Sex Differences in Circulating Soluble Urokinase-Type Plasminogen Activator Receptor (suPAR) Levels and Adverse Outcomes in Coronary Artery Disease.

Background Women have higher circulating levels of soluble urokinase-type plasminogen activator receptor (suPAR), and elevated suPAR is associated with cardiovascular risk. The independent association of sex with suPAR and the impact of sex on its association with cardiovascular risk are unknown. Methods and Results Plasma suPAR was measured using ELISA in 2 cohorts of 666 asymptomatic individuals (49 years, 65% women) and 4184 patients with coronary artery disease (63 years, 37% women). Independent association of sex with suPAR was studied using linear regression models adjusted for demographics, risk factors, and visceral adiposity in asymptomatic participants. Impact of sex on association of suPAR with all-cause mortality was studied in patients with coronary artery disease using multivariable-adjusted Cox models. Sex-specific suPAR cutoffs for predicting all-cause mortality were calculated. Asymptomatic women had 10% higher suPAR compared with men after adjusting for confounders, and visceral adiposity partly accounted for this association. Over a median follow-up of 5.2 years, 795 deaths were recorded in patients with coronary artery disease. Log2-transformed suPAR was independently associated with mortality (hazard ratio per 1-SD 1.72, 95% CI 1.60-1.85) and an interaction with sex was noted (P=0.005). Association of suPAR with mortality was slightly weaker in women (hazard ratio 1.61, 95% CI 1.41-1.83) compared with men (hazard ratio 1.83, 95% CI 1.67-2.00). However, using sex-specific suPAR cut-offs (4392 pg/mL for women and 3187 pg/mL for men), a similar mortality incidence was observed for both sexes (38.5% and 35.5%, respectively, P=0.3). Conclusions Women have 10% higher plasma suPAR levels compared with men. Elevated sex-specific plasma suPAR levels are equally predictive of risk of adverse events in both sexes.

Low Educational Attainment is a Predictor of Adverse Outcomes in Patients With Coronary Artery Disease.

Background Educational attainment is an indicator of socioeconomic status and is inversely associated with coronary artery disease risk. Whether educational attainment level (EAL) among patients with coronary artery disease influences outcomes remains understudied. Methods and Results Patients undergoing cardiac catheterization had their highest EAL assessed using options of elementary/middle school, high school, college, or graduate education. Primary outcome was all-cause mortality and secondary outcomes were a composite of cardiovascular death/non-fatal myocardial infarction and non-fatal myocardial infarction during follow-up. Cox models adjusted for clinically relevant confounders were used to analyze the association of EAL with outcomes. Among 6318 patients (63.5 years, 63% men, 23% black) enrolled, 16%, 42%, 38%, and 4% had received graduate or higher, college, high school, and elementary/middle school education, respectively. During 4.2 median years of follow-up, there were 1066 all-cause deaths, 812 cardiovascular deaths/non-fatal myocardial infarction, and 276 non-fatal myocardial infarction. Compared with patients with graduate education, those in lower EAL categories (elementary/middle school, high school, or college education) had a higher risk of all-cause mortality (hazard ratios 1.52 [95% CI 1.11-2.09]; 1.43 [95% CI 1.17-1.73]; and 95% CI 1.26 [1.03-1.53], respectively). Similar findings were observed for secondary outcomes. Conclusions Low educational attainment is an independent predictor of adverse outcomes in patients undergoing angiographic coronary artery disease evaluation. The utility of incorporating EAL into risk assessment algorithms and the causal link between low EAL and adverse outcomes in this high-risk patient population need further investigation.