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

Abstract

Objectives We sought to determine whether biomarkers ST2, GDF-15, NT-proBNP, and high-sensitivity Troponin I are elevated in HIV-infected patients and associated with cardiovascular dysfunction and all-cause mortality. Background HIV-infected individuals 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 gender-matched controls. Left ventricular systolic dysfunction (LVSD) was defined as ejection fraction <50%, diastolic dysfunction (DD) as ≥stage 1, and pulmonary hypertension as PASP ≥35mmHg. Mortality data was obtained from the National Death Index. Results HIV patients were a median 49 years and 80% male. Compared with controls, HIV patients had higher percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV patients, 45% had DD; only ST2 was associated with DD (RR 1.36, p=0.047). LVSD was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV patients and 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 subjects over a median 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (HR 2.04, p=0.010), GDF-15 (HR 1.42, p=0.0054), hsCRP (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 on antiretroviral therapy. Conclusions Among HIV-infected individuals, ST2 and GDF-15 are associated with both cardiovascular dysfunction and all-cause mortality and may be useful at identifying those at-risk for developing cardiovascular events and death.

Subclinical myocyte injury, fibrosis and strain in relationship to coronary plaque in asymptomatic HIV-infected individuals

“…In the general population, ST2 was not associated with increased left ventricular mass among patients referred for echocardiography (31). Recently, in an HIV positive cohort, ST2 was found to be strongly associated with diastolic dysfunction and mortality (32). In animal studies, soluble ST2 measured in the circulation is thought to act as a decoy receptor for the ST2 ligand which binds interleukin-33 (IL-33) (33).…”

Inflammation and Fibrosis in HIV

“…The two studies highlight the advantages of CMR in general over echocardiography with respect to reproducible measurements of ventricular volume and function 27 , smaller sample size 28 , and assessment of fibrosis, injury, and inflammation. Of note, markers of cardiac stress such as ST2 and cardiac inflammation, GDF-15 are associated with cardiac dysfunction and all-cause mortality in HIV 29 .…”

The Broad Spectrum of HIV-Related Cardiovascular Disease ∗

“…novel finding from this study(12) is the observation that increasing ST2 and GDF-15 levels significantly predicted mortality in HIV-infected patients. In the analysis, with each doubling of ST2, there was a 104% increased risk of mortality.…”