Arterial Stiffness as a Cardiovascular Risk Factor in Stage 5D Chronic Kidney Disease Patients: An Age Affair

ated this alteration with surrogate end points like left ventricular hypertrophy or intima media thickening or endothelial dysfunction. Until now, there are only 3 reasonably large studies in stage 5D CKD patients investigating the relationship between a main parameter of vascular stiffening like pulse wave velocity (PWV) and mortality and CV events [3–5] . These studies were all limited by the small number of clinical events which ranged from 73 [3] to 143 [5] and from 36 to 48 for all-cause and CV death [3, 4], respectively, and the largest of these studies [5] did not report information on CV death. Furthermore, formal interaction analysis for the identification of factors that can modify the relationship between PWV and clinical outcomes was performed in none of those studies. This is an important lack of information in the stage 5D CKD population. As a matter of fact, in community level studies, women appear to be more susceptible to the harmful effect of pulsatile arterial load on diastolic function [6] . Furthermore, an established biomarker of arterial stiffness like pulse pressure amplification, but not arterial pressure, predict mortality in the elderly [7] . Whether older age modifies the link between PWV and clinical outcomes has not been specifically tested in the cohort studies performed in stage 5D CKD patients so far [3–5] . In the general population, arterial stiffening is a strong risk factor for incident hypertension and cardiovascular (CV) events including fatal or nonfatal myocardial infarction, unstable angina, heart failure and ischemic or hemorrhagic stroke. Beyond and above hypertension, arterial stiffness per se has a relevant impact on CV disease because several treated hypertensives still show a high degree of arterial stiffness, a finding that may explain some of the residual CV risk that remains in well-controlled hypertension [1] . Widening in pulse pressure and high systolic pressure are recognized as robust markers of arterial stiffening. In this regard, it cannot be overemphasized that pulse pressure emerged as the strongest BP metric for the risk of death in a cohort of 37,069 patients across 752 hemodialysis facilities in the USA in a classical study published in the early years of the new millennium [2] . Although the damaging potential of arterial stiffening on the CV system has been unequivocally proven in the general population, gaps in our understanding of the clinical risks associated with arterial stiffening in some conditions and clinical settings remain. One of these conditions is stage 5D chronic kidney disease (CKD). Several studies in stages 3–5 CKD patients and in stage 5D CKD patients elucidated mechanisms responsible for arterial stiffening (depicted in fig. 1 ) and coherently associPublished online: November 30, 2016 Nephrology American Journal of