Adjustment For Body Mass Index Research Articles

Associations of perfluoroalkyl substances (PFAS) with lipid and lipoprotein profiles

BackgroundPerfluoroalkyl substances (PFAS) are man-made chemicals with unique properties that are widely distributed in humans and the environment. Recent studies suggest that PFAS are involved in cholesterol metabolism, however, the mechanisms underlying the associations are poorly understood.ObjectiveWe aimed to evaluate associations of plasma PFAS with detailed lipid and lipoprotein subfractions in an adult population of men and women.MethodsWe measured concentrations of cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein subclasses, as well as fatty acid and different phospholipid measures, using serum proton nuclear magnetic resonance (1H-NMR), and four plasma PFAS using liquid chromatography-mass spectrometry (UHPLC-MS/MS). Measurements were available for 493 participants (all aged 50 years, 50% female). Multivariable linear regression was used to estimate the association of four PFAS with 43 different 1H-NMR measures, with adjustment for body mass index (BMI), smoking, education, and physical activity.ResultsWe found that perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), but not perfluorohexanesulfonate (PFHxS), concentrations were consistently positively associated with concentrations of cholesterol in lipoprotein subfractions, apolipoproteins, as well as composite fatty acid- and phospholipid profiles. The most consistent associations were found for the relationship of PFAS with total cholesterol in intermediate-density lipoprotein (IDL), across all low-density lipoprotein (LDL) subfractions and small high-density lipoprotein (HDL). Moreover, we found weak to null evidence for an association of any of the measured 13 triglyceride lipoprotein subfractions with PFAS.ConclusionsOur results suggest that plasma PFAS concentrations are associated with cholesterol in small HDL, IDL and all LDL subfractions, as well as apolipoproteins and composite fatty acid and phospholipid profiles but to a lesser extent with triglycerides in lipoproteins. Our findings draw attention to the need for more detailed measurements of lipids across various lipoprotein subfractions and subclasses in assessing the role of PFAS in lipid metabolism.ImpactBy performing an in-depth characterization of circulating cholesterol and triglycerides in lipoprotein subfractions, apolipoprotein, fatty acid, and phospholipid concentrations, this study has expanded upon the limited literature available on the associations of plasma PFAS concentrations beyond clinical routine laboratory testing for lipids.

Association between insulin resistance and abnormal menstrual cycle in Saudi females with polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine disorder experienced by women of reproductive age and is marked by insulin resistance (IR) and menstrual cycle abnormalities. In this study, we set out to assess how the level of menstrual abnormalities relates to the degree of IR in women with PCOS. MethodsThe participants in this study were 93 women diagnosed with PCOS and 100 controls with regular vaginal bleeding. Data was collected through blood samples, physical examinations, and medical histories. The primary outcome measures were body mass index (BMI), fasting glucose, fasting insulin, homeostatic model assessment for IR (HOMA-IR), and hormonal parameters. ResultsValues for BMI and HOMA-IR were higher in PCOS cases than in controls [(28.6 ± 1.9 vs. 23.7 ± 2.3) and (2.29 ± 2.87 vs. 1.48 ± 1.02), respectively]. Oligomenorrhea was documented in 79.4% of women with PCOS, with the others experienced vaginal bleeding intervals under 45 days. The greater the menstrual irregularity, the higher the levels of luteinizing hormone/follicle-stimulating hormone and testosterone. Among the PCOS group, those with vaginal bleeding intervals of above 90 days had a higher HOMA-IR values (2.46 ± 2.77), after adjustments for age and BMI, than the participants who went<45 days between periods (2.01 ± 2.14) and those whose interval was 45–90 days (2.09 ± 2.43). ConclusionsMost of the participants with PCOS had obvious oligomenorrhea of at least 6 weeks between episodes of vaginal bleeding and had significantly higher insulin resistance than did the controls. This suggests that insulin resistance in PCOS cases may be predicted by the presence of clinically overt menstrual dysfunction.

Abstract 3015: Soluble CD137 and risk of hepatocellular carcinoma: nested case-control studies in cohorts in Shanghai and Singapore

Abstract Background: Chronic inflammation plays a significant role in hepatocellular carcinoma (HCC). With rising incidence and poor prognosis of HCC, identifying relatively less invasive biomarkers, especially inflammatory ones, may improve the assessment and stratification of HCC risk. The objective of our studies was to assess if CD8+ T cell cytokines in pre-diagnostic serum are associated with risk of HCC development. Methods: We conducted two parallel case-control studies of HCC nested within the Shanghai Cohort Study (SCS) and the Singapore Chinese Health Study (SCHS), two prospective cohorts of 81,000 individuals with 25+ years of follow-up. The serum concentrations of five CD8+ T cell cytokines ─ soluble CD137 (sCD137), soluble Fas (sFas), perforin, macrophage inflammatory protein 1-beta (MIP-1β), and tumor necrosis factor alpha (TNF-α) ─ were determined using Luminex bead-based immunoassay on 315 HCC cases and 315 individually matched controls in the SCS, and on 197 HCC case-control pairs in the SCHS. Conditional logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) for HCC with elevated levels of cytokines with adjustment for body mass index, alcohol drinking, cigarette smoking, seropositivity of hepatitis surface antigen (HBsAg), and history of diabetes. Results: sCD137 levels were statistically significantly higher in HCC cases than controls in both cohorts. Compared with the 1st quartile (Q1) of sCD137, multivariable-adjusted ORs (95% CI) of HCC for the 4th quartile (Q4) were 3.8 (1.7-8.3) in the SCS and 3.5 (1.4 -8.5) in the SCHS (both Ptrend’s &amp;lt; 0.001). Among HBsAg-negative individuals, ORs (95% CIs) for Q2, Q3, &amp; Q4 of sCD137 were 2.7 (1.5-4.9), 2.7 (1.4-5.0), and 4.5 (2.4-8.5), respectively, compared with Q1 (Ptrend &amp;lt; 0.001) in both SCS and SCHS combined. The corresponding ORs (95% CIs) among HBsAg- positive individuals were 21.0 (9.3-47.6), 34.1 (13.8-84.2), and 56.7 (23.3-137.9), respectively, with a P=0.095 for multiplicative interaction. The sCD137-HCC risk association remained constant over different time periods from blood draw to HCC diagnosis: ORs (95% CIs) for Q4 vs. Q1 were 4.7 (1.2-17.5) for &amp;lt;5 years, 3.7 (1.3-10.6) for 5-10 years, and 3.94 (1.6-9.5) for more than 10 years between blood collection and cancer diagnosis. sFas was positively associated with HCC risk in the SCHS but not in the SCS. There was no statistically significant association for perforin, MIP-1β, or TNF-α with HCC risk in either cohort. Conclusion: These novel and validated findings demonstrated that serum sCD137 levels were significantly elevated many years prior to HCC diagnosis, and had a potential synergistic effect with chronic viral infection on the HCC risk. sCD137 may be developed as a immune monitoring biomarker for risk stratification and assessment, which can lead to early diagnosis and improve prognosis of HCC patients. Citation Format: Claire E. Thomas, Jennifer J. Adibi, Allison L. Kuipers, Brenda Diergaarde, Hung N. Luu, Aizhen Jin, Woon-Puay Koh, Yu-Tang Gao, Jennifer Adams-Haduch, Renwei Wang, Anna Lokshin, Jaideep Behari, Jian-Min Yuan. Soluble CD137 and risk of hepatocellular carcinoma: nested case-control studies in cohorts in Shanghai and Singapore [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3015.

High cereal fibre but not total fibre is associated with a lower risk of type 2 diabetes: Evidence from the Melbourne Collaborative Cohort Study.

To assess the associations of total dietary fibre and fibre from different food sources (ie, cereal, fruit and vegetables) with the risk of diabetes. The Melbourne Collaborative Cohort Study enrolled 41 513 participants aged 40 to 69 years from 1990 to 1994. The first and second follow-ups were conducted in 1994 to 1998 and 2003 to 2007, respectively. Self-reported diabetes incidence was recorded at both follow-ups. We analysed data from 39 185 participants, with a mean follow-up of 13.8 years. The relationships between dietary fibre intake (total, fruit, vegetable and cereal fibre) and the incidence of diabetes were assessed using modified Poisson regression, adjusted for dietary, lifestyle, obesity, socioeconomic and other possible confounders. Fibre intake was categorized into quintiles. At total of 1989 incident cases were identified over both follow-up surveys. Total fibre intake was not associated with diabetes risk. Higher intake of cereal fibre (P for trend = 0.003), but not fruit (P for trend = 0.3) and vegetable fibre (P for trend = 0.5), was protective against diabetes. For cereal fibre, quintile 5 versus quintile 1 showed a 25% reduction in diabetes risk (incidence risk ratio [IRR] 0.75, 95% confidence interval [CI] 0.63-0.88). For fruit fibre, only quintile 2 versus quintile 1 showed a 16% risk reduction (IRR 0.84, 95% CI 0.73-0.96). Adjustment for body mass index (BMI) and waist-to-hip ratio eliminated the association and mediation analysis showed that BMI mediated 36% of the relationship between fibre and diabetes. Intake of cereal fibre and, to a lesser extent, fruit fibre, may reduce the risk of diabetes, while total fibre showed no association. Our data suggest that specific recommendations regarding dietary fibre intake may be needed to prevent diabetes.

A common variant rs2054564 in ADAMTS17 is associated with susceptibility to lumbar spondylosis

The molecular pathophysiology underlying lumbar spondylosis development remains unclear. To identify genetic factors associated with lumbar spondylosis, we conducted a genome-wide association study using 83 severe lumbar spondylosis cases and 182 healthy controls and identified 65 candidate disease-associated single nucleotide polymorphisms (SNPs). Replication analysis in 510 case and 911 control subjects from five independent Japanese cohorts identified rs2054564, located in intron 7 of ADAMTS17, as a disease-associated SNP with a genome-wide significance threshold (P = 1.17 × 10–11, odds ratio = 1.92). This association was significant even after adjustment of age, sex, and body mass index (P = 7.52 × 10–11). A replication study in a Korean cohort, including 123 case and 319 control subjects, also verified the significant association of this SNP with severe lumbar spondylosis. Immunohistochemistry revealed that fibrillin-1 (FBN1) and ADAMTS17 were co-expressed in the annulus fibrosus of intervertebral discs (IVDs). ADAMTS17 overexpression in MG63 cells promoted extracellular microfibrils biogenesis, suggesting the potential role of ADAMTS17 in IVD function through interaction with fibrillin fibers. Finally, we provided evidence of FBN1 involvement in IVD function by showing that lumbar IVDs in patients with Marfan syndrome, caused by heterozygous FBN1 gene mutation, were significantly more degenerated. We identified a common SNP variant, located in ADAMTS17, associated with susceptibility to lumbar spondylosis and demonstrated the potential role of the ADAMTS17-fibrillin network in IVDs in lumbar spondylosis development.

The effect of menopause on cardiovascular risk factors according to body mass index in middle-aged Korean women.

Menopausal status and obesity are associated with an increased risk for cardiovascular diseases. However, there are few studies on the effect of menopause on cardiovascular risk factors according to the degree of obesity during the menopausal transition. We aimed to evaluate the effect of menopause on cardiovascular risk factors according to body mass index (BMI) in middle-aged Korean women. We analyzed 361 postmenopausal women and 758 premenopausal women (age: 45-55 years) without diabetes mellitus, hypertension, or dyslipidemia, using a cohort database released by the Korean National Health and Nutrition Examination Survey 2016-2018. Subjects were divided into two groups based on BMI. Women who underwent a hysterectomy or were pregnant were excluded from this study. Differences between groups adjusted for age and BMI were assessed. Postmenopausal women (52 ± 2 years) were older than premenopausal women (48 ± 2 years), and BMI did not differ between the two groups (22.8 ± 2.9 vs. 23.0 ± 3.1 kg/m2). After adjustment for age and BMI in total and non-obese subjects (not obese subjects), postmenopausal women exhibited higher hemoglobin A1c and total cholesterol levels than premenopausal women. Subgroup analysis for 138 postmenopausal and 138 age- and BMI-matched premenopausal women showed that postmenopausal women had higher total cholesterol levels than premenopausal women with marginal significance (201 ± 25 vs. 196 ± 27 mg/dL). Menopausal status was associated with increased glucose and cholesterol levels independent of age and BMI in middle-aged Korean women. Menopausal status showed a significant relationship with increased total cholesterol levels even after adjusting for age and BMI in non-obese women but not obese women. Therefore, intensive monitoring and treating of lipid status is necessary to prevent cardiovascular events during the menopausal transition, especially in non-obese subjects.

Dynamic changes of serum taurine and the association with gestational diabetes mellitus: A nested case-control study.

There is a lack of risk factors that can effectively identify gestational diabetes mellitus (GDM) in early pregnancy. It is unclear whether serum taurine in the first trimester and dynamic changes have different characteristics in GDM women. Whether these features are associated with the occurrence of GDM has not yet been elucidated. The main objective of this study was to observe the dynamic changes of serum taurine during pregnancy and investigate the relationship between serum taurine levels and GDM in the first and second trimesters. This was a nested case-control study in 47 women with GDM and 47 age-matched normoglycemic women. We examined serum taurine at 8-12 weeks' gestation and 24-28 weeks' gestation. The serum taurine of the two groups was compared. Multivariable logistic regression analysis was performed to investigate how serum taurine was associated with GDM. The serum taurine concentration of GDM women was significantly lower than that of normoglycemic women in the first trimester(2.29 vs 3.94 μmol/L, P<0.001). As the pregnancy progressed, serum taurine concentration in normoglycaemic women decreased significantly(3.94 vs 2.47 μmol/L, P<0.001), but not in the GDM group(2.29 vs 2.37 μmol/L, P=0.249), resulting in the disappearance of differences between the two groups(2.47 vs 2.37 μmol/L, P=0.160). After adjustment for pre-pregnancy body mass index(BMI), fasting plasma glucose(FPG), and lipid profiles in the first trimester, the serum taurine concentration in the first trimester was negatively correlated with the risk of GDM(OR=0.017, 95% CI=0.003-0.107, P<0.001). Furthermore, dynamic change of serum taurine showed a significantly positive correlation with the risk of GDM(OR=9.909, 95% CI=3.556-27.610, P<0.001). Low serum taurine concentration in the first trimester was significantly associated with the development of GDM. As the pregnancy progressed, the association between serum taurine and GDM disappeared in the second trimester, which might be related to the inhibition of taurine transporter(TauT) activity by high glucose.

Genetically predicted visceral adipose tissue and risk of nine non-tumour gastrointestinal diseases: evidence from a Mendelian randomization study.

Numerous studies have linked visceral adipose tissue (VAT) to gastrointestinal diseases. However, it remains unclear whether these associations reflect causal relationships. We used a two-sample Mendelian randomization (MR) approach to elucidate the causal effect of VAT on nine non-tumour gastrointestinal diseases. The inverse-variance weighted method was used to perform the MR analyses. Complementary and multivariable MR analyses were performed to confirm the results. Genetically predicted higher VAT was associated with an increased risk of gastro-oesophageal reflux disease (GORD) (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.34; P = 3.06 × 10-4), duodenal ulcer (DU) (OR, 1.40; 95% CI, 1.10-1.77; P = 0.005), cholelithiasis (OR, 1.75; 95% CI, 1.53-2.00; P = 1.14 × 10-16), and non-alcoholic fatty liver disease (NAFLD) (OR, 2.68; 95% CI, 1.87-3.82; P = 6.26 × 10-8). There were suggestive associations between VAT and gastric ulcer (GU) (OR, 1.22; 95% CI, 1.01-1.48; P = 0.035) and acute pancreatitis (AP) (OR, 1.26; 95% CI, 1.05-1.52; P = 0.013). However, there was little evidence to support the associations between VAT and inflammatory bowel disease, irritable bowel syndrome, or chronic pancreatitis. The associations with GORD, GU, and NAFLD remained in the multivariable MR analyses with adjustment for body mass index (BMI). This study provided evidence in support of causal associations between VAT and GORD, GU, DU, cholelithiasis, AP, and NAFLD. Moreover, the associations between GORD, GU, and NAFLD were independent of the effect of BMI.

Type 2 Diabetes: Also a “Clock Matter”?

We investigated whether chronotype is associated with glycemic control, antidiabetic treatment, and risk of developing complications in patients with type 2 diabetes (T2DM). The diabetologists filled out an online questionnaire on the Google Form platform to collect the following parameters of subjects with T2DM: body mass index (BMI), fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c), diabetes history, antidiabetic treatment, diabetic complications, and chronotype categories. We enrolled 106 subjects with T2DM (M/F: 58/48; age: 63.3 ± 10.4 years; BMI: 28.8 ± 4.9 kg/m2). Thirty-five point eight% of the subjects showed a morning chronotype (MC), 47.2% an intermediate chronotype (IC), and 17% an evening chronotype (EC). EC subjects reported significantly higher HbA1c (p < 0.001) and FPG (p = 0.004) values, and higher prevalence of cardiovascular complications (CVC) (p = 0.028) and of subjects taking basal (p < 0.001) and rapid insulin (p = 0.01) compared to MC subjects. EC subjects reported significantly higher HbA1c (p < 0.001) and FPG (p = 0.015) than IC subjects. An inverse association was found between chronotype score, HbA1c (r = -0.459; p < 0.001), and FPG (r = -0.269; p = 0.05), remaining significant also after adjustment for BMI, age, and disease duration. EC is associated with higher prevalence of CVC and poorer glycemic control independently of BMI and disease duration in subjects with T2DM.

Vitamin D Intake, Blood 25-Hydroxyvitamin D, and Risk of Ovarian Cancer: A Meta-Analysis of Observational Studies.

Background: In vitro research suggests that vitamin D may protect against the risk of ovarian cancer. However, ecological and epidemiologic evidence is still debatable. Materials and Methods: We searched eligible studies via MEDLINE and Web of Science databases, as well as a hand search to examine the association between vitamin D intake or blood 25(OH)D (25-hydroxyvitamin D) and ovarian cancer risk in a meta-analysis. The overall relative risk (RR) was determined using a random-effect model. Results: For ovarian cancer incidence, 15 observational studies were included [5,634 cases for vitamin D intake and 975 cases for blood 25(OH)D]. For overall vitamin D intake (from food and supplements), the pooled RR of ovarian cancer risk for the highest versus lowest groups was 0.92 (95% confidence interval [CI]: 0.74-1.14). For blood 25(OH)D levels, however, people with high blood 25(OH)D levels had 37% lower risk of ovarian cancer than those with low levels (pooled RR = 0.63; 95% CI: 0.42-0.93). By study design, the inverse association was stronger in case-control studies than in prospective studies. The dose-response meta-analysis also supports the inverse association between blood 25(OH)D levels and ovarian cancer risk. When the pooled RRs were restricted to studies that adjusted for body mass index (BMI), they tended to be stronger, but the difference by adjustment for BMI was not significant. Conclusion: Our findings suggest that having a high blood 25(OH)D level is associated with a lower risk of ovarian cancer. More well-designed prospective studies are needed to confirm the link between vitamin D status and ovarian cancer risk.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Obesity Is Indirectly Associated with Sudden Cardiac Arrest through Various Risk Factors

Although obesity is a well-established risk factor of cardiovascular event, the linkage between obesity and sudden cardiac arrest (SCA) is not fully understood. Based on a nationwide health insurance database, this study investigated the impact of body weight status, measured by body-mass index (BMI) and waist circumference, on the SCA risk. A total of 4,234,341 participants who underwent medical check-ups in 2009 were included, and the influence of risk factors (age, sex, social habits, and metabolic disorders) was analyzed. For 33,345,378 person-years follow-up, SCA occurred in 16,352 cases. The BMI resulted in a J-shaped association with SCA risk, in which the obese group (BMI ≥ 30) had a 20.8% increased risk of SCA compared with the normal body weight group (18.5 ≤ BMI < 23.0) (p < 0.001). Waist circumference showed a linear association with the risk of SCA, with a 2.69-fold increased risk of SCA in the highest waist circumference group compared with the lowest waist circumference group (p < 0.001). However, after adjustment of risk factors, neither BMI nor waist circumference was associated with the SCA risk. In conclusion, obesity is not independently associated with SCA risk based on the consideration of various confounders. Rather than confining the findings to obesity itself, comprehensive consideration of metabolic disorders as well as demographics and social habits might provide better understanding and prevention of SCA.

Prevalence of sleep apnoea in patients with type 1 diabetes and its association with comorbidities and diabetic complications: A French nationwide prospective study.

To investigate sleep apnoea prevalence, factors influencing severity, and associations between sleep apnoea severity and micro-/macrovascular complications in a large population of patients with type 1 diabetes. This French multicentre prospective cohort study was conducted between July 2016 and June 2020. Adults with type 1 diabetes using an insulin pump were eligible. Home care provider nurses collected demographic and clinical data and set up oximetry to determine the oxygen desaturation index (ODI). No, mild-moderate and severe sleep apnoea were defined as ODI <15 events/h, 15 to <30 events/h and ≥30 events/h, respectively. Univariate and multivariate analyses were performed to identify factors associated with sleep apnoea, and associations between sleep apnoea severity and micro-/macrovascular complications were determined using logistic regression. Of 769 participants, 12.4% and 3.4% had mild-to-moderate or severe sleep apnoea, respectively. Factors significantly associated with sleep apnoea on multivariate analysis were age, sex, body mass index (BMI) and hypertension. After adjustment for age, sex and BMI, presence of severe sleep apnoea was significantly associated with macrovascular complications (odds ratio vs. no sleep apnoea: 3.96 [95% confidence interval 1.43-11.11]; P< 0.01), while mild-to-moderate sleep apnoea was significantly associated with presence of diabetic retinopathy (odds ratio 2.09 [95% confidence interval 1.10-3.74]; P< 0.01). Sleep apnoea is a significant comorbidity in patients with type 1 diabetes, especially with respect to diabetic complications. This highlights the need for sleep apnoea screening and management in these individuals.

Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life.

Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later life. Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical record-abstracted pregnancy information. A cognitive battery of 9 tests was conducted every 15 months. Global cognitive and domain-specific z scores (memory, executive/attention, visuospatial, and language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined. Of the 2,239 women, 1,854 (82.8%) had at least 1 pregnancy (1,607 all normotensive, 100 GH/CH, and 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E vs women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p < 0.05) in age- and education-adjusted models. There was an interaction (p = 0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p < 0.001) vs 12 + years (b = -0.11, p = 0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z scores compared with women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p < 0.001), language (beta = -0.03, p = 0.001), and attention (beta = -0.04, p < 0.001) z scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results. Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

Abstract P5-03-08: Joint associations of mammographic breast density and obesity on the presence of crown-like structures in the breast adipose tissue of breast cancer patients

Abstract Background: Obesity is an established risk factor for postmenopausal breast cancer and is associated with poor outcomes. Accumulating evidence suggests crown-like structures in the breast adipose tissue (CLS-B), a marker of local inflammation, play a role in explaining the obesity-breast cancer association. However, it is unknown whether breast tissue composition (i.e., the amount of fibroglandular tissue in the breast relative to fat) is related to CLS-B. Objective: We evaluated whether breast tissue composition, as reflected by mammographic breast density, is associated with breast adipose tissue inflammation, as indicated by the presence of CLS-B, and whether the combination of breast density and obesity increases the presence of CLS-B among newly diagnosed breast cancer patients. Methods: We examined the presence of CLS-B, detected by CD68 immunohistochemistry, in breast adipose tissue obtained via mastectomy from a quadrant uninvolved by tumor among 254 women with stage I–III breast cancer treated at Emory University Hospitals (2007–2012). Patient characteristics, including mammographic breast density (assessed on a mammogram up to 5 years before breast surgery) and body mass index (BMI) at diagnosis, were abstracted from electronic medical records. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification (1=almost entirely fat; 2=scattered fibroglandular densities; 3=heterogeneously dense; and 4=extremely dense); density was further categorized as fatty (BI-RADS 1-2) and dense (BI-RADS 3-4). Age and multivariable (MV)-adjusted logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the independent and joint associations of breast density (dense vs. fatty) and obesity (BMI ≥30 kg/m2 vs. &amp;lt; 30 kg/m2) on the presence of CLS-B. Multivariable models adjusted for age (continuous, years) and parity (nulliparous, parous) with mutual adjustment of BMI (continuous, kg/m2) or mammographic breast density (dense, fatty) depending on the model. Results: Women with obesity were more likely to have fatty breasts than women without obesity (52% vs. 27%). Obesity was strongly associated with the presence of CLS-B in age-adjusted (OR=3.11, 95% CI: 1.79, 5.48) and multivariable models (MV-OR=3.70, 95% CI: 1.96, 7.15). There was no apparent association between dense breast tissue and presence of CLS-B in the age-adjusted model (OR=1.04, 95% CI: 0.59, 1.85). After additional adjustment for BMI and parity, we noted that women with dense breasts had higher odds of having CLS-B compared to those with fatty breasts (MV-OR=2.13, 95% CI: 1.07, 4.41). MV-ORs from the joint model (common referent: not obese, fatty breasts) were 1.54 (95% CI: 0.62, 4.24) for women without obesity but with dense breasts, 3.18 (95% CI: 1.15, 9.56) for women with obesity and fatty breasts, and 6.24 (95% CI: 2.23, 19.2) for women with obesity and dense breasts. Conclusions: Our findings suggest that dense rather than fatty breast tissue is associated with breast adipose tissue inflammation among women with breast cancer. Results of the joint analyses suggest obesity is more strongly predictive of CLS-B presence than breast density. However, density may be an important risk factor for CLS-B among women without obesity while patients with obesity and dense breast tissue are the most likely to have CLS-B present. Future studies may consider the mechanisms by which density leads to increased presence of CLS-B. Joint Associations Table Table 1. Joint associations between mammographic breast density (MD) and body mass index (BMI) on the presence of crown-like structures in breast adipose tissue (CLS-B) among 254 women diagnosed with invasive breast cancel (stage I-III) at Emory University between 2007 and 2012 Citation Format: Maret L. Maliniak, Rebecca L. Seidel, Kimberly Bertrand, Lauren E. McCullough. Joint associations of mammographic breast density and obesity on the presence of crown-like structures in the breast adipose tissue of breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-08.

Abstract MP45: Nocturnal Hypoxemia, Obstructive Sleep Apnea and the Risk of Cardiovascular Diseases and Mortality: Insights From the Atherosclerosis Risk in Communities Participants of the Sleep Heart Health Study

Background: Nocturnal hypoxemia may better capture disease burden than obstructive sleep apnea (OSA). Using a subset of participants from the Atherosclerosis Risk in Communities (ARIC) study who participated in the Sleep Heart Health Study (SHHS), we examined the association of nocturnal hypoxemia and OSA with cardiovascular diseases (CVD) and mortality in a white, older cohort in the US. Methods: A total of 1,455 participants free of CVD had an in-home, overnight polysomnogram; nocturnal hypoxemia (% of total sleep time with oxygen saturation &lt;90%) and OSA (apnea-hypopnea index - # of apneas/hypopneas per hour of sleep) were derived from these readings. Incident CVD events and mortality were identified through the end of 2019 using annual telephone calls, hospital discharge lists and death certificates and were adjudicated by physician review. Included in this analysis were coronary heart disease (CHD), heart failure (HF), stroke, any CVD event (CHD, HF, or stroke), atrial fibrillation (AF), and all-cause mortality. We used Cox proportional hazards models to assess the association of nocturnal hypoxemia (categories: &lt;1%, 1-&lt;5%, ≥5%) and OSA (categories: &lt;5, 5-&lt;15, 15-&lt;30, ≥30) with each outcome. Results: At the sleep assessment, participants had a mean (SD) age of 62 (6) years, 53% were female, and 14% had a nocturnal hypoxemia ≥5%. Over a mean follow-up of 17.8 years, a total of 408 participants had any CVD event, and 602 died. Nocturnal hypoxemia ≥5% was associated with incident HF and all-cause mortality in the fully adjusted model (Table). Nocturnal hypoxemia ≥5% was also associated with incident CVD and AF in Model 1; however, adjustment for body mass index attenuated these associations (Table, Model 2). OSA was not associated with the outcomes in any model (data not shown). Conclusion: Further research is needed to understand the distinction between nocturnal hypoxemia and OSA and how they relate to the risk of CVD and mortality. It is possible that reducing nocturnal hypoxemia should be targeted over OSA for CVD prevention.

Abstract MP32: Body Weight Variability in Young Adulthood and Echocardiographic Precursors of Heart Failure in Later Life: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: The association between variability in body mass index (BMI) in early adulthood and cardiac structure and function in midlife has not been previously examined. Methods: We examined 2371 Coronary Artery Risk Development in Young Adults (CARDIA) participants who had BMI assessments across 25-years (CARDIA exam year 0 [1985-1986], 2 [1987-1989], 5 [1990-1991], 7 [1992-1993], 10 [1995-1996], 15 [2000-2001], 20 [2005-2006], and 25 [2010-2011]) as well as echocardiography data at the year-25 exam (2010-2011). BMI variability was assessed by standard deviation (SD) across 25 years. Adjusted multivariable linear regression models were used to assess the association between echocardiography variables (dependent variable) and SD of BMI (independent variable). Model 1 was adjusted for standard cardiac risk factors (age, sex, race, education, blood pressure, anti-hypertension medication use, smoking, fasting plasma glucose, alcohol consumption, physical activity, HDL and total cholesterol. Model 2 was additionally adjusted for mean BMI. Results: Among participants included in the analysis, mean [SD] age at the year 25 exam [2010-2011] was 50.4 [3.6] years; 44.5% were men; and 41.3% were black). In model 1, greater SD of BMI was associated with greater left ventricular mass (β 5.18g, p&lt;0.001), left ventricular global longitudinal strain 0.08, p=0.01, and left atrial volume (β 1.60ml, p&lt;0.001). Additional adjustment for mean BMI, attenuated associations (p&gt;.05 for all). Greater SD of BMI was associated with worse diastolic function (E/é) (β 0.11, p&lt;0.001). Observed association between BMI variability and E/é persisted even after accounting for mean BMI (β 0.08, p=0.01). Conclusions: Greater body weight variability in young adulthood was associated with modest unfavorable midlife alterations in diastolic function.

Abstract MP39: Associations of Disordered Eating and Weight Control Behavior With Cardiovascular Health Score: The Coronary Artery Risk Development in Young Adults Study

Introduction: Psychological and behavioral factors negatively impact cardiovascular health (CVH), defined by Life’s Simple 7. Few studies have investigated disordered eating and weight control behaviors and CVH, particularly outside of adolescence. Objective: To examine the cross-sectional and longitudinal associations of disordered eating and weight control behaviors with CVH among middle-aged adults. Methods: We studied CARDIA participants assessed between Y10 (1995-1996) and Y30 (2015-2016) excluding pregnant/breastfeeding individuals at Y10. The Questionnaire on Eating and Weight Patterns-Revised (QEWP-R) was administered at Y10 and used to create the Problematic Relationship to Eating and Food (PREF) score, an aggregate measure (range 0-8) of eight disordered eating and weight-related behaviors (anxiety surrounding food, compensatory behaviors, overeating, loss of control, distress surrounding overeating, distress surrounding loss of control, shape concerns, time spent dieting). Diet, physical activity, smoking, blood pressure, cholesterol, glucose, and body mass index (BMI) were measured at Y10 and Y30 (except diet at Y7 and Y20) and used to define CVH categories Low-to-Moderate (0-9) or High (10-14). Logistic regression analyses were used to evaluate associations between PREF score and CVH category. Results: We included 2,040 participants (mean age 35.2 years, 55% female, 43% Black). At Y10, every 1-unit increment in PREF was associated with 19% higher odds of Low-to-Moderate vs. High CVH in adjusted models ( Table ). At Y30 after 20 years of follow-up (mean age 55.3 years), every 1-unit increment in PREF at Y10 was associated with 11% higher odds of Low-to-Moderate vs. High CVH at Y30 in adjusted models ( Table ). Further adjustment for Y10 BMI attenuated the relationship (OR=0.93, 95%CI: 0.87-0.99). Conclusion: Higher levels of problematic behaviors and attitudes towards eating are associated with less optimal CVH throughout middle-age, likely through weight increases.

Abstract MP58: A Plasma Metabolite Score Related to Psychological Distress and Future Diabetes Risk: A Nested Case-Control Study in US Women

Introduction: Various forms of psychological distress, such as depression and anxiety, have been identified as risk factors for diabetes. However, there is limited evidence from population-based, epidemiologic studies investigating potential molecular mechanisms (e.g., metabolic dysregulation) linking psychological distress and diabetes development. Hypothesis: We assessed the hypothesis that a metabolite score reflecting psychological distress-related metabolic dysregulation is predictive of future diabetes risk in women. Methods: We conducted a nested case-control study of plasma metabolomics and diabetes risk in the Nurses’ Health Study, including 728 women (mean age: 55.2 years) with incident diabetes and 728 controls matched on age, race, fasting status, and time/date of blood collection. Blood samples were collected between 1989-1990 and incident diabetes was diagnosed between 1990-2012. Based on the metabolomic signature of chronic psychological distress we previously identified and validated in women (including coefficient estimates for individual metabolite associations), we calculated a weighted plasma metabolomic score of psychological distress comprised of 19 metabolites (e.g., serotonin, threonine, hippurate, biliverdin, glutamine, etc.). We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% CI for diabetes risk across quintiles of the distress-related metabolite score. Results: After adjusting for sociodemographic factors, family history of diabetes and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the distress-related metabolite score was 1.00 (reference) for Q1, 1.11 (0.77, 1.61) for Q2, 1.64 (1.14, 2.35) for Q3, 2.07 (1.42, 3.01) for Q4, and 2.35 (1.60, 3.47) for Q5. Each 1-unit increase in the score was associated with 26% higher diabetes risk (95% CI: 1.15, 1.38; p-trend&lt;0.0001). This association was moderately attenuated after additional adjustment for baseline body mass index (OR per 1-unit increase: 1.13; 95% CI: 1.02, 1.25; p-trend=0.02). Further, psychological distress assessed via self-report (defined as presence of depression or anxiety) was associated with modestly increased diabetes risk in the same sample (OR: 1.25; 95% CI: 1.01, 1.55). The metabolite score mediated 20.7% (95% CI: 5.1, 56.1) of the association between psychological distress and diabetes risk (p=0.0065). Conclusions: Our results suggest that the distress-related metabolite score was significantly associated with diabetes risk in women and partly mediated the association between self-reported psychological distress and diabetes risk. These findings provide supporting evidence that metabolic dysregulation may be an important mechanism underlying the observed association between psychological distress and diabetes risk.

Association of GDF15 levels with body mass index and endocrine status in β-thalassaemia.

GDF15 has emerged as a stress-induced hormone, acting on the brain to reduce food intake and body weight while affecting neuroendocrine function. Very high GDF15 levels are found in thalassaemia, where growth, energy balance and neuroendocrine function are impaired. We examined the relationships between GDF15 and anthropometric measures and endocrine status in β-thalassaemia. Cross sectional study. All β-thalassaemia patients attending the thalassaemia unit of Colombo North Teaching Hospital for blood transfusions. Anthropometric data, appetite scores, circulating GDF15, IGF, thyroid and reproductive hormone levels in 103 β-thalassaemia patients were obtained. GDF15 levels were markedly elevated in thalassaemia patients (24.2-fold with β-thalassaemia major compared with healthy controls). Among patients with β-thalassaemia major, the relationship between GDF15 and body mass index (BMI) was curvilinear with all individuals with GDF15 levels above 24,000 pg/mL having a BMI below 20 kg/m2 . After adjustment for BMI, age and Tanner stage, serum IGF1 concentrations correlated negatively with GDF15 in all thalassaemia patients (β = -.027, p = .02). We found a significant positive relationship between GDF15 and gonadotropin (in both sexes) and testosterone (in males). GDF15 levels were markedly elevated in patients with β-thalassaemia and its association with BMI is consistent with the known effect of GDF15 to reduce body weight. The inverse association between GDF15 with IGF1 levels may reflect a neuroendocrine impact of GDF15 or an indirect effect via impaired nutritional state. The positive association with testosterone in males and gonadotropins in both sexes, was surprising and should prompt further GDF15 studies on the hypothalamic pituitary gonadal axis.