Immediate drug hypersensitivity severity is associated with cardiovascular risk

Background: Drug hypersensitivity reactions (DHR) exhibit substantial clinical heterogeneity. Although established cardiovascular disease is a known risk factor for severe anaphylaxis, the impact of subclinical cardiovascular risk on DHR severity remains poorly understood. Objective: This study investigated the association between Systematic Coronary Risk Evaluation 2 (SCORE2) estimated cardiovascular risk and the severity of immediate-type DHRs. Methods: This retrospective study included 161 patients ages 40-69 years (median age, 49 years; 79.5% women) with immediate-type DHRs. To assess the subclinical risk, those with known cardiovascular disease, diabetes, or chronic kidney disease were excluded. Reaction severity was graded by using the Brown system, and SCORE2 was calculated by using clinical data from the 12 months preceding the reaction. Results: Reaction severity was graded as mild (35.4%), moderate (34.8%), or severe (29.8%). The median SCORE2 values were significantly higher in the severe group versus the mild group (4.10% versus 2.50%; p = 0.022). The proportion of patients in high or very high SCORE2 risk categories increased stepwise with reaction severity (35.1% in the mild group versus 64.6% in the severe group; p = 0.011). In an univariable ordinal logistic regression, each 1-point increase in SCORE2 percentage was associated with higher odds of greater reaction severity (odds ratio 1.144 [95% confidence interval, 1.041-1.257]; p = 0.005). This association remained significant after adjusting for the culprit drug class (p = 0.008). Conclusion: Higher subclinical cardiovascular risk, as estimated by SCORE2, is significantly associated with increased DHR severity. Analysis of these findings suggests that vascular reserve may modulate the clinical presentation of drug-induced allergic reactions, potentially aiding in clinical risk stratification.