Changes in blood pressure and arterial stiffness monitored using the cardio–ankle vascular index during hemodialysis

Although there are many commercially available statistical software packages, only a few implement a competing risk analysis or a proportional hazards regression model with time-dependent covariates, which are necessary in studies on hematopoietic SCT. In addition, most packages are not clinician friendly, as they require that commands be written based on statistical languages. This report describes the statistical software ‘EZR' (Easy R), which is based on R and R commander. EZR enables the application of statistical functions that are frequently used in clinical studies, such as survival analyses, including competing risk analyses and the use of time-dependent covariates, receiver operating characteristics analyses, meta-analyses, sample size calculation and so on, by point-and-click access. EZR is freely available on our website (http://www.jichi.ac.jp/saitama-sct/SaitamaHP.files/statmed.html) and runs on both Windows (Microsoft Corporation, USA) and Mac OS X (Apple, USA). This report provides instructions for the installation and operation of EZR.

The purpose of this study was to calculate robust quantitative estimates of the predictive value of aortic pulse wave velocity (PWV) for future cardiovascular (CV) events and all-cause mortality by meta-analyses of longitudinal studies. Arterial stiffness is increasingly recognized as a surrogate end point for CV disease. We performed a meta-analysis of 17 longitudinal studies that evaluated aortic PWV and followed up 15,877 subjects for a mean of 7.7 years. The pooled relative risk (RR) of clinical events increased in a stepwise, linear-like fashion from the first to the third tertile of aortic PWV. The pooled RRs of total CV events, CV mortality, and all-cause mortality were 2.26 (95% confidence interval: 1.89 to 2.70, 14 studies), 2.02 (95% confidence interval: 1.68 to 2.42, 10 studies), and 1.90 (95% confidence interval: 1.61 to 2.24, 11 studies), respectively, for high versus low aortic PWV subjects. For total CV events and CV mortality, the RR was significantly higher in high baseline risk groups (coronary artery disease, renal disease, hypertension) compared with low-risk subjects (general population). An increase in aortic PWV by 1 m/s corresponded to an age-, sex-, and risk factor-adjusted risk increase of 14%, 15%, and 15% in total CV events, CV mortality, and all-cause mortality, respectively. An increase in aortic PWV by 1 SD was associated with respective increases of 47%, 47%, and 42%. Aortic stiffness expressed as aortic PWV is a strong predictor of future CV events and all-cause mortality. The predictive ability of arterial stiffness is higher in subjects with a higher baseline CV risk.

The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis. Eventually, VSMC plasticity and signaling in both conductance and resistance arteries are highly relevant to the physiology of normal and early vascular aging. This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis. We further speculate on the contribution of cellular stiffness along the arterial tree to vascular wall stiffness. In addition, this review provides the latest advances in the identification of gene variants affecting arterial stiffening. Now that important hemodynamic and molecular mechanisms of arterial stiffness have been elucidated, and the complex interplay between ECM, cells, and sensors identified, further research should study their potential to halt or to reverse the development of arterial stiffness.