Inflammatory risk and cardiovascular events in patients without obstructive coronary artery disease: The ORFAN multicentre, longitudinal cohort study

Kenneth Chan, Elizabeth Wahome, Apostolos Tsiachristas, Alexios S Antonopoulos, Parijat Patel, Maria Lyasheva, Lucy Kingham, Henry West, Evangelos K Oikonomou, Lucrezia Volpe, Michail C Mavrogiannis, Edward Nicol, Tarun K Mittal, Thomas Halborg, Rafail A Kotronias, David Adlam, Bhavik Modi, Jonathan Rodrigues, Nicholas Screaton, Attila KardosJohn P Greenwood, Nikant Sabharwal, Giovanni Luigi De Maria, Shahzad Munir, Elisa McAlindon, Yogesh Sohan, Pete Tomlins, Muhammad Siddique, Andrew Kelion, Cheerag Shirodaria, Francesca Pugliese, Steffen E Petersen, Ron Blankstein, Milind Desai, Bernard J Gersh, Stephan Achenbach, Peter Libby, Stefan Neubauer, Keith M Channon, John Deanfield, Charalambos Antoniades, ORFAN Consortium, Joseph Selvanayagam

Research output: Contribution to journalArticlepeer-review

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Abstract

Background: Coronary computed tomography angiography (CCTA) is the first line investigation for chest pain, and it is used to guide revascularisation. However, the widespread adoption of CCTA has revealed a large group of individuals without obstructive coronary artery disease (CAD), with unclear prognosis and management. Measurement of coronary inflammation from CCTA using the perivascular fat attenuation index (FAI) Score could enable cardiovascular risk prediction and guide the management of individuals without obstructive CAD. The Oxford Risk Factors And Non-invasive imaging (ORFAN) study aimed to evaluate the risk profile and event rates among patients undergoing CCTA as part of routine clinical care in the UK National Health Service (NHS); to test the hypothesis that coronary arterial inflammation drives cardiac mortality or major adverse cardiac events (MACE) in patients with or without CAD; and to externally validate the performance of the previously trained artificial intelligence (AI)-Risk prognostic algorithm and the related AI-Risk classification system in a UK population. 

Methods: This multicentre, longitudinal cohort study included 40 091 consecutive patients undergoing clinically indicated CCTA in eight UK hospitals, who were followed up for MACE (ie, myocardial infarction, new onset heart failure, or cardiac death) for a median of 2·7 years (IQR 1·4–5·3). The prognostic value of FAI Score in the presence and absence of obstructive CAD was evaluated in 3393 consecutive patients from the two hospitals with the longest follow-up (7·7 years [6·4–9·1]). An AI-enhanced cardiac risk prediction algorithm, which integrates FAI Score, coronary plaque metrics, and clinical risk factors, was then evaluated in this population. 

Findings: In the 2·7 year median follow-up period, patients without obstructive CAD (32 533 [81·1%] of 40 091) accounted for 2857 (66·3%) of the 4307 total MACE and 1118 (63·7%) of the 1754 total cardiac deaths in the whole of Cohort A. Increased FAI Score in all the three coronary arteries had an additive impact on the risk for cardiac mortality (hazard ratio [HR] 29·8 [95% CI 13·9–63·9], p<0·001) or MACE (12·6 [8·5–18·6], p<0·001) comparing three vessels with an FAI Score in the top versus bottom quartile for each artery. FAI Score in any coronary artery predicted cardiac mortality and MACE independently from cardiovascular risk factors and the presence or extent of CAD. The AI-Risk classification was positively associated with cardiac mortality (6·75 [5·17–8·82], p<0·001, for very high risk vs low or medium risk) and MACE (4·68 [3·93–5·57], p<0·001 for very high risk vs low or medium risk). Finally, the AI-Risk model was well calibrated against true events. 

Interpretation: The FAI Score captures inflammatory risk beyond the current clinical risk stratification and CCTA interpretation, particularly among patients without obstructive CAD. The AI-Risk integrates this information in a prognostic algorithm, which could be used as an alternative to traditional risk factor-based risk calculators. 

Funding: British Heart Foundation, NHS-AI award, Innovate UK, National Institute for Health and Care Research, and the Oxford Biomedical Research Centre.

Original languageEnglish
Pages (from-to)2606-2618
Number of pages13
JournalThe Lancet
Volume403
Issue number10444
Early online date29 May 2024
DOIs
Publication statusPublished - 15 Jun 2024
Externally publishedYes

Keywords

  • Inflammation
  • Chest pain
  • Obstructive coronary artery disease

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