Central Artery Pulsatile Hemodynamics Are Associated With Cerebral Total, Periventricular, And Deep White Matter Lesions: Role Of Reservoir-excess Pressure Components

Introduction: Accumulating evidence suggests that increased central, rather than peripheral, blood pressure (BP) may be a better predictor of cardiovascular risk. The shape of the central BP waveform is determined by ventricular-arterial interactions that can be quantified via novel hemodynamic analyses, from which some parameters have been implicated in the development of cardiac, vascular, and renal dysfunction. Comparatively, the potential effect of central pulsatile hemodynamics on brain structure has been understudied. Thus, we sought to determine the association of novel central hemodynamic parameters with cerebral white matter lesions. Methods: Central BP waveforms were measured in 130 healthy adults (age 63±6y; 58% female) via non-invasive carotid tonometry and modeled using reservoir-excess pressure analysis to separate the central BP waveform into a reservoir (Rp TI ) and excess (Ep TI ) pressure component. Systolic (Sk) and diastolic (Dk) rate constants were estimated from the rate of increase and decrease of the Rp TI component, respectively. Total, periventricular, and deep cerebral white matter lesion volumes (WMLV) were estimated from T2 weighted and FLAIR MRI and adjusted for total intracranial volume. Results: Both Sk and Ep TI were correlated with total (Sk: r = -0.19, p = 0.033; Ep TI : r = 0.21, p = 0.016), periventricular (Sk: r = -0.18, p = 0.037; Ep TI : r = 0.23, p = 0.009), and deep (Sk: r = -0.28, p = 0.002; Ep TI : r = 0.20, p = 0.027) WMLV. The association of Sk with total ( B = -0.032; 95% confidence interval [CI] = -0.054, -0.010; p = 0.0056), periventricular ( B = -0.030; 95%CI = -0.051, -0.009; p = 0.0063), and deep ( B = -0.064; 95%CI = -0.101, -0.028; p <0.001) WMLV remained significant in multivariable analyses adjusting for age, sex, BMI, peripheral pulse pressure, carotid-femoral pulse wave velocity, heart rate, and non-HDL cholesterol. Additionally, the association between Ep TI and deep WMLV persisted in multivariable analysis ( B = 0.158; 95%CI = 0.045, 0.271; p = 0.007). Conclusion: Pulsatile components of central artery hemodynamics are associated with cerebral WMLV independent of traditional cardiovascular risk factors. In particular, Sk may represent a novel biomarker of early central BP-related cerebral white matter damage.