CV risk factors associated with VTE

December 20, 2007

Varese, Italy - A new meta-analysis has found that cardiovascular risk factors such as obesity, hypertension, and diabetes are associated with venous thromboembolism (VTE) [1]. Dr Walter Ageno (University of Insubria, Varese, Italy) and colleagues report their findings online December 17, 2007 in Circulation.

"We did confirm an association between some cardiovascular risk factors and VTE," Ageno told heart wire . The research has important clinical implications, he says, because a significant proportion of VTE, up to 47%, is currently classed as unprovoked in the absence of major known risk factors, such as cancer, trauma, and surgery. "But if patients are obese or hypertensive or have diabetes, then the VTE should not be considered as idiopathic but related to the presence of cardiovascular risk factors," he says.

If patients are obese or hypertensive or have diabetes, then the VTE should not be considered as idiopathic but related to the presence of CV risk factors.

"The clinical observation so far has been that patients with VTE are at increased risk of arterial thrombosis, whereas the other way around has not been proven. There are no studies that have concluded that patients with atherothrombosis are at increased risk of subsequent VTE. The reason for this discrepancy might very well be in the therapeutic approach," he explains. "Patients with atherothrombosis do receive aspirin and statins, and all these drugs have been shown to have a small but probably significant effect in reducing the risk of VTE. But patients with VTE receive short- to medium-term anticoagulation, and usually they are not studied for cardiovascular risk factors. VTE physicians are not really focused on that, they are more interested in seeing whether there is a cancer."

Thus, trials are needed to examine whether appropriate therapy for CV risk factors—such as aspirin and statins—and lifestyle changes will ameliorate the risk of VTE, he says.

First demonstration of link between most CV risk factors and VTE

Ageno explained to heart wire that recent studies have shown that VTE and atherosclerosis "are more connected than we previously thought, so we decided that if they are connected, maybe they share risk factors." Although it was already recognized that obesity is a mild risk factor for VTE, the evidence for other risk factors was flimsy. But when he and his colleagues looked in the literature, they found some studies suggesting there may be an association between diabetes and dyslipidemia and VTE, "but they were not sufficiently powered."

They subsequently analyzed all of these old studies that assessed one or more cardiovascular risk factors in patients with VTE, all of which had control groups. Twenty-one case-control and cohort studies with a total of 63 552 patients were included. Odds ratios or weighted means were calculated and pooled using a random-effects model.

Compared with control subjects, the risk of VTE was 2.33 for obesity, 1.51 for hypertension, 1.42 for diabetes mellitus, 1.18 for smoking, and 1.16 for hypercholesterolemia. Weighted mean HDL levels were significantly lower in VTE patients, whereas no difference was observed for total and LDL cholesterol, the researchers note.

"We not only were able to confirm the association between obesity and VTE but also could demonstrate for the first time an association between VTE and diabetes mellitus, hypertension, low HDL cholesterol, and high triglycerides," they observe.

Ageno said the estimated ORs for these variables, "although statistically significant, were not as high and not as evident as for established risk factors for VTE such as cancer or surgery. But the interesting thing is that these cardiovascular risk factors are much more common in the general population, and they often coexist."

"Given the multifactorial nature of VTE, it is highly likely that these risk factors for atherothrombosis possibly work together in provoking VTE and may be responsible for a substantial proportion of VTE in the general population," he says.

Treatment could lower cases of VTE?
Given the multifactorial nature of VTE, it is highly likely that these risk factors for atherothrombosis possibly work together in provoking VTE.

Ageno says there have been studies that have given support to the biological plausibility of an association between some cardiovascular risk factors and VTE, "but what we need to show now is that the treatment of these risk factors is able to prevent VTE."

He says there are a couple of ongoing studies evaluating the role of aspirin in the secondary prevention of VTE and that "the idea that statins could have an effect on VTE is not recent. A few years ago, there were a few substudies of major clinical trials that suggested that patients on statins had a lower incidence of VTE, and there have been a few editorials and literature reviews on the subject. However, I'm not aware of any adequate studies that were done afterward."

The problem currently is that a physician treating a patient with moderate- to high-risk dyslipidemia who had a VTE "would find it difficult to start statins, because they are not indicated in this population and in many countries would not be reimbursed. What the doctor will probably do is tell the patient to try to lose weight and make other lifestyle changes."

A large statin trial looking at this issue would be ideal but would require many patients, he notes. In addition, "a longitudinal study is needed showing that the presence of cardiovascular risk factors is in fact associated with increased risk of VTE," he notes.

"The results of our study may open new perspectives in the management of patients with VTE, in particular for those patients presenting with an apparently unprovoked event. Recognition of cardiovascular risk factors . . . may support new strategies for both primary and secondary prevention. In particular, the role of weight loss and antiplatelet and lipid-lowering therapy needs to be specifically assessed," he concludes.


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