Abstract Introduction Severe aortic valve stenosis (AVS) is the most common valvular heart disease in adults and remains associated with significant morbidity and mortality despite advances in surgical and interventional treatment strategies. Oxidative stress plays a key role in disease progression by promoting oxidation of LDL to oxLDL, which in turn promotes immune cell infiltration and calcification. LOX-1 facilitates oxLDL uptake and is enriched in atherosclerosis. Its soluble form, generated by cleavage, has been established as biomarker for plaque instability in atherosclerosis. However, its role in AVS remains unclear. Methods and Results To investigate the clinical relevance of sLOX-1 in AVS, we measured circulating sLOX-1 levels using ELISA in 200 patients with severe AVS before undergoing transcatheter aortic valve replacement (TAVR). Patients were stratified into tertiles based on sLOX-1 levels (median sLOX-1: 86 pg/ml). Baseline characteristics, including demographics, co-morbidities and echocardiographic measures of AVS severity, did not differ across tertiles. However, sLOX-1 levels were significantly associated with markers of systemic inflammation, including C-reactive protein (CRP) and white blood cell count, as well as adverse lipid profiles, particularly elevated triglyceride levels. Kaplan-Meier survival analysis revealed a significantly increased mortality rate in patients with high sLOX-1 levels. Importantly, this association persisted even after extensive multivariable adjustment for potential confounders, including age, BMI, lipid levels, CRP, statin treatment and several co-morbidities. There was no significant difference in secondary outcomes, including myocardial infarction, stroke, or major bleeding events at 12 months. In explanted human aortic valves, we detected expression of LOX-1, which was higher in patients with aortic valve stenosis compared to patients with aortic regurgitation. Conclusion Our findings indicate that sLOX-1 is strongly linked to systemic inflammation and adverse lipid profiles in patients with AVS. Elevated sLOX-1 levels are associated with increased mortality following TAVR, independent of traditional risk factors and AVS severity. These results suggest that sLOX-1 may serve as a novel biomarker and effector in AVS, highlighting the role of inflammation in disease progression and prognosis. Further studies are warranted to explore the role of sLOX-1 as predictor of disease progression in patients with moderate AVS and in AVS animal models.
Zaidi et al. (Sat,) studied this question.
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