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. Author manuscript; available in PMC: 2026 May 14.
Published in final edited form as: Circ Cardiovasc Imaging. 2025 May 14;18(7):e017248. doi: 10.1161/CIRCIMAGING.124.017248

Periaortic Fat Attenuation on Nongated Noncontrast Chest CT Images to Assess Changes in Arterial Inflammation: Impact of Atorvastatin

Guillaume Goudot 1,*, Shady Abohashem 1,*, Michael T Osborne 1, Wesam Aldosoky 1, Taha Z Ahmad 1, Michael T Lu 1, Borek Foldyna 1, Ahmed Tawakol 1
PMCID: PMC12263313  NIHMSID: NIHMS2083484  PMID: 40365683

Abstract

BACKGROUND:

Imaging markers of atherosclerotic inflammation are needed to enhance cardiovascular risk assessment and evaluate the impact of therapies. We sought to test the hypothesis that treatments impacting arterial inflammation can be evaluated using a simplified measure of periaortic fat attenuation (FA) assessed on noncontrast, nongated computed tomography (CT) of the descending thoracic aorta.

METHODS:

Measurements were performed on 18F-fluorodeoxyglucose positron emission tomography/CT images from a double-blind, randomized trial conducted between 2008 and 2009 that assessed the impact of statin therapy on arterial inflammation. Periaortic adipose tissue quantification was performed on the chest CT images over a 10 cm portion of the descending aorta. FA was determined as the mean attenuation of the entire volume of delineated periaortic fat. Arterial inflammation (aorta) and leukopoietic activity (bone marrow and spleen) were assessed by measuring standardized uptake values on 18F-fluorodeoxyglucose positron emission tomography images. Baseline relationships and changes from baseline to 12 weeks were assessed. All models evaluating FA were adjusted for baseline kilovoltage peak.

RESULTS:

Sixty subjects (79.9% male, mean age 60±8.9 years) with risk factors or established atherosclerosis (32 randomized to atorvastatin 10 mg, 28 randomized to atorvastatin 80 mg) were studied. On average, it took 88±17 seconds to assess FA per subject. At baseline, FA correlated with leukopoietic activity (r=0.412; P=0.021 and r=0.442; P=0.013, for bone marrow and spleen, respectively). Furthermore, FA correlated with aortic inflammation assessed on 18F-fluorodeoxyglucose positron emission tomography as quintiles (r=0.274; P=0.043). Moreover, high dose (versus low dose) atorvastatin was associated with a significant reduction in FA after 12 weeks (standardized β=−0.603; P=0.010) after adjustment for baseline FA, kilovoltage peak, and prior statin use.

CONCLUSIONS:

Periaortic FA is a marker of atherosclerotic inflammation that can be easily measured on nongated, nonenhanced chest CT images and be used to provide insights into the impact of therapies on atherosclerotic inflammation.

Keywords: arteritis, bone marrow, inflammation, risk factors, spleen

Arterial inflammation is an important component of atherosclerosis that associates with atherosclerotic plaque progression and the risk of thrombotic and embolic events.1–4 Arterial inflammation can be reproducibly assessed using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), associates with cardiovascular disease risk, and can be used to assess the impact of therapies.2,5 However, 18F-FDG-PET/CT imaging is not available for large-scale screening and is relatively expensive.6 Thus, more readily available imaging markers of atherosclerotic inflammation are needed.

Perivascular fat is highly metabolically active and secretes substances that regulate vascular wall constriction and inflammation.7–10 Recently, contrast-enhanced, ECG-gated CT images have been used to measure the attenuation of perivascular fat (in Hounsfield units). This measure correlates with vascular inflammation assessed using 18F-FDG-PET/CT3,4,11 and provides an early marker of arterial remodeling and atherosclerosis development.4,10,12 Furthermore, the perivascular fat signal has been shown to be reduced by therapies targeting arterial inflammation.13,14 However, while CT imaging is relatively commonly used, nongated, nonenhanced CT images represent the majority of CT imaging obtained. Hence, it is important to determine whether a similar measurement of perivascular fat attenuation (FA) can be obtained from these more commonly obtained CT images.

Thus, we sought to evaluate the feasibility of measuring periaortic FA on nongated, noncontrast-enhanced CT images to assess whether this biomarker could be used as an indicator of arterial inflammation in a retrospective cohort of individuals randomized to high versus low-dose atorvastatin. Specifically, we aimed to test the hypotheses that (1) Periaortic FA measured on CT associates with arterial inflammation measured on 18F-FDG-PET/CT images, and (2) FA is reduced among individuals randomized to high-dose (versus low-dose) atorvastatin over 12 weeks.

METHODS

The data supporting the findings are available from the corresponding author upon reasonable request.

Study Population

The parent study was a double-blind, randomized, active-comparator trial that assessed the effect of statin intensification on atherosclerotic inflammation using 18F-FDG-PET/CT and was conducted across 10 US centers between August 2008 and December 2009, with imaging performed at 6 imaging centers.5 Briefly, 163 adults with risk factors or with established atherosclerosis who were on no prior statin or on no more than a low-intensity statin were screened. Low-intensity statin was defined as atorvastatin ≤10 mg, simvastatin ≤20 mg, rosuvastatin ≤5 mg, pravastatin ≤40 mg, or fluvastatin ≤40 mg. Men and women aged 30 to 80 years were included if they had documentation or history of any 1 of the following: (1) coronary artery disease; (2) carotid artery disease; (3) cerebrovascular disease; (4) peripheral arterial disease defined by an ankle-brachial index ≥0.5 and ≤0.9; (5) type 2 diabetes; or (6) body mass index 30 to 40 kg/m2 (inclusive) and waist circumference >102 cm in men, and >88 cm in women. Additional inclusion criteria were low-density lipoprotein cholesterol ≥60 mg/dL and triglyceride level <350 mg/dL. Of those subjects, 83 were randomized to atorvastatin treatment (41 were randomized to atorvastatin 80 mg, while 42 were randomized to atorvastatin 10 mg). Sixty-seven subjects provided completed paired imaging sets, of which 64 provided adequate image quality for FA assessments, for inclusion in the final analysis (Figure 1). The study was conducted in compliance with the principles of the Declaration of Helsinki and according to Good Clinical Practice guidelines. The protocol was reviewed and approved by each center’s institutional review board. All participants provided written informed consent before any study procedures.

Figure 1. Flowchart of the study.

Figure 1.

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18F-FDG-PET indicates 18F-fluorodeoxyglucose positron emission tomography; PI, principal investigator; and TBR, target-to-background ratio.

PET/CT Imaging

18F-FDG-PET/CT imaging was conducted as described previously, using a prescribed protocol.5 Each subject underwent imaging at baseline and again 12 weeks after treatment randomization, using identical PET and CT protocols. In brief, FDG was administered intravenously (10 mCi) after an overnight fast, and PET/CT imaging was performed 2 hours later. At each imaging visit, a CT scan was obtained using a prespecified kilovoltage peak (kVp) and slice thickness. For most scans, the slice thickness was set at 3.5 mm with a tube voltage of 140 kVp (88% of scans). For the remaining 12%, the slice thickness was set at 5 mm with a tube voltage of 120 kVp.

Assessment of Periaortic FA

Adipose tissue segmentation was performed around the descending aorta using a semiautomated method that required a manual definition of borders. The periaortic adipose tissue was measured over contiguous slices to cover a column of 10 cm of the descending thoracic aorta starting distal to the left subclavian artery takeoff. The region of interest in each slice was defined as a circle with a diameter 10 mm larger than the anterior-posterior aortic diameter. CT attenuation thresholds were used to identify fat voxels (window width −195 to −45 Hounsfield units; window center −120 Hounsfield units)15,16 to calculate adipose volumes. FA was the mean attenuation of the entire volume of delineated periaortic fat. All image analyses were performed by an analyst, who was blinded to treatment and timepoints, on a dedicated workstation using the 3D-Slicer software, version 5.0.2.17,18 The average time to measure FA was assessed in a subset of 15 subjects.

Assessment of Leukopoietic Activity and Arterial Inflammation

Arterial inflammation, as well as bone marrow and splenic (ie, leukopoietic) activities, were measured on 18F-FDG-PET/CT images using previously validated methods (Figure 2). Briefly, arterial inflammation was assessed by measuring the 18F-FDG signal in 10 regions of interest within the wall of the descending aorta, using the CT images as a guide starting from the end of the aortic arch in the axial plane and down through the descending thoracic aorta.19 Similarly, bone marrow activity was assessed by quantifying the maximum derived standardized uptake value (SUV) from regions of interest placed within vertebral bodies from T1 to L5, and splenic activity was assessed by deriving the maximum SUV from 5 regions of interest in the spleen.19 The maximum SUVs per slice were averaged to calculate the 18F-FDG activity in each.

Figure 2. Measurement of periaortic fat with Slicer software.

Figure 2.

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Green delineation is performed around the descending thoracic aorta in a transverse view (A), section by section, starting after the aortic arch. This is performed over a 10 cm column, shown in the frontal section (B). Periaortic fat (voxel shown in yellow) is automatically delineated with the −195 to −45 Hounsfield unit window.

Statistical Analysis

The predefined primary end point was the relative mean change (ΔFA) in perivascular FA from baseline to 12 weeks between high-dose and low-dose statin groups. ΔFA was calculated as the absolute difference between follow-up FA and baseline FA (ΔFA=FA at 12 weeks – FA at baseline); the percentage change in FA was also assessed, which normalizes the observed differences relative to baseline values. The secondary study objective was to assess the association between leukopoietic activity and arterial inflammation on 18F-FDG-PET/CT and FA. The normality of continuous variables was assessed using the Shapiro-Wilk test. Normally distributed variables were compared using an independent sample t test, while non-normally distributed variables were compared using the Wilcoxon rank-sum test. Categorical variables were compared using the χ2 test or Fisher exact test when appropriate. Associations between continuous variables were assessed using linear regression models and the Pearson correlation coefficient for normally distributed data.

The covariables (ie, included baseline statin use, baseline kVp, baseline FA, and peri-aortic fat volume as covariates) included in the primary models assessing associations between treatment and ΔFA were a priori defined based on clinical relevance, prior literature, and variables that could potentially affect the primary outcome. Sensitivity analyses were additionally performed to further adjust for sex, race, and scanner type. Statistical analysis was conducted using SPSS Statistical software (v. 28; IBM Corporation, Armonk, NY), and a 2-sided P<0.05 was used to indicate significance.

RESULTS

Baseline Characteristics

Baseline characteristics for the individuals included in this retrospective imaging study are provided in Table 1. Subject characteristics were similar across treatment groups. On average, assessing FA on the CT images took 88±17 seconds per subject. The intraobserver intraclass and interobserver correlation coefficients for FA measurement were 0.82 and 0.78, respectively, thus showing a good reproducibility of the measurements.

Table 1.

Baseline Characteristics by Treatment Group

Variables All patients (n=60) 10 mg Atorvastatin (n=32) 80 mg Atorvastatin (n=28) P value
Age, mean (SD); y 60 (8.9) 61 (9.0) 59.5 (8.9) 0.555
Male 47 (79.7) 25 (80.6) 22 (78.6) 0.549
Race
 White 50 (84.7) 26 (83.9) 24 (85.7) 0.567
 Other races 10 (16.7) 5 (15.6) 5 (17.6)
Body mass index, kg/m2 31.12 (26.81–33.20) 30.83 (26.82–32.44) 31.99 (27.44–35.50) 0.219
Medical history
 Type 2 diabetes 22 (36.7) 14 (43.8) 8 (28.6) 0.172
 Coronary artery disease 25 (41.7) 12 (37.5) 13 (46.4) 0.331
 Obesity 39 (65) 19 (59.4) 20 (71.4) 0.241
 Prestudy statin use 36 (60) 21 (65.6) 15 (53.6) 0.246
 LDL cholesterol, mg/dL 101 (79–120) 100 (87–119) 102 (76.25–127.5) 0.844
 HDL cholesterol, mg/dL 42 (34–55) 46 (37, 61) 41.5 (32.25–50.00) 0.085
 Baseline FA (HU) −89.42 (−92.51 to −88.25) −89.41 (−90.68 to −88.40) −90.25 (−93.76 to −87.85) 0.480
 Baseline bone marrow SUV 2.47 (2.23–2.77) 2.45 (2.27–2.72) 2.51 (2.17–2.84) 0.981
 Baseline spleen SUV 2.53 (2.22–2.74) 2.49 (2.22–2.74) 2.55 (2.05–2.77) 1.000
 Baseline arterial SUV 2.20 (2.00–2.43) 2.27 (2.09–2.44) 2.14 (1.96–2.39) 0.094
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Data are represented as median (interquartile range), n (%) or mean (SD). FA indicates fat attenuation; HDL, high-density lipoprotein; HU, Hounsfield unit; LDL, low-density lipoprotein; and SUV, standardized uptake value.

Relationships Between Baseline Fat Attenuation and Leukopoietic and Arterial 18F-FDG Activities

At baseline, a significant correlation was observed between FA and leukopoietic activity, as assessed by bone marrow SUV (r=0.439; P=0.019) and splenic SUV (r=0.455; P=0.015), independent of baseline kVp and fat volume (Figure 3). In addition, while a nonsignificant trend between baseline FA and baseline arterial inflammation was observed (r=0.239; P=0.098), a significant correlation was evident using quintiles of baseline arterial inflammation (r=0.274; P=0.043) that was independent of baseline kVp and baseline statin use (Figure 4).

Figure 3. Correlations between fat attenuation (FA) measurement and leukopoietic tissue activity, defined as the standard uptake value (SUV) on 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) at baseline. Spleen metabolic activity (SUV; A) and bone marrow metabolic activity (SUV; B) both significantly correlate with FA.

Figure 3.

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*Partial correlation analysis adjusted for baseline kilovoltage peak (kVp) and periaortic fat volume.**Linear regression analysis adjusted for baseline kVp and periaortic fat volume.

Figure 4. Association between fat attenuation (FA) and arterial wall inflammation (in descending thoracic aorta) measures by 18F-FDG-PET.

Figure 4.

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*Adjusted for baseline kilovoltage peak (kVp) and previous statin use.

Effect of Treatment (Low Versus High Dose of Atorvastatin) on Mean Change in FA (ΔFA, %ΔFA)

High-dose atorvastatin (versus low dose) was associated with a significant absolute reduction in FA (ΔFA) after adjustment for baseline FA, baseline fat volume, kVp, and prior statin use (standardized β, −0.603 [95% CI, −1.056 to −0.150], P=0.010; Table 2; Figure 5). This association remained significant after further adjustment for sex, race, and scanner type (standardized β, −0.676 [95% CI, −1.183 to −0.168], P=0.010; Table 2; Figure 5). Similarly, after adjustment for baseline FA, baseline fat volume, kVp, and prior statin use, high-dose statin use was associated with a significant reduction in FA percent change (%ΔFA; standardized β, −0.621 [95% CI, −1.076 to −0.166], P=0.008; Table 2; Figure 5) over 12 weeks. Furthermore, we observed that the absolute change in CRP (C-reactive protein) was positively associated with the absolute change in FA (0.255 [95% CI, 0.051–0.460]; P=0.015), independent of baseline FA, kVp, and baseline CRP levels.

Table 2.

Effect of Treatment (Low vs High Dose of Atorvastatin) on Mean Change in Fat Attenuation (ΔFA, %ΔFA)

Treatment (low vs high dose of atorvastatin) Covariables Absolute FA change (ΔFA) FA percent change (%ΔFA)
Standardized β (95% CI) P value Standardized β (95% CI) P value
Univariate −0.463 (−0.978 to 0.053) 0.078 −0.481 (−0.995 to 0.033) 0.066
Baseline FA+baseline fat volume, kVp, prior statin use (Primary model) −0.603 (−1.056 to −0.150) 0.010 −0.621 (−1.076 to −0.166) 0.008
Baseline FA+baseline fat volume, kVp, prior statin use, sex, race and scanner used −0.676 (−1.183 to −0.168) 0.010 −0.692 (−1.204 to −0.1380) 0.009
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ΔFA=FA at 12 wk – FA at baseline. FA indicates fat attenuation; and kVp, kilovoltage peak.

Figure 5. Effect of treatment (low or high dose of atorvastatin) on fat attenuation (FA).

Figure 5.

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*Adjusted for baseline FA, kilovoltage peak (kVp), previous statin. dFA indicates difference in fat attenuation; and HU, Hounsfield unit.

DISCUSSION

This retrospective imaging analysis from a randomized, multicenter study highlights the feasibility of using descending thoracic periaortic FA as a potential marker of arterial inflammation. We observed that periaortic FA not only associates with the 18F-FDG measures of arterial inflammation but may also have value as a marker of therapeutic efficacy, as the FA signal decreased to a greater degree with high-dose statin than with low-dose (though the observed effect is moderate). Specifically, we observed that a dose of atorvastatin 80 mg daily was associated with a significant decrease in FA, while such an effect did not occur with 10 mg. Thus, the evaluation of thoracic periaortic fat by readily available nongated CT images may provide a marker to assess the impact of antiinflammatory treatments on atherosclerosis that may ultimately reduce cardiovascular mortality.

While this result is similar to the statin-induced reduction seen in arterial inflammation on 18F-FDG-PET, an important difference is the low-cost accessibility of this marker. It requires only a noncontrast chest CT without ECG-gating, making it an easy-to-access tool that may inform cardiovascular prevention strategies for a broad population.

Initially not considered a contributor to the atherosclerosis process, perivascular fat now appears to play an important role in its development by contributing to vascular contractile dysfunction and atherosclerosis when it becomes inflamed.20,21 The ability to select fat on CT using Hounsfield unit window volumes enables evaluation of its average attenuation, which is directly linked to local inflammation.22 Such an imaging marker is of obvious interest, as inflammation could be detected before the formation of plaques and vascular calcifications. Various vascular segments have been explored, including the coronary,4 carotid arteries,23 and aorta.15 Therefore, perivascular FA could help define the cardiovascular risk of young patients well before currently available tools, such as calcium scoring. Importantly, lipid-lowering treatments that reduce the risk of cardiovascular events, such as statins, do not diminish calcium score.24 In contrast, statins have been shown to reduce pericoronary fat adjacent to specific lesions using contrast-enhanced, gated CTs14 but have not yet been evaluated on a systematized segment on noncontrast, non-ECG-gated CT. Based on these results, periaortic FA could be tested as a potential marker for longer-term monitoring of the effects of lipid-lowering/anti-inflammatory treatments targeting the progression of atherosclerosis, making it possible to assess the efficacy of treatment before the onset of atherosclerotic plaques and before cardiovascular events with an accessible and low-cost imaging examination.

STUDY LIMITATIONS

Importantly, a substantial proportion of the patients were already on low-dose statins before the study start, thus those randomized to the low-dose group did not experience intensification of their treatment during the study. Hence, the impact of low-dose statin on FA among statin-naïve individuals requires further study. The short duration of the study is another important limitation, allowing only short-term assessment of FA changes. Early changes in FA are interesting for assessing the rapid effect of treatment. Still, it would be interesting to assess the longer-term consequences of the effect of statin treatment on periaortic fat changes. Additionally, the observed change in periaortic FA by statins is quantitatively modest, similar to that seen in pericoronary fat after statin treatment.14 Nevertheless, periaortic FA can be obtained with non-ECG gated, noncontrast CT, which is not the case for pericoronary FA measurements. Furthermore, given the short 12-week follow-up in our study, the detection of a significant change, albeit modest, is encouraging for the use of periaortic FA as a marker for therapeutic monitoring. Lastly, this study used multiple scanners, which used variable kVp and slice thicknesses. A uniform protocol for kVp and slice thickness would reduce variability in the measurement of periaortic FA. This should encourage a protocoled and automated measurement of periaortic fat to ensure minimal measurement variation and clinical relevance of the detected changes.

CONCLUSIONS

Using noncontrast, non-ECG-gated CT images, we observe that the easily obtained measurement of periaortic FA provides an index of vascular wall inflammation modifiable with statin therapy. Accordingly, assessing periaortic FA on noncontrast, nongated CT images as an imaging marker of atherosclerotic inflammation merits further investigation.

Supplementary Material

Supplemental Material is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCIMAGING.124.017248.

CLINICAL PERSPECTIVE.

This study assessed the feasibility of measuring periaortic fat attenuation (FA) on nongated computed tomography images to follow changes in arterial inflammation. Using a prospective multicenter study design, adults with risk factors or with established atherosclerosis, who were not taking high-dose statins, were randomized to low- versus high-dose atorvastatin (10 mg versus 80 mg). Patients were imaged using 18F-fluorodeoxyglucose positron emission tomography/computed tomography before and 12 weeks after randomization. FA associated with leukopoietic tissue activity and arterial inflammation as measured by 18F-fluorodeoxyglucose positron emission tomography. Moreover, high-dose atorvastatin was associated with a significant reduction in FA after 12 weeks (after adjustment for baseline FA and baseline kilovoltage peak). These results indicate the feasibility of employing widely available nongated computed tomography images to rapidly measure aortic FA and gain insights into the impact of treatments on arterial inflammation.

Sources of Funding

Dr Abohashem is supported, in part, by the American Heart Association (AHA) Second Century Early Faculty Independence Award (10.58275/AHA.24SCEFIA1256969.pc.gr.193937). Dr, Osborne is supported in part by NIH K23HL151909 and AHA 23SCISA1143491. Dr Goudot was awarded by the Société Française de Médecine vasculaire and Institut Servier. Dr Tawakol is supported, in part, by NIH HL164337, AR077187, HL109448, HL149516, and the International Atomic Energy Agency (IAEA) Coordinated Research Project E13048. Funding for the parent study was provided by Merck.

Disclosures

Dr Osborne receives consulting fees from WCG Clinical for unrelated work. Dr Tawakol institution receives grant support from the Lung Biotechnologies for unrelated work. The other authors report no conflicts.

Nonstandard Abbreviations and Acronyms

CRP

C-reactive protein

CT

computed tomography

FA

fat attenuation

18F-FDG-PET

18F-fluorodeoxyglucose positron emission tomography

kVp

kilovoltage peak

SUV

standardized uptake value

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