---
title: "Molecular Links Between Coronary Artery Disease and Cancer: Inflammation, Immunometabolism, Thromb"
id: "frontiers-in-immunology-14-molecular-basis-of-coronary-artery-disease-malignancy-comorbidity-inflammation"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-molecular-basis-of-coronary-artery-disease-malignancy-comorbidity-inflammation"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1903190"
published_at: "2026-08-12T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Molecular Links Between Coronary Artery Disease and Cancer: Inflammation, Immunometabolism, Thromb
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-molecular-basis-of-coronary-artery-disease-malignancy-comorbidity-inflammation
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1903190)
- **Published At:** 2026-08-12T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source provided is an article listed in Frontiers in Immunology titled “Molecular basis of coronary artery disease–malignancy comorbidity: inflammation, immunometabolism, thrombosis, and cardio-oncology translation.” - The page content available in the provided source is limited to journal navigation and site metadata; the article body, abstract, figures, methods, results, and conclusions were not present in the supplied source text. - Because the full manuscript content is absent, no study-specific data, experimental findings, patient cohorts, molecular mechanisms, biomarkers, or therapeutic recommendations could be extracted or summarized from the source. - Key topic terms implied by the title include **coronary artery disease**, **malignancy**, **inflammation**, **immunometabolism**, **thrombosis**, and **cardio-oncology translation**, but the source did not provide definitions, mechanistic detail, or evidence related to these concepts. - The only verifiable facts in the source are the article title, journal (Frontiers in Immunology), and the presence of site navigation and journal section listings; all other clinical or translational content was not reported in the supplied text. - For clinical use or citation, the full article text must be retrieved from the journal website or publisher record because the supplied source lacks the substantive content needed for evidence-based summary, guideline implications, or practice changes. - Recommended immediate actions are to obtain the original article PDF or full‑text HTML from Frontiers in Immunology, verify authorship and publication details, and then extract mechanistic findings, experimental methods, and translational recommendations directly from that full text. - Until the full article content is reviewed, clinicians and researchers should not infer trial results, biomarker performance, or treatment implications from the title alone; those specifics were not reported in the supplied source.
## Clinical Analysis & Structured Key Points
Frontiers | Molecular basis of coronary artery disease–malignancy comorbidity: inflammation, immunometabolism, thrombosis, and cardio-oncology translation REVIEW article Front. Immunol. , 12 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1903190 Published in Frontiers in Immunology Inflammation 7 impact factor 11.3 citescore Editor & Reviewers Edited by S G Sven Geissler Reviewed by C V Carlos Vera F H Farshad Heydari Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Figure 5 View in article Figure 6 View in article Figure 7 View in article Table 1 Core clinical and epidemiologic evidence linking CAD and malignancy. View in article Table 2 Mutation-specific CHIP programs relevant to CAD–malignancy comorbidity. View in article Table 3 Thrombotic phenotypes and dominant thromboinflammatory mechanisms in CAD–malignancy comorbidity. View in article Table 4 Mechanistic pathways and molecular mediators of CAD–malignancy comorbidity. View in article Table 5 Translational strategies and therapeutic interventions in CAD–malignancy comorbidity. View in article REVIEW article Front. Immunol. , 12 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1903190 Molecular basis of coronary artery disease–malignancy comorbidity: inflammation, immunometabolism, thrombosis, and cardio-oncology translation J L Junlin Li Y Z Yan Zhao M B Ming Bai * Department of Cardiovascular Medicine, Lanzhou University First Clinical Medical College, Lanzhou, China Article metrics View details Abstract Coronary artery disease (CAD) and malignancy frequently coexist in aging populations and share multiple risk factors, including smoking, obesity, diabetes, dyslipidemia, chronic inflammation, and metabolic dysfunction. However, increasing evidence suggests that CAD–malignancy comorbidity cannot be fully explained by epidemiological coincidence alone, although its causal direction remains difficult to establish because of shared risk factors, surveillance bias, reverse causality, cancer stage, and treatment exposure. Instead, convergent inflammatory, metabolic, thrombotic, and immune mechanisms may contribute to the observed clinical overlap. This review summarizes recent evidence linking CAD and cancer through chronic systemic inflammation, clonal hematopoiesis, inflammasome activation, immunometabolic remodeling, endothelial dysfunction, platelet activation, neutrophil extracellular trap formation, coagulation, and immune checkpoint disruption. Particular attention is given to clonal hematopoiesis as a molecular bridge between malignant predisposition and atherosclerosis, macrophage and T-cell immunometabolism as shared immune programs, and thromboinflammation as a mechanism connecting cancer-associated thrombosis with coronary vascular events. We further discuss cardio-oncology translation, including immune checkpoint inhibitor-related cardiovascular toxicity, CHIP-guided anti-inflammatory prevention, antiplatelet and antithrombotic strategies, endothelial-targeted interventions, and immune checkpoint-aware cardiovascular monitoring. Understanding these shared pathways may help move cardio-oncology beyond the management of therapy-induced cardiotoxicity toward mechanism-guided prevention and treatment of inflammatory, thrombotic, and immune mechanisms that jointly promote CAD progression and cancer development. Highlights CAD–malignancy comorbidity is driven by shared inflammatory, immunometabolic, thrombotic, and immune checkpoint-related mechanisms. Clonal hematopoiesis links cancer predisposition to atherosclerosis through macrophage remodeling and inflammasome activation. Precision cardio-oncology may require CHIP profiling, inflammatory biomarkers, thrombosis assessment, plaque imaging, and immune checkpoint-aware monitoring. 1 Introduction Coronary artery disease (CAD) and malignancy frequently coexist, particularly in aging populations, reflecting not only shared lifestyle and metabolic risk factors but also overlapping pathophysiological mechanisms ( 1 – 5 ). Traditional risk factors—including smoking, obesity, diabetes, chronic inflammation, dyslipidemia, immune senescence, and metabolic dysfunction—predispose individuals to both atherosclerotic cardiovascular disease and cancer. While these shared risk factors partially explain their co-occurrence, emerging evidence indicates that the association between CAD and malignancy is more than epidemiological coincidence, and may instead reflect convergent molecular programs that simultaneously predispose to vascular and oncologic disease ( 6 – 10 ). Several clinical studies have substantiated this concept. For example, Sun et al. demonstrated that systemic inflammation significantly modifies the association between cancer and CAD severity, indicating that inflammatory status acts as a key mediator rather than a passive correlate ( 11 ). Similarly, Zhao et al. reported that in lung cancer patients, the severity of coronary artery disease was more strongly associated with malignancy under high systemic inflammatory conditions, highlighting the importance of context-dependent immune activation ( 12 ). Large cohort analyses have also shown that patients with stable CAD exhibit an increased risk of subsequent cancer incidence and cancer-related mortality, with elevated levels of inflammatory and metabolic biomarkers serving as predictive indicators ( 13 ). Li et al. further corroborated these findings, providing evidence that CAD and cancer share overlapping risk profiles across diverse populations, suggesting that common pathophysiological pathways, rather than chance, drive their co-occurrence ( 14 ). Together, these studies suggest that CAD–malignancy comorbidity is a clinically significant phenomenon, in which inflammation, immune dysregulation, and metabolic perturbations may act as key mechanistic links. This recognition has important implications for risk stratification, patient monitoring, and the development of integrated cardio-oncology strategies. Based on clinical and mechanistic evidence, we propose that comorbidity between coronary artery disease (CAD) and malignancy arises from a dynamic, multilayered interplay rather than from shared risk factors alone. Persistent low-grade systemic inflammation drives endothelial dysfunction, leukocyte recruitment, and plaque instability in CAD, while simultaneously fostering tumor initiation, angiogenesis, immune evasion, and metastatic progression ( 15 – 19 ). Key inflammatory mediators such as IL-1β, IL-6, TNF-α, and chemokine gradients create a permissive microenvironment that bridges vascular and oncologic pathology. This inflammatory milieu is further shaped by immunometabolic reprogramming of innate and adaptive immune cells: macrophages and monocytes undergo glycolytic and lipid metabolic shifts, while T cells experience clonal expansion and checkpoint modulation. Such alterations contribute to chronic vascular inflammation and tumor-promoting immune suppression, with clonal hematopoiesis and inflammasome activation serving as central mechanistic drivers linking cardiovascular and cancer-associated immune remodeling. Beyond inflammation and immunometabolism, thromboinflammatory processes and therapy-related vascular perturbations further integrate CAD and malignancy. Platelet hyperactivation, prothrombotic endothelial states, and neutrophil extracellular trap formation promote vascular occlusion in CAD, while simultaneously facilitating tumor cell survival, immune evasion, and metastatic dissemination. Moreover, anticancer treatments—including immune checkpoint inhibitors and chemotherapies—can exacerbate cardiovascular risk by inducing immune activation, endothelial injury, or off-target cardiotoxicity, potentially destabilizing pre-existing plaques or triggering myocardial inflammation. Collectively, these interconnected processes—encompassing inflammation, immunometabolism, thromboinflammation, and therapy-induced vascular stress—constitute a unified framework for understanding CAD–malignancy comorbidity and provide a mechanistic basis for integrated clinical management, early detection, and targeted intervention at the interface of cardiology and oncology. Importantly, the CAD–malignancy association should not be interpreted as evidence of direct causation. Several major confounders may contribute to their co-occurrence, including advanced age, smoking, obesity, diabetes, dyslipidemia, hypertension, chronic kidney disease, systemic inflammation, cancer stage, and anticancer treatment exposure. In addition, surveillance bias may increase cancer detection among patients with CAD who undergo frequent medical evaluation, whereas reverse causality may occur when occult malignancy promotes inflammation, hypercoagulability, cachexia, or vascular events before cancer diagnosis. Therefore, this review interprets CAD–malignancy comorbidity as a clinically observed overlap shaped by both shared risk factors and biologically plausible mechanisms, rather than as a simple one-directional causal relationship. Figure 1 summarizes the central framework of CAD–malignancy comorbidity as a convergent immunovascular network rather than several isolated mechanisms. CHIP-driven myeloid remodeling is positioned as the key hub linking shared risk factors, inflammation, thrombosis, vascular injury, immune dysregulation, and cancer therapy-related stress. Figure 1 Central mechanistic model of CAD–malignancy comorbidity. Shared drivers, including aging, cardiometabolic risk factors, and cancer therapy, promote CHIP-driven myeloid remodeling. This hub amplifies inflammasome activation, immunometabolic stress, thromboinflammation, and endothelial/checkpoint disruption, thereby contributing to CAD progression, tumor-promoting inflammation, immune evasion, cancer-associated thrombosis, and metastasis. 2 Epidemiological and clinical evidence linking CAD and malignancy 2.1 CAD as a cancer-associated clinical phenotype A growing body of clinical evidence indicates that coronary artery disease (CAD) and malignancy are epidemiologically and biologically interconnected. Patients with established CAD may exhibit an increased risk of subsequent cancer incidence and cancer-related mortality, whereas patients with cancer frequently develop cardiovascular complications, including ischemic heart disease, arterial thrombosis, and accelerated vascular dysfunction ( 20 – 24 ). This bidirectional relationship suggests that CAD should not be viewed solely as a competing comorbidity in oncology patients, but also as a potential marker of a systemic disease state characterized by chronic inflammation, metabolic dysregulation, vascular injury, and immune remodeling. Campolo et al. provided important evidence supporting this concept by evaluating clinical and biological predictors of cancer incidence and mortality in patients with stable CAD ( 13 ). Their findings suggest that patients with CAD may represent a biologically vulnerable population in whom inflammatory and metabolic abnormalities contribute not only to cardiovascular events but also to cancer development and cancer-related death. This observation is important because it shifts the CAD–cancer relationship from a purely risk-factor-based association to a broader pathobiological framework. In this context, CAD may reflect long-standing exposure to systemic inflammatory and metabolic stressors that also favor oncogenesis. Similarly, Li et al. examined the interrelationship between coronary atherosclerotic disease and cancer and demonstrated that the two disease entities share overlapping clinical risk profiles ( 14 ). Age, smoking, diabetes, obesity, dyslipidemia, and chronic inflammatory burden are common determinants of both atherosclerosis and malignancy. However, these shared factors may not fully explain the observed association. Instead, they may interact with deeper biological processes, such as endothelial dysfunction, immune-cell activation, oxidative stress, and thromboinflammation, which create a permissive environment for both plaque progression and tumor initiation. Therefore, CAD may be interpreted as a cancer-associated clinical phenotype in selected populations, particularly when accompanied by persistent inflammation or metabolic dysfunction. This does not imply that CAD directly causes cancer in all patients, but rather that CAD may serve as a visible vascular manifestation of systemic biological programs that also contribute to malignancy risk. Recognizing this possibility is clinically relevant because it supports more integrated screening, risk stratification, and long-term surveillance strategies in patients with either disease. 2.2 Cancer type-specific association with CAD The relationship between CAD and malignancy is unlikely to be uniform across all tumor types. Different cancers vary substantially in their inflammatory phenotype, metabolic activity, thrombotic potential, treatment exposure, and association with traditional cardiovascular risk factors. Lung cancer is one of the most representative examples of CAD–malignancy overlap because it shares several major pathogenic drivers with coronary atherosclerosis, including cigarette smoking, chronic pulmonary and systemic inflammation, endothelial injury, oxidative stress, hypercoagulability, and immune activation ( 25 – 29 ). Zhao et al. showed that the anatomical severity of CAD was more strongly associated with lung cancer in patients with higher inflammatory status ( 12 ). This finding suggests that inflammation may act as a context-dependent amplifier of the CAD–cancer relationship. In patients with low inflammatory burden, shared risk factors such as age and smoking may explain much of the overlap. In contrast, in patients with high inflammatory burden, activated immune and vascular pathways may strengthen the biological connection between atherosclerosis and malignancy. Sun et al. further supported this concept by showing that inflammation modifies the association between cancer and CAD severity ( 11 ). This observation is particularly important because it implies that the CAD–malignancy relationship is not static. Rather, it may depend on the host inflammatory state, immune-cell composition, and vascular microenvironment. Inflammatory biomarkers may therefore help identify cancer patients who are more likely to harbor advanced coronary atherosclerosis, as well as CAD patients who may be at increased risk of malignancy. Cancer type-specific analysis is also important from a mechanistic perspective. Lung cancer may be strongly linked to CAD through smoking-induced endothelial injury and chronic inflammation. Pancreatic and gastric cancers may be more closely associated with hypercoagulability, platelet activation, and cancer-associated thrombosis. Hematologic malignancies or premalignant hematopoietic clones may be connected to CAD through clonal hematopoiesis and inflammasome activation. These differences indicate that CAD–malignancy comorbidity should not be studied as a single homogeneous entity. Instead, future research should define tumor-specific cardiovascular phenotypes according to inflammatory status, thrombotic risk, immune profile, and treatment exposure. 2.3 From association to mechanism: confounding, causality, and biological plausibility Before moving from epidemiological association to mechanistic interpretation, several methodological limitations must be considered. CAD and malignancy share many powerful upstream determinants, including aging, smoking, obesity, diabetes, dyslipidemia, hypertension, sedentary lifestyle, and chronic inflammatory burden ( 2 , 30 ). These factors may confound observational associations and make it difficult to determine whether CAD promotes cancer, cancer accelerates CAD, or both conditions arise from shared systemic biology. Surveillance bias is also relevant, because patients with established CAD often undergo more frequent clinical contact, imaging, and laboratory testing, which may increase the likelihood of cancer detection ( 1 , 3 ). Conversely, reverse causality should be considered because undiagnosed malignancy can induce inflammation, anemia, hypercoagulability, weight loss, endothelial injury, or thrombotic events before formal cancer diagnosis. Accordingly, the mechanisms discussed below should be viewed as biologically plausible and increasingly testable pathways that may explain part of the CAD–malignancy overlap, rather than as definitive proof of direct causation in all patients. Although traditional risk factors such as aging, smoking, diabetes, obesity, hypertension, and dyslipidemia explain part of the clinical overlap between CAD and cancer, they do not fully account for the depth and complexity of CAD–malignancy comorbidity. The emerging challenge is to move beyond epidemiological association and identify the molecular mechanisms that simultaneously promote vascular disease and malignant progression. Several candidate mechanisms are increasingly recognized. First, clonal hematopoiesis provides a compelling link between cancer predisposition and atherosclerosis. Age-associated hematopoietic clones carrying mutations in genes such as TET2, DNMT3A, JAK2, and ASXL1 can increase the risk of hematologic malignancy while also promoting vascular inflammation through altered monocyte and macrophage function ( 31 – 37 ). Second, macrophage inflammasome activation may serve as a central inflammatory mechanism connecting mutated hematopoietic clones, lipid accumulation, cytokine release, and plaque progression ( 38 – 42 ). Third, adaptive immune dysregulation, including T-cell clonal expansion, immune checkpoint imbalance, and loss of tolerance, may contribute to both tumor immune remodeling and atherosclerotic plaque inflammation. In addition, endothelial activation, platelet–tumor cell crosstalk, neutrophil extracellular trap formation, and coagulation cascade activation provide important thromboinflammatory links between cancer and CAD ( 43 – 47 ). In CAD, these processes contribute to plaque instability, arterial thrombosis, and acute coronary events. In cancer, they support tumor cell survival in circulation, metastatic seeding, immune evasion, and cancer-associated thrombosis. These shared mechanisms suggest that thrombosis is not merely a downstream complication but an active biological interface between cardiovascular and oncologic disease. Thus, the CAD–malignancy relationship should be understood as a continuum that progresses from shared clinical risk factors to shared molecular drivers. Epidemiological studies establish the clinical relevance of this comorbidity, whereas mechanistic studies explain how inflammation, immunometabolism, clonal hematopoiesis, endothelial dysfunction, platelet activation, and coagulation jointly shape disease progression. This mechanistic transition provides the foundation for the following sections of this review, which will examine chronic inflammation, clonal hematopoiesis, immunometabolic remodeling, thrombosis, and cardio-oncology translation as interconnected layers of CAD–malignancy comorbidity. To summarize the current clinical evidence supporting the association between CAD and malignancy, we organized representative epidemiological and cohort studies according to disease context, inflammatory status, and major clinical findings ( Table 1 ). Figure 2 illustrates how CAD and malignancy are linked through overlapping clinical, immune, and thromboinflammatory mechanisms. It highlights both shared systemic risk factors and molecular pathways that jointly contribute to disease progression in heart and tumor tissues. Table 1 First author Year Study type Key findings CAD/cancer focus PMID Sun M 2022 Cohort Systemic inflammation modifies association between CAD severity and cancer risk General CAD–Cancer asso
## Related Clinical Research

- [Hyperuricemia and Gout in People Living with HIV: Systematic Review and Meta-analysis Protocol](https://medichelpline.com/clinical-feed/plos-one-6-urate-dysregulation-hyperuricemia-and-gout-among-people-living-with-hiv-a.md)
- [Immune Checkpoint Inhibitor–Related Myositis, Myocarditis, and Myasthenia Gravis Overlap Syndrome:](https://medichelpline.com/clinical-feed/frontiers-in-immunology-11-immune-checkpoint-inhibitor-related-myositis-myocarditis-and-myasthenia-gravis.md)
- [CXCL10 rs8878 genotype associates with preserved T cells and 30‑day survival in sepsis](https://medichelpline.com/clinical-feed/frontiers-in-immunology-1-cxcl10-rs8878-identifies-a-genotype-associated-immune-phenotype-linked-to-t.md)
- [Single-cell scTWAS identifies immune cell–specific genes linked to gestational diabetes](https://medichelpline.com/clinical-feed/plos-one-0-leveraging-expression-quantitative-trait-loci-information-in-single-cell.md)
- [Obesity-related multimorbidity patterns and reduced quality of life in Iranian adults](https://medichelpline.com/clinical-feed/bmj-open-19-obesity-related-patterns-of-multimorbidity-and-their-association-with-health.md)

## Navigation
- [← Back to Infectious Disease Feed](https://medichelpline.com/clinical-feed/infectious-disease.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.