BACKGROUND: There are conflicting data on a potential association between atopic dermatitis (AD) and cardiovascular diseases (CVD). The aim of this study was to further explore this connection and whether there are biomarkers indicating the risk for CVD in AD patients. METHODS: We included 677 AD patients and 79 nonatopic controls from an observational multicenter case-control study (ProRaD: Prospective longitudinal study investigating the remission phase in patients with atopic dermatitis and other allergy-associated diseases). AD severity and atopic, metabolic, and cardiovascular conditions as well as risk factors were assessed. Serum samples were analyzed with targeted proteomics (cardiometabolics panel, Olink). RESULTS: We did not find an overall association between AD and CVD. However, AD patients without atopic comorbidities (pure AD) showed a significantly higher CVD prevalence than AD patients with atopic comorbidities (ADAC) (28.2% [37/131] vs. 14.7% [80/546], p <
0.002). Yet, this association could not be confirmed when controlling for cardiovascular risk factors. In pure AD, patients with CVD showed a more severe AD than those without CVD (median EASI [Eczema Area and Severity Index] 12.9 vs. 4.0, p <
0.002). In this subgroup of patients, EASI remained a significant predictor of CVD even in the adjusted model (adjusted odds ratio [aOR] = 1.05, p = 0.040). Forty serum cardiometabolic proteins were upregulated in AD patients compared with nonatopic controls. CC-chemokine ligand 18 (CCL18) was upregulated in both AD (p <
0.002) and CVD (p <
0.002) and its increase correlated with AD severity. CONCLUSIONS: Our study does not suggest an overall association between AD and CVD, but a more complex relation between the two conditions. Disease severity may be a risk factor for CVD in pure AD patients, but not in those with atopic comorbidities. CCL18 may be a biomarker for CVD.