Adjustment For Body Mass Index Research Articles

Sex-specific impact of GCKR rs1260326 polymorphism on metabolic traits in an older Japanese population: the Bunkyo Health Study.

Metabolic syndrome involves health problems influenced by aging and genetics. The glucokinase regulatory protein (GCKR) rs1260326 polymorphism (Leu446) is associated with metabolic traits. This study explores the impact of the GCKR rs1260326 polymorphism on metabolic traits in older Japanese with focusing on sex-specific differences. This cross-sectional study from the Bunkyo Health Study in Tokyo, Japan, examined 883 participants aged 65-84 years. Participants were excluded with diabetes, or on drug treatment for diabetes or dyslipidemia. The GCKR P446L polymorphism was analyzed and compared their characteristics of physical activity, dietary intake, body composition, and metabolic parameters. Study participants with GCKR rs1260326 genotypes (C/C 20.7%, C/T 47.6%, T/T 31.7%) had a median age of 72 years, and 60.4% were women. Men with the T/T genotype, as compared to the C/C genotype, had a lower body weight, body mass index (BMI), and skeletal mass index. This genotype also associated with lower fasting insulin, homeostasis model assessment of insulin resistance index (HOMA-IR), and higher Matsuda index, but not after adjustment for age, BMI, and physical activity. In contrast, women with the T/T genotype, compared to the C/C genotype, showed higher C-reactive protein, fibroblast growth factor 21, and Matsuda index. They also had lower fasting insulin, insulin area under the curve, and HOMA-IR; with these associations being independent of age, BMI, and physical activity. The GCKR rs1260326 genotype-affected metabolic traits differentially by sex in older Japanese. This highlights the need to consider sex differences in GCKR-related metabolic outcomes.

The relationship between lipoproteins and the risk of esophageal cancer: a Mendelian randomization study.

Esophageal cancer (EC) causes approximately 508,000 deaths annually, making it a significant cause of cancer-related mortality. While previous studies have suggested an association between lipoprotein levels and EC risk, the causal relationship remains unexplored. This study aims to investigate the causal link between lipoproteins and EC using Mendelian randomization (MR). This study employed MR to determine the causal effect between lipoproteins and EC risk, with body mass index (BMI) used as a confounder in multivariable MR (MVMR) analysis. Sensitivity analyses were conducted to assess the reliability of the results. Univariable MR (UVMR) analysis indicated that low-density lipoprotein (LDL) had a significant inverse association with EC risk (p = 0.03; OR = 0.89; 95%CI, 0.73-0.98), while high-density lipoprotein (HDL) and triglycerides showed no significant association. In the synthesis of findings across diverse datasets, LDL maintained a notable inverse association with the likelihood of EC (p < 0.001; OR = 0.89; 95%CI, 0.84-0.94). Triglyceride levels indicated a potential trend toward an adverse correlation with EC susceptibility (p = 0.03; OR = -0.94; 95%CI, 0.89-0.99), whereas HDL levels did not establish a definitive causal link with the occurrence of EC. MVMR analysis, adjusting for BMI, confirmed these findings. LDL exhibits a clear inverse causal relationship with EC risk, regardless of BMI adjustment. No causal effects were observed for HDL in relation to EC risk. Meanwhile, there is a small but statistically significant causal relationship between triglycerides and EC risk.

Correlation between HbA1c levels and left ventricular function in children with Type 1 Diabetes Mellitus

Background: Diabetic cardiomyopathy is one of the macrovascular complications in type 1 diabetes mellitus (T1DM). Left ventricular dysfunction primarily reflects diastolic dysfunction which is early sign of diabetic cardiomyopathy. Improved glycemic control can delay the onset and progression of this complication. An important indicator of long-term glycemic control is glycosylated hemoglobin (HbA1c). Objective: The aim of this study is to evaluate the correlation between HbA1c levels with left ventricular diastolic function in children with T1DM. Methods: This study was an observational study with cross-sectional design in children aged 1 month-18 years with T1DM, at Prof Dr. I.G.N.G. Ngoerah Hospital, Denpasar from November 2019–September 2021, using consecutive sampling. Glycosylated hemoglobin (HbA1c) was meassured by blood samping and LV function was assessed by using tissue Doppler imaging (TDI). Statistical analysis was done by Pearson and Spearman correlation test. A p-values of &lt;0.05 was considered statistically significant. Results: A total of 36 subjects were recruited in this study. There was a low positive correlation between HbA1c levels with E/e’ ratio (r=0.284, p=0.047), and MPI (r=0.358, p=0.020). After adjusting body mass index and duration of T1DM as confounding variables, we found a low positive correlation between HbA1c levels and E/e’ ratio (r=0.325, p=0.030), MPI (r = 0.390, p=0.020). Conclusion: HbA1C has a positive correlation with left ventricular diastolic function in children with T1DM.

Low vitamin D level increases women's breast cancer risks, Sulaimaniyah, Iraq: A case-control study.

Vitamin D (Vit D) is essential in maintaining calcium homeostasis and other body processes. It has been widely studied how Vit D affects cell cycle pathways and how it affects the development and prevention of breast cancer (BC). This study aimed to determine Vit D insufficiency linkage to the development of BC. In this case-control study, 130 women (65 BC patients and 65 healthy controls) aged 20-60 years who visited Shar Hospital Breast Center in Sulaimaniyah, Iraq, from December 2021 to May 2022 were included. Patients were selected after their diagnosis had been verified by breast ultrasound, mammography, and core biopsy. The ELISA test was used to measure the concentrations of serum Vit D and expressed in ng/ml. The results showed that the BC patients had considerably lower serum Vit D levels that were <20 ng/L in 66.1% (n=43) and 43.1% (n=28) in healthy controls. Compared to the control group (20.2±8.7), the mean Vit D level in BC patients was lower (17.8±8.6). A logistic regression test revealed a substantial increase in the risk of BC for low-level Vit D concentrations below 20 ng/L (OR 2.59, 95% CI 1.24-5.38; P=0.009). Vit D is still a significant risk factor for boosting the likelihood of developing BC after age and body mass index (BMI) adjustments (AOR 2.30, 95% CI 1.1-4.86; p=0.03 and AOR 3.67, 95% CI 1.55-8.7; p=0.002 for BC patients and controls, respectively). According to the outcomes of our investigations, we concluded that Vit D insufficiency raises the risk of BC among women in Sulaimaniyah, Iraq.

Longitudinally assessed maternal sleep position, measures of breathing during sleep, and fetal growth in high-risk pregnancies.

Subjective recall of supine sleep during pregnancy has been linked to increased risk of stillbirth, but longitudinal, objective data are lacking. We aimed to examine how sleep position and breathing parameters change throughout pregnancy, and investigated associations between maternal supine sleep, assessed objectively in early and late gestation, and fetal growth velocity in high-risk women. Women with singleton pregnancies and body mass index (BMI) ≥27 kg/m2 underwent level-III sleep apnea testing. Sleep position was assessed by accelerometry. We derived percentiles of estimated fetal weight and birthweight using FetalGPSR software, then calculated growth velocity as change in percentile/week between the second-trimester anatomy scan and birth. In total, 446 women were included, with N = 126 in the longitudinal sleep pattern analysis and N = 83 in the fetal growth analysis. Sleep-onset position and predominant sleep position were significantly correlated in both early (p = 0.001) and late (p < 0.01) pregnancy. However, supine going-to-bed position predicted predominant supine sleep in only 47% of women. Between early and late pregnancy there was a reduction in predominant supine sleepers (51.6% to 30.2%). Percent of sleep spent supine and oxygen desaturation index, in the third trimester, were significantly associated after BMI adjustment (B = 0.018, p = 0.04). Models did not suggest significant effects of early or late pregnancy supine sleep on growth velocity (p > 0.05). Going-to-bed position predicts predominant supine sleep in less than half of women with overweight and obesity. Time spent supine throughout pregnancy correlates with measures of sleep-disordered breathing. Maternal sleep position patterns did not affect fetal growth velocity in this high-risk population, but the study was not powered to detect differences.

Plasma levels of urea cycle related amino acids in association with risk of ischemic stroke: Findings from a nested case-control study

ObjectivesThe role of urea cycle related amino acids in the development of ischemic stroke (IS) remains unclear. The study aimed to evaluate the association of these amino acids with IS. Materials and MethodsWe conducted a case-control study nested within a cohort study in Changshu, Eastern China. A total of 321 cases and 321 controls matched by age and gender were finally included. Plasma levels of ornithine, arginine, spermidine, and proline were measured using ultra-high performance liquid chromatography–tandem mass-spectrometry (UHPLC–MS/MS). Odds ratios (ORs) and their 95 % confidence intervals (CIs) were calculated by conditional logistic regression analyses. ResultsPlasma ornithine was inversely associated with risk of IS [crude OR: 0.62 (95 % CI: 0.40-0.97)]. After adjustment for body mass index, smoking, hypertension, family history of stroke, estimated glomerular filtration rate, and total cholesterol, the corresponding ORs for the highest compared to the lowest quartiles was essentially unchanged [adjusted OR: 0.62 (95 % CI: 0.39-0.99)]. The risk association remained significant after repeating the analyses by excluding the first two years of follow-up. Plasma arginine, spermidine, and proline were not associated with the risk of IS. ConclusionWe observed that higher plasma levels of ornithine were associated with a lower risk of incident IS. Our novel findings suggest a protective role of ornithine in the pathogenesis of IS.

A Plasma Metabolite Score Related to Psychological Distress and Diabetes Risk: A Nested Case-control Study in US Women.

Psychological distress has been linked to diabetes risk. Few population-based, epidemiologic studies have investigated the potential molecular mechanisms (eg, metabolic dysregulation) underlying this association. To evaluate the association between a metabolomic signature for psychological distress and diabetes risk. 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 matched controls. Blood samples were collected between 1989 and 1990 and incident diabetes was diagnosed between 1992 and 2008. Based on our prior work, we calculated a weighted plasma metabolite-based distress score (MDS) comprised of 19 metabolites. We used conditional logistic regression accounting for matching factors and other diabetes risk factors to estimate odds ratios (OR) and 95% confidence intervals (CI) for diabetes risk according to MDS. After adjusting for sociodemographic factors, family history of diabetes, and health behaviors, the OR (95% CI) for diabetes risk across quintiles of the MDS was 1.00 (reference) for Q1, 1.16 (0.77, 1.73) for Q2, 1.30 (0.88, 1.91) for Q3, 1.99 (1.36, 2.92) for Q4, and 2.47 (1.66, 3.67) for Q5. Each SD increase in MDS was associated with 36% higher diabetes risk (95% CI: 1.21, 1.54; P-trend <.0001). This association was moderately attenuated after additional adjustment for body mass index (comparable OR: 1.17; 95% CI: 1.02, 1.35; P-trend = .02). The MDS explained 17.6% of the association between self-reported psychological distress (defined as presence of depression or anxiety symptoms) and diabetes risk (P = .04). MDS was significantly associated with diabetes risk in women. These results suggest that differences in multiple lipid and amino acid metabolites may underlie the observed association between psychological distress and diabetes risk.

Blood Pressure Trajectories Through the First Year Postpartum in Overweight or Obese Individuals Following a Hypertensive Disorder of Pregnancy.

Hypertensive disorders of pregnancy are associated with cardiovascular disease; however, patterns of blood pressure (BP) recovery are understudied. We compared pregnancy and postpartum BP trajectories among individuals with hypertensive disorders of pregnancy who developed persistent hypertension at 1-year postpartum compared with individuals with normalization of BP. We used data from a randomized clinical trial of individuals with overweight, obesity, and hypertensive disorders of pregnancy conducted in the first year after delivery. Pregnancy BPs were obtained during prenatal visits; postpartum BPs were prospectively obtained through home monitoring. Demographic characteristics and trajectories were compared by hypertensive status (systolic BP ≥130 mm Hg, diastolic BP ≥80 mm Hg, or use of antihypertensive medications) at 1 year. We used repeated BP measures to fit separate mixed-effects linear regression models for pregnancy and postpartum using restricted cubic splines. We included 129 individuals; 75 (58%) individuals progressed to hypertension by 1-year postpartum. Individuals with hypertension were older, delivered at earlier gestational ages, and had higher body mass index at 1-year postpartum compared with those with normalization. Individuals with hypertension had similar BP trajectories during pregnancy to those with BP normalization but a significantly different BP trajectory (P<0.01 for systolic and diastolic BPs) in the first year postpartum. These differences persisted in multivariable models after adjustment for early pregnancy body mass index, age, and severity of hypertensive disorder of pregnancy (P<0.01 for systolic and diastolic BPs). BP trajectories in the first year postpartum, but not during pregnancy, may provide important information for risk stratification after a hypertensive disorder of pregnancy. URL: https://clinicaltrials.gov; Unique identifier: NCT03749746.

Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization

BackgroundThe causal associations between psychiatric disorders and falls risk remains uncertain. Consequently, this study aimed to explore the causal relationship between genetically determined three common psychiatric disorders and the risk of falls based on Mendelian randomization (MR).MethodsThe genome-wide association study (GWAS) data for schizophrenia (SCZ) (N = 320,404), major depressive disorder (MDD) (N = 480,359), and Alzheimer's disease (AD) (N = 63,926) were obtained as exposures. The GWAS data for falls risk (N = 451,179) was obtained as outcome. Univariate Mendelian randomization (UVMR) was used to evaluate the direct causal relationship between SCZ, MDD, AD, and risk of falls. Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analysis was performed to assess the validity of the casualty. Multivariate Mendelian randomization (MVMR) analysis was conducted after adjusting body mass index and smoking initiation. Mediating MR was conducted to calculate the mediating effects of potential intermediaries.ResultsUVMR analysis showed that SCZ (OR 1.02, 95% CI 1.01–1.04, p = 8.03E−03) and MDD (OR 1.15, 95% CI 1.08–1.22, p = 1.38E−05) were positively associated with the risk of falls. Sensitivity analysis results were reliable and robust. MVMR results indicated that the relationship between MDD and SCZ and falls risk remained significant. Mediating MR results demonstrated that smoking initiation mediated partial causal effect of SCZ (0.65%, P = 0.03) and MDD (14.82%, P = 2.02E−03) on risk of falls.ConclusionsThis study provides genetic evidence for a causal relationship of individuals with SCZ and MDD on an increased risk of falls. Healthcare providers should be aware of the risk of falls in MDD and SCZ patients and develop strategies accordingly.

Bidirectional relationship between type 2 diabetes mellitus and coronary artery disease: Prospective cohort study and genetic analyses.

While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD. We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase / Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adj BMI]: Ncase / Ncontrol = 50,409/523,897) and for CAD ( Ncase / Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase / Ncontrol = 180,834/1,159,055). Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01-2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63-1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75 ), which was largely independent of BMI (T2DM adj BMI-CAD: rg = 0.31, P = 1.20 × 10 -36 ). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Impact of smoking cessation on non-alcoholic fatty liver disease prevalence: a systematic review and meta-analysis

ObjectivesThe negative effects of smoking on numerous cardiovascular and metabolic diseases have been widely acknowledged. However, the potential effect of smoking cessation is relatively unelucidated. The objective of this study...

Strong and graded associations between level of asthma severity and all-cause hospital care use and costs in the UK

BackgroundHospital admissions account for a large share of the healthcare costs incurred by people with asthma. We assessed the hospital care use and costs associated with asthma severity using the...

Educational patterning in biological health seven years apart: Findings from the Tromsø Study

BackgroundSocial-to-biological processes is one set of mechanisms underlying the relationship between social position and health. However, very few studies have focused on the relationship between social factors and biology at multiple time points. This work investigates the relationship between education and the dynamic changes in a composite Biological Health Score (BHS) using two time points seven years apart in a Norwegian adult population. MethodsWe used data from individuals aged 30 years and above who participated in Tromsø6 (2007–2008) and Tromsø7 (2015–2016) (n = 8117). BHS was defined using ten biomarkers measured from blood samples and representing three physiological systems (cardiovascular, metabolic, inflammatory). The higher the BHS, the poorer the health status. FindingsLinear regression models carried out on BHS revealed a strong educational gradient at two distinct time points but also over time. People with lower educational attainment were at higher risk of poor biological health at a given time point (βlow education Tromsø6=0.30 [95 %-CI=0.18–0.43] and βlow education Tromsø7=0.30 [95 %-CI=0.17–0.42]). They also presented higher longitudinal BHS compared to people with higher education (βlow education = 0.89 [95 %-CI=0.56–1.23]). Certain biomarkers related to the cardiovascular system and the metabolic system were strongly socially distributed, even after adjustment for sex, age, health behaviours and body mass index. ConclusionThis longitudinal analysis highlights that participants with lower education had their biological health deteriorated to a greater extent over time compared to people with higher education. Our findings provide added evidence of the biological embodiment of social position, particularly with respect to dynamic aspects for which little evidence exists.

Association between cytomegalovirus infection and cancer‑related mortality in the US adults

PurposeIn a nationwide cohort of US adults, an exploration of the association between cytomegalovirus (CMV) infection and cancer‑related mortality was conducted. Materials and methodsWe acquired data from the National Health and Nutrition Examination Survey III (1988–1994), including 11,138 individuals who were aged 18–90 years at enrollment and underwent CMV serology assessments. CMV infection was determined by CMV antibody testing. Cancer‑related mortality status was ascertained until December 2019 utilizing the National Death Index linkage data and determined by neoplasms. The Cox proportional hazard model was applied to estimate the potential association between CMV infection and the risk of cancer-related mortality. ResultsDuring a median follow-up of 26.1 years, 1514 cancer‑related deaths were identified in the study cohort. After adjusting for age, sex, and ethnicity, CMV infection was associated with a higher hazard of cancer‑related mortality (hazard ratio [HR]: 1.39, 95 % CI: 1.13, 1.70). Further adjustments for body mass index, family income, and smoking status slightly attenuated the magnitude of the association (HR: 1.24, 95 % CI: 1.00, 1.53). However, no significant interaction was observed among gender by subgroup analysis. ConclusionsCMV infection might be an independent risk factor for cancer‑related mortality among US adults. Future studies could focus on the mechanisms through which CMV infection influences mortality induced by neoplasms and develop targeted interventions to reduce the risk.

Association between BMI trajectories from childhood to early adulthood and the carotid intima-media thickness in early adulthood: Tehran lipid and glucose study

Background and aimsChildhood and adolescence overweight/obesity is an important predictor of obesity and increased long-term cardiometabolic abnormalities in adulthood. In this study, we aimed to investigate the association of body mass index (BMI) and waist circumference (WC) trajectories among children and adolescents with adulthood carotid intima-media thickness (cIMT) as a determinant of subclinical atherosclerosis.MethodsIn this prospective cohort study, 1265 participants aged 3 to 18 were followed up for 18 years. By using Latent Class Growth Analysis, three groups of BMI and WC trajectory were defined; low stable, moderate-increasing, and high-increasing. Linear and logistic regression analysis were used to investigate the association of each lifetime BMI and WC trajectory group with cIMT.ResultsAlthough the high-increasing BMI trajectory group was significantly associated with higher cIMT (ß=0.0464, P < 0.001), moderate-increase was not (ß=0.0096, P = 0.102); in reference to the low-stable BMI trajectory group. Among WC trajectory groups, both moderate- (ß=0.0177, P = 0.006) and high-increasing (ß=0.0533, P < 0.001), in reference to the low-stable group, were significantly associated with higher cIMT. The results did not change after adjustment for baseline BMI. The ORs of high-increasing BMI, moderate-increasing WC, and high-increasing WC trajectories were 3.24, 1.92, and 3.29, respectively for high cIMT.ConclusionOur study resulted that a high-increasing trajectory of childhood BMI and moderate- and high-increasing trajectories of childhood WC are associated with higher cIMT and higher risk of high-cIMT. Regular monitoring and screening of BMI and WC trajectory from childhood may improve identifying individuals with high risks of cardiovascular disease, more accurately.

Causal Association between Tea Intake and Acute Cerebrovascular Events: A Multivariate Mendelian Randomized Study in European Populations

BackgroundNumerous research works have investigated the association between tea consumption and the risk of acute cerebrovascular events; however, the results are inconsistent. ObjectivesWe used Mendelian randomization (MR) to evaluate the causal association between tea intake and several acute cerebrovascular events, including any ischemic stroke, large atherosclerotic stroke (LAS), cardiogenic embolic stroke (CES), small vessel stroke (SVS), intracranial hemorrhage (ICH), and subarachnoid hemorrhage (SAH). MethodsWe obtained summary genome-wide association study (GWAS) data on tea intake and acute cerebrovascular events in populations of European ancestry. The GWAS on tea intake is derived from the UK Biobank, where we have chosen single-nucleotide polymorphisms (SNPs) closely associated with it as instrumental variables. We also obtained summary data on ischemic stroke from a GWAS meta-analysis, as well as summary data on ICH and SAH from the FinnGen study. We first explored the causal association between tea intake and several acute cerebrovascular events using univariate Mendelian randomization (UVMR), and then further assessed the causal association between tea intake and SVS using multivariate Mendelian randomization (MVMR) corrected for multiple confounders. ResultsIn UVMR, genetically predicted increases in tea intake were linked to a lower risk of SVS (OR: 0.58; 95% CI: 0.39, 0.86). There was no causal association between tea intake and the risk of other acute cerebrovascular events. In the MVMR, our results show that there was still a significant causal association between drinking tea and SVS, after adjusting body mass index, total cholesterol, low-density lipoprotein cholesterol, diabetes, hypertension, smoking, and alcohol consumption. ConclusionThis MR study provides new genetic evidence that increased tea intake reduces the risk of SVS in the European population. However, possibly because of limited statistical power, the study did not find that tea consumption reduced the risk of several other acute cerebrovascular events.

Early life cardiovascular risk factor trajectories and vascular aging in midlife: a 30-year prospective cohort study

Abstract Background Vascular aging, as assessed by structural and functional arterial properties, is an independent predictor of cardiovascular outcomes. We aimed to explore the associations of individual cardiovascular risk factors from childhood to midlife and their accumulation over a 30-year span with vascular aging in midlife. Methods Using data from the ongoing cohort of Hanzhong Adolescent Hypertension study, 2180 participants aged 6 to 18 years at baseline were followed for over 30 years. Distinct trajectories of systolic blood pressure (SBP), body mass index (BMI), and heart rate (HR) from childhood to midlife were identified by group-based trajectory modeling. Vascular aging was assessed by carotid intima–media thickness (cIMT) or brachial-ankle pulse wave velocity (baPWV). Results We identified 4 distinct SBP trajectories, 3 distinct BMI trajectories and 2 distinct HR trajectories from childhood to midlife. Persistently-increasing SBP, high-increasing BMI, and high-stable HR were all shown to have a positive association with baPWV in midlife. For cIMT, similar associations were observed for persistently-increasing SBP and high-increasing BMI. After further adjustment for SBP, BMI and HR at the time of vascular assessment in 2017, associations were also observed for cardiovascular risk factor trajectories accumulation with baPWV (β=0.656 (95%CI, 0.265-1.047)] and with cIMT [β=0.045 (95%CI, 0.011-0.079)] in adulthood. Conclusions Longitudinal exposure to individual cardiovascular risk factors from childhood to midlife and cardiovascular risk factor accumulation were associated with an increased risk of vascular aging in midlife. Our study lends support for early targeting of risk factors in order to prevent cardiovascular disease later in life.Long-term SBP, BMI, HR trajectories

Abstract 15614: Pericardial and Abdominal Visceral Adiposity Are Associated With Increased Risk of Hospitalization or Death From SARS-CoV-2 Infection: A Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study

Background Obesity increases risk of death from SARS-CoV-2 infection. Excess ectopic fat may increase this risk through inflammation, hypercoagulability, and immune dysfunction. We hypothesized that greater pericardial (PAT) and visceral adipose tissue (VAT) would associate with higher risk of hospitalization or death from SARS-CoV-2. Methods C4R collected SARS-CoV-2 outcomes from US-based cohort studies. These were linked to chest and abdominal CT scans obtained from Jackson Heart (2007-2010) and CARDIA (2010-2011) studies. We standardized PAT across cohorts and VAT within each cohort to account for differences in VAT measurement protocols. Our outcome was COVID-related hospitalization or death from March 2020 to February 2023 assessed via questionnaires, serosurvey, and record review. Logistic regression models were adjusted for age, sex, race/ethnicity, education, smoking status, and cohort. We adjusted for body mass index (BMI) at COVID assessment in secondary models. Results We included 3002 subjects with mean (SD) age of 62 (6) years, of whom 62% were women, 41% White, 59% Black, 59% never smokers, and 13% current smokers. Sixty-one subjects (2%) had SARS-CoV-2 related hospitalization or death. Every 1-standard deviation (SD) increment in PAT volume was associated with 79% higher odds of hospitalization or death (95%CI 1.38-2.33, Fig A); the estimate was similar after adjusting for BMI (OR 1.71, 95%CI 1.27-2.31). Abdominal VAT was associated with higher odds of hospitalization or death (OR 1.47 per 1 SD, 95%CI 1.20-1.81, Fig B), even after adjustment for BMI (OR 1.35, 95%CI 1.05-1.72). Conclusion Greater pericardial or visceral adiposity measured 10-15 years prior to SARS-CoV-2 emergence, was associated with higher odds of hospitalization or death from SARS-CoV-2 independent of BMI. Lowering PAT and VAT may have collateral benefit for those who develop SARS-CoV-2 infection. Further study of the role of visceral adipose in viral infection is needed.

Abstract 15798: Clonal Hematopoiesis of Indeterminate Potential is Associated With Pro-Inflammatory Markers in Patients With Established Coronary Artery Disease

Introduction: Progression of atherosclerosis is a result of systemic inflammation. Clonal hematopoiesis of indeterminate potential (CHIP) has been shown to be associated with atherosclerosis, but pathways that lead to this are still not fully elucidated. Hypothesis: CHIP may contribute to atherosclerosis by facilitating low-grade inflammatory response. Methods: 130 patients younger than 80 years, who were hospitalized for acute coronary syndrome or for myocardial revascularization were included in this study and followed for 18 months post-intervention. Targeted next-generation sequencing (NGS) was performed on peripheral blood mononuclear cells to detect CHIP mutations with a variant allelic fraction &gt; 2% in 92 genes. Subsequently, multiplexed proteomic analysis with extension proximity assays (EPA) was used to quantify circulating pro-inflammatory biomarkers potentially related to CHIP. Results: Some 17.6 % (23) of 130 patients were detected with CHIP mutations. Patients with mutations in either DNA methyltransferase 3alpha (DNMT3A) or Tet methylcytosine dioxygenase 2 (TET2) showed significantly higher body mass index (BMI) ( p =0.010), inflammatory markers (high sensitivity C-reactive protein p =0.015, interleukin- 6 p =0.002, chemerin p =0.034) as well as higher markers of myocardial overload (troponin T p =0.022 and NT-proBNP). In multivariable model adjusted for BMI, age, and gender we found that the inflammatory markers HGF, IL10RB, IL5RA, IL18, OSM, PD-L1, TNFRSF9, and TNFSF14 presented statistically significant association with CHIP (p&lt;0.01). Interestingly, these differently expressed proteins form an overlapping network between TET2 and DNMT3A mutations pointing to cytokine receptor activity, inflammatory response, and leucocyte activation pathways. Conclusions: There is a significant association between CHIP and enhanced inflammatory response in patients with coronary artery disease, even after adjustment for age and BMI.

Inter-pregnancy interval and placental weight. A population based follow-up study in Norway

IntroductionWe studied changes in placental weight from the first to the second delivery according to length of the inter-pregnancy interval. MethodsWe followed all women in Norway from their first to their second successive singleton pregnancy during the years 1999–2019, a total of 271 184 women. We used data from the Medical Birth Registry of Norway and studied changes in placental weight (in grams (g)) according to the length of the inter-pregnancy. Adjustments were made for year and maternal age at first delivery, changes in the prevalence of maternal diseases (hypertension and diabetes), and a new father to the second pregnancy. ResultsMean placental weight increased from 655 g at the first delivery to 680 g at the second. The adjusted increase in placental weight was highest at inter-pregnancy intervals <6 months; 38.2 g (95 % CI 33.0g–43.4 g) versus 23.2 g (95 % CI 18.8g–27.7 g) at inter-pregnancy interval 6–17 months. At inter-pregnancy intervals ≥18 months, placental weight remained higher than at the first delivery, but was non-different from inter-pregnancy intervals 6–17 months. Also, after additional adjustment for daily smoking and body mass index in sub-samples, we found the highest increase in placental weight at the shortest inter-pregnancy interval. We estimated no difference in gestational age at delivery or placental to birthweight ratio according to inter-pregnancy interval. DiscussionPlacental weight increased from the first to the second pregnancy, and the increase was most pronounced at short inter-pregnancy intervals. The biological causes and implications of such findings remain to be studied.