High Genetic Gout Risk Associated With Increased Risk of CVD

Credit: Adobe Stock

A new study has found that a higher genetic risk of gout is significantly associated with an increased risk of cardiovascular disease (CVD), although adherence to a preventative, favorable lifestyle can significantly reduce CVD risk.¹

“The genetic architectures of hyperuricemia and gout are significantly different. A recently published genome-wide association study (GWAS) study showed that 13 single-nucleotide polymorphisms (SNPs) reached genome-wide significance between asymptomatic hyperuricemia and clinical gout.² Thus, the genetic association between gout and CVD should be elucidated separately from previous genetic studies on serum uric acid (SUA) and CVD. To assess the genetic risk of gout as an indicator of CVD, we employed an approach using polygenic risk score (PRS) generation based on SNP weights derived from an independent large-scale GWAS,” lead investigator Ki Won Moon, Department of Internal Medicine, Kangwon National University School of Medicine, Chuncheon, South Korea, and Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, and colleagues wrote.¹

Moon and colleagues collected data from a total of 224,689 participants of European descent from the UK Biobank (UKBB) and 50,364 participants of East Asian descent from the Korean Genome and Epidemiology Study (KoGES). They assessed genetic risk for gout using a PRS derived from a meta-GWAS (n=444,533) and evaluated incident CVD risk according to genetic risk, lifestyle and metabolic syndrome (MetS).

The investigators found that participants with high PRS had a 4.14-fold higher risk of gout (95% CI, 3.69-4.64; P <.001) than those with a low PRS group in the UKBB and the KoGES (adjusted OR 2.59 [95% CI, 1.80-3.75; P <.001). According to the multivariable Cox regression model, the investigators found that Gout-PRS was significantly associated with incident CVD, with individuals with a high PRS had a 1.10-fold higher risk of CVD (95% CI 1.04 to 1.17; P <.001) than those with a low PRS group in the UKBB. By subtype, adjusted HRs were 1.14 (95% CI, 1.05-1.24; P = .002) for coronary artery disease, 1.17 (95% CI 1.00 to 1.37; p=0.046) for myocardial infarction and 1.29 (95% CI 1.10 to 1.50; P < .001) for congestive heart failure. In KoGES, participants in the top 20% PRS group had a higher risk of incident CVD (adjusted HR, 1.31 [95% CI, 1.04-1.65; P = .024) than those in the bottom 20% PRS group.¹

Moon and colleagues also found that individuals with the top 20% PRS who had an unfavorable lifestyle had the highest risk for incident CVD (adjusted HR, 1.99; 95% CI, 1.73-2.30; P <.001) followed by those with high PRS who had a poor MetS status (adjusted HR 2.16; 95% CI, 1.94-2.42; P <.001) in the UKBB. Similarly, in the KoGES cohort, individuals with the top 20% PRS who had an unfavorable lifestyle had the highest risk for incident CVD (adjusted HR, 2.49; 95% CI, 1.52-4.08; P <.001) followed by those with the top 20% PRS who had a poor MetS status (adjusted HR, 1.83; 95% CI, 1.07-3.13; P = .027).¹

Furthermore, participants with the top 20% PRS for gout, unfavorable lifestyle, and poor MetS had a substantially increased 2.54-fold increased CVD risk compared with participants having the lowest expected risk (P for trend <.001). Overall, regardless of subgroup analyses of genetic risk, high MetS and a favorable lifestyle reduced the subsequent risk of CVD by 62% in those with high genetic risk (PRS top 20%) and by 46% in those with low genetic risk (bottom 20%). Notably, adherence to a favorable lifestyle significantly reduced the risk of CVD by 25% even in participants with low genetic risk with at least 4 components of MetS.¹

“In conclusion, our findings establish a link between the PRS for gout, lifestyle habits and an increased risk of CVD using 2 separate databases representing diverse ancestral backgrounds. 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. These findings suggest that therapeutic interventions based on the risk assessment of PRS for gout could enhance clinical outcomes through optimized personalized prevention,” Moon and colleagues concluded.¹

REFERENCES

1. Moon KW, Jung SH, Do H, et al. Cardiovascular risk according to genetic predisposition to gout, lifestyle and metabolic health across prospective European and Korean cohorts. RMD Open. 2024;10(4):e004552. Published 2024 Oct 8. doi:10.1136/rmdopen-2024-004552

2. Sandoval-Plata G, Morgan K, Abhishek A. Variants in urate transporters, ADH1B, GCKR and MEPE genes associate with transition from asymptomatic hyperuricaemia to gout: results of the first gout versus asymptomatic hyperuricaemia GWAS in Caucasians using data from the UK Biobank. Ann Rheum Dis 2021;80:1220–6. doi:10.1136/annrheumdis-2020-21979