Increased fasting plasma succinate levels are associated with higher resting heart rate in young sedentary adults

Succinate is a circulating metabolic intermediate and signaling metabolite associated with several physiological and immunometabolic processes. However, whether circulating succinate relates to resting cardiovascular physiology in humans remains poorly understood. Therefore, we examined the association between fasting plasma succinate concentrations and resting heart rate (HR) and heart rate variability (HRV) parameters in young sedentary adults.

We analyzed 85 sedentary young adults (18-25 years; 56 women) from the ACTIBATE study cohort (NCT02365129). Plasma succinate was measured enzymatically under fasting conditions. Resting heart rate (HR) and heart rate variability (HRV), non-invasive markers of autonomic function, were measured in fasting, thermoneutral conditions using the Polar RS800CX system.

Higher fasting succinate concentrations showed a modest positive association with resting HR (β=0.213; R²=0.074; P = 0.046), independent of sex and BMI. In exploratory sex-stratified analyses, the association remained significant in men (β=0.379; R²=0.200; P = 0.034) but not in women (β=0.112; R² =-0.024; P = 0.417), although no significant Succinate × Sex interaction was detected. Participants with succinate levels above the cohort median showed a higher resting HR (+4 bpm; 95% CI: +0.1 to +8.3; P = 0.045) compared with those below the median, despite comparable body composition and cardiometabolic profiles (all P≥0.105). There was no association between levels of succinate and any HRV parameters (all P≥0.226).

Elevated fasting plasma succinate is associated with higher resting HR in young sedentary adults. While causality cannot be inferred, these findings suggest that circulating succinate may represent a systemic metabolic marker associated with resting cardiovascular physiology in young adults. Longitudinal and mechanistic studies are warranted to clarify the physiological relevance and directionality of these associations.