Burden of systemic inflammation and associated health outcomes in adults with atherosclerotic cardiovascular disease managed in routine care

Abstract Background The burden and outcomes of inflammation in people with atherosclerotic cardiovascular disease (ASCVD) are poorly defined, particularly beyond the controlled settings of trials and research cohorts. Methods We conducted a longitudinal observational study of adults with ASCVD undergoing C-reactive-protein (CRP) testing in routine healthcare in Stockholm, Sweden. After excluding CRP tests associated with acute illness and patients with medications/conditions that bias CRP interpretation, the systemic inflammation of participants was defined over a 3-month ascertainment window. Baseline determinants of CRP≥2 mg/L were explored with logistic regression, and baseline CRP categories were compared via Poisson and Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events (MACE), heart failure hospitalization, and all-cause death. Result After applying inclusion/exclusion criteria, we identified 84,399 adults with ASCVD with a mean age of 71 years and of which 54% were men. In total, 60% had CRP≥2 mg/L. At baseline, female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anemia, were associated with CRP≥2 mg/L. Conversely, the use of RASi, antiplatelets, and lipid-lowering therapy were associated with lower odds. Over a median follow-up of 6.4 years and compared to people with CRP <2 mg/L, those with CRP≥2 mg/L had a higher rate of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications during follow-up (P<0.05 for all). They also had a higher rate of MACE [adjusted hazard ratio (HR), 1.30; 95% CI, 1.27–1.33], heart failure hospitalization [1.24; 1.20–1.39], and all-cause death [1.35; 1.20–1.30]. Results were consistent across subgroups and more granular CRP categories, and robust to the exclusion of extreme CRP values or early events. Conclusions Two in three adults with ASCVD have systemic inflammation. A CRP≥2 mg/L is associated with excess healthcare resource utilization as well as increased rates of MACE, heart failure, and death.