Key result
Elevated plasma tPA is linked to increased risk of aortic valve sclerosis.
Why the study?
Aortic valve sclerosis can progress to advanced aortic stenosis, but plasma biomarkers remain lacking, prompting investigation into whether endogenous t-PA is associated with this condition.
Is elevated plasma endogenous tissue-plasminogen activator (t-PA) associated with the presence of aortic valve sclerosis in patients undergoing echocardiography?
Cross-Sectional (n=295)
No
Is elevated plasma endogenous tissue-plasminogen activator (t-PA) associated with the presence of aortic valve sclerosis in patients undergoing echocardiography?
Effect estimate: C-statistic 0.698 (95% CI 0.639-0.758)
Elevated plasma t-PA levels are associated with aortic valve sclerosis and may serve as a potential diagnostic biomarker when combined with clinical factors.
May support t-PA as an adjunctive biomarker for aortic valve sclerosis; leaves open prospective validation before clinical use.
Background: Aortic valve sclerosis (AVSc), a common precursor to calcific aortic valve disease, may progress into advanced aortic stenosis with hemodynamic instability. However, plasma biomarkers of such a subclinical condition remain lacking. Since impaired fibrinolysis featuring dysregulated tissue plasminogen activator (t-PA) is involved in several cardiovascular diseases, we investigated whether endogenous t-PA was also associated with AVSc. Methods: Plasma t-PA levels were measured in 295 consecutive patients undergoing standard echocardiography and Doppler flow imaging. Multiple logistic regression analyses were used to assess the association between t-PA and AVSc. Receiver operating characteristic curve analysis was performed for determining the diagnostic value of t-PA for AVSc. The performance of adding t-PA to clinical signatures of AVSc was evaluated. Concentration of t-PA was assessed in human sclerotic and non-sclerotic aortic valves by histology and immunohistochemistry analysis. Results: Plasma t-PA was higher in patients with AVSc than in non-AVSc counterparts (median, 2063.10 pg/mL vs 1403.17 pg/mL, p < 0.01). C-statistics of plasma t-PA for discriminating AVSc was 0.698 (95%CI: 0.639-0.758). The performance of t-PA for identifying AVSc was better among male and non-hypertensive patients [C-statistics (95%CI): 0.712 (0.634-0.790) and 0.805 (0.693-0.916), respectively]. Combination of t-PA and clinical factors improved classification of the patients (category-free NRI: 0.452, p<0.001; IDI: 0.020, p=0.012). The concentration of t-PA was three times higher in sclerotic compared to non-sclerotic aortic valves. Conclusion: Elevated circulating t-PA level confers an increased risk for AVSc. Further prospective studies with larger sample size are needed to examine if tPA could serve as a diagnostic clinical marker for AVSc.
No takes yet. Share an insight, caveat, or question.
Chen et al. (2020) conducted a cross-sectional in Aortic Valve Sclerosis (AVSc) (n=295). Plasma tissue-plasminogen activator (t-PA) vs. Non-AVSc patients was evaluated on Discrimination of AVSc (C-statistic 0.698, 95% CI 0.639-0.758). Elevated plasma tissue-plasminogen activator levels were associated with an increased risk of aortic valve sclerosis, demonstrating a C-statistic of 0.698 for discriminating the condition.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: