Introduction: Impaired kidney function is a known risk factor for lower-extremity peripheral artery disease (PAD). Whether novel markers of kidney filtration like cystatin C and beta-2-microglobulin (B2M) differ in their associations with PAD risk compared to creatinine-based estimated glomerular filtration rate (eGFRcr) is unclear. Also, bone-mineral metabolism (BMM) disorders are commonly complicated with impaired kidney function, but it is not known whether BMM markers influenced by kidney function are associated with PAD.
Hypothesis: Novel filtration markers are more strongly associated with PAD risk than eGFRcr, and BMM markers are associated with PAD risk beyond kidney function.
Methods: Using data from 13215 ARIC Study participants free of clinical history of PAD at baseline (1990-1992), we applied Cox proportional hazards model to quantify the associations of biomarkers and eGFR equations incorporating these biomarkers (cystatin C, B2M, eGFRcr, and eGFR based on cystatin C and cr [eGFRcr-cys]) with PAD risk. We also evaluated whether BMM markers (fibroblast growth factor 23, parathyroid hormone, calcium and phosphorus) were associated with PAD after adjustment for eGFR. PAD was defined as hospitalizations with ICD-9 code of 440.2x and 440.3.
Results: During a median follow-up of 21 years, 587 participants had at least one hospitalization with a discharge code for PAD. The novel markers cystatin C and B2M showed stronger associations with PAD compared to eGFRcr (Table). When examining BMM markers, only elevated phosphorus level was associated with PAD risk and the association remained significant after adjustment for eGFRcr-cys (Table).
Conclusions: The novel filtration markers cystatin C and B2M are stronger in their association with PAD compared to eGFRcr. Moreover, higher phosphorus level was related to future PAD risk beyond kidney function. Our results suggest novel filtration markers may improve PAD risk assessment, and there is a possible role for phosphorus metabolism in the pathophysiology of PAD.