Pulse Pressure Modifies the Association Between Diastolic Blood Pressure and Decrease in Kidney Function: the Japan Specific Health Checkups (J-SHC) Study

Background Unlike systolic blood pressure (SBP), the prognostic value of diastolic blood pressure (DBP) in kidney function has not been established. We hypothesized that pulse pressure (PP), which is associated with arteriosclerosis, would affect the prognostic value of DBP. Methods This longitudinal study used data from the Japan Specific Health Checkups Study conducted between 2008 and 2014. The participants were stratified into 3 PP subgroups (low-PP ≤39, normal-PP 40–59, and high-PP ≥60 mmHg). The exposures of interest were SBP and DBP, and the association between SBP/DBP and kidney outcomes (30% decline in the estimated glomerular filtration rate from baseline) was examined in each PP subgroup using a Cox proportional hazards model. Results Among 725,022 participants, 20,414 (2.8%) developed kidney outcomes during a median follow-up period of 34.6 months. Higher SBP was consistently associated with a higher incidence of kidney outcome in all PP subgroups. Although DBP had a positive linear association with the incidence of kidney outcome in low-and normal-PP subgroups, both lower (≤60 mmHg) and higher (≥101 mmHg) DBP were associated with a higher incidence of kidney outcome in high-PP subgroup with U-shaped curve. Hazard ratios (95% confidence intervals) of ≤60 mmHg (reference: 61-80 mmHg in normal-PP subgroup) and ≥101 mmHg were 1.26 (1.15–1.38) and 1.86 (1.62–2.14), respectively. Conclusion In this large population-based cohort, DBP was differently associated with kidney outcome by PP levels; lower DBP was significantly associated with a higher incidence of kidney outcome in high-PP subgroup but not in low-and normal-PP subgroups. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Health and Labor Sciences Research Grants for Research on Design of the Comprehensive Health Care System for Chronic Kidney Disease (CKD) Based on the Individual Risk Assessment by Specific Health Checkup from the Ministry of Health, Labor, and Welfare of Japan and a Grant-in-Aid for Research on Advanced Chronic Kidney Disease (REACH-J), Practical Research Project for Renal Disease from the Japan Agency for Medical Research and Development (AMED), and JSPS KAKENHI Grant Number JP18K11131. ### 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: All procedures involving human participants were conducted in accordance with the ethical standards of the institutional and/or national research committee under whose jurisdiction the studies were conducted (Fukushima Medical University; IRB Approval Number #1485, #2771). 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 Due to the nature of this research, participants of this study did not agree for their data to be shared publicly, so supporting data is not available. * BMI : body mass index BP : blood pressure CKD : chronic kidney disease CI : confidence interval CVD : cardiovascular disease DBP : diastolic blood pressure eGFR : estimated glomerular filtration rate HR : hazard ratio PP : pulse pressure RCS : restricted cubic spline SBP : systolic blood pressure