Varicose Veins Increase Risk of Deep Venous Thrombosis, Pulmonary Embolism, Peripheral Artery Disease

Adults diagnosed with varicose veins are at a significantly higher risk of incident deep venous thrombosis (DVT), and may also be more likely to develop pulmonary embolism (PE) and peripheral artery disease (PAD), according to a new study in JAMA.

PeiChunChen PhD

Pei-Chun Chen, PhD

About 23% of adults are diagnosed with varicose veins in the US. While the condition has rarely been associated with serious health risks, previous studies have shown that patients with varicose veins have increased levels of inflammatory prothrombotic markers, which are thought to be associated with the pathophysiology of DVT, PE and PAD.

The Study

Those studies were cross-sectional or case-control studies, had small sample sizes, and didn’t verify the diagnosis of varicose veins, according to the study authors, led by Pei-Chun Chen, PhD, of the Department of Public Health at China Medical University. So, Chen and colleagues set out to further investigate a potential connection.Chen’s team conducted a retrospective cohort study using claims data from Taiwan’s National Health Insurance program that excluded any patients who were previously diagnosed with DVT, PE, or PAD. From 2001 to 2013, they monitored 212,984 patients aged 20 years and older who had varicose veins, and matched them with a control group of the same number of patients who didn’t. The varicose veins group and the control group contained patients of similar mean age (54.5 and 54.3 years, respectively) and sex (69.3% women and 70.3% women, respectively). Median follow-up duration was roughly 7 years for both groups and all 3 conditions

At time of follow-up, researchers found that the varicose veins group had higher incidence rates than the control group for DVT, PE and PAD, as follows:

• DVT: 6.55 in the varicose veins group vs 1.23 per 1000 person-years in the control group (10,360 vs 1980 cases); absolute risk difference (ARD), 5.32 (95% CI)
• 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)
• PAD: 10.73 for the varicose veins group vs 6.22 for the control group per 1000 person-years (16,615 versus 9709 cases); ARD 4.51 (95% CI).

The Implications

Hazard ratios for the varicose veins group compared with the control group were 5.30 (95% CI) for DVT, 1.73 (95% CI) for PE, and 1.72 (95% CI) for PAD.There are several possible explanations for the study’s findings, Chen said. Animal models have shown higher concentrations of macrophages, monocytes, neutrophils, lymphocytes, and matrix metalloproteinases in venous valves exposed to high pressure for prolonged periods, like in varicose veins.

Moreover, patients with chronic venous diseases have increased leukocyte adhesion and more activated leukocytes. Inflammation may promote a prothrombotic state that may facilitate venous thromboembolism, and patients with varicose veins have increased levels of inflammatory and prothrombotic markers.

Further research needs to be conducted to improve understanding of the link between PE, PAD and varicose veins. Because Chen’s study was observational, it was prone to bias due to unmeasured or unrecognized confounders.

“The magnitude of the association between varicose veins and PE and PAD was small, and therefore the possibility that it may be due to residual or unmeasured confounding cannot be excluded,” Chen told MD Magazine.

Still, the association between varicose veins and DVT was strong, he added.

“From this study, we believe that varicose veins are not merely a cosmetic or symptomatic concern,” Chen said. “Due to the strong relationship between varicose veins and the increased risk of more serious disease, patients with varicose veins deserve careful monitoring and early evaluation.”

As of now, it is unclear whether common varicose vein treatments like sclerotherapy, elastic stockings, leg elevation and exercise could mitigate the risk of DVT, PE and PAD. However, Chen noted that her team is currently undertaking another study to better understand how those treatments could mitigate the risk of the 3 conditions.

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