Combination of Migraine and Gestational Diabetes Poses Greater Risk for Premature Major Adverse Cardiovascular and Cerebrovascular Events

Cecilia Hvitfeldt Fuglsang Nielsen, MD, PhD

Findings from a recently published nationwide population-based longitudinal study of Danish women showed that migraine and gestational diabetes mellitus (GDM) were both independently associated with an increased risk of major adverse cardiovascular and cerebrovascular events (MACCE). The risk of premature MACCE was greatest among women with both migraine and GDM, although this risk estimate was imprecise.

Spanning from 1996 to 2018, the study included 1,307,456 women free of migraine and free of GDM, 56,811 women with migraine, 24,700 women with GDM, and 1484 women with migraine and GDM. All women included had at least 1 pregnancy during that time period. Published in Headache, the median age of the cohort ranged from 30 to 33 years, with the women free of migraine and free of GDM being youngest and women with both migraine and GDM being oldest.

Led by Cecilia Hvitfeldt Fuglsang Nielsen, MD, PhD, medical doctor in the Department of Clinical Medicine at Aarhus University, median (interquartile range) follow-up was 14.8 (8.8–20.4) years for women free of migraine and free of GDM; 11.5 (6.8–16.6) years for women with migraine; 9.9 (5.6–14.8) years for women with GDM; and 8.4 (5.2–13.0) years for women with migraine and GDM. Results showed a 20-year absolute risk of premature MACCE was 1.3% (95% CI 1.3–1.3%), 2.3% (95% CI 2.0–2.5%), 2.2% (95% CI 1.9–2.6%), and 3.7% (95% CI 1.7–6.8%) for those respective groups.

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In the analysis, women with both migraine and GDM had the greatest 20-year crude HR of premature MACCE compared with women free of migraine and free of GDM (2.76; 95% CI, 1.69-4.51). For women with migraine and those with GDM, the 20-year crude HRs were 1.78 (95% CI, 1.64-1.94) and 1.92 (95% CI, 1.68-2.19), respectively. Over the 20-year follow-up, women with both migraine and GDM had the highest standardized incident rate per 100,000 person years of premature MACCE (115.2; 95% CI, 70.6-188.1).

The study’s strengths include its large population sample, high follow-up completeness, and accurate coding for GDM. There were a number of limitations, including a potential risk of misclassification of migraine diagnoses and prescription records, lack of migraine subtype data, and an underestimation of migraine and GDM prevalence. In addition, although the study controlled for many confounders, there may still be residual or unmeasured factors affecting the findings. Furthermore, information on the presumed cause of stroke was lacking, which could have limited understanding of underlying pathophysiological mechanisms.

The 20-year absolute risk for women free of migraine and free of GDM was 0.4% (95% CI, 0.4-0.4%) for myocardial infarction (MI), 0.6% (95% CI 0.6–0.6%) for ischemic stroke, and 0.3% (0.3–0.3%) for hemorrhagic stroke. In comparison, those with both migraine and GDM had rates of 1.7% (95%CI 0.5–4.3%), 1.7% (95% CI 0.5–4.3%), and 0.3% (95% CI 0.1–1.0%), respectively. For women with just migraine, the estimates were 0.8% (95% CI 0.6–0.9%), 1.2% (95% CI 1.0–1.3%), and 0.5% (95% CI 0.4–0.6%), while for women with GDM, they were 1.0% (95% CI 0.8–1.3%), 1.0% (95% CI 0.8–1.2%), and 0.4% (95% CI 0.3–0.5%), respectively.

The adjusted HR among women with both migraine and GDM was 4.38 (95% CI 1.13–16.9) for premature MI; 2.00 (95% CI 0.84–4.78) for premature ischemic stroke; and 0.34 (95% CI 0.05–2.38) for premature hemorrhagic stroke. In sensitivity analyses, adjusting for BMI weakened the link between GDM and major cardiovascular events, had no effect for women with migraine, and strengthened the link for women with both migraine and GDM, though estimates for this group were less precise. Limiting the time period also reduced the strength of associations for all three groups.

REFERENCE
1. Fugslang CH, Pedersen L, Schmidt M, et al. The combined impact of migraine and gestational diabetes on long-term risk of premature myocardial infarction and stroke: A population-based cohort study. Headache. Published August 28, 2024. doi:10.1111/head.14821