This cohort study was conducted within the APAC study, based in the Kailuan community of Tangshan City, Hebei Province, China. Eligible participants were aged 40–80 years and underwent standardized questionnaires and physical examinations. We initially recruited 5,440 participants in 2010. We then excluded 235 individuals due to incomplete data on Cre, weight, and baPWV measurements at baseline. To ensure the reliability of the ratio and avoid bias from extreme physiological conditions, outliers with implausible body weight or creatinine values (outside the 1st–99th percentiles) were removed to ensure data validity. People who were pregnant, had cancer, or were bedridden were excluded. This adjustment left us with 5,205 participants for the cross-sectional analysis. For the longitudinal cohort analysis, we further excluded 3,374 participants who had baPWV ≥1,400 cm/s at baseline or who lacked baPWV measurements in 2012. As a result, 1,651 individuals were included in the longitudinal cohort analysis to examine the relationship between the Cre/BW ratio and arterial stiffness (Figure 1).

The study was conducted in compliance with the principles of the Declaration of Helsinki and was approved by the Ethics Committees of Kailuan General Hospital and Beijing Tiantan Hospital. All participants provided written informed consent.

The Cre/BW ratio was calculated at baseline. The Cre/BW ratio was defined as Cre (mg/dL) divided by the weight (kg) (19). Participants wore light clothing during weight measurements, and Cre levels were measured using the Jaffe kinetic rate technique. Blood samples were collected early in the morning from the antecubital vein for measurement of fasting blood glucose (FBG), total cholesterol (TC), triglycerides (TG), estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and high-sensitivity C-reactive protein (hs-CRP) (20). Additional baseline information was obtained using questionnaires. Monthly household income was two classified as <1,000¥, ≥1,000¥, and physical activity was categorized as none, occasional (<80 min/week), or regular (≥80 min/week). Smoking and drinking status was stratified by never, ever, and currently. Body mass index (BMI) was the result of the ratio of weight (kg) to the square of height (m). Blood pressure was measured in the sitting position using a mercury sphygmomanometer, and the average of three measurements was recorded as systolic blood pressure (SBP) and diastolic blood pressure (DBP). Hypertension was defined as SBP ≥140 mmHg or DBP ≥90 mmHg, use of antihypertensive medication, or self-reported history of hypertension. Diabetes was defined as FBG levels ≥7.0 mmol/L, use of glucose-lowering medication, or self-reported history of diabetes. Hyperlipidemia was defined as TC levels ≥5.17 mmol/L, use of lipid-lowering medicine, or self-reported history of hyperlipidemia.

Brachial-ankle pulse wave velocity was measured utilizing an automatic arteriosclerosis detection device (BP203RPE III; Omron Healthcare Co, Kyoto, Japan). Participants were required to lie on their backs in thin clothing and remain still during the measurement. Cuffs were fitted on both the arm and ankle. For analysis, the higher baPWV value from either side of the body was recorded. The measurement was repeated twice for each participant, and the maximum values from both sides of baPWV were employed for analysis. Prior to measurement, the participants rested for a minimum of 5 min in a dedicated air-conditioned room (24 ℃–26 ℃).

Arterial stiffness was categorized as baPWV ≥1,400 cm/s (21). In sensitivity analyses, atherosclerosis was considered present when baPWV ≥1,800 cm/s.

Participants were classified into three groups according to the tertiles of the Cre/BW ratio. Continuous variables were reported as median values with interquartile ranges (IQRs), while categorical variables were summarized as counts and percentages. The Wilcoxon and Kruskal–Wallis tests were used to assess differences among groups regarding continuous variables, while the chi-square test was utilized for categorical variables. Logistic regression models were developed to compute the odds ratios (ORs) and 95% confidence intervals (CIs) to explore the association between Cre/BW ratio and various outcomes in the analyses. Model 1 was unadjusted. Model 2 was adjusted for age, sex, education, BMI, income, smoking status, drinking status, hs-CRP, eGFR, FBG, TC, TG, and other risk factors. The selection of variables was based on known risk factors associated with arterial stiffness, which were incorporated in the model as potential confounding factors. Sensitivity analyses were performed using the alternative definition of arterial stiffness (baPWV ≥1,800 cm/s). To examine the association between the Cre/BW ratio and baPWV as continuous variables, we performed multivariable linear regression, adjusting for the confounding factors included in Model 2. To evaluate the impact of the Cre/BW ratio on arterial stiffness progression, ΔbaPWV was calculated as the difference between baPWV values at follow-up and baseline. Multivariable linear regression analysis was used to investigate the association between the Cre/BW ratio and ΔbaPWV, adjusting for baseline baPWV levels and the confounding factors included in Model 2. Furthermore, we conducted a comprehensive analysis of how the Cre/BW ratio influences outcomes as a continuous variable, using restricted cubic spline (RCS), while controlling for all previously cited covariates. We stratified analyses according to specific baseline characteristics—including age, gender, BMI, eGFR, and hypertension (no and yes)—to investigate potential effect modifications in greater depth in cross-sectional and longitudinal analyses.

Receiver operating characteristic (ROC) curves were generated to determine the area under the curve (AUC). We calculated the Youden index, sensitivity, and specificity of the Cre/BW ratio to assess the predictive value of arterial stiffness.

A total of 5,205 participants were included in the cross-sectional analysis, with a median age of 52.45 years (IQR, 45.64–61.52), of which 3,125 (60.04%) were men. Table 1 presents the baseline characteristics of participants categorized by tertiles of the Cre/BW ratio. Compared with those in the lowest Cre/BW ratio, those with a higher Cre/BW ratio tended to be older, male, more affluent, and better educated. The baseline characteristics of participants included and excluded were well balanced, as shown in Supplementary Table S1. Supplementary Table S2 further presents the baseline traits of the 1,651 participants in the longitudinal study, organized by their Cre/BW ratio.

A total of 3,227 participants exhibited baPWV measurements exceeding 1,400 cm/s. Table 2 shows the Cre/BW ratio tertiles with the prevalence of arterial stiffness. The prevalence increased with higher Cre/BW tertiles. In Model 1, the highest tertile was significantly associated with arterial stiffness (OR: 1.35; 95% CI, 1.18–1.55; P < 0.0001). This association remained significant after multivariable adjustment (Model 2 OR: 1.36; 95% CI, 1.21–1.64; P < 0.0001). Similar trends were observed in the sensitivity analysis (OR: 1.39; 95% CI, 1.10–1.77; P = 0.0056). The multivariate-adjusted curvilinear regression results showed a J-shaped association when baPWV was evaluated as a continuous variable (Figure 2).

Table 2 presents the ORs (95% CIs) in the longitudinal relationship with different tertiles of the Cre/BW ratio. We observed an increasing risk of incident arterial stiffness across increasing Cre/BW tertiles. A statistically significant association was observed between the highest Cre/BW ratio tertile and the prevalence of arterial stiffness in unadjusted model (OR: 1.68; 95% CI, 1.29–2.20; P = 0.0001). In Model 2, the highest Cre/BW ratio tertiles demonstrated a significantly greater risk of developing arterial stiffness in contrast to the lowest Cre/BW ratio tertiles (OR: 2.09; 95% CI, 1.52–2.87; P < 0.0001). Sensitivity analysis also confirmed similar results. In an additional longitudinal analysis using the change in baPWV (ΔbaPWV) as a continuous outcome, a higher Cre/BW ratio was associated with a greater increase in baPWV during follow-up (Supplementary Table S4).

In multivariable linear regression models treating baPWV as a continuous outcome (Table 3), we observed a significant positive association in both analyses. In the cross-sectional analysis, each 1-unit increase in the Cre/BW ratio was associated with a 36.16 cm/s higher baPWV (P < 0.0001). In the longitudinal analysis, each 1-unit increase in Cre/BW ratio was associated with an 84.55 cm/s higher baPWV at follow-up (P = 0.0003). These results were consistent with the findings from the logistic regression models.

To minimize the potential confounding effect of renal function on the Cre/BW ratio, we performed a stratified analysis based on eGFR levels (Table 4). In the longitudinal analysis, participants with normal renal function (eGFR ≥90 mL/min/1.73 m²) in the highest tertile of the Cre/BW ratio had a significantly increased risk of developing arterial stiffness compared with those in the lowest tertile (OR: 2.06; 95% CI: 1.21–3.49; P = 0.004). Table 5 and Supplementary Table S3 present the subgroup analysis data, demonstrating that the association between Cre/BW ratio and the risk of arterial stiffness was consistent across various subgroups. In the cross-sectional analysis (Table 5), we observed a more robust association between Cre/BW ratio and the risk of incident arterial stiffness among participants younger than 60 years (1.40; 95% CI, 1.15–1.71; P = 0.0481).

In the cross-sectional study, ROC curve evaluation identified 1.25 as the best cutoff value to predict the occurrence of arterial stiffness. This yielded an AUC of 0.534 (95% CI: 0.52–0.55, p < 0.0001), a sensitivity of 47.8%, a specificity of 58.9%, and a Youden index of 6.7% (Figure 3). Furthermore, the AUC for the Cre/BW ratio in longitudinal research is 0.566 (95% CI: 0.54–0.60, p < 0.0001) and the optimal cutoff value is 1.29 (sensitivity is 61%, specificity is 50%, and Youden index is 11%).