The association between heart rate variability and early kidney damage: The mediating role of blood lipid levels among hypertensive patients in a single-center cohort study

This study aimed to investigate the association between heart rate variability (HRV) and the risk of early kidney damage (EKD) among hypertensive patients, with particular emphasis on the mediating role of low-density lipoprotein cholesterol (LDL-C). This retrospective cohort study included 1250 hypertensive patients treated between 2015 and 2020 in Hebei Province, China, with follow-up data available through December 31, 2022. Participants were followed through routine clinical visits and electronic medical record review, during which renal function indicators were periodically reassessed. Baseline HRV was measured using 24-hour Holter monitoring, with the standard deviation of all normal-to-normal intervals (SDNN) as the primary HRV index. Cox proportional hazards models were used to estimate hazard ratios for EKD, adjusting for demographic, lifestyle, clinical, and laboratory factors. Exploratory mediation analysis assessed the indirect association via lipid parameters. Higher HRV was significantly associated with an increased risk of EKD. In the fully adjusted model, participants in the highest HRV quartile had approximately twice the EKD risk compared with those in the lowest quartile (hazard ratio = 2.00, 95% confidence interval: 1.85-2.15). Low-density lipoprotein cholesterol statistically explained 22.5% of the association between HRV and EKD. Sensitivity analyses, including medication adjustment, alternative HRV metrics, spline modeling, competing-risk regression, and age stratification, confirmed the robustness of the findings. Elevated HRV, measured by 24-hour Holter-derived SDNN, was associated with increased EKD risk in hypertensive patients, with LDL-C acting as a significant intermediary factor. These findings highlight the potential value of integrating autonomic function assessment and lipid monitoring in early renal risk stratification among hypertensive populations.