High-throughput targeted proteomics discovery approach and spontaneous reperfusion in ST-segment elevation myocardial infarction
American Heart Journal, 2019
Shavadia J., Granger C., Alemayehu W., Westerhout C., Povsic T., Brener S., van Diepen S., Defilippi C., Armstrong P.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology | Serum |  Olink Target 96 |
Abstract
Objectives: To explore associations between spontaneous reperfusion (SR) in ST-segment elevation myocardial infarction (STEMI) using a multi-marker cardiovascular proteins strategy.
Background: Although SR prior to primary percutaneous coronary intervention (pPCI) is associated with improved outcomes, its pathophysiology remains unclear.
Methods: We evaluated STEMI patients from the Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI) trial treated with pPCI within 6 hours from symptom onset. SR was core-lab defined as pre-PCI Thrombolysis in Myocardial Infarction (TIMI) flow 2 or 3. Ninety-one cardiovascular disease-related serum biomarkers drawn prior to PCI were analyzed using a high throughput “targeted discovery” panel. Expression levels for individual biomarkers were compared between patients with/without SR. A hierarchical clustering method of biomarkers identified clusters of biomarkers that differentiated the two groups. Associations between individual biomarkers and clusters with SR were further evaluated by multivariable logistic regression.
Results: Of 683 patients studied, 290 had spontaneous reperfusion; those with compared to without SR were more likely non-inferior STEMI, had lower clinical acuity, and lower baseline levels of troponin and creatine kinase. SR was associated with a lower occurrence of 90-day composite of death, heart failure or cardiogenic shock. Fifty-two of 91 individual biomarkers were significantly univariably associated with SR. Forty-five remained significant with adjustment for false discovery rate. Using cluster analysis, 26 biomarkers clusters were identified, explaining 72% of total covariance, and 13 biomarker clusters were significantly
associated with SR after multivariable adjustment. SR was associated with higher mean expression levels of proteins in all 13 clusters. The cluster most strongly associated with SR consisted of novel proteins across various distinct, yet inter-linked pathobiological processes (kallikrein-6, matrix extracellular phosphoglycoprotein, matrix mettaloproteinaise-3 and elafin).
Conclusion: Spontaneous reperfusion prior to pPCI in STEMI was associated with a lower risk of adverse clinical events. These exploratory data from a targeted discovery proteomics platform identifies novel proteins across diverse, yet complementary, pathobiological axes that show promise in providing mechanistic insights into spontaneous reperfusion in STEMI.