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Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study

Title: Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: a cohort study
Authors: Kaura, A
Hartley, A
Panoulas, V
Glampson, B
Shah, ASV
Davies, J
Mulla, A
Woods, K
Omigie, J
Shah, AD
Thursz, MR
Elliott, P
Hemmingway, H
Williams, B
Asselbergs, FW
O'Sullivan, M
Lord, GM
Trickey, A
Sterne, JA
Haskard, DO
Melikian, N
Francis, DP
Koenig, W
Shah, AM
Kharbanda, R
Perera, D
Patel, RS
Channon, KM
Mayet, J
Khamis, R
Item Type: Journal Article
Abstract: 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 (<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. 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.
Issue Date: 22-Feb-2022
Date of Acceptance: 11-Jan-2022
URI: http://hdl.handle.net/10044/1/95383
DOI: 10.1371/journal.pmed.1003911
ISSN: 1549-1277
Publisher: Public Library of Science (PLoS)
Journal / Book Title: PLoS Medicine
Volume: 19
Issue: 2
Copyright Statement: © 2022 Kaura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: General & Internal Medicine
11 Medical and Health Sciences
Publication Status: Published
Conference Place: United States
Article Number: ARTN e1003911
Appears in Collections:National Heart and Lung Institute
School of Public Health



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