SupplementalResults.pdf

Mild kidney dysfunction (MKD) increases cardiovascular disease (CVD) risk. Vascular dysfunction, including vascular endothelial dysfunction and aortic stiffening, is a key antecedent to CVD, but the impact of MKD on vascular function in midlife/older (ML/O) adults is not established. Moreover, sex is a biological variable that influences vascular function, but whether sex modulates the effects of MKD on vascular function is unclear. Vascular endothelial function (brachial artery flow-mediated dilation, FMD_BA) and aortic stiffness (carotid-femoral pulse wave velocity, PWV_CF) were compared in 93 ML/O men and postmenopausal women with MKD (estimated glomerular filtration rate [eGFR]: 60-89mL/min/1.73m²) versus 78 ML/O adults without MKD (healthy controls; eGFR: ≥90mL/min/1.73m²) (age: 50+ years). Circulating markers of inflammation and oxidative stress were also assessed. FMD_BA was lower in men with MKD (4.0±0.3%) versus healthy controls (5.7±0.7%; <i>P</i>=0.0093) and correlated with eGFR (r_s=0.28, <i>P</i>=0.0017). There was no difference in FMD_BA between women with MKD (4.7±0.4%) and healthy controls (4.7±0.5%; <i>P</i>=0.98) and no relation with eGFR. PWV_CF was higher in men with MKD (9.4±0.2m/s) versus controls (8.4±0.3m/s; <i>P</i>=0.030) and correlated with eGFR (r=-0.34, <i>P</i>=0.0013). However, PWV_CF was not different between women with MKD (9.3±0.5m/s) and controls (10.1±0.4m/s; <i>P</i>=0.099) and not related to eGFR. The observed effects of MKD on vascular function were independent of traditional CVD risk factors and medication use. There were no differences in markers of inflammation nor oxidative stress between controls and MKD. Our findings suggest that vascular dysfunction may contribute to increased CVD risk associated with MKD in ML/O men but not postmenopausal women.

轻度肾功能不全（Mild kidney dysfunction, MKD）可升高心血管疾病（cardiovascular disease, CVD）的发病风险。血管功能异常涵盖血管内皮功能障碍（vascular endothelial dysfunction）与主动脉硬化（aortic stiffening），是心血管疾病的关键前驱病变，但目前尚未明确轻度肾功能不全对中年及以上（midlife/older, ML/O）人群血管功能的影响。此外，性别作为影响血管功能的生物学变量，其是否可调节轻度肾功能不全对血管功能的作用仍不明确。
本研究纳入93例合并轻度肾功能不全的中年及以上男性与绝经后女性（postmenopausal women），其估算肾小球滤过率（estimated glomerular filtration rate, eGFR）为60~89mL/min/1.73m²；同时纳入78例无轻度肾功能不全的中年及以上健康对照者，年龄均≥50岁，eGFR≥90mL/min/1.73m²。研究对两组的血管内皮功能（肱动脉血流介导的舒张功能，brachial artery flow-mediated dilation, FMD_BA）与主动脉僵硬度（颈股动脉脉搏波速度，carotid-femoral pulse wave velocity, PWV_CF）进行了比较，并检测了循环炎症与氧化应激标志物水平。
结果显示，合并轻度肾功能不全的男性其FMD_BA显著低于健康对照者（4.0±0.3% vs 5.7±0.7%；*P*=0.0093），且与eGFR呈正相关（r_s=0.28，*P*=0.0017）。而合并轻度肾功能不全的女性其FMD_BA与健康对照者无显著差异（4.7±0.4% vs 4.7±0.5%；*P*=0.98），且与eGFR无相关性。颈股动脉脉搏波速度（PWV_CF）方面，合并轻度肾功能不全的男性显著高于健康对照者（9.4±0.2m/s vs 8.4±0.3m/s；*P*=0.030），且与eGFR呈负相关（r=-0.34，*P*=0.0013）。但合并轻度肾功能不全的女性其PWV_CF与健康对照者无显著差异（9.3±0.5m/s vs 10.1±0.4m/s；*P*=0.099），且与eGFR无相关性。
上述轻度肾功能不全对血管功能的影响独立于传统心血管疾病危险因素与用药情况。健康对照者与轻度肾功能不全患者的炎症及氧化应激标志物水平无显著差异。本研究结果提示，血管功能异常可能是中年及以上男性合并轻度肾功能不全时心血管疾病风险升高的相关机制，但绝经后女性并未出现这一现象。