From:  Emerging cardiac CT biomarkers: a systematic review of diagnostic and prognostic utility in cardiovascular disease

 Summary of biomarkers, outcomes, and effect measures.

AuthorYearBiomarker(s) assessedOutcomes evaluatedIncluded in systematic reviewEffective measures reported
Nakahara et al. [1]2017Coronary artery calcification (CAC)Cardiovascular events, risk stratificationYesCAC (Agatston score): independent predictor of future cardiac events; reclassified risk beyond Framingham; significant utility in asymptomatic intermediate-risk individuals.
Budoff et al. [2]2016CT plaque metricsHemodynamic lesion significanceYesSensitivity 79–88%, specificity 55–63%
AUC 0.75–0.77 for CTA vs. invasive FFR
Faulder et al. [3]2024CT-derived fractional flow reserve (FFR-CT)Agreement with invasive FFRYesSpearman r = 0.67; diagnostic accuracy 82.2% (sensitivity 80.9%, specificity 83.1%); accuracy ≥ 90% when FFR-CT > 0.90 or < 0.49, but drops to 54–87% in the intermediate range (0.74–0.82).
Channon et al. [4]2022Perivascular fat attenuation, plaque featuresCAD risk stratificationNoNarrative review: no quantitative effect size reported; describes qualitative associations between perivascular fat attenuation, plaque characteristics, and CAD risk stratification.
Cundari et al. [5]2024EAT, FAI, LAP, FFR-CTMACE, ischemia, mortalityYesOR 1.5–2.3; AUC 0.76–0.88
Schuijf et al. [6] 2020CT perfusion, plaque featuresINOCA diagnosisYesPrevalence: 8% (31/381) had CT-defined INOCA; compared to those without ischemia, INOCA patients had higher total atheroma volume (118 mm³ vs. 60 mm³, P = 0.008), more positive remodeling (13% vs. 1%, P = 0.006), and increased LAP volume (20 mm³ vs. 10 mm³, P = 0.007).
Lima and Schuijf [7]2020CT perfusion, scar imagingCAD risk phenotypingNoExpert narrative: no quantitative effect size reported; highlights potential prognostic value of combining CT perfusion and scar imaging for CAD risk assessment.
Williams et al. [8]2020LAPMIYesAdjusted HR 1.60 (1.10–2.34) per doubling of LAP burden; > 4% burden → HR 4.65 (2.06–10.50); strongest predictor of MI.
Klüner et al. [9]2021FAICV risk stratificationYesReported HRs for elevated FAI vs. low FAI/no HRP (e.g., HR ~6.26 for adjusted cardiac risk in FAI-high/HRP group vs. FAI-low/HRP-negative); also described improvements in risk discrimination (e.g., AUC gains) when adding FAI beyond standard risk markers.
Rajiah et al. [10]2022FFR-CTClinical integration/interpretationYesReports diagnostic thresholds (FFR-CT > 0.80 normal; 0.76–0.80 borderline; ≤ 0.75 abnormal), discusses increased specificity of CTA when FFR-CT is used, and clinical decision-making implications (ICA vs. medical management).
Nørgaard et al. [11] 2019FFR-CTDiagnostic workflowYesConsensus-based diagnostic algorithms and reporting standards for FFR-CT interpretation.
Manubolu et al. [12]2024EATPlaque burdenYesMean density: 77.2  ±  4.6 HU & volume 118.5 ± 41.2 cm³; each +1 HU in EAT density → +7% fibrous-fatty plaque (P < 0.03); no association with EAT volume.
Gallone et al. [13]2023HRP featuresMACEYesOR 1.6–2.5; AUC up to 0.83
Nørgaard et al. [14]2022FFR-CTMACE prognosisYesMeta-analysis of 5 studies (5,460 patients): FFR-CT ≤  0.80 vs. > 0.80 RR = 2.31 (95% CI 1.29–4.13, P = 0.005); every −0.10-unit FFR-CT → RR = 1.67 (95% CI 1.47–1.87, P < 0.001).
Mathew et al. [15]2018FFR-CTGuidance in angiographyYesReports increased specificity of FFR-CT vs. CTA for detecting hemodynamically significant lesions; FFR-CT considered cost-effective as a gatekeeper to invasive angiography.
Schuijf et al. [16]2018FFR-CT, perfusionClinical utility of cardiac FFR-CTYesDiagnostic accuracy of FFR-CT and CTP imaging (sensitivity, specificity) compared to invasive FFR; describes thresholds for functional ischemia; discusses incremental benefit beyond CTA.
Kimura et al. [17]2015FFR-CT cost metricsCost analysisNoCost per patient; no OR/HR. Economical Model on cost effectiveness.
Yu et al. [18]2025FAIMACE in young patientsYesHR 2.37 (95% CI 1.38–4.07)
van der Bijl et al. [19]2022PAT attenuationDiagnostic/prognostic rolesNoDescribes how PCAT attenuation has shown associations with CAD risk and outcomes and emphasizes its potential prognostic implications.
Deseive et al. [20]2018LAP volumeCardiac eventsYesHR 2.3 (95% CI 1.4–3.7)
Yamaura et al. [21]2022LAP burdenPredictors in asymptomatic patientsYesPercent LAP independently predicted cardiac events: HR 3.05 (95% CI 1.09–8.54, P = 0.033); AUC improved from 0.637 (CACS) to 0.728 with CACS + EAT (P = 0.013).
Antoniades and Shirodaria [22]2019Perivascular fat mapsCoronary inflammationNoDiagnostic performance (sensitivity, specificity) of FAI in detecting coronary inflammation.
Abdulkareem et al. [23]2022EAT via AIImaging quantificationYesReports high accuracy for CT slice classification (~98%) and segmentation (Dice ~0.84), with strong correlation (r ≈ 0.97) between automated and manual measures for both EAT volume and attenuation.
Oikonomou et al. [24]2019CT inflammation markersPlaque prognosisNoDescribes diagnostic accuracy metrics for plaque morphology; prognostic associations (mortality) for FAI in cited cohorts; improved model discrimination when CT biomarkers are added.
Vecsey-Nagy et al. [25]2024LAP burdenCAD risk evaluationYesOR 1.62 per doubling of LAP burden for hscTnI ≥ 5 ng/L (95% CI 1.17–2.32, P = 0.005); adjusted OR 1.57 (1.07–2.37, P = 0.026). Mediation analysis linking LAP to troponin elevation via plaque rupture processes.
Alyami et al. [26]2023Non-calcified plaque (NCP)Prevalence in asymptomatic adultsYesSystematic review (14 studies, n = 37,808): overall NCP prevalence 10% (95% CI 6–13%); obstructive NCP 1.1% (0.7–1.5%).
Alfakih et al. [27]2018CTA biomarkersCAD evaluationYesSummarizes diagnostic accuracy (sensitivity, specificity, overall performance) of FFR-CT compared with invasive FFR from cited trials and highlights associated health-economic benefits and reductions in unnecessary invasive angiography.
Coerkamp et al. [28]2025FAICV risk reclassificationYesRetrospective cohort of high-risk patients, FAI led to 62% reclassification in ASCVD risk categories, 22% up-classified, 40% down-classified; no HR/OR reported.
Cai et al. [29]2023FFR-CTIschemia detectionYesCorrelation r = 0.80–0.82 (95% CI 0.70–0.88); AUC = 0.768–0.857 for ischemia detection by FFR-CT, highest at 2 cm distal to stenosis (AUC 0.857).
Yu et al. [31]2020FAIPredict ischemia severityYesOR  =  1.028 per 1 HU (%), P = 0.01; combined model (DS + PVAT + plaque): AUC = 0.821; integrated DS + FAI + FFR-CT model: AUC = 0.917.
Pontone et al. [32]2021CT perfusionDiagnostic valueNoSummarize diagnostic performance improvements of dynamic perfusion CT over anatomical CTA; mentions the ability to detect ischemia more reliably and reduce overestimation of disease severity.
Imai et al. [33]2019FFR-CT, plaque featuresNon-obstructive CAD ischemiaYesArea remodeling index: AUC = 0.921; percent plaque area: AUC = 0.681; myocardial mass: AUC = 0.641.
Min et al. [34]2022Plaque volume vs. FFRDiagnostic accuracyYesischemic (PAV 15.2  ±  9.5%, TPV 694.6  ±  485.1 mm3); non-ischemic (PAV 9.2  ±  7.3%, TPV 422.9  ±  387.9 mm3). No AUC or correlation values reported.
Simantiris et al. [35]2024Perivascular fat (FAI)CAD riskYesReports higher PCAT attenuation in plaque vs. healthy segments (~–34 HU vs. –56 HU); elevated FAI linked to impaired coronary flow reserve; in type 2 diabetes, LAD PCAT attenuation independently predicted CV events, and adding it to adverse CCTA features improved discrimination (ΔAUC ≈ 0.05).
Oikonomou et al. [36]2018FAI Cardiac mortalityYesHR 2.06–2.15 per 1SD increase in FAI; ΔAUC +0.049 (cardiac), +0.075 (all-cause) over models including RCA calcium, HRP, and clinical risk factors.
Khan et al. [37]2023EAT volumePlaque vulnerability and ischemiaYesHigh EAT (> 125 mL) independently associated with positive remodeling (P = 0.038); no difference in ischemia (P ≥ 0.34).

AUC: area under the curve; CAD: coronary artery disease; CCTA: coronary CT angiography; CT: computed tomography; CTP: CT myocardial perfusion; EAT: epicardial adipose tissue; HR: hazard ratio; HU: Hounsfield unit; MACE: major adverse cardiac events; MI: myocardial infarction; OR: odds ratio; PVAT: perivascular adipose tissue; TPV: total plaque volume; HRP: high-risk plaque; DS: diameter stenosis; INOCA: Ischemia with No Obstructive Coronary Artery Disease; FAI: fat attenuation index; LAP: low-attenuation plaque.