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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1111-1120 |
| Number of pages | 10 |
| Journal | Liver International |
| Volume | 40 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2020 |
Funding
This study was supported by grants from the National Institutes of Health/National Heart, Lung, and Blood Institute to Dr Khan (KL2TR001424) and Dr VanWagner (K23HL136891). Research reported in this publication was supported, in part, by the National Institutes of Health's National Center for Advancing Translational Sciences, Grant Number KL2TR001424 (SSK). The Coronary Artery Risk Development in Young Adults Study (CARDIA) is conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with the University of Alabama at Birmingham (HHSN268201800005I & HHSN268201800007I), Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I) and Kaiser Foundation Research Institute (HHSN268201800004I). This manuscript has been reviewed by CARDIA for scientific content. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors take responsibility for decision to submit the manuscript for publication. Dr Khan had full access to all the data in this study and takes responsibility for the integrity of the data and the accuracy of the data analysis. The authors thank the participants of the CARDIA study for their long-term commitment and important contributions to this study.
Keywords
- computed tomography
- hepatic
- metabolic syndrome
- obesity
- steatosis
ASJC Scopus subject areas
- Hepatology
