Gout-prone genetic profile predicts higher cardiovascular disease risk
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Key takeaways:
- A polygenic gout risk score was positively associated with cardiovascular disease incidence, regardless of ancestry.
- Cardiovascular risk dropped with favorable metabolic health and lifestyle.
A genetic predisposition for gout predicts an increased risk for cardiovascular disease, but a healthy lifestyle can curb that risk, according to data published in RMD Open.
“Despite the active research on the relationship between [serum uric acid (SUA)] levels and [cardiovascular disease (CVD)], the genetic relationship between gout and CVD has not been sufficiently studied,” Ki Won Moon, of the department of internal medicine at the Kangwon National University School of Medicine, in South Korea, and colleagues wrote.
“Clinically, hyperuricemia and gout are different phenotypes,” they added. “Although hyperuricemia is a risk factor for gout, only a minority of patients with hyperuricemia develop gout. Additionally, asymptomatic hyperuricemia generally does not require medical treatment, whereas gout often necessitates lifelong management. ... Thus, the genetic association between gout and CVD should be elucidated separately from previous genetic studies on SUA and CVD.”
To investigate relationship between lifestyle habits, genetic gout risk and the development of cardiovascular disease, Moon and colleagues analyzed two large datasets, including people of varying ancestries. In all, the analysis included 224,689 participants of European descent from the U.K. Biobank and 50,364 of East Asian descent from the Korean Genome and Epidemiology Study.
The researchers used a polygenic risk score based on a previous study to assess genetic predisposition to gout. Lifestyle habits under analysis included smoking, alcohol consumption, obesity, physical activity and eating habits, while metabolic health status was assessed based on how many — out of five — metabolic syndrome criteria were met.
According to the researchers, individuals with a higher genetic gout risk demonstrated greater chances of developing cardiovascular disease vs. those with low genetic gout risk, no matter their ancestry. However, the likelihood of cardiovascular disease dropped significantly with good metabolic health and a favorable lifestyle, regardless of genetic risk for gout. Specifically, cardiovascular disease risk fell by 62% (HR = 0.38; 95% CI, 0.31-0.46) among those with high gout risk and 46% among those with low gout risk (HR = 0.54; 95% CI, 0.43-0.67).
“Our findings establish a link between the [polygenic risk score (PRS)] for gout, lifestyle habits and an increased risk of CVD using two separate databases representing diverse ancestral backgrounds,” Moon and colleagues wrote. “Additionally, we demonstrated that it is possible to reduce the risk of CVD by changing modifiable risk factors, lifestyle habits and metabolic health profiles.
“The effect of adherence to a healthy lifestyle was greater in individuals with a higher genetic risk,” they added. “These findings suggest that therapeutic interventions based on the risk assessment of PRS for gout could enhance clinical outcomes through optimized, personalized prevention.”
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