Association between plasminogen activator inhibitor‐1 in young adulthood and nonalcoholic fatty liver disease in midlife: CARDIA

Abstract

Abbreviations: AOR, adjusted odds ratio; BMI, body mass index; CARDIA, coronary artery risk development in young adults; CI, confidence interval; CT, computed tomography; HDL-C, high-density lipoprotein cholesterol; HIV, human immunodeficiency virus; HTN, hypertension; HU, Hounsfield units; LA, liver attenuation; LDL-C, low-density lipoprotein cholesterol; MRI, magnetic resonance imaging; NAFLD, nonalcoholic fatty liver disease; PAI-1, plasminogen activator inhibitor-1; SBP, systolic blood pressure; SD, standard deviation; US, ultrasound; US-FLI, ultrasound fatty liver index; VCTE, vibration-controlled transient elastography. AbstractBackground: 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.

The Central Role of PAI-1 in COVID-19: Thrombosis and beyond

“…These data help connect the well-established and fundamental role of metabolism with aging and build on studies demonstrating the contributions of insulin and insulin-like growth factor in senescence across a variety of experimental model organisms ( Caenorhabditis elegans , Drosophila , and rodents). We and others have additionally demonstrated the broader relevance of PAI-1 in the general population by documenting the association of circulating PAI-1 levels with cardiometabolic diseases in large, community-based cohort studies, such as the Coronary Artery Risk Development in Young Adults study, the Multi-Ethnic Study of Atherosclerosis study, and the Framingham Heart Study ( 9 , 15 ).…”

Plasminogen Activator Inhibitor-1 Levels in Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis

“…A thorough assessment of the full-texts was performed afterward for the remaining total of 54 articles. Of these, 21 were excluded as follows: 17 studies were conference abstracts or papers [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39], 2 articles were conducted in languages other than English, Romanian or German (1 in Spanish and 1 in Russian language) [40,41], 1 article was a study involving HIV patients [42], 1 study was a letter [43]. A total of 33 articles were included in our qualitative synthesis, 11 of which were included in the quantitative analysis .…”

Prothrombotic and Inflammatory Markers in Elderly Patients with Non-Alcoholic Hepatic Liver Disease before and after Weight Loss: A Pilot Study

“…The link between PAI-1 and the metabolic syndrome with obesity was established many years ago [ 27 ], and increased PAI-1 level can be now considered a true component of the syndrome. The production of PAI-1 by adipose tissue, in particular by tissue from omentum, has been demonstrated and could be an important contributor to the elevated plasma PAI-1 levels observed in insulin resistant patients supporting the notion that PAI-1 can be a link between NAFLD, insulin resistance and cardiovascular disease [ 28 , 29 ].…”