Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: The Heart and Soul Study

• Published in: PloS one Vol. 13; no. 12; p. e0208042
• Main Authors: Dubin, Ruth F, Whooley, Mary, Pico, Alexander, Ganz, Peter, Schiller, Nelson B, Meyer, Craig
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17-12-2018; Public Library of Science (PLoS)
• Subjects: Acid phosphatase; Acid phosphatase (tartrate-resistant); Acid resistance; Aged; Aged, 80 and over; Analysis; Angiogenesis; Angioplasty; Angiopoietin; Angiopoietin-2 - blood; Atherosclerosis; Biology and Life Sciences; Biomarkers - blood; Biotechnology industries; Cardiology; Chronic kidney failure; Coagulation; Computer and Information Sciences; Coronary artery disease; Extracellular Matrix Proteins - blood; Female; Glomerular Filtration Rate; Health aspects; Health risks; Heart; Heart attacks; Heart diseases; Heart failure; Heart Failure - blood; Heart Failure - diagnosis; Heart Failure - etiology; Heart Failure - therapy; Hemodialysis; Homology; Hospitalization; Hospitalization - statistics & numerical data; Humans; Hypertrophy; Kidney diseases; Kidneys; Male; Markers; Measurement methods; Medicine and Health Sciences; Middle Aged; Nephrology; Notch1 protein; Patients; Plasma proteins; Prognosis; Proteins; Proteomics; Receptor, Notch1 - blood; Regression analysis; Renal Insufficiency, Chronic - blood; Renal Insufficiency, Chronic - complications; Risk Assessment; Risk factors; Statistical methods; Tartrate-Resistant Acid Phosphatase - blood; Transplants & implants; Veterans; United States; United States > US; San Francisco California; California
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0208042

Patients with chronic kidney disease (CKD) are at increased risk for heart failure (HF). We aimed to investigate differences in proteins associated with HF hospitalizations among patients with and without CKD in the Heart and Soul Study.
We measured 1068 unique plasma proteins from baseline samples of 974 participants in The Heart and Soul Study who were followed for HF hospitalization over a median of 7 years. We sequentially applied forest regression and Cox survival analyses to select prognostic proteins. Among participants with CKD, four proteins were associated with HF at Bonferroni-level significance (p<2.5x10(-4)): Angiopoietin-2 (HR[95%CI] 1.45[1.33, 1.59]), Spondin-1 (HR[95%CI] 1.13 [1.06, 1.20]), tartrate-resistant acid phosphatase type 5 (HR[95%CI] 0.65[0.53, 0.78]) and neurogenis locus notch homolog protein 1 (NOTCH1) (HR[95%CI] 0.67[0.55, 0.80]). These associations persisted at p<0.01 after adjustment for age, estimated glomerular filtration and history of HF. CKD was a significant interaction term in the associations of NOTCH1 and Spondin-1 with HF. Pathway analysis showed a trend for higher representation of the Cardiac Hypertrophy and Complement/Coagulation pathways among proteins prognostic of HF in the CKD sub-group.
These results suggest that markers of heart failure differ between patients with and without CKD. Further research is needed to validate novel markers in cohorts of patients with CKD and adjudicated HF events.