High Pulse-Wave Velocity Defines a Very High Cardiovascular Risk Cohort of Dialysis Patients under Age 60

Abstract

Background: Patients with end-stage renal disease (ESRD) are at a high risk of cardiovascular mortality (CVM). In patients with ESRD, arterial stiffness increases at an earlier age when compared to the general population and this contributes to the overall risk of cardiovascular mortality. The main objective of this study was to clarify the interplay between age and cardiovascular alterations in ESRD. Methods: Prospective, observational cohort study initiated in April 1987 until the end of 1998 with events recorded until the end of the year 2000 at the F.H. Manhes Hospital Center, Fleury-Mérogis (in the Paris/Ile de France area). Results: The study population consisted of 278 ESRD patients undergoing dialysis therapy. The mean ± SD age was 53 ± 16 years. The mean pulse-wave velocity (PWV) was ∼11 m/s, with ∼37% of patients having a PWV >12 m/s. During the follow-up period, 91 patients died from CV causes. PWV >12 m/s was associated with CVM in the unadjusted model but lost its prognostic value in patients >60 years (p for interaction = 0.008). In patients ≤60 years, PWV was found to be a strong and independent predictor of CVM with hazards ratio (95% CI) of 14.382 (7.120-29.047), p < 0.001, and it improved the prognostic reclassification of a model containing well-established prognostic variables. According to multivariable regression analysis, aortic PWV was strongly associated with age (R² = 0.37, p < 0.001). Conclusion: A PWV >12 m/s provides important prognostic information in ESRD patients under 60 years of age, whereas in older patients, its prognostic relevance is lost. These findings are of critical relevance for early intervention guidance and trial end-point/treatment effect interpretation.

Arterial Stiffness in Chronic Kidney Disease and End-Stage Renal Disease

“…1). Premature vascular aging and arterial stiffening are observed with the progression of CKD [16-18]. The most characteristic arterial change observed is the arterial stiffening, more pronounced in the aorta than in peripheral arteries [6, 19].…”

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

“…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 associ-In a paper published in this issue of the Journal [8] , Ferreira et al [8], for the first time, test the hypothesis that age may be a crucial factor modifying the relationship between PWV and all-cause and CV mortality. The study, now extended to 278 patients, builds upon the seminal cohort described by Blacher et al [3] , in the first paper reporting the predictive power of PWV for all-cause and CV mortality in stage 5D CKD patients.…”

“…Only when confirmed in at least in one additional, sufficiently large, external cohort can the PWV-age interaction be proposed for prognostic purposes. Even though the stateof-the-art prognostic analyses like risk discrimination and risk reclassification have been applied, correctly so, Ferreira et al [8] refrain themselves from suggesting that their findings are important for prognosis. Rather, they interpret their findings in an etiologic/therapeutic perspective concluding that PWV may serve to guide CV therapy in stage 5D CKD patients.…”

“…Given the exceedingly high HR of this condition and the lack of benefit of several treatments tested in previous studies in the same population, such a trial appears to be of obvious clinical importance. If and when the trial will be done, the fresh findings by Ferreira et al [8] will prove useful for defining the target population whereupon focusing the therapeutic intervention(s) aimed at modifying arterial rigidity. Indeed, if confirmed in future analyses in existing databases and in future observational studies, Ferreira et al [8] data indicate that younger rather than older dialysis patients may be more likely to benefit from effective intervention(s) impinging upon arterial rigidity.…”

“…If and when the trial will be done, the fresh findings by Ferreira et al [8] will prove useful for defining the target population whereupon focusing the therapeutic intervention(s) aimed at modifying arterial rigidity. Indeed, if confirmed in future analyses in existing databases and in future observational studies, Ferreira et al [8] data indicate that younger rather than older dialysis patients may be more likely to benefit from effective intervention(s) impinging upon arterial rigidity. Because of the paramount role of CV disease in the high mortality rate of dialysis patients, investigating the issue is not at all a trivial problem.…”