Systemic Inflammation and Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease and Chronic Kidney Disease

BACKGROUND: Systemic inflammation (SI), measured by high-sensitivity C-reactive protein (hsCRP), is common in both atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD). OBJECTIVES: The objectives of the study was to evaluate the association between SI and cardiovascular and economic outcomes among Veterans with ASCVD and CKD. METHODS: We conducted an analysis of Veterans with ASCVD and CKD with hsCRP testing between 2008 and 2022. We classified Veterans as with SI (hsCRP 2-10 mg/L) and without SI (hsCRP <2 mg/L). The primary outcome was the 3-point major adverse cardiovascular event (MACE) composite: death, myocardial infarction, and stroke. Additional outcomes included acute care utilization and health care costs. We evaluated the adjusted association between SI and clinical outcomes, acute care utilization, and costs via Cox regression, negative binomial regression, and gamma regression, respectively. RESULTS: Veterans with SI (n = 39,006) were younger (72.5 [SD: 9.1] vs 73.6 [SD: 9.1] years; P < 0.001) and had a higher prevalence of peripheral arterial disease (48.4% [18,860/39,006] vs 43.8% [10,152/23,176]; P < 0.001). Over a median follow-up of 4.2 years (IQR: 2.1-7.0; total of 307,074 person-years), the MACE rate was 11.64 (95% CI: 11.48-11.79) compared with 8.66 (95%CI: 8.49-8.83) per 100 patient-years in the group with vs without SI (P < 0.001). After adjustment, the HR for SI was 1.40 (95% CI: 1.36-1.43) for MACE. SI was significantly associated with increased hospitalizations (IRR: 1.24; 95% CI: 1.20-1.29) and $4,115 (95% CI: $1,878-$6,353) in additional costs over 1 year. CONCLUSIONS: Among Veterans with ASCVD and CKD, SI was associated with an increased risk of MACE and higher health care utilization and costs.