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Signal Acquisition, Score Interpretation, and Economics of a Non-Invasive Point-of-Care Test for Coronary Artery Disease
Published on: August 9, 2024
Platelet surface expression of cyclophilin A is associated with increased mortality in patients with symptomatic
Dominik Rath1, Saskia von Ungern-Sternberg1, David Heinzmann1
1Department of Cardiology, University Hospital Tübingen, Tübingen, Germany.
Insights
Cyclophilin A (CyPA) platelet levels and a specific gene variant (PPIA rs6850) impact cardiovascular disease prognosis. Lower CyPA expression and carrying the minor allele of PPIA rs6850 are linked to worse outcomes in symptomatic patients.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Genetics
Background:
- Cyclophilin A (CyPA) is crucial for cellular functions.
- Elevated CyPA on platelets correlates with hypertension and hypercholesterolemia in stable coronary artery disease (CAD).
- CyPA expression on platelets decreases in acute myocardial infarction.
Purpose of the Study:
- To examine the link between CyPA platelet surface expression and a CyPA gene polymorphism (PPIA rs6850).
- To assess their association with prognosis in patients experiencing symptomatic cardiovascular disease.
Main Methods:
- 335 patients with symptomatic CAD were followed for 1080 days.
- Endpoints included all-cause death, myocardial infarction (MI), ischemic stroke, and bleeding.
- Genotyping for CyPA PPIA rs6850 was performed in 752 patients.
Main Results:
- Lower CyPA platelet surface expression (< median) correlated with worse prognosis (combined endpoint, all-cause death).
- Homozygous carriers of the minor PPIA rs6850 allele had worse event-free survival (combined endpoint, MI) versus major allele carriers.
Conclusions:
- CyPA platelet expression is linked to mortality risk.
- The CyPA PPIA rs6850 polymorphism is associated with recurrent MI in symptomatic CAD.
- CyPA may serve as a biomarker for risk stratification and personalized therapy in cardiovascular disease.
Background:
Cyclophilin A (CyPA) is an important intracellular molecule mediating essential cellular functions such as signaling and protein folding. Enhanced CyPA platelet surface expression is associated with hypertension and hypercholesterolemia in patients with stable coronary artery disease (CAD). In patients with acute myocardial infarction CyPA platelet surface expression is significantly decreased. The aim of this study was to investigate possible associations of CyPA platelet surface expression and a clinically relevant CyPA single-nucleotide polymorphism (CyPA PPIA rs6850) with prognosis in patients with symptomatic cardiovascular disease.
Materials And Methods:
Blood was obtained from 335 consecutive patients with symptomatic CAD. All patients were followed up for 1080 days for endpoints all-cause death, myocardial infarction (MI), ischemic stroke, and bleeding. The primary combined endpoint was defined as a composite of all-cause death and/or MI and/or ischemic stroke. Cyclophilin A platelet surface expression levels less than or equal to the median were significantly associated with a worse prognosis (combined endpoint and all-cause death) when compared to CyPA greater than the median. Genotyping for CyPA PPIA rs6850 was performed in 752 patients with symptomatic CAD. Homozygous carriers of the minor allele showed a significantly worse cumulative event-free survival for both combined endpoint and MI when compared to carriers of the major allele.
Conclusion:
The CyPA platelet surface expression is associated with mortality whereas CyPA PPIA rs6850 is associated with recurrent MI in patients with symptomatic CAD. Cyclophilin A might offer a new biomarker for risk stratification and tailoring therapies in patients with cardiovascular disease.
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