Abstract 3479: Emerging Cardiovascular Risk Factors That Account For A Significant Portion Of Attributable Mortality Risk In Chronic Kidney Disease: A Precis Study.

Background: Chronic kidney disease (CKD) increases cardiovascular risk and mortality. However, traditional cardiovascular risk factors do not adequately account for the substantial increase in mortality observed in CKD. Methods and Results: Prospective cohort study of 4,680 consecutive new patients from a tertiary care preventive cardiology program from 1996 to 2005. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) method. Baseline levels of traditional (LDL-C, HDL-C, triglycerides, total cholesterol, fasting glucose) and emerging risk factors (apolipoprotein (apo) A1 and apoB, lipoprotein(a), fibrinogen, homocysteine, and CRP) were examined. All-cause mortality was obtained by social security death index. There were 278 deaths for a median follow up of 22 months. CKD (eGFR ≤ 60ml/min) was strongly associated with mortality after adjusting for traditional cardiovascular risk factors (Hazard ratio (HR), 2.31, 95% CI=1.77–3.11, p<0.001) and with addition of propensity score (HR = 2.33, 95% CI=1.75–3.10, p<0.001). Of all the traditional and emerging risk factors monitored, only addition of homocysteine and fibrinogen significantly attenuated the association between CKD and mortality (adjusted HR = 1.73, 95% CI=1.23–2.34, p<0.001), explaining 38% of the attributable mortality risk from CKD. A significant interaction (p = 0.004) between homocysteine and eGFR was observed whereby annual mortality rate in CKD subjects with homocysteine < 10 μmol/L (bottom tertile) was similar to those with normal renal function (1% per year), while homocysteine levels ≥ 12.5 μ mol/L (top tertile) were associated with a 7 fold higher mortality risk. Conclusion: Homocystiene and fibrinogen levels explain 38% of the attributable mortality risk from CKD.