Imaging of coronary inflammation for cardiovascular risk prediction
Authors: Amir A Mahabadi, Tienush Rassaf
Journal: The Lancet (2018)

Inflammation plays an important part in the development of atherosclerosis and is a predictor of cardiovascular disease manifestation.1Libby P Theroux P Pathophysiology of coronary artery disease.Circulation. 2005; 111: 3481-3488Crossref PubMed Scopus (1262) Google Scholar Although circulating biomarkers of inflammation—eg, high sensitivity C-reactive protein—are associated with cardiovascular risk, they might not adequately reflect inflammatory activity in the coronary arteries at the individual patient level. Epicardial and perivascular adipose tissue—surrounding the heart and coronary arteries—secretes proinflammatory and anti-inflammatory cytokines and chemokines locally, and these tissues are associated with the extent and progression of coronary atherosclerosis and hard coronary events.2Packer M Epicardial adipose tissue may mediate deleterious effects of obesity and inflammation on the myocardium.J Am Coll Cardiol. 2018; 71: 2360-2372Crossref PubMed Scopus (253) Google Scholar, 3Mahabadi AA Lehmann N Kalsch H et al.Association of epicardial adipose tissue with progression of coronary artery calcification is more pronounced in the early phase of atherosclerosis: results from the Heinz Nixdorf recall study.JACC Cardiovasc Imaging. 2014; 7: 909-916Crossref PubMed Scopus (114) Google Scholar, 4Mahabadi AA Berg MH Lehmann N et al.Association of epicardial fat with cardiovascular risk factors and incident myocardial infarction in the general population: the Heinz Nixdorf Recall Study.J Am Coll Cardiol. 2013; 61: 1388-1395Crossref PubMed Scopus (334) Google Scholar, 5Mahabadi AA Reinsch N Lehmann N et al.Association of pericoronary fat volume with atherosclerotic plaque burden in the underlying coronary artery: a segment analysis.Atherosclerosis. 2010; 211: 195-199Summary Full Text Full Text PDF PubMed Scopus (123) Google Scholar However, a link between imaging-based signs of local inflammation within the fat depot and subsequent events has not been established. In The Lancet, Evangelos Oikonomou and colleagues report findings of a post-hoc analysis of prospectively obtained outcome data from two independent clinical cohorts in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort).6Oikonomou 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; (published online Aug 28.)http://dx.doi.org/10.1016/S0140-6736(18)31114-0Summary Full Text Full Text PDF PubMed Scopus (361) Google Scholar 3912 participants underwent coronary angiography (CT) to measure perivascular fat attenuation around the right coronary artery. The authors note a strong and independent association of the pericoronary fat attenuation index (FAI) with all-cause mortality (hazard ratio [HR] 1·49, 95% CI 1·20–1·85, p=0·0003 in the derivation cohort; 1·84, 1·45–2·33, p<0·0001 in the validation cohort) and cardiac mortality (HR 2·15, 95% CI 1·33–3·48, p=0·0017 in the derivation cohort; 2·06, 1·50–2·83, p<0·0001 in the validation cohort). To our knowledge, this is the first large and prospective study to show that a non-invasive imaging-based measure of local coronary inflammation can predict cardiovascular risk. Currently, non-contrast cardiac CT is done routinely for risk stratification in primary prevention, to quantify coronary artery calcification as an imaging-based test of subclinical atherosclerosis.7Detrano R Guerci AD Carr JJ et al.Coronary calcium as a predictor of coronary events in four racial or ethnic groups.N Engl J Med. 2008; 358: 1336-1345Crossref PubMed Scopus (2128) Google Scholar By contrast, coronary CTA is suggested for symptomatic patients with a low-to-intermediate pretest likelihood, allowing exclusion of coronary artery disease because of its high negative predictive value.8Hoffmann U Truong QA Schoenfeld DA et al.Coronary CT angiography versus standard evaluation in acute chest pain.N Engl J Med. 2012; 367: 299-308Crossref PubMed Scopus (633) Google Scholar Assessment of coronary inflammation represents a novel aspect in the evaluation of coronary CTA and, as shown by Oikonomou and colleagues,6Oikonomou 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; (published online Aug 28.)http://dx.doi.org/10.1016/S0140-6736(18)31114-0Summary Full Text Full Text PDF PubMed Scopus (361) Google Scholar it improves prediction, discrimination, and reclassification of all-cause and cardiac mortality. The present results accord with previous findings of different measures from this imaging technology—eg, severity of coronary artery disease and high-risk plaque characteristics—to predict future events.9Ferencik M Mayrhofer T Bittner DO et al.Use of high-risk coronary atherosclerotic plaque detection for risk stratification of patients with stable chest pain: a secondary analysis of the PROMISE randomized clinical trial.JAMA Cardiol. 2018; 3: 144-152Crossref PubMed Scopus (235) Google Scholar, 10Nielsen LH Botker HE Sorensen HT et al.Prognostic assessment of stable coronary artery disease as determined by coronary computed tomography angiography: a Danish multicentre cohort study.Eur Heart J. 2017; 38: 413-421PubMed Google Scholar When combining information from the extent of plaque burden, plaque composition, and coronary inflammation, coronary CTA has the potential to allow for more accurate risk prediction compared with the Agatston coronary calcium score as assessed by non-contrast cardiac CT. This possibility could lead to an expansion of indications for coronary CTA to prevention cohorts. One hurdle of the study by Oikonomou and colleagues, however, is that it is based on patients who underwent clinically indicated CTA and represent a high proportion of symptomatic patients. It remains unclear whether the observed findings can be translated to a primary or secondary prevention cohort, making future studies indispensable to confirm the effectiveness of coronary inflammation assessment to predict outcome in appropriate populations. Importantly, in the present study, the value of coronary inflammation to predict future mortality was independent of coronary plaque burden and high-risk plaque characteristics. Moreover, the perivascular FAI was not associated with coronary calcium score or local calcium burden in the adjacent vascular segment. This finding suggests that measures of coronary inflammation from coronary CTA provide complementary information to the anatomical information of plaque burden and composition. To date, it remains unclear whether and how coronary inflammation can be modulated and treated. In a subgroup analysis of the present study, some patients with a high perivascular FAI were advised to initiate treatment with statins or aspirin, and they showed an improved outcome because the perivascular FAI was no longer predictive of cardiac risk in these individuals (HR 2·85, 95% CI 0·44–18·49; p=0·25). However, the perivascular FAI was highly predictive in those who did not receive any recommendations for change of management after coronary CT (HR 18·71, 95% CI 2·01–174·04; p=0·0101). Although statins are effective to prevent cardiovascular events in patients with elevated inflammatory biomarkers and lead to a change in epicardial fat,11Ridker PM Danielson E Fonseca FA et al.Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.N Engl J Med. 2008; 359: 2195-2207Crossref PubMed Scopus (5288) Google Scholar, 12Alexopoulos N Melek BH Arepalli CD et al.Effect of intensive versus moderate lipid-lowering therapy on epicardial adipose tissue in hyperlipidemic post-menopausal women: a substudy of the BELLES trial (Beyond Endorsed Lipid Lowering with EBT Scanning).J Am Coll Cardiol. 2013; 61: 1956-1961Crossref PubMed Scopus (117) Google Scholar further studies are crucial to assess the effect of prevention strategies such as statins and anti-inflammatory approaches on the modification of coronary inflammation to ultimately improve patients' outcomes. The strengths of the study by Oikonomou and colleagues include that CT examinations were done with various scanning protocols and derived from different CT vendors and scanner generations. This diversity makes quantification of coronary inflammation a robust marker, readily available as an additional readout of routinely undertaken CT examinations. However, measurement of the pericoronary FAI is relatively time-consuming and currently restricted to centres with dedicated expertise in this area. This complexity necessitates automated software programs, enabling quick and reliable quantification of the perivascular FAI to allow its implementation in everyday clinical routine. If these obstacles are resolved, characterisation of coronary inflammation in addition to detection of atherosclerosis could have a role in preventive cardiology. We declare no competing interests. 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 dataThe perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation. High perivascular FAI values (cutoff ≥–70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients. Full-Text PDF Open Access