الفهرس 
GOUTOnly 14 pages are availabe for public view
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Abstract
G
out is a disease caused by the deposition of MSU crystals that leads to acute and chronic inflammation and tissue damage. The condition is directly linked to hyperuricemia, which is caused by purine metabolic disorder and/or reduced uric acid excretion. MSU crystal deposition can cause clinical manifestations such as flares, persistent arthritis, and/or tophi.
Increased MSU crystal burden, such as in patients with subcutaneous tophi or higher crystal load as assessed by ultrasound, increases the risk of CVDs. Recurrent low-grade inflammation episodes, associated with elevated concentrations of proinflammatory cytokines, reactive oxygen species, formation of neutrophil extracellular traps, endothelial dysfunction, and platelet hyperactivity, are characteristic of gout. This inflammation is a significant risk factor for CVD and can precipitate atherosclerosis. CIMT is a surrogate marker for subclinical atherosclerosis and CVDs.
SCL is a soluble glycoprotein produced mainly by mature osteocytes. It is a natural inhibitor of the canonical Wnt pathway, which is one of the key elements of bone formation. SCL, originating from excessive local production in calcified vessels, may also spill over the circulation contributing to vascular pathophysiology (e.g., atherosclerosis, arterial stiffness, and VC) and low bone turnover. SCL is also linked to periarticular bone loss, indicating a possible role in mediating tophus-related bone erosion.
Our study aimed to detect subclinical carotid atherosclerosis in gouty patients and its relation to MSK US manifestations and serum SCL levels.
This study was conducted on 30 Egyptian gouty patients aged more than 18 years old, who were referred to the outpatient clinic of Physical Medicine, Rheumatology and Rehabilitation department at Ain Shams University Hospitals, Cairo, Egypt. Patients were diagnosed gout based on ACR/ EULAR classification criteria of gout.
Patients were classified into two groups; group A included 15 patients with diagnostic MSK US manifestation of gout (DC sign) with or without at least one of the following (aggregate, tophus, erosion, SE, SH, or PD), and group B included 15 patients without MSK US manifestations.
All patients were subjected to full medical history taking, and thorough clinical examination. Laboratory investigations such as CBC, ESR, CRP, sUA, serum creatinine level, total cholesterol, HDL, LDL, and TGs, HbA1c, in addition to assessment of serum SCL levels were done to all patients. Radiological investigations included MSK ultrasonography on both knee and first MTP joints and carotid duplex ultrasonography for measurement of CIMT were done. Serum SCL level was measured in all patients.
Our study revealed that:
No significant differences were found between the two groups for age, gender, weight, height, BMI, smoking status, joint tenderness, ULT, and ULT intake duration.
There were no significant differences between the two groups regarding ESR, CRP, hemoglobin level, platelets, serum creatinine, sUA, total cholesterol, HDL, LDL, and TGs
There was a longer disease duration in group A patients compared to group B patients.
Serum SCL level measurement in patients of group A and group B ranged from (27.42 – 194.3 ng/ml) with a median of 57.3 ng/ml for patients of group A and ranged from (14.68-46.76 ng/ml) with a median of 18.84 ng/ml for patients of group B. The serum level of SCL was significantly higher in group A patients than that in group B patients.
The study found that the optimal serum SCL level to detect gouty patients with positive findings in MSK US was greater than 25.05 ng/ml, with a sensitivity of 100% and specificity of 93.33%. The area under the curve (AUC) was 0.982, indicating a high level of accuracy of the test at 98.2%.
The mean CIMT of group A patients was 1.02 ± 0.15 mm, and the mean CIMT of group B patients was 0.82±0.18 mm. The CIMT was significantly higher in group A patients than that in group B. Carotid plaque (>1 mm) was detected in two patients in group A while no plaques were detected in group B patients.
Patients with serum SCL levels greater than 25.05 ng/ml demonstrated a statistically significant increase in CIMT greater than 0.9 mm, compared to patients with SCL levels less than or equal to 25.05 ng/ml.
There was a significant positive correlation between serum SCL and serum uric acid.
There was a significant negative correlation between HDL and serum uric acid.
There was a significant positive correlation between CIMT and disease duration of gout.
CONCLUSION
I
n conclusion, patients with MSK US manifestations of gout are liable to subclinical carotid atherosclerosis more than patients without. SCL at a certain level >25.05 ng/ml in gouty patients might predispose to radiographic findings of MSK US of gout and subclinical atherosclerosis.
RECOMMENDATIONS
Screening for serum SCL is helpful in gouty patients.
Interventional studies on volunteers to determine the effects of antisclerostin antibody (romozumab) on the atherosclerosis process in gouty patients.
Interventional studies to determine the effect of ULT on MSK US findings and accelerated atherosclerosis in gouty patients are recommended.
Measurement of CIMT using carotid duplex ultrasonography is a very useful tool for the detection of subclinical atherosclerosis in gouty patients.
Lifestyle modifications like exercise, quitting smoking, reduction of body weight, and control of hypertension are helpful in reducing the complications of the disease and atherosclerosis.
Future studies on large numbers of patients with longer duration are recommended to investigate the change in serum sclerostin level and disease activity by serial assessment and not a single one.
Future studies should focus on identifying disease-related predictors for atherosclerosis progression among gouty patients to understand the underlying mechanism of accelerated atherosclerosis in these patients.