Introduction and aim
Arterial stiffening increases the transmission of pulsatile energy into the cerebral circulation, and both arterial stiffness and cerebral pulsatility increase during middle age, potentially representing a critical window for cerebrovascular change. Carotid-femoral pulse wave velocity (PWV), a measure of central arterial stiffness is related to peripheral endothelial function, while middle cerebral artery (MCA) pulsatility index (PI) and the amplitude and kinetic cerebrovascular reactivity (CVR) responses to carbon dioxide are indicative of cerebrovascular function. Given PWV reaches the cerebral circulation through pulsatile transmission, and CVR is largely an endothelial-dependent response, central arterial stiffness could relate to cerebrovascular function through both pulsatile and endothelial pathways. However, evidence relating central arterial stiffness to CVR is limited. Given this, and that these relationships remain unexamined in inactive middle-aged adults, this study investigated whether PWV, PI, and the amplitude and kinetic CVR responses to hypercapnia are associated in this population.
Methods
Seventeen inactive middle-aged adults (10 males, 49.2±8.9 years) completed a single experimental visit. Carotid-femoral PWV was measured by applanation tonometry as the transit distance between the carotid and femoral sites divided by the pulse transit time, with ECG gating. Participants were then fitted with transcranial Doppler ultrasound and a gas analyser to continuously measure middle cerebral artery blood velocity (MCAv) and end-tidal CO2 (PETCO2). Hypercapnic CVR was assessed during 4 min of 6% CO2 inhalation and the MCAv kinetic response to hypercapnia was modelled using a mono-exponential model to derive amplitude, time delay, time constant, and mean response time. Hypocapnic CVR was assessed during 1 min of voluntary hyperventilation at 25 breaths·min⁻¹. Resting PI was calculated as (MCAv maximum − MCAv minimum) / MCAv mean. Associations were assessed using partial correlations adjusting for age, with statistical significance set at p < 0.05.
Results
Hypercapnic CVR (1.99±0.34 cm·s⁻¹·mmHg⁻¹) was significantly associated with kinetic amplitude (23.4±4.7 cm·s⁻¹; r = 0.63, p = 0.009) but not with the time constant (21.8±7.3 s), time delay (15.8±4.1 s), or mean response time (37.6±8.3 s; all |r| ≤ 0.23, all p ≥ 0.395). Hypocapnic CVR (1.37±0.47 cm·s⁻¹·mmHg⁻¹) was not associated with any kinetic parameter (all |r| ≤ 0.35, all p ≥ 0.178) or with hypercapnic CVR (r = −0.26, p = 0.339). Neither PWV (7.6±1.7 m·s⁻¹) nor PI (0.82±0.10) were associated with hypercapnic CVR, hypocapnic CVR, or any kinetic parameter (all |r| ≤ 0.49, all p ≥ 0.055), and PWV and PI were not associated with each other (r = −0.01, p = 0.985).
Conclusion
Central arterial stiffness and MCA pulsatility were not associated with each other, nor with cerebrovascular reactivity or its kinetic parameters, in inactive middle-aged adults. This indicates that peripheral vascular measures may not reflect cerebrovascular function in this population. Further work in larger cohorts is needed to confirm these relationships and clarify the peripheral and cerebral vascular changes occurring in middle age.