Association of plasminogen activator inhibitor-1 and low-density lipoprotein heterogeneity as a risk factor of atherosclerotic cardiovascular disease with triglyceride metabolic disorder: a pilot cross-sectional study

Background We hypothesized that an increase in plasminogen activator inhibitor 1 (PAI-1) might reduce lowdensity lipoprotein (LDL) particle size in conjunction with triglyceride (TG) metabolism disorder, resulting in an increased risk of atherosclerotic cardiovascular disease (ASCVD). Methods This study was carried out as a hospital-based cross-sectional study in 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital. The estimated LDL-particle size was measured as relative LDL migration using polyacrylamide gel electrophoresis with the LipoPhor system. The plasma PAI1 level, including the tissue PA/PAI-1 complex and the active and latent forms of PAI-1, was determined using a latex photometric immunoassay method. Results A multivariate regression analysis after adjustments for ASCVD risk factors showed that an elevated PAI-1 level was an independent predictor of smaller-sized LDL-particle in both the overall patients population (beta=0.209, P<0.0001) and a subset of patients with a serum low-density lipoprotein cholesterol (LDL-C) level lower than 100 mg/dl (beta=0.276, P<0.0001). Furthermore, an increased BMI and TG-rich lipoprotein related markers [TG, remnant-like particle cholesterol, apolipoprotein (apo) B, apo C-II, and apo C-III] were found to be independent variables associated with an increased PAI-1 level in multivariate regression models. A statistical analysis of data from nondiabetic patients with wellcontrolled serum LDL-C levels yielded similar findings. Furthermore, in the 310 patients followed up for at least 6 months, a multiple-logistic regression analysis after adjustments for ASCVD risk factors identified the percent changes of the plasma PAI-1 level in the third tertile compared with those in the first tertile as being independently predictive of decreased LDL-particle size [odds ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02]. Conclusion The plasma PAI-1 levels may be determined by the degree of obesity and TG metabolic disorders. These factors were also shown to be correlated with a decreased LDL-particle size, increasing the risk of ASCVD, even in nondiabetic patients with well-controlled serum LDL-C levels. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.