Chronic Spontaneous Urticaria Linked to Increased Heart Disease Risk

Individuals diagnosed with chronic spontaneous urticaria (CSU) are at a moderately increased risk of multiple cardiovascular diseases, with conduction disorders showing the most consistent and significant association, according to a study published in Allergy.¹

CSU is a mast cell-driven inflammatory skin condition that affects up to 1% of adults and is known for its unpredictable symptoms and substantial negative impact on a patient's quality of life.² While previous studies have shown a possible link between CSU and cardiovascular health, the results have been inconsistent.

“Previous epidemiologic studies have yielded inconsistent results, with some reporting no increase in major adverse cardiovascular events (MACE) and others identifying higher odds of arrhythmias, coronary atherosclerosis, and hypertension,”³ the authors explained. “Furthermore, a recent large mortality study found elevated all-cause and cause-specific mortality, including ischemic heart disease, among patients with CSU.⁴ These findings, combined with the known pro-inflammatory, pro-thrombotic, and metabolic alterations in CSU, suggest the potential for increased cardiovascular risk, but robust longitudinal evidence is lacking.”

To address this gap, the researchers performed a retrospective, propensity-score–matched cohort study leveraging extensive data from the US Collaborative Network of the TriNetX electronic health records database, which encompasses more than 129 million patients.¹

The study included 105,593 adult patients with CSU, defined as repeated International Classification of Diseases, 10th Revision, Clinical Modification L50 codes at least 6 weeks apart, who were matched 1:1 to non-CSU controls on key demographics and cardiovascular risk factors. The median follow-up period for the matched cohorts was approximately 3 years.

CSU was significantly associated with an increased risk across all 6 predefined cardiovascular outcomes assessed over a period of 3 months to 5 years post-index. The adjusted hazard ratios (aHRs) for cardiovascular outcomes in patients with CSU were:

• MACE: aHR of 1.25 (95% CI, 1.17-1.33)
• Venous thromboembolism: aHR of 1.63 (95% CI, 1.45-1.83)
• Conduction disorders: aHR of 1.82 (95% CI, 1.66-2.01)
• Carditis: aHR of 1.86 (95% CI, 1.77-1.95)
• Valvular heart disease: aHR of 1.67 (95% CI, 1.54-1.82)
• Rheumatic heart disease: aHR of 1.65 (95% CI, 1.39-1.97)

All of these associations were statistically significant (P < .0001) and were robust across sensitivity and most subgroup analyses. Conduction disorders showed the most consistent elevation in risk across sex and race/ethnicity subgroups.

“The observed associations are biologically plausible,” the authors wrote. “CSU is characterized by chronic systemic inflammation, with elevated C-reactive protein, interleukin-6, and tumor necrosis factor, all linked to incident cardiovascular events and mortality. CSU is also associated with metabolic syndrome components such as obesity, hypertension, diabetes, and dyslipidemia, which may further promote vascular injury.”

The activation of coagulation and complement pathways in CSU could also contribute to a pro-thrombotic and pro-arrhythmic environment, the authors noted.

The findings add to prior cross-sectional and case-control observations, as they establish a temporal relationship between a CSU diagnosis and subsequent cardiovascular disease in a large, longitudinal cohort.

While the study had limitations, including its reliance on diagnostic coding, the potential for residual confounding, and an inability to establish causality or assess treatment effects, the consistency of the results across multiple analyses strengthens their validity, the authors explained.

“In conclusion, CSU is associated with a moderately increased risk of multiple cardiovascular diseases, most consistently conduction disorders,” the authors wrote. “Given the morbidity and mortality associated with these conditions, clinicians should consider routine cardiovascular risk assessment in CSU management, with attention to symptoms or signs of arrhythmia. Further research should explore the impact of disease control and targeted therapy on cardiovascular outcomes in this patient population.”

References

1. Curman P, Thaci D, Ludwig RJ. Increased cardiovascular risk in chronic spontaneous urticaria: a large real-world cohort study. Allergy. Published online October 25, 2025. doi:10.1111/all.70128

2. Tbakhi B, Ware K, Park HS, Bernstein JS, Bernstein JA. An overview of chronic spontaneous urticaria: diagnosis, management, and treatment. Allergy Asthma Immunol Res. 2025;17(5):531-546. doi:10.4168/aair.2025.17.5.531

3. Andrade LF, Haq Z, Abdi P, et al. Association of cardiovascular disease and chronic spontaneous urticaria: a case-control study. Am J Clin Dermatol. 2024;25(5):849-851. doi:10.1007/s40257-024-00881-0

4. Kolkhir P, Bieber K, Hawro T, et al. Mortality in adult patients with chronic spontaneous urticaria: a real-world cohort study. J Allergy Clin Immunol. 2025;155(4):1290-1298. doi:10.1016/j.jaci.2024.11.036