Obesity Ups Cerebral Venous Thrombosis Risk in Women on OCs

March 16, 2016

Women who are obese and are taking oral contraceptives have a significantly increased risk for cerebral venous thrombosis (CVT), a new study suggests.

The study, published online in JAMA Neurology on March 14, was conducted by a group led by Jonathan M. Coutinho, MD, Academic Medical Centre, Amsterdam, the Netherlands.

He explained to Medscape Medical News that CVT is a severe disease — much more serious than most peripheral thromboses.

"It mainly affects young adults and is associated with a 5% to 10% mortality rate. Another 20% of patients are left disabled, and many more have long-term complaints that interfere with their quality of life. A large percentage do not go back to work after having a CVT," Dr Coutinho said.

"We already know oral contraceptives increase thrombosis risk, and this study adds to concerns about this, particularly in obese women," he added. "It may be preferable to think about other methods of contraception instead in obese women."

Dr Coutinho says it is probably not appropriate to routinely advise against the use of oral contraceptives in obese women from this one study. "But I would recommend that doctors are aware of the increased risk in obese patients and to discuss other possible options with such patients."

He explained that his group has been working with CVT for many years. "So we see a lot of patients with this condition. We've noticed that many of them are obese and we wanted to examine this in a scientific way."

His team at Academic Medical Centre collaborated with colleagues from Inselspital Hospital University, Bern, Switzerland, who were also active in this field, and with a group in Leiden, the Netherlands.

"We pooled our data to see if we could confirm that obesity was a risk factor for developing cerebral venous thrombosis," Dr Coutinho said. "And indeed we did find that to be the case, with obese individuals being 2 to 3 times more likely to have a CVT compared with those of normal weight."

The researchers then stratified the results, looking for differences between groups and whether certain groups are at higher risk. When they stratified by sex, they found that obesity only appeared to increase risk for CVT in women but not in men.

"When we looked at women in more detail, we found that obesity was only associated with increased risk of CVT in women using oral contraceptives, and in this group the risk was very pronounced — 30 times higher than normal," Dr Coutinho reported.

Obesity in women not using oral contraceptives was not associated with increased CVT risk. "We know use of oral contraceptives increases risk of thrombosis, including CVT, but this increased risk appears to be greatly enhanced if the woman is obese," he added.

Absolute Risk Still Low

"However, while the relative risk is very high, the absolute risk of developing CVT is still small," he said. "It has an incidence of about 1.3 per 100,000 per year overall, so we have to put our results into perspective."

"We have shown a very pronounced result, but our study was relatively small. It would be desirable if our results could be confirmed in an independent study."

Dr Coutinho noted that obesity is considered a risk factor for deep-vein thrombosis (DVT). He explained that it has been thought that DVT results from an incomplete venous return from the leg. This may be more common in obese patients, who may move less.

"But while I can see how obesity may be a risk factor for clots in the legs, which are affected by movement, I can't see that this would explain the increase in CVT," he noted. "Maybe it is more related to biochemical changes, changes in clotting factors, which increase in obesity and with oral contraceptive use."

For the current case-control study, the researchers identified 186 patients with CVT (case-patients) from the Amsterdam and Bern hospitals and 6134 controls taken from the control population of a different study of risk factors for venous thrombosis.

After adjustment for sex, age, history of cancer, ethnicity, smoking status, and oral contraceptive use, results showed that obesity (body mass index [BMI] of 30 kg/m2 or greater) was associated with an increased risk for CVT (adjusted odds ratio [OR], 2.63; 95% confidence interval, 1.53 - 4.54).

Stratification by sex revealed a strong association between CVT and obesity in women (OR, 3.50) but not in men (OR, 1.16). Further stratification revealed that in women who used oral contraceptives, overweight and obesity were associated with an increased risk for CVT in a dose-dependent manner, with a BMI of 25.0 to 29.9 kg/m2 showing an OR of 11.87 and a BMI of 30 kg/m2 or greater having an OR of 29.26 compared with normal-weight women not using oral contraceptives.

In an accompanying editorial, Chirantan Banerjee, MD, Medical University of South Carolina, Charleston, says that "given the lack of prospective data thus far, this is an important study because of the use of appropriate controls, predefined confounders, and appropriate subgroups."

He also points out some limitations, including a small number of individuals without oral contraceptive use, unmatched historical controls, and missing BMI data in 15.9% of case-patients.

Noting that use of oral contraceptives has also been associated with increased risk for arterial ischemic stroke in obese women, Dr Banerjee concludes that: "Better counseling and education of obese women informing them of the increased risk would be prudent, as would be consideration of alternate nonhormonal OC [oral contraceptive] options."

This study is supported by grants from The Netherlands Organization for Scientific Research, the Dutch Thrombosis Society, the Remmert Adriaan Laan Foundation, and the Swiss Heart Foundation. Dr Coutinho and Dr. Banerjee have disclosed no relevant financial relationships. Disclosures for the study coauthors appear in the paper.

JAMA Neurol. Published online March 14, 2016. Full text  Editorial

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