BACKGROUNDChronic psychological stress is a risk factor for cardiovascular disease and mortality. Circulating hematopoietic progenitor cells (CPCs) maintain vascular homeostasis, correlate with preclinical atherosclerosis, and prospectively predict cardiovascular events. We hypothesize that (1) chronic caregiving stress is related to reduced CPC number, and (2) this may be explained in part by negative interactions within the family.METHODSWe investigated levels of stress and CPCs in 68 healthy mothers - 31 of these had children with an autism spectrum disorder (M-ASD) and 37 had neurotypical children (M-NT). Participants provided fasting blood samples, and CD45(+)CD34(+)KDR(+) and CD45(+)CD133(+)KDR(+) CPCs were assayed by flow cytometry. We averaged the blom-transformed scores of both CPCs to create one index. Participants completed the perceived stress scale (PSS), the inventory for depressive symptoms (IDS), and reported on daily interactions with their children and partners, averaged over 7 nights.RESULTSM-ASD exhibited lower CPCs than M-NT (Cohen's d=0.83; p⩽0.01), controlling for age, BMI, and physical activity. Across the whole sample, positive interactions were related to higher CPCs, and negative interactions to lower CPCs (allp's<0.05). The adverse effects of group on CPCs were significantly mediated through negative interactions with the child (indirect β=-0.24, p⩽0.01). In the full model, greater age (β=-0.19, p=0.04), BMI (β=-0.18, p=0.04), and negative interactions with the child (β=-0.33, p<0.01) were independently associated with lower CPCs. M-ASD had a less healthy lipid profile (total cholesterol/HDL), which in turn, was associated with lower CPCs.CONCLUSIONSChronic stress adversely impacts CPC number, an early-stage biomarker that predicts subclinical atherosclerosis and future CVD events, independent of traditional cardiovascular risk factors and inflammatory factors. Among maternal caregivers, child-related interpersonal stress appears to be a key psychological predictor of stress-related CVD risk.