European Heart Journal (2021) 42, 4166–4168 EDITORIAL

doi:10.1093/eurheartj/ehab589

The legs are a pathway to the heart:

connections between chronic venous
insufficiency and cardiovascular disease
Naomi M. Hamburg *

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Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA

Online publish-ahead-of-print 12 October 2021

This editorial refers to ‘Chronic venous insufficiency, cardiovascular disease, and mortality: a population study’, by J.H.
Prochaska et al., https://doi.org/10.1093/eurheartj/ehab495.

Shared Risk Factors

Obesity
Aging
Chronic Venous Disease Smoking Cardiovascular Disease
Telangiectasia Diabetes Mellitus Mortality
Edema
Heart Failure
Hyperpigmentation
Peripheral Artery Disease
Ulcers Shared Pathophysiology
Endothelial Dysfunction
Inflammation
Thrombosis

Graphical Abstract Intersections of chronic venous disease and cardiovascular disease.

During evaluation of varicose veins, my patients frequently ask me

..
..
whether the ‘bad circulation’ in the legs indicates that they are going ..
to develop heart disease. My typical answer is reassuring, explaining
..
..
that the veins in the leg are different from the arteries in the heart ..
that cause heart attacks. I encourage heart-healthy walking and diet
..
..
but not additional concern about cardiovascular risk. The manuscript ..
..
by Prochaska and colleagues in this issue of the European Heart Journal ..
challenges our conventional thinking about the separation of venous
and arterial disease and has important clinical implications.1
Chronic venous disease has a high global prevalence, with diverse
manifestations ranging from telangiectasia to varicose veins and, in
advanced cases, ulcerations.2 The underlying pathophysiology
involves venous hypertension in the legs induced by several potential
factors including venous valve dysfunction leading to retrograde
blood flow, calf muscle pump dysfunction, and systemic
haemodynamic changes including in obesity and right heart failure.
Diagnosis of chronic venous disease relies on typical physical examin-
ation features that are included in the Clinical, Etiology, Anatomic,
Pathophysiology (CEAP) classification system: telangiectasia or re-
ticular veins, varicose veins, oedema, pigmentation or lipodermato-
sclerosis, and ulceration. Treatment involves compression therapy
for all and interventional therapy in selected patients. Prior studies
.. have explored the risk factors for chronic venous disease that include
..
.. age, obesity, female sex, smoking, family history, and prior venous
.. thrombosis.3–5
..
.. The presence of shared risk factors for chronic venous disease and
.. cardiovascular disease spurred the epidemiological investigation by
..
.. Prochaska and colleagues from the Gutenberg Heart Study.1 In
.. 12 423 adult participants in the population-based cohort study, the
..
.. investigators classified chronic venous disease using the CEAP system

* Corresponding author. Whitaker Cardiovascular Institute, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA. Tel: þ1 617 638 7260, Fax:
þ1 617 414 1563, Email: nhamburg@bu.edu
C The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.
Published on behalf of the European Society of Cardiology. All rights reserved. V
Editorial 4167

..
by assessing lower extremity appearance on physical examination
and digital photographs (graded by independent investigators), and
self-reported venous symptoms. Cross-sectional analysis at the base-
line examination confirmed a high prevalence of any chronic venous
disease (36.5%). Lower extremity oedema had the highest prevalence
(30%) and ulceration the lowest prevalence. Women had a higher
burden of chronic venous disease compared with men, with disease
shifting toward greater severity with advancing age. In addition to the
previously reported association of obesity, hypertension, and smok-
ing with chronic venous disease,6 the current study reports higher
rates of estimated cardiovascular risk based on the Framingham Risk
Score with increasing severity of chronic venous disease. Further,
participants with chronic venous disease had an existing burden of
.. whether the genetics of the spectrum of chronic venous disease iden-
.. tify shared pathways with heart failure or arterial diseases.
..
.. The findings generate many questions that will warrant investiga-
.. tion in future studies. The current study did not include functional
..
.. venous evaluation including venous hypertension and venous reflux
.. that would help elucidate the aetiology of venous symptoms. The fol-
..
.. low-up study only evaluated for all-cause mortality without identifica-
.. tion of specific types of cardiovascular events. It remains likely that
..
.. chronic venous disease has differential associations with atheroscler-
.. otic, thrombotic, and heart failure events. The excess burden of
..
.. chronic venous disease in women warrants additional evaluation to
.. determine whether there are sex differences in the associations be-
..
.. tween venous and arterial diseases.15

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cardiovascular diseases including prior venous thrombo-embolism, a
.. The American Heart Association ran a public awareness campaign
..
known inducer of chronic venous disease, but also peripheral artery .. to ‘Take Your Socks Off’ at the doctors to identify the presence of
disease. Patients with established heart failure in the MyoVasc cohort
.. peripheral artery disease. The study by Prochaska et al. supplies an-
..
had a high prevalence of advanced chronic venous disease (C4–C6) .. other reason to examine our patients’ legs for signs of chronic venous
..
of 14%.
... disease as a window to the heart. In patients without established car-
Evaluation of 6-year follow-up data demonstrated that chronic .. diovascular disease and those with heart failure, observation for the
venous disease predicts all-cause mortality in models adjusting for .. presence of varicose veins, oedema, skin changes, and ulcers provides
..
cardiovascular risk factors, and persisted in analyses excluding partici- .. a simple clinical marker for excess risk. I will still explain to my
pants with prevalent cardiovascular disease at baseline. The predict- .. patients with chronic venous disease that varicose veins are not the
..
ive value of chronic venous disease was also demonstrated in the .. same as blocked arteries. But, I will be sure to comprehensively evalu-
MyoVasc cohort of patients with established heart failure. While not .. ate for the presence of cardiovascular risk factors, encourage exer-
..
the first study to connect venous disease to cardiovascular events,7 .. cise and risk factor modification, and await future research to identify
the current study adds comprehensive assessment of the spectrum .. the impact of venous targeted therapies on cardiovascular disease.
..
of chronic venous disease, indicating that advancing severity by CEAP ..
class portends higher risk of mortality. One interpretation of the ele- ..
.. Funding
vated mortality risk with chronic venous disease includes the impact ..
of shared risk factors that adversely influence the heart and drive ven- .. Dr. Hamburg is supported by grants from the American Heart
.. Association 20SFRN35120118 and 20YVNR35500014 and the National
ous hypertension. Given that leg oedema was the most common .. Institutes of Health U54HL120163.
manifestation of chronic venous disease, it is also possible that the
..
..
heightened risk reflects leg oedema as an initial sign of undetected .. Conflict of interest: none declared.
heart failure.8,9 This possibility is supported by the stronger associ-
..
..
ation of venous insufficiency with oedema and skin changes with .. References
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