Cumulative C-reactive protein exposure links to COPD risk in adults with cardiovascular-kidney-metabolic syndrome stages 0–3 (no overt CVD): A prospective cohort study

ObjectiveCardiovascular-Kidney-Metabolic (CKM) syndrome, characterized by interconnected metabolic, cardiovascular, and renal dysfunctions, is linked to chronic low-grade inflammation, a key driver of comorbidities like chronic obstructive pulmonary disease (COPD). C-reactive protein (CRP), a sensitive inflammation biomarker, may predict COPD risk in CKM stages 0-3 (no overt CVD), but longitudinal patterns of CRP remain underexplored.MethodsIn this prospective cohort study, we included 4,887 participants aged ≥45 years with CKM stages 0-3 and without prior COPD from the China Health and Retirement Longitudinal Study (CHARLS). CRP was measured in 2012 and 2015. Longitudinal change patterns were identified using k-means clustering. Cumulative CRP exposure (cumCRP) was calculated as the area under the curve. Incident COPD was defined based on self-reported physician diagnosis plus objective evidence of airflow limitation (peak expiratory flow <80% predicted) in 2018. Multivariable logistic regression was used to assess associations.ResultsFour CRP change patterns were identified: stable low-risk (Class 1), rapidly increasing (Class 2), significant improvement (Class 3), and persistently high-risk (Class 4). Compared to Class 1, Class 4 was associated with a 69% higher COPD risk (adjusted OR=1.69, 95% CI: 1.28-2.23). High cumCRP (tertile 3 vs. 1) increased COPD risk by 65% (OR=1.65, 95% CI: 1.32-2.08). The association was stronger in advanced CKM stages 0-3 (no overt CVD), particularly Stage 3.ConclusionsLongitudinal CRP change patterns and cumulative CRP exposure are independently associated with incident COPD in individuals with CKM stages 0-3 (no overt CVD). Persistently elevated or rapidly increasing CRP may help identify high-risk individuals for targeted monitoring and early intervention.