Loss of Vascular Smooth-Muscle Activity During Moderate Physical Activity as a Hallmark of Aging in Human Subjects

Studies have shown a higher risk of adverse outcomes after cardiac surgery in patients with reduced complexity of arterial-pressure dynamics (APD). We hypothesized that this effect is caused by age-related loss of vascular smooth-muscle activity (VSMA). This hypothesis was tested using data from 30 humans and a validated, large-scale theoretical model of circulation with VSMA blocked (T-model). The results were also verified in a realistic physical model of circulation (P-model, Fig.1). Methods: ECG and APD data were recorded using a high-fidelity system (APEX, PinMed, Inc.) during moderate physical activity (handgrip followed by leg lifts) in 30 subjects (age: 46±10y, 53% female; pressure ranges for systolic, diastolic, and mean: 90-210, 49-116, and 67-147mm, respectively). Results: T-model accurately predicted APD in older subjects ≥48y (n=13, r 2 =0.74; Fig.2); this effect was preserved in both females and males, but not in younger subjects (n=17, r 2 =0.13). The difference between the older and younger subjects was pronounced (40%) and significant (p=0.01, F-test). In P-model, changes in cardiac force produced changes in central arterial pressure that were in excellent agreement with those observed in humans ≥48y (r 2 =0.93, Fig.3). Conclusions: Loss of VSMA during physical activity could serve as an important prognostic/diagnostic indicator of cardiovascular aging and disease.