Combination of Biomarkers Identified That Predicts Disease Progression in IPH

The ratio between the proteins MMP2 and TIMP4 in blood samples of idiopathic pulmonary arterial hypertension (iPAH) patients was found to predict disease worsening and mortality in a German study.

It also correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance, and other indicators of disease progression.

The study, “Plasma MMP2/TIMP4 Ratio at Follow-up Assessment Predicts Disease Progression of Idiopathic Pulmonary Arterial Hypertension,” was published online in the journal Lung.

The proteins MMPs and TIMPs are thought to play a role in regulating the remodeling and repair process for tissues in the lung and heart. An imbalance of MMPs and TIMPs causes the accumulation of extracellular matrix (ECM), which is often associated with diseases like pulmonary hypertension (PH), lung fibrosis, heart failure, or myocardial infarction (heart attack).

But while MMPs and TIMPs have been studied as isolated biomarkers, studies show than the MMP/TIMP ratio is a better marker for the accumulation of ECM and progression of fibrotic diseases.

Researchers at the University of Regensburg in Germany, in collaboration with Novartis, examined 24 iPAH patients from the Germen Giessen PH referral center diagnosed between 2003 and 2012.

Clinical worsening and deaths were recorded until June 2015. At the first follow-up after diagnosis, researchers conducted laboratory and clinical examinations, and measured the levels of several MMPs and TIMPs in the patients’ blood.

The ratios of selected biomarkers (MMP2, MMP9, TIMP1, and TIMP4) at follow-up examination showed that the MMP2 to TIMP4 ratio had a better correlation with measures of disease severity and the degree of heart functioning in patients with iPAH.

“MMP2/TIMP4 ratio was detected as a marker of disease severity and right ventricular function as well as a predictor for survival and time to clinical worsening and therefore might help for guidance of disease progression in iPAH patients at [follow-up examination],” the researchers noted.

“In conclusion, in PAH patients, MMP2/TIMP4 ratio at follow-up assessment was shown to be a promising biomarker for the classification of disease severity and prognosis in terms of clinical worsening as well as survival despite the small sample size,” they wrote.

“The prognostic role of MMPs and TIMPs at diagnosis was demonstrated previously. Further research is necessary to confirm our findings in a larger prospective trial,” the researchers added.