Migraine Linked to Higher Stroke Risk After Surgery

Megan Brooks

January 13, 2017

Surgery patients with migraine are at increased risk for ischemic stroke in the perioperative period and hospital readmission within 30 days of discharge, a hospital registry study suggests.

"Migraine should be incorporated in the assessment for risk of perioperative stroke," Matthias Eikermann, MD, PhD, from Massachusetts General Hospital and Harvard Medical School in Boston, told Medscape Medical News.

The study was published online January 10 in the British Medical Journal.

High Readmission Rate

"An association between a history of migraine and increased risk of ischemic stroke has been established by many epidemiological studies. However, those studies showed an association over a long period of time," Dr Eikermann said.

For the study the investigators assessed the risk for perioperative ischemic stroke and hospital readmission in surgical patients with and without migraine. They had data on 124,558 patients who had surgery at Massachusetts General Hospital and two affiliated community hospitals between January 2007 and August 2014. The patients had a mean age of 52.6 years, and a little more than half were women (54.5%).

Altogether, 10,179 (8.2%) patients had any migraine diagnosis, of whom 1278 (12.6%) had migraine with aura and 8901 had (87.4%) had migraine without aura.

According to the authors, 771 (0.6%) perioperative strokes occurred within 30 days of surgery. The highest rate of perioperative strokes occurred after vascular surgery (4.0%), followed by cardiac (3.5%) and neurosurgical (2.4%) procedures, which are considered to be high-risk surgical procedures for perioperative thromboembolic complications, the researchers say.

Overall, compared with patients without migraine, patients with migraine had an increased risk for perioperative ischemic stroke (adjusted odds ratio [OR], 1.75; 95% confidence interval [CI], 1.39 - 2.21). The association remained after adjustment for disease and surgery factors, such as age, sex, and pre-existing vascular disease, that may pose an increased risk for stroke.

The perioperative stroke risk was higher in patients with migraine with aura (adjusted OR, 2.61; 95% CI, 1.59 - 4.29) than in those with migraine without aura (adjusted OR, 1.62; 95% CI, 1.26 - 2.09).

The researchers note that for every 1000 surgical patients, the predicted absolute risk for perioperative ischemic stroke is 2.4. This increases to 4.3 for every 1000 patients with any migraine diagnosis, 3.9 for migraine without aura, and 6.3 for migraine with aura.

In total, 10,088 patients were readmitted to hospital within 30 days of surgery and patients with migraine had a higher rate of readmission (adjusted OR, 1.31; 95% CI, 1.22 - 1.41).

"Our results indicating that migraine is associated with an increased risk of 30- day hospital readmission are important to both patients and hospital administrators. Readmissions strain healthcare systems with a large economic burden and serve as clinical performance measurement," Dr Eikermann said.

Practice Guideline Implications

In exploratory analyses, patients with migraine had statistically significantly higher frequencies of readmission due to neurologic diseases (P < .001), diseases of the circulatory system (P = .002; also in the subgroup "cerebrovascular disease," P = .005), diseases of the digestive system (P = .04), and "signs, symptoms, and ill-defined conditions," such as pain, syncope/collapse, or nausea/vomiting (P < .001), the researchers note.

"Our data show that patients with migraine do not only get readmitted more frequently for stroke but also due to other signs of symptoms associated with migraine, such as gastrointestinal symptoms and pain," said Dr Eikermann.

"Possible preventable risk factors for perioperative stroke in patients with migraine which have been identified in our exploratory analysis should be considered and further analyzed in future studies," he added.

It's possible, added Dr Eikermann, that "pain, hypotension, dehydration, and perioperative withholding of anticoagulation therapy may aggravate surgery- induced hypercoagulability and further facilitate perioperative thrombus formation in patients with migraine, resulting in ischemia and induction of spreading depolarization in migraine-susceptible brains."

"Perioperative physicians, such as surgeons and anesthesiologists, should take the new knowledge on the migraine-stroke association into account as they write treatment guidelines to prevent perioperative thromboembolic events," he said.

"In addition, clinicians taking care of patients with migraine perioperatively may pay more attention to other signs and symptoms that we know frequently lead to hospital readmissions, such as pain and gastrointestinal symptoms such as nausea and vomiting."

"Provocative" Study Raises Questions

Reached for comment, Dr Noah Rosen, director, Northwell Health's Headache Center in Great Neck, New York, described the study as "interesting and provocative."

"However, it raises more questions than it answers. It is important to know that a history of migraine, particularly migraine with aura, may be a risk factor for perioperative stroke, but the connection itself is unclear."

It's unclear whether certain surgeries pose more of a risk than others, Dr Rosen said.

"For example, are surgeries involving blood vessels more risky, or longer surgeries? Are small, brief surgeries safer? Additionally, is migraine itself the risk, or undiagnosed comorbid conditions such as incomplete blood vessels in the brain (circle of Willis), holes in the heart (patent foramen ovale), arteriovenous shunts or even depression and anxiety?"

Dr Rosen also wondered whether the risk could be explained by the medications being used for migraine treatment, such as triptans for acute care or valproic acid for preventive treatment.

Other questions include whether patients with migraine were more likely to see doctors and therefore have surgical issues come to the attention of a physician and whether hospitalizations were prolonged because of complications due to migraine events and that increased the risk.

"Overall this is an interesting study — particularly in light of other research that shows women with migraine (particularly migraine with aura) are at a higher stroke risk. However, much more work needs to be done to elucidate this issue," he said.

The study had no commercial funding. Dr Eikermann has received funding for research projects from Merck, has an equity stake at Calabash Bioscience Inc, and received funding from a research grant from the Buzen Fund, established by Jeffrey Buzen and Judith Buzen.

BMJ. Published online January 10, 2017. Full text

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