Inverse Association Research Articles

#1980 Past peritonitis episodes are linked to decreased peritoneal Immune Cell Function and Associated with Chronic Increased Peritoneal Inflammation

Abstract Background and Aims Chronic peritoneal inflammation and infectious complications occur in a significant proportion of PD patients. A relationship between peritoneal IL-6 levels and local immunocompetence is suspected. To analyse local immunocompetence, an ex-vivo stimulation assay of PD effluent was developed. The aim of this study was to analyse peritoneal inflammation and immunocompetence in a PD cohort in relation to clinical outcomes. Method Prospectively, 245 routinely performed 4-hour PETs (143 patients, 2679 patient-months) of patients exclusively receiving 2. generation PD fluids (two-chamber, pH neutral, low amount of glucose degradation products) were analysed. An ex-vivo cell stimulation protocol of the fresh effluents was performed of all PETs. Peritoneal immune cell function was analysed using ex-vivo Toll-like receptor (LPS/Pam3Cys) stimulated IL-6 release as an index of immunocompetence. The molecular effects of effluent components and the addition of alanyl-glutamine to PD fluid were analysed in heterologous cell stimulation experiments and using an effluent proteomics and metabolomics approach. Results IL-6 in the effluent showed no association with various patient characteristics (incl. RRF, underlying disease, peritonitis episodes, time on PD). A significant association of peritoneal IL-6 with solute transport rates and systemic markers of uremic inflammation was found. IL-6 in effluent (HR 2.54) and stimulated 1 h effluent (HR 0.34) was predictive of subsequent peritonitis episodes. An inverse association was observed with ex-vivo stimulated IL-6 release from peritoneal cells (P = .02), most pronounced in patients with a history of peritonitis (P = .008). Patients with above median elevated IL-6 levels showed reduced peritoneal immune cell function. The results were validated in an independent multi-centre PD cohort (n = 48). A proteomics (n = 17) and targeted metabolomics (patients n = 134, 1004 metabolites) analysis of PD effluents show an overrepresentation of apoptosis and neutrophil degranulation pathways in patients with elevated effluent IL-6 levels and reduced response mechanisms to pathogens when compared to effluents from patients with low effluent IL-6 levels. Heterologous donor-PBMC stimulation (4 Healthy donors) with 4h PET PD-effluents of 20 patients showed reduced immunocompetence with elevated IL-6 (P = .038) and improved immunocompetence when 8 mM alanyl-glutamine were added to the PD fluid during the dwell. These results could also be validated in a post-hoc analysis of a RCT testing alanyl-glutamine addition to PD fluid for 8 weeks in PD patients. Conclusion This is the first longitudinal study to show the relationship between peritoneal inflammation and impaired immune function of peritoneal cells, possibly predisposing to infectious complications. The possible underlying mechanistic link may represent the biological correlate (“immune-paralysis”) for PD patients at increased risk for recurrent episodes of peritonitis.

Neighbourhood-level policing as a racialised gendered stressor: multilevel analysis of police stops and preterm birth in Seattle, Washington

BackgroundMost studies capturing the health effects of police violence focus on directly impacted individuals, but a burgeoning field of study is capturing the indirect, community-level health effects of policing. Few...

Prospective associations of leucocyte subtypes and obesity with the risk of developing cutaneous malignant melanoma in the UK Biobank cohort

BackgroundObesity is associated with chronic low-grade inflammation, which is linked to cancer development. Abdominal obesity (a body mass index, ABSI), however, has unusually been associated inversely with cutaneous malignant melanoma (CMM), while general obesity (body mass index, BMI) is associated positively. Leucocytes participate in inflammation and are higher in obesity, but prospective associations of leucocytes with cutaneous malignant melanoma are unclear.MethodsWe examined the prospective associations of neutrophil, lymphocyte, and monocyte counts (each individually), as well as the prospective associations of ABSI and BMI, with cutaneous malignant melanoma in UK Biobank. We used multivariable Cox proportional hazards models and explored heterogeneity according to sex, menopausal status, age (≥ 50 years at recruitment), smoking status, ABSI (dichotomised at the median: ≥73.5 women; ≥79.8 men), BMI (normal weight, overweight, obese), and time to diagnosis.ResultsDuring a mean follow-up of 10.2 years, 2174 CMM cases were ascertained in 398,450 participants. There was little evidence for associations with neutrophil or lymphocyte counts. Monocyte count, however, was associated inversely in participants overall (HR = 0.928; 95%CI: 0.888–0.971; per one standard deviation increase; SD = 0.144*109/L women; SD = 0.169*109/L men), specifically in older participants (HR = 0.906; 95%CI: 0.862–0.951), and more clearly in participants with low ABSI (HR = 0.880; 95%CI: 0.824–0.939), or with BMI ≥ 25 kg/m2 (HR = 0.895; 95%CI: 0.837–0.958 for overweight; HR = 0.923; 95%CI: 0.848–1.005 for obese). ABSI was associated inversely in pre-menopausal women (HR = 0.810; 95%CI: 0.702–0.935; SD = 4.95) and men (HR = 0.925; 95%CI: 0.867–0.986; SD = 4.11). BMI was associated positively in men (HR = 1.148; 95%CI: 1.078–1.222; SD = 4.04 kg/m2). There was little evidence for heterogeneity according to smoking status. The associations with monocyte count and BMI were retained to at least 8 years prior to diagnosis, but the association with ABSI was observed up to 4 years prior to diagnosis and not for longer follow-up time.ConclusionsMonocyte count is associated prospectively inversely with the risk of developing CMM in older individuals, while BMI is associated positively in men, suggesting a mechanistic involvement of factors related to monocytes and subcutaneous adipose tissue in melanoma development. An inverse association with ABSI closer to diagnosis may reflect reverse causality or glucocorticoid resistance.

#3011 Pathophysiological link between renal and cardiovascular disease in patients with type 2 diabetes mellitus: preliminary results from a proteomic study

Abstract Background and Aims Diabetic kidney disease (DKD) affects nearly 40% of people with diabetes and is the leading cause of chronic kidney disease (CKD). A high prevalence of cardiovascular disease (CVD) is known in this population. Indeed, DKD and CVD are often related and lead to worse outcomes in type 2 diabetes mellitus (T2D), i.e. cardiac fibrosis and CV events are frequently described in patients with DKD. However, specific associations and accurate prediction biomarkers for DKD and CVD progression in T2D are still lacking as various proteins may play a multi-mechanistic role. Lipocalin-2 (LCN2) is involved in several pathophysiological processes (inflammation, renal disease and cardiometabolic complications in CKD). Its leukocyte-chemoattractant effect has shown to reduce CVD in experimental models of cardiomyopathy when suppressed. Excess LCN2 in CKD is a determinant of disease progression, but also a potent mediator of cardiac injury in CKD. Insulin-like growth factor binding proteins (IGFBPs) also play an important role in cell homeostasis by regulating cell transcription, migration, and apoptosis. IGFBP-3 down-regulation has demonstrated to be a predictor of rapid renal progression in T2DM. On the other hand, IGFBP-6 increases when GFR drops, being involved in the pathophysiological process of CKD as an apoptosis-inducing protein In this context, a proteomic-based approach would optimise the clinical utility of multiple plasma biomarkers. The aim was to identify proteins associated with DKD, cardiac fibrosis (estimated by the PICP biomarker) and the presence of a new CV event. Method A prospective cohort of 91 T2D patients, with a minimum follow-up of 3 years (mean: 4 years) was analysed. We evaluated the association between rates of change in GFR and PICP during follow-up (fold-change: end/initial) and their interaction with the development of a composite of cardiovascular (CV) events: CV death, stroke, ischaemic heart disease, atrial fibrillation, valvular heart disease and CV-related hospitalisation. In addition, ninety-two proteins were quantified in serum samples using a multiplex proximity extension assay with high-throughput protein detection technology (Olink proteomics, Cardiometabolic panel). Associations between variations in these proteins and changes in PICP and eGFR (all expressed as fold change from baseline) were assessed using linear regression analyses adjusted for their respective baseline values. All analyses were adjusted by multiple testing (Benjamini-Hochberg, FDR = 0.05%) using R software. Results Sixty-eight (74.7%) men and 23 (25.3%) women were included in the analysis. The mean age at baseline was 65.8 years, and the mean follow-up was 4 years (minimum 3 years). Sixteen cardiovascular events were recorded. An inverse association was observed between GFR and PICP (p = 0.003). Interaction analysis showed that this correlation occurred only in patients with incident CV events (p for interaction <0.001) (Fig. 1). By proteomic analysis (Fig. 2) several proteins were found to be significantly related to one of the three parameters studied (change in GFR, change in PICP and change with cardiovascular event), of which 3 proteins presented an overlap for all the parameters analysed: Lipocalin 2 (LCN2) and Insulin-like growth factor binding proteins 3 and 6 (IGFBP3 and IGFBP6). Interestingly, LCN2 and IGFBP6 were more highly expressed in patients with CV events whereas IGFBP3 was downregulated in these patients. Conclusion In patients with DKD, worsening enal function is associated with elevated circulating levels of the collagen synthesis biomarker PICP, particularly in those who developed at least one CV event. The link shown with LCN2, IGFBP-6 and IGFBP-3 shed light on possible multi-mechanistic pathways involved in DKD and narrow the scope towards a common pathway involving an interaction between pro-apoptotic and local inflammatory factors.

#532 Association between blood flow measured within 30 days from AV access creation and the risk of thrombosis

Abstract Background and Aims The use of arteriovenous (AV) access for hemodialysis (HD) is hampered by the risk of dysfunction and thrombosis. Various factors affect the risk of AV access thrombosis, such as age, female sex, hematocrit, vessels’ diameter and anatomy, and patients’ comorbidities (e.g. diabetes mellitus, thrombophilia, chronic inflammatory disease). Previous studies have reported contradictory results on the prognostic value of intraoperative blood flow (Qa) measurements. Finally, only few studies have investigated the association between postoperative Qa measurements and thrombosis risk. Therefore, current guidelines report that there is not enough evidence to suggest routine assessment of AV access Qa for surveillance. This study aimed to analyze the association between Qa, measured at the first post-operative visit (within 30 days from creation), and thrombosis risk, in distal and proximal autologous AV fistulae (dAVF and pAVF), and AV grafts (AVG). Method This retrospective cohort study included all AV accesses created in San Paolo Hospital (Milan, IT) between January 1st 2013 and December 31st 2022, with a post-operative Qa measurement available within 30 days from the date of creation. AV accesses were classified as dAVF, pAVF and AVG. Qa was measured by ultrasound as the product of the cross-sectional area and the time-averaged mean velocity, in the feeding artery. The thrombosis-free survival of dAVF, pAVF and AVG was plotted using the Kaplan Meier method. The association between Qa and the risk of thrombosis was studied by Cox proportional hazard models, adjusted for patient's age and sex. Non-linearity was assessed using natural splines. Results A total of 218 AV accesses (92 dAVF, 76 pAVF, and 50 AVG) were created in 191 patients. At baseline, patients had a median age of 69 years, 70% were male, 42% were already on HD treatment, and overall, they had a high prevalence of hypertension, diabetes mellitus and cardiovascular comorbidities. At first post-operative visit, median Qa was 922 [698, 1278] ml/min, 1260 [917, 1825] ml/min, and 1665 [1195, 2508] ml/min, respectively for dAVF, pAVF, and AVG (p <0.001). During a median follow up time of 1.35 [0.55, 2.62] years, 66 AV access thrombosis occurred. The thrombosis-free survival rates for dAVF, pAVF and AVG were 84%, 97%, and 51% at 1 year, and 63%, 66%, and 19% at 5 years (Fig. 1). For dAVF we found a significant L-shaped association between Qa measured at the first post-operative visit and thrombosis risk, with the lowest risk found at Qa of 1289 ml/min and an exponential risk increase for dAVF with Qa <800 ml/min (Fig. 2). Particularly, for dAVF with Qa < 1289 ml/min, we found a 39% increased risk of thrombosis for every 100 ml/min decrease in Qa (aHR 1.39, 95% CI 1.10-1.75, p 0.006). In pAVF, Qa showed a trend of inverse linear association with the risk of thrombosis, although not reaching statistical significance (aHR 1.06, 95% CI 0.96-1.17, p 0.24, for every 100 ml/min decrease in Qa). In AVG, Qa was not associated with the risk of thrombosis (aHR 1.01, 95% CI 0.97-1.06, p 0.57, for every 100 ml/min decrease in Qa). Conclusion In our cohort we found that Qa, measured at the first post-operative visit, is associated with the risk of thrombosis in dAVF, but not in pAVF and AVG. In particular, in dAVF the association is non-linear with the lowest risk in our cohort found at Qa equal to 1289 ml/min, with an exponentially increasing risk for Qa <800 ml/min. Our findings suggest that post-operative flow assessment may be a useful tool to identify dAVF at higher risk of thrombosis and allow a closer monitoring or possible preventive interventions.

Micronutrient Patterns and Low Intake of Vitamin A, Vitamin D, Folate, Magnesium, and Potassium Among Prediabetes and Type 2 Diabetes Patients.

Background Assessing micronutrient intake is important in identifying deficiencies that may contribute to insulin resistance, poor glycemic control, and increased risk of diabetes-related complications. The study's objectives were to evaluate micronutrient intake in prediabetes (PD) and type 2 diabetes (T2DM) patients compared to recommended dietary intakes (RDI) and to determine the associations between the micronutrient patterns and both anthropometric measurements and biomarkers of diabetes. Methods This cross-sectional study was conducted on 349 patients with T2DM and 252 patients with PD. Micronutrient intake was evaluated using a validated food frequency questionnaire. Micronutrient patterns were extracted from factor analysis using principal component analysis with varimax rotation. Participants in the highest tertile were considered to have the highest adherence to the corresponding micronutrient pattern. Results T2DM patients had a significantly lower intake of vitamin E (9.4 ± 0.2 vs. 10.1 ± 0.3 mg; p = 0.048), vitamin D (44.3 ± 1.1 vs. 48.9 ± 1.7 IU; p = 0.020), and thiamin (1.3 ± 0.1 vs. 1.4 ± 0.1 mg; p = 0.013) compared to PD patients. All patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium and a significantly higher intake of vitamin B12 and copper compared to RDI. Three distinct micronutrient patterns were identified within each group. In the PD group, the Fe-Mn-Se pattern correlated significantly with waist circumference (WC) and fasting plasma glucose (FPG). The Vit.C-K-Folate pattern showed significant associations with body fat (BF). The Vit.B2-P-Vit.B12 pattern was significantly linked to WC, body mass index (BMI), BF, FPG, and serum insulin (SI). For the T2DM patients, the K-Folate-Mg pattern displayed an inverse and significant association with weight and WC. The Iron-Se-Vit.B3 pattern showed a significant association with low-density lipoprotein (LDL) cholesterol, triglycerides, and total cholesterol. The Vit.B2-P-Ca pattern was significantly associated with fasting plasma glucose (FPG). Conclusion This study demonstrated that T2DM patients had significantly lower vitamin E, vitamin D, and thiaminintake than PD patients. Both T2DM and PD patients had a significantly lower intake of vitamin A, vitamin D, folate, magnesium, and potassium compared to the RDI. Among the identified micronutrient patterns, only the K-Folate-Mg pattern exhibited a significant association withreduced body weight and WC.

#2836 Prevalence and risk factors associated with chronic kidney disease among type-2 diabetes mellitus patients – a single centre experience

Abstract Background and Aims Globally, diabetes mellitus is one of the major causes of increased morbidity. One of the key complications of T2D is chronic kidney disease (CKD). Current evidence demonstrates that people with type 2 diabetes (T2D) are at a higher risk of developing chronic kidney disease (CKD) with greater morbidity and mortality. So, we aimed to find out the prevalence of CKD among T2DM patients and to evaluate the correlation between age, duration of diabetes, HbA1c, and UACR with eGFR among T2DM patients. Method An observational cross-sectional study was conducted at department of medicine, tertiary care hospital for 2 months. Along with demographic and anthropometric data The following clinical data were collected: estimated glomerular filtration rate (eGFR), serum creatinine, urinary albumin creatinine ratio (UACR), and HbA1c levels. Spearman rank correlation was used to determine the correlation between eGFR and various parameters. Results A total of 96 patients were included in the study. 65% of the study participants were sedentary and 35% were physically active. 41 (42.7%) were obese and 21 (21.9%) were overweight. The mean Duration of diabetes is 5.62 ± 4.68 years. The mean estimated glomerular filtration rate (eGFR) is 74.33 ± 31.01 mL/min/1.73 m2. The Prevalence of CKD is 35.4%. 21.8% belongs to G3a category and 8.3% belongs to G3b category. Spearman's correlation coefficient test revealed negative correlation between eGFR and duration of diabetes, HbA1c and UACR (Spearman's correlation coefficient values are −0.577, −0.595 and −0.709 respectively). Conclusion In conclusion, nearly 1/3rd of study participants reported CKD. Our study provides consistent and recent clinical data showing an inverse association of eGFR with age and duration of diabetes. This study highlights that age and duration of diabetes are key parameters associated with declining renal functions in people with T2DM.

Adherence to physical activity recommendations and associations with self-efficacy among Norwegian adolescents: trends from 2017 to 2021

BackgroundThe crucial role of physical activity (PA) in promoting well-being and overall health of adolescents is widely acknowledged. Previous global studies have consistently revealed low adherence to PA recommendations among adolescents, emphasizing potential links between PA engagement and self-efficacy in school-based populations. However, there is a need for further exploration of this relationship, in particularly gender differences and taking into account the potential influences of the COVID-19 pandemic. The objective of this study is to provide a comprehensive description of adherence to PA recommendations and its associations with self-efficacy in Norwegian school-based adolescents over the period from 2017 to 2021.MethodsCross-sectional data on physical activity (PA) levels and self-efficacy among 13–19-year-old Norwegian adolescents were collected from the Norwegian Ungdata Survey during the period 2017 to 2021. The survey, conducted in Norwegian lower- and upper-secondary schools, was administered electronically during school hours. All data collected is anonymous and has received approval from the Norwegian Agency for Shared Services in Education and Research (SIKT). Statistical analyses were performed using SPSS software.ResultsGirls consistently exhibited lower adherence to PA recommendations (17.6–19.8%) compared to boys (27.7–31.1%) each year from 2017 to 2021 (all p < 0.01). Similarly, girls reported lower self-efficacy (14.1 to 14.8 out of 20) than boys (15.5 to 15.9) during the same period (all p < 0.01). Regression analyses highlighted robust positive associations between PA and self-efficacy in those adhering to PA recommendations (i.e., physically active at least 5 times a week) and strong inverse associations for those reporting inactivity (never active) in both girls and boys from 2017 to 2021.ConclusionAdolescents in Norway report PA adherence ranging from 15 to 30%, with girls consistently exhibiting lower adherence to PA recommendations and reporting lower self-efficacy than boys. Notably, there are substantial associations between self-efficacy and both adherence to PA recommendations and inactivity over time. These findings underscore the significance of promoting adherence to PA recommendations during adolescence, especially among girls. Policymakers in Norway should focus on initiatives to increase PA levels among adolescents in both lower and upper secondary schools.

Combined oral contraceptive utilization and uterine fibroid incidence: A prospective study in a cohort of African-American women.

Published associations between combined oral contraceptive use and uterine fibroid development have lacked prospective imaging with ultrasound to distinguish between incident and prevalent fibroids. The Study of Environment, Lifestyle, and Fibroids prospectively followed fibroid-free, African-American women (the group with the highest disease burden in the U.S.) to identify incident cases. We examined associations between combined oral contraceptive use and the 40-month cumulative risk of fibroids. History of hormonal contraceptive use was collected via telephone interview at enrollment. Fibroid identification was performed using transvaginal ultrasonography at enrollment, and at 20 and 40-months of follow-up. Inverse probability weights for exposures and censoring were used to construct weighted risk ratios (wRR) and weighted risk different (wRD) estimators which control for differences in fibroid risk factors between exposure groups. In addition, unweighted fully adjusted log-binomial regression models (aRR) were run for comparison. Of the 1,308 participants in the analysis sample, 70% had used combined oral contraceptives and 17% developed fibroids by 40 months. We observed an inverse association between ever use of combined oral contraceptives and cumulative fibroid incidence (wRR: 0.78; 95% Confidence Interval (CI): 0.60, 1.00; wRD: -0.05, 95% CI: -0.11, 0; aRR: 0.76, 95% CI: 0.60, 0.98). Fibroid incidence was greater in participants who started using combined oral contraceptives after age 17 years than among younger initiators, though the restriction to ever-users made this estimate less precise (wRR: 1.25; 95% CI: 0.89, 1.76; wRD: 0.04, 95% CI: -0.02, 0.10). No consistent patterns of fibroid incidence were seen among ever-users for duration of, or years since, last combined oral contraceptives use.

#2684 Free light chains levels in ANCA associated vasculitis: a new potential inflammatory biomarker

Abstract Background and Aims Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a systemic disease characterized by an immune-mediated process where inflammation plays a central role. The widely available serum biomarkers of inflammation are not always able to detect ongoing disease activity in ANCA-associated vasculitis (AAV) patients. Free light chains (FLCs) expression levels have been proposed as new promising biomarker in some immune-mediated and inflammatory diseases. The aim of this study is to evaluate the expression levels of FLCs in patients affected by AAV and investigate the potential effect of rituximab treatment on FLCs levels. Method We conducted a retrospective multicenter study enrolling AAV patients in complete remission of AAV (defined as BVAS/GPA = 0); those with clinical suspicion of underlying hematologic malignancy were excluded. We analyzed κ and λ FLCs serum concentrations and evaluated their correlation with biomarkers of immune system activation, such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum immunoglobulin (Ig) levels, serum C3 and C4 complement and albumin levels (which has a negative correlation with acute inflammatory phase). We assessed impact of rituximab (RTX) therapy within the last 6 months on the same laboratory parameters. Results A total of 137 patients with AAV were recruited, who were gender balanced, had an average age of 68 years and an estimated glomerular filtration rate of 68 (43-89) mL/min/1.73 m2. Fifty-one patients received rituximab treatment (RTX group), while 86 patients were on other immunosuppressive maintenance therapies (non-RTX group). In comparison to non-RTX group, patients treated with RTX experienced higher complement C3 levels, lower ESR levels and lower FLCs κ (p = 0.063) and λ (p = 0.013) levels. The differences between RTX and non-RTX groups in terms of FLCs were even more prominent after correction to total Ig concentration (p = 0.004 for κ /Ig and p = 0.003 for λ /Ig, respectively). Both, serum free κ and λ levels were found to correlate significantly with ESR (R = 0.55 and p < 0.001 for κ; R = 0.53 and p < 0.001 for λ) and albumin (R = ‒0.38 and p < 0.001 for κ; R = ‒0.33 and p < 0.001 for λ). Additionally, serum free κ levels showed an inverse association with C3 (R = ‒0.18 and p = 0.041). Conclusion In subjects with AAV, FLC levels were found to be associated with markers of inflammation and complement activation; hence FLCs levels may represent a promising biomarker for detection of subclinical inflammation in AAV patients on maintenance therapy. Rituximab therapy showed a potential to reduce the levels of markers of subclinical inflammation, including FLCs.

#2610 Low skeletal muscle mass and low skeletal muscle quality are associated with thoracic aorta calcification in dialysis patients

Abstract Background and Aims Cardiovascular disease (CVD) is the leading cause of mortality in dialysis patients. Thoracic aorta calcification (TAC) is a common cardiovascular complication in dialysis patients and is independently associated with CVD. Sarcopenia, particularly low skeletal muscle mass, has been found to be associated with increased cardiovascular risk in dialysis patients. This study aims to explore the relationship between skeletal muscle quality and skeletal muscle mass at the first lumbar vertebra (L1) level determined by opportunistic CT scans (chest CT) and TAC, with the goal of providing valuable opportunities for identifying and intervening in high-risk CVD patients. Method We included 2514 patients for cross-sectional analysis, who underwent dialysis in four centers in China from 2020 to 2023 and all had chest CT scans including the L1 level. Additionally, we conducted a follow-up study on TAC in patients who initiated dialysis between 2014 and 2019 as part of the earlier research, including 215 patients who had undergone at least two chest CT scans for cohort analysis. At the L1 level, we assessed skeletal muscle quality [by skeletal muscle density (SMD), HU] and skeletal muscle mass [by skeletal muscle index (SMI), cm2/m2] in dialysis patients. Measurements of thoracic aorta calcification scores (TACS) and calcification scores for three segments of the thoracic aorta, including ascending aorta calcification score (ATACS), aortic arch calcification score (AoACS), and descending thoracic aorta calcification score (DTACS), were obtained in dialysis patients. Patients were divided based on their annual calcification score growth rate: those with a rate greater than or equal to the average annual increase were classified into the rapid progression group, while those with a rate less than the average were classified into the slow progression group (including those with no progression). Multivariable linear regression models were employed to assess the relationships between SMI and SMD with TACS. Multivariable logistic regression models were used to evaluate the associations of SMl and SMD with the risk of rapid progression of TACS. Results The mean (SD) age of participants was 56 (15) years, with 58.2% being male. The prevalence of TAC was 82.2%, while the prevalence of ascending thoracic aorta calcification (ATAC), aortic arch calcification (AoAC), and descending thoracic aorta calcification (DTAC) was 21.4%, 75.3%, and 68.8%, respectively. Over an average follow-up period of 3.22 years, the progression rate of TAC was 85.6%. Comparing the highest quartile of SMD to the lowest quartile, a significant inverse association was observed with TAC (beta −1.19, 95% CI −1.55— −0.83; P < 0.001). Similarly, comparing the highest quartile of SMI to the lowest quartile, a significant inverse association was found with TAC (beta −0.59, 95% CI −0.92— −0.26; P = 0.001). SMI and SMD, as continuous variables, were both significantly negatively correlated with TAC. Higher SMD was associated with a reduced risk of rapid progression of TAC; after full adjustment, for every 1 SD increase in SMD, the risk of TAC rapid progression decreased by 46% (aOR 0.54, 95% CI 0.32—0.91; P = 0.021). SMI showed no significant association with the rapid progression of TAC. The associations of SMI and SMD with AoAC and DTAC were consistent with their associations with TAC, except for ATAC. The ROC curve analysis indicated that incorporating SMD into the model enhanced the discriminative ability for stratifying the risk of rapid progression of thoracic aorta calcification. Conclusion After adjusting for cardiovascular risk factors and inflammatory markers, higher skeletal muscle quality and higher skeletal muscle mass were significantly associated with lower TAC. Improving skeletal muscle quality in initial dialysis patients may reduce the risk of rapid TAC progression.

Dietary creatine is associated with lower serum neurofilament light chain levels.

Low creatine availability may be linked to an elevated risk of neuronal damage, yet this association remains inadequately explored at the population level. Utilizing 2013-2014 National Health and Nutrition Examination Survey data, the current study found a negative correlation between dietary creatine intake and serum levels of neurofilament light chain (NfL; a biomarker for neuronal damage) in a cohort of 1912 individuals (52.2% females) aged 20-75 years. This inverse association persisted even after adjusting for other nutritional variables known to influence neuronal viability. The observed pattern, where increased dietary creatine intake was associated with reduced circulating NfL levels, suggests potential protective effects of creatine against neuronal injury.

#745 Age and gender specific reference values for renal volume and association with risk factors for chronic kidney disease in a general population

Abstract Background and Aims Renal volume (RV) is associated with renal function and with a variety of cardiovascular risk factors (CVRF). We analyzed RV by magnetic resonance imaging (MRI) in a large population-based study (Study of Health in Pomerania; SHIP-TREND) and tested the influence of age, sex, smoking status, BSA, systolic and diastolic blood pressure, type 2 diabetes, HDL-C, LDL-C, estimated glomerular filtration rate (eGFR) and uric acid on RV. Method 1,815 participants without kidney disease (930 women) aged 21-81 years were included in our study. Right and left RV with and without body surface area (BSA) indexation were compared among three age groups (22-39 years, 40-59 years, 60-81 years) by median and interquartile range and tested separately in women and men. Results eGFR, uric acid, right and left RV were higher in men compared to women (all p < 0.001). Left kidney were larger than right kidneys (both sexes). With age, RV showed a continuously decreasing trend in women and an upside down U-shape relation in men. In multivariable linear regression models, current smoking (β = 14.96, 95% CI 12.12; 17.79), BSA (β = 97.66, 95% CI 90.4; 104.93), diastolic blood pressure (β = 0.17, 95% CI 0.01; 0.32), and eGFR (β = 0.57, 95% CI 0.50; 0.65) were positively associated with both left and right renal volume whereas uric acid (β = −0.03, 95% CI −0.05; −0.01) showed an inverse association with RV. Interestingly, the same eGFR correlated with higher RV in men compared to women. Conclusion Reference values for RV are different for age-groups and sex. For any given age, female kidneys are smaller than male kidneys. RV associates positively with eGFR, but for any chosen eGFR, renal volume in females is lower compared to males. RV decreases with age, but in men, RV first increases in the age group 40-59 years before finally decreasing with a faster decline after 60 years. This may reflect hyperfiltration and glomerular hypertrophy associated with the presence of CVRF.

#2370 Creatinine, cystatin C, muscle mass, and mortality: findings from a primary and replication population-based cohort

Abstract Background and Aims Creatinine measures are used as initial test to derive eGFR and confirmatory testing with circulating cystatin C is recommended when creatinine-based eGFR is considered less accurate due to deviant muscle mass. Low muscle mass is associated with increased risk of premature mortality. However, the associations of circulating creatinine and cystatin C with muscle mass and mortality remain unclear and require further investigation to better inform clinical decision-making. This study aimed to disentangle these complex relationships and better inform clinical decisions on marker reliability in varying settings by investigating whether cystatin C adjustment could clarify the associations of circulating creatinine with muscle mass and mortality. Method We conducted a prospective, observational cohort study including 8, 437 community-dwelling adults enrolled in the Dutch PREVEND study and 5, 033 in the U.S. NHANES. Associations of serum creatinine and/or cystatin C with muscle mass surrogates and mortality were quantified with linear and Cox proportional-hazards regression, respectively. Missing observations in covariates were multiply imputed using Substantive Model Compatible Fully Conditional Specification. Results Mean (SD) age of PREVEND and NHANES participants (50% and 48% male) were 49.8 (12.6) and 48.7 (18.7) years, respectively. Median (Q1-Q3) serum creatinine and cystatin C were 0.79 (0.69-0.90) and 0.90 (0.70-1.00) mg/dl and 0.87 (0.78-0.98) and 0.91 (0.80-1.10) mg/l, respectively. Higher serum creatinine was associated to greater muscle mass, while serum cystatin C was not associated with muscle mass. Adjusting both markers for each other strengthened the positive relationship between serum creatinine and muscle mass and revealed an inverse association between serum cystatin C and muscle mass. In the PREVEND cohort, 1, 636 (19%) deaths were registered over a median follow-up of 12.9 (5.8-16.3) years with a 10-year mortality rate (95% CI) of 7.6% (7.1-8.2%). In the NHANES, 1, 273 (25%) deaths were registered over a median follow-up of 17.9 (17.3-18.5) years with a 10-year mortality rate of 13.8% (12.8-14.7%). Both markers were associated with increased mortality (Fig. panels A and B). Notably, when adjusted for each other, higher serum creatinine was associated with decreased mortality (Fig. panel C), while the association between serum cystatin C and increased mortality strengthened (Fig. panel D). The shapes of the associations in the PREVEND study and NHANES were almost identical. Conclusion The strong association between serum creatinine and muscle mass challenges its reliability as GFR marker, necessitating a more cautious approach in its clinical use. The minimal association between serum cystatin C and muscle mass supports its increased use as a more reliable alternative in routine clinical practice.

Susceptibility to Electronic Cigarette and Consumption Patterns in Adolescents.

The use of electronic cigarettes (ECs) is a major problem globally. Susceptibility and curiosity are important factors that develop prior to the onset of substance use, such as ECs, and are therefore considered as predictors. Both factors are used to obtain an extended index of susceptibility (ESIe-c), which allows the identification of adolescents who are at risk of starting to use these devices. The aim of this study was to determine the prevalence of EC consumption and to assess the association of possible predictors with susceptibility to use and experimentation with ECs among adolescents. A cross-sectional study was carried out in 377 adolescents (53.0% female). Participants were compared according to their experimentation with ECs. A total of 45.9% had already used electronic cigarettes, and 20.8% were current users. Among those who had not tried electronic cigarettes, 43.3% had a medium-high susceptibility to EC initiation. Consumption among close friends, receiving offers of consumption and alcohol consumption were associated with initiation. There was an inverse association between a medium susceptibility index electronic cigarette score and the consumption of cigarettes and positive affect; on the other hand, the lack of premeditation was associated with a higher susceptibility index score. Intrapersonal factors and social factors seem to influence the ESIe-c and onset of EC use, respectively. The main conclusion in this study is that susceptibility is influenced by intrapersonal factors such as affectivity and impulsivity through the lack of premeditation, and by social factors such as EC consumption by best friends.

The role of plant-based dietary patterns in reducing COVID-19 risk and/or severity in adults: A systematic review and meta-analysis of observational studies

Background & AimsPlant-based dietary patterns (PBDs) might protect against COVID-19 risk and reduce severity of infection. This systematic review with meta-analysis aimed to examine the association between PBDs and risk of COVID-19 infection, hospitalization, intensive care unit (ICU) admission, and/or mortality, in adults. MethodsPubmed, Embase, CINAHL and Web of Science were searched for observational studies, published in English up to 3rd April 2023, comparing the highest with the lowest adherence to a specific PBD. Data were screened, extracted, and risk of bias assessed using the Newcastle-Ottawa Quality Assessment Scale, by independent reviewers. ResultsSeven studies (one cross-sectional, three case-control, and three prospective cohort), reporting on 649,315 participants, were eligible. Across them, there were 8,512 events of COVID-19 infection (six studies), and 206 events of COVID-19 hospitalization (four studies), in addition to one study reporting on a composite hospitalization outcome (740 events). The pooled analysis showed that PBDs are associated with a 59% (odds ratio (OR)=0.41, 95% confidence intervals (CI) 0.23-0.59; two studies) and 18% (OR=0.82, 95% CI 0.78-0.85; three studies) reduction in COVID-19 infection risk in case-control and cohort studies, respectively. The pooled analysis of one case-control and two cohort studies showed an inverse association between high adherence to a PBD and risk of COVID-19 hospitalization (OR=0.38, 95% CI 0.04-0.72). ConclusionFindings suggest a protective role of PBDs against the risk of COVID-19 infection and severity. More studies are needed to establish the association between PBDs and risk of ICU admission and mortality due to COVID-19.

Prevalence of high-risk human papillomavirus genotypes in outpatient Malian women living with HIV: a pilot study.

Long-term exposure to high-risk human papillomavirus (Hr-HPV) is a well-known necessary condition for development of cervical cancer. The aim of this study is to screen for Hr-HPV using vaginal self-sampling, which is a more effective approach to improve women's adherence and increase screening rates. This pilot study included a total of 100 Women living with HIV (WLWHIV), recruited from the Center for Listening, Care, Animation, and Counseling of People Living with HIV in Bamako. Hr-HPV genotyping was performed on Self-collected samples using the Cepheid GeneXpert instrument. The median age of WLWHIV was 44 (interquartile range [IQR], 37-50) years. Approximately 92% of the study participants preferred self-sampling at the clinic, and 90% opted to receive result notifications via mobile phone contact. The overall prevalence of Hr-HPV among study participants was 42.6%, and the most frequent Hr-HPV sub-types observed were HPV18/45 (19.1%), HPV31/35/33/52/58 (13.8%), and HPV39/68/56/66 (12.8%), followed by HPV16 (5.3%), and HPV51/59 (5.3%). WLWHIV under 35 years of age had a higher frequency of Hr-HPV compared to their older counterparts, with rates of 30% versus 11.1% (p = 0.03). The duration of antiretroviral treatment showed an inverse association with Hr-HPV negativity, with patients on treatment for 15 (IQR, 10-18) years versus 12 (IQR = 7-14) years for Hr-HPV positive patients (95% CI [1.2-5.8], t = 3.04, p = 0.003). WLWHIV with baseline CD4 T-Cell counts below 200 exhibited a higher frequency of Hr-HPV compared to those with baseline CD4 T-Cell counts above 200 (17.9% versus 1.9%, p = 0.009). However, other demographics and clinical factors, such as marital status, age of sexual debut, parity, education, history of abortion, history of preeclampsia, and cesarean delivery, did not influence the distribution of Hr-HPV genotypes. Our findings indicate that WLWHIV under the age of 35 years old exhibited the highest prevalence of Hr-HPV infection, with HPV18/45 being the most prevalent subtype. Additionally, WLWHIV with baseline CD4 T-Cell counts below 200 showed the highest infection rates.

Racial and ethnic differences in epithelial ovarian cancer risk: an analysis from the Ovarian Cancer Association Consortium.

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander (NHPI) women. Participants included 1734 Asian (785 cases, 949 controls), 266 NHPI (99 cases, 167 controls), 1149 Hispanic (505 cases, 644 controls), and 24,189 White (9,981 cases, 14,208 controls) women from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (p ≤ 0.02) was observed for oral contraceptive (OC) use, parity, tubal ligation and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in NHPI and Asian women. The inverse association for tubal ligation with risk was most pronounced for NHPI participants (OR=0.25, 95% CI 0.13-0.48), versus Asian and White participants, respectively (OR=0.68, 95% CI 0.51-0.90; OR=0.78, 95% CI 0.73-0.85). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could in part be due to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies.

Fish consumption and depression in Korean population: The Korea National Health and Nutrition Examination Survey, 2013–2021

BackgroundEpidemiological studies in some populations showed that dietary intake of fish may be inversely associated with depression, but large studies in Korean population are limited. Thus, we investigated the association between fish consumption and depression, considering the serving size of fish, in Korean adults. MethodsThis study was based on the data from the Korea National Health and Nutrition Examination Survey (2013−2021), which is a large nationally representative study of Korean population. Fish consumption was assessed with a 24-hour dietary recall, and physician-diagnosed depression status was assessed using questionnaires from the health interview survey. Multivariable logistic regression models adjusting for demographic, lifestyle, and dietary factors were used to calculate odds ratios (OR) and 95 % confidence intervals (CI) for depression. ResultsA total of 31,632 adults aged 19–64 years were included in the analysis. After adjusting for covariates, highest fish consumption (≥4 servings/week) was significantly associated with 26 % lower odds of depression compared to the lowest fish consumption (<1 servings/week) (OR 0.74; 95 % CI, 0.60–0.92, P for trend = 0.007). A similar inverse association was found in female adults (OR 0.76; 95 % CI, 0.59–0.97, P for trend = 0.018), but no significant association was found in male adults (OR 0.75; 95 % CI, 0.49–1.15, P for trend = 0.223). LimitationsSince KNHANES is a cross-sectional study, it is difficult to evaluate the causal relationship between fish consumption and depression risk. ConclusionsThis study results suggest that high fish consumption is associated with lower risk of depression in Korean adults, especially in female adults.

Comparison of Heart Rate Variability in Thai Older Adults with Hypertension, Pre-Hypertension, and Normotension.

This study aims to compare HRV variables across three cohorts: normotensive (NT), prehypertensive (pre-HT), and hypertensive (HT) and to assess the relationship between the blood pressure (BP) and HRV parameters. Employing a cross-sectional design, 64 older participants were categorized based on the Joint National Committee's criteria into NT (n = 10), pre-HT (n = 33), and HT (n = 21) groups. Anthropometric data, lipid profiles, and HRV indices were evaluated. HRV data were obtained from the Polar V800 chest strap device using HRV Kubios software for data analysis of short-term recordings lasting 10 minutes. This analysis encompasses both time and frequency domain assessments. The time domain includes the standard deviation of NN intervals (SDNN), the root mean square of successive RR interval differences (RMSSD), and the percentage of successive RR intervals differing by over 50 ms (pNN50). The frequency domain includes low frequency (LF), high frequency (HF), and the ratio of LF-to-HF power (LF/HF). Data were statistically analyzed via one-way analysis of variance (ANOVA) and Pearson correlation. The HT group exhibited significantly lower values in SDNN, pNN50, LF power, and HF power in comparison to the NT group (P < 0.05). Moreover, the HT group had a significantly lower SDNN value compared to the pre-HT group (P < 0.05). Inverse associations were uncovered between systolic and diastolic blood pressure and SDNN, pNN50, and HF power (P < 0.05). Multiple regression further highlighted the significance of systolic and pulse pressure concerning HF power (P < 0.05). HRV indices are reduced in Thai older adults with HT compared with those with NT. Monitoring HRV in older adults can provide valuable insights into autonomic function and cardiovascular disease risk.