Varicose Veins Linked to Increased Risk of DVT

Patients with varicose veins are five times more likely than those without the condition to develop deep vein thrombosis (DVT), according to a large retrospective study from Taiwan. The study also found increased risk of pulmonary embolism (PE) and PAD in patients with varicose veins, but the researchers say unmeasured confounders make the meaning of those associations less clear.

“Whether the association between varicose veins and DVT is causal or represents a common set of risk factors requires further research,” write investigators led by Shyue-Luen Chang, MD (Chang Gung Memorial Hospital, Taoyuan, Taiwan).

Chang and colleagues hypothesize that the high degree of inflammation and prothrombotic markers associated with varicose veins may give rise to DVT, PE, or PAD.

Ronald S. Winokur, MD (Weill Cornell Medicine, New York, NY), who was not involved in the study, told TCTMD that the idea of a connection between varicose veins and DVT is not a new concept, but it is controversial because there is little in the way of evidence to prove it. From a pure physiological standpoint, he added, it makes little sense that varicose veins could lead to a DVT in the absence of risk factors.

“Varicose veins really only affect the superficial venous system, not the deep venous system,” he said, noting that people with the condition typically have normal blood flow in the deep venous system without slowing or reversal of flow.

DVT Risk Highest in the First Year

The study, published online February 27, 2018 in JAMA, included 212,984 Taiwanese patients with varicose veins and 212,984 controls. Women accounted for more than twice the number of patients compared with men. Over follow-up of more than 7 years, more patients with than without varicose veins developed DVT (HR 5.30; 95% CI 5.05-5.56) and also had higher rates of PE (HR 1.73; 95%CI 1.54-1.94) and PAD (HR 1.72; 95%CI 1.68-1.77).

According to the researchers, the DVT risk was highest within the first year after the diagnosis of varicose veins. Men with varicose veins had a higher overall risk of DVT than women (HR 6.11; 95% CI 5.63-6.64 vs HR 4.88; 95% CI 4.60-5.18) when compared with propensity-matched controls, and younger patients (aged 20-34 years) were at greater risk than older age groups, with an HR of 14.17 (95% CI 10.15-19.78) versus an HR of 3.96 (95% CI 3.56-4.40) for patients aged 75 and over.

In multivariable analyses, the association between varicose veins and DVT, PE, and PAD remained after controlling for risk factors such as hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, and malignancy. The researchers reported that “extreme scenarios” were required to remove the associations in their analyses.

Something Missing

Chang and colleagues note that other studies have attempted to demonstrate the link between varicose veins and DVT, including a case-control study that found 1.6- to 10.5-fold increase in the odds of DVT among varicose vein patients. However, they caution that information on significant potential confounders, including smoking and obesity, was not available in the claims data used in their study and could account for the higher rates of not only DVT, but also PE and PAD.

Speaking with TCTMD, however, Winokur remained unconvinced. An unaccounted-for confounder may be the key to the findings, he said, adding that he does not believe the association the researchers have shown is true.

“They’re missing something that’s present in these patients that is not present in other people, meaning just because we’re seeing a correlation between varicose veins and DVT in this study over time in the [Taiwanese] population doesn’t mean that all the patients who happen to have varicose veins didn’t also have something else,” Winokur said. “Maybe they all had treatment, maybe they all had stripping surgery that could have led to a higher incidence of DVT. Maybe there’s something they take as a medication [in Taiwan] for varicose veins that happens to be a prothrombotic agent and all of these patients happen to be taking that and are diagnosed with a DVT down the road. I think there must be some hidden confounder here that they didn’t look at in the study.”

I think there must be some hidden confounder here that they didn’t look at in the study. Ronald S. Winokur

As for the theory by Chang and colleagues that the DVT may arise from inflammation related to varicose veins, Winokur said most, if not all, of that inflammation is localized.

“As long as there is blood flowing and people are walking and are active, there should be blood pumping in the deep system,” he added. “I guess that’s another part of this that [the researchers] were unable to capture and that is, how active were these people?”

Winokur said more study is needed to look more closely at procoagulant factors.

“If it’s true that varicose vein patients have a higher risk of DVT, then we should probably be doing thrombophilia testing on a cohort of patients with varicose veins and try to identify what it is that’s leading to the DVT,” he said. “Potentially, it’s partly maybe a factor that’s leading to their risk for varicose veins. But I don’t think it’s the varicose veins themselves that are causing [the DVTs].”

TCTMD contacted Chang and colleagues to respond to Winokur’s concerns, but had not replied at the time of publication.