TY - JOUR
T1 - Circulating Interleukin-6 is a biomarker for coronary atherosclerosis in nonalcoholic fatty liver disease
T2 - Results from the Multi-Ethnic Study of Atherosclerosis
AU - Simon, Tracey G.
AU - Trejo, Maria Esther Perez
AU - McClelland, Robyn
AU - Bradley, Ryan
AU - Blaha, Michael J.
AU - Zeb, Irfan
AU - Corey, Kathleen E.
AU - Budoff, Matthew J.
AU - Chung, Raymond T.
N1 - Publisher Copyright:
© 2018 Elsevier B.V.
PY - 2018/5/15
Y1 - 2018/5/15
N2 - Background: Biomarkers to predict the presence and severity of subclinical cardiovascular disease (CVD) in nonalcoholic fatty liver disease (NAFLD) are lacking. Methods: 3876 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), without known chronic liver disease underwent baseline non-contrast cardiac CT, with NAFLD defined by validated liver:spleen ratio (L:S) < 1.0, and subclinical CVD defined by coronary artery calcium (CAC) score > 0. Randomly-selected subgroups underwent detailed inflammatory marker testing, including LpPLA2 mass (N = 2951), activity (N = 3020), high-sensitivity C-reactive protein (hsCRP; N = 3849), and interleukin-6 (IL-6; N = 3764). Among those with NAFLD, we estimated the prevalence of CAC > 0 and CAC > 100 for each SD biomarker increase, using multivariable log-binomial regression models adjusted for cardiometabolic risk factors. Results: Seventeen percent (N = 668) of participants met the criteria for NAFLD. NAFLD participants were younger (mean age 61 ± 10 vs. 63 ± 10 years, p <.0001) but more likely to have an elevated BMI (mean 31.1 ± 5.5 vs. 28.0 ± 5.2 kg/m2, p <.0001), diabetes (22% vs. 11%, p <.0001), and increased inflammatory biomarkers, including LpPLA2 activity, hsCRP and IL-6 (all p <.0001). Among NAFLD participants, IL-6 was the only biomarker independently associated with prevalent CAC > 0 (PR = 1.06 [1.00–1.11]), or CAC > 100 (PR = 1.09 [1.02–1.17]). In contrast, circulating LpPLA2 mass/activity and hsCRP were not associated with either the prevalence or severity of subclinical CVD (all p >.05). Conclusion: In a large, multi-ethnic population with NAFLD, IL-6 is independently associated with the prevalence and severity of subclinical atherosclerosis. Further research into the longitudinal effects of NAFLD on progressive CVD will determine whether IL-6 is a marker or mediator of NAFLD-related atherosclerosis.
AB - Background: Biomarkers to predict the presence and severity of subclinical cardiovascular disease (CVD) in nonalcoholic fatty liver disease (NAFLD) are lacking. Methods: 3876 participants from the Multi-Ethnic Study of Atherosclerosis (MESA), without known chronic liver disease underwent baseline non-contrast cardiac CT, with NAFLD defined by validated liver:spleen ratio (L:S) < 1.0, and subclinical CVD defined by coronary artery calcium (CAC) score > 0. Randomly-selected subgroups underwent detailed inflammatory marker testing, including LpPLA2 mass (N = 2951), activity (N = 3020), high-sensitivity C-reactive protein (hsCRP; N = 3849), and interleukin-6 (IL-6; N = 3764). Among those with NAFLD, we estimated the prevalence of CAC > 0 and CAC > 100 for each SD biomarker increase, using multivariable log-binomial regression models adjusted for cardiometabolic risk factors. Results: Seventeen percent (N = 668) of participants met the criteria for NAFLD. NAFLD participants were younger (mean age 61 ± 10 vs. 63 ± 10 years, p <.0001) but more likely to have an elevated BMI (mean 31.1 ± 5.5 vs. 28.0 ± 5.2 kg/m2, p <.0001), diabetes (22% vs. 11%, p <.0001), and increased inflammatory biomarkers, including LpPLA2 activity, hsCRP and IL-6 (all p <.0001). Among NAFLD participants, IL-6 was the only biomarker independently associated with prevalent CAC > 0 (PR = 1.06 [1.00–1.11]), or CAC > 100 (PR = 1.09 [1.02–1.17]). In contrast, circulating LpPLA2 mass/activity and hsCRP were not associated with either the prevalence or severity of subclinical CVD (all p >.05). Conclusion: In a large, multi-ethnic population with NAFLD, IL-6 is independently associated with the prevalence and severity of subclinical atherosclerosis. Further research into the longitudinal effects of NAFLD on progressive CVD will determine whether IL-6 is a marker or mediator of NAFLD-related atherosclerosis.
KW - Atherosclerosis
KW - Biomarker
KW - Cardiovascular disease
KW - Fatty liver
KW - Inflammation
KW - Nonalcoholic fatty liver disease
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U2 - 10.1016/j.ijcard.2018.01.046
DO - 10.1016/j.ijcard.2018.01.046
M3 - Article
C2 - 29579601
AN - SCOPUS:85044109366
SN - 0167-5273
VL - 259
SP - 198
EP - 204
JO - International Journal of Cardiology
JF - International Journal of Cardiology
ER -