Migraine and subclinical atherosclerosis: endothelial dysfunction biomarkers and carotid intima-media thickness: a case-control study

DOI: https://doi.org/10.1007/s10072- 019- 3710- 5

Abstract-Summary This study evaluated the relationships between plasma endothelial dysfunction bio- markers and carotid intima–media thickness (IMT) in young adult females with migraine.

The CRP, TBARS, vWF, and IMT levels were increased in the migraine com- pared with the control group (p < 0.001, p = 0.02, p < 0.001, and p < 0.001, respectively).

After adjusting for confounders, multiple linear regression analysis revealed that systolic arterial blood pressure, CRP, vWF, TBARS, and right and left internal carotid artery (ICA) IMT were independently positively correlated with migraine (p < 0.01, p = 0.004, p = 0.023, p = 0.024, p = 0.032, and p = 0.048, respectively).

Multiple logistic regression analysis revealed that right ICA IMT was indepen- dently associated with ergotamine and triptan and left ICA IMT was independently associated with ergotamine (p = 0.013, p = 0.026, and p = 0.017, respectively).

Significant correlations were found between LDL lipoprotein and carotid IMT in

the migraine group (p < 0.05).

Carotid IMT enhancement and elevated TBARS, vWF, and CRP levels in migraine subjects during a migraine attack could be regarded as consequences of migraine attack pathophysiology.

The independent associations between triptan and ergotamine consumption and enhanced carotid IMT suggest that repeated use of these vasoconstrictive antimi- graine agents may have additional effects on carotid IMT.

Extended: After adjusting for age, differences between the M and control groups

persisted for vWF, TBARS, and carotid IMT.

After adjusting for confounders, multiple linear regression analysis revealed no

significant differences between M with and without aura.

Carotid IMT enhancement and elevated TBARS, vWF, and CRP levels in M subjects during M attack, which are signs of subclinical atherosclerosis and endo- thelial dysfunction, could be regarded as the consequences of M attack pathophysiology.

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2 Mechanisms

The independent associations of triptan and ergotamine use with carotid IMT enhancement suggest that repeated use of these vasoconstrictive antimigraine agents may have an additional influence on the carotid IMT.

Introduction It has been reported that certain features of the systemic and cranial vascular struc- tures change during an M attack and between attacks [404, 531].

The inflammatory process in M and the associated vascular risk may disrupt the vascular endothelial function and structure of the vascular wall and may lead to atherosclerosis and vascular disease.

Endothelial dysfunction has been reported in M, and carotid IMT was recently

reported to be increased in M [532–535].

Only a few studies have investigated the relationships between various endothe- lial function biomarkers and carotid IMT in M, and these have obtained conflicting results [532, 536].

This study evaluated the plasma biomarkers related to endothelial function and the carotid IMT, as a marker of structural vascular impairment, in young adult females with M and assessed the correlations of endothelial plasma biomarkers with carotid IMT.

Methods Exclusion criteria included (1) history of M < 1 year; (2) >15 days of headache per month; (3) use of antimigraine drugs > 10 days/month; (4) history of cerebrovascu- lar or cardiovascular disease, arterial hypertension (blood pressure > 140/90 mmHg), diabetes mellitus, or hyperlipidemia (low-density lipoprotein cholesterol ≥ 160 mg/dL); (5) body mass index (BMI) <18 kg/m2 or >35 kg/m2; (6) smoke >1 pack/day cigarettes; (7) current pregnancy, lactation, or hormonal contraceptive use; (8) alcohol or substance abuse; (9) drug use (e.g., antiplatelet agents, anticoagu- lants, statins, or hormonal drugs); and (10) possible “symptomatic migraine” in which magnetic resonance imaging showed arteriovenous malformations, ischemic infarcts, brain tumors, or other conditions that may be associated with M. Patients with high CRP (≥10 mg/L) levels were excluded from the study because such levels may represent nonspecific inflammation and lack positive predictive value [537].

Results After adjusting for confounders, multiple linear regression analysis revealed no sig- nificant differences between M with and without aura.

Univariate analysis revealed significant correlations between LDL lipoprotein and right common carotid artery (CCA; r = 0.451, p = 0.018) and right bulbus (r = 0.376, p = 0.028) IMT in the M group.

There were significant correlations between VAS and vWF (r = 0.230, p = 0.049) and between M duration and right CCA (r = 0.281, p = 0.015), left CCA (r = 0.261, p  =  0.025), right bulbus (r = 0.344, p  =  0.003), and left bulbus (r = 0.282, p = 0.015) IMT.

After adjusting for confounders, a multiple linear regression analysis revealed

that M duration was independently positively correlated with right ICA IMT.

2.4 Lifestyle

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Discussion Previous studies reported no differences in the endothelial dysfunction biomarkers of the M and control groups [538, 539].

Although the endothelial dysfunction biomarkers were high during an attack and the carotid IMT thickness was increased in the M group, we did not find any correla- tions between carotid IMT and endothelial dysfunction biomarkers.

Contrasting our study, coagulation factor II was associated with migraine, espe- cially M with aura, in the previous study, which included older participants, both sexes, and those with vascular risk factors [533].

Contrasting our results, a previous study reported that the CRP levels of M patients and controls were similar; however, the previous study included those with vascular risk factors and concomitant diseases, and the mean age of participants in that research was 55 years [540].

The strength of our study is that it is the first to assess the relationship between endothelial dysfunction markers and carotid IMT in young adult female M partici- pants with restricted vascular risk factors.

Conclusions Carotid IMT enhancement and elevated TBARS, vWF, and CRP levels in M sub- jects during M attack, which are signs of subclinical atherosclerosis and endothelial dysfunction, could be regarded as the consequences of M attack pathophysiology.

Early diagnosis and adequate M prophylaxis to reduce M attack frequently could

prevent the progression of atherosclerosis in young adult M females.

Acknowledgement A machine generated summary based on the work of Yilmaz Avci, Aynur; Akkucuk, Mehmet Husamettin; Torun, Ebru; Arikan, Serap; Can, Ufuk; Tekindal, Mustafa Agah. 2019 in Neurological Sciences.

2.4

Lifestyle

Machine generated keywords: dietary, intake, sleep, diet, exercise, food, trigger, physical activity, episodic migraine, stress, trigger migraine, health, prevention, improve, review

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