Trajectories of C-reactive protein levels after incident myocardial infarction and its association with risk of recurrent cardiovascular events in Danish patients – a registry-based cohort study

Background C-reactive protein (CRP) is a well-established marker of inflammation and is widely measured in the Danish hospital setting. Myocardial infarction (MI) causes an acute inflammatory response, including an increase in CRP, which is also an established risk factor for both incident and recurrent MI. Clinical trials are underway investigating the protective effect of targeted anti-inflammatory treatment in high cardiovascular disease-risk patient populations. While most previous studies have analyzed risk of major adverse cardiovascular events (MACE) using a single CRP measurement, we here model the risk using all available CRP measurements following acute MI. Purpose The aim of the present study was to identify trajectories of CRP following incident MI and investigate their association with the risk of recurrent MACE, including death. Methods In this nationwide Danish registry-based cohort study we identified patients with first-time MI in 2018-2021. To identify distinct inflammatory trajectories, latent class trajectory modelling was applied to repeated CRP measurements obtained during routine clinical care within the first 120 days following the incident MI. Individuals were assigned to the latent classes based on their posterior probability of latent class membership, reflecting shared patterns of CRP over time. The posterior probabilities served as exposure in the Cox proportional hazard regression analysis of recurrent MACE (stroke, recurrent MI or all-cause death) within 3 years of the incident MI, adjusting for sex, age STEMI/non-STEMI type, geographic region, calendar year of MI, education and comorbidity index (M3). Results Among 22,769 individuals who survived 120 days following hospitalization with incident MI, we identified three probable latent classes of CRP trajectory (Figure): A low CRP class (Class 1) characterized by a relatively modest rise in CRP during the acute MI followed by a gradual decline (41.3% of the cohort); An intermediate CRP class (Class 2) characterized by a large initial surge in CRP, followed by a steady decline although stabilizing at a higher level than the low CRP class (44.2%); And a high CRP class (Class 3) characterized by a large acute surge which remained high throughout the 120 days (14.6%). The high CRP class was older, had a longer duration of hospitalization, and had more comorbidities than the other classes (Table). In total, 15.4% (n=3511) individuals experienced MACE during follow-up. The probability of allocation to the high CRP class trajectory was associated with increased risk of MACE (adjusted hazard ratio [HR]: 2.00 [95% confidence interval: 1.80-2.22]) compared with the low CRP class trajectory, and for the intermediate CRP class trajectory the adjusted HR was 1.34 (1.20-1.49). Conclusion The present results demonstrated different trajectories of CRP after MI and corroborate that sustained inflammation following incident MI is associated with poor prognosis.