Varicose Veins and Incident Venous Thromboembolism (VTE) or Peripheral Artery Disease (PAD) | Peripheral Arterial Disease | JN Learning | AMA Ed Hub [Skip to Content]
[Skip to Content Landing]

Association of Varicose Veins With Incident Venous Thromboembolism and Peripheral Artery Disease

Educational Objective
To learn whether patients with varicose veins may be at increased risk of venous thrombosis, pulmonary embolism, or peripheral artery disease.
1 Credit CME
Key Points

Question  Are varicose veins associated with an increased risk of developing deep venous thrombosis (DVT), pulmonary embolism (PE), or peripheral artery disease (PAD)?

Findings  In this retrospective cohort study from Taiwan that included 425 968 adults, the presence of varicose veins was associated with a significantly increased risk of incident DVT (hazard ratio [HR], 5.30), PE (HR, 1.73), and PAD (HR, 1.72).

Meaning  This study found a significant association between varicose veins and DVT, and less clear potential associations with PE and PAD; further research is needed to understand whether the association with DVT is causal.


Importance  Varicose veins are common but rarely associated with serious health risks. Deep venous thrombosis (DVT), pulmonary embolism (PE), and peripheral artery disease (PAD) are also vascular diseases but associated with serious systemic effects. Little is known about the association between varicose veins and the incidence of other vascular diseases including DVT, PE, and PAD.

Objective  To investigate whether varicose veins are associated with an increased risk of DVT, PE, or PAD.

Design, Setting, and Participants  A retrospective cohort study using claims data from Taiwan’s National Health Insurance program. Patients aged 20 years and older with varicose veins were enrolled from January 1, 2001-December 31, 2013, and a control group of patients without varicose veins were matched by propensity score. Patients previously diagnosed with DVT, PE, or PAD were excluded. Follow-up ended December 31, 2014.

Exposures  Presence of varicose veins.

Main Outcomes and Measures  Incidence rates of DVT, PE, and PAD were assessed in people with and without varicose veins. Cox proportional hazards models were used to estimate relative hazards, with the control group as reference.

Results  There were 212 984 patients in the varicose veins group (mean [SD] age, 54.5 [16.0] years; 69.3% women) and 212 984 in the control group (mean [SD] age, 54.3 [15.6] years; 70.3% women). The median follow-up duration was 7.5 years for DVT, 7.8 years for PE, and 7.3 years for PAD for patients with varicose veins, and for the control group, follow-up duration was 7.6 years for DVT, 7.7 years for PE, and 7.4 years for PAD. The varicose veins group had higher incidence rates than the control group for DVT (6.55 vs 1.23 per 1000 person-years [10 360 vs 1980 cases]; absolute risk difference [ARD], 5.32 [95% CI, 5.18-5.46]), for PE (0.48 for the varicose veins group vs 0.28 for the control group per 1000 person-years [793 vs 451 cases]; ARD, 0.20 [95% CI, 0.16-0.24]), and for PAD (10.73 for the varicose veins group vs 6.22 for the control group per 1000 person-years [16 615 vs 9709 cases]; ARD, 4.51 [95% CI, 4.31-4.71]). The hazard ratios for the varicose veins group compared with the control group were 5.30 (95% CI, 5.05-5.56) for DVT, 1.73 (95% CI, 1.54-1.94) for PE, and 1.72 (95% CI, 1.68-1.77) for PAD.

Conclusions and Relevance  Among adults diagnosed with varicose veins, there was a significantly increased risk of incident DVT; the findings for PE and PAD are less clear due to the potential for confounding. Whether the association between varicose veins and DVT is causal or represents a common set of risk factors requires further research.

Sign in to take quiz and track your certificates

Buy This Activity

JN Learning™ is the home for CME and MOC from the JAMA Network. Search by specialty or US state and earn AMA PRA Category 1 CME Credit™ from articles, audio, Clinical Challenges and more. Learn more about CME/MOC

Article Information

Corresponding Author: Pei-Chun Chen, PhD, Department of Public Health, China Medical University, No. 91 Hsueh-Shih Rd, Taichung, Taiwan 40402 (

Accepted for Publication: January 18, 2018.

Author Contributions: Drs S-L Chang and Chen had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: S-L Chang, Huang, Lee, Hu, Chen.

Acquisition, analysis, or interpretation of data: S-L Chang, Hsiao, S-W Chang, CJ Chang, Chen.

Drafting of the manuscript: S-L Chang, Lee, Hu, Chen.

Critical revision of the manuscript for important intellectual content: S-L Chang, Huang, Hsiao, S-W Chang, CJ Chang, Chen.

Statistical analysis: S-W Chang, Chen.

Obtained funding: S-L Chang, Huang, CJ Chang.

Administrative, technical, or material support: Lee, Hsiao, S-W Chang, CJ Chang.

Supervision: Hu, CJ Chang, Chen.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This study was supported by grants from Chang Gung Medical Research Program (CIRPD1D0032) and from the Taiwan Ministry of Science and Technology (MOST 103-2314-B-002 -038 -MY3).

Role of the Funder/Sponsor: Chang Gung Medical Research Program and Taiwan Ministry of Science and Technology had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We thank Shu-Ru Lee, MS, (Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan), for data analysis assistance. Ms Lee was not compensated for her contribution.

Beebe-Dimmer  JL, Pfeifer  JR, Engle  JS, Schottenfeld  D.  The epidemiology of chronic venous insufficiency and varicose veins.  Ann Epidemiol. 2005;15(3):175-184.PubMedGoogle ScholarCrossref
Maurins  U, Hoffmann  BH, Lösch  C, Jöckel  KH, Rabe  E, Pannier  F.  Distribution and prevalence of reflux in the superficial and deep venous system in the general population—results from the Bonn Vein Study, Germany.  J Vasc Surg. 2008;48(3):680-687.PubMedGoogle ScholarCrossref
Hamdan  A.  Management of varicose veins and venous insufficiency.  JAMA. 2012;308(24):2612-2621.PubMedGoogle ScholarCrossref
Kaplan  RM, Criqui  MH, Denenberg  JO, Bergan  J, Fronek  A.  Quality of life in patients with chronic venous disease: San Diego population study.  J Vasc Surg. 2003;37(5):1047-1053.PubMedGoogle ScholarCrossref
Piazza  G.  Varicose veins.  Circulation. 2014;130(7):582-587.PubMedGoogle ScholarCrossref
Poredos  P, Spirkoska  A, Rucigaj  T, Fareed  J, Jezovnik  MK.  Do blood constituents in varicose veins differ from the systemic blood constituents?  Eur J Vasc Endovasc Surg. 2015;50(2):250-256.PubMedGoogle ScholarCrossref
Riva  N, Donadini  MP, Ageno  W.  Epidemiology and pathophysiology of venous thromboembolism: similarities with atherothrombosis and the role of inflammation.  Thromb Haemost. 2015;113(6):1176-1183.PubMedGoogle ScholarCrossref
Lee  AJ, MacGregor  AS, Hau  CM,  et al.  The role of haematological factors in diabetic peripheral arterial disease: the Edinburgh Artery Study.  Br J Haematol. 1999;105(3):648-654.PubMedGoogle ScholarCrossref
Engbers  MJ, Karasu  A, Blom  JW, Cushman  M, Rosendaal  FR, van Hylckama Vlieg  A.  Clinical features of venous insufficiency and the risk of venous thrombosis in older people.  Br J Haematol. 2015;171(3):417-423.PubMedGoogle ScholarCrossref
Müller-Bühl  U, Leutgeb  R, Engeser  P, Achankeng  EN, Szecsenyi  J, Laux  G.  Varicose veins are a risk factor for deep venous thrombosis in general practice patients.  Vasa. 2012;41(5):360-365.PubMedGoogle ScholarCrossref
National Health Insurance Administration, Ministry of Health and Welfare, Taiwan. National Health Insurance in Taiwan 2015-2016 Annual Report. Accessed November 18, 2017.
Austin  PC.  An introduction to propensity score methods for reducing the effects of confounding in observational studies.  Multivariate Behav Res. 2011;46(3):399-424.PubMedGoogle ScholarCrossref
Austin  PC.  A comparison of 12 algorithms for matching on the propensity score.  Stat Med. 2014;33(6):1057-1069.PubMedGoogle ScholarCrossref
Lipsitch  M, Tchetgen Tchetgen  E, Cohen  T.  Negative controls: a tool for detecting confounding and bias in observational studies.  Epidemiology. 2010;21(3):383-388.PubMedGoogle ScholarCrossref
Prasad  V, Jena  AB.  Prespecified falsification end points: can they validate true observational associations?  JAMA. 2013;309(3):241-242.PubMedGoogle ScholarCrossref
Mamdani  M, Sykora  K, Li  P,  et al.  Reader’s guide to critical appraisal of cohort studies: 2.  BMJ. 2005;330(7497):960-962.PubMedGoogle ScholarCrossref
Austin  PC.  The performance of different propensity score methods for estimating marginal hazard ratios.  Stat Med. 2013;32(16):2837-2849.PubMedGoogle ScholarCrossref
Greenland  S, Lash  TL. Analysis of unmeasured confounders—external adjustment. In: Rothman  KJ, Greenland  S, Lash  TL, eds.  Modern Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:348-351.
Lu  L, Mackay  DF, Pell  JP.  Meta-analysis of the association between cigarette smoking and peripheral arterial disease.  Heart. 2014;100(5):414-423.PubMedGoogle ScholarCrossref
Cheng  YJ, Liu  ZH, Yao  FJ,  et al.  Current and former smoking and risk for venous thromboembolism: a systematic review and meta-analysis.  PLoS Med. 2013;10(9):e1001515.PubMedGoogle ScholarCrossref
Chang  FC, Hu  TW, Lo  SY, Yu  PT, Chao  KY, Hsiao  ML.  Quit smoking advice from health professionals in Taiwan: the role of funding policy and smoker socioeconomic status.  Tob Control. 2010;19(1):44-49.PubMedGoogle ScholarCrossref
Kasza  J, Wolfe  R, Schuster  T.  Assessing the impact of unmeasured confounding for binary outcomes using confounding functions.  Int J Epidemiol. 2017;46(4):1303-1311.PubMedGoogle ScholarCrossref
Cornfield  J, Haenszel  W, Hammond  EC, Lilienfeld  AM, Shimkin  MB, Wynder  EL.  Smoking and lung cancer: recent evidence and a discussion of some questions.  J Natl Cancer Inst. 1959;22(1):173-203.PubMedGoogle Scholar
Mäkivaara  LA, Ahti  TM, Luukkaala  T, Hakama  M, Laurikka  JO.  Persons with varicose veins have a high subsequent incidence of arterial disease: a population-based study in Tampere, Finland.  Angiology. 2007;58(6):704-709.PubMedGoogle ScholarCrossref
Bergan  JJ, Schmid-Schönbein  GW, Smith  PD, Nicolaides  AN, Boisseau  MR, Eklof  B.  Chronic venous disease.  N Engl J Med. 2006;355(5):488-498.PubMedGoogle ScholarCrossref
Sam  RC, Hobbs  SD, Darvall  KA,  et al.  Chronic venous disease in a cohort of healthy UK Asian men.  Eur J Vasc Endovasc Surg. 2007;34(1):92-96.PubMedGoogle ScholarCrossref
Groenwold  RH, Sterne  JA, Lawlor  DA, Moons  KG, Hoes  AW, Tilling  K.  Sensitivity analysis for the effects of multiple unmeasured confounders.  Ann Epidemiol. 2016;26(9):605-611.PubMedGoogle ScholarCrossref
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
If you are not a JN Learning subscriber, you can either:
Subscribe to JN Learning for one year
Buy this activity
With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right

Name Your Search

Save Search
With a personal account, you can:
  • Track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience

Lookup An Activity



My Saved Searches

You currently have no searches saved.

With a personal account, you can:
  • Access free activities and track your credits
  • Personalize content alerts
  • Customize your interests
  • Fully personalize your learning experience
Education Center Collection Sign In Modal Right