Dogra Gursharan, Irish Ashley, Chan Dick, Watts Gerald
School of Medicine and Pharmacology, University of Western Australia, Australia.
Am J Kidney Dis. 2006 Dec;48(6):926-34. doi: 10.1053/j.ajkd.2006.08.008.
Conventional cardiovascular risk equations underestimate the risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD), implying a role for novel risk factors. Our aim was to compare vascular function and arterial compliance, known markers of CVD, between patients with CKD and healthy controls and examine their association with traditional and novel CVD risk factors.
Vascular function was determined by using high-resolution ultrasonography to measure brachial artery endothelial-dependent flow-mediated dilatation (FMD) and endothelial-independent glyceryl trinitrate (GTN)-mediated dilatation. Arterial compliance was measured by using pulse contour analysis to generate large-artery (C1) and small-artery (C2) compliance. We also examined the relationship between vascular function, arterial compliance and blood pressure, lipid and lipoprotein levels, insulin resistance, inflammation, oxidative stress, and calcium and phosphate levels in 105 patients with CKD and 40 healthy controls.
Vascular function and arterial compliance were significantly impaired in patients with CKD compared with healthy controls: mean FMD, 3.8% +/- 0.3% (SE) versus 5.7% +/- 0.6%; GTN-mediated dilatation, 15.7% +/- 0.9% versus 19.6% +/- 1.0%; C1, geometric mean, 12.1 mL/mm Hg; 95% confidence interval (CI), 11.2 to 13.1 versus 15.1 mL/mm Hg; 95% CI, 13.7 to 16.5; and C2, 3.8 mL/mm Hg; 95% CI, 3.4 to 4.3 versus 5.0 mL/mm Hg; 95% CI, 4.2 to 6.0; all P < 0.05. Patients with CKD had greater waist-hip ratios, systolic blood pressures (SBPs), pulse pressures, triglyceride levels, oxidized low-density lipoprotein levels, high-sensitivity interleukin 6 levels, and Homeostasis Model Assessment (HOMA) scores (all P < 0.05) and lower high-density lipoprotein levels (P < 0.001). In patients with CKD, HOMA score and SBP were associated negatively with FMD (model R(2) = 0.28; P < 0.001), and SBP and waist-hip ratio were associated negatively with GTN-mediated dilatation (model R(2) = 0.25; P < 0.001). Pulse pressure was associated negatively with C1 (R(2) = 0.37; P < 0.001), and pulse pressure and high-sensitivity interleukin 6 level were associated negatively with C2 (model R(2) = 0.36; P < 0.001).
Insulin resistance, inflammation, systolic hypertension, and increased pulse pressure, but not dyslipidemia, were associated with vascular dysfunction and may be targets for future interventional strategies to reduce CVD risk in patients with CKD.
传统的心血管风险方程低估了慢性肾脏病（CKD）患者患心血管疾病（CVD）的风险，这意味着存在新的风险因素。我们的目的是比较CKD患者与健康对照者之间的血管功能和动脉顺应性（已知的CVD标志物），并研究它们与传统和新的CVD风险因素的关联。
通过使用高分辨率超声测量肱动脉内皮依赖性血流介导的扩张（FMD）和内皮非依赖性硝酸甘油（GTN）介导的扩张来确定血管功能。使用脉搏轮廓分析来生成大动脉（C1）和小动脉（C2）顺应性，以此测量动脉顺应性。我们还研究了105例CKD患者和40例健康对照者的血管功能、动脉顺应性与血压、脂质和脂蛋白水平、胰岛素抵抗、炎症、氧化应激以及钙和磷水平之间的关系。
与健康对照者相比，CKD患者的血管功能和动脉顺应性显著受损：平均FMD分别为3.8%±0.3%（标准误）和5.7%±0.6%；GTN介导的扩张分别为15.7%±0.9%和19.6%±1.0%；C1的几何平均值分别为12.1 mL/mm Hg，95%置信区间（CI）为11.2至13.1，而健康对照者为15.1 mL/mm Hg，95%CI为13.7至16.5；C2分别为3.8 mL/mm Hg，95%CI为3.4至4.3，而健康对照者为5.0 mL/mm Hg，95%CI为4.2至6.0；所有P<0.05。CKD患者的腰臀比、收缩压（SBP）、脉压、甘油三酯水平、氧化型低密度脂蛋白水平、高敏白细胞介素6水平和稳态模型评估（HOMA）评分更高（均P<0.05），而高密度脂蛋白水平更低（P<0.001）。在CKD患者中，HOMA评分和SBP与FMD呈负相关（模型R² = 0.28；P<0.001），SBP和腰臀比与GTN介导的扩张呈负相关（模型R² = 0.25；P<0.001）。脉压与C1呈负相关（R² = 0.37；P<0.001），脉压和高敏白细胞介素6水平与C2呈负相关（模型R² = 0.36；P<0.001）。
胰岛素抵抗、炎症、收缩期高血压和脉压升高与血管功能障碍相关，而非血脂异常，它们可能是未来降低CKD患者CVD风险的干预策略的目标。
