Continuous Body Mass Index Research Articles

Extent and impact of obesity in patients with diabetes and acute myocardial infarction - experience from a national cohort

Abstract Background Elevated body mass index (BMI) has an adverse effect on cardiovascular riskfactors where diabetes and coronary artery disease increases with obesity. However, less in known about the prevalence and the grades of obesity in a diabetes population with acute myocardial infarction (AMI) and the impact on prognosis. Further, for the moment there is a shortage of access to cardioprotective weight loss medications as Glucagon Like Peptide Receptor Agonists (GLP-1 RA). Purpose To explore features and grades of obesity in patients with diabetes and AMI and impact on outcome in a national perspective. Methods All patients with diabetes and AMI admitted for coronary angiography in Sweden the years 2010-2021 were included. Information on BMI was collected at the time of angiography and grouped into obesity categories: low BMI (<18.5 kg/m2), normal BMI (18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), obesity grade 1 (30.0-34.9 kg/m2), obesity grade 2 (35.0-39.9 kg/m2) and obesity grade 3 (≥40.0 kg/m2). Information on baseline characteristics and outcome was collected from national registries. Mortality was followed until March 2022. Restricted cubic spline analysis of association between continuous BMI and age-adjusted mortality was performed where normal BMI served as a reference with Hazard Ratio (HR) 1.0. Results Of 19 378 patients with diabetes, 67% were men and 46% suffered a STEMI. Normal BMI was present in 21%, overweight in 41%, obesity grade 1 in 25%, obesity grade 2 in 9% and obesity grade 3 in 3% (Figure 1). Age was decreasing with grade of obesity (72 years in normal BMI vs. 62 years in obesity grade 3, p<0.001). Hypertension and hyperlipidaemia were more common in patients with more severe obesity than in those with normal BMI (67% vs. 80%, p<0.001, and 44% vs. 50%, p<0.001, in normal BMI and obesity grade 3 respectively) while a higher proportion of those with normal BMI had suffered a previous MI (10% vs. 6% in obesity grade 3, p<0.001) and a previous stroke (10% vs. 5% in obesity grade 3, p<0.001). In patients with normal BMI STEMI was more common (51% vs. 39%, p<0.001) than in those with obesity grade 3. In patients with obesity grade 3 GLP-1 RA was used in 14% compared to 4% in those with normal BMI. Figure 2 depicts age-adjusted HR and 95% Confidence Interval for mortality for different BMI levels with a U-shaped pattern illustrating that associated mortality risk is higher when obesity is present especially grade 2 and 3. Conclusion Obesity is common affecting around one third of patients with diabetes and AMI and impacts survival. This strengthens that after AMI use of effective weight loss cardioprotective treatment should be prioritised in patients with diabetes and obesity especially if severe.

Association of Prepregnancy Cardiometabolic Factors With Gestational Diabetes Among Asian Populations in the United States

BackgroundAsian individuals are among the highest immigrant group to the United States and at particularly high risk of gestational diabetes, which is associated with long-term maternal cardiovascular disease. Limited data are available on the association of prepregnancy cardiometabolic risk factors with gestational diabetes among Asian American subjects. ObjectivesThis study sought to determine the association of prepregnancy hypertension and body mass index (BMI) among Asian ancestry subgroups and by maternal nativity. MethodsUsing data from the National Vital Statistics System from 2016 to 2019, the prevalence of gestational diabetes, stratified according to prepregnancy hypertension and obesity, was examined according to maternal race. Predicted probability of gestational diabetes with continuous BMI was calculated across Asian ancestry subgroups and by maternal nativity. ResultsAmong 13.3 million pregnancies, gestational diabetes occurred in 6.5%. Asian subjects had the highest prevalence (12.3%). Among those with prepregnancy hypertension, Asian subjects had the highest prevalence (29.3%). Across the range of BMI (18-42 kg/m2), Asian subjects had the highest predicted probability. There was substantial heterogeneity across Asian ancestry subgroups between the association of BMI with gestational diabetes, with highest probability among Japanese and Korean American subjects at BMI >23 kg/m2. Predicted probability of gestational diabetes was higher for mothers born outside the United States among all Asian subgroups, except for Japanese American subjects. ConclusionsAsian American individuals have the highest prevalence of gestational diabetes at any BMI and with hypertension. Substantial variation in risk is present across Asian subgroups. Findings suggest a need for more tailored screening and intervention for gestational diabetes among Asian American subjects, with a specific focus on risk for individuals born outside the United States.

Low body mass index and risk of mortality after mitral transcatheter edge-to-edge repair procedure: The "obesity paradox".

Most patients undergoing the mitral transcatheter edge-to-edge repair (TEER) technique are elderly comorbid patients. Low body mass index (BMI) < 23 kg/m2 has been identified in other elderly populations as a risk factor, but has not been studied sufficiently in mitral TEER. We aimed to study the impact of low BMI (23 kg/m2) on the outcome after mitral TEER. Patients undergoing first-time TEER for mitral regurgitation at a single tertiary center were included, with the exclusion of patients with preprocedural hemodynamic instability or missing BMI. The primary endpoint was all-cause mortality. Secondary endpoints were long-term major bleeding or admission with heart failure. A total of 120 patients (mean age 76 ± 10 years, 76% men) were included in the study. Thirty-nine (31%) had low BMI. Patients with low BMI had a similar symptomatic benefit as patients with BMI ≥ 23 kg/m2 at 1 year regarding decrease in diuretics dose and decrease in New York Heart Association(NYHA)class (p > 0.05). In a multivariable Cox regression analysis, BMI as a continuous variable (hazard ratio [HR]: 0.93 [95% confidence interval, CI: 0.87-0.99],p = 0.03) and low BMI (HR: 1.99 [95% CI: 1.12-3.52], p = 0.02) were associated with the primary outcome. Low BMI was not significantly associated with major bleeding (subdistribution hazard ratio [SHR]:2.39 [95% CI: 0.96-5.97], p = 0.06) or admission with heart failure (SHR: 1.06 [95% CI: 0.61-1.88], p = 0.83) during follow-up with univariable competing risk regression analysis. Low BMI is a risk factor for mortality after mitral valve TEER, confirming the presence of an "obesity paradox" in this population and should receive attention in patient selection.

Water intake and obesity: By amount, timing, and perceived temperature of drinking water.

Water intake has been suggested to be associated with weight control, but evidence for optimal water intake in terms of amount, timing, and temperature is sparse. Additionally, genetic predisposition to obesity, which affects satiety and energy expenditure, might interact with water intake in regulating individual adiposity risk. We conducted a cross-sectional study recruiting 172 Korean adults. Information on water intake and lifestyle factors was collected through self-reported questionnaires, and height, weight, and waist circumference (WC) were measured by researchers. The oral buccal swab was performed for genotyping of FTO rs9939609, MC4R rs17782313, BDNF rs6265 and genetic risk of obesity was calculated. Linear regression was performed to estimate mean difference in body mass index (BMI) and WC by water intake and its 95% confidence interval (95% CI). As a sensitivity analysis, logistic regression was performed to estimate odds ratio (OR) of obesity/overweight (BMI of ≥23kg/m2; WC of ≥90cm for men and of ≥80cm for women) and its 95% CI. Drinking >1L/day was significantly associated with higher BMI (mean difference: 0.90, 95% CI 0.09, 1.72) and WC (mean difference: 3.01, 95% CI 0.62, 5.41) compared with drinking ≤1L/day. Independent of total water intake, drinking before bedtime was significantly associated with lower BMI (mean difference: -0.98, 95% CI -1.91, -0.05). The results remained consistent when continuous BMI and WC were analyzed as categorical outcomes. By perceived temperature, drinking >1L/day of cold water was associated with higher BMI and WC compared with drinking ≤1L/day of water at room-temperature. By genetic predisposition to obesity, a positive association between water intake and WC was confined to participants with low genetic risk of obesity (P interaction = 0.04). In conclusion, amount, timing, and perceived temperature of water intake may be associated with adiposity risk and the associations might vary according to genetic predisposition to obesity.

Trajectories of Body Mass Index and Risk for Diabetes Complications and All-Cause Mortality in Finnish Type 2 Diabetes Patients.

We aimed to assess how longitudinal body mass index (BMI) trajectories are associated with diabetes complications and all-cause mortality in Finnish patients with type 2 diabetes (T2D). In this cohort study, electronic health records from public primary and specialized healthcare services in all 13 municipalities of North Karelia, Finland, were utilized. This study included a total of 889 adults with newly diagnosed T2D in 2011 or 2012 (mean age at baseline 62.0 years). Individual BMI trajectories from the T2D diagnosis until 2014 were estimated and grouped by growth mixture modeling (GMM). Hazard ratios (HRs) with 95% confidence intervals (CIs) for microvascular complications, macrovascular complications, any diabetes complications, and all-cause mortality from 2015 to 2022 across BMI trajectory groups were estimated using Cox regression models. Three distinct BMI trajectory groups were identified using GMM and labeled as follows: "stable" (n = 774, 87.1%), "decreasing" (n = 87, 9.8%), and "increasing" (n = 28, 3.1%). During a median follow-up of 8 years, there were 119 (13.3%) patients with microvascular complications, 187 (21.0%) with macrovascular complications, 258 (29.0%) with any diabetes complications, and 180 (20.2%) deaths. Compared with the "stable" BMI, the "increasing" BMI was associated with an increased risk of microvascular complications (HR = 2.88, 95% CI: 1.32 to 6.28), macrovascular complications (HR = 2.52, 95% CI: 1.17 to 5.43), and any diabetes complications (HR = 2.21, 95% CI: 1.16 to 4.20). The "decreasing" BMI was associated with an increased risk of all-cause mortality (HR = 1.90, 95% CI: 1.14 to 3.15), compared to the "stable" BMI. Our findings underscore the significance of continuous BMI monitoring and weight management in patients with T2D. Tailored treatments are crucial for efficiently preventing weight gain and reducing the risk of diabetes complications.

EXAMINING THE ASSOCIATION BETWEEN HYDRATION STATUS AND OBESITY IN OLDER ADULTS

Abstract Adequate hydration is an important modifiable determinant of overall physical health within community-dwelling older adults. Research and clinical practice often use urine osmolarity and bioelectrical impedance analysis (BIA) to assess hydration status. Prior evidence links inadequate hydration to increased obesity, typically measured by body mass index (BMI). However, this association has not yet been evidenced in community-dwelling older adults, especially in low-income settings. This cross-sectional study assessed 103 older adults (16 men, 87 women; mean age 75.7 ± 7.19 years; BMI 26.8 ± 5.22 kg/m2). Total body water (TBW), intracellular water (ICW), fat mass (FM) and fat-free mass (FFM) were measured using multi-frequency BIA (InBody S10). Linear regression analysis examined continuous BMI. TBW/FFM and ICW/FFM as hydration indicators showed weak correlation with FM (TBW/FFM: r = 0.357, p &amp;lt; 0.001; ICW/FFM: r = -0.243, p = 0.013). However, only TBW/FFM significantly correlated with BMI (TBW/FFM: r = 0.236, p = 0.016; ICW/FFM: r = -0.143, p = 0.151). These results suggest TBW/FFM and ICW/FFM may not adequately indicate hydration status while maintaining sensitivity to body composition in adults aged 60-96 years. Further research should examine these findings using urine osmolarity as the hydration assessment.

Independent and joint associations of cardiorespiratory fitness and BMI with dementia risk: the Cooper Center Longitudinal Study

ObjectiveThis study aimed to examine the association of midlife fitness and body mass index (BMI) with incident dementia later in life.Design and participantsA cohort study of 6428 individuals (mean age...

Prognostic significance of growth differentiation factor-15 across the BMI spectrum in patients with chronic heart failure: Insights from the SUPPORT trial

Abstract Background Obesity is a risk factor for cardiovascular diseases including heart failure (HF), yet patients with obesity have better outcomes than their leaner counterparts in HF (i.e. the obesity paradox). We sought to investigate whether growth differentiation factor-15 (GDF15), an emerging biomarker in HF reflecting inflammation and oxidative stress, is a prognostic indicator across the body mass index (BMI) spectrum in chronic heart failure (CHF). Methods Serum levels of GDF15 and its prognostic significance across BMI were examined in a total of 1,040 Japanese patients with CHF enrolled in a randomized clinical trial of the SUPPORT trial (supplemental benefit of an angiotensin receptor blocker in hypertensive patients with stable heart failure using olmesartan) (mean age 66.0±9.9 years, 26% female). Patients were categorized into four groups: underweight (BMI &amp;lt;18.5 kg/m2; n = 56), normal (BMI 18.5-22.9; n = 304), overweight (BMI 23-24.9; n = 257), and obese (BMI ≥25; n = 423) defined based on the WHO recommendation for Asian-Pacific population. Results The underweight group consisted of older patients with a higher prevalence of NYHA class III and reduced left ventricular ejection fraction (LVEF) compared to obese patients (mean age 69.0 vs 64.7 years, NYHA class III 17.9 vs 5.9%, and mean LVEF 49.3 vs 55.5%; all p&amp;lt;0.05). Median GDF15 level in the underweight group was higher (1,864 pg/mL [IQR 1,070-2,626]) but was similar in overweight and obese groups (1,285 [953, 1772] and 1,220 [888-1,789], respectively) compared to normal BMI group (1,276 [879-2,018]). During follow-up (median 10.3 years), 540 composite events of HF hospitalization or all-cause death occurred. The risk was higher in the underweight group (adjusted HR 1.8, 95%CI [1.3-2.5]) and lower in the obesity group (adjusted HR 0.8 [95% CI 0.6-0.9]) compared to the normal BMI group. An increased GDF15 incurred a consistently higher risk from underweight to obese groups; per unit increase in logGDF15 (pg/mL) was associated with 4.1, 2.4, 1.7 and 2.4 times higher risk, respectively. The optimal cut-off point for discriminating those with and without the composite events was 1,343 pg/mL in overall patients. This cut-off value performed well as a prognostic indicator across the continuous BMI spectrum including those with higher BMI (Figure). Conclusions The prognostic significance of GDF15 persisted across the BMI spectrum in patients with CHF. GDF15 may be useful for providing prognostic information across patients with a diverse range of BMI even in those with modest outcomes.HF events in high GDF15 across BMI

Observational and genetic associations of adiposity with cardiopulmonary multimorbidity: Linear and nonlinear Mendelian randomization analysis.

Whether adiposity traits are causal risk factors for cardiopulmonary multimorbidity (CP-MM) remains largely unknown. The aim of this study was to examine the causal role of adiposity traits in the development of CP-MM. This study involved 408,886 participants from the UK Biobank who had complete phenotypic and genetic data. Cox regression and Mendelian randomization (MR) analyses were conducted separately for observational and causal associations. During a median follow-up of 8.7 years, 1492 incident CP-MM were ascertained. In observational analysis, individuals with obesity had a hazard ratio (HR) of 1.51 (95% confidence intervals [CI]: 1.30-1.75) for developing CP-MM, compared with those with normal body mass index (BMI). Restricted cubic spline analyses showed a U-shaped relationship between continuous BMI and CP-MM (p < 0.001), whereas WHRadjBMI exhibited a linear relationship (p = 0.828). Joint analysis revealed that maintaining ideal waist-hip ratio (WHR) in adults with overweight is still effective in preventing CP-MM. In linear MR analysis, 1 kg/m2 increase in genetically predicted BMI and per 1% higher in genetically predicted WHRadjBMI was associated with 9% and 10% higher risk for incident CP-MM, respectively. Nonlinear MR analyses demonstrated linearity between genetically predicted BMI or WHRadjBMI and CP-MM. Adiposity may play a causal role in CP-MM development and represent a promising approach for multimorbidity prevention.

Higher Maternal Body Mass Index Is Associated With Lower Placental Expression of EPYC: A Genome-Wide Transcriptomic Study.

Elevated body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. The placental transcriptome may elucidate molecular mechanisms underlying these associations. We examined the association of first-trimester maternal BMI with the placental transcriptome in the Gen3G prospective cohort. We enrolled participants at 5 to 16 weeks of gestation and measured height and weight. We collected placenta samples at delivery. We performed whole-genome RNA sequencing using Illumina HiSeq 4000 and aligned RNA sequences based on the GTEx v8 pipeline. We conducted differential gene expression analysis of over 15 000 genes from 450 placental samples and reported the change in normalized gene expression per 1-unit increase in log2 BMI (kg/m2) as a continuous variable using Limma Voom. We adjusted models for maternal age, fetal sex, gestational age at delivery, gravidity, and surrogate variables accounting for technical variability. We compared participants with BMI of 18.5 to 24.9 mg/kg2 (N = 257) vs those with obesity (BMI ≥30 kg/m2, N = 82) in secondary analyses. Participants' mean ± SD age was 28.2 ± 4.4 years and BMI was 25.4 ± 5.5 kg/m2 in early pregnancy. Higher maternal BMI was associated with lower placental expression of EPYC (slope = -1.94, false discovery rate [FDR]-adjusted P = 7.3 × 10-6 for continuous BMI; log2 fold change = -1.35, FDR-adjusted P = 3.4 × 10-3 for BMI ≥30 vs BMI 18.5-24.9 kg/m2) and with higher placental expression of IGFBP6, CHRDL1, and CXCL13 after adjustment for covariates and accounting for multiple testing (FDR < 0.05). Our genome-wide transcriptomic study revealed novel genes potentially implicated in placental biologic response to higher maternal BMI in early pregnancy.

The relationships between Physical activity and asthma control and Body Mass Index (BMI) in patients with asthma

Objective Asthma is one of the most common chronic conditions in developed countries. We examined whether physical activity (PA) is related to asthma control and body mass index (BMI) in asthma patients. Methods Cross-sectional data collected on PA (ActiGraph GT3X-BT), asthma control (the Asthma Control Questionnaire; ACQ), and BMI were examined in 206 adults (mean[sd] age 47.2[13.8] years; 49.5% had an obese BMI) with clinically diagnosed asthma. Relationships between PA and continuous BMI and asthma control were assessed using linear regression. Differences in PA across obesity (non-obese: <30 Kg/m2/obese: ≥30 Kg/m2) and asthma control categories (controlled: ≤0.75/uncontrolled: >0.75 ACQ score) were also examined. Results Median (p25, p75) steps counts and peak cadence were 6035 (4248, 8461) steps/day and 123 (115, 133) steps in a minute, respectively. There were nearly 2000 fewer steps/day among those with uncontrolled asthma versus controlled and among those with obese BMI versus nonobese, respectively (both p < 0.05). In regression models adjusted for relevant covariates each 1-unit increase in ACQ score was associated with −686 [95%CI −997, −13] (p ≤ 0.05) average steps/day. The statistical significance of these findings was attenuated (p ≥ 0.05) when BMI was added to the model. However, the point estimate was not reduced (-766 [95%CI −1060, 34]. Conclusions Overall step counts were low in this population despite peak cadence values suggesting that most participants could perform moderate intensity activity. Increasing step counts should be considered an important lifestyle intervention goal in obese and non-obese asthma patients with low PA levels.

Maternal Underweight is Associated with Lower Fracture Risk after Pregnancy: A Nationwide Register-Based Study in Finland

Lower body mass index (BMI) is associated with a higher risk for osteoporotic fractures in the postmenopausal population. However, in the fertile-aged population, the association between BMI and risk for fracture is not well studied. Our aim, therefore, is to investigate whether lower BMI (<18.5 kg/m2) affects the risk for fractures requiring hospitalization after delivery in fertile-aged women when compared to women of normal weight (18.5 ≤ BMI < 25 kg/m2). In this nationwide registry-based cohort study, all pregnancies were gathered from the National Medical Birth Register. The data were linked with data from the Care Register for Health Care, which includes information of all fractures leading to hospitalization or treated as outpatients for fertile-aged females (15–49 years), for the period 2004–2018. The annual rate of pregnancies with maternal pre-pregnancy underweight in a high-income country was calculated. Cox regression was used to calculate adjusted hazard ratios (aHR) of lower BMI for the risk for fracture within 5 years after delivery. The association between the risk of fracture and continuous BMI was assessed using logistic regression and presented with adjusted odds ratios (aORs) with 95% CIs. In total, 20,784 women were included in the underweight group and 344,753 in the normal weight group. Women in the underweight group had a lower overall risk for any fractures during the 5-year follow-up (aHR 0.75, CI 0.61–0.94). The odds for all fractures (aOR 1.07, CI 1.04–1.09 per BMI-unit upwards for all fractures) increased as pre-pregnancy BMI increased. Despite previous findings of a higher risk for fractures for underweight patients in the older population, the risk for fractures after pregnancy was lower among fertile-aged women with lower BMI.

Abstract PD12-07: PD12-07 The effect of BMI on the pathological response after neoadjuvant systemic therapy in breast cancer patients: a nationwide retrospective study

Abstract Background: Neoadjuvant systemic therapy is increasingly applied in breast cancer patients to improve surgical and oncological outcomes. There is only limited data from clinical practice on the relevance of body mass index (BMI) on the pathologic complete response (pCR) rate following neoadjuvant systemic treatment (NST). We aimed to retrospectively analyze the impact of BMI on pCR after NST for Dutch breast cancer patients. Methods: Patients diagnosed with invasive breast cancer between 2019 and 2021 who were treated with NST followed by a surgical procedure, were selected from the Netherlands Cancer Registry (NCR). Patients were divided into three groups based on BMI: patients with underweight/normal weight (BMI&amp;lt; 25 kg/m2), patients with overweight (BMI 25-29.9 kg/m2) and patients with obesity (BMI&amp;gt;30 kg/m2). Patients with unknown BMI, ER/PR/HER2 or pCR status were excluded for analysis. The primary outcome was pCR after NST. The association between BMI and pCR was estimated using logistic regression models with the expression of odds ratios (ORs). Results: After applying in- and exclusion criteria, 4430 patients were included for analysis, statified into four molecular breast cancer subtypes; HR+/HER2- (n=2256), HR+/HER2- (n=722), HR-/HER2+ (n=405) and HR-/HER2- (n=1047). The predictors age, differentiation grade, histological type, clinical tumor (cT) and nodal (cN) stage and molecular breast cancer subtype were found siginificant for achieving pCR after NST. Multivariabele regression analysis identified differentiation grade, cT and cN stage and molecular subtype as independent predictors for pCR after NST. There was no association between pCR and (continuous or categorical) BMI. Above mentioned analyses performed by stratification according to molecular breast cancer subtype, also showed no statistically meaningful association between BMI and pCR. Conclusion: In this nationwide retrospective cohort study, evaluating 3340 patients with invasive breast cancer, we found no evidence of BMI being a predictive factor for achieving pCR following NST in neither the whole cohort, nor stratified according to molecular breast cancer subtype. Table 1. Multivariable regression analysis of the total cohort Citation Format: Britt Jansen, Anke Gielen, Mariette Agteroff, Marissa van Maaren, Sandra Beijer, Martine Moossdorff, Marjolein Smidt, Emily Postma. PD12-07 The effect of BMI on the pathological response after neoadjuvant systemic therapy in breast cancer patients: a nationwide retrospective study [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 PD12-07.

Abstract P240: Higher Body Mass Index is Associated With Lower Placental Expression of EPYC: Results From a Genome-Wide Transcriptomic Study in the Gen3G Cohort

Background: Elevated maternal body mass index (BMI) in pregnancy is associated with adverse maternal and fetal outcomes. Identification of alterations in the placental transcriptome may elucidate molecular markers of the biological pathways underlying these associations. Methods: We investigated the association of first trimester maternal BMI with the placental transcriptome in Gen3G, a large population-based pregnancy cohort. We completed RNA sequencing of 449 placental samples and performed differential gene expression analysis of over 15,000 genes (Limma Voom). We used maternal BMI as a continuous variable, with estimates reported as change in normalized gene expression per 1-unit increase in BMI (kg/m2), as well as a categorical variable (participants with normal weight (N=270) vs. obesity (N=82)), with RNA expression estimates reported as log2 fold changes. We adjusted models for maternal age, fetal sex, gestational age and 6 surrogate variables inferred from the expression data to adjust for batch effects and other unmeasured sources of variability. We accounted for multiple testing using False Discovery Rate (FDR). Sensitivity analyses were performed by removing cases of gestational diabetes and hypertensive disorders in pregnancy. Results: At enrollment in early pregnancy, participants had a mean ± SD age of 28.2 ± 4.4 years and measured BMI of 25.4 ± 5.5 kg/m 2 ; 57% of participants were categorized in normal weight, 22% in overweight and 18% in obesity BMI categories. Maternal BMI was significantly associated with decreased expression of EPYC , a gene that regulates fibrillogenesis (slope= -0.14, FDR-adjusted P=1.68x10 -5 for continuous BMI; log2 fold change= -1.71, FDR-adjusted P=1.06x10 -2 for obesity vs. normal weight). Both sensitivity analyses with the removal of gestational diabetes and hypertensive disorders revealed similar associations for EPYC . Conclusions: We identified an association between elevated maternal BMI and downregulation of EPYC expression in the placenta. Additional studies are required to examine the role of placental EPYC expression in maternal and fetal health.

Abstract P548: Epigenome-Wide Association Meta-Analysis of Obesity in African Americans

Background: Despite considerable advances in obesity genetics, much remains to be learned regarding the pathway from genes to obesity development. Prior studies have shown that that 40-70% of the variation in body mass index (BMI), a measure of obesity, is due to heritable factors, yet BMI-identified genetic variants only account for a limited portion of the heritability. Research suggests epigenetic variation, which reflects both genetic and environmental influence, may account for some of the missing heritability. However, such studies have largely been conducted in primarily European ancestry populations, despite the disproportionate burden of obesity in African Americans (AAs). Methods: To identify CpG sites associated with BMI in AAs, we conducted an epigenome-wide association study (EWAS) using participants from the Jackson Heart Study (JHS, n=1604) and a subset of AA participants from the Multi-Ethnic Study of Atherosclerosis (MESA, n=179) using the Illumina HumanMethylationEPIC array (~850K CpG sites). Analyses were stratified by study and sex and meta-analyzed using an inverse-variance weighted approach. EWAS was performed using a linear regression model with methylation M-values (n=573,388 CpGs) as the outcome and continuous BMI as the predictor. Covariates in the linear models included age, centered-mean-age-squared, smoking status (never/past/current), 10 genetic ancestry principal components, and Houseman-estimated blood cell proportions. Results: The meta-analysis resulted in 204 CpGs that reached epigenome-wide significance (p &lt; 8.72 x 10 -8 ) after multiple-testing correction, and these include both previously identified and novel BMI-associated sites. 48 of the 204 have been previously reported in EWAS of obesity phenotypes, 11 of which were in studies of AAs. 156 of the methylation sites significantly associated with BMI in this study are novel, and potentially AA-specific. Differentially methylated region (DMR) analysis showed significant association of these CpGs in the promoters of genes previously associated with obesity traits, such as SOCS3, ABCG1, and TGFB1 , although TGFB1 had not previously been associated in AAs. In addition, the DMR analysis revealed novel obesity-associated CpGs in genes, including JAK3, which has previously been shown to have differential gene expression in association with BMI in MESA. Conclusion: We identified novel, potentially AA-specific, methylation sites associated with BMI in the largest African-ancestry EWAS conducted thus far, supporting that continued analysis in diverse populations is crucial for increased understanding of obesity.

Type 1 diabetes management: Room for improvement.

Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.

Excess body weight and specific types of depressive symptoms: Is there a mediating role of systemic low-grade inflammation?

ObjectivesObesity is associated with an increased risk of depression. Systemic low-grade inflammation, a plausible consequence of obesity, has also been linked to depression. However, the potential mediating effects of systemic low-grade inflammation on the association between excess body weight and specific symptom domains of depression remain uncertain. This study examined whether systemic low-grade inflammation mediated the associations of excess body weight (overweight and obesity) with subsequent overall, cognitive-affective, and somatic depressive symptoms. DesignThis study used a prospective cohort design. MethodsThe final analytical sample included 4,942 adults aged ≥50 years drawn from the English Longitudinal Study of Ageing (ELSA). Body mass index (BMI) and covariates were ascertained at baseline (wave 4, 2008/09). Continuous BMI scores were divided into four categories: ‘normal weight’ (18.5 ≤ BMI <25 kg/m2); ‘overweight’ (25 ≤ BMI <30 kg/m2); ‘obesity’ (BMI ≥30 kg/m2); in addition to ‘excess body weight’ (‘overweight’ and ‘obesity’ combined). Covariates included sociodemographic variables, behavioural factors, and chronic physical conditions. Serum concentrations of CRP were measured at wave 6 (2012/13). Depressive symptoms were assessed at baseline and ten years later (wave 9, 2018/19), using the 8-item Centre for Epidemiological Studies Depression (CES-D) Scale. Two symptom domains were constructed, distinguishing between cognitive-affective (depressed mood, loneliness, sadness, enjoyment in life, and happiness) and somatic (sleep problems, low energy levels, and fatigue) symptoms. Mediation analyses were performed to examine whether CRP statistically mediated the associations between BMI categories and depressive symptoms. ResultsIn multivariable-adjusted analyses, excess body weight was associated with elevated somatic (OR = 1.231, 95% CI: 1.029, 1.473), but not cognitive-affective or overall depressive symptoms at follow-up. Higher CRP was associated with elevated somatic (OR = 1.156, 95% CI: 1.061, 1.259), but not cognitive-affective or overall depressive symptoms. CRP acted as a partial mediator (14.92%) of the association between excess body weight and elevated somatic, but not cognitive-affective, or overall depressive symptoms. ConclusionSystemic low-grade inflammation may partially explain the association of excess body weight with somatic depressive symptoms, but not the associations with cognitive-affective or overall depressive symptoms.

Abstract 12547: Obesity as Risk Factor for Malignant Ventricular Arrhythmias in Phospholamban Cardiomyopathy

Introduction: The pathogenic phospholamban (PLN) p.Arg14del mutation can cause severe arrhythmogenic cardiomyopathy. However, disease penetrance and clinical course are heterogenous and can differ largely between affected individuals. The impact of external factors - such as lifestyle - on the clinical course has not been studied yet. Hypothesis: We hypothesized that obese PLN mutation carriers have worse clinical outcomes, characterized by a higher burden of malignant ventricular arrhythmias (MVA). Methods: PLN p.Arg14del mutation carriers from the Dutch PLN registry with available follow-up (FU) data were included. MVA was defined as either sustained ventricular tachycardia, ventricular fibrillation, appropriate implantable cardioverter defibrillator intervention or (aborted) cardiac arrest. Patients were categorized into three groups based on their body mass index (BMI): normal weight (BMI 18.5 - 24.9 kg/m 2 ), overweight (25.0 - 29.9 kg/m 2 ) and obese (BMI &gt; 30.0 kg/m 2 ). Mutation carriers with a BMI &lt; 18.5 kg/m 2 or MVA at baseline were excluded. Results: A total of 179 PLN mutation carriers were included in this analysis: 105 (58.7%) normal weight, 59 (33.0%) overweight, 15 (8.4%) obese. The obese group had the highest percentage of MVA (26.7%), followed by the overweight (13.6%) and normal weight (4.8%) groups, as shown in the Kaplan-Meier curve (log-rank 0.016). Continuous BMI was significantly correlated with the incidence of MVA during FU: hazard ratio 1.15 [1.04 - 1.27; p=0.006] per 1-unit increase of BMI, adjusted for age, sex and comorbidities (hypertension, type 2 diabetes mellitus, dyslipidemia, coronary heart disease). Additionally, BMI value predicted MVA with an area under the curve of 0.73 [0.63 - 0.84; p=0.002]. Conclusions: In PLN p.Arg14del mutation carriers, high BMI values and obesity are associated with higher incidence of MVA. This suggests a potential role for lifestyle intervention in the management of this genetic cardiomyopathy.

Elevated body mass index increases the risk of cardiovascular events in hypertensive patients accompanied with obstructive sleep apnea: A cohort study

BackgroundEffects of body mass index (BMI) on cardiovascular events are inconsistent. We aimed to investigate the association of BMI with cardiovascular events in hypertensives with obstructive sleep apnea (OSA). MethodsHypertensives with OSA diagnosed with polysomnography between 2011 and 2013 in UROSAH cohort were followed up till Jan 2021. Outcomes were non-fatal cardiovascular events and cardiac death. Cox regression was used to estimate the relationship of continuous and categorical BMI with total and specific outcomes. Sensitivity analyses were performed by excluding those on OSA treatment or underweight patients. Stratified analyses were conducted by parameters including sex and age. Results2239 hypertensives with OSA were included with 405 normal weight (BMI<25 kg/m2), 1164 overweight (25–29.9 kg/m2) and 670 obesity (≥30 kg/m2). 206 non-fatal cardiovascular events and 18 cardiac death were recorded during 6.6 years follow-up. Compared with normal weight group, overweight (HR=1.53, 95%CI: 1.01–2.32, P = 0.047) and obesity groups (1.85, 1.19–2.86, P = 0.006) showed increased risk for cardiovascular events, significant in obesity group and marginal in overweight group in fully-adjusted model. In specific events, obesity showed significantly elevated HR for non-fatal cardiovascular events (1.64, 1.04–2.60, P = 0.035). Continuous BMI showed significantly increased HR for total and specific events in all models. Sensitivity analysis yielded consistent results. In stratification analysis, stronger association between obesity and cardiovascular events was observed in the young (HR=5.97, P interaction=0.030). ConclusionsBMI is in positive association with cardiovascular events in hypertensives with OSA, emphasizing importance of maintaining healthy BMI for prevention of adverse events in this population, on the basis of guideline-recommended treatment.

The association between different body mass index levels and midterm surgical revascularization outcomes.

There are conflicting results regarding the relationship between overweight/obesity and the outcomes of coronary artery bypass graft surgery (CABG), termed "the obesity paradox". This study aimed to evaluate the effects of body mass index (BMI) on the midterm outcomes of CABG. This historical cohort study included all patients who underwent isolated CABG at our center between 2007 and 2016. The patients were divided into five categories based on their preoperative BMIs (kg/m2): 18.5≤BMI<25, 25≤BMI<30, 30≤BMI<35, 35≤BMI<40, and BMI≥40. Patients with BMIs below 18.5 kg/m2 were excluded. The endpoints of this study were all-cause mortality and major adverse cardio-cerebrovascular events (MACCEs), comprising acute coronary syndromes, cerebrovascular accidents, and all-cause mortality at five years. For the assessment of the linearity of the relationship between continuous BMI and the outcomes, plots for time varying hazard ratio of BMI with outcomes were provided. Of 17 751 patients (BMI = 27.30 ±4.17 kg/m2) who underwent isolated CABG at our center, 17 602 patients (mean age = 61.16±9.47 y, 75.4% male) were included in this study. Multivariable analysis demonstrated that patients with pre-obesity and normal weight had similar outcomes, whereas patients with preoperative BMIs exceeding 30 kg/m2 kg/m2 had a significantly higher risk of 5-year all-cause mortality and 5-year MACCEs than those with pre-obesity. Additionally, a positive association existed between obesity degree and all-cause mortality and MACCEs. Further, BMIs of 40 kg/m2 or higher showed a trend toward higher MACCE risks (adjusted hazard ratio, 1.32; 95% confidence interval, 0.89 to 1.95), possibly due to the small sample size. A nonlinear, albeit negligible, association was also found between continuous BMI and the study endpoints. Our findings suggest that preoperative obesity (BMI>30 kg/m2) in patients who survive early after CABG is associated with an increased risk of 5-year all-cause mortality and 5-year MACCEs. These findings indicate that physicians and cardiac surgeons should encourage patients with high BMIs to reduce weight for risk modification.