Inflammatory and cholesterol risks and rates of major cardiovascular events among patients with atherosclerotic cardiovascular disease in routine care

Aims: Inflammation and hyperlipidaemia play a pivotal role in atherosclerotic cardiovascular disease (ASCVD), and inflammatory risk may outweigh cholesterol risk among statin-treated patients. However, it is unclear how these risks relate to ASCVD outcomes in a real-world population. Methods and results: Observational study of 39 638 ASCVD adults in Stockholm's healthcare (2007-21) who underwent routine testing for high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDL-C). Groups were defined by LDL-C (≥1.8 vs. < 1.8 mmol/L) and hsCRP (≥2 vs. < 2 mg/L): as low risk, high cholesterol risk (CR) alone, high inflammatory risk (IR) alone, and combined high cholesterol and inflammatory risk (CIR). Primary outcome was major adverse cardiovascular (CV) events (MACE); secondary outcomes included all-cause death, CV death, and heart failure (HF) hospitalization. Mean age at baseline was 69 years, 61% were men, 19.4% had chronic kidney disease (CKD), and 61% were receiving lipid-lowering therapy (LLT). Over follow-up (median 4.5 years), 5349 MACE, 7955 deaths (2088 CV deaths) and 4286 HF hospitalizations occurred. Compared with patients with low risk, those with IR or CIR experienced the highest MACE risk (HR 1.39; 95% CI 1.26-1.54 for CIR, HR 1.18; 1.05-1.33 for IR), followed by CR (HR 1.12; 1.01-1.24). Elevated hsCRP, with or without elevated LDL-C, was strongly associated with secondary outcomes, while CR alone was not. Patterns were generally consistent across CKD and LLT subgroups. Conclusion: In routine care high inflammatory risk, alone or with high cholesterol risk, is a stronger predictor of adverse outcomes than high cholesterol alone.