Aortic Stiffness and Pulsatile Pressures as Potential Mediators of Chronic Kidney Disease Induced Impaired Diastolic Function.

Abstract

Purpose: We assessed whether aortic stiffness and pulsatile pressures can mediate chronic kidney disease (CKD)-associated impaired diastolic function.

Participants and methods: In 276 black Africans including 46 CKD (19 non-dialysis; 27 dialysis) and 230 control subjects, pulse wave velocity (PWV) estimated aortic stiffness and pulsatile pressures (forward and backward wave pressure, central systolic blood pressure (CSBP) and pulse pressure (CPP)) were determined by applanation tonometry; e' as an index of left ventricular active relaxation and E/e' as a measure of left ventricular filling pressure or passive relaxation were evaluated by echocardiography.

Results: In age, sex, traditional cardiovascular risk factor and mean arterial pressure (MAP) adjusted regression models, CKD was inversely associated with e' (p = 0.03) and directly with E/e' (p < 0.01). The CKD-e' relationship was attenuated and no longer significant (p = 0.31) upon additional adjustment for aortic PWV but not pulsatile pressures (p = 0.03-0.05). In product of coefficient mediation analysis, PWV accounted for 47.6% of the CKD-e' association. CSBP (22.9%) and CPP (18.6%) but not PWV (11.3%) accounted for a significant and relevant proportion of the CKD-E/e' relationship. However, CKD remained strongly associated with E/e' independent of aortic function measures (p < 0.01). Treatable covariates that were or tended to be consistently associated with diastolic function included MAP (p < 0.01) and diabetes (p = 0.02-0.07) for the CKD-e' and CKD-E/e' relations, respectively.

Conclusion: Aortic stiffness rather than pulsatile pressures mediates CKD-related impaired left ventricular active relaxation. By contrast, aortic pulsatile pressures (and not stiffness) contribute to CKD-related left ventricular filling pressures but do not fully account for the respective association.