Darvish Sanna, Coppock McKinley E, Murray Kevin O, Craighead Daniel H, Chonchol Michel, Nowak Kristen L, Seals Douglas R, Rossman Matthew J
Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States.
Department of Medicine-Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, Colorado, United States.
Am J Physiol Heart Circ Physiol. 2025 Aug 1;329(2):H401-H408. doi: 10.1152/ajpheart.00332.2025. Epub 2025 Jul 7.
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) and aortic stiffness (carotid-femoral pulse wave velocity, PWV) were compared in 93 ML/O men and postmenopausal women with MKD [estimated glomerular filtration rate (eGFR): 60-89 mL/min/1.73 m] versus 78 ML/O adults without MKD (healthy controls; eGFR: ≥90 mL/min/1.73 m) (age: 50+ yr). Circulating markers of inflammation and oxidative stress were also assessed. FMD was lower in men with MKD (4.0 ± 0.3%) versus healthy controls (5.5 ± 0.5%; = 0.0097) and correlated with eGFR ( = 0.30, = 0.0073). There was no difference in FMD between women with MKD (4.7 ± 0.4%) and healthy controls (4.8 ± 0.5%; = 0.86) and no relation with eGFR. PWV was higher in men with MKD (9.4 ± 0.2 m/s) versus controls (8.4 ± 0.3 m/s; = 0.030) and correlated with eGFR ( = -0.34, = 0.0013). However, PWV was not different between women with MKD (9.3 ± 0.5 m/s) and controls (10.1 ± 0.4 m/s; = 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 in postmenopausal women. Midlife/older (ML/O) adults with mild kidney dysfunction (MKD) are at an increased CVD risk compared with ML/O adults with normal kidney function. We assessed whether ML/O men and postmenopausal women with MKD exhibit vascular dysfunction compared with ML/O adults without MKD. We observed MKD-related vascular dysfunction in men but not in women. Thus, vascular dysfunction may contribute to MKD-associated increases in CVD risk in men but is unlikely to contribute to the increased risk in postmenopausal women.
轻度肾功能不全（MKD）会增加心血管疾病（CVD）风险。血管功能障碍，包括血管内皮功能障碍和主动脉硬化，是CVD的关键先兆，但MKD对中年/老年（ML/O）成年人血管功能的影响尚未明确。此外，性别是影响血管功能的生物学变量，但性别是否调节MKD对血管功能的影响尚不清楚。对93名患有MKD的ML/O男性和绝经后女性[估计肾小球滤过率（eGFR）：60 - 89 mL/min/1.73 m²]与78名无MKD的ML/O成年人（健康对照；eGFR：≥90 mL/min/1.73 m²）（年龄：50岁及以上）的血管内皮功能（肱动脉血流介导的扩张，FMD）和主动脉僵硬度（颈股脉搏波速度，PWV）进行了比较。还评估了炎症和氧化应激的循环标志物。患有MKD的男性的FMD（4.0±0.3%）低于健康对照（5.5±0.5%；P = 0.0097），且与eGFR相关（r = 0.30，P = 0.0073）。患有MKD的女性的FMD（4.7±0.4%）与健康对照（4.8±0.5%；P = 0.86）之间无差异，且与eGFR无关。患有MKD的男性的PWV（9.4±0.2 m/s）高于对照组（8.4±0.3 m/s；P = 0.030），且与eGFR相关（r = -0.34，P = 0.0013）。然而，患有MKD的女性的PWV（9.3±0.5 m/s）与对照组（10.1±0.4 m/s；P = 0.099）之间无差异，且与eGFR无关。观察到的MKD对血管功能的影响独立于传统的CVD危险因素和药物使用。对照组和MKD组之间在炎症标志物和氧化应激方面无差异。我们的研究结果表明，血管功能障碍可能导致ML/O男性中与MKD相关的CVD风险增加，但绝经后女性并非如此。与肾功能正常的ML/O成年人相比，患有轻度肾功能不全（MKD）的中年/老年（ML/O）成年人患CVD的风险增加。我们评估了患有MKD的ML/O男性和绝经后女性与无MKD的ML/O成年人相比是否表现出血管功能障碍。我们观察到男性存在与MKD相关的血管功能障碍，而女性没有。因此，血管功能障碍可能导致男性中与MKD相关的CVD风险增加，但不太可能导致绝经后女性风险增加。
