From protection to predisposition: A narrative review of sex‐specific vascular responses to acute stressors across the lifespan

Abstract

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, with females exhibiting relative biological protection against CVD compared to males through hormonal and nonhormonal mechanisms—a protection that diminishes with age. While previous research has identified early risk factors in CVD pathogenesis, the physiological mechanisms underlying sex and age differences remain poorly understood. To date, no review has synthesized perturbation‐focused studies to clarify sex differences and female physiology, so this narrative review characterized these differences by outlining vascular responses to five acute, commonly encountered perturbations: ischemia–reperfusion injury (IRI), hyperglycemia, hyperlipemia, cold pressor test (CPT), and mental stress. Our synthesis of studies investigating arterial stiffness and endothelial dysfunction, two established early cardiovascular risk factors, reveals sex differences: across perturbations, males respond more uniformly whereas females show greater variability. Specifically, endothelial function responses to IRI and CPT suggest that females may exhibit protection against these perturbations. Most perturbation‐outcome interactions reflect age and hormonal effects, with postmenopausal females often exhibiting the greatest dysfunction. Future research should directly examine sex differences and female‐specific responses after IRI and hyperlipemia. By clarifying sex differences and female‐specific vascular responses to acute perturbations, this work advances understanding of cardiovascular pathophysiology and informs targeted prevention of CVD.