Soluble urokinase Plasminogen Activator Receptor (suPAR) is associated with educational attainment in patients with coronary artery disease

Abstract

Abstract Background Biological mediators of adverse social determinants of health may include chronic low-grade inflammation. Elevation of circulating soluble urokinase Plasminogen Activator Receptor (suPAR) levels indicates activation of inflammatory and immune pathways and is associated with cardiovascular outcomes, independent of C-reactive protein (CRP) levels. Purpose We investigated whether the adverse impact of lower educational attainment on all-cause and cardiovascular mortality is mediated by elevated suPAR levels in patients with coronary artery disease (CAD). Methods In 3,164 patients undergoing coronary angiography, we investigated multivariable associations, including demographic characteristics, behavioral and clinical risk factors, between suPAR levels collected at the time of angiography and self-reported educational attainment, and assessed the relationship between lower educational level (defined as high school degree or less as highest educational qualification) and outcomes using Cox proportional hazard and Fine and Gray’s sub-distribution competing risk models. Mediation analyses were performed to assess the total effect of education on mortality, and the indirect effects through hs-CRP and suPAR on survival stratified by education using accelerated failure time models under exponential distribution. Results Mean age of the cohort was 64.5±11.9 years, with 32% women and 8.1±3.8 years follow-up. SuPAR levels were 9.0% [95% CI 6.3–11.8, p <0.0001] higher in patients achieving a lower (≤high school) compared to a higher (≥college) education after full covariate adjustment including hs-CRP levels. Lower educational attainment was associated with a higher risk of cardiovascular death (HR 1.39 [95% CI 1.15–1.68, p=0.0008]). After adjustment for demographic, clinical and behavioral covariates, and hs-CRP levels, this effect remained significant (HR 1.29 [95% CI 1.06–1.57, p=0.01]). However, after adjustment for suPAR levels, the effect of a lower educational level on cardiovascular mortality became insignificant. Values were similar for all-cause death. SuPAR levels mediated 49% and hs-CRP levels 17% of the association between lower educational attainment and cardiovascular mortality. Conclusion SuPAR importantly mediates 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.Figure 1Central Illustration