By Dr Menaka Sharma
At a glance, varicose veins raise cosmetic concerns, and signal an underlying medical problem.
We know they can cause pain, edema, skin changes, thrombophlebitis, and ulceration.
The challenge is not convincing doctors that varicose veins matter. The challenge is understanding whether we have fully appreciated what they represent.
Traditionally, we have all studied and viewed varicose veins as the endpoint of a mechanical process:
1.Valves fail, 2.Reflux develops, 3.Venous pressure rises, and 4.Veins dilate.
Increasingly, evidence suggests that this explanation captures only part of the story.
The emerging literature points toward a more intriguing possibility. What appears to be a straightforward venous disorder may actually reflect a complex interaction of chronic inflammation, endothelial dysfunction, and vascular remodelling, and interestingly, genetic susceptibility!
We are also aware that in some patients, the visible varicosity may even be the first clue to a deeper pathology hiding upstream.
The question is no longer whether varicose veins are cosmetic, they are definitely not just cosmetic.
The question is whether they are more informative than we currently think.
The Genetics Question
One of the most curious observations in venous disease is that exposure does not equal outcome.
Millions of people spend decades standing for prolonged periods. Some develop severe chronic venous disease in their forties, while others reach old age with minimal venous changes. We are no strangers to the classical risk factors such as obesity, pregnancy, age, and prolonged standing, but these explain only part of this variation.
Recent genetic studies have begun to provide answers.
A landmark genome-wide association study involving nearly half a million individuals identified multiple genetic loci associated with varicose veins, many of which are involved in vascular development, extracellular matrix organization, smooth muscle biology, and inflammatory regulation.
These findings suggest that some patients may possess an inherited susceptibility to venous disease long before the first visible varicosity appears. Rather than asking why the valve failed, researchers are increasingly asking why the vein was vulnerable in the first place.
Subsequent genomic studies have reinforced this concept, identifying additional genetic pathways that may influence venous wall integrity and disease progression. The implication is important: varicose veins may not be solely acquired disease. In many patients, they may represent the interaction between environmental stressors and a genetically predisposed venous system.
The Vein Wall Is Not a Passive Bystander
For decades, venous hypertension was viewed as the primary driver of disease.
Current evidence suggests a more complex picture.
Recent reviews have highlighted the role of endothelial dysfunction, oxidative stress, leukocyte recruitment, inflammatory signalling, and extracellular matrix remodelling throughout the course of chronic venous disease. Sustained hemodynamic stress appears to trigger biological changes within the venous wall that further impair vascular function, creating a self-perpetuating cycle of inflammation and remodelling (Does this sound similar to a very well-known pathogenesis? Let us know!)
In other words, the vein is not simply being stretched passively.
It is actively changing.
This distinction may seem subtle, but it changes how we view the disease.
Varicose veins begin to resemble other chronic vascular disorders in which inflammation and tissue remodelling are central drivers of progression rather than mere consequences of structural failure.
Sometimes the Vein Is Not the Disease
Perhaps the most underappreciated aspect of varicose veins is that they can occasionally function as a clinical clue rather than a final diagnosis.
Most varicosities represent primary venous disease. Some do not.
Pelvic venous disorders, ovarian vein reflux, proximal venous obstruction, post-thrombotic disease, and syndromes such as May–Thurner syndrome can all manifest with lower-limb varicosities.
In these situations, the visible vein may be analogous to jaundice in hepatobiliary disease: important in itself, but potentially pointing toward a deeper pathology. Advanced venous evaluation increasingly relies on identifying these underlying drivers rather than focusing exclusively on superficial reflux.
This perspective becomes particularly relevant in patients with recurrent varicose veins, atypical distributions, disproportionate symptoms, or disease progression despite apparently adequate treatment.
The question shifts from “How do we treat this?” to “How do we treat this, and why did this develop in one individual and not the other?”
Summary
The statement that varicose veins are more than a cosmetic issue is undoubtedly true.
A more interesting conclusion, however, is that they may be more than a diagnosis.
Emerging evidence suggests that varicose veins are not merely dilated superficial veins but the visible manifestation of a complex vascular process involving genetic susceptibility, endothelial dysfunction, chronic inflammation, and structural remodelling. In selected patients, they may even serve as the first clue to pathology elsewhere in the venous system.
As our understanding of venous disease evolves, perhaps the most important lesson is this:
The visible vein is often the end of the chapter we see, but only the beginning of the story we should be asking about.
References
1. Abrashev H, Abrasheva D, Nikolov N, et al. A Systematic Review of Endothelial Dysfunction in Chronic Venous Disease—Inflammation, Oxidative Stress, and Shear Stress. Int J Mol Sci. 2025;26:3660. PMID: 40332237.
2. Costa D, Andreucci M, Ielapi N, et al. Molecular Determinants of Chronic Venous Disease: A Comprehensive Review. Int J Mol Sci. 2023;24(3):1928. PMID: 36768250.
3. Fukaya E, Flores AM, Lindholm D, et al. Clinical and Genetic Determinants of Varicose Veins: Prospective, Community-Based Study of ≈500,000 Individuals. Circulation. 2018;138(25):2869–2880. PMID: 30566020.
4. Helkkula P, et al. Genome-wide association study of varicose veins identifies novel susceptibility loci and therapeutic targets. Commun Biol. 2023.
5. Shadrina AS, et al. Varicose veins of lower extremities: Insights from the first large-scale genetic study. PLoS Genet. 2019.
6. Patel SK, Surowiec SM. Venous Insufficiency. StatPearls. Updated 2024.
By Author
Dr Menaka Sharma
MBBS, IGGMC Nagpur
Co-Author
Dr Danish Sheikh (Kaif)
MBBS, MS General Surgery, FIAGES, FMAS, MACS
Consultant General & Laparoscopic Surgeon
Central Hospital & Critical Care Centre