Untreated Migraine Associated With Increased Arterial Stiffness

arteriosclerosis, narrowing blood vessels
arteriosclerosis, narrowing blood vessels
Patients with untreated migraine have increased arterial stiffness and plasma dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) levels.

Patients with untreated migraine have increased arterial stiffness and plasma dephosphorylated-uncarboxylated matrix-Gla-protein (dp-ucMGP) levels, compared with age- and sex-matched controls, according to study results published in Headache.

Previous studies have reported an association between migraine and increased cardiovascular risk and arterial stiffness, although the underlying mechanism for this association is unclear. Arterial stiffness is a functional marker of vascular disease. Vitamin K2 has protective properties against arterial calcification. Plasma concentration of dp-ucMGP may reflect vitamin K2 status and was found to be associated with the extent of vascular calcification, arterial stiffness, and development of cardiovascular events among patients without migraine.

The goal of the current study was to assess arterial stiffness and vitamin K2 status among patients with migraine, compared with controls.

The case-control, observational study included patients diagnosed with migraine at the Hamidy Medical Center outpatient clinic, Tripoli, Lebanon, and age- and sex-matched controls selected from visitors to the same center. Arterial stiffness was measured using carotid-femoral pulse wave velocity (cfPWV), and plasma dp-ucMGP levels were used as a marker for vitamin K2 status.

The cohort included a total of 146 participants: 73 patients with migraine and 73 matched controls (mean age 31.9±8.4 years, 89.0% women).

Compared with healthy controls, subjects with migraine had statistically significantly higher levels of serum dp-ucMGP (454.3 ± 116.7 vs 379.8 ± 126.6 pmol/L, P <.001), worse cfPWV (7.2 ± 1.1 vs 6.4 ± 0.8 m/s, P <.001), and faster heart rates (77.5 ± 10.2 vs 70.6 ± 10.6 beats per minute, P <.001).

Vitamin K2 deficiency (eg, dp-ucMGP ≥ 500 pmol/L) was numerically more frequent among subjects with migraine (31.5% [23/73]), compared with the control group (21.9% [16/73]), but this difference was not statistically significant (P =.193).

An additional exploratory analysis, comparing patients who have migraine with aura with age- and sex-matched healthy controls, revealed an independent association between cfPWV and dp-ucMGP levels with a 0.18-m/s cfPWV increase for every 100-pmol/L increase in dp-ucMGP. This association was not evident in patients with migraine without aura, compared with their matched healthy controls.

The study had several limitations, according to the researchers, including the observational design, small sample size, and a potential population bias and measurement bias.

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“This study demonstrates that subjects with untreated migraine have higher arterial stiffness than age and sex-matched controls and higher inactive dp-ucMGP plasma levels,” concluded the researchers. They add that “in subjects with migraine and aura, higher level of inactive dp-ucMGP is significantly associated with increased arterial stiffness.”

Disclosure: This clinical trial was supported by Nattopharma ASA, Norway and Omicron Pharmaceuticals, Lebanon. Please see the original reference for a full list of authors’ disclosures.


Mansour AG, Ahdab R, Daaboul Y, et al. Vitamin K2 Status and arterial stiffness among untreated migraine patients: a case-control study [published online ahead of print, 2019 Nov 25]. Headache. 2019;10.1111/head.13715. doi:10.1111/head.13715