Cardiovascular Health and Autonomic Dysfunction in Adults with Limb Amputation

Following lower-limb amputation, 50% of adults do not survive 5 years. High mortality rates are attributed to cardiovascular disease. Adults with lower-limb amputation have greater cardiovascular disease burden when compared to peers without amputation with similar risk profiles, suggesting unidentified contributors to poor cardiovascular health. Reduced peripheral muscle pump from the loss of the limb leads to lower stroke volume during cardiac contractions, requiring an increase in heart rate via the sympathetic branch of the autonomic nervous system to maintain adequate cardiac output. While acutely this imbalance in autonomic function may be a necessary adaptation, sustained sympathetic hyperactivity has been associated with cardiovascular disease and mortality. Yet, research on autonomic dysfunction and cardiovascular health among individuals with limb amputation is sparse. Our recent research finds signs of both autonomic nervous system dysfunction and poor cardiovascular health among adults with lower-limb amputation. Therefore, the long-term goal of this research line is to determine if autonomic dysfunction is a key modifiable predictor of cardiovascular disease and mortality among adults with lower-limb amputation. This line of research may inform new clinical treatment pathways for adults following lower-limb amputation, in that, interventions may target autonomic dysfunction to mitigate risk of cardiovascular damage, events, and mortality. As an initial step in this research line, we propose a cross-sectional, case-control study of 40 adults with lower-limb amputation who will be compared to 40 sex- and age-matched healthy controls. Individuals will receive onsite examinations at the University of Delaware or their local prosthetic clinic that include assessment of autonomic function and cardiovascular health. Autonomic nervous system dysfunction will be evaluated with cardiovagal and exercise testing, infrared thermography, sensory testing, and 7 days of remote, continuous cardiac monitoring. Cardiovascular health will be evaluated with ultrasound imaging of the common carotid, internal carotid, femoral, and popliteal arteries. Aim 1 will determine the extent to which autonomic dysfunction is associated with common carotid and internal carotid arterial health. Aim 2 will determine the extent to which signs of sympathetic nervous system hyperactivity within the residual limb, i.e., reduced temperature and increased pain sensitivity, are present and associated with regional cardiovascular health, e.g., femoral and popliteal arterial flow. Exploratory Aim 3 will use more sophisticated research methods, i.e., applanation tonometry and echocardiography, to evaluate arterial stiffness and cardiac function; associations between markers of cardiovascular health and autonomic dysfunction will be explored. Successful completion of the proposed project will inform a subsequent R01 grant evaluating the role of autonomic nervous system dysfunction in predicting future cardiovascular damage, disease, and mortality in adults with lower-limb amputation using a longitudinal, cohort study design.