Blood Levels of 3 Proteins May Help Distinguish HFpEF-PH From PAH

Elevated levels of three blood proteins — AMBP, LPL and glyoxalase I — may help identify and distinguish people with pulmonary hypertension linked to heart failure with preserved ejection fraction, called HFpEF-PH, from those with pulmonary arterial hypertension or PAH, a study suggests.

Differentiating between the two is key, researchers say, because PAH-specific therapies actually may worsen HFpEF-PH, which has no effective treatments.

The study, “Plasma tumour and metabolism related biomarkers AMBP, LPL and Glyoxalase I differentiate heart failure with preserved ejection fraction with pulmonary hypertension from pulmonary arterial hypertension,” was published in the International Journal of Cardiology.

Pulmonary arterial hypertension (PAH) is when high blood pressure occurs in arteries that supply blood to the lungs. It is associated with blood vessel tightening and structural alterations in pulmonary arteries. HFpEF-PH, meanwhile, is characterized by an inability of the heart’s lower left chamber to function properly, meaning that it pumps out less blood than the body needs.

Compared with those with PAH, people with HFpEF-PH are generally older and frequently have other health conditions.

Cardiac function changes shared with PAH often make the diagnosis of HFpEF-PH more challenging. But distinguishing between these types of hypertension is important, as life expectancy of PAH patients increases. Additionally, treatments specific to PAH have been shown to worsen HFpEF-PH, according to the researchers.

Notably, PAH has been labeled a “cancer-like” condition, since it involves cellular pathways that are cancer hallmarks, including cell proliferation and resistance to programmed-cell death (as opposed to death caused by injury).

Increasing evidence suggests that heart failure and cancer may share common mechanisms and risks factors, such as inflammation and metabolic disorders.

Based on this, researchers in Sweden hypothesized that tumor- and metabolism-related biomarkers may be useful in distinguishing HFpEF-PH from PAH.

To test this, the team analyzed blood samples collected from 115 PH patients, divided into two groups: treatment-naïve PAH (48 patients who had not received therapy), and left-heart failure-PH (67 patients). Among those with LHF-PH, 31 patients had preserved ejection fraction — identified by how much blood leaves the heart each time it contracts — and 36 had reduced ejection fraction. Blood samples collected from 20 healthy participants, who served as controls, also were included.

The analysis focused on 69 tumor and metabolism-related proteins. Blood flow dynamics also were assessed by right heart catheterization. In this procedure, a thin, flexible tube called a catheter is passed into a vein in the neck, arm, or groin to measure the pulmonary arteries’ pressure and show the heart’s capacity to pump blood.

Of the initial proteins, 36 (just over half) were eligible for further diagnostic and prognostic testing.

Results showed that the levels of two proteins — called alpha-1-microglobulin/bikunin precursor (AMBP) and lipoprotein lipase (LPL) — were significantly higher in HFpEF-PH patients compared with those individuals with PAH, reduced ejection fraction, and healthy subjects.

Bloods levels of other proteins — specifically, endocan, FABP4, gastrotropin, glyoxalase I, IGF1R, IGFBP7, kallikrein 6 and 11, and pappalysin-1 — were higher in the left heart failure with PH group versus participants with PAH.

Further analysis revealed that the combination of AMBP, LPL, and glyoxalase I could distinguish HFpEF-PH from PAH with a sensitivity of 87.1% and a specificity of 85.4%.

Sensitivity is the ability to correctly identify those with a given disease, whereas specificity refers to correctly identifying those without it.

Also, AMBP levels in the blood correlated with pulmonary arterial wedge pressure — an estimate of pressure in the left side of the heart — in participants with HFpEF-PH. The findings also showed that endocan, FABP4, gastrotropin, glyoxalase I, IGF1R, IGFBP7, kallikrein 11, and pappalysin-1 could differentiate HFpEF-PH from PAH.

Overall, these findings suggest that higher levels of AMBP, LPL, and glyoxalase I in the blood may “may facilitate the distinction of HFpEF-PH from PAH,” the researchers wrote.

“Future studies directed toward validating and exploring the clinical deployment of AMBP, LPL and glyoxalse I as biomarkers to distinguish HFpEF-PH from PAH are warranted,” they concluded.