Iida K, et al. - This study tested a notion that an increase in plasminogen activator inhibitor 1 (PAI-1) in association with triglyceride (TG) metabolism disorder might attenuate low-density lipoprotein (LDL) particle size, conferring increased risk for atherosclerotic cardiovascular disease (ASCVD). As per observations, the degree of obesity and TG metabolic disorders were acknowledged as possible determinants of plasma PAI-1 levels. Moreover, there was a correlation between these factors and a decreased LDL-particle size, increasing the risk of ASCVD, even in nondiabetic patients with well-controlled serum low-density lipoprotein cholesterol (LDL-C) levels.

Methods

• This hospital-based cross-sectional study was conducted from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital and, included a total of 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD.
• The estimated LDL-particle size was measured as relative LDL migration using polyacrylamide gel electrophoresis with the LipoPhor system.
• A latex photometric immunoassay method was used to determine the plasma PAI-1 level, including the tissue PA/PAI-1 complex and the active and latent forms of PAI-1.

Results

• Researchers found that in both the overall patients population (β=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 (β=0.276, P<0.0001), an elevated PAI-1 level independently predicted smaller-sized LDL-particle, after adjustments for ASCVD risk factors in a multivariate regression analysis.
• Furthermore, it was demonstrated in multivariate regression models that 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 the independent variables associated with an increased PAI-1 level.
• Data reported similar findings from a statistical analysis of data from nondiabetic patients with well-controlled serum LDL-C levels.
• Additionally, a multiple-logistic regression analysis performed in the 310 patients followed up for at least 6 months, revealed that after adjusting for ASCVD risk factors, the percent changes of the plasma PAI-1 level in the third tertile versus those in the first tertile were independently predictive of decreased LDL-particle size [odds ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02].