Patrick T Campbell1, Lisa B VanWagner2,3, Laura A Colangelo3, Cora E Lewis4, Anne Henkel2, Veeral H Ajmera5, Donald M Lloyd-Jones1,3, Douglas E Vaughan1,3, Sadiya S Khan3. 1. Department of Medicine, Northwestern University, Chicago, IL, USA. 2. Division of GI & Hepatology, Northwestern University, Chicago, IL, USA. 3. Department of Preventive Medicine, Northwestern Universtiy, Chicago, IL, USA. 4. Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA. 5. Division of GI & Hepatology, University of California San Diego, San Diego, CA, USA.
Abstract
BACKGROUND: Prior studies have demonstrated a cross-sectional association between elevated plasminogen activator inhibitor-1 (PAI-1) levels and nonalcoholic fatty liver disease (NAFLD). However, there are no prospective longitudinal assessments of the association between PAI-1 and NAFLD. We aimed to describe the association between PAI-1 levels in early adulthood with NAFLD in midlife. METHODS: Among the 5115 participants in the coronary artery risk development in young adults (CARDIA) study, participants were randomly selected from a subset that was free of obesity, diabetes and hypertension at the 1992-1993 exam and attended the 2005-2006 exam (n = 996). A subset of participants (n = 896) also had CT liver fat measured (2010-2011). Participants with secondary causes of steatosis were excluded (n = 87). NAFLD was defined as liver attenuation ≤51 Hounsfield units. Logistic regression models assessed the association between PAI-1 and NAFLD. RESULTS: Of 809 participants, 53% were female, 37% black with a mean age of 32 years. Median PAI-1 level at 1st assessment (1992-1993) was 23.4 ng/mL among participants with NAFLD vs 11.9 ng/mL among those without NAFLD (P < .0001). Median PAI-1 level at 2nd assessment (2005-2006) was 55.6 ng/mL among participants with NAFLD vs 19.5 ng/mL among those without NAFLD (P < .0001). Higher PAI-1 levels were independently associated with NAFLD (1st assessment adjusted OR [AOR] 2.16 per 1 standard deviation higher log(PAI-1) level (95% confidence interval [CI] 1.63-2.85); 2nd assessment AOR 2.71 (95% CI 2.03-3.61)). CONCLUSIONS: Plasma PAI-1 levels in young adulthood were independently associated with NAFLD in midlife. Further studies may indicate whether PAI-1 plays a role in NAFLD pathophysiology.
BACKGROUND: Prior studies have demonstrated a cross-sectional association between elevated plasminogen activator inhibitor-1 (PAI-1) levels and nonalcoholic fatty liver disease (NAFLD). However, there are no prospective longitudinal assessments of the association between PAI-1 and NAFLD. We aimed to describe the association between PAI-1 levels in early adulthood with NAFLD in midlife. METHODS: Among the 5115 participants in the coronary artery risk development in young adults (CARDIA) study, participants were randomly selected from a subset that was free of obesity, diabetes and hypertension at the 1992-1993 exam and attended the 2005-2006 exam (n = 996). A subset of participants (n = 896) also had CT liver fat measured (2010-2011). Participants with secondary causes of steatosis were excluded (n = 87). NAFLD was defined as liver attenuation ≤51 Hounsfield units. Logistic regression models assessed the association between PAI-1 and NAFLD. RESULTS: Of 809 participants, 53% were female, 37% black with a mean age of 32 years. Median PAI-1 level at 1st assessment (1992-1993) was 23.4 ng/mL among participants with NAFLD vs 11.9 ng/mL among those without NAFLD (P < .0001). Median PAI-1 level at 2nd assessment (2005-2006) was 55.6 ng/mL among participants with NAFLD vs 19.5 ng/mL among those without NAFLD (P < .0001). Higher PAI-1 levels were independently associated with NAFLD (1st assessment adjusted OR [AOR] 2.16 per 1 standard deviation higher log(PAI-1) level (95% confidence interval [CI] 1.63-2.85); 2nd assessment AOR 2.71 (95% CI 2.03-3.61)). CONCLUSIONS: Plasma PAI-1 levels in young adulthood were independently associated with NAFLD in midlife. Further studies may indicate whether PAI-1 plays a role in NAFLD pathophysiology.
Authors: Vanessa Xanthakis; Danielle M Enserro; Joanne M Murabito; Joseph F Polak; Kai C Wollert; James L Januzzi; Thomas J Wang; Geoffrey Tofler; Ramachandran S Vasan Journal: Circulation Date: 2014-10-01 Impact factor: 29.690
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