Association not found in those who experience migraine without aura

Migraine with aura increases a woman’s chance of cardiovascular disease (CVD) compared to women with migraine without aura, or those who did not report migraines, according to a cohort study of women age 45 and older.

“Although diabetes and current smoking were associated with higher rates of major CVD, migraine with aura was more strongly associated with the rate of major CVD than obesity or unfavorable lipid levels, and had a similar association as with elevated systolic blood pressure or high total cholesterol,” Tobias Kurth, MD, ScD, Institute of Public Health, Charité – Universitätsmedizin Berlin, Berlin, Germany, and colleagues reported in JAMA. “The association patterns were similar for specific CVD events.”

In their study, Kurth and colleagues found that “the adjusted incidence rate of major CVD was 3.36 cases per 1000 person-years (95% CI, 2.72-3.99) among women with migraine with aura (adjusted for other dichotomous vascular risk factors and confounding variables) and 2.11 per 1000 person-years (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P value comparing the adjusted incidence rates of migraine without aura versus migraine with aura <.001).”

Only diabetes (adjusted incidence rate, 5.76 [95% CI, 4.68- 6.84]; P value comparing the incidence rate to that of migraine with aura <.001) and current smoking (adjusted incidence rate, 4.29 [95% CI, 3.79-4.79]; P value comparing the incidence rate with that of migraine with aura = .02) were associated with a higher adjusted incident rate of CVD, they explained.

The mechanisms of action for the association between migraine with aura and CVD are not well understood, the study authors wrote. While past research suggested that “elevated vascular biomarkers leading to endothelial dysfunction, other vascular pathology, open patent foramen ovale, genetic predisposition, or migraine-specific or other pain medication use” may be the culprits upping CVD risk in this patient population, the association still stymies the experts.

As for medication use, Kurth and colleagues noted that “not only patients with migraine with aura use such treatment.” They added that “cortical spreading depolarization, the electrophysical mechanisms involved in migraine aura, can play a role in stroke and potentially in other vascular events.”

Kurth and colleagues culled data from the Women’s Health Study, which randomized 39,876 female health professionals age 45 or older to low-dose aspirin versus placebo or vitamin E versus placebo from 1992-1995. At baseline, no participants had a history of CVD or cancer. For the current analysis, participants were followed through Dec. 31, 2018. The women self-reported cardiovascular events.

The primary outcome was major CVD (myocardial infarction, stroke, CVD death).

In all, there were 27,858 women in the analysis, whose average age at baseline was 54.6 years. In the year prior to baseline, 1,435 (5.2%) reported migraine with aura, compared with 26,423 (94.8%) who did not — 2,177 (7.8%) reported migraine without aura and 24,246 (87.0%) reported they did not have migraine.

In the mean follow-up of 22.6 years (629 353 total person-years), the study participants reported:

  • 1,666 major CVD events.
  • 887 strokes (fatal and nonfatal).
  • 629 myocardial infarctions (fatal and nonfatal).
  • 391 deaths due to CVD.

“The crude overall incidence rate per 1000 person-years was 2.87 for major CVD, 1.52 for total stroke, 1.07 for myocardial infarction, and 0.62 for deaths due to CVD,” they study authors noted.

And, as previously noted, the adjusted incidence rate of major CVD was significantly higher for women who reported migraine with aura than those who experienced migraines with no aura, or who did not experience migraines.

“The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95%CI, 2.02-2.56]), high triglycerides (2.67 [95%CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95%CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95%CI, 2.76-4.81]), high total cholesterol (2.85 [95%CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95%CI, 2.38-3.05]),” Kurth and colleagues wrote.

Also, after adding migraine with aura to each vascular risk factor, the adjusted incidence rate of CVD was higher than for having a vascular risk factor alone.

“The incremental increase in the incidence rate ranged from 1.01 additional cases per 1000 person-years, when migraine with aura was added to body mass index, to 2.57 additional cases per 1000 person-years, when migraine with aura was added to diabetes,” the study authors pointed out.

They noted that the women in the study who reported migraine with aura were “slightly younger, had higher triglycerides levels, and more frequently reported a family history of premature myocardial infarction.” These women also reported less alcohol consumption, but they were more likely to have used postmenopausal hormones at some point.

While the strengths of the study include the large cohort and the wealth of available data, including the confirmation of CVD events and the homogeneity of the study population, the authors noted that the study has several limitations, primarily the self-reporting of migraines and vascular risk factors. Also, while migraine with aura and vascular risk factors were reported at baseline, these conditions could change over time. Also, the study authors did not have details on how the participants were managing their migraines and vascular conditions. Other limitations include the lack of generalizability to other populations and a lack of reporting whether patients experienced changes in migraine frequency.

Lastly, this study shows association, not causation, and requires confirmation through further research.

  1. Migraine with aura appeared to increase a woman’s risk of CVD and was more strongly associated with the rate of major CVD than obesity or unfavorable lipid levels, with an association comparable to elevated systolic blood pressure or high total cholesterol.

  2. Be aware that while this is a large cohort study from the Women’s Health Study, its findings only show association, not causation, and require confirmation through further research.

Candace Hoffmann, Managing Editor, BreakingMED™

Kurth reported receiving personal fees from Eli Lilly, Newsenselab, CoLucid, Total, Novartis, and Daiichi Sankyo, as well as grants from Amgen during the conduct of the study and personal fees from BMJ outside the submitted work.

Cat ID: 35

Topic ID: 82,35,308,914,35,192,925