[Penultimate pulse wave velocity, better than baseline pulse wave velocity, predicted mortality in Italian ESRD cohort study - a case for daily hemodialysis for ESRD patients with accelerated pulse wave velocity changes].

BACKGROUND: Cardiac disease remains the major cause of death among ESRD patients. Indeed, the risk of cardiovascular events in ESRD is reported to be at least 3.4 fold higher than that of the general population. Moreover, annual mortality rates among ESRD patients on hemodialysis approximate 20%, with cardiovascular disease accounting for almost half of this mortality profile. Despite this knowledge, so far we have been unable to identify treatable pathogenetic factors among ESRD patients to help reverse these poor cardiovascular outcomes. The difficulty to prognosticate cardiovascular mortality in ESRD remains elusive. However, in 2011, our group, for the first time, had demonstrated that cyclic variations of arterial stiffness as measured by pulse wave velocity (PWV) before and after hemodialysis determined mortality differences within an ESRD cohort. We have therefore examined the impact of individual patient-level translational PWV changes over time on mortality outcomes in an Italian ESRD cohort.

STUDY DESIGN AND SETTING: Prospective observational study, 2007-2010, in an Italian ESRD cohort who underwent in-center outpatient conventional thrice weekly hemodialysis.

METHODS: PWV was measured by the foot-to-foot method and repeated after six months. Coronary artery calcification (CAC) was measured at 0, 12 and 24 months. Routine clinical data and patient demographics were recorded and mortality outcomes were analyzed.

RESULTS: Between 2007 and 2010, 466 Italian ESRD patients, 229 males and 237 females, age 19-97 (65.6) years, were followed up for 28.9 months. 128 patients (74M:54F) died. The major causes of death were acute myocardial infarction (AMI) in 47 (37%) patients (age 70, 26M:21F) and sudden death (SD) in 29 (23%) patients (age 72, 19M:10F). Paired PWV data was available in 308 surviving patients and in 106 patients who died. Baseline PWV was lower in surviving vs dead patients 8.46 +/- 1.8 vs 9.43 +/- 3.75 (p=0.0005). Repeat PWV values were unchanged in the 308 survivors (8.46 +/- 1.8 vs 8.53 +/- 1.85, p=0.5, NS). Repeat PWV values increased in the 106 patients who died from 9.43 +/- 3.75 to 12.11 +/- 4.18 (p<0.0001). Of the 29 patients who died from SD, death occurred <12 hours after the last dialysis (ATLD) in 7, >24 hours ATLD in 20 and >48 hours ATLD in 17. Of the 47 patients who died from AMI, 6 died <12 hours ATLD, 35 died >24 hours ATLD and 23 died >48 hours ATLD. Of the 14 ESRD patients in the cohort that died from hyperkalemia, 3 died <12 hours ATLD, 11 died >24 hours ATLD, and 7 died >48 hours ATLD. CAC data scatter did not allow for adequate statistical subgroup analysis but overall, baseline CAC values were higher in the AMI/SD dead patients vs surviving patients.

CONCLUSIONS: This is the first report to show a scalable and direct relationship between translational follow up PWV changes after six months versus observed cardiovascular mortality in an ESRD cohort. We have shown, for the first time, that penultimate PWV, better than baseline PWV, predicted cardiovascular mortality in this ESRD cohort. Moreover, higher proportions of the ESRD deaths from AMI, SD and hyperkalemia occurred during the long inter-dialytic (weekend) period when ESRD patients went for 3 days without hemodialysis. We propose that PWV be monitored among all new ESRD patients, and be repeated after six months of initiation of chronic hemodialysis. Our group had earlier demonstrated in 2012 that daily dialysis reduced PWV in chronic hemodialysis patients. From these study findings, we have proposed that ESRD patients who exhibit elevated initial PWV values, or more so, ESRD patients who demonstrate accelerated PWV values after six months on maintenance chronic hemodialysis should be converted to daily hemodialysis protocol. Furthermore, such patients may require more intense cardiovascular analysis by cardiologists. Further research into new preventative or therapeutic options in this area of ESRD care is warranted.