Urate crystal deposition is associated with inflammatory markers and carotid artery pathology in patients with intercritical gout: results from the NOR-Gout study

Abstract

BackgroundGout is of unknown reason associated with cardiovascular disease. Ultrasound is sensitive for detecting crystal deposition and plasma calprotectin is a sensitive inflammatory marker. This study explores the associations between crystal deposition, inflammation and carotid artery pathology.MethodA cross-sectional analysis of baseline assessments from the NOR-Gout study was undertaken. Crystal deposition was assessed by ultrasound (double contour, tophi, aggregates) and dual-energy CT (DECT) and laboratory assessments included plasma calprotectin. The carotid arteries were bilaterally examined for carotid intima–media thickness (cIMT) and presence of plaques. Spearman correlations, Mann-Whitney tests and linear regression analyses were used to explore associations between crystal deposition, inflammatory markers,and carotid pathology.Results202 patients with intercritical gout (95.5% men, mean (SD) age 56.5 (13.8) years, disease duration 7.9 (7.7) years) were included. Calprotectin was correlated with all scores of crystal deposition by ultrasound (r=0.26–0.32, p<0.001) and DECT (r=0.15, p<0.05). cIMT was correlated with sum score aggregates (r=0.18–0.22, p<0.05). Patients with large tophi had higher levels of calprotectin as well as more frequent carotid plaque (p<0.05).ConclusionsStudy findings point towards crystal deposition contributing to subclinical inflammation with subsequent vascular implications. However, future longitudinal studies are needed to confirm such causal relationships.

Lifestyle factors predict gout outcomes: Results from the NOR-Gout longitudinal 2-year treat-to-target study

“…Elevated lipid levels were also seen in patients with tophi. We have earlier described increased levels of inflammation with increased calprotectin in our gout cohort 32 with a relationship to large tophi as a poor disease outcome. Tight-control treat-to-target intervention was no longer performed after year 1 which could explain why changes of lipid levels especially primarily observed during year 1.…”

Uric Acid and Chronic Kidney Disease: Still More to Do

“… 37 These “silent crystals” can still be associated with evidence for systemic inflammation that may have an indirect role in the progression of kidney disease and cardiovascular events. 38 Indeed, both elevated monocyte counts and high levels of highly sensitive C-reactive protein levels are found in patients with a history of gout. 39 , 40 Some studies have found that allopurinol treatment can lower highly sensitive C-reactive protein levels.…”

Gout and hyperuricaemia: modifiable cardiovascular risk factors?

“…Today, numerous experimental studies have enable to better define the negative impact of hyperuricaemia and gout on the cardiovascular system ( 18 , 19 ). As indicated in Figure 1 , several mechanisms are involved, one of which is an accumulation of uric acid crystals in tissues (including in the heart and certain vessels ( 31 , 32 ), the development of systemic inflammation with activation of neutrophils and macrophages and stimulation of pro-inflammatory cytokines associated with an inflammasome activation, endothelial dysfunction, and increase oxidative stress ( 33 ). These factors, some of which are responsible for joint disorders, are nowadays recognized as being implicated in the development of atherosclerosis and cardiovascular complications ( 34 , 35 ).…”