). Additional adjustment for body mass index or visceral fat attenuated the results slightly, although all associations remained statistically significant (P for all ≤ .01). CONCLUSIONS: In a community-based cohort, individuals with hepatic steatosis without known liver disease had higher mean serum concentrations of systemic markers of inflammation. Studies are needed to determine whether treatment of hepatic steatosis reduces systemic inflammation.
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