“The relationship between gout and cardiovascular (CV) disease risk is central to the management of gout, since patients with gout have a six-fold higher risk of suffering from CV events compared with the general population,” explains Tristan Pascart, MD. “We suspect that this is closely related to chronic inflammation due to the deposition of monosodium urate (MSU) crystals. Previous studies indicate that patients with clinical subcutaneous tophi have the highest CV disease and mortality risks. However, since tophaceous patients represent just 20% of the gout population, we needed to determine if MSU crystal deposition beyond tophi had an impact.”

For a paper published in Rheumatology (Oxford), Dr. Pascart and colleagues aimed to determine whether the volume of MSU crystal deposition measured with dual-energy computed tomography (DECT) is predictive of short-term mortality and development of CV comorbidities and diabetes mellitus. Patients with a diagnosis of gout, having had baseline DECT scans of their knees and feet to measure the volume of MSU crystal deposition, were included in the study. Risk factors for mortality and a composite variable (onset of any cardiometabolic event) were examined using multivariable Cox models.

MSU Crystal Volume Linked With Cardiometabolic Comorbidities

“Data on treatments, CV events, and mortality were assessed at 1, 2, and 3 years,” Dr. Pascart says. “We could then assess how the occurrence of CV events and mortality were related to other factors (eg, pre-existing comorbidities, serum urate [SU] levels), including the volume of MSU crystals measured with DECT.”

During follow-up 10.9% of study participants died, among whom 42.8% had a CV cause of death; 13.2% of patients presented with a new cardiometabolic comorbidity. Factors associated with mortality risk were baseline DECT volume of MSU crystals (hazard ratio [HR], 1.02) and baseline SU levels (HR, 1.04). “The only significant association in multivariate analysis was the volume of MSU crystals measured with DECT, meaning that is was the only independent predictor of a new CV event in our study,” Dr. Pascart notes (Table).

“We believe our results not only add to existing knowledge of gout by showing that the volume of MSU crystals, more than tophi, is linked to CV and mortality risks, but also emphasize how patients with gout with high crystal burdens should have their CV disease risk closely monitored,” he says. “Assessing the volume of the MSU crystal burdens not only helps predict the risk of future flares, but also helps identify patients with higher CV risk than expected.”

Manage CV Conditions Proactively

Dr. Pascart stresses that physicians be aware that patients with gout have a greater than average risk for CV events and mortality. “This is particularly true for patients with high crystal burdens, both seen in clinical examination when tophi are present, and also those who have numerous crystals that are only detected with DECT,” he says. “We suggest a more systematic assessment of MSU crystal volumes with DECT and for clinicians to be proactive in managing CV conditions in patients with high volumes.”

The study team suggests that future research examine how reducing SU levels in patients with gout helps control CV disease and mortality risk. “Monitoring the evolution of MSU crystal volume with DECT over time, and its relationship with new CV events and mortality, would be a great step forward,” Dr. Pascart adds.