CRISP CT – the Fat Attenuation Index Imaging Biomarker is Predictive of Risk of Cardiac Mortality and Offers Greater Prognostic Value than Routine Coronary Computed Tomography Angiography Alone
– Insight into the CRISP-CT study, which was presented at the European Society of Cardiology Congress, Munich, Germany, 25–29 August, 2018
Atherosclerosis is a common disease in which plaques, formed from fatty deposits, develop in the inner layers of arteries. Over time, these plaques grow and bulge inside the arteries and impede blood flow.1 The uneven surface and narrowing of the arteries contributes to clot formation and thrombosis, which can lead to obstruction of blood flow.1
Myocardial infarction (MI) often occurs following rupture of atherosclerotic plaques.2 Notably, in around half of MI cases, plaque size caused a narrowing of the artery of less than 50% – in these cases, MI follows the rupture of a relatively small plaque.3 It is recognised that inflammation drives rupture of plaques;2 indeed, inflammation may be predictive of MI.
Coronary computed tomography angiography (CTA) is a widely used non-invasive imaging modality for diagnosing coronary artery disease; however, this test focuses on identification of anatomically significant narrowing of the coronary artery.4 Traditional CTA therefore may not detect a risk of MI in patients with small plaque formations that, in conjunction with inflammation, pose a risk of rupturing and leading to MI.5
The recently developed perivascular fat attenuation index (FAI) captures inflammation-induced changes: reduced adipogenesis, increased lipolysis and increased oedema, driving a shift from ‘fatty’ to ‘watery’ content in perivascular fat. FAI has demonstrated efficacious early detection of coronary inflammation when used along with routine coronary CTA.6
The Cardiovascular risk prediction using computed tomography study (CRISPT-CT) assessed whether the FAI could act as an imaging biomarker for clinical MI identification.5 Nearly 4,000 consecutively enrolled patients from two CTA study sites – forming the derivation and validation cohorts – were investigated using FAI analysis performed alongside routine CTA diagnosis.5
In both cohorts, high FAI values in the perivascular fat of the proximal right coronary artery, left anterior descending artery and left circumflex artery were associated with a significantly higher adjusted risk of all-cause mortality. Elevated FAI values were only associated with prospective cardiac mortality risk when assessing the right coronary artery and the left anterior descending artery, and not in the left circumflex artery. Consequently, FAI analysis was restricted to the proximal right coronary artery. As cardiac mortality correlated with increasing FAI, a cut-off value (−70.1 HU) was chosen to stratify patients as either high- or low-FAI.5
After adjustment for other risk factors (including coronary disease, calcium scores, age and sex), high FAI was prognostic for cardiac death. For prediction of both non-fatal acute MI and cardiac death, FAI provided markedly greater prognostic value than routinely used CTA or risk scoring systems.
Further practical considerations arose from subgroup analyses. The close association between high FAI and cardiac mortality was independent of indications for coronary CTA referral and presenting symptoms, including chest pain. Interestingly, in patients initiated on statins or aspirin after CTA, FAI was not predictive of mortality risk.5 The CRISP-CT investigators note this may mean that the risk factors identified by FAI may be modifiable with medical treatment – this will require further robust investigation in a randomised clinical trial setting.
Integration of the FAI into routine coronary CTA diagnosis may help capture patients at high risk of MI due to small plaques and inflammation, who would otherwise potentially be missed with CTA alone.
1. Rafieian-Kopaei M, Setorki M, Doudi M, et al. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med. 2014;5:927–46.
2. Joshi NV, Toor I, Shah AS, et al. Systemic atherosclerotic inflammation following acute myocardial infarction: myocardial infarction begets myocardial infarction. J Am Heart Assoc. 2015;4:e001956.
3. Fishbein MC, Siegel RJ. How big are coronary atherosclerotic plaques that rupture? Circulation. 1996;94:2662–6.
4. Douglas PS, Hoffmann U, Patel MR, et al. Outcomes of anatomical versus functional testing for coronary artery disease. N Engl J Med. 2015;372:1291–300.
5. Oikonomou EK, Marwan M, Desai MY, et al. Non-invasive detection of coronary inflammation using computed tomography and prediction of residual cardiovascular risk (the CRISP CT study): a post-hoc analysis of prospective outcome data. Lancet. 2018;392:929–39.
6. Antonopoulos AS, Sanna F, Sabharwal N, et al. Detecting human coronary inflammation by imaging perivascular fat. Sci Transl Med. 2017;9:eaal2658.
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