The decline of renal function aggravates arterial stiffness: a large-scale cross-sectional and longitudinal study

ABSTRACT Purpose: Many studies investigated the one-single-direction relationship between arterial stiffness and chronic kidney dysfunction, particularly in patients with end-stage renal disease. The bidirectional relevance between kidney function decline and arterial stiffness in general population remains unknown. This study aimed to address the temporary relationship between arterial stiffness and renal function. Materials and Methods: This large-scale observational study comprised one cross-sectional and one longitudinal population sample totalling 67,060 individuals aged over 18 years with brachial-ankle pulse wave velocity (baPWV) and estimated glomerular filtration rate (eGFR) measurements available. Associations with potential risk conditions were analysed using multiple regression analyses. Cox proportional model was used to investigate the association of arterial stiffness and incident chronic kidney disease (CKD). Cross-lagged path analysis was further conducted to analyze the temporal relationship between baPWV and eGFR. Results: Multiple regression analyses showed that baPWV was inversely associated with eGFR. Compared with the lower baPWV tertile group, higher baPWV was a predictor of CKD risk, with increased HRs for three baPWV tertile groups [HR=2.17 (1.26-3.76), P for trend <0.05]. Accordingly, lower eGFR was significantly associated with higher arterial stiffness risk, even after full-adjusted [HR=1.21 (1.02-1.44), P for trend <0.05]. In the path analysis, the coefficient of the association between baseline baPWV and follow-up eGFR was lower than the effect of baseline eGFR for follow-up baPWV (-0.063 Vs. -0.077, P <0.001). Conclusions: Decrease of eGFR appeared to aggravate arterial stiffness, which unravelling a new understanding of the role kidney dysfunction played in arterial stiffening. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Natural Science Foundation of China [grant number 81800393, 82170437, 81901842, 81974054], the Outstanding Young Investigator of Hunan province [grant number 2020JJ2056, 2018JJ1048], the Hunan Youth Talent Project [grant number 2019RS2014], the Key Research and Development Project of Hunan province [grant number 2020WK2010], the National Key Research and Development Project of China [grant number 2018YFC1311300, 2019YFF0216304, 2019YFF0216305], China Primary Health Care Foundation [grant number YLGX-WS-2020003], and National Key R&D Program of China [grant number 2018YFC1311300]. The funders played no role in the study design, data collection, analysis, decision to publish or preparation of the manuscript. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocols were approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Details of the study population were published in https://doi.org/10.1016/j.jacc.2019.12.039.