Coronary Perivascular Fat Biomarkers in Vascular Inflammation: Scientific Review and Clinical Implications

Abstract

Coronary perivascular fat (PVAT) has emerged as a dynamic biomarker and mediator of vascular inflammation, playing a pivotal role in the pathogenesis and progression of atherosclerotic cardiovascular disease (ASCVD). Recent advances in imaging and molecular biology have elucidated the multifaceted contributions of PVAT to vascular homeostasis, inflammation, and clinical outcomes. This review synthesizes current evidence on the epidemiology, mechanisms, clinical features, diagnostic modalities, and therapeutic implications of coronary perivascular fat biomarkers, emphasizing their value in risk stratification and personalized care for patients with or at risk of ASCVD.

Introduction

Vascular inflammation is central to the development and destabilization of atherosclerotic plaques, with coronary perivascular adipose tissue (PVAT) recognized as both a sensor and effector of inflammatory processes. Traditionally considered a passive fat depot, PVAT is now understood to exert paracrine and endocrine effects on the adjacent coronary vasculature, modulating endothelial function, immune cell infiltration, and smooth muscle activity. The identification and quantification of PVAT-derived biomarkers have expanded the arsenal of tools available for early detection of vascular inflammation, risk prediction, and therapeutic monitoring in clinical practice. This article reviews the current understanding and clinical relevance of coronary perivascular fat biomarkers in vascular inflammation, integrating recent PubMed-indexed research and guideline recommendations.

Epidemiology / Disease Burden

The burden of ASCVD remains the leading cause of morbidity and mortality worldwide. Epidemiological studies reveal that increased PVAT volume and altered composition are highly prevalent in individuals with traditional risk factors such as obesity, metabolic syndrome, and type 2 diabetes mellitus. Multicenter imaging studies utilizing computed tomography (CT) and magnetic resonance imaging (MRI) have demonstrated that coronary PVAT expansion correlates with higher incidence of major adverse cardiovascular events (MACE), independent of traditional risk factors. Notably, populations with high prevalence of metabolic dysregulation exhibit greater PVAT inflammation, implicating this depot as a key contributor to the global burden of vascular disease.

Pathophysiology

PVAT is anatomically contiguous with the adventitia of coronary arteries and is uniquely positioned to influence vascular biology. Under physiological conditions, PVAT secretes anti-inflammatory adipokines and vasodilatory factors such as adiponectin and nitric oxide, maintaining vascular tone and homeostasis. In the setting of metabolic stress or systemic inflammation, PVAT undergoes phenotypic transformation characterized by increased infiltration of pro-inflammatory macrophages, upregulation of cytokines (e.g., interleukin-6, tumor necrosis factor-alpha), oxidative stress, and altered adipokine secretion. These changes promote endothelial dysfunction, vascular smooth muscle cell proliferation, and plaque vulnerability. The release of free fatty acids and inflammatory mediators from PVAT amplifies local and systemic vascular inflammation, establishing a feed-forward loop that accelerates atherogenesis.

Risk Factors

Risk factors for increased PVAT inflammation and adverse biomarker profiles overlap with those of ASCVD, including central obesity, insulin resistance, dyslipidemia, hypertension, and sedentary lifestyle. Genetic predisposition, chronic systemic inflammation (e.g., autoimmune diseases), and certain pharmacotherapies (e.g., steroids, antipsychotics) may also modulate PVAT biology. Recent evidence suggests that ethnic and sex-specific differences in PVAT distribution and activity contribute to disparities in cardiovascular risk among populations. Importantly, modifiable lifestyle factors such as dietary patterns, physical activity, and weight management directly impact PVAT characteristics and associated biomarker profiles.

Clinical Features

While PVAT inflammation itself is largely subclinical, its consequences manifest as accelerated coronary atherosclerosis, endothelial dysfunction, and increased propensity for plaque rupture. Clinical features associated with heightened PVAT activity include early-onset coronary artery disease, rapid progression of coronary calcification, and higher rates of recurrent ischemic events. Biomarkers derived from PVAT, such as increased perivascular fat attenuation index (FAI) on CT and elevated circulating levels of adipokines (e.g., leptin, resistin), have been linked to impaired vascular function and adverse event rates in both primary and secondary prevention cohorts.

Diagnosis

Advances in imaging technologies have enabled noninvasive quantification and characterization of coronary PVAT. Coronary computed tomography angiography (CCTA) with measurement of FAI has become a validated tool for assessing perivascular inflammation. Higher FAI values correlate with localized vascular inflammation and predict future cardiovascular events beyond traditional risk factors and coronary calcium scoring. Positron emission tomography (PET) imaging using radiotracers targeting inflammatory pathways also provides insights into PVAT activity and its interplay with coronary plaque biology. Blood-based biomarkers, including adipokines and pro-inflammatory cytokines, complement imaging findings but lack specificity for local coronary inflammation. Integration of imaging and circulating biomarkers enhances risk stratification and guides personalized management strategies.

Treatment & Management

Therapeutic strategies targeting PVAT inflammation are primarily focused on addressing underlying metabolic derangements and systemic risk factors. Intensive lifestyle modification, including weight loss, dietary optimization (e.g., Mediterranean diet), and regular physical activity, has been shown to reduce PVAT volume and improve its secretory profile. Pharmacologic interventions such as statins, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and anti-inflammatory agents (e.g., colchicine) have demonstrated beneficial effects on PVAT inflammation and cardiovascular outcomes in selected populations. The use of targeted therapies modulating adipokine signaling and immune cell infiltration remains an area of active investigation.

Recent Advances / Emerging Therapies

Recent research has focused on the use of advanced imaging biomarkers, such as FAI and PET-based measurements, to monitor therapeutic response and refine risk prediction models. Novel pharmacologic agents targeting PVAT inflammation, including monoclonal antibodies against interleukin-1β and inhibitors of NLRP3 inflammasome, are undergoing clinical evaluation. Early-phase studies suggest that modulation of PVAT biology may provide incremental benefit in reducing residual inflammatory risk among patients with well-controlled traditional risk factors. Integration of artificial intelligence (AI)-driven image analysis holds promise for enhancing detection and quantification of PVAT biomarkers in routine clinical practice.

Guideline Recommendations

Current guidelines from major cardiovascular societies emphasize the importance of comprehensive risk assessment incorporating emerging biomarkers of vascular inflammation, including PVAT-derived metrics, in selected patient populations. The 2021 European Society of Cardiology (ESC) guidelines recognize the prognostic value of coronary FAI in refining risk stratification among individuals with intermediate-risk profiles. American Heart Association (AHA) statements endorse the use of advanced imaging, including CCTA, for detection of subclinical coronary inflammation, particularly in patients with ambiguous clinical presentations or discordant risk factor profiles. Integration of PVAT biomarkers into clinical algorithms remains an evolving field, necessitating further validation and cost-effectiveness analyses.

Conclusion

Coronary perivascular fat biomarkers represent a rapidly advancing frontier in the assessment and management of vascular inflammation. Their unique anatomical and functional properties position them as both contributors and indicators of atherogenic processes. Incorporation of PVAT-derived imaging and molecular biomarkers into clinical practice enhances the precision of cardiovascular risk assessment, informs therapeutic decision-making, and opens new avenues for targeted intervention. Ongoing research and technological innovation will continue to refine their utility, ultimately improving outcomes for patients at risk of ASCVD.