Soluble urokinase Plasminogen Activator Receptor (suPAR) mediates the effect of a lower education level on adverse outcomes in patients with coronary artery disease.

AIMS: To investigate whether the adverse impact of lower educational attainment on mortality risk in patients with coronary artery disease (CAD) is mediated by the activation of inflammatory and immune pathways, estimated as elevated soluble urokinase plasminogen activator receptor levels. METHODS AND RESULTS: In 3164 patients undergoing coronary angiography, we investigated multivariable associations between suPAR and educational attainment and assessed the relationship between a lower educational level (defined as a high-school degree or less as the highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray's subdistribution competing risk models. The potential mediating effect through suPAR and high-sensitivity C-reactive protein (hs-CRP) was assessed using mediation analysis. A total of 1814 patients (57.3%) had achieved a higher (≥college) education level and 1350 patients (42.7%) a lower (≤high school) education level. Soluble urokinase plasminogen activator receptor levels were 9.0% [95% confidence interval (CI) 6.3-11.8, P ≤ 0.0001] higher in patients with lower educational qualifications than in those with higher educational qualifications after covariate adjustment. Lower educational attainment was associated with a higher risk of cardiovascular death after adjustment for demographic, clinical, and behavioural covariates, including CAD severity and heart failure history, medication use, and hs-CRP levels [hazard ratio 1.26 (95% CI 1.02-1.55, P = 0.03)]. However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular death became insignificant. Values were similar for all-cause death. Soluble urokinase plasminogen activator receptor levels mediated 49% and hs-CRP levels 17% of the cardiovascular death risk attributable to lower educational attainment. CONCLUSION: Circulating suPAR levels importantly mediate the effects of lower educational attainment on mortality, indicating the importance of systemic inflammation and immune dysregulation as biologic mediators of adverse social determinants of health.

In patients with coronary artery disease (CAD), we demonstrate that nearly half of the higher risk of all-cause and cardiovascular mortality associated with lower educational attainment as a measure of socioeconomic status is mediated by systemic inflammation and immune dysregulation, which can be estimated by measuring the circulating soluble urokinase plasminogen activator receptor (suPAR) levels. Even after accounting for differences in cardiovascular risk factors, lower educational attainment is associated with higher mortality risk in patients with CAD and there is activation of inflammatory pathways and immune dysregulation in those with lower (≤high school) educational attainment than in those with higher (≥college) educational attainment, estimated as higher circulating suPAR levels.Almost half of the higher risk for adverse outcomes observed in those with lower educational attainment appears to be due to systemic inflammation and immune dysregulation and can be estimated from measuring suPAR levels.

High sensitivity troponin I as a biomarker for cardiac allograft vasculopathy: Evaluation of diagnostic potential and clinical utility.

INTRODUCTION: Cardiac allograft vasculopathy (CAV) limits long-term survival in heart transplant (HTx) recipients. The use of biomarkers in CAV surveillance has been studied, but none are used in clinical practice. The predictive value of high-sensitivity troponin I (hsTnI) has not been extensively investigated in HTx recipients. METHODS: HTx patients undergoing surveillance coronary angiograms and enrolled in the Emory Cardiovascular Biobank had plasma hsTnI measured. CAV grade was assessed using ISHLT nomenclature. Multivariable cumulative link mixed modeling was performed to determine association between hsTnI level and CAV grade. Patients were followed for adverse outcomes over a median 10-year period. Kaplan-Meier survival analysis and Cox proportional hazard modeling were performed. RESULTS: Three hundred and seventy-two angiograms were analyzed in 156 patients at a median 8.9 years after transplant. hsTnI levels were positively correlated with concurrent CAV grade after adjustment for age, age at transplant, sex, BMI, hypertension, diabetes, hyperlipidemia, estimated glomerular filtration rate, and history of acute cellular rejection (p = .016). In an adjusted Cox proportional hazard model, initial hsTnI level above the median (4.9 pg/mL) remained a predictor of re-transplantation or death (hazard ratio 1.82; 95% confidence interval 1.16-2.90; p = .01). CONCLUSION: An elevated hsTnI level reflects severity of CAV and is associated with poor long-term outcomes in patients with HTx.