The risks of inflammation and metabolism in distinct phenotypes of bicuspid aortic valve–associated aortopathy and aortic dissection: A population-based cohort study

Abstract

Background

Bicuspid aortic valve is frequently associated with progressive dilation of the ascending aorta and aortic root, predisposing patients to life-threatening complications such as aortic dissection. The roles of systemic inflammation and glucose-lipid metabolism in bicuspid aortic valve–associated aortopathy remain poorly defined.

Methods

We retrospectively analyzed 1,678 bicuspid aortic valve patients diagnosed between 2008 and 2024. Imaging, echocardiographic, and peripheral blood biochemical data were collected. Principal components analysis was used to generate composite metabolic and inflammatory scores. Random forest, LASSO regression, and SHAP (SHapley Additive exPlanations) methods were used for feature selection. Logistic and Cox regression models, along with restricted cubic spline analysis and Kaplan-Meier curves, were applied to evaluate risk factors for aortic dilation and Stanford type A aortic dissection.

Results

Ascending aortic dilation (≥40 mm) was present in 66.98% of patients, and aortic root dilation in 19.79%. Both metabolic and inflammatory scores were significantly associated with ascending aortic diameter, but only the metabolic score remained independently associated with root diameter after adjustment. Triglyceride-glucose and monocyte-to-lymphocyte ratio were identified as the key metabolic and inflammatory markers. Triglyceride-glucose was independently associated with ascending aortic dilation (odds ratio = 2.15, P < .001), but not with Stanford type A aortic dissection. Monocyte-to-lymphocyte ratio was independently associated with both ascending aortic dilation (odds ratio = 3.17, P = .001) and Stanford type A aortic dissection (hazard ratio = 8.87, P < .01). A monocyte-to-lymphocyte ratio threshold of 0.38 stratified Stanford type A aortic dissection risk (log-rank P = .003). For aortic root dilation, neither the monocyte-to-lymphocyte ratio nor the triglyceride-glucose index showed significant independent associations overall. Subgroup analysis revealed that the triglyceride-glucose index was significantly associated with increased root diameter only in patients with aortic root diameter <40 mm.

Conclusions

Systemic metabolic and inflammatory states are key contributors to ascending aortic dilation, but not to aortic root dilation, in patients with bicuspid aortic valve. Monocyte-to-lymphocyte ratio is a robust predictor of Stanford type A aortic dissection, offering a potential biomarker for early risk stratification and surgical decision making. These findings support the presence of phenotype-specific mechanisms in bicuspid aortic valve–associated aortopathy and underscore the distinct roles of inflammation and metabolism in different aortopathy phenotypes.