Estimating inflammatory risk in atherosclerotic cardiovascular disease: plaque over plasma?

Abstract

Inflammation is an important driver of disease in the context of atherosclerosis, and several landmark trials have shown that targeting inflammatory pathways can reduce cardiovascular event rates. However, the high cost and potentially serious adverse effects of anti-inflammatory therapies necessitate more precise patient selection. Traditional biomarkers of inflammation, such as high-sensitivity C-reactive protein, show an association with cardiovascular risk on a population level but do not have specificity for local plaque inflammation. Nowadays, advancements in non-invasive imaging of the vasculature enable direct assessment of vascular inflammation. Positron emission tomography (PET) tracers such as 18F-fluorodeoxyglucose enable detection of metabolic activity of inflammatory cells but are limited by low specificity and myocardial spillover effects. 18F-sodium fluoride is a tracer that identifies active micro-calcification in plaques, indicating vulnerable plaques. Gallium-68 DOTATATE targets pro-inflammatory macrophages by binding to somatostatin receptors, which enhances specificity for plaque inflammation. Coronary computed tomography angiography (CCTA) provides high-resolution images of coronary arteries, identifying high-risk plaque features. Measuring pericoronary adipose tissue attenuation on CCTA represents a novel marker of vascular inflammation. This review examines both established and emerging methods for assessing atherosclerosis-related inflammation, emphasizing the role of advanced imaging in refining risk stratification and guiding personalized therapies. Integrating these imaging modalities with measurements of systemic and molecular biomarkers could shift atherosclerotic cardiovascular disease management towards a more personalized approach.

Keywords: atherosclerosis; computed tomography; imaging; inflammation; positron emission tomography.

Graphical Abstract

Estimating inflammatory risk: from population-based plasma markers to personalized medicine. ASCVD, atherosclerotic cardiovascular disease; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin 6; ¹⁸F-FDG, 18F-fluorodeoxyglucose; ⁶⁸Ga-DOTATATE, gallium-68 DOTATATE; ¹⁸F-NaF, 18F-sodium fluoride; PCATa, pericoronary adipose tissue attenuation; CCTA–HRP, coronary computed tomography angiography–high-risk plaque.

Figure 1

Different techniques to estimate (plaque) inflammation. Systemic inflammation markers include hsCRP (high-sensitivity C-reactive protein) and IL-6 (interleukin-6). Imaging-based inflammation assessments include ¹⁸F-FDG (18F-fluorodeoxyglucose) for glucose uptake, ⁶⁸Ga-DOTATATE (Gallium-68 DOTATATE) for M1 macrophages, and ¹⁸FNaF (18F-Sodium Fluoride) for detecting microcalcification and active calcification within plaques. PCATa (Pericoronary Adipose Tissue attenuation) and CCTA-HRP (Coronary Computed Tomography Angiography – High-Risk Plaque) provide structural and compositional plaque evaluations.