Heart rate thresholds as integrative biomarkers: a systems approach to exercise physiology and cardiovascular regulation.

Heart rate (HR) kinetics during exercise reflect complex interactions between cardiovascular, autonomic, and metabolic systems. Yet, traditional assessments, such as maximal HR or HR reserve, fail to capture HR adjustments to metabolic transitions and mechanical signals sent from skeletal muscle, respiratory muscles, and the vascular system. This perspective introduces a novel systems physiology framework for analyzing HR thresholds in synchronization with ventilatory and metabolic transitions. A biphasic regulation model is proposed where Phase 1 is governed by afferent reflex mechanisms (e.g., metaboreflex, baroreflex) driving an exponential HR increase (heart rate inflection point, HRIP), while Phase 2 reflects β₁-adrenergic receptor saturation, leading to a plateau or deflection in HR (heart rate deflection point, HRDP). Using this framework, we propose new analytical strategies to assess threshold agreement and physiological synchronization across bodily systems. Our approach has practical applications in tailored exercise prescriptions and clinical diagnostics. We argue that HR thresholds may reflect activation of the exercise pressor reflex and shifts in sympathetic activity. By moving beyond isolated biomarkers, this model promotes a more integrative and dynamic understanding of exercise physiology.