Although the relationship between migraine and cardiovascular disease (CVD) has been studied, several questions remain unanswered. Herein we contrast the rate of diagnosed CVD as well as of risk ...factors for CVD in individuals with migraine with and without aura (MA and MO) and in controls.
In this case-control study, migraineurs (n = 6,102) and controls (n = 5,243) were representative of the adult US population. Headache diagnosis was formally assigned using a validated mailed questionnaire which also obtained details on treatment, comorbidities, and other variables. CVD events were obtained based on self-reported medical diagnosis. Risk factors for CVD and modified Framingham scores were computed.
In unadjusted analyses, migraine overall and MA were associated with myocardial infarction, stroke, and claudication, and MO was associated with myocardial infarction and claudication. Migraineurs were more likely than controls to have a medical diagnosis of diabetes (12.6% vs 9.4%, odds ratio OR 1.4, 95% confidence interval CI 1.2-1.6), hypertension (33.1% vs 27.5%, OR 1.4, 95% CI 1.3-1.6), and high cholesterol (32.7% vs 25.6%, OR 1.4, 95% CI 1.3-1.5). Risk was highest in MA, but remained elevated in MO. Framingham scores were significantly higher in MO and MA than in controls. After adjustments (gender, age, disability, treatment, CVD risk factors), migraine remained significantly associated with myocardial infarction (OR 2.2, 95% CI 1.7-2.8), stroke (OR 1.5, 95% CI 1.2-2.1), and claudication (OR 2.69, 95% CI 1.98-3.23).
Both migraine with and without aura are associated with cardiovascular disease (CVD) and with risk factors for CVD. However, since our sample size is large, the clinical relevance of the differences is yet to be established.
The authors estimated the prevalence and severity of cutaneous allodynia (CA) in individuals with primary headaches from the general population.
We mailed questionnaires to a random sample of 24,000 ...headache sufferers previously identified from the population. The questionnaire included the validated Allodynia Symptom Checklist (ASC) as well as measures of headache features, disability, and comorbidities. We modeled allodynia as an outcome using headache diagnosis, frequency and severity of headaches, and disability as predictor variables in logistic regression. Covariates included demographic variables, comorbidities, use of preventive medication, and use of opioids.
Complete surveys were returned by 16,573 individuals. The prevalence of CA of any severity (ASC score >or=3) varied with headache type. Prevalence was significantly higher in transformed migraine (TM, 68.3%) than in episodic migraine (63.2%, p < 0.01) and significantly elevated in both of these groups compared with probable migraine (42.6%), other chronic daily headaches (36.8%), and severe episodic tension-type headache (36.7%). The prevalence of severe CA (ASC score >or=9) was also highest in TM (28.5%) followed by migraine (20.4%), probable migraine (12.3%), other chronic daily headaches (6.2%), and severe episodic tension-type headache (5.1%). In the migraine and TM groups, prevalence of CA was higher in women and increased with disability score. Among migraineurs, CA increased with headache frequency and body mass index. In all groups, ASC scores were higher in individuals with major depression.
Cutaneous allodynia (CA) is more common and more severe in transformed migraine and migraine than in other primary headaches. Among migraineurs, CA is associated with female sex, headache frequency, increased body mass index, disability, and depression.
To evaluate the disability profile and patterns of treatment and health care use for chronic migraine (CM) in the general population, in contrast to episodic migraine.
We identified 24,000 headache ...sufferers, drawn from more than 165,000 individuals representative of the US population. This sample has been followed up with annual surveys using validated questionnaires for the diagnosis of episodic migraine and CM. As a part of the survey, subjects were asked to report the specific medications currently used for their most severe headaches, as well as level of satisfaction with treatment.
Our sample consisted of 520 individuals with CM and 9,424 with episodic migraine. Over a 3-month period, more than half of the individuals with CM missed at least 5 days of household work, compared with 24.3% of those with episodic migraine (p < 0.001). Reduced productivity in household work for at least 5 days over 3 months was reported by 58.1% and 18.2% (p < 0.001); at least 5 days of missed family activities was reported by 36.9% and 9.5% (p < 0.001). The majority of the CM sufferers (87.6%) had previously sought care to discuss their headaches with a health professional. Migraine-specific acute treatments were used by 31.6% of respondents with CM and 24.8% with episodic migraine. Around 48% of the individuals with CM were satisfied with their acute therapies. Just 33.3% of those with CM were currently using preventive medications.
Chronic migraine (CM) is more disabling than episodic migraine in the population. Although most individuals with CM sought medical care for this disorder, the majority did not receive specific acute or preventive medications.
Migraine, especially migraine with aura (MA), is an established risk factor for ischemic lesions of the brain. Recent evidence has also linked migraine to a broader range of ischemic vascular ...disorders including angina, myocardial infarction, coronary revascularization, claudication, and cardiovascular mortality. The mechanisms which link migraine to ischemic vascular disease remain uncertain and are likely to be complex. Cortical spreading depression, the presumed substrate of aura, may directly predispose to brain lesions and that would explain why MA is consistently demonstrated as a risk factor for cerebral ischemia, while for migraine without aura (MO), the evidence is less consistent. Additionally, individuals with migraine have a higher prevalence of risk factors known to be associated with cardiovascular disease (CVD), including hypertension, diabetes, and hyperlipidemia. The increased prevalence of CVD risk factors is also higher for MA than for MO. Since the evidence linking migraine and CVD is getting robust, neurologists should be aware of this association. Individuals with MO seem to be at little increased risk of CVD. MA is associated with an increased risk of ischemic stroke and likely also for other ischemic CVD events. Accordingly, heightened vigilance is recommended for modifiable cardiovascular risk factors in migraineurs, especially with MA. Ultimately, it will be important to determine whether MA is a modifiable risk factor for CVD and if preventive medications for migraine or antiplatelet therapy might reduce the risk of CVD in patients with MA.
1) To reassess the prevalence of migraine in the United States; 2) to assess patterns of migraine treatment in the population; and 3) to contrast current patterns of preventive treatment use with ...recommendations for use from an expert headache panel.
A validated self-administered headache questionnaire was mailed to 120,000 US households, representative of the US population. Migraineurs were identified according to the criteria of the second edition of the International Classification of Headache Disorders. Guidelines for preventive medication use were developed by a panel of headache experts. Criteria for consider or offer prevention were based on headache frequency and impairment.
We assessed 162,576 individuals aged 12 years or older. The 1-year period prevalence for migraine was 11.7% (17.1% in women and 5.6% in men). Prevalence peaked in middle life and was lower in adolescents and those older than age 60 years. Of all migraineurs, 31.3% had an attack frequency of three or more per month, and 53.7% reported severe impairment or the need for bed rest. In total, 25.7% met criteria for "offer prevention," and in an additional 13.1%, prevention should be considered. Just 13.0% reported current use of daily preventive migraine medication.
Compared with previous studies, the epidemiologic profile of migraine has remained stable in the United States during the past 15 years. More than one in four migraineurs are candidates for preventive therapy, and a substantial proportion of those who might benefit from prevention do not receive it.
Neck pain is common among individuals with migraine, but there is a lack of information of how this comorbidity can be associated with cervical muscle function. This controlled cross-sectional study ...aimed to compare cervical muscle function, activity, and sensitization in women with migraine, neck pain, both, and neither.
This study included women, between 18 and 55 years old, with either episodic migraine with or without aura, without any concomitant headache diagnosis; chronic neck pain, with at least moderate intensity and mild disability; or neither headache nor neck pain. Pain pressure threshold, allodynia, muscle strength, and endurance and cervical muscles activity were evaluated.
One hundred subjects, with mean age of 30.4 years old, were stratified by diagnosis (n = 25 per group) and by self-reported pain during tests. Lower endurance during flexion was observed for migraine and neck pain (34s) relative to neck pain alone (45s), migraine (40s), and controls (58s) (p = 0.04). For extensor endurance, means were 142s, 166s, 215s, and 270s, respectively (p < 0.001). Endurance times were impacted by the presence of test-induced pain decreasing about 40%-53% of the performance. Diagnostic groups did not differ significantly in strength (p > 0.05), but all pain groups presented significantly higher proportion of test-induced pain, lower muscle activity during the maximal isometric voluntary contractions, and lower pressure pain thresholds.
Patients with migraine, chronic neck pain, and the association of both present altered cervical muscle function and activity. Also, test-induced pain impacts significantly on neck muscles endurance.
The diagnosis of migraine and chronic neck pain is associated with altered function and activity of the cervical muscles. However, the test-induced pain had an important contribution to worse cervical muscle endurance. This suggests that the therapeutic approach should focus on de-sensitization of the trigeminal-cervical complex when dealing with the comorbidity of migraine and cervical pain.
Summary Background Calcitonin gene-related peptide (CGRP) is a validated target for the treatment of episodic migraine. Here we assess the safety, tolerability, and efficacy of TEV-48125, a ...monoclonal anti-CGRP antibody, in the preventive treatment of high-frequency episodic migraine. Methods In this multicentre, randomised, double-blind, placebo-controlled, phase 2b study, we enrolled men and women (aged 18–65 years) from 62 sites in the USA who had migraine headaches 8–14 days per month. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1:1:1; stratified by sex and use of concomitant preventive drugs) after a 28 day run-in period to three 28 day treatment cycles of subcutaneous 225 mg TEV-48125, 675 mg TEV-48125, or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Patients reported headache information daily using an electronic diary. Primary endpoints were change from baseline in migraine days during the third treatment cycle (weeks 9–12) and safety and tolerability. The secondary endpoint was change relative to baseline in headache-days during weeks 9–12. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered at ClinicalTrials.gov , number NCT02025556. Findings Between Jan 8, 2014, and Oct 15, 2014, we enrolled 297 participants: 104 were randomly assigned to receive placebo, 95 to receive 225 mg TEV-48125, and 96 to receive 675 mg TEV-48125. The least square mean (LSM) change in number of migraine-days from baseline to weeks 9–12 was −3·46 days (SD 5·40) in the placebo group, −6·27 days (5·38) in the 225 mg dose group, and −6·09 days (5·22) in the 675 mg dose group. The LSM difference in the reduction of migraine-days between the placebo and 225 mg dose groups was −2·81 days (95% CI −4·07 to −1·55; p<0·0001), whereas the difference between the placebo and 675 mg dose group was −2·64 days (−3·90 to −1·38; p<0·0001). LSM differences in the reduction of headache-days were −2·63 days (−3·91 to −1·34; p<0·0001) between the placebo group and 225 mg dose group and −2·58 days (−3·87 to 1·30; p <0·0001) between the placebo group and the 675 mg dose group. Adverse events occurred in 58 (56%) patients in the placebo group, 44 (46%) patients in the 225 mg dose group, and 57 (59%) patients in the 675 mg dose group; moderate or severe adverse events were reported for 29 (27%) patients, 24 (25%) patients, and 26 (27%) patients, respectively. Interpretation TEV-48125, at doses of 225 mg and 675 mg given once every 28 days for 12 weeks, was safe, well tolerated, and effective as a preventive treatment of high-frequency episodic migraine, thus supporting advancement of the clinical development programme to phase 3 clinical trials. Funding Teva Pharmaceuticals.
Summary Background Benefits of calcitonin-gene related peptide (CGRP) inhibition have not been established in chronic migraine. Here we assess the safety, tolerability, and efficacy of two doses of ...TEV-48125, a monoclonal anti-CGRP antibody, in the preventive treatment of chronic migraine. Methods In this multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel-group phase 2b study, we enrolled men and women (aged 18–65 years) from 62 sites in the USA who had chronic migraine. Using a randomisation list generated by a central computerised system and an interactive web response system, we randomly assigned patients (1:1:1, stratified by sex and use of concomitant preventive drugs) to three 28-day treatment cycles of subcutaneous TEV-48125 675/225 mg (675 mg in the first treatment cycle and 225 mg in the second and third treatment cycles), TEV-48125 900 mg (900 mg in all three treatment cycles), or placebo. Investigators, patients, and the funder were blinded to treatment allocation. Daily headache information was captured using an electronic diary. Primary endpoints were change from baseline in the number of headache-hours during the third treatment cycle (weeks 9–12) and safety and tolerability during the study. Secondary endpoint was change in the number of moderate or severe headache-days in weeks 9–12 relative to baseline. Efficacy endpoints were analysed for the intention-to-treat population. Safety and tolerability were analysed using descriptive statistics. This trial is registered with ClinicalTrials.gov , number, NCT02021773. Findings Between Jan 8, 2014, and Aug 27, 2014, we enrolled 264 participants: 89 were randomly assigned to receive placebo, 88 to receive 675/225 mg TEV-48125, and 87 to receive 900 mg TEV-48125. The mean change from baseline in number of headache-hours during weeks 9–12 was −59·84 h (SD 80·38) in the 675/225 mg group and −67·51 h (79·37) in the 900 mg group, compared with −37·10 h (79·44) in the placebo group. The least square mean difference in the reduction of headache-hours between the placebo and 675/225 mg dose groups was −22·74 h (95% CI −44·28 to −1·21; p=0·0386), whereas the difference between placebo and 900 mg dose groups was −30·41 h (−51·88 to −8·95; p=0·0057). Adverse events were reported by 36 (40%) patients in the placebo group, 47 (53%) patients in the 675/225 mg dose group, and 41 (47%) patients in the 900 mg dose group, whereas treatment-related adverse events were recorded in 15 (17%) patients, 25 (29%) patients, and 28 (32%) patients, respectively. The most common adverse events were mild injection-site pain and pruritus. Four (1%) patients had serious non-treatment-related adverse events (one patient in the placebo group, one patient in the 675/225 mg group, and two patients in the 900 mg group); no treatment-related adverse events were serious and there were no relevant changes in blood pressure or other vital signs. Interpretation TEV-48125 given by subcutaneous injection every 28 days seems to be tolerable and effective, thus supporting the further development of TEV-48125 for the preventive treatment of chronic migraine in a phase 3 trial. Funding Teva Pharmaceuticals.
We describe the epidemiology and comorbidities of migraine, which affects 12% of adults in occidental countries. Prevalence is three times higher in women, but 6% of men are affected, making it the ...most prevalent neurologic disorder in men. Although migraine is a remarkably common cause of temporary disability, many migraineurs have never consulted a physician for the problem. Many disorders are comorbid with migraine. For some such as depression, the association has been well described, but for others, the relationship has been recently suggested, such as in the case of clinical and subclinical vascular brain lesions and coronary heart disease.
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