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Novel biomarkers linked to CV dysfunction, mortality in patients with HIV
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Two novel biomarkers, ST2 and growth differentiation factor-15, were associated with CV dysfunction and all-cause mortality in patients with HIV, according to recent data.
Eric A. Secemsky, MD, from the division of cardiology at Massachusetts General Hospital, and colleagues assessed the presence and association of biomarkers including ST2, growth differentiation factor-15 (GDF-15), N-terminal pro–B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin I with CV dysfunction and mortality in adults with and without HIV.
The study included 332 adults with HIV and 50 age- and sex-matched participants. The cohort was 80% male and the median age was 49 years. All participants were enrolled in the SCOPE study from September 2004 to March 2011 and were followed until December 2012 or time of death.
Compared with the control group, levels of all biomarkers, excluding ST2, were higher among patients with HIV. An analysis adjusted for age, sex and estimated glomerular filtration rate (eGFR) demonstrated that more patients with HIV exceeded predefined CVD risk thresholds for ST2 (> 35 ng/mL; 31% vs. 14%; P = .01); GDF-15 (> 1,200 pg/mL; 40% vs. 0%; P < .001) and NT-proBNP (> 300 pg/mL; 9.5% vs. 0%; P = .02).
During a median follow-up of 6 years, 38 deaths occurred among patients with HIV and three deaths occurred in the control group. The 5-year mortality rate was 10.3% in the HIV group vs. 4% in the control group (P = .094). Twelve deaths in the HIV group were related to CV causes; in these patients, the median ST2 level was 38.1 ng/mL and the median GDF-15 level was 1,777.4 pg/mL. Nine patients who died exceeded the predefined CVD risk thresholds for ST2 or GDF-15; five patients had elevated levels of both biomarkers.
Further analysis demonstrated that ST2 (HR = 2.04; P = .01), GDF-15 (HR = 1.42; P = .005), high-sensitivity C-reactive protein (HR = 1.25; P = .023) and D-dimer (HR = 1.49; P = .029) were independent predictors of all-cause mortality. The association was strongest with ST2, which yielded a 104% increased risk with each replication, according to the results.
Patients with HIV and controls had a median left ventricular ejection fraction of 61%. Fourteen HIV patients and no controls had an LVEF of less than 50%. Diastolic dysfunction was observed in 45% of patients with HIV vs. 28% of controls (P = .02). ST2 was the only biomarker that was significantly associated with diastolic dysfunction. LV systolic dysfunction was reported in only 5% of patients with HIV. Pulmonary hypertension, defined as systolic pulmonary artery pressure of at least 35 mm/Hg, was observed in 27% of patients with HIV and was independently associated with GDF-15 (RR = 1.8; P = .04), NT-proBNP (RR = 1.18; P = .007) and cystatin C (RR = 1.54; P = .03).
The results were similar after researchers limited their findings to patients who were receiving antiretroviral therapy (79%) and those with undetectable viral loads (60%).
The researchers concluded that these findings “may be useful at identifying those at risk for developing CV events and death.”
In an accompanying editorial, Monica R. Shah, MD, FACC, deputy chief of the heart failure and arrhythmias branch and AIDS coordinator for the NHLBI, said CV clinicians play a crucial role in HIV care. Based on these study findings, Shah suggested that providers screen young, asymptomatic patients with HIV for elevated biomarker levels.
“The use of these biomarkers in clinical practice may help providers more accurately risk-stratify patients with HIV and better individualize diagnostic testing and medical therapy,” she wrote. “Thus, the findings from this study have the potential to influence clinical management.” – by Stephanie Viguers
Disclosure: Secemsky and Shah report no relevant financial disclosures.
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