Protein Carbamylation in Chronic Systolic Heart Failure: Relation to Renal Impairment and Adverse Long-Term Outcomes
Abstract
Background Protein carbamylation, a post-translational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. We examine the relationship between plasma protein-bound homocitrulline (PBHCit) levels, a marker of protein lysine residue carbamylation, with cardio-renal function and long-term outcomes in chronic systolic heart failure. Methods and Results In 115 patients with chronic systolic HF (LVEF≤35%), we measured plasma PBHCit by quantitative mass spectrometry and performed comprehensive echocardiography with assessment of cardiac structure and performance. Adverse long-term events (death, cardiac transplant) were tracked for 5 years. In our study cohort, the median PBHCit level was 87 [IQR: 59, 128] μmol/mol Lysine. Higher plasma PBHcit levels were associated with poorer renal function (eGFR Spearman’s r= −0.37, p0.10 for each). Furthermore, elevated plasma PBHCit levels were not related to indices of cardiac structure or function (p>0.10 for all examined) except modestly with increased right atrial volume index (RAVi; r=0.31, p=0.002). PBHCit levels predicted adverse long-term events (Hazard ratio [HR]: 1.8, 95% CI 1.3– 2.6, p<0.001), including following adjustment for age, eGFR, MPO and NT-proBNP (HR: 1.9, 95% CI: 1.2–3.1, p=0.006). Conclusions In chronic systolic HF, protein carbamylation is associated with poorer renal but not cardiac…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 115 participants or records.
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