High Sensitivity Troponin and Risk of Incident Peripheral Arterial Disease in Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort [CRIC] Study).

Patients with chronic kidney disease (CKD) are at increased risk for peripheral arterial disease (PAD). A novel biomarker to accurately and reliably predict new onset PAD in high risk patients is needed. High sensitivity troponin (HsTP) is a new assay which allows detection of very low troponin levels with high precision. We sought to explore the association between HsTP and risk of PAD in CKD. The Chronic Renal Insufficiency Cohort (CRIC) is a prospective cohort of 3,939 individuals with mild to moderate CKD using age related criteria for glomerular filtration rate. High sensitivity troponin T was measured at study enrollment. Patients with previous history of PAD or coronary artery disease were excluded. Patients were followed for new-onset adjudicated PAD, and the association between HsTP and incident PAD was examined. A total of 2,909 participants free of PAD and coronary artery disease at enrollment were included in this analysis. Over a mean follow up 7.4 years [interquartile ranges 5.8 to 8.5] years, 79 (2.7%) patients developed PAD. The 3-, 6-, and 9-year incidence of PAD was 1.00%, 2.03%, and 2.72%, respectively. At 9 years, the cumulative rates of PAD increased with HsTP (Quartile 1: 0.3%, Quartile 2: 2.4%, Quartile 3: 3.7%, Quartile 4: 10.7%; p <0.001). After adjusting for clinical risk factors of PAD, patients in the third quartile (Hazards ratio 5.89, 95% confidence interval: 1.31 to 26.47, p = 0.021) and fourth quartile of HsTP (Hazards ratio 10.24, 95% confidence interval 2.23 to 47.08, p = 0.003) had higher risk of PAD compared with lowest quartile of HsTP. HsTP had good discrimination of PAD at 3 years (area under the curve [AUC] 0.76), 6 years (AUC 0.79) and 9 years (AUC 0.80). Addition of HsTP to Framingham risk score improved model discrimination of PAD. In conclusion, in patients with mild-moderate CKD, HsTP levels are associated with and predictive of risk of incident PAD. This association remains significant despite adjustment for traditional PAD risk factors and chronic kidney disease.