High uric acid levels in blood tied to greater risk of PAH
Therapies that lower these levels may benefit PAH patients, scientists suggest
Elevated blood levels of uric acid are associated with a higher risk of pulmonary arterial hypertension (PAH) at the genetic level, a data study reported.
“Overall, this study confirmed, from a genetic perspective, the causal relationship between serum UA [uric acid] levels and PAH,” the researchers wrote. They also suggested that treatments working to lower these levels might benefit PAH patients.
The study, “Serum uric acid and pulmonary arterial hypertension: A two-sample Mendelian randomization study,” was conducted by a team in China and published in the journal Heart & Lung.
High uric acid levels known cause of gout, a type of inflammatory arthritis
PAH is characterized by elevated blood pressure in the pulmonary arteries of the lungs, restricting blood flow to those organs and making the heart work harder to pump blood throughout the body.
Differences in genetic information from person to person impact vascular remodeling, the hallmark PAH changes in the structure and arrangement of blood vessels. While 80% of patients have idiopathic disease, with no identified cause, mutations in the BMPR2, SMAD9, and CAV1 genes are associated with an increased likelihood of familial PAH.
Uric acid is a product of metabolism, primarily excreted through the kidneys, and some genes have been associated with its synthesis and excretion. While known for its link to gout, a type of inflammatory arthritis, uric acid levels also have been connected to various cardiovascular diseases. Previous research suggests that high levels damage blood vessels in the lungs, potentially contributing to PAH.
“Nevertheless, the precise causal connection between uric acid and PAH remains elusive,” the researchers wrote.
They used a technique called Mendelian randomization, conducted among individuals of European descent, to determine whether high UA levels could be a cause of PAH. Mendelian randomization employs genetic variants to explore whether genetic factors cause certain traits.
Data from the Chronic Kidney Disease Genetic Consortium and a genome-wide association study that included 343,836 samples were used to compare uric acid levels in PAH patients to those of healthy individuals, a control group. A genome-wide association study is an approach used in genetics to link specific genetic variations with particular diseases.
Results showed a significant link between the acid levels and PAH, with every standard deviation increase in uric acid corresponding to a 28.8% rise in the risk of the disease. Standard deviation is a measure of how dispersed data are in relation to the mean. Sensitivity tests confirmed the robustness of the findings.
“Our study revealed a positive correlation between UA and PAH, with elevated UA significantly increasing the risk of developing PAH. This result is consistent with current clinical research and meta-analysis,” the researchers wrote. A meta-analysis pools data from multiple studies. “Our [randomization] analysis provides robust evidence of a causal link between serum UA and PAH, suggesting UA’s potential as a biomarker and therapeutic target for PAH.”
Potential for therapies that lower uric acid to also help PAH patients
Researchers favored targeted screening for PAH in people with elevated blood levels of uric acid, and studies into whether therapies that lower its levels might offer new ways of managing the disease. Medications like allopurinol, a common gout treatment that lowers uric acid, might be of benefit to people with PAH, they suggested.
“The findings of this study have profound clinical implications for the screening and treatment of PAH. According to our research, UA is a pathogenic [disease-causing] factor in PAH,” the team wrote.
Among study limitations noted by the scientists were genetic data from European populations, which may limit the applicability of its findings to other ethnic groups. The work also did not consider the impact of age, sex, and environmental factors on uric acid levels.
According to the scientists, future research should focus on exactly how uric acid drives PAH by looking at vascular remodeling and changes in the cells that line blood vessels. Studies also are needed into the efficacy and safety for PAH patients of therapies that lower uric acid levels.
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