In the JournalsPerspective

Migraines increase risk for CVD

Patients with migraine had an increased risk for ischemic stroke, hemorrhagic stroke, MI, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published in The BMJ.

Kasper Adelborg, MD, postdoctoral fellow in the department of clinical epidemiology at Aarhus University Hospital in Denmark, and colleagues analyzed data from 51,032 patients (median age, 35 years; 29% men) with a first time primary or secondary diagnosis of migraine from the Danish National Patient Registry from January 1995 to November 2013. Patients who were diagnosed with migraine before 1995 or had a history of stroke, MI, peripheral artery disease, AF or atrial flutter, VTE or HF were excluded from the study.

Matched cohorts

Each patient with migraine was matched with 10 patients free from migraine (n = 510,320). The same exclusion criteria were used for this cohort.

The incident outcomes of interest were PAD, MI, hemorrhagic or ischemic stroke, AF or atrial flutter, VTE and HF.

At the index date, patients with migraine had a slightly higher burden of comorbidity and CV risk factors compared with those without migraine.

After 19 years of follow-up, cumulative incidences per 1,000 patients for the migraine cohort compared with the general population was 45 vs. 25 for ischemic stroke, 25 vs. 17 for MI, 13 vs. 11 for PAD, 11 vs. 6 for hemorrhagic stroke, 27 vs. 18 for VTE, 19 vs. 18 for HF and 47 vs. 34 for AF or atrial flutter, respectively.

After adjusting for covariables, migraine was linked to ischemic stroke (adjusted HR = 2.26; 95% CI, 2.11-2.41), MI (aHR = 1.49; 95% CI, 1.36-1.64), hemorrhagic stroke (aHR = 1.94; 95% CI, 1.68-2.23), AF or atrial flutter (aHR = 1.25; 95% CI, 1.16-1.36) and VTE (aHR = 1.59; 95% CI, 1.45-1.74).

Migraine was not associated with HF (adjusted HR = 1.04; 95% CI, 0.93-1.16) or PAD (adjusted HR = 1.12; 95% CI, 0.96-1.3).

Increased risk at 1 year

The risk for CVD was higher in patients during the first year after a migraine diagnosis. CVD risk was also increased in women and patients who had migraines with aura.

“Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment,” Adelborg and colleagues wrote. “Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder.”

In a related editorial, Tobias Kurth, MD, professor at the Institute of Public Health at Charité–Universitätsmedizin Berlin, and colleagues wrote: “We now have plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker. However, whether migraine itself is the problem or whether the disease is a marker of another underlying cause remains unclear. From the patient’s perspective, this knowledge, coupled with a lack of evidence on any possible solutions to lower cardiovascular risk, contributes to feelings of anxiety, helplessness and frustration.” – by Darlene Dobkowski

Disclosures: Adelborg reports no relevant financial disclosures. Kurth reports he has provided methodological expertise to Amgen and CoLucid and received honorarium from Novartis.

Patients with migraine had an increased risk for ischemic stroke, hemorrhagic stroke, MI, venous thromboembolism, and atrial fibrillation or atrial flutter, according to a study published in The BMJ.

Kasper Adelborg, MD, postdoctoral fellow in the department of clinical epidemiology at Aarhus University Hospital in Denmark, and colleagues analyzed data from 51,032 patients (median age, 35 years; 29% men) with a first time primary or secondary diagnosis of migraine from the Danish National Patient Registry from January 1995 to November 2013. Patients who were diagnosed with migraine before 1995 or had a history of stroke, MI, peripheral artery disease, AF or atrial flutter, VTE or HF were excluded from the study.

Matched cohorts

Each patient with migraine was matched with 10 patients free from migraine (n = 510,320). The same exclusion criteria were used for this cohort.

The incident outcomes of interest were PAD, MI, hemorrhagic or ischemic stroke, AF or atrial flutter, VTE and HF.

At the index date, patients with migraine had a slightly higher burden of comorbidity and CV risk factors compared with those without migraine.

After 19 years of follow-up, cumulative incidences per 1,000 patients for the migraine cohort compared with the general population was 45 vs. 25 for ischemic stroke, 25 vs. 17 for MI, 13 vs. 11 for PAD, 11 vs. 6 for hemorrhagic stroke, 27 vs. 18 for VTE, 19 vs. 18 for HF and 47 vs. 34 for AF or atrial flutter, respectively.

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After adjusting for covariables, migraine was linked to ischemic stroke (adjusted HR = 2.26; 95% CI, 2.11-2.41), MI (aHR = 1.49; 95% CI, 1.36-1.64), hemorrhagic stroke (aHR = 1.94; 95% CI, 1.68-2.23), AF or atrial flutter (aHR = 1.25; 95% CI, 1.16-1.36) and VTE (aHR = 1.59; 95% CI, 1.45-1.74).

Migraine was not associated with HF (adjusted HR = 1.04; 95% CI, 0.93-1.16) or PAD (adjusted HR = 1.12; 95% CI, 0.96-1.3).

Increased risk at 1 year

The risk for CVD was higher in patients during the first year after a migraine diagnosis. CVD risk was also increased in women and patients who had migraines with aura.

“Current migraine guidelines do not recommend use of aspirin and clopidogrel in the prophylaxis of migraine, but clinicians should consider whether patients at particularly high risk of cardiovascular diseases would benefit from anticoagulant treatment,” Adelborg and colleagues wrote. “Ultimately, it will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease in patients with this common disorder.”

In a related editorial, Tobias Kurth, MD, professor at the Institute of Public Health at Charité–Universitätsmedizin Berlin, and colleagues wrote: “We now have plenty of evidence that migraine should be taken seriously as a strong cardiovascular risk marker. However, whether migraine itself is the problem or whether the disease is a marker of another underlying cause remains unclear. From the patient’s perspective, this knowledge, coupled with a lack of evidence on any possible solutions to lower cardiovascular risk, contributes to feelings of anxiety, helplessness and frustration.” – by Darlene Dobkowski

Disclosures: Adelborg reports no relevant financial disclosures. Kurth reports he has provided methodological expertise to Amgen and CoLucid and received honorarium from Novartis.

    Perspective
    Carl J. Pepine

    Carl J. Pepine

    The association between migraine headache and CV events had been inconsistent, but this study adds important new information on the long-term risk for CV events among patients with a first-time diagnosis of migraine headache from a contemporary Danish registry. The strengths include its size (> 50,000 patients with migraine) and its contemporary (1995-2013) data. Migraine was associated with significantly increased risks for MI, stroke, venous thromboembolism and atrial fibrillation/flutter, and risks were greater among women vs men.

    These data add to our recent analysis (Rambarat CA, et al. Am J Med. 2017;doi:10.1016/j.amjmed.2016.12.028) showing migraine may be an important risk factor for most CVDs among women under evaluation for suspected ischemic heart disease in the WISE cohort. More than 24% reported a history of migraine headache and these participants had an 83% excess risk for a CV event, among CV death, nonfatal MI, HF or stroke (HR = 1.83; 95% CI, 1.22-2.75) at 6.5 years’ follow-up vs. women without migraine history.

    This result was driven mainly by a more than twofold increase in stroke risk (HR = 2.33; CI 1.16-4.68), but risks for all CV events were numerically greater among participants with migraines.

    • Carl J. Pepine, MD, MACC
    • Cardiology Today Chief Medical Editor University of Florida, Gainesville

    Disclosures: Pepine reports no relevant financial disclosures.

    Perspective
    Marysia S. Tweet

    Marysia S. Tweet

    This is a large, matched cohort study assessing the association of migraine diagnosis and subsequent CVD among the Danish general population. Over 51,000 patients with migraine were matched on age, sex, and calendar year to over 510,000 controls. Although absolute risk was low, the researchers found higher risk for MI, ischemic stroke, hemorrhagic stroke, venous thromboembolism and AF/ atrial flutter among those with migraines, who were predominantly young women.

    The findings are consistent with other studies, which have found that migraines are associated with increased risk for CVD. This study specifically assesses for several specific CVD-related outcomes. They also found that although the associations were stronger in women than men and in those with aura than those without aura, all of those subgroups had increased associated risk. An important note is that the migraine cohort did have a slightly increased CV risk factor burden at index time, as shown in a table.

    These findings further demonstrate the importance for considering migraine history in the assessment of CV risk and discussion of preventative measures. It is also hypothesis-generating regarding mechanisms of disease, particularly among young women, which can prompt much-needed further dedicated studies.

    Due to limitations in the study design and coding diagnoses, certain factors such as reproductive history, oral contraceptive use, diagnosis of fibromuscular dysplasia (if known) and the presence of patent foramen ovale (if known) were not assessed. Given that the large proportion of patients were young women, these factors would be helpful for further understanding the relevance and significance of the associations found. Also, among those who had MI, identifying the mechanism of MI (eg, plaque rupture vs. paradoxical embolus vs. spontaneous coronary artery dissection vs. other) would again be helpful to attempt to better unify hypotheses regarding mechanisms of disease. Specifically, myocardial infarction due to spontaneous coronary artery dissection and a condition called fibromuscular dysplasia both predominantly affect young women, and recent studies of persons with these conditions have demonstrated notable prevalence of migraine history.

    • Marysia S. Tweet, MD, FACC
    • Cardiology Today Next Gen Innovator Assistant Professor of Medicine Department of Cardiovascular Medicine Mayo Clinic, Rochester, Minnesota

    Disclosures: Tweet reports that she is currently supported by the Office of Research on Women’s Health Building Interdisciplinary Research Careers in Women’s Health.

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