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Understanding The Migraine-Cardiovascular Connection

Posted on May 14 2025, By: Cerebral Torque

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Understanding The Migraine-Cardiovascular Connection

New research reveals surprising links between migraine and cardiovascular health. This offers us some insights for prevention and personalized treatment
May 2025 | Based on recent research from The Journal of Headache and Pain

The Paradox: Migraine as a Cardiovascular Risk Factor

If you live with migraine, especially migraine with aura, you might be surprised to learn about its complex relationship with cardiovascular health. Recent research has shown a paradoxical connection between migraine and cardiovascular risk that may influence prevention strategies and treatment options.

Key Research Finding

A 2025 study published in The Journal of Headache and Pain explored genetic factors connecting migraine and coronary artery disease. Surprisingly, researchers found that specific genetic variants linked to endothelial cell function (EC-PRS) were associated with both increased coronary artery disease risk and DECREASED migraine risk.

Migraine has increasingly been recognized as an independent cardiovascular risk factor, associated with major cardiovascular and cerebrovascular events. However, the biological mechanisms behind this connection are complex and do NOT follow traditional atherosclerotic pathways. Basically, it's not clogged arteries causing the increase of cardiovascular and cerebrovascular events, but something else. 

The Non-Traditional Cardiovascular Risk Factor

Migraine's Unique Cardiovascular Profile
Traditional CV Risk Factors Often Not Present
Large-Vessel Atherosclerosis Not Typically Associated
Coronary Severity Scores Often Lower in Migraine Patients
Migraine with Aura Higher CV Risk Than Obesity

Unlike conventional cardiovascular risk factors such as hypertension, diabetes, or obesity (which often cluster together), migraine represents a "non-atherosclerotic" or "non-traditional" risk factor. In fact, women with migraine and suspected cardiac ischemia showed less severe angiographic coronary artery disease compared to those without migraine.

What is EC-PRS?

The Endothelial Cell-specific Polygenic Risk Score (EC-PRS) consists of 35 single nucleotide polymorphisms associated with coronary artery disease. Recent research found that this genetic score is not only linked to coronary artery disease but also associated with a decreased risk of migraine headaches (OR per 1 SD increase = 0.94).

Biological Mechanisms: Beyond Simple Explanations

The biology connecting migraine and cardiovascular risk unfolds with far greater complexity than previously thought. Researchers have identified several potential pathways that might explain this paradoxical relationship.

1
Endothelial Dysfunction
May play a role in migraine pathophysiology, particularly during aura phases, but evidence is inconsistent
2
Neuropeptide Activity
Altered in migraine patients, with reduced peripheral microvascular neuropeptide action observed in studies
3
Lipid Profiles
Complex relationship between LDL cholesterol and migraine risk, influenced by aura status and migraine activity
4
Genetic Factors
EC-PRS and other genetic markers suggest shared but complex biological pathways

Neuropeptides: A Key Connection

Calcitonin gene-related peptide (CGRP) is a crucial vasodilatory neuropeptide in migraine pathophysiology. It serves as both a target for anti-migraine therapies and a protective molecule under ischemic circumstances. Other neuropeptides like PACAP and VIP may also play important roles in the migraine-cardiovascular connection.

Implications for Treatment: The Statin Connection

One of the most intriguing findings from recent research is the potential role of statins in migraine management. Studies have identified associations between the HMG-CoA reductase gene and migraine risk, especially with aura.

A recent Mendelian randomization study demonstrated significant associations between lipid-modifying drug target genes and a lower risk of migraine, particularly with the enhancement of LPL (lipoprotein lipase) and inhibition of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase).
Potential Benefits of Statins for Migraine Patients
Migraine Frequency Potential Reduction
Triptan Usage Potential Reduction
Cost-Effectiveness Relatively Low-Cost Option
Effectiveness Varies Based on Lifestyle & Comorbidities

While larger randomized studies are needed, statins present a promising adjunct preventive option for migraine. Their effectiveness appears to vary based on lifestyle factors and comorbid conditions, highlighting the importance of personalized treatment approaches.

Personalized Prevention Strategies

Understanding your specific migraine and cardiovascular risk profile can help guide personalized prevention strategies. Based on the latest research, here are some key considerations:

Key Considerations for Personalized Prevention

  • Migraine Type: Patients with migraine with aura have different risk profiles than those without aura
  • Migraine Activity Status: Research shows higher cardiovascular risk in those with a migraine history but not necessarily active migraine
  • Lipid Profiles: Regular monitoring may be beneficial, especially for those with additional risk factors
  • Blood Pressure Management: Crucial for all migraine patients to control this potentially compounding risk factor
  • Hormonal Influences: Women should discuss contraception options with healthcare providers, especially with migraine with aura

Summary of Migraine-Cardiovascular Research Findings

This table summarizes the key findings from recent research on the connection between migraine and cardiovascular health.

Category Key Findings
Genetic Connections EC-PRS associations:
  • Increased risk of coronary artery disease
  • Decreased risk of migraine headaches (OR per 1 SD increase = 0.94)
  • Risk modified by LDL-C levels
Suggests shared but complex genetic pathways between migraine and cardiovascular disease
Vascular Pathways
  • Large-vessel atherosclerosis: Not typically associated with migraine
  • Endothelial dysfunction: May be involved in migraine attacks, particularly in aura phase
  • Neuropeptide action: Observed to be lower in migraine patients
Migraine appears to be a "non-atherosclerotic" cardiovascular risk factor
Lipid Connections Complex relationships:
  • Conflicting data on LDL-C involvement in migraine
  • Presence of aura and migraine activity status influence lipid profiles
  • Association between HMG-CoA reductase gene and increased migraine risk
Treatment Implications
  • Statins: Potential for reducing migraine frequency and triptan usage
  • Effectiveness: Varies based on lifestyle factors and comorbid conditions
  • Research needed: To better integrate lipid-lowering therapies into individualized treatment strategies
Suggests potential for personalized treatment approaches based on individual risk profiles

What This Means For You

If you live with migraine, especially migraine with aura, this research provides valuable insights into your cardiovascular health:

Action Steps for Migraine Patients

  • Discuss your cardiovascular risk profile with your healthcare provider, mentioning this research
  • Consider comprehensive screening for cardiovascular risk factors, even if you don't have traditional risks
  • If appropriate, ask about the potential benefits of statins as part of your migraine management strategy
  • For women with migraine with aura who need contraception, discuss non-estrogen options
  • Maintain regular follow-ups to monitor both migraine activity and cardiovascular health

While this research provides exciting new directions for migraine care, remember that treatment decisions should always be made in consultation with your healthcare provider, who can help develop a plan tailored to your specific needs and risk profile.

The complex biological factors linking migraine and cardiovascular disease opens new avenues for personalized prevention and treatment strategies that may benefit millions of individuals with migraine.

References

  1. Al-Hassany L, van Drie RWA, Boucherie DM, MaassenVanDenBrink A. Unraveling the paradox: cardiovascular risk profiling in migraine– a correspondence. The Journal of Headache and Pain. 2025;26:113.
  2. Marston NA, Kamanu FK, Melloni GEM, et al. Endothelial cell-related genetic variants identify LDL cholesterol-sensitive individuals who derive greater benefit from aggressive lipid lowering. Nat Med. 2025;31(3):963–969.
  3. Kurth T, Rist PM, Ridker PM, et al. Association of Migraine With Aura and Other Risk Factors With Incident Cardiovascular Disease in Women. JAMA. 2020;323(22):2281–2289.
  4. Makhlouf HA, Hassan AK, Almosilhy NA, et al. Exploring the association between statins use or HMG-CoA reductase inhibition and migraine: a systematic review and meta-analysis. J Headache Pain. 2025;26(1):23.
  5. Al-Hassany L, Boucherie DM, Creeney H, et al. Future targets for migraine treatment beyond CGRP. J Headache Pain. 2023;24(1):76.
  6. Bi Y, Zhu Y, Tang S, Huang Y. Lipids, lipid-modifying drug target genes and migraine: a Mendelian randomization study. J Headache Pain. 2023;24(1):112.
  7. Ibrahimi K, Rist PM, Carpenet C, et al. Vascular Risk Score and Associations With Past, Current, or Future Migraine in Women: Cohort Study. Neurology. 2022;99(16):e1694–701.

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