Migraine and the risk of cardiovascular and cerebrovascular events: a meta-analysis of 16 cohort studies including 1 152 407 subjects

Abstract

ObjectivesTo perform an updated meta-analysis to evaluate the long-term cardiovascular and cerebrovascular outcomes among migraineurs.SettingA meta-analysis of cohort studies performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.Data sourcesThe MEDLINE, Web of Science and Cochrane Central Register of Controlled Trials databases were searched for relevant articles.ParticipantsA total of 16 cohort studies (18 study records) with 394 942 migraineurs and 757 465 non-migraineurs were analysed.Primary and secondary outcome measuresMajor adverse cardiovascular and cerebrovascular events (MACCE), stroke (ie, ischaemic, haemorrhagic or non-specified), myocardial infarction (MI) and all-cause mortality. The outcomes were reported at the longest available follow-up.Data analysisSummary-adjusted hazard ratios (HR) were calculated by random-effects Der-Simonian and Liard model. The risk of bias was assessed by the Newcastle-Ottawa Scale.ResultsMigraine was associated with a higher risk of MACCE (adjusted HR 1.42, 95% confidence interval [CI] 1.26 to 1.60, P<0.001, I2=40%) driven by a higher risk of stroke (adjusted HR 1.41, 95% CI 1.25 to 1.61, P<0.001, I2=72%) and MI (adjusted HR 1.23, 95% CI 1.03 to 1.43, P=0.006, I2=59%). There was no difference in the risk of all-cause mortality (adjusted HR 0.93, 95% CI 0.78 to 1.10, P=0.38, I2=91%), with a considerable degree of statistical heterogeneity between the studies. The presence of aura was an effect modifier for stroke (adjusted HR aura 1.56, 95% CI 1.30 to 1.87 vs adjusted HR no aura 1.11, 95% CI 0.94 to 1.31, P interaction=0.01) and all-cause mortality (adjusted HR aura 1.20, 95% CI 1.12 to 1.30 vs adjusted HR no aura 0.96, 95% CI 0.86 to 1.07, Pinteraction<0.001).ConclusionMigraine headache was associated with an increased long-term risk of cardiovascular and cerebrovascular events. This effect was due to an increased risk of stroke (both ischaemic and haemorrhagic) and MI. There was a moderate to severe degree of heterogeneity for the outcomes, which was partly explained by the presence of aura.PROSPERO registration number CRD42016052460.

Migraine and cerebrovascular diseases: Epidemiology, pathophysiological, and clinical considerations

“…Although 3 meta‐analyses showed conflicting results regarding intracranial bleeding, migraine appears to be associated to increased risk of hemorrhagic stroke, particularly in women younger than 45 years . Migraine subtypes were not associated with hemorrhagic stroke .…”

“…Stroke is a heterogeneous disease and presents as an episode of neurological dysfunction caused by focal CNS infarction attributable to ischemia, whose symptoms persist for >24 hours or until death . Between 2005 and 2018, 5 meta‐analyses included studies involving any stroke, ischemic stroke, any hemorrhagic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage as outcomes . In 2 meta‐analyses, the overall risk of stroke was high in migraineurs …”

“…It was also difficult to infer temporal relationships between the onset and activity of migraine and any occurrences of cerebrovascular events . A time‐dependent association may actually exist, as longer follow‐up resulted in increased risks . Therefore, the existing data cannot be deemed conclusive, because nonsignificant results may be derived not only from a true lack of relationships but also from short follow‐ups and low statistical power …”

The Risks or Lack Thereof of Migraine Treatments in Vascular Disease

“…A meta‐analysis of the association between migraine and cardiovascular diseases included 16 studies with 1,152,407 participants . A total of 394,942 patients had migraine, and 757,465 were controls.…”

Serum Vitamin B12 and Methylmalonic Acid Status in Migraineurs: A Case‐Control Study

“…[3][4][5][6][7][8] The latter factor, Hcy, has been recently acknowledged as a predictor for a number of cardiovascular and atherosclerotic disorders including ischemic heart disease and stroke. 10 In this direction, previous findings revealed that hyperhomocysteinemia as a neuroexcitatory sulfurcontaining molecule that may result in reactive oxygen species (ROS) release, endothelial function disturbance, cellular damage, and activation of platelets which consequently lead to the initiation of migraine attacks by changing pain threshold and sensitization of head pain sensitive structures. 10 In this direction, previous findings revealed that hyperhomocysteinemia as a neuroexcitatory sulfurcontaining molecule that may result in reactive oxygen species (ROS) release, endothelial function disturbance, cellular damage, and activation of platelets which consequently lead to the initiation of migraine attacks by changing pain threshold and sensitization of head pain sensitive structures.…”