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Genetic Risk of Gout Linked to Increased Cardiovascular Risk

A higher genetic predisposition to gout increases the risk of cardiovascular disease, but adhering to a healthy lifestyle can significantly reduce this risk.

By

Lana Pine

 |  Published on October 24, 2024

5 min read

Genetic Risk of Gout Linked to increased Cardiovascular Risk

Credit: iDoPixBox

A higher genetic predisposition to gout is significantly associated with an increased risk of cardiovascular disease (CVD). However, adherence to a favorable lifestyle, such as maintaining ideal metabolic syndrome (MetS) and healthy habits, can significantly reduce this risk, even in individuals with a high genetic risk.

“The findings of this study could lead to a deeper understanding of the genetic basis of gout in relation to CVD, emphasizing the importance of polygenic risk scores (PRS) in predicting disease susceptibility,” an international team of investigators said.

Previous research has suggested gout is linked to an increased risk of CVD, including congestive heart failure, coronary artery disease, myocardial infarction, peripheral artery disease and cardiovascular mortality. As such, current recommendations for gout encourage patients to be screened for CVD comorbidities.

According to the American Heart Association, lifestyle habits, such as smoking, alcohol consumption, diet, obesity and physical activity play an important role in developing CVD.

Investigators used data from two diverse cohorts of patients from different ancestries, with 224,689 participants of European descent from the UK Biobank and 50,364 participants of East Asian descent from the Korean Genome and Epidemiology Study analyzed to assess the relationship between gout risk, genetic factors, lifestyle habits and incident CVD. Genetic risk for gout was determined using a PRS from a meta-genome-wide association study.

Lifestyle factors were categorized as unfavorable, intermediate and favorable. Metabolic health status was determined according to the presence of the five components of MetS, developed from the International Diabetes Federation consensus report. Status was categorized as ideal, intermediate and poor.

The mean age of participants was 57 years in the UK Biobank cohort. A total of 1.8% had a history of gout and 5.6% were diagnosed with CVD during the follow-up period. In the Korean group, the mean age was 53.7 years, 0.7% had a history of gout and 1.3% reported incident CVD.

Individuals with a high genetic risk for gout had a higher risk of incident CVD compared with those with low genetic risk regardless of ancestry. Patients in the top 20% PRS who had an unfavorable lifestyle had the highest risk of incident CVD, followed by individuals with high PRS who had a poor MetS status regarding joint associations. Both analyses showed clinical significance. Those with high PRS for gout, unfavorable lifestyle and poor metabolic health had a 2.54 times higher CVD risk compared with individuals in the lowest expected risk group.

Results also showed a reduction in CVD risk by up to 62% in those who adhered to favorable lifestyle habits and ideal MetS, regardless of their genetic predisposition to gout.

Investigators said that while there is a link between genetic predisposition to gout and lifestyle factors and the risk of CVD, results cannot necessarily indicate causality. Additionally, they suggest the development of a standardized method to assess lifestyle habits as the definitions of lifestyle and MetS were different for each cohort. They were also unable to determine how metabolic health status and lifestyle behaviors changed over time as information was collected at enrollment. They recommend future research focuses on refining a cross-ancestry PRS to more effectively apply this method across a variety of populations.

“The effect of adherence to a healthy lifestyle was greater in individuals with a higher genetic risk,” investigators emphasized. “These findings suggest that therapeutic interventions based on the risk assessment of PRS for gout could enhance clinical outcomes through optimized personalized prevention.”