The intricate relationship between dermatological conditions and cardiovascular health represents a critical, yet often overlooked, intersection in modern medical research. Emerging evidence suggests that this "cardiocutaneous axis" requires us to better understand how cutaneous manifestations can serve as significant indicators of underlying cardiovascular pathologies, presenting novel diagnostic and therapeutic opportunities.
So what do we know about cardiocutaneous connections so far?
Pathophysiological Connections
Broadly, genetic and epigenetic factors significantly influence pathophysiological mechanisms by creating unique inflammatory response patterns. Specific gene polymorphisms and epigenetic modifications modulate immune regulation, contributing to individual susceptibility to dermatological and cardiovascular conditions.
Let’s take a closer look at the molecular underpinnings of dermatologic and cardiovascular manifestations (Table 1):
- Pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are known to activate endothelial cells and trigger oxidative stress mechanisms. These can manifest as vascular wall remodeling—more specifically, atherosclerosis—through endothelial cell damage and increased lipid peroxidation, triggering other inflammatory cascades.
- T-cell activation and the NF-κB signaling pathway are key mediators in the inflammatory cascade, particularly in regulating gene expression such as those involved with chronic inflammatory responses, yielding immune-mediated vascular damage.
- The JAK-STAT signaling pathway emerges as a critical mechanism in inflammatory signal transduction, influencing immune cell proliferation and differentiation.
Clinical Implications
While the overall impact on patient care remains unclear, awareness of this intersection can inform early diagnosis and intervention as well as improved prognosis and quality of life. Practical approaches include:
- Increased awareness of multi-systemic conditions
- Comprehensive patient histories and physicals, including assessments for risk of chronic and inflammatory conditions as well as drug-related complications
- Holistic and interdisciplinary approaches to care
- Empowerment of patients through effective education and counseling
Key factors involved in the clinical implementation of these improvements include increased familiarity with clinical guidelines, application of advanced imaging to assess cardiovascular risks in dermatological settings, and advancements in genetic testing and biomarkers. These can aid in the early detection and risk stratification of both dermatological and cardiovascular diseases.
Additionally, new and emerging treatments on the horizon have demonstrated efficacy in managing dermatological conditions with cardiovascular comorbidities and potentially mitigating mortality associated with cardiovascular disease.
The skin-heart connection reminds us that in medicine, no organ system exists in isolation. As we continue to unravel the complexities of this bidirectional relationship, we pave the way for more integrated, comprehensive, and personalized patient care.
To learn more about cardiocutaneous connections, check out the "Challenging Cutaneous Oncology Cases: Lessons Learned and The Role of the Dermatologist in Reducing Cardiovascular Risk in Psoriasis" session at the 2025 Dermatology Foundation Clinical Symposium.
Table 1. Associations between dermatologic and cardiovascular manifestations and their potential pathophysiological mechanism(s). APLA = antiphospholipid antibodies; CAD = coronary artery disease; HF = heart failure; IHD = ischemic heart disease; PAH = pulmonary arterial hypertension; PVD = peripheral vascular disease; SLE = systemic lupus erythematosus
Dermatological Manifestation | Cardiovascular Manifestation | Common Inflammatory Pathways |
Livedo reticularis | Cholesterol embolization syndrome, endocarditis | IL-1β, TNF-α, oxidative stress, endothelial dysfunction, complement system activation |
Xanthomata | Hyperlipidemia | IL-1β, TNF-α, oxidative stress, endothelial dysfunction, macrophage mediated inflammation |
Acanthosis nigricans | Metabolic syndrome, insulin resistance, obesity | Chronic inflammation, NF-κB, oxidative stress |
Autoimmune phenomena | Raynaud's phenomenon, vasculitis | T-cell receptors, JAK-STAT, NF-κB, oxidative stress, chronic inflammation, immune cell recruitment, vascular remodeling |
Cyanosis, clubbing, Osler's nodes, Janeway lesions, Splinter hemorrhages | Infective endocarditis, congenital heart disease, HF | TNF-α, IL-1β, IL-6, endothelial cell dysfunction, oxidative stress |
Psoriasis | Cerebrovascular events, IHD, PVD, CAD | Genetic polymorphisms in IL-23 and TNF-α, oxidative stress, endothelial dysfunction, chronic inflammation |
Atopic dermatitis, SLE, dermatomyositis | Heart attack, stroke, atherosclerosis | NF-κB, JAK-STAT, chronic inflammation, APLA |
Scleroderma | PAH, CAD, HF | TNF- α , IL-6, chronic inflammation, endothelial dysfunction, NF-κB, oxidative stress |
References
American Academy of Dermatology Association. Heart disease: 12 warning signs that appear on your skin. Accessed January 23, 2025. https://www.aad.org/public/diseases/a-z/heart-disease-warning-signs
Gelfand JM, Song WB, Langan SM, Garshick MS. Cardiodermatology: the heart of the connection between the skin and cardiovascular disease. Nat Rev Cardiol. Published online November 13, 2024. doi:10.1038/s41569-024-01097-9
Katira A, Katira R. Dermatological manifestations of cardiac conditions. Br J Cardiol. 2022;29(1):9. Published 2022 Mar 8. doi:10.5837/bjc.2022.009
Kaye AD, Islam RK, Tong VT, et al. Cutaneous Dermatologic Manifestations of Cardiovascular Diseases: A Narrative Review. Cureus. 2024;16(10):e72336. Published 2024 Oct 24. doi:10.7759/cureus.72336
Sheth S. More than skin deep: Recognizing cardiovascular co-morbidities in medical dermatology. A Fellow's Voice. Am J Prev Cardiol. 2022;11:100374. Published 2022 Aug 18. doi:10.1016/j.ajpc.2022.100374
Song WB, Soffer DE, Gelfand JM. Using Guidelines of Care to Lower Cardiovascular Risk in Patients with Psoriasis. Dermatol Clin. 2024;42(3):417-428. doi:10.1016/j.det.2024.02.008