Framingham-Based Cardiovascular Risk Estimates Among People With Episodic Migraine in the US Population: Results from the American Migraine Prevalence and Prevention (AMPP) Study


  • Funding: The American Migraine Prevalence and Prevention (AMPP) Study was funded through a research grant to the National Headache Foundation (NHF) from McNeil-Janssen Scientific Affairs (MJSA) LLC, Raritan, NJ. The AMPP Study database was donated by MJSA to the NHF for use in various projects. Additional funding for this manuscript was provided by Merck & Co. (Kenilworth, NJ) and CoLucid Pharmaceuticals (Cambridge, MA), now a wholly owned subsidiary of Eli Lilly and Company (Indianapolis, IN).

  • Conflict of Interest: Richard B. Lipton, MD, is the Edwin S. Lowe Professor of Neurology at the Albert Einstein College of Medicine in New York. He receives research support from the National Institutes of Health (NIH): 2PO1 AG003949 (Program Director), 5U10 NS077308 (PI), 1RO1 AG042595 (Investigator), RO1 NS082432 (Investigator), K23 NS09610 (Mentor), K23AG049466 (Mentor). He also receives support from the Migraine Research Foundation and the National Headache Foundation. He serves on the editorial board of Neurology and as senior advisor to Headache. He has reviewed for the NIA and NINDS, holds stock options in eNeura Therapeutics and Biohaven Holdings; serves as consultant, advisory board member, or has received honoraria from: American Academy of Neurology, Alder, Allergan, American Headache Society (AHS), Amgen, Autonomic Technologies, Avanir, Biohaven, Biovision, Boston Scientific, Colucid, Dr. Reddy's Laboratories/Promius Pharma, Electrocore, Eli Lilly, eNeura Therapeutics, GlaxoSmithKline, Merck, Pernix, Pfizer, Supernus, Teva, Trigemina, Vector, Vedanta. He receives royalties from Wolff's Headache, 8th Edition, Oxford Press University, 2009, Wiley and Informa.

    Michael L. Reed, PhD, is managing director of Vedanta Research, which has received support funded by Allergan, Amgen, Colucid Pharmaceuticals, Endo Pharmaceuticals, GlaxoSmithKline, Merck, Novartis, Ortho-McNeil, Teva Pharmaceuticals, Zogenix, and Dr. Reddy's Laboratories/Promius Pharma via grants from the NHF.

    Tobias Kurth, MD, ScD, has received grants from the Else-Kröner-Fresenius-Stiftung/German Scholars Organization, the US NIH, and the French National Research Agency. He is a consultant for Amgen on a scientific project, for which the Charité - Universitätsmedizin Berlin receives research funds. He has received honoraria for editorial services from The British Medical Journal (BMJ) and Cephalalgia. As a board of trustee member of the International Headache Society (IHS), he has received compensation of travel and accommodation expenses by the IHS.

    Kristina Fanning, PhD, is an employee of Vedanta Research, which has received support funded by Allergan, Amgen, Colucid Pharmaceuticals, Endo Pharmaceuticals, GlaxoSmithKline, Merck, Novartis, Ortho-McNeil, Teva Pharmaceuticals, Zogenix, and Dr. Reddy's Laboratories/Promius Pharma via grants from the NHF.

    Dawn C. Buse, PhD, has received grant support and honoraria from Allergan, Amgen, Avanir, Biohaven, Eli Lilly, Dr. Reddy's Laboratories/Promius Pharma, the AHS, and the NHF. She is an employee of Montefiore Medical Center, which has received research support funded by Allergan, Amgen, Avanir, CoLucid Pharmaceuticals, Dr. Reddy's Laboratories/Promius Pharma, Teva Pharmaceuticals, and Zogenix, both directly and via grants to the NHF. She is on the editorial board of the Journal of Headache and Pain, Current Pain and Headache Reports, and Pain Pathways Magazine.



Cardiovascular (CV) events, conditions, and procedures (ECPs) are common in persons with migraine and are a contraindication to triptan and ergot use. In a prior study, we estimated that there are 2.6 million American adults with episodic migraine (EM) who have had CV ECPs. However, the prior analysis did not assess persons with migraine without CV ECPs who are at high risk for a first cardiovascular disease (CVD) event.


To use the Framingham nonlaboratory CVD events risk equation to estimate the number of individuals with EM who are at elevated risk for a first CVD event in the next 10 years using data from the American Migraine Prevalence and Prevention Study, and then to extrapolate the findings to the US population to estimate the scope of people with EM for whom triptan and ergot therapies may be problematic.


Data from respondents to the 2009 American Migraine Prevalence and Prevention (AMPP) Study questionnaire aged ≥22 who met criteria and headache day frequency for EM were included in this cross-sectional analysis. Ten-year, first CVD event risk was calculated using the nonlaboratory Framingham CV disease risk score (FRS). Variables were collected via respondent self-report and included sex, age, height, and weight to calculate body mass index (BMI), smoking status, and the presence of hypertension and diabetes among other variables. Standard FRS cut scores of ≥21 for women and ≥16 for men were used, which indicate a 30% or greater risk of a first CVD event in the next 10 years. History of CV ECPs was collected via self-report of ever having the ECP and for events and conditions that were diagnosed by a physician. We applied rates of positive ECPs and rates of high FRS to age and sex stratified estimates of the number of people with EM in the US derived from 2015 US Census data to estimate rates of both in the population.


The AMPP Study analysis sample included 5227 women and 1496 men with EM. Results showed that 69.5% of women and 73.4% of men had at least one CV risk factor from the FRS, 38.9% of women and 41.6% of men had ≥2 risk factors, and 18.6% of women and 19.1% of men had ≥3 risk factors. The proportion of women with high FRS was 0% for those aged 22-39, 0.8% (95%CI: 0.5-1.2%) among 40- to 59-year-olds and 15.2% (95% CI: 13.3-17.4%) among the ≥60 age group. For men, the corresponding proportions were 0, 7.3% (95% CI: 5.7-9.4%), and 53.0% (95% CI: 4.7-58.1%). Projecting to a national US sample, the number of persons with EM and high FRS was 403,000 for women and 510,000 for men. The proportion of women and men at high risk for future CV events based on a prior CV ECP, a high FRS or both increased with age from 20-39 (women 4.5%, men 4.2%), 40-59 (women 11.8%, men 18.6%), and ≥60 (women 31.2%, men 61.8%). An estimated 141,000 men aged 40-59 and 187,000 aged ≥60 and 34,000 women aged 40-59 and 181,000 women aged ≥60 in the US population with EM have not had a CV ECP but are at increased risk for a future CV event within the next 10 years based upon their FRS alone.


Among people with EM in the US population, the number of women and men with relative contraindications to triptans and ergots based on a high FRS includes over 900,000 women and men. This includes more than half a million individuals with EM who have not had a prior CV ECP.