Hyperuricemia could contribute to PAH

Blood sampling tube for uric acid analysis.

A recent report published in Heart & Lung outlines a likely causal relationship between hyperuricemia and pulmonary arterial hypertension (PAH). The study’s findings conclude that high levels of uric acid (UA) could serve as a risk factor for the condition and may be a therapeutic target to help treat or prevent PAH.

According to study author Jiang Li, PhD, of the Second Xiangya Hospital of China’s Central South University, the complete list of underlying causes of PAH is unknown. However, scientists do believe that genetics play a key role, and prior research has identified several genes associated with the disorder.

The production and secretion of uric acid is also affected by genetics, the researchers said. The purpose of the study was to help them understand the possible link between UA and PAH.

The investigators used Mendelian randomization to evaluate publicly available data sets. Their analysis, which incorporated statistics related to genetic PAH risk and genome-wide association study data, demonstrated the causal relationship of UA levels and PAH at a genetic level.

“Our study further validates previous observational findings indicating elevated UA levels in most PAH patients,” wrote Dr. Li and colleagues. “Moreover, it establishes UA as a risk for PAH, with elevated levels associated with an increased relative risk of developing the condition, providing supporting evidence for the direct pathogenic role of UA in PAH pathophysiology.”

While the exact reason for the causation wasn’t clear, the research team presented three hypotheses. They said high UA levels (hyperuricemia) could:

  1. Lead to endothelial dysfunction
  2. Elevate levels of growth factors, thereby stimulating smooth muscle cell proliferation and triggering inflammatory responses
  3. Increase expression of angiotensin II, thereby elevating pulmonary arterial pressure and oxidative stress

The authors cited several study limitations, including that the databases were based on European cohorts (and results may not apply to other populations) and adjustments were not made based on factors such as age, gender or environment, which can impact UA levels.

Dr. Li also highlighted the clinical implications of their findings, mentioning that the current five-year survival rate for PAH is less than 60%. Any improvements to screening, diagnosis, treatment or management of risk factors of PAH would be of great value to patients suffering from the condition.

For example, based on the causative results, the researchers suggested targeted screening measures of people with hyperuricemia to determine their risk of developing PAH.

“Such interventions could include exploring new pharmacological agents or optimizing existing therapies to better manage UA levels and potentially improve clinical outcomes in PAH,” they wrote.

They also noted that future studies should examine the impact of high UA levels on endothelial dysfunction and vascular remodeling.

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