Sublingual microcirculation-derived glycocalyx barrier impairment independently predicts progression of asymptomatic...

Coronary microvascular dysfunction has been confirmed to be associated with cardiac diastolic dysfunction (DD). The endothelial glycocalyx (EG) is essential for maintaining microvascular homeostasis, and its degradation is related to coronary microvascular dysfunction. However, direct assessment of coronary EG integrity remains technically challenging. Notably, the sublingual microcirculation provides a non-invasive window into systemic microvascular health, which is relevant to coronary microvascular status in conditions of diffuse endothelial dysfunction. Whether EG integrity assessed at the sublingual site is associated with the presence and progression of DD remains unclear.

This prospective observational study enrolled 503 retired workers aged ≥60 years without overt heart failure from a single center in China. EG integrity was assessed at baseline using sidestream dark field imaging-derived perfused boundary region (PBR) of the sublingual microcirculation, with a higher PBR indicating greater glycocalyx barrier impairment. Diastolic function was evaluated by echocardiography according to the 2016 ASE/EACVI criteria at baseline and after a median follow-up of 23 months. Multivariable logistic regression and linear mixed-effects models were used to evaluate cross-sectional and longitudinal associations.

The prevalence of ALVDD at baseline was 9.74% (n = 49). PBR was significantly higher in participants with ALVDD than in those with normal diastolic function (2.43 vs. 1.84 μm, P < 0.01). After adjustment for the HOMAGE score, each 0.1 μm increase in PBR was independently associated with a 12% higher odds of ALVDD (OR 1.12, 95% CI 1.06-1.18, P < 0.01). Adding PBR to the HOMAGE score significantly improved discriminative ability (AUC from 0.656 to 0.712, P = 0.04; NRI 0.73, P = 0.02). During follow up, participants with higher baseline PBR showed significantly greater annual deteriorations in E/e' ratio and septal/lateral e' velocities compared with those with lower PBR (all P for trend <0.01).

Greater EG barrier impairment, non-invasively quantified by sublingual PBR, is independently associated with both the presence and longitudinal progression of ALVDD in an elderly Chinese population. PBR may serve as a useful marker for early detection of diastolic deterioration and and raises the hypothesis that PBR could serve as a potential target for preventive interventions, which requires prospective validation.