Stam Frank, van Guldener Coen, Becker Annemarie, Dekker Jacqueline M, Heine Robert J, Bouter Lex M, Stehouwer Coen D A
Department of Internal Medicine, Academic Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.
J Am Soc Nephrol. 2006 Feb;17(2):537-45. doi: 10.1681/ASN.2005080834. Epub 2005 Dec 28.
Mildly impaired renal function is associated with cardiovascular morbidity and mortality. There are indications that endothelial dysfunction and/or chronic inflammation, which play an important role in atherothrombosis, are present in early stages of renal insufficiency. This study investigated whether and to which extent endothelial dysfunction and inflammation were related to renal function and contributed to renal function-associated cardiovascular mortality in a population-based cohort (n = 613), aged 50 to 75 yr, that was followed with a median duration of 12.5 yr. During follow-up, 192 individuals died (67 of cardiovascular causes). At baseline, renal function was estimated with serum creatinine, the Cockcroft-Gault formula, and the Modification of Diet in Renal Disease equation of GFR (eGFR). Endothelial function was estimated by plasma von Willebrand factor, soluble vascular cell adhesion molecule-1, and the urinary albumin-creatinine ratio. Inflammatory activity was estimated by plasma C-reactive protein and soluble intercellular adhesion molecule-1. Renal function was mildly impaired (mean eGFR 68 +/- 12 ml/min per 1.73 m(2)) and independently associated with von Willebrand factor (standardized beta -0.09; 95% confidence interval [CI] -0.18 to -0.002; P < 0.05), soluble vascular cell adhesion molecule-1 (standardized beta -0.14; 95% CI -0.22 to -0.05; P < 0.01), and albumin-creatinine ratio (standardized beta -0.15; 95% CI -0.23 to -0.08; P < 0.001) but not with markers of inflammatory activity. Renal function was inversely associated with cardiovascular and all-cause mortality. The relative risk for cardiovascular mortality but not all-cause mortality associated with renal function decreased from 1.22 to 1.12 per 5 ml/min per 1.73 m(2) decrease of eGFR after adjustment for markers of endothelial dysfunction. In conclusion, endothelial dysfunction was related to renal function and contributed to the excess in cardiovascular mortality in this population-based cohort with mild renal insufficiency.
轻度肾功能损害与心血管疾病的发病率和死亡率相关。有迹象表明，在动脉粥样硬化血栓形成中起重要作用的内皮功能障碍和/或慢性炎症存在于肾功能不全的早期阶段。本研究调查了在一个年龄为50至75岁、中位随访时间为12.5年的基于人群的队列（n = 613）中，内皮功能障碍和炎症是否以及在何种程度上与肾功能相关，并导致与肾功能相关的心血管死亡率。在随访期间，192人死亡（67人死于心血管疾病）。在基线时，用血清肌酐、Cockcroft-Gault公式和肾脏疾病饮食改良方程估算肾小球滤过率（eGFR）来评估肾功能。通过血浆血管性血友病因子、可溶性血管细胞黏附分子-1和尿白蛋白-肌酐比值评估内皮功能。通过血浆C反应蛋白和可溶性细胞间黏附分子-1评估炎症活性。肾功能轻度受损（平均eGFR为68±12 ml/min per 1.73 m²），且与血管性血友病因子（标准化β -0.09；95%置信区间[CI] -0.18至-0.002；P < 0.05）、可溶性血管细胞黏附分子-1（标准化β -0.14；95% CI -0.22至-0.05；P < 0.01）和白蛋白-肌酐比值（标准化β -0.15；95% CI -0.23至-0.08；P < 0.001）独立相关，但与炎症活性标志物无关。肾功能与心血管死亡率和全因死亡率呈负相关。在校正内皮功能障碍标志物后，每1.73 m²的eGFR每降低5 ml/min，与肾功能相关的心血管死亡率的相对风险从1.22降至1.12，但全因死亡率的相对风险未降低。总之，在内皮功能障碍与肾功能相关，并导致了该轻度肾功能不全的基于人群的队列中心血管死亡率过高。
