Published online Aug 28, 2020. doi: 10.4329/wjr.v12.i8.184
Peer-review started: March 9, 2020
First decision: April 25, 2020
Revised: June 16, 2020
Accepted: July 19, 2020
Article in press: July 19, 2020
Published online: August 28, 2020
Gout, caused by hyperuricemia and subsequent deposition of aggregated monosodium urate crystals (MSU) in the joints or extra-articular regions, is the most common inflammatory arthritis. There is increasing evidence that gout is an independent risk factor for hypertension, cardiovascular disease progression and mortality. Gout patients are at higher risk of life-threatening myocardial infarction and stroke. However, the exact mechanisms by which gout confers this increased cardiovascular risk are still poorly understood.
Dual energy computed tomography (DECT) has been previously used to diagnose gout and accurately visualize MSU deposits within the joints. MSU deposits identified by DECT in regions other than the joints, such as the vasculature, have been anecdotally treated as artifacts. However, it is possible that in hyperuricemic individuals, MSU may actually be deposited within the vessel wall and possibly lead to an inflammatory cascade.
The aim of this study was to determine if DECT can quantify deposition of MSU within the vessel wall of individuals with gout and to measure volume of urate deposits to determine if this deposition is increased in these gout patients as compared to healthy controls.
Fifty adult subjects were recruited from a single-center urban academic hospital to participate in this study. 31 subjects had gout, and 18 were healthy controls. Of the 31 gout patients, 16 subjects had tophaceous gout, and the remaining 15 were non tophaceous. All study participants underwent dual energy computed tomography (DECT) scans of the chest and abdomen using a second-generation Siemens somatom Force 2 × 192 slice dual source computed tomography scanner. Images were analyzed using a specific segmentation algorithm to differentiate calcium and urate depositions within the arterial vessel wall (aorta, coronaries and iliacs) using the Siemens syngo via software package. Total volume of areas coded green by the DECT material decomposition algorithm (indicating MSU deposition) with the entire aorta was computed using a semi-automated volume assessment program from manually drawn regions of interest. The number of distinct green spots on images within the aorta were also computed. Unadjusted differences in the total volume of MSU and the number of green spots in the aorta between the gout and healthy control groups were assessed via the Mann-Whitney U exact test. An exploratory subgroup analysis was performed to compare differences in total volume and number of green spots between the tophaceous and non-tophaceous gout groups using the nonparametric methods described above.
Gout subjects had significantly higher volume of MSU within the entire aorta and the number of deposits (green spots on image) was significantly higher in the gout group compared to the controls. However, after adjustment for age, gender, history of cardiovascular disease and diabetes, there was no significant difference between the gout and control groups with respect to MSU volume. Older age was associated with higher total green coded volume on images (P = 0.08) and larger number of green spots (P = 0.03). Exploratory subgroup analysis of tophaceous and non-tophaceous gout showed no significant differences between the groups for either total MSU volume in the aorta (P = 0.63) or the number of green spots (P = 0.55). A significantly larger proportion of subjects in the gout group had MSU deposits in the coronaries and iliac arteries. Specifically, 55% (n = 16/29) of the subjects in the gout group had potential uric acid deposits in the coronary arteries compared to 0% in the control group (P < 0.001).
The results of this study show that patients with gout have increased green coded regions and MSU deposition within their vasculature and that the total volume of these regions within the aorta of individuals with gout was significantly higher than the controls. Similarly, the proportion of individuals with MSU deposits within the coronary vessels and iliacs was higher in patients with gout compared to controls. To our knowledge, this is amongst the first few studies to demonstrate such a relationship. This study has provided compelling data regarding vascular deposition of MSU in patients with gout and could lead to future studies that examine whether this finding has implications for the increased cardiovascular disease risk in individuals with gout. In the future, this study could benefit from a larger sample size as well as from the availability of serum inflammatory biomarkers and serum urate data for correlating with the results. Further independent confirmatory studies in newly developed animal models or in human cadavers with histological confirmation may also shed light on the sensitivity, specificity, and accuracy of DECT in quantifying vascular urate depositions.