Association between Migraine and Cardiovascular Diseases among Women of a Tertiary Care Hospital, Hyderabad – A Case–Control Study

ABSTRACT IMAGE

INTRODUCTION

Migraine is a common, disabling, primary headache disorder with systemic vascular involvement, autonomic dysfunction, and a wide range of ischemic vascular disorders. Individuals with migraine particularly migraine with aura are at risk for both ischemic and hemorrhagic forms of stroke, hypertension, ischemic heart disease, myocardial infarction (MI), angina, coronary revascularization procedures, and vascular mortality.^[1] Although the exact mechanisms to explain increased vascular events are not fully understood, hypertension, smoking, and the use of oral contraceptives have been found to increase the risk of ischemic stroke for young women with migraine.^[2] The poor control of blood pressure may exacerbate the frequency and severity of migraine when they are coexistent.^[3]

Although the absolute effect of migraine on “vascular risks” is small, good practice parameters dwell on treating and reducing existing cardiovascular risk factors through lifestyle modification, encouraging smoking cessation, and advocating the wise use of agents such as ergot alkaloids and oral contraceptives, after a risk-benefit analysis.^[4]

Therefore, this study was taken with a primary objective to compare the association between cardiovascular diseases (CVDs) and migraine along with other conventional risk factors among the cases and controls. A secondary objective was to evaluate the risk factors among cases having migraine with and without aura.

MATERIALS AND METHODS

RESULTS

Our study included 382 women, 191 cases of those having any of the CVDs and 192 as controls without having any of the CVDs. Among the CVDs – hypertensives were 189 (99.4%), stroke 1 (0.3%), and coronary artery disease 1 (0.3%); on comparison of general characteristics among cases and controls, there was a statistically significant association between age, educational status, occupation, physical activity, family history, BMI, and CVDs [Table 1].

Among those with any of the CVDs, there was a statistically significant association with the presence of migraine [Figure 1]. The odds for the presence of migraine among those having any of the CVDs were 12.35 times compared to those without migraine (confidence interval [CI] 7.12–21.41).

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Figure 1:

Associatio n between migraine and cardiovascular diseases. (Chi-square=98.95 chi-square used to show association between cardiovascular disease presence and absence with and without history of migraine. ie 2x2 table ; P value 0.0001, CVD-Cardiovascular disease, H/o-History of migraine).

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Among the cases-on evaluation of various risk factors for the status of migraine with aura and without aura, we found no significant association between education, occupation, presence of diabetes mellitus, regular physical activity, overweight, and obesity. Only a statistically significant association was found between frequent intake of junk food and migraine with aura having a higher percentage [Table 2]. Alcohol and tobacco consumption was found only among 2 of our study participants.

Since cases of hypertension were predominant, on subgroup analysis – we found uncontrolled hypertension to be more among those in migraine with Aura patients compared to those without aura. However, it was not statistically significant [Table 3].

DISCUSSION

Our case–control study included 191 cases having any of the CVDs; with predominant hypertensives constituting 98%, stroke at 1%, and coronary artery disease at 1%. Among the general characteristics, we found significant risk factors of increased age, illiterates, housewives, presence of diabetes mellitus, family history, and increased BMI having any of the CVD. There was a statistical association between migraine and CVD with an OR of 12.35 times (7.12–21.4). Among these cases, we found only regular intake of junk food to be the statistically significant factor among migraineurs with aura. A comparison of the status of hypertension with migraine status, it revealed that uncontrolled status was more predominant among migraineurs with aura compared to those without aura.

These findings were consistent with the Gupta and Srivastava study, namely, that migraineurs were at a higher risk of any of the CVDs than those without having an OR of 2.77 (1.56–4.90) in the fully adjusted model. Following subgroup analysis, migraineurs with aura had higher ORs than migraineurs without aura for the association between migraine or severe headache and CVD.^[4]

This has also been supported by a Danish population-based cohort study wherein after 18 years of follow-up, migraine patients had an increased risk of MI (OR 1.49, CI 95%: CI: 1.36–1.64), ischemic stroke (OR 2.26, CI 95%: CI: 2.11–2.41), and hemorrhagic stroke (OR 1.94, 95% CI: 1.68–2.23).^[8] In a study of 115,541 young, middle-aged female nurses in the Nurses’ Health Study II, which revealed a positive correlation between migraine and MI (OR 1.39, 95% CI: 1.18–1.64), stroke (OR 1.62, 95% CI: 1.37–1.92), angina pectoris/coronary revascularization (OR 1.73, 95% CI: 1.29–2.32), and cardiovascular mortality (OR 1.37, 95% CI: 1.02–1.83). The association between migraine and a higher risk of MI and stroke (including unspecified, ischemic, and hemorrhagic stroke) as well as a higher risk of death from cardiovascular causes was discovered by a recently published meta-analysis of 18 prospective cohort studies involving 1.6 million migraine sufferers. The majority of the explanations for the moderate to high degree of heterogeneity in cardiovascular outcomes seen in these studies are with migraineurs with the presence of aura.^[9]

Although extensive literature has described the association between migraine and CVD in recent decades, the underlying mechanisms appear complex and multidimensional. From a pathophysiological perspective, the association between migraine and CVD may reflect the possibility that common cellular and molecular bases underlie the pathogenesis of both diseases. Decreased number and function of endothelial progenitor cells, endothelial dysfunction, limited vasoconstriction, platelet aggregation, and excessive activation of the coagulation cascade are key events closely linked to the pathogenesis of migraine, and these factors also play a crucial role in accelerating the development of CVD.^[10-13] The cardiovascular system may be adversely affected by certain migraine treatments, including non-steroidal anti-inflammatory drugs, triptans, and ergotamine. This effect seems to worsen as migraine dosage and intensity increase.^[14]

Furthermore, there is evidence that migraines may play a role in the development of CVD because they have been closely linked to established risk factors for CVDs, such as hypertension, diabetes, and hypercholesterolemia, all of which are more prevalent in individuals who experience aura-producing migraines by raising the risk profiles of other CVDs.^[15]

In a study by Wang et al. about migraine and CVDs, there was a positive association between migraine and CVD.^[16] Given the high frequency of migraine in the general population, the impact of increased cardiovascular risk associated with migraine appears to be minimal at the individual level; however, at the population level, migraine may result in a significant risk of CVD. The risk of CVD in male and female adult residents over the next 10 years was estimated using QRISK3 risk prediction models that included migraine as an indicator for cardiovascular risk stratification. These results suggest that migraine is becoming more widely acknowledged as a significant risk. It is essential in clinical practice to identify migraine patients who are at high risk of CVD, and it is a factor to take into account.^[17] Early detection and identification of the CVD process in patients with migraine and early initiation of pharmacological interventions may also improve the prognosis of patients with migraine and CVD. As per the latest guidelines 2022 from the German Society of Neurology, the beta-blockers propranolol and metoprolol, the calcium antagonist flunarizine, as well as the anticonvulsants valproic acid and topiramate, and the antidepressant amitriptyline are effective in migraine prevention treatment.^[18]

In contrast to all these studies, Sacco et al. in their review article on conventional vascular risk factors: Their role in the association between migraine and CVDs concluded from their review that there was no solid evidence to demonstrate an increased burden of conventional vascular risk factors in migraineurs, with the only significant have dyslipidemia and cigarette smoking.^[19]

This extreme variation could be explained by the differences in selection criteria, study designs, operational definitions used to define migraine, and inadequate control of confounders such as age and gender.

Although we have attempted to review the literature and address potential risk factors as much as possible, given that CVD is an amalgamation of several complex and multifaceted diseases, there may still be unidentified or unmeasured confounders, which could also play a role in the pathogenesis of CVDs.

Limitations are we need to have cohort studies to establish biological plausibility in the near future. Moreover, since the self-reported question of migraine status was assessed, there are high chances of recall biases due to the retrospective nature of self-assessment measures.

CONCLUSION

This study showed that migraine with aura has a significant association with CVDs with 90% of women having a history of migraine, henceforth proving that women have a higher preponderance than men. Hence, migraine a benign and episodic condition can also be one of the risk factors for CVD, and determining whether prevention strategies in migraine patients can reduce the cardiovascular burden is of utmost importance. Modification of lifestyle factors including avoidance of frequent intake of junk food such as noodles, fried potatoes, chips, and coke can become a targeted intervention to reduce the risk. Physical activity on a regular basis is important along with adequate control of disease status that is crucial for the prevention of further complications.