Liam Davenport

June 23, 2016

SAN DIEGO — Levels of the inflammatory marker C-reactive protein (CRP) are significantly elevated in young adults with migraine, which may not only offer insights into the pathogenesis of the condition but also point to novel therapeutic avenues, researchers say.

Delegates here at the American Headache Society (AHS) 58th Annual Scientific Meeting heard that levels of the protein, as measured on high-sensitivity CRP (hsCRP) assay, were higher by 11% in people with migraine compared with those in unaffected individuals, rising to 17% among women.

Gretchen Tietjen, MD, professor and chair of neurology and director of UTMC Headache Treatment and Research Program, University of Toledo, Ohio, and colleagues say the study findings show "a positive association between migraine diagnosis and elevated hsCRP, with a significant effect size," particularly in young women.

Conflicting Results

Although there has been a great deal of interest in potential association between markers of inflammation and migraine, the evidence linking increased CRP levels with the condition is limited, and there have been conflicting results from population-based studies. However, it is notable that those studies were conducted in different age groups from that in the current analysis.

The researchers therefore examined data on 9269 adults aged 24 to 32 years taking part in Wave 4 of the Add Health Study, as part of which participants discussed diagnoses of migraine, depression, and anxiety with their healthcare provider. In addition, dried capillary whole blood spots were obtained from the individuals during in-home visits, on which blood hsCRP assay was performed.

The team found that 1049 (11.3%) participants reported migraine.

Linear regression analysis, taking into account sociodemographic factors, body mass index, infections, current pregnancies, subclinical symptoms, anxiety, and depression, indicated that mean hsCRP levels were significantly higher in individuals with migraine than in those without.

Specifically, participants with migraine had an hsCRP level of 5.54 ± 9.04 mg/L vs 4.40 ± 7.47 mg/L in those without migraine (P < .001).

Although women had higher mean hsCRP levels than men, the difference in levels between those with and without migraine was significantly different only in men, at 3.63 ± 6.32 mg/L vs 3.05 ± 5.25 mg/L in men (P = .03) and 6.26 ± 9.78 mg/L vs 5.75 ± 8.97 mg/L in women (P = .08).

Interestingly, when all potential confounding factors were taken into account, migraine was significantly associated with log hsCRP levels across the whole sample, at an r value of 0.11 (P = .04), and in women, at an r value of 0.17 (P = .01), but not in men (r = 0.01; P = .94).

Dr Tietjen believes that the relationship between CRP levels and migraine could be direct. "I think that it is possible that it is a consequence of having migraine, in that, when there's changes within the brain in the endothelium, that can increase levels of things like [CRP] and inflammation," she said.

Noting that the relationship was more pronounced in women, she added: "Whether it has something to do with endothelial activation being more easily triggered in women than in men I think is interesting, but I don't think we can say for sure why we would see it more frequently in women than men."

Nevertheless, Dr Tietjen said the current findings may point to therapies that target inflammation in general, and CRP levels in particular, potentially being beneficial in migraine.

She highlighted the JUPITER trial, in which the statin rosuvastatin was shown to reduce the incidence of major cardiovascular events in individuals with high CRP levels, although she acknowledged that concerns have been raised about the study's methodology.

In addition, Catherine Buettner MD, MPH, and colleagues conducted a randomized, double-blind, placebo-controlled trial of simvastatin plus vitamin D, finding that the combination is effective for prevention of headache in adults with episodic migraine.

"Why would it be an effective migraine treatment unless something tied into the migraine pathogenesis had either something to do with cholesterol or inflammation or something that statins actually work on?" Dr Tietjen commented.

"I did think that that was very intriguing, as [CRP] might be something that would guide us as to which patients would be most likely to respond to which therapies," she added.

Dr Tietjen concluded: "I think it's an area ripe for more study, but I do believe that it makes sense in what we're learning both about the importance of the endothelium potentially in migraine and the fact that we are seeing that some therapies that actually have an effect on [CRP] may be effective in migraine in a relatively young, healthy population of people."

Commenting on these findings, Stephen Silberstein, MD, professor, Department of Neurology, Thomas Jefferson University and Jefferson Health, and director, Jefferson Headache Center, Department of Neurology, Jefferson Hospital for Neuroscience, Philadelphia, Pennsylvania, said the results "look interesting."

However, he told Medscape Medical News that the wide overlap in the confidence intervals were "of concern" and limited the degree to which the study could be interpreted.

No funding declared. The authors have disclosed no relevant financial relationships.

American Headache Society (AHS) 58th Annual Scientific Meeting: Abstract 182685. Presented June 9, 2016.

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