Protein sLR11 Linked to Lung Blood Pressure in Heart Failure Patients

Measuring levels of protein sLR11 in the blood could be useful in testing for pulmonary hypertension (PH) in people who have heart failure, according to a new study.

The study, “Circulating sLR11 levels predict severity of pulmonary hypertension due to left heart disease,” was published in the journal PLOS One.

Heart failure is when the heart cannot pump out enough blood to supply the body with needed oxygen and nutrients. Often, heart failure can cause PH; in fact, PH caused by left heart disease, called group 2 PH or PH-LHD, is the most common kind of PH.

Diagnosing PH-LHD or any other kind of PH typically requires right heart catheterization (RHC), which is an invasive procedure used to measure the pressure in the lungs’ blood vessels. Given this procedure’s invasiveness, there is an ongoing search for less invasive tests that might be options.

The protein sLR11 (soluble low-density lipoprotein receptor with 11 ligand-binding repeats) is related to the activity of smooth muscle cells, such as the muscles that help squeeze blood through the circulatory system. sLR11 levels can be measured in the blood, and recent evidence has suggested that levels of the protein are elevated in people with pulmonary arterial hypertension. These findings have suggested that measuring this protein may be useful for diagnosing or monitoring PH.

Here, researchers in Japan assessed this novel marker in PH-LHD. The team analyzed data for 34 patients who underwent surgery for severe mitral regurgitation (a type of heart disease in which a valve on the left side of the heart does not close properly) at Juntendo University between 2005 and 2012. About two-thirds of the patients were men, the mean age was 64.8, and 10 patients had PH-LHD.

Before undergoing surgery, all patients underwent RHC to measure mean pulmonary artery pressure (mPAP), or blood pressure in the lungs. At the same time, sLR11 levels in the blood were analyzed.

Statistical analyses revealed a significant correlation between blood sLR11 levels and mPAP; in other words, individuals with high mPAP tended to have high sLR11 levels and vice versa. Consistently, average sLR11 levels were significantly higher in patients with PH-LHD (14.7 vs. 9.7 nanograms/ml).

Additional analyses showed that these levels could predict mPAP with similar accuracy as levels of BNP (brain natriuretic peptide), an established marker of PH severity.

The researchers then divided the patients into those with high or normal levels of sLR11. (“High” levels were defined as greater than 9.4 ng/ml, based on prior data.)

Over five years of follow-up, five (25%) patients in the high-sLR11 group were hospitalized for heart failure, and two died. By contrast, in the normal-sLR11 group, there were no hospitalizations or deaths recorded during follow-up. Statistical analyses showed that patients in the high-sLR11 group were at significantly higher risk of hospitalization, but a significant effect on mortality could not be detected.

“Although no significant difference in all-cause mortality was evident, two deaths occurred in the high-sLR11 group,” the researchers concluded. “These results suggest that sLR11 level reflects the severity of pulmonary hemodynamics [blood flow] and can predict long-term prognosis in LHD patients.”

“Measuring sLR11 may thus prove useful for the early detection and treatment of PH-LHD,” they added.

The researchers noted that this study is limited by the small number of participants. They noted the need for larger studies to clarify the role of sLR11 in PH-LHD.