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

TL;DR

This study finds that high inflammation, with or without high cholesterol, is a stronger predictor of heart problems than high cholesterol alone in patients with heart disease.

Contribution

The study demonstrates that inflammatory risk is more strongly associated with adverse cardiovascular outcomes than cholesterol risk in real-world ASCVD patients.

Findings

Patients with high inflammatory risk (IR) or combined inflammatory and cholesterol risk (CIR) had higher rates of major cardiovascular events than those with high cholesterol risk alone.

Elevated hsCRP was strongly linked to all-cause death, cardiovascular death, and heart failure hospitalization, regardless of LDL-C levels.

Results were consistent across subgroups, including those with chronic kidney disease and those on lipid-lowering therapy.

Abstract

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.

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.

In routine care high inflammatory risk, alone or with high cholesterol risk, is a stronger predictor of adverse outcomes than high cholesterol alone.

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