Does insomnia modify the association between C-reactive protein and migraine? The Tromsø Study 2015–2016

Abstract

Background The relationship between high sensitivity C-reactive protein and migraine is unclear. The aim of this cross-sectional population-based study was to investigate the association between high sensitivity C-reactive protein and types of headache, and to evaluate the impact of insomnia on this association. Methods A total of 20,486 (63%) out of 32,591 invited, aged ≥40 years or older, participated in the seventh wave of the Tromsø study conducted in 2015–2016 and had valid information on headache, insomnia and high sensitivity C-reactive protein. The influence of insomnia on the association between questionnaire-based diagnoses of headache and elevated high sensitivity C-reactive protein defined as >3.0 mg/L was assessed using multiple logistic regression, estimating prevalence odds ratio with 95% confidence intervals. Results A total of 6290 participants (30.7%) suffered from headache during the last year. Among these, 1736 (8.5%) fulfilled the criteria of migraine, 991 (4.8%) had migraine with aura, 746 (3.6%) migraine without aura (3.8%), and 4554 (22.2%) had non-migrainous headache. In the final multi-adjusted analysis, elevated high sensitivity C-reactive protein was associated with headache (odds ratio 1.10, 95% confidence interval 1.01–1.20), migraine (odds ratio 1.17, 95% confidence interval 1.01–1.35), and migraine with aura (odds ratio 1.23, 95% confidence interval 1.01–1.53). No association was found between elevated high sensitivity C-reactive protein and migraine without aura or non-migrainous headache. The association between high sensitivity C-reactive protein and migraine was strongly dependent on insomnia status. Among individuals with insomnia, elevated high sensitivity C-reactive protein was associated with migraine (odds ratio 1.49, 95% confidence interval 1.02–2.17), and migraine with aura (odds ratio 1.59, 95% confidence interval 1.03–2.45), whereas no such relationship was found among those without insomnia. Conclusions In this cross-sectional study, participants with migraine, in particular migraine with aura, were more likely to have elevated high sensitivity C-reactive protein, evident only among those with insomnia.

The impact of C-reactive protein levels on headache frequency. The HUNT Study 2006-2008

“…The detection limit was 0.03 mg/L, and samples without detectable hs-CRP were assigned this value. In the present study we replicated the strategy used in previous published studies from the Tromsø study [29,31] defining normal hs-CRP as 0-3.00 mg/L and elevated as 3.01-20.00 mg/L. Participants with hs-CRP values >20.00 mg/L, which probably indicate some acute or chronic disease [32], were excluded (n=527) ( Fig.1).…”

“…The present population-based study of a large unselected adult population replicate the methodological design used in the Tromsø Study [29], including similar questionnaire-based diagnoses for headache and insomnia, identical categories of hs-CRP, and replication of the statistical analyses with adjustments for the same type of potential confounders.…”

“…Previously, a prospective study has demonstrated higher level of CRP in individuals with shorter sleep duration [28]. In a recent population-based cross-sectional study from Northern Norway, elevated hs-CRP was associated with migraine, but only among those with co-existing insomnia [29]. However, since the results on hs-CRP and migraine are conflicting, and the relationship to insomnia only reported in one study, it is important to replicate the analyses in other population-based study with similar design.…”

“…All details of the headache questionnaire have been published elsewhere [33], and all questionnairebased headache diagnoses were identical to those presented in the Tromsø study [29]. Subjects who answered "no" to the screening question ("Have you suffered from headache during the last 12 months?")…”

“…The questionnaire-based diagnosis of insomnia was based on the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, 5th ed. ), and was nearly identical to the insomnia diagnosis used in the Tromsø study [29]. To fulfil the proxy diagnosis of insomnia the participants had to answer "several times a week" to at least one out of the three questions, asking whether they had "difficulties falling asleep at night", whether they "woke up repeatedly during the night", and/or whether they "woke up too early and could not get back to sleep" [36].…”