Inflammation is associated with high disease burden and adverse outcomes in patients with atherosclerotic cardiovascular disease and chronic kidney disease: a real-world evidence study

Abstract

Atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD) often coexist, worsening patient prognosis. Inflammation, commonly assessed by C-reactive protein (CRP), is a potential therapeutic target. Trials of inflammation-targeted therapies highlight the need for evidence on the clinical impact of CV inflammation in patients with ASCVD and CKD. To estimate the prevalence of inflammation in Israeli patients with ASCVD and CKD and determine its association with CV, renal, and mortality outcomes. This cohort study used electronic medical records from a national health maintenance organisation (HMO), obtained between 1 January 2010 and 1 June 2025. Patients ≥25 years old with incident diagnoses of both ASCVD and CKD recorded between 1 January 2011 and 1 June 2025 and ≥1 CRP measurement after the two diagnoses were included. Inflammation was defined as CRP ≥2 mg/L. CRP tests >20 mg/L, tests taken during hospitalisation or emergency care, and tests taken ≤30 days after ASCVD/CKD diagnosis were excluded. The first eligible CRP measurement served as index date. Exclusion criteria were: <12 months of continuous enrolment with the HMO, record of autoimmune or chronic inflammatory condition, or use of medications affecting CRP levels or indicating a chronic inflammatory or infectious condition (≤7 days pre-index). Outcomes included all-cause mortality, 3-point major adverse cardiovascular events (3P-MACE), individual CV outcomes, and renal outcomes. The ASCVD+CKD+inflammation group was compared to a reference group with ASCVD and CKD, without inflammation. Inverse probability weighting (IPW) balanced baseline characteristics between the groups and weighted Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (CI). Follow-up continued until the earliest: outcome of interest, death, disenrollment, or end of study. The final cohort after IPW included 22,931 patients (mean±SD age: 73.9±10.2 years; 44.1% female); 70.7% had inflammation (Table). Median (IQR) follow-up was 33.1 (15.7–61.6) months; patients in the CV inflammation group experienced significantly higher rates (HR; 95% CI) of all-cause mortality (1.34; 1.26–1.43), 3P-MACE (1.21; 1.08–1.37), heart failure (1.38; 1.23–1.55), peripheral revascularisation (1.34; 1.15–1.57), non-fatal myocardial infarction (1.41; 1.20–1.67), non-fatal stroke (1.20; 1.03–1.41), end-stage renal disease (1.33; 1.19–1.49), and acute kidney injury (1.24; 1.07–1.43), compared with patients without inflammation (Figure). Inflammation is highly prevalent in patients with ASCVD and CKD and is associated with increased mortality and adverse cardiovascular and renal outcomes. These real-world findings show the high disease burden in this population and highlight an unmet need for novel therapies targeting inflammation in patients with ASCVD and CKD.ASCVD CKD_ESC 2026 Abstract FigureASCVD CKD_ESC 2026 Abstract Table