Increased plasminogen activator inhibitor-1 (PAI-1) and its associations with metabolic risk in healthy young adults with early life stress.

OBJECTIVES: We aimed to characterize the interplay between early life stress (ELS), metabolic syndrome (MetS), and plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system implicated in cardiometabolic diseases. We also examined the understudied intersection of ELS, physical activity and PAI-1. METHODS: Healthy young adults ages 18-40 (N=200; 68% female) were recruited from the community. Participants with ELS (N=118) experienced childhood maltreatment, and the majority (n=92) also experienced childhood parental loss. Control participants (N=82) had no history of childhood maltreatment or parental loss. Participants had no current cardiometabolic or thrombotic conditions. Fasting plasma samples were assessed for markers of metabolic risk and total PAI-1 using the Bio-Plex Pro Human Diabetes Panel (Bio-Rad Laboratories). A composite metabolic risk z-score (MetS risk) was computed from the mean standardized z-scores of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, total cholesterol, LDL and HLD cholesterol, fasting plasma glucose, and hemoglobin A1c. RESULTS: We found that a history of ELS was linked to both higher PAI-1 levels and a higher MetS risk score. ELS was associated with a higher MetS Z-score in adulthood via increased circulating PAI-1 levels (Average Causal Mediation Effect [ACME]= 0.07, p = 0.036). ELS was also linked to increased PAI-1 levels via greater MetS z-scores (ACME = 0.02, p < 0.001). There was a significant interaction effect of ELS and exercise on PAI-1 levels (p = 0.03), such that engaging in higher levels of daily exercise was linked to lower PAI-1 levels in individuals with ELS. CONCLUSION: Healthy young adults with ELS have elevated PAI-1 levels and metabolic risk scores. Among individuals with ELS, exercise is linked to lower PAI-1 levels, suggesting a potential direction for early intervention.

Increased Cardiometabolic Risk in Healthy Young Adults With Early Life Stress.

OBJECTIVE: This study aimed to evaluate the relationship between early life stress (ELS) and metabolic risk in healthy young adults and assess the role of health behaviors. METHODS: Young adults aged 18 to 40 years ( N = 190) with no medical conditions or medication usage were recruited from the community. Participants with ELS ( N = 113) had a history of childhood maltreatment, and most also experienced parental loss ( n = 88). Controls ( N = 77) had no history of maltreatment or parental loss. Standardized interviews and self-reports assessed demographics, adversity, medical/psychiatric history, and health behaviors. Blood pressure and anthropometrics were measured, and fasting plasma assayed for lipid profiles, glucose, insulin level, and hemoglobin A 1c . We calculated both a clinical cut-point and continuous composite metabolic risk score based on clinical risk factors and the mean of z scores of each measure, respectively. RESULTS: ELS was significantly associated with increased clinical cut-point ( ß = 0.68, 95% confidence interval [CI] = 0.20-1.17, p = .006) and continuous ( ß = 0.23, 95% CI = 0.08-0.038, p = .003) composite metabolic risk scores. On sensitivity analysis, the association of ELS with the continuous composite metabolic risk score was reduced to a trend after adjusting for a range of psychosocial and health predictors ( ß = 0.18, 95% CI = 0.00-0.36, p = .053), with both diet and college graduate status significant in the model. CONCLUSIONS: Healthy young adults with a history of ELS have increased metabolic risk scores as compared with controls. This relationship may be partially due to health behaviors and socioeconomic factors. These findings underline that ELS is an early contributor to metabolic risk.