Coronary Inflammation Appeared Far More Common Than Structural Disease
In an asymptomatic primary-prevention cohort, coronary perivascular inflammation turned up with surprising frequency on coronary computed tomography angiography, even when the arteries looked normal by conventional imaging. The study assessed the CT-derived fat attenuation index score (FAI-Score) in 84 consecutive adults with no prior coronary artery disease, combining vessel-level imaging with clinical, metabolic, and biomarker profiling across two clinical sites.
The central message is simple and clinically disruptive: a normal lumen did not reliably mean a quiet vessel wall environment.
Mean age was 53.7 years, 63.1% of participants were men, and the cohort was explicitly asymptomatic. Yet 42.9% of participants had elevated FAI-Score at or above the 75th percentile, and 17.9% met the study’s threshold for very high inflammation at or above the 90th percentile. Multi-vessel inflammation was present in 17.9% of the cohort, and the right coronary artery was the vessel most often affected, with 13.1% reaching the 90th percentile threshold there.
Inflammation and Plaque Burden Split Apart
The most clinically striking observation was the disconnect between inflammation and visible coronary disease. Among participants with normal luminal anatomy, defined as CAD-RADS 0, 46.2% carried elevated FAI-Score. Among those with zero plaque burden, 47.2% still had elevated FAI-Score. Every person with very high FAI-Score had CAD-RADS 0.
Inflammation was present where angiographic appearance suggested calm.
This separation matters because perivascular fat attenuation is not a cosmetic imaging signal. It reflects a biologic response in the adipose tissue that surrounds coronary arteries, a region increasingly understood as an active participant in vascular injury. Local inflammation can alter adipocyte lipid handling, shift the attenuation characteristics of surrounding fat, and serve as a marker of vascular immune activity before luminal narrowing becomes apparent. In other words, the vessel can be biologically active long before it is anatomically obstructed.
Routine Risk Markers Missed the Signal
Conventional circulating biomarkers offered little help in identifying which participants carried inflamed vessels. ApoB, non-HDL cholesterol, HbA1c, and the PREVENT-ASCVD 10-year risk score showed no association with binary FAI-Score elevation. In this cohort, the usual primary-prevention toolkit did not map onto the CT-derived inflammatory phenotype.
High-sensitivity C-reactive protein behaved differently, but not in a way that would make bedside triage easy. Median hs-CRP was 0.8 mg/L, and the marker showed an inverse correlation with maximum vessel FAI-Score, with Spearman ρ of −0.27 and p=0.014. The direction of this association is not intuitive at first glance and argues against simple substitution of one inflammatory readout for another. Systemic hs-CRP and localized coronary perivascular inflammation do not appear to be interchangeable signals.
Body mass index was the only secondary correlate that survived false discovery rate correction, with an AUC of 0.71, p=0.001, and all-test FDR q=0.028. Regularized multivariable modeling produced modest out-of-sample discrimination for FAI-Score elevation, with cross-validated AUC also at 0.71. The signal was measurable, but not strong enough to reconstruct the phenotype from routine clinical data alone.
Men Carried a Heavier Inflammatory Burden
Sex differences were substantial. Men had higher rates of elevated FAI-Score than women, 52.8% versus 25.8%, with p=0.016. The gap widened at the higher threshold: 26.4% of men versus 3.2% of women reached the 90th percentile, p=0.007.
This pattern fits the broader cardiovascular observation that men often manifest coronary risk earlier in life, but the imaging readout here suggests something more specific than simple event incidence. The perivascular fat phenotype may be registering earlier vascular inflammatory activity in men even before overt plaque formation or stenosis emerges. A structurally normal scan therefore does not erase sex-based biological differences in coronary risk.
Why the Right Coronary Artery May Matter
The right coronary artery was the most frequently involved vessel in the high-inflammation range. The study did not assign a mechanistic explanation, and caution is warranted before reading too much into the distribution. Still, vessel-specific variability is biologically plausible, given differences in coronary geometry, motion, wall stress, and local adipose-vessel interactions that may influence perivascular fat signaling.
The importance of vessel-level analysis is that it can expose heterogeneity hidden by patient-level summaries. A person may have a single inflamed coronary segment while the rest of the coronary tree appears comparatively quiet. That pattern would be lost if imaging were reduced to a binary yes-or-no plaque assessment.
Primary Prevention May Need a Third Dimension
Primary prevention has traditionally leaned on three pillars: risk factors, circulating biomarkers, and structural imaging. This study adds a fourth dimension, the inflammatory state of the coronary environment itself, measured noninvasively through FAI-Score. The finding is especially relevant in asymptomatic adults, where clinicians often rely on the absence of symptoms, the absence of plaque, or favorable lab values to reassure themselves that risk is low.
FAI-Score challenges that reassurance. It identifies a biologic abnormality that can coexist with zero plaque and normal luminal anatomy, raising the possibility that current risk assessment tools under-recognize a subset of people with active coronary inflammation. If future studies link this phenotype to hard outcomes in asymptomatic primary-prevention populations, imaging-derived inflammation may become a useful complement to traditional risk estimation rather than a replacement for it.
For now, the data support a narrower conclusion: coronary inflammation is common, often silent, and not captured by standard screening markers in this cohort.
Study Limits Shape the Interpretation
The cohort was small, with 84 participants, and the design was cross-sectional rather than outcome-based. The population came from two clinical sites, and all authors were employees of the sponsoring company, which makes independent replication especially important. Because the study measured prevalence and correlates rather than events, it cannot establish whether elevated FAI-Score independently predicts myocardial infarction, revascularization, or cardiovascular death in asymptomatic adults.
The most useful next step is not speculation about treatment, but outcome validation in larger, diverse primary-prevention populations. Until then, FAI-Score remains a biologically compelling marker whose clinical role is still being defined by studies like this one.