New Study Sheds Light on Vitiligo-CHD Association

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Affecting approximately 0.5 to 2% of the global population, vitiligo’s clinical manifestations extend beyond the skin, with increasing evidence suggesting systemic implications. Among these, the potential association between vitiligo and cardiovascular diseases (CVD), particularly coronary heart disease (CHD), has become a growing area of interest.¹ However, observational studies to date have yielded conflicting outcomes, necessitating a more robust methodological approach to determine causality.

Methods

Most recently, researchers employed a bidirectional 2-sample Mendelian randomization (MR) design to investigate the causal relationship between vitiligo and CVD.² MR utilizes genetic variants as instrumental variables (IVs), minimizing confounding and reverse causality, which are common limitations of traditional observational studies. In addition, a 2-step mediation analysis was performed to explore the potential mechanistic role of inflammatory cytokines in this association.

Results

From a pool of genome-wide significant single nucleotide polymorphisms (SNPs), 42 IVs associated with vitiligo were identified, with all exceeding the F-statistic threshold of 10, indicating strong instruments. The MR analysis revealed a potential causal association between vitiligo and increased risk of CHD (OR = 1.021; 95% CI = 1.003–1.039; p = 0.015). No significant associations were found between vitiligo and 12 other cardiovascular outcomes, including stroke, hypertension, and myocardial infarction. This result remained directionally consistent across MR methods (inverse variance weighted [IVW], MR-Egger, weighted median, and weighted mode). A replication analysis in an independent cohort supported this finding, strengthening the robustness of the CHD association.

Sensitivity analyses further validated the findings, showing no evidence of horizontal pleiotropy, and excluding the presence of reverse causality from CVD to vitiligo. While the association between vitiligo and CHD did not remain statistically significant after Bonferroni correction (p = 0.3), the consistency in replication suggests the possibility of a type II error due to conservative correction methods.

The 2-step mediation MR analysis identified CCL11 (also known as eotaxin-1), a chemokine, as a potential mediator in the causal pathway. Vitiligo was negatively associated with CCL11 levels (OR = 0.9804; p = 0.023), while CCL11 was positively associated with CHD risk (OR = 1.0954; p = 0.002). The mediation proportion was estimated at −14.3%, indicating a suppression effect—where reduced CCL11 levels in vitiligo may attenuate the risk of CHD. Bioinformatics analyses confirmed CCL11’s involvement in chemokine-mediated signaling and vascular inflammation, aligning with its known role in atherogenesis.

Previous studies have associated vitiligo with subclinical atherosclerosis and metabolic disturbances that elevate CVD risk. For example, increased carotid intima-media thickness and atherosclerotic plaques in vitiligo patients have been reported, along with higher rates of metabolic syndrome and elevated homocysteine levels—factors known to contribute to coronary pathology.

Discussion

Despite its strengths—including the use of MR design, GWAS summary statistics, and replication—the study has limitations. The data predominantly represent European populations, limiting generalizability. Additionally, the lack of individual-level data precluded stratified analyses based on disease characteristics or treatment history. Lastly, while CCL11 emerged as a mediator, researchers stated other pathways likely contribute to the complex interplay between autoimmunity and cardiovascular health.

Conclusion

This study provides genetic evidence of a potential causal association between vitiligo and CHD, partially mediated by inflammatory mechanisms involving CCL11. Although the association did not withstand correction for multiple testing, researchers stated replication results suggest it remains biologically and clinically meaningful. These findings underscore the need for further research, particularly in diverse populations and with expanded mechanistic exploration, to better understand and mitigate cardiovascular risk in patients with vitiligo.

References

1. Conrad N, Verbeke G, Molenberghs G, et al. Autoimmune diseases and cardiovascular risk: a population-based study on 19 autoimmune diseases and 12 cardiovascular diseases in 22 million individuals in the UK. Lancet. 2022;400(10354):733-743. doi:10.1016/S0140-6736(22)01349-6
2. Zhang X, Pu L, Pu C, He Q. Associations and mediators between vitiligo and cardiovascular diseases: a Mendelian randomization study. Sci Rep. 2025 Apr 1;15(1):11110. doi: 10.1038/s41598-025-95638-y. PMID: 40169829; PMCID: PMC11961564.