Analysis of Causal Relationship Between Gout and Hypertension

Gout has an incidence of 2.74 per 1,000 person-years and is linked to increased risks of mortality and comorbidities. It is an inflammatory disease caused by the accumulation of monosodium urate in and around the joints due to elevated levels of serum urate (hyperuricaemia) in the blood. Of the comorbidities associated with gout, cardiovascular disease and hypertension are two of the most commonly reported. There have been several studies that have investigated the relationship between gout and hypertension, with studies suggesting hyperuricemia is associated with arterial stiffness, insulin level, alterations in the renin-angiotensin system, and endothelial dysfunction. However, many of these studies were observational, and causality between gout and hypertension could not be established.

“Our work aims to assess the causal relationship between gout and hypertension,” authors wrote regarding their study published in Arthritis Research & Therapy. Using prospectively collected genetic information, 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs) were included in the analysis. The authors of the study used a novel model of Mendelian randomization (MR), a method of using measured variation in genes of known function to examine the causal effect of a modifiable exposure on disease, to examine the causality between the liability of gout on hypertension and vice versa, using five SNPs associated with gout and 10 SNPs associated with hypertension.

MR analysis was conducted using two methods: inverse-variance weighted (IVW) and polygenic risk score (PRS). IVW method, a more suitable than the random-effects method, aggregates two or more random variables to minimize the variance of the weighted average. PRS, on the other hand, is used to represent the total number of genetic variants that an individual has in order to assess their heritable risk of developing a particular disease.

Of the study participants, 3.86% had gout and 13.52% had hypertension. The mean age of participants was 51.1 years. Patients with gout and/or hypertension were more likely to be male, be older, have increased BMI and urate levels, and have worse kidney function.

After MR analysis, the authors found a significant positive causal effect of the liability of gout on hypertension in both the IVW and PRS methods. Causality was estimated to be the same before and after involving confounding variables.

“The present study supported a causal effect of gout on hypertension, but multiple MR analyses have not provided conclusive evidence to support a direct causal effect of the urate level on hypertension,” the authors said. “Therefore, the causal effect of gout on hypertension may be mediated by the urate level, in combination with other urate-independent pathways.”