- •Migraine is associated with a reduced cerebrovascular reactivity (CVR) compared to normal controls.
- •Younger age is associated with reduced CVRs of the posterior cerebral artery (PCA) in patients with migraine.
- •Younger age of onset fully explains the reduced PCA CVR in younger migraineurs.
- •Longer disease duration negatively modifies the effect of age of onset on the PCA CVR.
Previous studies reported an increased risk of ischemic stroke in younger migraineurs. We aimed to investigate the association between age and cerebrovascular reactivity (CVR) to vasodilatory stimuli in cerebral arteries in patients with migraine and normal controls.
In this cross-sectional study, we recruited 248 patients with migraine and 105 normal controls at Samsung Medical Center between October 2015 and July 2018. CVR was measured interictally by using the transcranial Doppler breath-holding test. For the arteries which showed a correlation between age and CVR, we conducted univariable and multivariable linear regression analysis to assess the independent effect of age on CVR. The path analysis was performed to assess mediating effects of the age of onset and disease duration on the age-CVR association.
Patients had reduced CVR in all tested arteries compared to normal controls. A correlation between age and CVR was present in the posterior cerebral artery (PCA) only in patients (Pearson's correlation coefficient = 0.160, p = 0.012). In patients, younger age was independently associated with lower CVR in the PCA (multivariable B = 0.003, 95% CI = 0.0002–0.005, p = 0.033 adjusted for sex, migraine subtype, and headache frequencies). The path analysis showed that the age of onset fully mediated the effect of age on PCA CVR, while longer disease duration negatively modified the effect of age of onset (p for interaction = 0.018).
In migraineurs, younger age was associated with CVR reduction in the PCA. Younger age of onset may be a hidden risk factor mediating the paradoxical association between age and CVR. This association might explain an increased risk of stroke in younger migraineurs.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of the Neurological Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Risk of ischaemic stroke in people with migraine: systematic review and meta-analysis of observational studies.BMJ. 2005; 330: 63
- Migraine and risk of cardiovascular disease in women.JAMA. 2006; 296: 283-291
- The migraine-stroke connection.J. Stroke. 2016; 18: 146-156
- Migraine and cardiovascular disease: systematic review and meta-analysis.BMJ. 2009; 339: b3914
- Migraine and hemorrhagic stroke: a meta-analysis.Stroke. 2013; 44: 3032-3038
- Migraine and risk of cardiovascular disease in women: prospective cohort study.BMJ. 2016; 353i2610
- Migraine and stroke: a complex association with clinical implications.Lancet Neurol. 2012; 11: 92-100
- Migraine and incidence of ischemic stroke: a nationwide population-based study.Cephalalgia. 2017; 37: 327-335
- Stroke epidemiology: a review of population-based studies of incidence, prevalence, and case-fatality in the late 20th century.Lancet Neurol. 2003; 2: 43-53
- Decreased number and function of endothelial progenitor cells in patients with migraine.Neurology. 2008; 70: 1510-1517
- Interictal cerebral and systemic endothelial dysfunction in patients with migraine: a case-control study.J. Neurol. Neurosurg. Psychiatry. 2015; 86: 1253-1257
- Endothelial progenitor cells: a new key for endothelial dysfunction in migraine.Neurology. 2012; 79: 474-479
- Migraine and biomarkers of endothelial activation in young women.Stroke. 2009; 40: 2977-2982
- Cerebrovascular reactivity to l-arginine in the anterior and posterior cerebral circulation in migraine patients.Acta Neurol. Scand. 2011; 124: 269-274
- Systemic and cerebral endothelial dysfunction in chronic migraine. A case-control study with an active comparator.Cephalalgia. 2016; 36: 552-560
- Migraine as a risk factor for subclinical brain lesions.JAMA. 2004; 291: 427-434
- Development of White matter hyperintensity is preceded by reduced cerebrovascular reactivity.Ann. Neurol. 2016; 80: 277-285
- S. Headache Classification Committee of the International Headache, The International Classification of Headache Disorders, 3rd edition (beta version), Cephalalgia. 33. 2013: 629-808
- Peripheral vascular dysfunction in migraine: a review.J. Headache Pain. 2013; 14: 80
- Pulse wave velocity study in middle-aged migraineurs at low cardiovascular disease risk.Headache. 2011; 51: 1239-1244
- Cranial and peripheral interictal vascular changes in migraine patients.Cephalalgia. 2003; 23: 96-104
- Endothelial function in migraine: a cross-sectional study.BMC Neurol. 2010; 10: 119
- Markers of endothelial function in migraine patients: results from a bi-center prospective study.Cephalalgia. 2015; 35: 877-885
- Migraine and endothelial function: the HUNT3 Study.Cephalalgia. 2016; 36: 1341-1349
- A systematic review of dynamic cerebral and peripheral endothelial function in lacunar stroke versus controls.Stroke. 2010; 41: e434-e442
- Endothelial function and dysfunction: testing and clinical relevance.Circulation. 2007; 115: 1285-1295
- Endothelial function testing as a biomarker of vascular disease.Circulation. 2003; 108: 2054-2059
- Endothelial and smooth muscle cells dysfunction distal to recanalized chronic total coronary occlusions and the relationship with the collateral connection grade.JACC Cardiovasc. Interv. 2012; 5: 170-178
- Induction of vascular progenitor cells from endothelial cells stimulates coronary collateral growth.Circ. Res. 2012; 110: 241-252
- Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease.Neurology. 2014; 83: 1424-1431
- Association between migraine and cervical artery dissection: the Italian project on stroke in young adults.JAMA Neurol. 2017; 74: 512-518
- Ischemic stroke subtypes and migraine with visual aura in the ARIC study.Neurology. 2016; 87: 2527-2532
- Cerebrovascular reactivity to acetazolamide and outcome in patients with symptomatic internal carotid or middle cerebral artery occlusion: a xenon-133 single-photon emission computed tomography study.Stroke. 2002; 33: 1857-1862
- Spreading depolarization may link migraine and stroke.Headache. 2014; 54: 1146-1157
- Vulnerability to infarction during cerebral ischemia in migraine sufferers.Stroke. 2018; 49: 573-578
- Migraine headache and ischemic stroke risk: an updated meta-analysis.Am. J. Med. 2010; 123: 612-624
- Migraine and risk of stroke: a national population-based twin study.Brain. 2017; 140: 2653-2662
- Endothelin-1 potently induces Leao's cortical spreading depression in vivo in the rat: a model for an endothelial trigger of migrainous aura?.Brain. 2002; 125: 102-112
- Structural brain changes in migraine.JAMA. 2012; 308: 1889-1897
Published online: January 24, 2019
Accepted: January 23, 2019
Received in revised form: January 8, 2019
Received: September 26, 2018
© 2019 Elsevier B.V. All rights reserved.