The Burden of Migraine in Adults with Atrial Septal Defect: A Nationwide Cohort Study

DOI: https://doi.org/10.1038/s41598- 019- 43895- z

Abstract-Summary We aimed to investigate migraine diagnoses in a hospital setting, use of prescription migraine medicine and levels of serotonin in patients with atrial septal defect.

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2 Mechanisms

Patients with atrial septal defect had an increased risk of receiving a migraine diagnosis (HR 3.4 (95% CI: 2.6–4.6)) and receiving migraine medicine (HR 1.8 (95% CI: 1.2–2.5)).

The risk of having very high plasma serotonin levels was increased in patients with atrial septal defect compared with the control group, but there was no differ- ence in the median values between the two groups.

Migraine and use of migraine medicine were increased in atrial septal defect

patients.

Plasma serotonin was severely elevated in 18% of the patients with atrial sep-

tal defect.

Extended: The risk of being diagnosed with migraine when symptoms appear could be elevated compared with patients who might never be hospitalized, thus overestimating the risk of migraine in the ASD patients.

The risk of using migraine medicine is not reduced 10 year after closure.

Introduction Migraine has been widely associated with right-to-left shunts and the incidence in patients with a persistent foramen ovale (PFO) [423] is reported as high as 25–40% [424, 425].

Migraine has also been related to cerebral embolisms, and supports the theory of both platelet activation and shear stress induced by the embolism, as well as micro embolisms through the shunt as an independent activator of migraine, and platelet inhibitors have shown good results in symptom reduction in migraine patients with PFO [426–429].

In patients with an atrial septal defect (ASD) [430], the primary shunt direction

is left-to-right.

Several studies have linked ASDs with migraine and found prevalences similar to that seen in right-to-left shunts [423, 431–433] with suggestions that size of the shunt influences the risk of migraine [434].

We seek to investigate the burden of migraine in the ASD patients by investigat- ing their risk of hospitalisation with a migraine diagnosis, the use of prescription migraine medicine both before and after closure and the levels of serotonin in patients with an unclosed shunt.

Methods We included all patients registered with an ASD diagnosis in The Danish National Patient Registry (DNPR), which contains information on all in and out patient hos- pital contacts since 1977 including all diagnoses, dates of admission, dates of dis- charge and procedures performed.

The ASD diagnosis of all patients identified in the registry was validated manu-

ally by review of medical records by two independent physicians.

During this review, a small number of patients had an ASD diagnosis or closure

performed before the initiation of the Danish national patient registry.

2.3 Comorbidities

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We included a separate population of ASD patients after validation of hospital records of patients under the age of 15 years given an ASD diagnosis in Danish hospitals between 1963 and 1974.

Cox proportional hazards regression was used to determine hazard ratios (HR) of receiving a migraine diagnosis for ASD patients, from birth or the beginning of the registry.

Results 62 (2.74%) ASD patients received prescription migraine medicine, which was sig- nificantly higher than in the comparison cohort where 368 (1.62%) received medi- cine (p < 0.001).

The overall risk of receiving prescription migraine medication was increased in the ASD patients compared with the comparison cohort with a HR adjusted for gender and stroke of 1.8 (95% CI: 1.2–2.5).

For patients with no closure, 22 received migraine medicine, which was signifi- cantly more than in the comparison cohort where 106, received migraine medicine (p = 0.001), HR 2.2 (95% CI: 1.4–3.5).

In patients with closure of the defect, a total of 40 patients received migraine

medicine.

The risk of receiving migraine medicine after closure, for those with no previous history of migraine medicine prescriptions, was not statistically different from the comparison cohort (HR 1.44, 95% CI: 0.8–2.5).

Discussion In this nationwide cohort study we found that patients with an ASD had an increased risk of receiving a migraine diagnosis compared with the comparison cohort, regard- less of closure of the defect.

The increased risk of using prescription migraine medicine in the ASD patients supports the finding that these patients have either; a higher prevalence of migraine, or the severity of the migraine is increased, thus requiring medicine more often than the comparison cohort.

The risk of receiving prescription migraine medicine was not significantly increased in patients with no history of migraine before closure when compared with the background population, indicating that the risk of severe de novo migraine might not be increased after closure.

Patients with an ASD have an increased risk of receiving a hospital related migraine diagnosis, of receiving prescription migraine medicine and have a higher risk of having very high plasma serotonin levels when compared with a gender and age matched comparison cohort.

Acknowledgement A machine generated summary based on the work of Nyboe, Camilla; Nymann, Ann Hyldahl; Ovesen, Anne-Sif; Elisabeth Hjortdal, Vibeke. 2019 in Scientific Reports.

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