When Alopecia Areata Signals More than Hair Loss

Alopecia areata (AA), long regarded as a localized autoimmune condition of the hair follicles, may have broader systemic implications than previously appreciated. A recent systematic review and meta-analysis published in Frontiers in Immunology challenges the perception of AA as a disease confined to dermatologic boundaries, presenting evidence of an association between AA and cardiovascular disease (CVD).

The authors systematically searched four major databases through December 6, 2024, identifying five eligible studies conducted in the United States, Korea, and Taiwan. These included four retrospective cohort studies and one matched case-control study. All studies evaluated CVD outcomes in patients diagnosed with AA compared with individuals without AA. Study quality was assessed using the Newcastle–Ottawa Scale, with all included studies meeting criteria for medium to high quality.

Key design features included:

• A combined sample of 238,270 patients with AA
• Observational designs only (no randomized trials)
• Use of adjusted risk estimates, pooled with a random-effects model due to heterogeneity
• Subgroup analyses by AA severity and CVD subtype

Key Findings and Their Clinical Meaning

Across the pooled analysis, AA was associated with a significantly increased odds of CVD compared with controls (odds ratio [OR] 1.71; p < 0.01). This signal became more pronounced when disease severity was considered. Patients with the most extensive forms of AA, such as alopecia totalis or alopecia universalis (AT/AU), demonstrated a markedly higher risk of CVD (OR 3.80; p = 0.0017). In contrast, no significant association was observed between patch-type AA and cardiovascular outcomes (p = 0.6241).

Shared Immune Pathways

The authors contextualize these epidemiologic findings within a shared immunologic framework. Both AA and atherosclerotic cardiovascular disease involve dysregulated immune responses, including activation of cytotoxic CD8⁺ NKG2D⁺ T cells, IFN-γ–mediated signaling, and systemic cytokine imbalance. In AA, these mechanisms contribute to collapse of hair follicle immune privilege; in vascular disease, similar pathways have been implicated in endothelial dysfunction and plaque instability.

The review also references prior observational and exploratory studies reporting higher circulating levels of cardiac-associated biomarkers, such as cardiac troponin I, CRP, and N-terminal pro–B-type natriuretic peptide, as well as proteomic enrichment of atherosclerosis-related proteins in patients with AA. These molecular findings are hypothesis-generating and do not establish clinical cardiovascular disease, but they lend biological plausibility to a systemic inflammatory signal accompanying severe AA.

Extensive AA could function as a marker of heightened inflammatory activity, conceptually similar to other immune-mediated conditions such as psoriasis or systemic lupus erythematosus, which are already recognized to carry increased cardiovascular risk. Importantly, the review does not suggest that AA causes cardiovascular disease, but rather that disease severity and immune activation may identify a subset of patients with elevated vulnerability.

Subgroup Analyses

Notably, subgroup analyses with specific cardiovascular endpoints showed no statistically significant relationship between AA and ischemic stroke (OR 1.13) or myocardial infarction (OR 0.84). This finding suggests that the observed cardiovascular risk may be driven by broader or mixed CVD outcomes.

The analysis also highlights potential demographic and lifestyle risks. In one study, men with AA experienced acute myocardial infarction earlier and with increased incidence than women, despite men having a lower overall prevalence of AA. Additionally, smoking further amplified cardiovascular risk. Another study reported higher CVD hazard ratios in episodic or clinically active AA, whereas individuals with long-standing disease showed no significant increase—raising the possibility that immune activity, rather than disease duration alone, is more relevant to cardiovascular outcomes.

What This Means for Clinical Practice

The authors acknowledge several important limitations. All included studies originated from Asia and North America, limiting generalizability to other populations. Diagnostic criteria for AA subtypes were not standardized, and definitions of cardiovascular outcomes varied across studies, contributing to heterogeneity. Moreover, adjustment for key confounding variables was inconsistent, constraining causal inference.

Despite these uncertainties, this meta-analysis reframes AA, particularly severe subtypes, as a condition that may warrant broader medical attention beyond hair regrowth. While routine cardiovascular screening for all patients with AA is not yet evidence-based, the data suggests that patients with extensive disease represent a subgroup in whom cardiovascular risk assessment may be reasonable.

Reference:

Lu J, Cao X, Feng Y, Yu Y, Lu Y. Association between alopecia areata and cardiovascular disease: a systematic review and meta-analysis. Front Immunol. 2025;16:1643709. doi:10.3389/fimmu.2025.1643709.