肾功能、骨矿物质代谢标志物与外周动脉疾病的未来风险。
Kidney function, bone-mineral metabolism markers, and future risk of peripheral artery disease.
机构信息
Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
University of California at San Diego, San Diego, CA, USA.
出版信息
Atherosclerosis. 2017 Dec;267:167-174. doi: 10.1016/j.atherosclerosis.2017.09.020. Epub 2017 Sep 22.
BACKGROUND AND AIMS
Reduced kidney function is a risk factor for lower-extremity peripheral artery disease (PAD). However, the associations of novel filtration markers with PAD are yet to be quantified. Moreover, little is known on whether bone-mineral metabolism (BMM) markers are related to incident PAD beyond kidney function.
METHODS
Using data from 12,472 participants at baseline (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) study, we comprehensively quantified the associations of kidney related markers with incident PAD (defined as hospitalizations with diagnosis of lower-extremity atherosclerosis, revascularization, or amputation). Kidney related markers of interest included estimated glomerular filtration rate (eGFR) (based on creatinine, cystatin C, and both), cystatin C, beta-2 microglobulin (B2M), and BMM markers (serum fibroblast growth factor 23, parathyroid hormone, calcium, and phosphorus).
RESULTS
During a median follow-up of 21 years, 471 participants developed incident PAD. Low eGFR was significantly associated with future PAD risk, with slightly stronger relationship when cystatin C was used (adjusted hazard ratio [HR] 6.3-8.3 for eGFR <30 and 2.4-3.5 for eGFR 30-59 vs. eGFR ≥90 mL/min/1.73 m). Among all filtration markers, B2M had the strongest association with incident PAD (HR for top vs. bottom quartile 2.60 [95% CI: 1.91-3.54] for B2M vs. 1.20 [0.91-1.58] for creatinine-based eGFR). Among BMM markers, only phosphorus remained significant for PAD risk beyond potential confounders, including kidney function (HR 1.47 [1.11-1.94] in top quartile).
CONCLUSIONS
Kidney dysfunction was independently associated with future PAD risk, particularly when assessed with cystatin C and B2M. Among the BMM markers tested, phosphorus was most robustly associated with incident PAD beyond kidney function. Our results suggest the potential usefulness of novel filtration markers for PAD risk assessment and the possible role of phosphorus in the pathophysiology of PAD.
背景和目的
肾功能下降是下肢外周动脉疾病（PAD）的一个危险因素。然而，新型滤过标志物与 PAD 的关联尚未被量化。此外，人们对骨骼矿物质代谢（BMM）标志物是否与肾功能以外的 PAD 发病有关知之甚少。
方法
利用来自动脉粥样硬化风险社区（ARIC）研究的 12472 名参与者基线（1990-1992 年）的数据，我们全面量化了与肾脏相关的标志物与 PAD 发病的关联（定义为下肢动脉粥样硬化、血运重建或截肢的住院治疗）。与肾脏相关的标志物包括估计肾小球滤过率（基于肌酐、胱抑素 C 和两者）、胱抑素 C、β-2 微球蛋白（B2M）和 BMM 标志物（血清成纤维细胞生长因子 23、甲状旁腺激素、钙和磷）。
结果
在中位随访 21 年期间，471 名参与者发生了 PAD 发病事件。低 eGFR 与未来 PAD 风险显著相关，当使用胱抑素 C 时，相关性略强（eGFR <30 时调整后的 HR 为 6.3-8.3，eGFR 30-59 时为 2.4-3.5，eGFR ≥90 mL/min/1.73 m）。在所有滤过标志物中，B2M 与 PAD 发病的相关性最强（B2M 最高四分位与最低四分位的 HR 为 2.60[95%CI：1.91-3.54]，基于肌酐的 eGFR 为 1.20[0.91-1.58]）。在 BMM 标志物中，只有磷在包括肾功能在内的潜在混杂因素之外与 PAD 风险相关（最高四分位的 HR 为 1.47[1.11-1.94]）。
结论
肾功能障碍与未来 PAD 风险独立相关，特别是当使用胱抑素 C 和 B2M 评估时。在测试的 BMM 标志物中，磷与 PAD 发病的相关性最强，超出了肾功能的影响。我们的结果表明，新型滤过标志物在 PAD 风险评估中具有潜在的应用价值，磷在 PAD 发病机制中的作用可能是一个重要的研究方向。
Zotero 插件