KIDNEY FUNCTION, BONE-MINERAL METABOLISM MARKERS, AND FUTURE RISK OF PERIPHERAL ARTERY DISEASE: THE ATHEROSCLEROSIS RISK IN COMMUNITES (ARIC) STUDY

peripheral artery disease;kidney dysfunction;estimated glomerular filtration rate;novel filtration markers;cystatin C;beta-2 microglobulin;bone-mineral metabolism markers;phosphorus;critical limb ischemia;Epidemiology

Yang, ChaoMatsushita, Kunihiro ;

Johns Hopkins University

关键词: peripheral artery disease;    kidney dysfunction;    estimated glomerular filtration rate;    novel filtration markers;    cystatin C;    beta-2 microglobulin;    bone-mineral metabolism markers;    phosphorus;    critical limb ischemia;    Epidemiology;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/59359/YANG-THESIS-2016.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Background: Kidney dysfunction is a known risk factor for lower-extremity peripheral artery disease (PAD). Although novel filtration markers like cystatin C and beta-2-microglobulin demonstrate stronger associations with coronary heart disease, stroke, and heart failure compared to creatinine-based estimated glomerular filtration rate (eGFRcr), whether this pattern holds for PAD is unclear. Also, bone-mineral disorders are important complications of kidney dysfunction, but little is known whether bone-mineral metabolism (BMM) markers are associated with future PAD risk beyond kidney function.Methods: Using data from 12,437 ARIC Study participants free of clinical history of PAD at baseline (1990-1992), we first quantified the associations of clinical categories of eGFR based on creatinine, cystatin C, and both with PAD risk. Subsequently, we evaluated quartiles of these eGFRs, cystatin C, beta-2 microglobulin, as well as BMM markers (fibroblast growth factor 23, parathyroid hormone, calcium and phosphorus). PAD was defined as hospitalizations with ICD-9 codes for lower-extremity atherosclerosis, revascularization and amputation.Results: During a median follow-up of 21 years, 471 participants had at least one hospitalization with a discharge code for PAD. Low eGFR was significantly associated with future PAD risk, independent of traditional cardiovascular risk factors, with slightly stronger relationship when cystatin C was used (5.3-7.5 fold higher risk for eGFR <30 and 2.5-3.7 fold higher risk for eGFR 30-59 vs. eGFR ≥90 ml/min/1.73m2). Novel filtration markers, particularly B2M, appeared to have stronger association with incident PAD than eGFRcr (adjusted hazard ratios (HRs) for top vs. bottom quartile 2.85 (95% CI: 2.10- 3.88) vs. 1.30 (95% CI: 0.98-1.71)). The association was consistent after adjustment for BMM markers or restricting to critical limb ischemia as an outcome. Among BMM markers, top vs. bottom quartile of phosphorus remained significant for PAD risk beyond potential confounders including kidney function (HR 1.43, 95% CI: 1.08-1.88).Conclusions: Kidney dysfunction was significantly associated with future PAD risk independently of potential confounders and BMM markers, particularly when cystatin C and B2M were taken into account. Among BMM markers, phosphorus was most robustly associated with future PAD. Our results suggest the usefulness of novel filtration markers for PAD risk assessment and the unique contribution of phosphorus to the pathophysiology of PAD.