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
Yunyu Liu, Jun Gong, Jian Zhang, Juntao Tan, Chao TanObjective
Cardiovascular-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.
Methods
In 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.
Results
Four 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.
Conclusions
Longitudinal 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.