SAT0319 SUBCLINICAL ATHEROSCLEROSIS IN INDIAN PATIENTS WITH SCLERODERMA – CLINICAL AND SEROLOGICAL ASSOCIATIONS
Authors: H. Gangadharan Nair, M. K. Rai, M. Singh, A. Anuja, K. Singh, N. Mohindra, N. Jain, S. Kumar, V. Agarwal, D. Misra
Journal: Annals of the Rheumatic Diseases (2020)

Background: Scleroderma has been associated with increased risk of cardiovascular events, however,studies on this from India are sparse.We evaluated clinical and serological factors associated with subclinical atherosclerosis in Indian patients with scleroderma, in a cross-sectional design. Objectives: To compare carotid intima-medial thickness (CIMT, mean value of both carotids) as a measure of subclinical atherosclerosis (SCA) between patients with scleroderma (n=61) fulfilling 2013 ACR/EULAR criteria, and healthy controls (n=41). - To compare clinical (body mass index – BMI, waist-hip ratio – WHR, fasting lipid profile) and serological factors (microparticles, endothelial microparticles, inflammatory cytokines associated with increased cardiovascular risk) between patients with scleroderma and healthy controls. - To identify factors associated with SCA in scleroderma patients. Methods: Subclinical atherosclerosis(SCA) was defined by presence of carotid plaques, or increased CIMT &gt;2 standard deviations compared with Indian reference standards for age and sex. Total microparticles (TMP) were measured of plasma after ultracentrifugation as per previously described protocol using microbeads of 3 μm size (TMP were of size 0.1-1 μm); of these, microparticles positive for CD31 and CD142 were endothelial microparticles (EMP). Serum cytokines (IL-1, IL-6, TNF-α, IL-17) were measured by ELISA using manufacturer instructions. Linear regression was used to identify the determinants of CIMT in scleroderma. Binomial logistic regression was used to identify factors associated with subclinical athersclerosis in scleroderma. Variable Patients with scleroderma (n=61 ) Healthy controls (n=41 ) p value Age 37.8 ± 11.92 35.37 ± 6.69 0.2375 Gender (M:F ) 11:50 6:35 0.6516 Diabetes/Hypertension/Tobacco use 1/2/0 0/0/0 NS Body mass index (kg/m2 ) 20.11 ± 3.82 24.38 ± 4.45 &lt;0.0001 Waist-hip ratio 0.86 ± 0.11 0.89 ± 0.07 0.1251 Total cholesterol (mg/dL ) 142.5 ± 30.7 147.3 ± 39.5 0.4948 Triglycerides (mg/dL ) 99.4 ± 37 121.4 ± 46 0.0087 HDL cholesterol (mg/dL ) 46.9 ± 4.9 46.1 ± 4.2 0.4029 LDL cholesterol (mg/dL ) 93.6 ± 10.5 93.3 ± 7.5 0.8520 VLDL cholesterol (mg/dL ) 19.9 ± 7.4 24.7 ± 9.7 0.0057 Carotid intima-medial thickness (mm ) 0.68 ± 0.10 0.53 ± 0.03 &lt;0.0001 Total microparticles (per ± L ) 12913 ± 2493 6272 ± 1533 &lt;0.0001 Endothelial microparticles (per ± L ) 2623 ± 1032 829 ± 439.5 &lt;0.0001 Serum IL-1 ± (pg/mL ) 38.19 ± 13.46 31.38 ± 18.29 0.0326 IL-6 (pg/mL ) 176.6 ± 85.74 128.9 ± 53.61 0.0020 IL-17 (pg/mL ) 56.3 ± 20.45 53.89 ± 20.51 0.5611 TNF ± (pg/mL ) 49.65 ± 26.71 42.09 ± 30.41 0.1879 Results: Despite lower BMI, triglycerides and VLDL cholesterol, CIMT was significantly higher in patients with scleroderma. Patients with scleroderma had significantly higher total microparticles and endothelial microparticles in plasma, and serum IL-1± and IL-6 (Table 1). On multivariable regression, age was the only significant determinant of CIMT. 28 (45.9%) patients had SCA; 13 (21.3%) had carotid plaques. Patients with SCA had higher proportion of males (9/28 in those with SCA vs 2/33 in those without SCA). Binomial logistic regression did not identify any other significant predictors of SCA. Table 1 Comparison between patients with scleroderma and healthy controls Serum IL-1± (pg/mL) 38.19 ± 13.46 31.38 ± 18.29 0.0326 IL-6 (pg/mL) 176.6 ± 85.74 128.9 ± 53.61 0.0020 IL-17 (pg/mL) 56.3 ± 20.45 53.89 ± 20.51 0.5611 TNF± (pg/mL) 49.65 ± 26.71 42.09 ± 30.41 0.1879 Conclusion: Patients with scleroderma had significant burden of subclinical atherosclerosis, which could not be explained by traditional or novel cardiovascular risk factors. References: [1] Psarras A, Soulaidopoulos S, Garyfallos A, Kitas G, Dimitroulas T. A critical view on cardiovascular risk in systemic sclerosis. Rheumatol Int. 2017 Jan; 37(1):85-95. [2] Jung C, Drummer K, Oelzner P, Figulla HR, Boettcher J, Franz M, et al. The association between endothelial microparticles and inflammation in patients with systemic sclerosis and Raynaud’s phenomenon as detected by functional imaging. Clin HemorheolMicrocirc. 2015; 61(3):549-557. Acknowledgments: Supported by IRA(Indian Rheumatology Association) Research Grant to DP Misra. Disclosure of Interests: None declared