Sex- and gender-specific associations between psychological distress and vascular dysfunction: insights from oxygenation-sensitive cardiac MRI

Background Psychological distress—including stress, depression, anxiety, trauma, and anger—is an independent risk factor for cardiovascular disease (CVD) that disproportionately affects women, yet underlying biological mechanisms remain unclear.1 Oxygenation-sensitive cardiac MRI (OS-CMR), combined with a vasoactive breathing maneuver, enables non-invasive assessment of coronary vascular function without contrast or pharmacologic stress.2 Purpose To investigate the association between psychological distress and coronary vascular dysfunction, as assessed by OS-CMR, and the influence of sex and gender on this relationship. We hypothesized that stress would be linked to altered myocardial oxygenation, particularly in females and those with higher femininity. Methods In this prospective cross-sectional study, 118 adults without overt CVD (63.6% female; mean age 50.4±7.1 years) underwent 3T OS-CMR with a standardized breathing maneuver. Myocardial oxygenation indices were semi-automatically derived from two mid-ventricular short-axis slices using dedicated software and a custom MATLAB pipeline. Psychological distress was assessed using validated measures for perceived stress, depression, anxiety, trauma-related symptoms, and anger. Scores were standardised (z-transformed) and averaged to generate a composite stress score representing overall psychological distress burden. Analyses were stratified by sex and the GENESIS-PRAXY gender score (0-1; 0=more masculine, 1=more feminine).3 Linear associations were examined using Pearson correlations and multivariable regression models adjusted for age and traditional CV risk factors (two-sided p<0.05). Results In females, the composite score correlated with OS-CMR–derived end-systolic (r=0.355, p=0.002) and peak systolic (r=0.298, p=0.010) oxygenation changes, with no significant correlations in males (all p>0.05) (Figure 1). In adjusted models, stress remained independently associated with end-systolic (β=0.337[0.008–0.040], p=0.003) and peak systolic (β=0.280[0.003–0.032], p=0.019) oxygenation changes in females, but not males (all p>0.05) (Table 1). Moreover, stress correlated with gender score (r=0.313, p=0.0005). In gender-stratified analyses, stress correlated with end-systolic and peak systolic oxygenation changes in those with higher femininity (both r=0.286, p=0.028), but not higher masculinity (all p≥0.25) (Figure 1). These associations remained significant in adjusted regression models for higher femininity (end-systolic: β=0.283[0.001–0.036], p=0.037; peak systolic: β=0.286[0.001–0.035], p=0.040), but not higher masculinity (all p>0.05) (Table 1). Conclusions Psychological distress is independently associated with altered myocardial oxygenation responses in females and in individuals with higher femininity, but not in males or those with higher masculinity. These findings support sex- and gender-specific coronary vascular mechanisms linking stress to early CVD progression.