Inverse Association Research Articles

489-P: Familial Hypercholesterolemia Is Not Associated with Type 2 Diabetes Presence in Patients Undergoing a Genetic Cascade Screening Program

Introduction and Objective: Epidemiological and genetic studies have shown an inverse association between hypercholesterolemia and type 2 diabetes (T2DM), particularly in Familial Hypercholesterolemia (FH). Defects in LDL receptor gene (LDLR) may lead to beta-cell apoptosis, and statin therapy might complicate it. The study evaluated biomarkers related to T2DM severe hypercholesterolemic patients in a genetic FH cascade screening program. Methods: Cross-sectional study, 1,431 patients with severe hypercholesterolemia, with FH-causing genes or not. T2DM was diagnosed by ADA criteria or by the use of antidiabetic medications. Results: A total of 797 patients with genetically confirmed FH (96.6% with variations in the LDLR, 47.7 ± 15.0 years; 56.7% female; baseline LDL-C 199 ± 74 mg/dL, body mass index (BMI) 27.55 ± 4.85 kg/m², 27.1% with previous cardiovascular disease, (CVD)) and 634 patients without FH variants (56.04 ± 12.6 years; 67.4% female; baseline LDL-C 191 ± 66 mg/dL, BMI: 26.91 ± 5.05 kg/m², 25.1% CVD were analyzed. FH patients were younger (p<0.001), leaner (p=0.004), and had a higher proportion of males (p< 0.001). At baseline, 67.8% of FH received statin therapy, compared to 87.4% of non-FH patients (p<0.001). The prevalence of T2DM at baseline was 13.4% in the FH group vs. 21.8% (odds ratio-OR 0.555, 95%CI 0.420-0.732, p<0.001). However, this association lost significance after multivariate analysis. Factors independently associated with T2DM included age (OR: 1.049, 95% CI: 1.032-1.066, p < 0.001), BMI (OR: 1.111, 95% CI: 1.073-1.151, p < 0.001), triglycerides (OR: 1.003, 95% CI: 1.001-1.005, p< 0.001), hypertension (OR: 2.845, 95% CI: 1.886-4.292, p < 0.001), and previous CVD (OR: 1.901, 95% CI: 1.324-2.729, p < 0.001). No association was observed with genetic defects or statin therapy. Conclusion: Among this group of hypercholesterolemic individuals, T2DM was not less prevalent in those with molecularly confirmed FH. Disclosure F.C.P. Maia: Other Relationship; Eli Lilly and Company. Speaker's Bureau; Amgen Inc, Novo Nordisk. M.H. Miname: Speaker's Bureau; Novartis Pharmaceuticals Corporation, Ache, Novo Nordisk. K.A.P. Maia: Research Support; Lilly USA LLC. Speaker's Bureau; Novo Nordisk, Novartis Pharmaceuticals Corporation, Servier Laboratories. H. Takematsu: None. P.G. Lorente: None. M.H. Mizuta: None. R. Santos: Research Support; Amgen Inc, Sanofi. Consultant; ESPERION Therapeutics, Inc., Daiichi Sankyo. Speaker's Bureau; Daiichi Sankyo. Research Support; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Kowa Company, Ltd, Novartis Pharmaceuticals Corporation. Speaker's Bureau; Novo Nordisk. Research Support; Ionis Pharmaceuticals. Speaker's Bureau; Novartis Pharmaceuticals Corporation.

Nutritional profile of the diet according to circadian clock genes in the European Prospective Investigation into Cancer and Nutrition (EPIC) chronodiet study.

Nutritional profile of the diet according to circadian clock genes in the European Prospective Investigation into Cancer and Nutrition (EPIC) chronodiet study.

Coffee consumption and mortality in colorectal cancer patients: Does the co-existence of cardiometabolic disease matter?

Although coffee consumption may have a U-shaped nonlinear relationship with all-cause mortality in colorectal cancer (CRC) patients, it is unclear whether this association could differ in the presence of prevalent cardiometabolic disease (CMD). Therefore, we assessed the association of coffee consumption with mortality in CRC patients stratified by CMD status at diagnosis. We used data from a prospective cohort of 1769 patients with stage I-III CRC. Coffee consumption was self-reported using a food frequency questionnaire at diagnosis. Mortality data were retrieved from the Personal Records Database. CMD was defined as prevalent cardiovascular disease (CVD) or diabetes at diagnosis of CRC. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards models with and without restricted cubic splines (RCS) while adjusting for relevant confounders. During a median (quartile1, quartile 3) follow-up of 7.7 (5.6, 9.3) years, we observed 128 deaths in participants without CMD and 250 deaths in those with CMD. The five-year survival rate was 88% and 83% for participants without and with CMD, respectively. Among participants without CMD, consuming 2-4 cups/d and >4 cups/d of coffee compared to <2 cups/d was associated with a 60% (HR: 0.40, 95% CI: 0.26-0.63) and a 41% (HR: 0.59, 95% CI: 0.39-0.89) lower risk of mortality, respectively. In participants with CMD, consuming 2-4 cups/d of coffee compared to <2 cups/d was associated with a 31% (HR: 0.69, 95% CI: 0.51-0.93) lower risk of mortality, while no association was observed for >4 cups/d (HR:0.82, 95%CI:0.59-1.14). The RCS showed a U-shaped, nonlinear inverse association between coffee consumption and mortality in participants without and with CMD (P-value for nonlinearity: 0.001), but the inverse association was stronger in those without CMD. We observed a U-shaped, nonlinear inverse association between coffee consumption and mortality in CRC patients regardless of their CMD status. More mechanistic studies are needed to understand how consuming coffee may lower mortality risk in CRC patients.

Evaluating the association between dietary zinc intake and cancer risk: Insights from NHANES 2021–2023 with stratified and multivariate analyses.

e22589 Background: Various studies have examined the relationship between dietary zinc (Zn) intake and cancer risk. While some have shown no substantial link, others have proposed an inverse association with colorectal and pancreatic cancers. Given these inconsistencies, we aimed to assess the relationship between dietary Zn intake and cancer diagnosis while adjusting for demographic variables. Methods: A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) of the U.S. population from 2021 to 2023. Participants' Zn intake and cancer diagnoses were assessed through surveys. Chi-square tests were used to examine the association followed by logistic regression analyses to adjust for potential confounders, including age, gender, and smoking status. A stratified analysis by age groups was conducted to explore potential age-related differences, with a p-value &lt;0.05 being significant. Results: A total of 11,933 respondents' data was analyzed consisting of a majority of females(53.28%). Non-Hispanic whites(52.10%) were the most common ethnicity and 60–79 years(33.75%) represented the most common age group. 61.35% had low Zn intake with the mean ± SD value being 8.12 ± 2.5 mg/day. The chi-square test showed a significant association between Zn intake and cancer diagnosis(χ²=223.5478, p&lt;0.0001). Logistic regression analysis revealed that age was the strongest predictor of cancer diagnosis with individuals aged 60–79 years having significantly higher odds compared to those under 20(OR&lt;0.001, p&lt;0.0001). Zn intake and smoking were not significantly associated, although light smokers showed a marginally protective effect(OR=0.431, 95% CI=0.190–0.979). Stratified analysis showed an inverse association between Zn intake and cancer among the 41-60 age group(p=0.0114). The ROC curve analysis indicated poor predictive ability of Zn intake for cancer diagnosis(c-statistic of 0.520). Conclusions: Unlike previous studies showing a protective effect of Zn intake against various cancers, our findings indicate no overall significance. A notable inverse relationship was observed in the 41–60 age group, suggesting potential age-dependent effects. These findings challenge existing data and the complex relationship between Zn and cancer risk. Further studies are needed to explore the findings.

Dietary fiber intake, genetic predisposition of gut microbiota, and the risk of metabolic dysfunction-associated steatotic liver disease.

Dietary fiber intake, genetic predisposition of gut microbiota, and the risk of metabolic dysfunction-associated steatotic liver disease.

High adherence to a food guide may be associated with lower 24-h urinary sodium excretion and sodium-to-potassium ratio, and higher potassium excretion.

High adherence to a food guide may be associated with lower 24-h urinary sodium excretion and sodium-to-potassium ratio, and higher potassium excretion.

Clinical trials of vitamin D supplementation and cardiovascular disease: A synthesis of the evidence.

Clinical trials of vitamin D supplementation and cardiovascular disease: A synthesis of the evidence.

Obesity, chemotherapy dosing, and toxicity: Results from the Optimal Breast Cancer Chemotherapy Dosing study.

547 Background: ASCO guidelines state that most cytotoxic drugs should be dosed according to full body surface area (BSA) without limiting the dose on the basis of obesity. This approach is supported by a lack of evidence to suggest that patients with obesity, when fully-dosed, experience higher risk of toxicity. Indeed, historical evidence suggests that obese, fully-dosed patients may experience lower risk of neutropenia than normal weight patients. However, questions remain regarding the representativeness of historical trial data on which this evidence is based. We examined this issue in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study. Methods: The OBCD Study is a real-world cohort of 34,109 women diagnosed with stage I-IIIA breast cancer at Kaiser Permanente Northern California and Kaiser Permanente Washington between 2004-2019. Among women receiving the full dose of chemotherapy at treatment initiation (≥90% of intended dose, n = 7,644), we examined risk of toxicities in women with obesity (BMI ≥30 kg/m 2 ) compared to non-obese women (BMI 18.5- &lt; 30 kg/m 2 ). We examined hematologic (neutropenia, anemia, thrombocytopenia) and non-hematologic (nephrotoxicity, hepatotoxicity, neuropathy, and cardiotoxicity) toxicities. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression, adjusted for covariates including prevalent comorbid conditions. Secondary analyses examined associations pertaining to specific BMI groups and also stratified by administration schedule (standard vs dose-dense). Results: Fully-dosed patients with obesity experienced lower risk of neutropenia (HR: 0.80; 95% CI: 0.73-0.88) and any hematologic toxicity (HR: 0.83; 95% CI: 0.75-0.91) but increased risk of neuropathy (HR: 1.34; 95% CI: 1.18-1.52), cardiotoxicity (HR: 2.30; 95% CI: 1.13-4.67), and non-hematologic toxicities overall (HR: 1.31; 95% CI: 1.15-1.48). The strength of these associations increased with increasing BMI category. The inverse association between obesity and hematologic toxicity was evident for standard administration schedules (HR: 0.54; 95% CI: 0.45-0.66) but not dose-dense schedules. However, the positive association between obesity and non-hematologic toxicities persisted regardless of administration schedule. Conclusions: Women with obesity given the full BSA-determined chemotherapy dose are less likely to experience neutropenia than fully-dosed non-obese women. Importantly, this holds among patients with more severe obesity, but not when restricted to newer dose-dense administration schedules. Findings also suggest that fully-dosed patients with obesity may experience higher risks for neuropathy and cardiotoxicity. These findings highlight the importance of better understanding the risks and benefits of dosing strategies as treatments and patient populations continue to evolve.

Deciphering the association of cholesteryl ester transfer protein (CETP) gene polymorphisms with high-density lipoprotein cholesterol (HDL-c) levels in the Bangladeshi population.

Deciphering the association of cholesteryl ester transfer protein (CETP) gene polymorphisms with high-density lipoprotein cholesterol (HDL-c) levels in the Bangladeshi population.

Loneliness and cognitive function in older adults living in Latin America: A systematic review.

Loneliness and cognitive function in older adults living in Latin America: A systematic review.

Epigenome-wide association study of pregnancy exposure to green space and placental DNA methylation.

Epigenome-wide association study of pregnancy exposure to green space and placental DNA methylation.

Pitavastatin-induced cholesterol deficiency elevates serum biomarkers associated with statin-related adverse effects in rats.

Statins are prescribed to manage hypercholesterolemia. While effective, these medications are associated with adverse effects, particularly myopathy. Cholesterol is essential for muscle function, and its depletion - especially by lipophilic statins - may contribute to muscle damage. Pitavastatin mainly targets hepatic cholesterol synthesis with minimal direct effect on muscle tissue. This study investigates the impact of pitavastatin-induced cholesterol depletion on skeletal muscle. Male Sprague-Dawley rats were divided into three groups: control (n = 10), pitavastatin-treated on a normal diet (ND, n = 10), and pitavastatin-treated on a high-cholesterol diet (HCD, n = 10). Pitavastatin (15 mg/kg/day) was administered orally for 6 weeks. Serum lipid profile, hepatic injury markers (alanine aminotransferase, aspartate aminotransferase), muscle damage markers (creatine phosphokinase), and bone metabolism indicators (alkaline phosphatase, calcium, phosphate, or magnesium) were analyzed. Pitavastatin significantly reduced total cholesterol and low-density lipoprotein cholesterol in both ND and HCD groups (P < 0.05) without affecting triglycerides, high-density lipoprotein cholesterol, or very-low-density lipoprotein. The ND group showed significant elevations in alanine aminotransferase, aspartate aminotransferase, and creatine phosphokinase compared to the control and HCD groups (P < 0.05), suggesting cholesterol depletion contributes to hepatic and muscle damage. The HCD group exhibited reduced elevations in these markers, indicating a protective role of dietary cholesterol. No significant differences were observed in alkaline phosphatase, calcium, phosphate, or magnesium. Bivariate correlation analysis showed an inverse association between total cholesterol and liver enzyme markers. Pitavastatin-induced cholesterol depletion increased hepatic and muscle damage markers. Dietary cholesterol may mitigate these effects, highlighting the importance of cholesterol homeostasis in statin therapy.

Higher PFOS exposure associated with higher SHBG in third trimester. The Odense Child Cohort.

Higher PFOS exposure associated with higher SHBG in third trimester. The Odense Child Cohort.

A Longitudinal Study of Organizational Stressors and Mental Health in the Irish Olympic Team Before and After the “Tokyo 2020” (2021) Olympic Games

Aims: The primary aim of the present study was to assess the relationship between organizational stressors and mental health and well-being indicators of the Irish Olympic Team before and after the “Tokyo 2020” Olympic Games. A secondary aim was to examine the differences in mental health and well-being between the athletes and staff of Team Ireland pre- and post-Games. Method: The Irish Olympic Team comprised 271 members (116 athletes and 155 team staff). Participants were sent an online survey package 2 weeks pregames (Time 1) and 4 weeks postgames (Time 2). A total of 98 participants (36% response rate) responded at Time 1, and 70 participants (26% response rate) responded at Time 2. Measures included the Organizational Stressor Indicator for Sport Performers, the Mental Health Continuum–Short Form, and the Sport Mental Health Assessment Tool 1. Results: There was a significant inverse association between organizational stressors and mental well-being at both Time 1 (β = −0.46) and Time 2 (β = −0.35) and from pre- to post-Games (β = −0.48). There was a significant positive association between organizational stressors and risk of mental health symptoms at both Time 1 (β = 0.69) and Time 2 (β = 0.67) and from pre- to post-Games (β = 0.34). At Time 1, team staff (75%) reported significantly greater risk of mental health symptoms than athletes (50%); however, at Time 2, athletes (80%) reported significantly greater risk of mental health symptoms than staff (50%). The overall number of participants flourishing decreased from pre- (43%) to post-Games (31%). Conclusion: Findings have implications for mental health support provision, which tends to be athlete focused but might forget about team staff, and to consider preevent provision but to also not forget about postevent care.

Prognostic Implications of Magee Equation 3 and Residual Cancer Burden in Patients Receiving Neoadjuvant Chemotherapy for Hormone Receptor-Positive HER2-Negative Breast Cancer.

Prognostic Implications of Magee Equation 3 and Residual Cancer Burden in Patients Receiving Neoadjuvant Chemotherapy for Hormone Receptor-Positive HER2-Negative Breast Cancer.

Healthy lifestyle and the risk of endometrial cancer.

The incidence and mortality rate of endometrial cancer (EC) is increasing worldwide. Modifiable lifestyle factors associated with an increased or decreased risk of cancer typically cluster. Therefore, this study aimed to investigate the association between a healthy lifestyle, measured with a Healthy Lifestyle Index (HLI), based on diet, smoking, alcohol consumption, physical activity and Body Mass Index (BMI), and the risk of EC. A case-cohort analysis was conducted using data from the prospective Netherlands Cohort Study on Diet and Cancer (n = 62,573). At baseline in 1986, participants (aged 55-69) completed a questionnaire on potential cancer determinants. Data on aforementioned risk factors were used to calculate an HLI-score, ranging 0-20, with higher scores reflecting a healthier lifestyle. Cox regression analyses were used to estimate hazard ratios (HR's) and 95 % confidence intervals (CI's) for the association between HLI-score and EC risk in 414 cases and 1593 subcohort women, after 20.3 years of follow-up. After stratification by smoking status, Cox regression was applied using an HLI-score without smoking. The HR for the total HLI score was 0.86 (95 %CI 0.78-0.94) per 1 standard deviation (SD) increment. The HR for the HLI score without smoking component was 0.75 (95 %CI 0.67-0.83) for non-smokers (never smoked or former smoker >10 years ago) and 0.85 (95 %CI 0.70-1.02) for recent smokers (current or former smoker <10 years ago), all per 1 SD increment. Sensitivity analyses excluding each HLI component show that BMI and physical activity are the main drivers of the inverse association between HLI-score and EC. A healthier lifestyle, measured with an HLI based on diet, alcohol consumption, physical activity, BMI and smoking is associated with a reduced EC risk. The association is stronger for non-smokers.

The role of emotional intelligences, self-esteem and time management among young adults

This study explored the relationships among emotional intelligence, self-esteem, and time management in 202 young adults aged 18 to 26. Employing a quantitative, correlational, cross- sectional design, standardized self-report scales were used to assess these constructs. The research aimed to understand their interconnections and potential implications. Findings revealed a significant negative correlation between self-esteem and time management, suggesting higher self- esteem was associated with poorer time management. No significant correlation was found between emotional intelligence and time management, and a significant negative correlation emerged between emotional intelligence and self-esteem. Regression analysis confirmed self- esteem as a significant negative predictor of time management, while emotional intelligence did not. Mediation analysis indicated that emotional intelligence did not mediate the relationship between self-esteem and time management. The study concluded that the relationships between these factors in young adults are complex and not always as expected. The inverse association between self-esteem and time management challenges conventional assumptions. The lack of a significant link between emotional intelligence and time management suggests emotional abilities alone may not ensure effective time regulation. The findings emphasize the need for integrated interventions combining emotional and self-perceptual development with explicit time management training.

Association of planetary health diet index with depression and mortality in the United States

BackgroundGiven the changes in global environmental conditions and dietary patterns, understanding the potential impact of dietary factors on the risk of depression is crucial. The Planetary Health Diet Index (PHDI) is a dietary scoring system that integrates human health and environmental sustainability. This study aims to evaluate the association between the PHDI, the risk of depression, and mortality.MethodsData from the National Health and Nutrition Examination Survey 2005–2018. Depression was assessed using Patient Health Questionnaire-9 (PHQ-9), with a score ≥ 10 indicating depression. PHDI calculated from 14 self-reported dietary groups, ranges from 0 to 140. Multivariable weight logistic and linear regression explored the association of PHDI with depression and total PHQ-9 score. Cox proportional hazards regression examined PHDI associations with mortality. Additional analyses included restricted cubic spline (RCS), threshold analyses, subgroup analyses, and multiple imputation.ResultsAdjusting for confounding variables, each 10-point increase in PHDI was associated with an 11% lower risk of depression (OR = 0.89, 95% CI = 0.84, 0.94), 0.13 score of total PHQ (β=-0.13, 95% CI=-0.18, -0.08), and 17% of all-cause mortality (HR = 0.83, 95% CI = 0.73, 0.95). RCS indicated an inverse L-shaped association between PHDI and depression, and threshold effects analyses showed that the above associations were more significant in those with PHDI ≥ 76.01.ConclusionsAdherence to the PHDI dietary pattern is associated with a reduced risk of both depression and all-cause mortality. PHDI may provide dietary guidance for the early prevention and intervention of depression.

The path to mental health: Associations between walkability and depression prevalence in west Virginia

Despite increasing awareness of walkable neighborhoods’ health benefits, the relationship between walkability and mental health remains unclear. This study examined the relationship between walkability and depression in West Virginia which has the highest rate of depression according to 2023 CDC report. Increasing neighborhood walkability was hypothesized to result in a reduction in mental health encounters. Using the most recent census tract boundaries in West Virginia (N = 546), National Walkability Index (NWI) scores were aggregated from 2019 block group data to tract-level averages. Depression prevalence was obtained from CDC PLACES, and population data were sourced from the U.S. Census Bureau. Multiple imputations were applied to address missing data as the result of mismatches between the 2019 NWI and 2024 tract boundaries, and regression analyses were conducted using both imputed and complete-case datasets. In the imputed model, no significant association was found between walkability and depression (β = 0.03, p = 0.631). However, the complete-case model revealed a small but statistically significant positive relationship between walkability and depression (β = 0.04, p = 0.046). Population showed a consistent inverse association with depression in both models. Contrary to prior assumptions, higher walkability was associated with increased depression in the complete-case analysis. These findings highlight the complex relationship between the built environment and mental health and suggest that walkability alone may not be protective against depression. Future studies should incorporate additional contextual and sociodemographic factors while examining such a relationship.

High expression of HECW1 is associated with the poor prognosis and cancer progression of gastric cancer

BackgroundThe E3 ubiquitin ligase HECW1 was found to be involved in ubiquitination modifications during malignant progression of multiple tumors. However, the prognostic role of HECW1 expression in gastric cancer (GC) remains unclear.MethodsThe Tumor Immunoassay Resource (TIMER2.0) system evaluated the association of HECW1 with tumor-infiltrating lymphocytes in carcinomas. The UALCAN assessed HECW1 mRNA expression levels in GC tissues and examined their associations with clinicopathological characteristics. The Kaplan Meier-plotter analyzed the effect of HECW1 on the survival of GC patients. The cBioPortal retrieved information about genetic variants in HECW1 gene. Protein‒protein interaction (PPI) networks associated with HECW1 were explored using the STRING database. The functional effects of HECW1 on GC cells were evaluated through proliferation (Cell Counting Kit-8), apoptosis (Flow cytometry), and migration (Transwell and wound healing assays). The RNA-Seq was applied to explore the underlying mechanisms.ResultsHECW1 demonstrated significant overexpression in GC tumor tissues, correlating with adverse clinical outcomes. Clinically, elevated HECW1 expression exhibited an inverse association with tumor-infiltrating CD8+ T lymphocytes while demonstrating a positive correlation with macrophages, DCs, and neutrophils infiltration, suggesting its potential involvement in tumor immune evasion mechanisms. Functional validation revealed that HECW1 knockdown markedly suppressed GC cell proliferation and migratory capacity, concurrently promoting apoptotic cell death. Mechanistic investigations identified that HECW1 exerts its oncogenic effects through dysregulation of the Hippo signaling pathway, with its silencing effectively attenuating tumor progression via pathway modulation.ConclusionsHECW1 upregulation is significantly associated with poor prognosis and immune infiltration in GC patients, emphasizing its potential as a prognostic biomarker.