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Background There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. Methods and findings We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups ( Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP 15 mg/L makes it unlikely that sepsis was a major contributor. Conclusions These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. Trial registration ClinicalTrials.gov - NCT03507309, Author(s): Amit Kaura 1,2, Adam Hartley 1,2, Vasileios Panoulas 1,2, Ben Glampson 2, Anoop S. V. Shah 1,2,3, Jim Davies 4, Abdulrahim Mulla 2, Kerrie Woods 4, Joe Omigie 5, [...]