Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals

• Published in: JACC. Heart failure Vol. 3; no. 8; pp. 591 - 599
• Main Authors: Secemsky, Eric A., MD, Scherzer, Rebecca, PhD, Nitta, Elaine, MPH, Wu, Alan H.B., PhD, Lange, David C., MD, Deeks, Steven G., MD, Martin, Jeffrey N., MD, Snider, James, PhD, Ganz, Peter, MD, Hsue, Priscilla Y., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2015
• Subjects: Adult; biomarkers; Biomarkers - blood; Cardiovascular; cardiovascular dysfunction; Cohort Studies; death; Echocardiography; Female; Heart Failure - blood; Heart Failure - diagnosis; Heart Failure, Diastolic - blood; Heart Failure, Diastolic - diagnosis; HIV; HIV Infections - blood; HIV Infections - diagnosis; Humans; Hypertension, Pulmonary - blood; Hypertension, Pulmonary - diagnosis; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; mortality; Natriuretic Peptide, Brain - blood; Outcome Assessment (Health Care); Peptide Fragments - blood; Predictive Value of Tests; Receptors, Cell Surface - blood; Reference Values; Survival Rate; DD; ART; death; antiretroviral therapy; pulmonary hypertension; GDF; LVEF; high-sensitivity C-reactive protein; interquartile range; cardiovascular dysfunction; left ventricular ejection fraction; growth differentiation factor; NT-proBNP; PHTN; interleukin; cardiovascular disease; IL; biomarkers; International Classification of Diseases-Ninth Revision; hsTnI; IQR; CVD; high-sensitivity troponin I; ICD-9; HIV; mortality; diastolic dysfunction; human immunodeficiency virus; hsCRP; N-terminal pro–B-type natriuretic peptide
• ISSN: 2213-1779; 2213-1787
• DOI: 10.1016/j.jchf.2015.03.007

Abstract Objectives This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. Background HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. Methods Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction <50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index. Results Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. Conclusions Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.