Blood biomarkers: Harbingers of heart failure, respiratory tract infections in stroke

Blood biomarker panels prove to be useful in the prediction of two major complications of stroke, namely acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs), early after hospital admission, as shown in a study.

A panel including vascular adhesion protein‐1, N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), and d‐dimer accurately foretells ADHF. Meanwhile, a panel comprising interleukin (IL)‐6, von Willebrand factor (vWF), and d‐dimer offers precise prediction of RTI. 

“[R]ather than testing individual markers, we tested automatically derived biomarker panels, which might be complementary tools to achieve a better prediction,” the investigators said. 

“In fact, biomarker panels might be more valuable to reflect the complexity of the disease and its consequences, with several impaired biological pathways that might be reflected by automatically selected biomarkers,” they added. [Acta Pharmacol Sin 2018;39:1068-1072]

In the study, the investigators analysed 14 biomarkers from blood samples of 938 adult patients collected within the first 6 hours after ischaemic stroke onset. ADHF and RTI occurred in 19 (2 percent) and 86 (9.1 percent) patients, respectively.

The PanelomiX algorithm facilitated selection of panels with the best accuracy for predicting ADHF and RTI. The three‐biomarker panel for ADHF (vascular adhesion protein‐1 >5.67, NT‐proBNP >4.98, d‐dimer >5.38) was positive when any one of the markers was above the cutoff. It was 89.5-percent sensitive and 71.7-percent specific. [J Am Heart Assoc 2021;doi:10.1161/JAHA.120.018946]

On the other hand, the panel for predicting RTI (IL‐6 >3.97, vWF >3.67, d‐dimer >4.58) was positive when at least two of the markers were above the cutoff, yielding sensitivity of 82.9 percent and specificity of 59.8 percent.

“Of the nine patients with both complications, seven were positive for both panels, one was positive for only the RTI panel, and the other patient was negative for both panels,” the investigators noted.

Alone, each panel significantly predicted the stroke complication (panel for ADHF: odds ratio [OR], 10.1, 95 percent CI, 3–52.2; p<0.0001; panel for RTI: OR, 3.73, 95 percent CI, 1.95–7.14; p<0.0001). When added to established clinical predictors, the panels improved the accuracy of the model in terms of area under the curve, from 0.80 to 0.88 for ADHF (p=0.038) and from 0.78 to 0.81 for RTI (p=0.048).

“Our results, if confirmed, might have clinical implications,” according to the investigators. “Both biomarker panels have a high sensitivity, resulting in a detection of most of the true‐positive patients.”

Despite the limitations of the study, including the possibility of missing data and small number of ADHF events, among others, the investigators expressed optimism that by predicting ADHF and RTI immediately after stroke onset, the panels can help clinicians to monitor and treat patients at high-risk of these complications as early as possible. This should shorten the length of hospital stay or even cut mortality risk.

“In the case of RTI, there is no evidence that antibiotic prophylaxis prevents the onset of these infections or reduces the mortality of these patients, but whether selective antibiotic prophylaxis in high‐risk patients or alternative prophylactic measures such as immunomodulatory therapies are effective is being studied,” they said. [J Stroke Cerebrovasc Dis 2018;27:3137-3147]