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

Abstract

SummaryBackgroundCoronary artery inflammation inhibits adipogenesis in adjacent perivascular fat. A novel imaging biomarker—the perivascular fat attenuation index (FAI)—captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA). However, the ability of the perivascular FAI to predict clinical outcomes is unknown.MethodsIn the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort). Perivascular fat attenuation mapping was done around the three major coronary arteries—the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery. We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features.FindingsBetween 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17–89]). Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19–87]). Median follow-up was 72 months (range 51–109) in the derivation cohort and 54 months (range 4–105) in the validation cohort. In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other. Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33–3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50–2·83; p<0·0001 in the validation cohort). The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35–24·40; p<0·0001 for cardiac mortality; 2·55, 1·65–3·92; p<0·0001 for all-cause mortality). This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90–10·88; p<0·0001 for cardiac mortality; 3·69, 2·26–6·02; p<0·0001 for all-cause mortality). Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality.InterpretationThe 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 cardia...

Relation of cardiac adipose tissue to coronary calcification and myocardial microvascular function in type 1 and type 2 diabetes

“…As the epicardial adipose tissue is a transducer of the harmful effects of systemic inflammation and metabolic disorders on the heart it may represent an important treatment target [10,23]. A recent study analyzed the adipose tissue surrounding coronary arteries during coronary artery bypass grafting interventions; Two important findings were demonstrated (1) there was increased inflammation of the adipose tissue surrounding the coronary arteries during acute myocardial infarction; and (2) treatment with metformin had an ameliorative effect on the inflammation in the peri-coronary fat and reduced the risk of major cardiovascular events at 12-month follow-up in persons with prediabetes and acute myocardial infarction [24].…”

Potential role of perivascular adipose tissue in modulating atherosclerosis

“…Moreover, atherosclerotic plaque size and complex lipid core composition were positively correlated with PVAT volume and macrophage infiltration in a postmortem study of human subjects [13]. Thus, imaging of coronary PVAT holds promise as a non-invasive method to detect unstable coronary lesions [49,50].…”

“…Currently, most available methods to evaluate vascular inflammation provide structural information only and cannot specifically discriminate vulnerable atherosclerotic lesions [48]. However, coronary arteries with atherosclerotic plaques appear to have a larger amount of PVAT encroaching into their outer adventitia as detected by computed tomography (CT) [49]. Moreover, atherosclerotic plaque size and complex lipid core composition were positively correlated with PVAT volume and macrophage infiltration in a postmortem study of human subjects [13].…”

“…Oikonomou et al [49] analyzed two prospective cohorts who received coronary CT scans and found the PVAT FAI to be a strong predictor of all-cause and cardiac mortality. Moreover, the PVAT FAI was observed to be beneficial in the risk stratification of patients without coronary artery disease who might benefit from intensive primary therapy to reduce their CVD risk.…”

Imaging inflammation in atherosclerosis: Exploring all avenues

“…17,18 Further, recent advances in coronary computed tomography angiography (CCTA) technology allow to detect coronary inflammation by capturing perivascular fat attenuation. 19 Given the widespread use of CCTA as well as novel CCTA acquisition techniques ranging in a sub-millisievert fraction of effective radiation dose, 20 the prognostic performance of SST 2 -targeted probes will have to be validated against novel imaging biomarkers derived from CCTA before they may advance from research tools to clinical applications. Future studies should also address potential synergistic applications of nuclear imaging techniques and CCTA, with the ultimate goal to identify the vulnerable plaque, the vulnerable artery, and, most importantly, the vulnerable patient.…”