Abstract 4360368: <u>SYSTEMIC INFLAMMATION AND CARDIOVASCULAR EVENTS AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE</u>

Background: Patients with chronic kidney disease (CKD) present high risk of new or recurrent cardiovascular events despite traditional risk factor management. Research Question: To assess whether systemic inflammation is independently associated with the hazard of cardiovascular events among patients with CKD not on kidney replacement therapy, with or without atherosclerotic cardiovascular disease (ASCVD) history. Methods: The CKD-Renal Epidemiology and Information Network (CKD-REIN) is a prospective cohort study of adult patients with CKD stage 2 to 5 conducted in 40 nationally representative nephrology outpatient facilities in France. Hs-CRP was measured centrally in plasma samples collected at baseline (2013-2016) with an immunoturbidimetric method. Systemic inflammation was defined by a hs-CRP ≥2 mg/L; patients with hs-CRP &gt;20 mg/L were excluded from the analysis (n= 117). We also examined hs-CRP as a continuous variable. Cox proportional hazards models were performed to estimate hazard ratios (HRs) and 95%CI of major cardiovascular events (MACE, the composite of stroke, myocardial infarction and cardiovascular death) and of hospitalized heart failure (HHF). Models were adjusted for age, sex, smoking, diabetes, systolic blood pressure, body mass index, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, history of ASCVD, LDL cholesterol, and the prescriptions of renin angiotensin system inhibitor, beta-blocker, aspirin and statin (SGLT2 inhibitors were not on the market in France at the time of data collection). Results: We included 2078 patients: 67% men, mean age 67±13 years, mean eGFR 36±12 mL/min/1.73m 2 , 38% with history of ASCVD. Median (IQR) hs-CRP concentration was 2.4 (1.1;5.1) mg/L. After a median follow-up of 5 years, 191 patients had a MACE and 397, HHF. After controlling for potential confounders, a two-fold increase in Hs-CRP was associated with a 14% higher hazard of MACE (95% CI, 2% to 28%) and a 26% higher hazard of HHF (95% CI, 13% to 40%). Compared to patients without ASCVD or systemic inflammation, those with ASCVD alone or with concomitant ASCVD and systemic inflammation had twice to thrice the hazard of cardiovascular events (Figure). Conclusions: In CKD patients not on kidney replacement therapy, systemic inflammation, as measured through hs-CRP, is associated with the onset cardiovascular events independently of traditional risk factors.