Using data from the Women's Health Initiative Observational Study (WHI-OS), researchers show a positive association between trans fat intake and incidence of ischemic stroke that persisted even after adjustment for major lifestyle, cardiovascular, and dietary factors.
However, the association appeared to be reversed with aspirin use in this population.
Previous research showed evidence of a link between trans fatty acids and coronary heart disease but there hasn't been much investigation into trans fats and ischemic stroke, said one of this study's authors, Ka He, MD, associate professor, Departments of Nutrition and Epidemiology, University of North Carolina Gillings School of Global Public Health in Chapel Hill. "This study is the first to confirm that trans fatty acids are a risk factor of ischemic stroke."
Fat intake
The study included 87,025 women aged 50 to 79 years with no history of stroke or transient ischemic attack (TIA) at baseline who were enrolled in the WHI-OS, a cohort of postmenopausal women recruited between 1994 and 1998.
At enrollment and at a 3-year follow-up visit, the women completed a food-frequency questionnaire (FFQ). Among other things, the FFQ asked about frequency of intake of fats in meat and dairy, fats used in cooking, added fats, and reduced-fat foods, over the previous 3 months.
Researchers gained information on ischemic stroke through self-reports during annual medical history updates. Additional details were gleaned from medical charts, brain imaging, and death certificates.
Over a follow-up of 663,041 person-years, there were 1049 cases of ischemic stroke. After age and race were considered, trans fat intake was associated with a higher risk for stroke (hazard ratio [HR] for the fifth vs first quintile of trans fat intake, 1.49; 95% confidence interval [CI], 1.22 - 1.82; P for trend = .0002).
The association remained significant after adjustment for major lifestyle variables, such as body mass index (BMI), smoking, and physical activity; for health conditions, including history of coronary heart disease, atrial fibrillation, or diabetes; and for potential dietary confounders, such as fruit and vegetable intake and use of vitamin E (HR, 1.39; 95% CI, 1.08 - 1.79; P for trend = .048).
There was no evidence of interaction between trans fat intake and statin use, alcohol intake, or hormone replacement therapy use.
In addition, no significant association was seen for other types of fat or total fat, raising doubts that dietary fats act through dyslipidemia to cause cerebral infarction. However, this lack of association wasn't too surprising to Dr. He. "More and more studies suggest that types of fat are more important than total fat," he said.
This study did show some increased risk with saturated fats, but it wasn't significant. "It's possible that saturated fats can increase the risk to some extent but the magnitude may not be big enough to show statistical significance," said Dr. He.
Although he expected there might be an inverse association between the healthier polyunsaturated fats and strokes, "in our study, we just didn't see anything," said Dr. He. "Some other previous studies showed the same results."
The association between trans fats and ischemic stroke remained positive (HR, 1.11) after TIAs were included as ischemic stroke cases. This, said Dr. He, may indicate similarities between these types of stroke or suggest that trans fatty acids affect both with a similar mechanism. There were no or weak associations between cholesterol and ischemic stroke.
Stroke types
Women with higher trans fat intake had elevated incidence of lacunar (there were 269 such strokes in this study) and cardioembolic strokes (n = 234), but not atherothrombotic infarctions (n = 101), the subtype of ischemic stroke associated with elevated total cholesterol and decreased high-density lipoprotein cholesterol.
Although the study was one of the largest of its kind and included more than 1000 cases of stroke, this may still not have provided enough statistical power. "Even though we see increased risk for those subtypes of stroke, statistically it was not significant, the major reason probably being that we don't have enough cases," said Dr. He.
The researchers also investigated the possibility that participants changed their diet if they developed a health condition. But although slightly attenuated, the association remained significant when updates on participants' dietary information was stopped after a reported diagnosis of diabetes mellitus, myocardial infarction, revascularization, peripheral artery disease, or carotid artery disease.
Aspirin use appeared to lower the stroke risk. Among 67,288 non–aspirin users, the HR for ischemic stroke in the highest versus lowest quintile of trans fat intake was 1.66, but among 19,736 aspirin users, it was 0.95. "That suggests that aspirin use may counteract the potential adverse effect of trans fatty acids on ischemic stroke," commented Dr. He.
According to the authors, platelet aggregability increases with advancing age, possibly more so among women than men. In addition to functioning as an antiplatelet agent, aspirin also reduces inflammation, they said.
Caution against "Overselling"
Asked to comment on these results, Michael J. Schneck, MD, professor of neurology and neurosurgery, associate director, Stroke Unit, Loyola University Medical Center, Maywood, Illinois, and a member of the American Academy of Neurology, said the study is intriguing and the first to confirm the observation that increased trans fat intake affects stroke risk. The study also supports the argument for a healthy diet, said Dr. Schneck.
However, he told Medscape Medical News, as with other observational diet studies, this one has limitations. For one thing, the dietary information was self-reported, and, although the study accounted for such risk factors as smoking and physical inactivity, the participants with the highest trans fat intake were also the least healthy.
"I would be careful in the overselling of this paper," said Dr. Schneck. "This is a real phenomenon but my question is, how much of a real phenomenon?" He added that the findings need to be replicated in other populations.
Dr. Schneck said he found it interesting that large-vessel strokes were not associated with trans fat intake. "I could understand that trans fats are linked to higher risk with lacunar infarction, but I was surprised that they were not associated with other subtypes of stroke. That's a bit confusing to me based on their arguments that trans fats are associated with inflammation."
He said he was not in agreement on the authors' theory that the stroke prevention benefit of aspirin may be unique to postmenopausal women because of their greater risk for platelet aggregability. "The observation that aspirin is better for ischemic stroke in women but not men, and that aspirin is better in heart disease in men but not women, is just a reflection of the nature of the various cohort studies and is driven by quirks of the randomized trials."
He stressed that cutting trans fats from the diet is solid dietary advice for everyone, not just older women. "It really isn't that you can eat trans fats until you go into menopause and then have to clean up your act," he said. "You don't wait until menopause to stop eating trans fats; you start before that."
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