Past observational studies have shown a link between hypertension and gout, but whether a causal relationship existed was unclear, according to Chang-Fu Kuo, MD, PhD.
For a study published in Arthritis Research & Therapy, Dr. Kuo and colleagues sought to assess if there is a causal relationship between gout and hypertension. The researchers obtained genetic information from 88,347 individuals and 686,439 single-nucleotide polymorphisms (SNPs). They utilized a novel model of Mendelian randomization (MR) with coarsened exposures to explore the causality between the liability of gout on hypertension and vice versa.
Four SNPs linked with gout and 10 SNPs linked with hypertension were used after removal of SNPs associated with confounders. To estimate effect size, the researchers utilized the polygenic risk score (PRS) and inverse-variance weighted (IVW) methods. They conducted the MR analysis with coarsened exposures with and without adjustments for covariates.
Certain Medications May Raise the Risk for Gout
Among all participants, 3.68% had gout and 13.52% had hypertension (men, 31.9%; mean age, 51.1). After adjusting for measured confounders, MR analysis with coarsened exposures demonstrated a significant positive causal effect of the liability of gout on hypertension in both the PRS method (relative risk [RR], 1.10; 95% CI, 1.02-1.19; P=0.0092) and the IVW method (RR, 1.10; 95% CI, 1.03-1.19; P=0.0077). No causal effect of the liability of hypertension on gout was observed, however.
The fact that no evidence was found that hypertension causes gout suggests that the link between hypertension and gout may not be caused directly by hypertension, Dr. Kuo and colleagues noted, adding that it may be facilitated by other pathways. For example, they pointed out that certain medications, such as diuretics, may raise the risk for gout by increasing the serum urate level through the reduction of renal urate excretion.
“Modified MR with coarsened exposures model revealed a robust causal role of the liability of gout in hypertension onset but not a causal role of hypertension in gout onset,” the study authors wrote. “Thus, it may be beneficial for clinicians to view gout as a chronic disease with important systemic effects rather than simply acute self-limiting arthritis.”