Prevalence of asymptomatic hyperuricemia and its association with prediabetes, dyslipidemia and subclinical inflammation markers among young healthy adults in Qatar

Aim The aim of this study is to investigate the prevalence of asymptomatic hyperuricemia in Qatar and to examine its association with changes in markers of dyslipidemia, prediabetes and subclinical inflammation. Methods A cross-sectional study of young adult participants aged 18 - 40 years old devoid of comorbidities collected between 2012 and 2017. Exposure was defined as uric acid level, and outcomes were defined as levels of different blood markers. De-identified data were collected from Qatar Biobank. T-tests, correlation tests and multiple linear regression were all used to investigate the effects of hyperuricemia on blood markers. Statistical analyses were conducted using STATA 16. Results The prevalence of asymptomatic hyperuricemia is 21.2% among young adults in Qatar. Differences between hyperuricemic and normouricemic groups were observed using multiple linear regression analysis and found to be statistically and clinically significant after adjusting for age, gender, BMI, smoking and exercise. Significant associations were found between uric acid level and HDL-c p = 0.019 (correlation coefficient -0.07 (95% CI [-0.14, -0.01]); c-peptide p = 0.018 (correlation coefficient 0.38 (95% CI [0.06, 0.69]) and monocyte to HDL ratio (MHR) p = 0.026 (correlation coefficient 0.47 (95% CI [0.06, 0.89]). Conclusions Asymptomatic hyperuricemia is prevalent among young adults and associated with markers of prediabetes, dyslipidemia, and subclinical inflammation.

Early azathioprine in acute Vogt-Koyanagi-Harada disease: a prospective 24-month follow-up study with multimodal imaging and electroretinogram

Background: First-line immunosuppressive therapy (IMT) associated with high-dose corticosteroid (CS) has been proposed for the treatment of acute Vogt-Koyanagi-Harada disease (VKHD) to prevent chronicity and to prevent long-term CS side effects. However, there are very few studies that systematically evaluated visual and inflammatory outcomes in acute VKHD with early IMT. This study aimed to evaluate the outcome of high-dose corticosteroids with early addition of azathioprine (AZA) in patients with acute Vogt-Koyanagi-Harada disease (VKHD) followed for 24-month with systematic multimodal and electroretinogram exams.Methods: Prospective interventional study. Fifteen consecutive patients (30 eyes) with acute VKHD at a tertiary uveitis referral centre were followed for 24 months with systematic multimodal and full-field electroretinogram (ffERG) exams. Patients were treated with intravenous methylprednisolone followed by oral prednisone 1mg/kg/daily (CS) with slow taper and AZA introduction within 4 months. Anterior uveitis relapse, subclinical inflammation, best-corrected visual acuity (BCVA) and ffERG parameters were analyzed.Results: Fifteen patients (14 female) with a median age of 32 years were included. In the first month, 27 eyes (90%) had BCVA ≥20/40; at M24, all eyes (100%) had BCVA ≥20/25. Uveitis resolved in 28 eyes (93.3%) and became chronic recurrent in 2 eyes (6.7%); subclinical inflammation was still present in all eyes during the 24-month follow-up. ffERG parameters initially improved in all eyes; at M24, 23 eyes (76.7%) had subnormal results and 20 eyes (66.7%) had stable parameters. Eyes with very early treatment (n=12) had lower indocyanine green angiography score than eyes with early treatment (n=18) at M1 (p=0.012), but they had similar rates of recurrence, complications and ffERG parameters. Conclusion: Early AZA associated with high-dose corticosteroid was effective in improving BCVA and in controlling clinical inflammation. Isolate subclinical inflammation persisted in all eyes with no impact on ffERG in, at least, two thirds of these eyes, indicating that isolate subclinical inflammation may not be enough to indicate treatment increment.

Association of circulating MR-proADM with all-cause and cardiovascular mortality in the general population: Results from the KORA F4 cohort study

Background and aim Despite its vasodilatory effect, adrenomedullin and its surrogate mid-regional pro-adrenomedullin (MR-proADM) have been found to be positively associated with all-cause and cardiovascular mortality. However, the underlying mechanisms thereof remain unclear and the associations were mostly shown in geriatric cohorts or in patients with chronic diseases. Therefore, we aimed to investigate the possible involvement of abdominal obesity, selected adipokines, and biomarkers of subclinical inflammation in the association of MR-proADM with mortality in a population based study cohort. Methods Prospective analysis of the KORA F4 study; median follow-up 9.1 (8.8–9.4) years. Complete data on MR-proADM and mortality was available for 1551 participants, aged 56.9±12.9 years (mean±SD). Correlation and regression analyses of MR-proADM with overall (BMI) and abdominal obesity (waist circumference), selected adipokines and biomarkers of subclinical inflammation. Cox proportional hazard models on the association of MR-proADM with all-cause and cardiovascular mortality with adjustment for cardiovascular risk factors and selected biomarkers in study subgroups (n = 603–1551). Results MR-proADM associated with all-cause (HR (95%CI): 2.37 (1.72–3.26) and 2.31 (1.67–3.20)) and cardiovascular mortality (4.28 (2.19–8.39) and 4.44 (2.25–8.76)) after adjustment for traditional cardiovascular risk factors including BMI or waist circumference, respectively. MR-proADM was further associated with four out of seven examined adipokines (leptin, retinol-binding protein-4, chemerin, and adiponectin) and with five out of eleven examined biomarkers of subclinical inflammation (high-sensitivity C-reactive protein, interleukin-6, myeloperoxidase, interleukin-22, and interleukin-1 receptor antagonist) after multivariable adjustment and correction for multiple testing. However, only IL-6 substantially attenuated the association of MR-proADM with all-cause mortality. Conclusions We found an association of MR-proADM with (abdominal) obesity, selected adipokines, and biomarkers of subclinical inflammation. However, the association of MR-proADM with mortality was independent of these parameters. Future studies should investigate the role of IL-6 and further characteristics of subclinical inflammation in the association between MR-proADM and all-cause mortality.

Association of Fatty Liver (Non-Alcoholic), Metabolic Syndrome and Subclinical Inflammation on Mild Renal Inadequacy

Background: Non-alcoholic liver disease causes liver damage and influences the insulin production, metabolic and inflammatory pathways and renal sufficiency. Aim: To find an association of fatty liver, metabolic syndrome and subclinical inflammation on mild renal inadequacy. Study design: Comparative analytical study Place and duration of study: Department of Medicine, Bolan Medical College Quetta from 1st January 2020 to 30th June 2021. Methodology: One hundred and twenty patients were enrolled. They were divided in two groups; 60 controls and 60 non-alcoholic fatty liver disease patients age between 30-55 years of age included. Their demographic, ultrasonography, anthropometric measurements and biochemical details were recorded. Results: There were 34 men out of 60 having NA fatty liver with a mean age of 45±5.8 years. Mild renal inadequacy was seen in 21, metabolic syndrome in 27, hypertension in 18 and diabetes in 8 of non-alcoholic fatty liver patients with a mean raised CRP as 1.5±0.8mg/L. Conclusion: Non-alcoholic fatty liver presence in addition to metabolic syndrome and subclinical inflammation effect on mild renal inadequacy Key words: Fatty liver, Metabolic syndrome, Subclinical inflammation, Mild renal inadequacy

Prevalence of Asymptomatic Hyperuricemia and its Association with Prediabetes, Dyslipidemia and Subclinical Inflammation Markers among Young Healthy Adults in Qatar

Aim: To investigate the prevalence of asymptomatic hyperuricemia in Qatar and to examine its association with changes in markers of dyslipidemia, prediabetes and subclinical inflammation. Methods: A cross-sectional study of young adult participants aged 18 - 40 years old devoid of comorbidities. Exposure was defined as uric acid level, and outcomes were defined as levels of different blood markers. De-identified data were collected from Qatar BioBank. T-tests, correlation tests and multiple linear regression were all used to investigate the effects of hyperuricemia on blood markers. Statistical analyses were conducted using STATA 16. Results: The prevalence of asymptomatic hyperuricemia is 21.2% among young adults in Qatar. Differences between hyperuricemic and normouricemic groups were observed using multiple linear regression analysis and found to be statistically and clinically significant after adjusting for age, gender, BMI, smoking and exercise. Significant associations were found between uric acid level and HDL-c p = 0.019 (correlation coefficient -0.07 (95% CI [-0.14, -0.01]); c-peptide p = 0.018 (correlation coefficient 0.38 (95% CI [0.06, 0.69]) and monocyte to HDL ration (MHR) p = 0.026 (correlation coefficient 0.47 (95% CI [0.06, 0.89]). Conclusion: Asymptomatic hyperuricemia is prevalent among young adults and associated with markers of prediabetes, dyslipidemia, and subclinical inflammation.

Reappraising the role of baseline plasma C-reactive protein levels on recurrence after catheter ablation of persistent atrial fibrillation: insight from EARNEST-PVI trial

Background Subclinical inflammation is an important pathogenesis of developing and sustaining atrial fibrillation (AF). Because AF itself contribute to the inflammatory response, the role of baseline subclinical inflammation on AF recurrence after catheter ablation (CA) remains controversial in patients with persistent AF. Purpose To evaluate whether baseline plasma C-reactive protein (CRP) levels, a sensitive marker of inflammation, are associated with AF recurrence following CA. Methods The analysis was performed from the EARNEST-PVI trial, a randomized controlled trial designed to assess a CA strategy for persistent AF, which was conducted in the Osaka region of Japan. A total of 441 patients (median age, 67 years; 26% female; 25% long-standing persistent AF) whose plasma CRP levels were measured at baseline were included in this study. Results At baseline, a median (interquartile range) of plasma CRP level was 0.10 [0.06–0.19] mg/dl. Plasma CRP levels significantly increased at discharge (0.83 [0.21–1.84] mg/dl, p<0.001) and decreased 1 year after CA (0.10 [0.05–0.20] mg/dl, p=0.040) compared to the baseline value. During the follow-up of 1 year, 115 patients (26%) experienced AF recurrence, and the incidence was significantly higher in 124 patients with low CRP levels at baseline (cut-off ≤0.06 mg/dl) than the other 317 patients (33.9% vs. 23.0%, p=0.017). After adjustment of age, gender, body mass index, long-standing persistent AF, CA strategy, and plasma brain natriuretic peptide levels, low plasma CRP levels was a significant predictor of AF recurrence (hazard ratio, 1.51; 95% confidence interval, 1.02–2.24; p=0.042). Conclusions Low plasma CRP levels at baseline predicted AF recurrence in the EARNEST-PVI trial. Reappraising the role of CRP on AF recurrence may be needed in patients with persistent AF. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Johnson & Johnson KK

Fibrinogen-to-Albumin Ratio in Familial Mediterranean Fever: Association with Subclinical Inflammation

Background Familial Mediterranean fever (FMF) is the most seen monogenic periodic fever syndrome characterised by bouts of fever and serositis. It is known that subclinical inflammation (SI) can persist in the symptom-free period and lead to amyloidosis even under colchicine treatment. This study aimed to evaluate the role of the fibrinogen-to-albumin ratio (FAR) in FMF and its correlation with SI. Material and Methods A total of 112 patients with FMF and 78 controls were enrolled in this retrospective study. Demographic, laboratory and genetic data were obtained from the hospital records. Results The FAR values of the FMF cases were significantly higher than the control group (p<0.001). In the FMF group, the patients with SI had higher FAR values than those without SI (p<0.001). FAR was positively correlated with SI (r=0.413, p<0.001). The receiver operating characteristic curve analysis showed that FAR had a higher area under the curve value than albumin and fibrinogen. Conclusion Detecting SI in patients with FMF is crucial in preventing amyloidosis, the most devastating complication of FMF. FAR is a simple, inexpensive, easily obtained indicator which can be used for reflecting SI in FMF.

Rivaroxaban compared with low-dose aspirin in individuals with type 2 diabetes and high cardiovascular risk: a randomised trial to assess effects on endothelial function, platelet activation and vascular biomarkers

Aims/hypothesis Individuals with type 2 diabetes mellitus and subclinical inflammation have stimulated coagulation, activated platelets and endothelial dysfunction. Recent studies with the direct factor Xa inhibitor rivaroxaban in combination with low-dose aspirin demonstrated a significant reduction of major cardiovascular events, especially in individuals with type 2 diabetes and proven cardiovascular disease. Therefore, we asked the question of whether treatment with rivaroxaban could influence endothelial function, arterial stiffness and platelet activation. Methods We conducted a multi-centre, prospective, randomised, open-label trial in 179 participants with type 2 diabetes (duration 2–20 years), subclinical inflammation (high-sensitivity C-reactive protein 2–10 mg/l) and at least two traits of the metabolic syndrome to compare the effects of the direct factor Xa inhibitor rivaroxaban (5 mg twice daily) vs aspirin (100 mg every day) on endothelial function (assessed by forearm occlusion plethysmography), skin blood flow (assessed by laser-Doppler fluxmetry), arterial stiffness (assessed by pulse wave velocity) and serum biomarkers of endothelial function and inflammation. Furthermore, we investigated phosphorylation of vasodilator-stimulated phosphoprotein (VASP) in platelets, the concentration of platelet-derived microparticles (PMPs) and the effects of isolated PMPs on HUVEC proliferation in vitro. Results Rivaroxaban treatment for 20 weeks (n = 89) resulted in a significant improvement of post-ischaemic forearm blood flow (3.6 ± 4.7 vs 1.0 ± 5.2 ml/100 ml, p = 0.004), a numerically increased skin blood flow and reduced soluble P-Selectin plasma level vs aspirin. We did not find significant differences of arterial stiffness or further biomarkers. Neither rivaroxaban nor aspirin influenced VASP phosphorylation of platelets. The number of PMPs increased significantly with both rivaroxaban (365.2 ± 372.1 vs 237.4 ± 157.1 μl−1, p = 0.005) and aspirin (266.0 ± 212.7 vs 201.7 ± 162.7 μl−1, p = 0.021). PMPs of rivaroxaban-treated participants stimulated HUVEC proliferation in vitro compared with aspirin. Rivaroxaban was associated with a higher number of bleeding events. Conclusions/interpretation Our findings indicate that the direct factor Xa inhibitor rivaroxaban improved endothelial function in participants with type 2 diabetes and subclinical inflammation but also increased the risk of bleeding. Trial registration: ClinicalTrials.gov NCT02164578. Funding The study was supported by a research grant from Bayer Vital AG, Germany. Graphical abstract