Multi-Biomarker Panel Predicts CV Events in Patients With Chronic Kidney Disease

Among patients with chronic kidney disease (CKD), a sharp increase in the risk of cardiovascular events occurs with a decline in glomerular filtration rate (GFR), especially those with GFR below 60 mL/min/1.72m².

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James L. Januzzi, MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at the Corrigan Minehan Heart Center at Massachusetts General Hospital, Reza Mohebi, MD, a research fellow at Mass General, and colleagues created a biomarker panel that can guide clinicians in stratifying the risk of CV events in this patient population. The development and validation of the panel are reported in the International Journal of Cardiology.

Deriving the Panel

The team used findings from the CASABLANCA study at Mass General, in which patients who underwent coronary or peripheral arterial angiography were followed for CV events for two years. This substudy included 1,095 patients who underwent coronary angiography:

• Derivation set—Data on 649 patients were used to choose the biomarkers in the panel
• Validation set—Data on 446 patients with CKD (29% female, mean age 67) were used to validate the panel's performance

The researchers started with a commercially available biomarker panel that predicts incident CV events (HART CVE, Prevencio, Kirkland, WA). Using a machine learning algorithm and targeted proteomics from blood samples of patients with CKD, they identified a final panel of four proteins, each of which reflects a different pathway of CVD pathophysiology:

• N-terminal pro-B type natriuretic peptide—The well-established cardiac stress marker
• Kidney injury molecule-1—Highly upregulated after acute ischemia–reperfusion injury in the kidneys
• Osteopontin—Regulates myofibroblast differentiation and production of collage 1 production, among other biological processes; elevated levels have been linked with increased cardiac fibrosis
• Tissue inhibitor of matrix metalloproteinase-1—Involved in the degradation of extracellular matrix; linked to cardiac fibrosis and hypertrophy

Assigning Risk Groups

The prognostic model was transformed into scores from 0 to 10. The 446 patients with CKD were divided into two groups of CV event risk; they were considered at higher risk if their score on the panel was ≥5.526, determined to be the optimal cutpoint.

CKD status was divided into two groups:

• Stage 1 to 2—GFR >60 mL/min/1.72m² and <120 mL/min/1.72m² (n=378, 85%)
• Stage 3 to 5—GFR <60 ml/min/1.72m² (n=68, 15%)

Results

Over the two years of follow-up, 74 CV events were recorded. When patients were divided into four risk groups, the incidence of CV events was:

• CKD stage 1 to 2 and CV lower risk—5.2 cases per 100 person-years
• CKD stage 1 to 2 and CV higher risk—19.7
• CKD stage 3 to 5 and CV lower risk—3.3
• CKD stage 3 to 5 and CV higher risk—29.0

The C-statistic for predicting CV events among all 446 patients was 0.77 (95% CI, 0.72–0.82).

Within CKD staging groups, the risk of CV events was:

• CKD stage 1 to 2—HR, 2.82 for patients with CV higher risk vs. those at CV lower risk (P<0.001)
• CKD stage 3 to 5—HR, 8.32 (P=0.038)

Opportunities to Improve Care

Measuring this biomarker panel before coronary catheterization may allow individualized assessment of the risk of CV events among patients with CKD.

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