Association of Biomarker Clusters With Cardiac Phenotypes and Mortality in Patients With HIV Infection.

Abstract

BACKGROUND:

Although individual cardiac biomarkers are associated with heart failure risk and all-cause mortality in HIV-infected individuals, their combined use for prediction has not been well studied.

METHODS AND RESULTS:

Unsupervised k-means cluster analysis was performed blinded to the study outcomes in 332 HIV-infected participants on 8 biomarkers: ST2, NT-proBNP (N-terminal pro-B-type natriuretic peptide), hsCRP (high-sensitivity C-reactive protein), GDF-15 (growth differentiation factor 15), cystatin C, IL-6 (interleukin-6), D-dimer, and troponin. We evaluated cross-sectional associations of each cluster with diastolic dysfunction, pulmonary hypertension (defined as echocardiographic pulmonary artery systolic pressure ≥35 mm Hg), and longitudinal associations with all-cause mortality. The biomarker-derived clusters partitioned subjects into 3 groups. Cluster 3 (n=103) had higher levels of CRP, IL-6, and D-dimer (inflammatory phenotype). Cluster 2 (n=86) displayed elevated levels of ST2, NT-proBNP, and GDF-15 (cardiac phenotype). Cluster 1 (n=143) had lower levels of both phenotype-associated biomarkers. After multivariable adjustment for traditional and HIV-related risk factors, cluster 3 was associated with a 51% increased risk of diastolic dysfunction (95% confidence interval, 1.12-2.02), and cluster 2 was associated with a 67% increased risk of pulmonary hypertension (95% confidence interval, 1.04-2.68), relative to cluster 1. Over a median 6.9-year follow-up, 48 deaths occurred. Cluster 3 was independently associated with a 3.3-fold higher risk of mortality relative to cluster 1 (95% confidence interval, 1.3-8.1), and cluster 2 had a 3.1-fold increased risk (95% confidence interval, 1.1-8.4), even after controlling for diastolic dysfunction, pulmonary hypertension, left ventricular mass, and ejection fraction.

CONCLUSIONS:

Serum biomarkers can be used to classify HIV-infected individuals into separate clusters for differentiating cardiopulmonary structural and functional abnormalities and can predict mortality independent of these structural and functional measures.

• Authors: Rebecca Scherzer, Sanjiv J Shah, Eric Secemsky, Javed Butler, Carl Grunfeld, Michael G Shlipak, Priscilla Y Hsue
• Journal: Circulation. Heart failure (Circ Heart Fail) Vol. 11 Issue 4 Pg. e004312 (04 2018) ISSN: 1941-3297 [Electronic] United States
• PMID: 29615435 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © 2018 The Authors.

Chemical References

• Biomarkers
• Interleukin-1 Receptor-Like 1 Protein
• Troponin T
• C-Reactive Protein

Topics

• Adult
• Biomarkers (blood)
• C-Reactive Protein (analysis)
• Female
• HIV Infections (blood, complications)
• Heart Failure (blood, mortality)
• Humans
• Hypertension, Pulmonary (complications)
• Interleukin-1 Receptor-Like 1 Protein
• Male
• Middle Aged
• Phenotype
• Risk Factors
• Troponin T (blood)