Plasma soluble urokinase-type plasminogen activator receptor level is independently associated with coronary microvascular function in patients with non-obstructive coronary artery disease

Abstract Introduction Stratification for subsequent coronary events among patients with coronary artery disease (CAD) is of considerable interest due to the potential to guide secondary preventive therapies. Soluble urokinase-type plasminogen activator receptor (suPAR) is expressed on various cells involved in atherogenesis and plaque instability, and has been associated with poor clinical outcomes in patients with various conditions. Purpose In this study we investigated the potential role of suPAR as a prognostic biomarker for adverse outcome in patients with CAD, and acute coronary syndrome (ACS) in particular. Methods Plasma levels of suPAR were measured in a cohort of 1,703 patients (AtheroGene Study) with documented coronary artery disease –including 626 patients with ACS and 1077 patients with stable angina pectoris (SAP). The main outcome measures were defined as cardiovascular death and non-fatal myocardial infarction (MI). Survival curves for the endpoints considered were computed according to thirds of the suPAR distribution. The equality of survival curves was tested using the log-rank test. Multivariable models adjusted for common cardiovascular risk factors and the biomarkers CRP, NT-proBNP and high-sensitivity troponin I (hs-TnI) in particular were also computed. Results The prognostic utility of suPAR was evidenced by survival curves stratified for tertiles of circulating suPAR levels –both, in the overall cohort (p=0.00062), and in the ACS cohort (p=0.00099) with a median follow-up of 3,5 years. In multivariable-adjusted Cox regression analyses the hazard ratio (HR) for the prediction of cardiovascular death was 3.60 for log-transformed suPAR levels (p<0.001) in the overall CAD cohort, whereas it was 3.34 (p=0.003) in the ACS cohort. The HR regarding prediction of the combined outcome cardiovascular death and/or non-fatal MI during follow-up was 2.19 (p<0.001) in the overall cohort, and 2.56 (p<0.001) in the ACS cohort. After multivariate adjustment, including conventional cardiovascular risk factors and hs-TnI, suPAR, after log transformation, still enabled a reliable and strong prediction of future cardiovascular death with a HR of 3.17 (p<0.001) in the overall CAD cohort, and a HR of 2.85 (p=0.014) in the ACS cohort. Conclusions Our study demonstrates that suPAR has a strong prognostic value independent of hs-TnI in secondary prevention settings, and thereby might represent a valuable biomarker for risk estimation in CAD. Acknowledgement/Funding Stiftung Rheinland-Pfalz für Innovation, European Union 7th Framework Programme, DZHK e.V., ERA-Net, Abbott Diagnostics

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Abstract 14283: Coronary Microvascular Function is Correlated With Peak Exercise Capacity in Patients With Unexplained Cardiac Exertion Symptoms and Non-obstructive Coronary Artery Disease

Circulation ◽

10.1161/circ.142.suppl_3.14283 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Ali Ahmad ◽

Michel Corban ◽

Takumi Toya ◽

Frederik H Verbrugge ◽

Jaskanwal D Sara ◽

...

Keyword(s):

Coronary Artery Disease ◽

Cardiac Output ◽

Coronary Artery ◽

Exercise Capacity ◽

Obstructive Coronary Artery Disease ◽

Microvascular Function ◽

Peak Exercise ◽

Artery Disease ◽

Response To Exercise ◽

Coronary Microvascular Function

Introduction: Coronary microvascular dysfunction (CMD) is prevalent in symptomatic patients with no obstructive coronary artery disease. We postulated that exercise capacity and cardiac output augmentation in response to exercise are linked to coronary microvascular function in this patient population. Methods: Fifty-one consecutive patients with unexplained cardiac exertion symptoms, non-obstructive coronary artery disease on angiography (<50% stenosis), and normal left ventricular ejection fraction (>50%) who underwent concurrent clinically indicated coronary reactivity testing and invasive cardiopulmonary exercise testing (CPEX) were included. Microvascular function was assessed by coronary flow reserve (CFR; hyperemic/resting flow) in response to intracoronary adenosine injection. Cardiac output (CO) was calculated at rest and peak exercise using Fick’s formula. CO limitation was defined as a measured (peak CO - resting CO) <80% than the expected [6*absolute ΔVO 2 (Peak VO 2 -Rest VO 2 ) increase in CO in L/min]. The relationship between CFR, maximal exercise capacity, and CO augmentation at peak exercise was explored. Results: Patients were 56.6±10.5 years old and 73% were females. CFR had a modest positive correlation with measured increase in CO (r=0.42; P=0.003) ( Fig 1A ), and with maximal ergometric exercise capacity [in Watts/Kg] (Pearson’s r=0.33, P=0.02) ( Fig 1B ). Patients with, vs. without impaired cardiac limitations during exercise, had significantly lower CFR levels (2.6±0.5 vs 3.1±0.7; P=0.01) ( Fig 2 ). Conclusion: Impaired coronary microvascular function is associated with lower peak exercise capacity and reduced cardiac output augmentation in response to exercise, underscoring the functional ramification of CMD in symptomatic patients.

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