Comorbid and co-occurring conditions in migraine and associated risk of increasing headache pain intensity and headache frequency: results of the migraine in America symptoms and treatment (MAST) study

DOI: https://doi.org/10.1186/s10194- 020- 1084- y

Abstract-Summary Migraine has many presumed comorbidities which have rarely been compared between samples with and without migraine.

Examining the association between headache pain intensity and monthly head- ache day (MHD) frequency with migraine comorbidities is novel and adds to our understanding of migraine comorbidity.

Modeling within the migraine cohort assessed rates of conditions as a function of

headache pain intensity, MHD frequency, and their combination.

People with migraine were significantly (p < 0.001) more likely to report insom- nia (OR 3.79 [3.6, 4.0]), depression (OR 3.18 [3.0, 3.3]), anxiety (OR 3.18 [3.0 3.3]), gastric ulcers/GI bleeding (OR 3.11 [2.8, 3.5]), angina (OR 2.64 [2.4, 3.0]) and epilepsy (OR 2.33 [2.0, 2.8]), among other conditions.

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Increasing headache pain intensity was associated with comorbidities related to inflammation (psoriasis, allergy), psychiatric disorders (depression, anxiety) and sleep conditions (insomnia).

Increasing MHD frequency was associated with increased risk for nearly all con- ditions and most prominent among those with comorbid gastric ulcers/GI bleeding, diabetes, anxiety, depression, insomnia, asthma and allergies/hay fever.

In regression models controlled for sociodemographic variables, all conditions

studied were reported more often by those with migraine.

Whether entered into the models separately or together, headache pain intensity

and MHD frequency were associated with increased risk for many conditions.

Extended: Increasing MHD frequency was associated with increased risks for

nearly all conditions.

Increasing MHD frequency was associated with increasing risk for angina (5–9

MHDs, ≥21 MHDs) and hypertension (5–9 MHDs, ≥21 MHDs).

Increasing MHD frequency was associated with increasing risk for all general medical conditions studied: gastric ulcer/GI bleeding (5–9 MHDs OR 1.24 [1.01, 1.52], ≥21 MHDs OR 2.21 [1.63, 2.99]), kidney disease (5–9 MHDs OR 0.95 [0.68, 1.34], ≥21 MHDs OR 1.52 [0.93, 2.49]), vitamin D deficiency (5–9 MHDs OR 1.08 [0.97, 1.19], ≥21 MHDs OR 1.66 [1.39, 1.99]) and diabetes (5–9 MHDs OR 1.20 [1.04, 1.40], ≥21 MHDs OR 2.00 [1.59, 2.51]).

Increasing MHD frequency was associated with increasing risk for anxiety (5–9 MHDs OR 1.33 [1.22, 1.46], ≥21 MHDs OR 2.13 [1.8, 2.53]), depression (5–9 MHDs 1.31 [1.2, 1.44], ≥21 MHDs OR 2.26 [1.91, 2.69]) and insomnia (5–9 MHDs 1.47 [1.33, 1.63], ≥21 MHDs OR 2.46 [2.07, 2.94]).

Increasing MHD frequency was associated with increasing risk for asthma (5–9 MHDs OR 1.10 [0.99, 1.23], ≥21 MHDs OR 1.84 [1.53, 2.22]), allergy/hay fever (5–9 MHDs 1.23 [1.13, 1.34], ≥21 MHDs OR 1.79 [1.51, 2.12]), and rosa- cea (5–9 MHDs 0.93 [0.76, 1.15], ≥21 MHDs OR 1.47[1.05, 2.05]) but not for psoriasis.

Background Prior work has also found that rates of some comorbid health problems increased with headache day frequency among people with migraine.

The Migraine in America Symptoms and Treatment (MAST) Study was under- taken to evaluate patterns of migraine consultation, diagnosis, treatment and comor- bid health burden among a representative non-clinical sample of people with migraine with an average of at least one headache day per month.

Within the migraine cohort, we evaluated the impact of headache pain intensity, MHD frequency, and the combined effect of these variables on the rates of occur- rence for comorbid health conditions.

We aimed to lay the groundwork for more detailed study of specific condi- tions by providing an overview of population comorbidity rates in persons with active migraine as well as to examine their association with sociodemographics and key headache characteristics—headache pain intensity and headache frequency.

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2 Mechanisms

Methods Respondents meeting the symptom criteria and headache frequency criteria (3 or more headache days in the prior 3 months and at least 1 headache in the past 30 days) were included in the migraine cohort.

Respondents who did not meet migraine symptom criteria were classified as non-migraine control subjects, and those with inactive or low frequency headache were excluded from the analysis.

Multivariable binary logistic regression models were performed to assess differ- ences in the likelihood of each comorbid condition as a function of the presence of a positive migraine screen, adjusting for sociodemographics (gender, age category, Hispanic ethnicity, race, marital status, employment status, and household income). Additional binary logistic regression modeling was implemented among the migraine cohort to assess first, the association of MHD frequency with each comor- bid or associated health problem, second the association with headache pain inten- sity, and third to assess the combined effect of MHD frequency and headache pain intensity.

Results The migraine vs. non-migraine group had a higher proportion of respondents aged 18–54 and a lower proportion of those aged 55 and older (p < 0.001).

Results for peripheral artery disease followed a similar pattern for age and gen- der but only the 5–9 MHD category compared to 1–4 days was associated with a statistically significant increased risk for this condition.

The findings for hypertension and high cholesterol followed same pattern for age, gender, employment status and household income, and in addition, being mar- ried was associated with increased odds of hypertension (OR 1.12 [1.02, 1.22]) and high cholesterol (OR 1.12 [1.02, 1.23]).

For vitamin D deficiency, older age was associated with increased risk, but the risk was reduced among men, non-Hispanics, Whites, and those married and employed.

Age and being male were associated with increased risk, as was each MHD fre-

quency category.

Discussion We also found that headache pain intensity was associated with higher risk for comorbidities including gastric ulcer disease, inflammatory disorders (psoriasis, allergy) and psychiatric (anxiety, depression) and sleep conditions (insomnia).

Several studies have reported that rates of comorbidities increase by headache day frequency among people with migraine comparing people with EM and CM and/or stratifying by low, moderate and high frequency EM [339–346].

The risk of asthma in patients with migraine has been shown to be increased in a population-based cohort study of 6647 adult patients and comorbid asthma is asso- ciated with increased risk of new onset CM [347].

Finally, in assessing comorbid health problem risk in the population, compari- sons between the migraine and non-migraine cohorts were adjusted for sociodemo- graphic covariates; and this was also true in assessing the potential incremental

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comorbid health problem risk associated with headache pain intensity and increas- ing MHD frequency within the migraine cohort.

Conclusions Future work is required to differentiate the causal sequence (direct causality, reverse causality, shared underlying predisposition), the potential confounding role of migraine treatment (i.e., NSAIDs may lead to gastric ulcers), as well as shared risk factors or potential detection bias.

Exploration of the pathways that drive these comorbidities in migraine patients

may lead to insights that clarify pathophysiology and improve treatment.

Acknowledgement A machine generated summary based on the work of Buse, Dawn C.; Reed, Michael L.; Fanning, Kristina M.; Bostic, Ryan; Dodick, David W.; Schwedt, Todd J.; Munjal, Sagar; Singh, Preeti; Lipton, Richard B. 2020 in The Journal of Headache and Pain.

Psychiatric and cognitive comorbidities of persistent post- traumatic headache attributed to mild traumatic brain injury