Stiff vessels approached in a flexible way: advancing quantification and interpretation of arterial stiffness

Introduction: Although pulse wave velocity (PWV), a proxy of arterial stiffness, is a strong predictor of cardiovascular complications, it is confounded by blood pressure (BP) and heart rate at the time of examination. Furthermore, establishing whether an artery behaves stiffer or less stiff does not inform a clinician on the cause of the stiffening. Quantification of arterial stiffness: This paper focuses on BP as a confounder of PWV. We developed a method to patient-specifically determine the dependence of PWV on BP — on average 1 m/s per 10 mmHg diastolic BP — and used it to disentangle BP-dependent and -independent stiffening in hypertension and cancer patients. We furthermore showed that the so-called cardio-ankle vascular index (CAVI) — a measure deemed BP-independent — shows a residual BP-dependence that is readily correctable using a modified equation (CAVI₀). Both developed methods are directly applicable to clinical measurements in individual patients. Interpretation of arterial stiffness: We developed a computer modelling procedure to disentangle contributions of the individual wall components — collagen, elastin, and smooth muscle — to arterial stiffening as observed in patients. Our model-based approach shows that with ageing, the biomechanical phenotype shifts from elastin-dominated to collagen-dominated load bearing. Model-based assessment of arterial wall mechanics provides a promising tool to further improve interpretation of arterial stiffness measurements in patients. Further development of such methodology applied to various mouse models may improve the understanding and interpretation of arterial stiffening in ageing and disease.