Sex-related cardiometabolic differences in ME/CFS patients

<h2>Abstract</h2> Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multisystem disease that affects more females than males. Core symptoms include persistent fatigue, post-exertional malaise (PEM), unrefreshing sleep, cognitive dysfunction, and orthostatic intolerance. Although the underlying mechanisms are not fully understood, cardiovascular and metabolic imbalances are commonly reported alterations associated with the condition. However, sex-based approaches to better understand these pathophysiological features have received limited attention. To address this gap, we investigated potential sex-related cardiometabolic differences in female (n = 70) and male (n = 25) ME/CFS patients, compared to healthy controls (female, n = 27; male, n = 18). Univariate analysis revealed that female patients exhibited higher heart rates during both sitting and standing, but lower pulse pressure index, stroke volume, and stroke volume index during standing, compared to healthy controls. In contrast, male patients showed elevated diastolic blood pressure (BP) in both positions, along with increased mean arterial BP while standing. Circulating levels of advanced oxidation protein products (AOPP), a marker of oxidative stress, were elevated exclusively in male ME/CFS patients, while no differences were observed in females compared to their respective healthy controls. Correlation and multivariate analyses complemented and supported the observed sex-related differences in cardiometabolic parameters, particularly during standing. In conclusion, our sex-based analysis showing cardiometabolic differences in ME/CFS patients—particularly during standing—may contribute to future research focused on improving patient stratification and developing more tailored clinical management strategies.