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Myocardial infarction, stroke and cardiovascular mortality among migraine patients: a systematic review and meta-analysis

Authors:
Chester Yan Hao Ng at National University of Singapore
Chester Yan Hao Ng
Benjamin YQ Tan at National University Health System
Benjamin YQ Tan
Yao Neng Teo at National University of Singapore
Yao Neng Teo
Yao Hao Teo at National University of Singapore
Yao Hao Teo
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Background An increasing number of studies have shown an association between migraine and cardiovascular disease, in particular cardio- and cerebro-vascular events. Methods Three electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for prospective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients. A random effects meta-analysis model was used to summarize the included studies. Results A total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 controls. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23–1.51; p = < 0.001), unspecified stroke (hazard ratio, 1.30; 95% CI, 1.07–1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03–1.78; p = 0.03) and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07–1.92; p = 0.02). Subgroup analysis of migraine with aura found a further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard ratio, 1.27; 95% CI, 1.14–1.42; p = < 0.001). Conclusion Migraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura increases the risk of overall cardiovascular mortality.
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Vol:.(1234567890)
Journal of Neurology (2022) 269:2346–2358
https://doi.org/10.1007/s00415-021-10930-x
1 3
REVIEW
Myocardial infarction, stroke andcardiovascular mortality
amongmigraine patients: asystematic review andmeta‑analysis
ChesterYanHaoNg1 · BenjaminY.Q.Tan1,2· YaoNengTeo1· YaoHaoTeo1· NicholasL.X.Syn1·
AloysiusS.T.Leow1· JamieS.Y.Ho3· MarkY.Chan1,4· RaymondC.C.Wong1,4· PingChai1,4·
AmandaCheeYunChan1,2· VijayKumarSharma1,2· LeonardL.L.Yeo1,2· Ching‑HuiSia1,4 · JonathanJ.Y.Ong1,2
Received: 7 November 2021 / Revised: 2 December 2021 / Accepted: 3 December 2021 / Published online: 8 January 2022
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2021
Abstract
Background An increasing number of studies have shown an association between migraine and cardiovascular disease, in
particular cardio- and cerebro-vascular events.
Methods Three electronic databases (PubMed, Embase and Scopus) were searched from inception to May 22, 2021 for pro-
spective cohort studies evaluating the risk of myocardial infarction, stroke and cardiovascular mortality in migraine patients.
A random effects meta-analysis model was used to summarize the included studies.
Results A total of 18 prospective cohort studies were included consisting of 370,050 migraine patients and 1,387,539 con-
trols. Migraine was associated with myocardial infarction (hazard ratio, 1.36; 95% CI, 1.23–1.51; p = < 0.001), unspecified
stroke (hazard ratio, 1.30; 95% CI, 1.07–1.60; p = 0.01), ischemic stroke (hazard ratio, 1.35; 95% CI, 1.03–1.78; p = 0.03)
and hemorrhagic stroke (hazard ratio, 1.43; 95% CI, 1.07–1.92; p = 0.02). Subgroup analysis of migraine with aura found a
further increase in risk of myocardial infarction and both ischemic and hemorrhagic stroke, as well as improved substantial
statistical heterogeneity. Migraine with aura was also associated with an increased risk of cardiovascular mortality (hazard
ratio, 1.27; 95% CI, 1.14–1.42; p = < 0.001).
Conclusion Migraine, especially migraine with aura, is associated with myocardial infarction and stroke. Migraine with aura
increases the risk of overall cardiovascular mortality.
Keywords Migraine· Aura· Myocardial infarction· Stroke· Mortality
Introduction
Migraine is a primary headache disorder with the majority of
those affected experiencing an episodic course [1]. It is the
second most common cause of disability globally, account-
ing for 4.9% of total years lived with disability between 1990
and 2019 [2]. The global prevalence, based on data from
204 countries, is estimated to be 14% [2]. Migraine attacks
are characterised by unilateral, moderate-to-severe intensity
throbbing headaches which are worsened by physical activ-
ity or head movement [3]. Without treatment, attacks can last
from 4 to 72h in duration with episodes commonly associ-
ated with reversible neurological and systemic symptoms
including nausea, vomiting, photophobia and phonophobia
[4]. Up to a third of migraine patients also experience visual,
sensory or other transient central nervous system symptoms
preceding headaches which are classified as migraine with
aura [4]. The pathophysiology behind these processes is
Chester Yan Hao Ng and Benjamin Y. Q. Tan have contributed
equally as first authors.
Ching-Hui Sia and Jonathan J. Y. Ong have co-supervised this
study as senior authors.
* Ching-Hui Sia
ching_hui_sia@nuhs.edu.sg
1 Department ofMedicine, Yong Loo Lin School ofMedicine,
National University ofSingapore, Singapore, Singapore
2 Division ofNeurology, Department ofMedicine, National
University Health System, Singapore, Singapore
3 Academic Foundation Year Programme, North Middlesex
University Hospital Trust, London, UK
4 Department ofCardiology, National University Heart Centre
Singapore, National University Health System, Singapore,
Singapore
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Available evidence suggests 2fold increased risk of stroke among patients with migraine [7,8], and recurrence of stroke in young populations [9]. Studies including a recent meta-analysis demonstrated greater risk particularly in individuals aged less than 45 years, women with migraine with aura (MA), oral contraceptive users, and smokers [8, 10,11]. A recent follow-up study from South Korea that included individuals aged > 40 years also showed 35% greater risk among migraineurs [12]. ...
... Previous studies [7,[14][15][16], including two meta-analyses [8,11] have consistently shown greater risk in individuals with MA compared to those without aura. A study in the US reported a signi cant association between migraine with visual aura and ischemic stroke (HR 1.7, 95% CI 1. [13,27,28]. ...
... The differences in the inclusion criteria, de nition of variables, discrepancy in lifestyles, as well as genetic background should be considered when interpreting the study. Consistent with our ndings, a recent meta-analysis including all these studies suggested signi cant association only between MA and ischemic stroke [11]. ...
Risk of stroke in patients with migraine. A register-linked HUNT study
Preprint
Full-text available
  • Feb 2024
Background The association between migraine and stroke remains unclear. The aim of this large population-based 15-year follow-up study was to investigate whether primary headache disorders, including subtypes of migraine, increase the risk of stroke. Methods This population-based 15-year follow-up study used baseline headache data from the third Trøndelag Health Study (HUNT3) performed between 2006 and 2008. The HUNT3 headache data were linked to the Norwegian National Stroke Register that includes stroke diagnoses recorded from 2012 until December 2021. The association between stroke and headache status was investigated in individuals aged ≥ 20 years without stroke at baseline. Prospective associations were evaluated using multivariable Cox proportional hazard models with 95% confidence intervals (CIs). Separate sub-group analyses by age and sex were performed. Results Among 37,364 included participants, 1,095 (2.9%) developed stroke, whereof 13.4% were younger than 55 years. In the multi-adjusted model, reporting migraine with aura (MA) at baseline was associated with increased risk of stroke at follow-up (HR 1.55, 95% CI 1.16–2.08) compared with those without headache. The increased risk of stroke was most evident among individuals with MA who were less than 55 years old (HR 1.98, 95% CI 1.20–3.27) and among women (HR 1.64, 95% CI 1.12–2.41). Conclusions During 15 years of follow-up, individuals with MA were more likely to suffer from stroke compared to those without headache. The relationship with MA was even stronger in women, and for young individuals aged < 55 years.
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... The efficacy and safety of statins in preventing ischemic stroke are firmly established, and they are widely used in clinical practice 11 . Accumulating evidence shows that migraine increases the risk of ischemic stroke 15,16 . Therefore, the discovery of the causal pathways of migraine related to lipids may contribute to improve our understanding of the mechanisms leading to the development of migraine. ...
HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study
Article
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  • May 2024
Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30–1.84, P = 6.87 × 10 ⁻⁷ ). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.
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... The exact mechanisms underlying the association between migraine and cardio-and cerebro-vascular events are still not well understood. [38][39] Interestingly, one important result of our study is related to the less prevalent cardiovascular risk factors in triptan users, compared to controls, also pointing the careful attention of physicians prescribing triptan, as also suggested by others [1,40,41]. This selection bias was, at least partially, controlled in our study through the use of a propensity score (study groups are well balanced in terms of cardiovascular history). ...
Triptan use in elderly over 65 years and the risk of hospitalization for serious vascular events
Article
Full-text available
  • Apr 2024
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Background Several studies have focused on the use of triptan and the risk of acute vascular events but the existence of such association is still debated and has never been quantified in patients over 65 years. To assess whether triptan use among older is associated with an increased risk of hospitalization for acute vascular events. Methods A propensity score-matched cohort study was designed using the French national health insurance database linked to hospital stays. Patients aged ≥ 65 years, newly treated by triptans between 2011 and 2014, were included… The primary event was hospitalization for an acute ischemic vascular event within de 90 days following triptan initiation. Association with triptan exposure was investigated through cox regression model, considering exposure at inclusion, and with exposure as a time-varying variable A case-crossover (CCO) and a self-controlled case series (SCCS) analyses were also conducted to address potential residual confounding. Results The cohort included 24, 774 triptan users and 99 096 propensity matched controls (mean (SD) age: 71 years (5.9), 74% of women). Within 90 days after cohort entry, 163 events were observed in the triptan group, and 523 in the control group (0.66% vs. 0.53%, adjusted hazard ratio (aHR) exposed/not exposed 1.25 95%CI [1.05–1.49]; aHR time−varying 8.74 [5.21–14.66]). The association was significant (CCO) for all events (adjusted odds ratio (aOR1.63 [1.22–2.19]) with a more consistent association with cerebral events (aOR 2.14 [1.26–3.63]). The relative incidence (RI) for all events was 2.13 [1.76–2.58] in the SCCS, for cardiac (RI: 1.67 [1.23–2.27]) and for cerebral events (RI: 3.20, [2.30–4.45]). Conclusion The incidence of acute vascular events was low among triptan users. We found that triptan use among older may be associated with a low increased risk for acute vascular events, which may be more marked for cerebral events such as stroke, than for cardiac events.
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... The mechanism underlying the associations between migraine and myocardial infarction is presumed to be multifactorial. It may be the result of an increased prevalence of other conditions such as vasculopathies, hypercoagulable states, and patent foramen ovale, particularly observed in individuals with migraine with aura [53,54]. Although attempts have been made to explain the possible association between the use of anti-CGRP-mAbs and CV events, the literature is limited and remains controversial. ...
Cardiovascular Adverse Drug Reactions of Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies for Migraine Prevention: An Analysis from the European Spontaneous Adverse Event Reporting System
Article
  • Feb 2024
  • BIODRUGS
Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) have recently been approved for the prevention of migraine, and their safety profile is not fully characterized. The aim of this study was to evaluate the adverse drug reactions (ADRs) of anti-CGRP-mAbs through the analysis of individual case safety reports (ICSRs) collected in the EudraVigilance (EV) database, with a specific focus on cardiovascular (CV) ADRs. Data on ICSRs recorded between July 2018 and December 2022 in the EV database, involving one of the anti-CGRP-mAbs for migraine prevention—erenumab (ERE), galcanezumab (GMB), fremanezumab (FMB), and eptinezumab (EPT)—were included in the analysis. All ICSRs reporting at least one CV ADR, as identified within the MedDRA® System Organ Classes (SOCs) “cardiac disorders” or “vascular disorders,” were selected for the analysis. The frequency of disproportionate reporting was expressed as the reporting odds ratio (ROR) with its 95% confidence interval (CI), to evaluate the frequency of reporting of CV ADRs for each anti-CGRP-mAb compared with all other monoclonal antibodies (mAbs). A case-by-case analysis was conducted paying particular attention to serious CV ADR reports, focusing on the type of seriousness, age group, sex, and concomitant drugs. A total of 9441 ICSRs were recorded in the EV database from 2018 to 2022, of which more than half were related to ERE (58.9%), followed by GMB (21.4%), FMB (19.0%), and EPT (0.7%). CV ICSRs accounted for 1205 cases (12.8%), with a total of 1599 CV ADRs. The CV ICSRs were mainly related to female patients (82.6%) aged 18–64 years (73.4%). Of the reported CV ADRs, 67.5% were considered serious. Among the total number of ICSRs related to each anti-CGRP-mAb, those associated with FMB had a higher percentage of CV ADRs (n = 253; 14.1%), followed by ERE (n = 707; 12.7%), EPT (n = 8; 12.7%), and GMB (n = 237; 11.7%). A higher frequency of reporting hypertension was shown for ERE (ROR = 1.45; 95% CI = 1.14–1.85). Pallor was mainly observed with FMB (5.00; 1.68–14.89), as well as deep vein thrombosis (3.86; 1.57–9.51), hot flush (2.16; 1.43–3.25), and palpitations (1.48; 1.05–2.08). Atrial fibrillation (2.36; 1.02–5.46) and myocardial infarction (2.21; 1.37–3.58) were mostly reported for GMB. The analysis of anti-CGRP-related CV ADRs was consistent with the information reported in the literature. However, hypertension with ERE, atrial fibrillation and myocardial infarction with GMB, as well as pallor, deep vein thrombosis, hot flush, and palpitations with FMB were not reported in the Summary of Product Characteristics (SmPCs). Considering this, more post-marketing analyses are needed to improve knowledge on the CV safety profiles of anti-CGRP-mAbs, especially for the last approved medication, EPT.
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Migraine and risk of atrial fibrillation: A 9-year follow-up based on the Trøndelag Health Study
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  • May 2024
  • CEPHALALGIA
Background Data from some population-based studies have indicated an increased risk of atrial fibrillation (AF) among patients with migraine, particularly among individuals with migraine with aura. The present study aimed to assess the association between primary headache disorders and AF. Methods In a population-based 9-year follow-up design, we evaluated the questionnaire-based headache diagnosis, migraine and tension-type headache (TTH) included, collected in the Trøndelag Health Study (HUNT3) conducted in 2006–2008, and the subsequent risk of AF in the period until December 2015. The population at risk consisted of 39,340 individuals ≥20 years without AF at HUNT3 baseline who answered headache questionnaire during HUNT3. The prospective association was evaluated by multivariable Cox proportional hazard models with 95% confidence intervals (CIs). Results Among the 39,340 participants, 1524 (3.8%) developed AF during the 9-year follow up, whereof 91% of these were ≥55 years. In the multivariable analyses, adjusting for known confounders, we did not find any association between migraine or TTH and risk of AF. The adjusted hazard ratios (HRs) were respectively 0.84 (95% CI = 0.64–1.11) for migraine, 1.16 (95% CI = 0.86–1.27) for TTH and 1.04 (95% CI = 0.86–1.27) for unclassified headache. However, in sensitivity analyses of individuals aged ≥55 years, a lower risk of AF was found for migraine (HR = 0.53; 95% CI = 0.39–0.73). Conclusions In this large population-based study, no increased risk of AF was found among individuals with migraine or TTH at baseline. Indeed, among individuals aged ≥55 years, migraine was associated with a lower risk for AF.
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Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine
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  • May 2024
  • HEADACHE
Objective To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. Background Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug‐device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). Methods The STOP 101 was a Phase 1 open‐label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open‐label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. Results In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9–15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4–17.1) at 5 min post‐dose, persisting up to 30 min post‐dose for systolic BP (6.3 mmHg; 95% CI 3.0–9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9–11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non‐serious, vascular treatment‐emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off‐protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. Conclusion In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV‐related contraindications.
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Association between migraine and venous thromboembolism: a Mendelian randomization and genetic correlation study
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Objective Previous observational studies have reported an increased risk of venous thromboembolism (VTE) among individuals with migraine. This study aimed to investigate the causal effect of migraine on the development of VTE, as well as explore the genetic correlation between them. Methods We conducted a two-sample Mendelian randomization (MR) study using publicly available summary statistics from large-scale genome-wide association studies for migraine and VTE. Linkage disequilibrium score regression analysis was performed to estimate the genetic correlation between migraine and VTE. Results There were several shared risk variants (p-value < 5 × 10⁻⁸) between migraine and VTE. Linkage disequilibrium score regression analysis found a significant positive genetic correlation between migraine and VTE. The genetic correlations based on two migraine datasets were 0.208 (se = 0.031, p-value = 2.91 × 10⁻¹¹) and 0.264 (se = 0.040, p-value = 4.82 × 10⁻¹¹), respectively. Although main MR analysis showed that migraine was associated with an increased risk of VTE (odds ratio = 1.069, 95% confidence interval = 1.022–1.118, p-value = 0.004), the association attenuated to non-significance when using several other MR methods and using another set of genetic instruments. In addition, evidence of heterogeneity was found. Reverse MR analysis showed VTE was associated with increased risk of migraine with aura (odds ratio = 1.137, 95% confidence interval = 1.062–1.218, p-value = 2.47 × 10⁻⁴) with no evidence of pleiotropy and heterogeneity. Conclusion We showed suggestive evidence indicating an association between migraine and increased risk of VTE. Additionally, we found robust evidence suggesting that VTE is associated with an increased risk of migraine. The positive genetic correlation indicates that migraine and VTE has shared genetic basis. Further investigations will be necessary to address potential sex-specific effects in the analysis.
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The individual and global burden of migraine is of such significance that there are accelerated efforts to develop new therapies. New migraine therapeutics are needed to address the current deficiencies that exist in the efficacy and adherence rate of approved anti-migraine medications. The recent discovery of the calcitonin gene related peptide as an add-on to the role of serotonin has markedly increased the range of new treatment options for acute and chronic migraine. Despite this, tackling the complexity of migraine disorders requires a complete understanding of its pathophysiology. Preclinical animal models can shed light on disease-related pathophysiology, including migraine. Indeed, the use of animal models has been instrumental in developing many therapeutics. However, an animal model is limited by the predictive and face validity of that model, and this extends to preclinical migraine models. In this review, a summary of the current understanding of the pathophysiology of migraine is given from both a preclinical and clinical perspective, and an emphasis is placed on the animal models of migraine. We will discuss the strengths and pitfalls of common preclinical migraine models as well as experimental research areas to explore further.
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Increased Cardio-ankle Vascular Index Values in Migraine Patients With Aura
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  • Jan 2024
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Patients with migraine with aura are at an increased risk of cardiovascular disease. There are limited data on arterial stiffness in migraine patients with aura. The present study evaluated arterial stiffness in these patients using the cardio-ankle vascular index (CAVI). This prospective study included 50 patients with migraine with aura (43 female, mean age 38.9 ± 9.9 years). The patient group was matched for age and gender with 50 healthy individuals with no history of migraine (43 female, mean age 39.3 ± 10.3 years). All patients and control subjects underwent a comprehensive clinical evaluation by an experienced neurologist and were interviewed about their headache histories. There was no significant difference in baseline demographic characteristics and echocardiographic parameters between migraine with aura patients and the control group. Both right and left CAVI values were significantly higher in the patients with migraine with aura (6.5 ± 1.2 vs 6.1 ± 0.7, P = .043 and 6.6 ± 1.2 vs 6.1 ± 0.7, P = .009, respectively). Arterial stiffness is an important mediator of cardiovascular diseases. We found that CAVI, a novel marker of the arterial stiffness, is increased in patients with migraine with aura.
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Shorter visual aura characterizes young and middle-aged stroke patients with migraine with aura
Article
Full-text available
  • Feb 2022
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Objective To identify the clinical profile and aura characteristics of patients with Migraine with Aura (MwA) having acute cerebral ischemia, we compared stroke phenotype and risk factors in stroke patients with (S+MwA+) or without (S+MwA−) MwA and aura features in MwA patients with (S+MwA+) or without (S−MwA+) stroke. Methods In this retrospective multicenter case–control study, we reviewed stroke phenotypes and vascular risk factors in S+MwA+ and S+MwA− patients younger than 60 years and risk factors and aura type, duration, onset age, and the frequency in the previous year in S+MwA+ patients and S−MwA+ subjects matched for age and disease history, investigated for patent foramen ovale (PFO). Results 539 stroke (7.7% S+MwA+) and 94 S−MwA + patients were enrolled. S+MwA+ patients were younger (p =.0.004) and more frequently presented PFO [OR 4.89 (95% CI 2.12–11.27)], septal interatrial aneurism [OR 2.69 (95% CI 1.15–6.27)] and cryptogenic ischemic stroke (CIS) [OR 6.80 (95% CI 3.26–14.18)] than S+MwA− subjects. Significant atherosclerosis was not detected in S+MwA+ patients. Compared to S−MwA+, S+MwA+ patients were characterized by visual [OR 3.82 (95% CI 1.36–10.66)] and shorter-lasting (20.0 min IQr 13.1 vs 30.0 min IQr 25.0; p < 0.001) aura, and PFO [OR 1.26 (95% CI 1.03–1.54)]. Regression analysis evidenced that only shorter aura duration associated with stroke (p = 0.001). High-risk PFO was equally represented in S+MwA−, S+MwA+, S−MwA+ groups. Conclusions Shorter visual aura and CIS characterize MwA patients with stroke. Although more prevalent, PFO can not be considered the main responsible for the increased stroke risk in MwA patients but as a part of a complex multifactorial condition.
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The PRISMA 2020 statement: An updated guideline for reporting systematic reviews
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The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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Association between Migraine and the Risk of Stroke: A Bayesian Meta-Analysis
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There are still inconsistent results about association between migraine and stroke risk in studies. This paper was to review findings on the association between migraine (with or without aura) and stroke risk. We searched articles in the Embase and PubMed up to January 2021. Two independent reviewers extracted basic data from individual studies using a standardized form. Quality of studies was also assessed using the Newcastle–Ottawa Scale. We conducted a meta-analysis, both classical and Bayesian approaches. We identified 17 eligible studies with a sample size more than 2,788,000 participants. In the fixed effect model, the results demonstrated that migraine was positively associated with the risk of total stroke, hemorrhagic stroke, and ischemic stroke. Nevertheless, migraine was associated with only total stroke in the random effects model (risk ratio (RR) 1.31, 95%CI: 1.06–1.62). The probability that migraine increased total stroke risk was 0.978 (RR 1.31; 95% credible interval (CrI): 1.01–1.72). All types of migraine were not associated with ischemic stroke and hemorrhagic stroke. Under three prior distributions, there was no association between migraine and the risk of ischemic stroke or hemorrhagic stroke. Under the non-informative prior and enthusiastic prior, there was a high probability that migraine was associated with total stroke risk.
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The Efficacy of Percutaneous Patent Foramen Ovale Closure on Migraine: a Meta-Analysis of Randomized Controlled Trials and Observational Studies
Article
Full-text available
Objectives: Whether patent foramen ovale (PFO) closure is effective on migraine is controversial. This article was aimed at assessing the efficacy of PFO closure on migraine based on randomized controlled trials (RCTs) and observational studies. Methods: We searched PubMed, Embase, and Cochrane databases up to October 2020 evaluating PFO closure versus control in patients with migraine, then conducted a meta-analysis of all RCTs and observational studies, respectively. The main outcomes were (1) respond rate: complete cessation of migraine; (2) reduction in the frequency of migraine attacks per month; and (3) reduction in migraine days per month. Results: Seven studies (3 RCTs and 4 observational studies), containing 887 migraine patients, were identified. (1) The respond rate of PFO closure on migraine was significantly higher than control group both in RCT subgroup and observational studies subgroup (OR 3.86, 95% CI 1.35-11.04, P = 0.01 in RCTs; OR 8.28, 95% CI 2.31-29.67, P = 0.001 in observational studies). (2) Reduction in frequency of migraine attacks was higher in PFO closure group compared with control group in the RCT subgroup analysis (mean difference (MD) = 0.57, 95% CI 0.23-0.90, P = 0.0009). (3) Reduction in migraine days was also higher in PFO closure group compared with control group in the RCT subgroup analysis (MD = 1.33, 95% CI 0.35-2.31, P = 0.008). Conclusions: PFO closure might be suitable for migraine patients, especially for migraine with aura, by cessation of migraine headaches or reducing migraine attacks and migraine days.
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Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019
Article
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  • Oct 2020
  • LANCET
Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990-2010 time period, with the greatest annualised rate of decline occurring in the 0-9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10-24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10-24 years were also in the top ten in the 25-49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50-74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and development investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation.
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Erenumab does not alter cerebral hemodynamics and endothelial function in migraine without aura
Article
Full-text available
  • Aug 2020
Objective To assess whether erenumab influences cerebral vasomotor reactivity and flow-mediated dilation in migraine patients. Methods Consecutive migraineurs prescribed erenumab at our Headache Centre and age and sex-matching controls were invited to participate in this observational longitudinal study. Patients were evaluated for cerebral vasomotor reactivity to hypercapnia (breath-holding index) in middle and posterior cerebral arteries and for brachial corrected flow mediated dilation at baseline (T0), after 2 weeks from the first erenumab injection (T2) and after 2 weeks from the fourth Erenumab injection (T18). Patients displaying a reduction of at least 50% in monthly migraine days after completing the fourth month of therapy were classified as responders. Results Sixty patients and 25 controls agreed to participate. Middle and posterior cerebral artery mean flow velocities, breath-holding index and flow-mediated dilation did not differ at T0 and from T0 to T2 in patients and controls. In patients, we neither observed a variation of the explored variables from T0 to T18 nor an interaction between evaluation times (T0–T2 or T0–T18) and chronic condition at T0, responder state or erenumab fourth dose. Conclusions Our findings demonstrate that erenumab preserves cerebral vasomotor reactivity and flow-mediated dilation in migraineurs without aura.
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Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults
Article
  • Nov 2020
Objective To assess the association between migraine and cryptogenic ischemic stroke (CIS) in young adults, with subgroup analyses stratified by sex and presence of patent foramen ovale (PFO). Methods We prospectively enrolled 347 consecutive patients aged 18‐49 with a recent CIS and 347 age‐ and sex‐matched (±5 years) stroke‐free controls. Any migraine and migraine with (MA) and migraine without aura (MO) were identified by a screener, which we validated against a headache‐neurologist. We used conditional logistic regression adjusting for age, education, hypertension, diabetes, waist‐to‐hip ratio, physical inactivity, current smoking, heavy drinking, and oral estrogen use to assess independent association between migraine and CIS. The effect of PFO on the association between migraine and CIS was analyzed with logistic regression in a subgroup investigated with transcranial Doppler bubble screen. Results The screener performance was excellent (Cohen’s Kappa >0.75) in patients and controls. Compared with non‐migraineurs, any migraine (odds ratio [OR] 2.48, 95% confidence interval 1.63‐3.76) and MA (OR 3.50, 2.19‐5.61) were associated with CIS, whereas MO was not. The association emerged both in women (OR 2.97 for any migraine, 1.61‐5.47; OR 4.32 for MA, 2.16‐8.65) and men (OR 2.47 for any migraine, 1.32‐4.61; OR 3.61 for MA, 1.75‐7.45). Specifically for MA, the association with CIS remained significant irrespective of PFO. MA prevalence increased with increasing magnitude of the right‐to‐left shunt in patients with PFO. Interpretation MA has a strong association with CIS in young patients, independent of vascular risk factors and presence of PFO.
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Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women
Article
  • Jun 2020
Importance Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear. Objective To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors. Design, Setting, and Participants Female health professionals in the US (the Women’s Health Study cohort) with lipid measurements and no CVD at baseline (1992-1995) were followed up through December 31, 2018. Exposures Self-reported migraine with aura compared with migraine without aura or no migraine at baseline. Main Outcomes and Measures The primary outcome was major CVD (first myocardial infarction, stroke, or CVD death). Generalized modeling procedures were used to calculate multivariable-adjusted incidence rates for major CVD events by risk factor status that included all women in the cohort. Results The study population included 27 858 women (mean [SD] age at baseline, 54.7 [7.1] years), among whom 1435 (5.2%) had migraine with aura and 26 423 (94.8%) did not (2177 [7.8%] had migraine without aura and 24 246 [87.0%] had no migraine in the year prior to baseline). During a mean follow-up of 22.6 years (629 353 person-years), 1666 major CVD events occurred. The adjusted incidence rate of major CVD per 1000 person-years was 3.36 (95% CI, 2.72-3.99) for women with migraine with aura vs 2.11 (95% CI, 1.98-2.24) for women with migraine without aura or no migraine (P < .001). The incidence rate for women with migraine with aura was significantly higher than the adjusted incidence rate among women with obesity (2.29 [95% CI, 2.02-2.56]), high triglycerides (2.67 [95% CI, 2.38-2.95]), or low high-density lipoprotein cholesterol (2.63 [95% CI, 2.33-2.94]), but was not significantly different from the rates among those with elevated systolic blood pressure (3.78 [95% CI, 2.76-4.81]), high total cholesterol (2.85 [95% CI, 2.38-3.32]), or family history of myocardial infarction (2.71 [95% CI, 2.38-3.05]). Incidence rates among women with diabetes (5.76 [95% CI, 4.68-6.84]) or who currently smoked (4.29 [95% CI, 3.79-4.79]) were significantly higher than those with migraine with aura. The incremental increase in the incidence rate for migraine with aura ranged from 1.01 additional cases per 1000 person-years when added to obesity to 2.57 additional cases per 1000 person-years when added to diabetes. Conclusions and Relevance In this study of female health professionals aged at least 45 years, women with migraine with aura had a higher adjusted incidence rate of CVD compared with women with migraine without aura or no migraine. The clinical importance of these findings, and whether they are generalizable beyond this study population, require further research.
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