• Amit Kaura, Adam Hartley, Vasileios Panoulas, Ben Glampson, ShahAnoop S VASV0000-0002-2825-3419National Heart and Lung Institute, Imperial College London, London, United Kingdom.NIHR Imperial Biomedical Research Centre, Imperial College London and Imperial College Healthcare NHS Trust, London, United Kingdom.Londo, Jim Davies, Abdulrahim Mulla, Kerrie Woods, Joe Omigie, Anoop D Shah, Mark R Thursz, Paul Elliott, Harry Hemmingway, Bryan Williams, Folkert W Asselbergs, Michael O'Sullivan, Graham M Lord, Adam Trickey, Jonathan Ac Sterne, Dorian O Haskard, Narbeh Melikian, Darrel P Francis, Wolfgang Koenig, Ajay M Shah, Rajesh Kharbanda, Divaka Perera, Riyaz S Patel, Keith M Channon, Jamil Mayet, and Ramzi Khamis.
• National Heart and Lung Institute, Imperial College London, London, United Kingdom.
• PLoS Med. 2022 Feb 1; 19 (2): e1003911e1003911.

BackgroundThere 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 FindingsWe 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 (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor.ConclusionsThese 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 RegistrationClinicalTrials.gov - NCT03507309.

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