Soluble Urokinase‐Type Plasminogen Activator Receptor and High‐Sensitivity Troponin Levels Predict Outcomes in Nonobstructive Coronary Artery Disease

Abstract

Background Multiple biomarkers have been independently and additively associated with major adverse cardiovascular events in patients with coronary artery disease. We investigated the prognostic value of suPAR (soluble urokinase‐type plasminogen activator receptor) and hsTnI (high‐sensitivity troponin I) levels in symptomatic patients with no obstructive coronary artery disease. We hypothesized that high levels of these biomarkers will be associated with the risk of future adverse outcomes. Methods and Results Plasma levels of suPAR and hsTnI were measured in 556 symptomatic patients with no obstructive coronary artery disease. A biomarker risk score was calculated by counting the number of biomarkers above the median in this cohort (suPAR>2523 pg/mL and hsTnI>2.7 pg/mL). Survival analyses were performed with models adjusted for traditional risk factors. All‐cause death and major adverse cardiovascular events (cardiovascular death, myocardial infarction, stroke, and heart failure) served as clinical outcomes over a median follow‐up of 6.2 years. Mean age was 57±10 years, 49% of the cohort patients were female, and 68% had a positive stress test. High suPAR and hsTnI levels were independent predictors of all‐cause death (hazard ratio=3.2 [95% CI, 1.8–5.7] and 1.3 [95% CI, 1.0–1.7], respectively; both P <0.04) and major adverse cardiovascular events (hazard ratio=2.7 [95% CI, 1.4–5.4] and 1.5 [95% CI, 1.2–2.0], respectively; both P <0.002). Compared with a biomarker risk score of 0, biomarker risk scores of 1 and 2 were associated with 19‐ and 14‐fold increased risk of death and development of major adverse cardiovascular events, respectively. Conclusions Among symptomatic patients with no obstructive coronary artery disease, higher levels of suPAR and hsTnI were independently and additively associated with an increased risk of adverse events. Whether modification of these biomarkers will improve risk in these patients needs further investigation.

Prognostic value of soluble urokinase‐type plasminogen activator receptor in coronary artery disease: A meta‐analysis

“…OMCE incidence was reported as a study endpoint in three studies 11,13,15 . Fixed‐effects modelling showed that there was no substantial heterogeneity across these trials (I 2 = 9.8%; p = 0.330).…”

“…Eight studies provided all‐cause mortality rates 10–17 . The degree of heterogeneity for this outcome was found to be very high (I 2 = 96.0%; p = 0.000).…”

Risk Factors Predisposing to Angina in Patients with Non-Obstructive Coronary Arteries: A Retrospective Analysis

“…Similar results were obtained in the American study, in which most NOCAD patients had no increase in CRP [ 61 ]. Nevertheless, several studies showed that 30–55% of NOCAD patients demonstrated a substantial increase in CRP levels [ 62 , 63 , 64 ], although CRP levels did not correlate with increased mortality rates [ 64 , 65 ]. Interestingly, higher CRP levels were also reported in patients with arterial hypertension [ 66 ] and endothelial dysfunction [ 61 ].…”

“…Raised troponin levels in symptomatic patients are a substantial predictor of MACE [ 65 ]. Interestingly, patients with NOCAD who presented a significant increase in troponin due to a specific non-myocardial cause were at the same risk of death and MACE as patients with OCAD and elevated troponins during the 1-year follow-up [ 76 ].…”

Prognostic Value of Soluble Urokinase-Type Plasminogen Activator Receptor and High-Sensitivity C-Reactive Protein on Postoperative Mortality in Patients Undergoing Elective On-Pump Cardiac Surgery

“…[11][12][13][14] Moreover, multiple studies have found increasing suPAR values to be prognostic for adverse events and mortality in patients with confirmed or suspected cardiovascular disease. 6,7,[36][37][38][39] To the extent of the authors' knowledge, only one study has investigated suPAR's prognostic ability in relation to cardiac surgery and demonstrated that increasing preoperative levels of suPAR were associated with higher risk of postoperative complications and 30-day mortality. 20 However, the study exclusively comprised patients with aortic stenosis for aortic valve replacement.…”