Proteomic analysis of heart failure hospitalization among patients with chronic kidney disease: The Heart and Soul Study
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Key result
Among patients with chronic kidney disease, higher plasma levels of Angiopoietin-2 were associated with an increased risk of heart failure hospitalization (HR 1.45), while NOTCH1 was associated with a decreased risk (HR 0.67).
Why the study?
Patients with CKD face an increased risk for HF, prompting investigation into differences in proteins associated with HF hospitalizations among patients with and without CKD.
Which plasma proteins are associated with heart failure hospitalization in patients with chronic kidney disease?
Population
974 participants with and without CKD in The Heart and Soul Study
Comparison
Patients with vs without CKD
Design
Prospective cohort study
Follow-up
Median of 7 years
Authors
Discussion
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Implication
Should not yet guide HF risk assessment in CKD; hypothesis-generating for proteomic biomarkers and requires prospective validation.
Study Design
Type
Cohort (n=974)
Multicenter
Yes
Structured PICO
Which plasma proteins are associated with heart failure hospitalization in patients with chronic kidney disease?
P
Population
974 participants with stable coronary artery disease (18% female, mean age 67 years), including 364 with chronic kidney disease, followed for a median of 7 years for heart failure hospitalization.
E
Exposure
Measurement of 1068 unique plasma proteins from baseline samples
O
Outcome
Heart failure hospitalizationhard clinical
Main Result
Hazard Ratio: 1.45 (95% CI 1.33–1.59)
p-value: p=<2.5x10-4
Specific proteomic markers, including Angiopoietin-2 and NOTCH1, are uniquely associated with heart failure hospitalization in patients with chronic kidney disease.
Limitations
- Patients all had coronary artery disease, so results may not generalize to heart failure of non-ischemic origin.
- Did not differentiate between heart failure with preserved versus reduced ejection fraction.
- Etiology of chronic kidney disease was not adjudicated.
- Proteomic investigation was limited to plasma, which may not represent tissue-specific biological mechanisms.
- Only 1068 proteins were measured, representing a small portion of the human proteome.
- Requires validation in other cohorts of patients with CKD
- Requires validation with adjudicated HF events
Cite This Study
Dubin et al. (2018) conducted a cohort in Chronic kidney disease and stable coronary artery disease (n=974). Plasma protein levels (e.g., Angiopoietin-2, NOTCH1) vs. Per 1-SD lower protein level was evaluated on Heart failure hospitalization (HR 1.45, 95% CI 1.33, 1.59, p=<2.5x10-4). Among patients with chronic kidney disease, higher plasma levels of Angiopoietin-2 were associated with an increased risk of heart failure hospitalization (HR 1.45), while NOTCH1 was associated with a decreased risk (HR 0.67).
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