Study Suggests 8-OHdG Levels May Serve as PAH Biomarker

Levels of serum oxidative 8-Hydroxy-2'-deoxyguanosine (8-OHdG) appeared to correlate with exercise capacity and functional class in patients with pulmonary arterial hypertension (PAH), according to a new report.

The study, published in the Journal of the Brazilian Medical Association, suggests the measure could be a useful biomarker to determine severity of the disease.

As corresponding author Fatma Yilmaz Coskun, PhD, of Turkey’s Gaziantep University, and colleagues explained, patients with PAH experience progressive remodeling of the distal pulmonary arteries, eventually leading to an increase in pulmonary artery pressure and pulmonary vascular resistance. Left untreated, Coskun and colleagues said, it can lead to right heart failure and premature death.

The authors said there are significant gaps in scientists’ understanding of the pathophysiology of PAH, though the latest research suggests inflammation and increased oxidative status may play a role in the disease’s progression. Increased oxidative stress can lead to DNA damage, which appears to be associated with remodeling in the pulmonary arteries.

That’s where 8-OHdG comes in. It is the most common product of oxidative DNA damage in humans, Coskun and colleagues explained.

“This oxidative, modified DNA product has extensively been investigated as a marker of the degree of oxidative damage to DNA due to its stability,” they wrote. “The increased levels of 8-OHdG are associated with carcinogenesis, cardiovascular disease, and diabetes.”

The investigators therefore wanted to evaluate whether 8-OHdG levels might align with PAH severity.

They took serum samples from 25 patients who had been diagnosed with idiopathic PAH, familial PAH, or PAH associated with congenital heart disease, analyzing the samples for 8-OHdG. They then asked patients to take the 6-minute walking test and paired those results with WHO functional class assessments and serum brain natriuretic peptide (BNP) levels in hopes of finding associations between disease severity and 8-OHdG. They also compared the results with 22 age- and sex-matched controls.

The results were mixed. On the one hand, the investigators did not find a statistically significant difference between the PAH levels in the patients and controls. Yet, they did find a negative correlation between 6-minute walking distances and 8-OHdG, and they also found that patients in functional classes III and IV had higher levels of 8-OHdG than those in classes I and II.

The authors said they were surprised that they did not find a link between BNP levels and 8-OHdG, even though both have been identified as markers of PAH severity. The reason, they said, could come down to different characteristics of the biomarkers.

“BNP is mainly secreted from the cardiomyocytes in response to cardiac stretch, and its levels can range widely in short time periods, according to volume status and treatments in patients with heart failure,” they wrote. “In contrast, 8-OHdG is a stable marker of oxidative DNA damage, and it seems to reflect an established pathophysiological status; therefore, its levels may not show changes parallel to BNP under acute circumstances.”

Coskun and colleagues pointed to a number of limitations of their research. The sample size was relatively small, and the patients all sought care at a single health care center. Furthermore, some 80% of patients in the study were clinically stable, with functional classes I or II. They also noted that 76% of patients had PAH associated with congenital heart disease, a subtype of PAH in which the role of inflammation is less well-understood.

The authors said their findings point to important potential research avenues, although they said the results should be interpreted in light of the limitations.

“8-OHdG might be a potential candidate as a noninvasive parameter for the classification of severity of the patients with PAH; however, it requires further research,” they concluded.

Reference:

Coskun FY, Taysı S, and Kayıkçıoğlu M. Can serum 8-hydroxy-2'-deoxyguanosine levels reflect the severity of pulmonary arterial hypertension?. Rev Assoc Med Bras (1992). 2021;67(10):1437-1442. doi:10.1590/1806-9282.20210640