Elevated C-Reactive Protein Levels Linked With Migraines Occurring 15 Days or More, or With Aura

A recent study examined whether some earlier research that found increased high sensitivity C-reactive protein (hs-CRP) levels in patients with migraine as well as patients with migraine and insomnia could be reproduced in a large-scale population-based study in Norway.

Researchers said the previous results on hs-CRP and migraine are mixed, and the relationship to insomnia limited; the aim of this study was to evaluate the cross-sectional association between hs-CRP and types of headache, and to see whether the relationship to insomnia could be reproduced.

A total of 50,807 (54%) people out of 94,194 invited participated in the third wave of the Nord-Trøndelag Health Study (The HUNT Study) conducted in 2006—2008. The HUNT study is one of the largest health studies ever performed and began in 1984. Researchers used 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 in participants age 20 or older.

Out of the total, 38,807 (41%) had valid measures of hs-CRP and answered questions on headache and insomnia. Elevated hs-CRP was defined as > 3.0 mg/L to 20.00 mg/L from nonfasting blood samples, but those with values greater than 20.00 mg/L were excluded on the rationale that it may have indicated some acute or chronic disease.

A total of 13,990 (36.0%) participants suffered from headache during the last year, 3793 (9.8%) met the migraine criteria of migraine, 2139 (5.5%) had migraine with aura (MA), 1654 (4.3%) migraine without aura (MO), and 10,197 (26.3%) had other headaches. Cross-sectional data showed that elevated hs-CRP was associated with headache ≥7 days/month, especially evident for migraine with aura.

Subjects with headache were more likely to be women, younger, and employed compared with those without headache.

After adjusting for all potential confounding factors, elevated hs-CRP was associated with migraine (OR, 1.14; 95% CI, 1.04—1.25) and migraine with aura (OR, 1.15; 95% CI, 1.03–1.29).

The association was strongest among individuals with headache ≥15 days/month for any headache (OR, 1.26; 95% CI, 1.08—1.48), migraine (OR, 1.62; 95% CI, 1.21–2.17), and migraine with aura (OR, 1.84; 95% CI, 1.27–2.67). No clear relationship was found between elevated hs-CRP and headache less than 7 days per month or with insomnia.

The authors said it may be noteworthy that hs-CRP is linked with risk of cardiovascular events, and that ischemic cardiovascular disease has a stronger association to migraine with aura than to migraine without aura.

Reference

Hagen K, Stovner LJ, Nilsen KB, Kristoffersen ES, Winsvold BS. The impact of C-reactive protein levels on headache frequency in the HUNT study 2006—2008 [published online September 26, 2019]. BMC Neurology. doi: 10.1186/s12883-019-1462-8.