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      Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women

      1 , 2 , 2 , 2 , 2 , 2
      JAMA
      American Medical Association (AMA)

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          Abstract

          <div class="section"> <a class="named-anchor" id="ab-joi200047-1"> <!-- named anchor --> </a> <h5 class="title" id="d668511e272">Question</h5> <p id="d668511e274">Is there an association between migraine with aura and cardiovascular disease (CVD) incidence rates in women, relative to that of other major vascular risk factors? </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-2"> <!-- named anchor --> </a> <h5 class="title" id="d668511e277">Findings</h5> <p id="d668511e279">In this cohort study that included 27 858 female health professionals aged at least 45 years, the adjusted incidence rate of major CVD was 3.36 per 1000 person-years for women who reported migraine with aura and 2.11 per 1000 person-years for women who reported migraine without aura or no migraine, a difference that was statistically significant. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-3"> <!-- named anchor --> </a> <h5 class="title" id="d668511e282">Meaning</h5> <p id="d668511e284">Among female health professionals aged at least 45 years, self-reported migraine with aura was associated with increased incidence rates of CVD, but the clinical importance of this finding remains to be determined. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-4"> <!-- named anchor --> </a> <h5 class="title" id="d668511e288">Importance</h5> <p id="d668511e290">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-5"> <!-- named anchor --> </a> <h5 class="title" id="d668511e293">Objective</h5> <p id="d668511e295">To estimate the CVD incidence rate for women with migraine with aura relative to women with other major vascular risk factors. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-6"> <!-- named anchor --> </a> <h5 class="title" id="d668511e298">Design, Setting, and Participants</h5> <p id="d668511e300">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-7"> <!-- named anchor --> </a> <h5 class="title" id="d668511e303">Exposures</h5> <p id="d668511e305">Self-reported migraine with aura compared with migraine without aura or no migraine at baseline. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-8"> <!-- named anchor --> </a> <h5 class="title" id="d668511e308">Main Outcomes and Measures</h5> <p id="d668511e310">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. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-9"> <!-- named anchor --> </a> <h5 class="title" id="d668511e313">Results</h5> <p id="d668511e315">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 ( <i>P</i> &lt; .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. </p> </div><div class="section"> <a class="named-anchor" id="ab-joi200047-10"> <!-- named anchor --> </a> <h5 class="title" id="d668511e321">Conclusions and Relevance</h5> <p id="d668511e323">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. </p> </div><p class="first" id="d668511e326">This cohort study uses Women’s Health Study data to compare the association of migraine with aura vs other major vascular risk factors (diabetes, hypertension, dyslipidemia, smoking, BMI, CVD family history) with incidence of cardiovascular disease. </p>

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          Most cited references25

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          A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women.

          Randomized trials have shown that low-dose aspirin decreases the risk of a first myocardial infarction in men, with little effect on the risk of ischemic stroke. There are few similar data in women. We randomly assigned 39,876 initially healthy women 45 years of age or older to receive 100 mg of aspirin on alternate days or placebo and then monitored them for 10 years for a first major cardiovascular event (i.e., nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes). During follow-up, 477 major cardiovascular events were confirmed in the aspirin group, as compared with 522 in the placebo group, for a nonsignificant reduction in risk with aspirin of 9 percent (relative risk, 0.91; 95 percent confidence interval, 0.80 to 1.03; P=0.13). With regard to individual end points, there was a 17 percent reduction in the risk of stroke in the aspirin group, as compared with the placebo group (relative risk, 0.83; 95 percent confidence interval, 0.69 to 0.99; P=0.04), owing to a 24 percent reduction in the risk of ischemic stroke (relative risk, 0.76; 95 percent confidence interval, 0.63 to 0.93; P=0.009) and a nonsignificant increase in the risk of hemorrhagic stroke (relative risk, 1.24; 95 percent confidence interval, 0.82 to 1.87; P=0.31). As compared with placebo, aspirin had no significant effect on the risk of fatal or nonfatal myocardial infarction (relative risk, 1.02; 95 percent confidence interval, 0.84 to 1.25; P=0.83) or death from cardiovascular causes (relative risk, 0.95; 95 percent confidence interval, 0.74 to 1.22; P=0.68). Gastrointestinal bleeding requiring transfusion was more frequent in the aspirin group than in the placebo group (relative risk, 1.40; 95 percent confidence interval, 1.07 to 1.83; P=0.02). Subgroup analyses showed that aspirin significantly reduced the risk of major cardiovascular events, ischemic stroke, and myocardial infarction among women 65 years of age or older. In this large, primary-prevention trial among women, aspirin lowered the risk of stroke without affecting the risk of myocardial infarction or death from cardiovascular causes, leading to a nonsignificant finding with respect to the primary end point. Copyright 2005 Massachusetts Medical Society.
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            The role of spreading depression, spreading depolarization and spreading ischemia in neurological disease.

            The term spreading depolarization describes a wave in the gray matter of the central nervous system characterized by swelling of neurons, distortion of dendritic spines, a large change of the slow electrical potential and silencing of brain electrical activity (spreading depression). In the clinic, unequivocal electrophysiological evidence now exists that spreading depolarizations occur abundantly in individuals with aneurismal subarachnoid hemorrhage, delayed ischemic stroke after subarachnoid hemorrhage, malignant hemispheric stroke, spontaneous intracerebral hemorrhage or traumatic brain injury. Spreading depolarization is induced experimentally by various noxious conditions including chemicals such as potassium, glutamate, inhibitors of the sodium pump, status epilepticus, hypoxia, hypoglycemia and ischemia, but it can can also invade healthy, naive tissue. Resistance vessels respond to it with tone alterations, causing either transient hyperperfusion (physiological hemodynamic response) in healthy tissue or severe hypoperfusion (inverse hemodynamic response, or spreading ischemia) in tissue at risk for progressive damage, which contributes to lesion progression. Therapies that target spreading depolarization or the inverse hemodynamic response may potentially treat these neurological conditions.
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              Migraine and cardiovascular disease: systematic review and meta-analysis

              Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. Design Systematic review and meta-analysis. Data sources Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. Data extraction Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. Results Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. Conclusion Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.
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                Author and article information

                Journal
                JAMA
                JAMA
                American Medical Association (AMA)
                0098-7484
                June 09 2020
                June 09 2020
                : 323
                : 22
                : 2281
                Affiliations
                [1 ]Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany
                [2 ]Division of Preventive Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
                Article
                10.1001/jama.2020.7172
                7284297
                32515815
                adfc6a95-1787-4743-96bc-ad384ae85d2b
                © 2020
                History

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