Beyond traditional risk factors: the impact of cumulative inflammation and remnant cholesterol on myocardial infarction in a prospective cohort study

The residual risk of myocardial infarction (MI) persists despite the management of traditional risk factors. Although remnant cholesterol and systemic inflammatory activity, reflected by high-sensitivity C-reactive protein (hs-CRP), may contribute to atherothrombosis, their long-term combined impact on MI remains unclear. In all, 42,303 participants from the Kailuan prospective cohort (2006–2010) with repeated remnant cholesterol and hs-CRP measurements were included. Cumulative exposure to remnant cholesterol and hs-CRP was calculated across three visits. Participants were stratified into six groups according to cumulative remnant cholesterol (below/above median) and cumulative hs-CRP concentrations (< 1, 1–3, ≥ 3 mg/L). Incident MI was ascertained through insurance and hospital records, with a median follow-up period of 10.99 years. During a median follow-up of approximately 11.0 years, 741 MI events were identified. The risk of MI increased progressively with increasing cumulative hs-CRP levels in both cumulative remnant cholesterol strata. Participants with concurrent cumulative remnant cholesterol and high cumulative hs-CRP levels had the greatest risk (HR 3.16, 95% CI 2.37–4.20). The associations remained robust across age, sex, body mass index, hypertension, and diabetes, and sensitivity analyses excluded early events, cancer, acute infection and major cardiovascular diseases at baseline. Women appeared to demonstrate a more pronounced relative risk under dual high exposure. Long-term cumulative exposure to elevated RC and systemic inflammation was associated with markedly increased MI risk. Simultaneous assessment of cumulative lipid-related and inflammatory burden may improve long-term risk stratification, help identify individuals who may benefit from intensive preventive care, and support combined lipid-lowering and inflammation-targeted strategies for MI prevention.