Visualizing subclinical biomarkers of endothelial dysfunction associated with cardiovascular risk using oxygenation-sensitive cardiovascular magnetic resonance

Background Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) with vasoactive breathing maneuvers is a needle-free, non-invasive assessment of coronary vascular function. By tracking myocardial oxygenation changes across hyperventilation and breath-hold, OS-CMR detects endothelial-dependent dysfunction with excellent agreement against invasive testing. If dysfunction can be detected early in a high-risk metabolic syndrome (MetS) cohort, this may provide an opportunity for early intervention to prevent overt CVD. Purpose To assess the association between OS-CMR–derived vasoactive responses and risk factors in individuals with MetS, as noninvasive markers of early endothelial dysfunction. Methods In this prospective, single-centre cross-sectional study, healthy controls and participants with ≥3 MetS risk factors (without overt CVD) underwent 3T CMR including OS-CMR at baseline and across a post-hyperventilation long breath-hold. Using certified software and a custom Python pipeline, percent-change curves of myocardial signal intensity (MI) and heterogeneity (HET) were derived for vasoconstriction (HV-MORE: baseline vs post-hyperventilation) and vasodilation (B-MORE: early vs late breath-hold). MI and HET curves were visually inspected, and five OS-CMR biomarkers (selected a priori based on prior links to endothelial dysfunction) were compared between groups using t-tests or Mann–Whitney tests as appropriate. Associations with overall risk burden (INTERHEART) were investigated using correlation and univariable regression, and association to individual cardiometabolic variables were studied using backwards selection multivariable regression. Results 34 healthy controls (50% female, 55±10 years) and 34 MetS subjects (50% female, 55±10 years) were studied. OS-CMR vasoactive curves showed overlap for mean intensity, across both vasoconstrictive and vasodilative response, but a distinctly heterogeneous vasodilation response was observed in the MetS group (Figure 1). Of five biomarkers, late-diastolic vasodilatory heterogeneity (B-MOREHET-AUC) showed significantly higher values in MetS participants compared to controls (median 130 [-112, 349], vs -40.8 [-321, 115], p=0.008) (Figure 2). This heterogeneous response was associated with increased INTERHEART risk score (r=0.25, p=0.04; R²=0.06, β=12.9 p=0.04). In multivariable analysis, sex, age, waist circumference, and creatinine (model R²=0.14, p=0.01) were retained as the most significant variables associated with the OS-CMR biomarker; with waist circumference independently associated to B-MOREHET-AUC (β=9.46, p=0.004). Conclusions OS-CMR detected a subclinical, heterogeneous vasodilatory pattern consistent with early endothelial dysfunction in MetS, associated with cardiometabolic risk burden and central adiposity. By revealing vascular abnormalities in asymptomatic individuals, OS-CMR may support preventative strategies to mitigate progression to overt CVD.