Inflammatory Proteins May Predict Course of PH-Left Heart Disease

Higher blood levels of IL-6 and PTX3 in LHF-PH patients tied to poorer outcomes

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Blood levels of IL-6 and PTX3 — two inflammatory proteins — could serve as prognostic biomarkers in people with pulmonary hypertension (PH) associated with left-sided heart disease, a study suggests.

Higher levels of both were linked to a greater risk of dying and higher levels of NT-proBNP, a known biomarker of heart failure. IL-6 was also associated with higher pressure in the pulmonary artery that carries blood from the heart to the lungs — a hallmark of PH.

In patients who underwent a heart transplant, levels of these inflammatory molecules generally declined post-surgery.

“Future larger studies to validate and investigate the direct clinical applicability of IL-6 and PTX3 as potential prognostic biomarkers are encouraged,” the researchers wrote.

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The study, “Higher plasma IL-6 and PTX3 are associated with worse survival in left heart failure with pulmonary hypertension,” was published in the American Heart Journal Plus: Cardiology Research and Practice

PH can arise as a complication of heart failure, in particular, failure of the heart’s left ventricle, the chamber responsible for pumping oxygenated blood throughout the body. In people with left heart disease, PH can lead to more severe symptoms and a worse prognosis.

Inflammation is thought to play a significant role in the progression of heart failure, raising the possibility that some inflammatory proteins might serve as prognostic biomarkers, or indicators of a patient’s likely outcomes.

IL-6 and PTX3 at significantly higher levels in patients’ blood

Researchers in Sweden examined levels of 65 inflammatory proteins in the blood of people with PH due to left-sided heart failure — called LHF-PH — and a control group of healthy adults in order to identify potential biomarkers.

Samples were collected from 67 patients (40% women) and 20 controls (50% women) between October 2011 and February 2017. Patients’ median age was 63 and the median age of controls was 41.

Over a median follow-up of 5.7 years, 25 patients died and 19 received a heart transplant.

Blood analyses revealed that the inflammatory proteins IL-6 and PTX3 were significantly elevated in patients relative to controls. In the subset of patients who had a heart transplant, levels of both were significantly lower after the procedure compared with before.

Increasing amounts of each protein were associated with poorer survival among the LFH-PH patients. Both were also linked to NT-proBNP, a non-active prohormone released in response to changes in pressure within the heart, including heart failure.

Right heart catheterization was used to assess various parameters of heart function. Increased pressure in the pulmonary arteries was found to link with higher IL-6 levels.

People taking angiotensin-converting enzyme (ACE) inhibitors, a class of medications used to lower blood pressure and treat heart failure, had significantly higher levels of PTX3 than those not on this medicine. PTX3 was also significantly higher after heart transplant among patients with diabetes compared with those without diabetes.

The findings overall “are in line with previous research and present an interesting approach for new prognostic biomarkers to be used clinically in patients with LHF-PH,” the researchers wrote.

They noted, however, that the study is limited by its small size and the younger age of controls relative to patients. The impact of certain medications, such as immunosuppressants, also needs to be assessed.

“Future studies are needed to validate our results in larger cohorts as well as investigate the impact of age, demographics, and comorbidities on the proteins’ levels,” the researchers wrote.