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Item Adiposity has unique influence on the renin-aldosterone axis and blood pressure in black children(Elsevier, 2013-11) Yu, Zhangsheng; Eckert, George; Liu, Hai; Pratt, J. Howard; Tu, Wanzhu; Medicine, School of MedicineOBJECTIVE: To comparatively examine the effects of adiposity on the levels of plasma renin activity (PRA), plasma aldosterone concentration (PAC), and aldosterone-renin ratio (ARR) in young black and white children. STUDY DESIGN: We prospectively assessed 248 black and 345 white children and adolescents. A novel analytical technique was used to assess the concurrent influences of age and body mass index (BMI) on PRA, PAC, and ARR. The estimated effects were depicted by colored contour plots. RESULTS: In contrast to whites, blacks had lower PRA (2.76 vs 3.36 ng/mL/h; P < .001) and lower PAC (9.01 vs 14.59 ng/dL; P < .001). In blacks, BMI was negatively associated with PRA (P = .001), consistent with an association with a more expanded plasma volume; there was no association with PAC. In whites, BMI was positively associated with PAC (P = .005); we did not detect a BMI-PRA association. The effects of BMI on ARR were directionally similar in the two race groups but more pronounced in blacks. Mean systolic blood pressure was greater in blacks with lower PRA (P < .01), higher PAC (P = .015), and higher ARR (P = .49). CONCLUSIONS: An increase in adiposity was associated with a suppressed PRA in blacks and an increase in PAC in whites. The unique relationship between adiposity and renin-aldosterone axis in blacks suggests the possible existence of a population-specific mechanism characterized by volume expansion, which could in turn enhance the influences of adiposity on blood pressure in black children and adolescents.Item Are Cardiovascular Risk Factors Stronger Predictors of Incident Cardiovascular Disease in U.S. Adults With Versus Without a History of Clinical Depression?(Oxford University Press, 2018-12) Polanka, Brittanny M.; Berntson, Jessica; Vrany, Elizabeth A.; Stewart, Jesse C.; Psychology, School of ScienceBackground Several mechanisms underlying the depression-to-cardiovascular disease (CVD) relationship have been proposed; however, few studies have examined whether depression promotes CVD through potentiating traditional cardiovascular risk factors. Purpose To test the combined influence of three cardiovascular risk factors and lifetime depressive disorder on incident CVD in a large, diverse, and nationally representative sample of U.S. adults. Methods Respondents were 26,840 adults without baseline CVD who participated in Waves 1 (2001–2002) and 2 (2004–2005) of the National Epidemiologic Survey on Alcohol and Related Conditions. Lifetime depressive disorder, tobacco use, hypertension, and incident CVD were determined from structured interviews, and body mass index (BMI) was computed from self-reported height and weight. Results Logistic regression models predicting incident CVD (1,046 cases) revealed evidence of moderation, as the interactions between lifetime depressive disorder and current tobacco use (p = .002), hypertension (p < .001), and BMI (p = .031) were significant. The Former Tobacco Use × Lifetime Depressive Disorder interaction was not significant (p = .85). In models stratified by lifetime depressive disorder, current tobacco use (OR = 1.78, 95% CI = 1.36–2.32, p < .001 vs. OR = 1.41, 95% CI = 1.24–1.60, p < .001), hypertension (OR = 2.46, 95% CI = 1.98–3.07, p < .001 vs. OR = 1.39, 95% CI = 1.28–1.51, p < .001), and BMI (OR = 1.10, 95% CI = 1.01–1.20, p = .031 vs. OR = 1.03, 95% CI = 0.99–1.07, p = .16) were stronger predictors of incident CVD in adults with versus without a lifetime depressive disorder. Conclusions Our findings suggest that amplifying the atherogenic effects of traditional cardiovascular risk factors may be yet another candidate mechanism that helps to explain the excess CVD risk of people with depression.Item Association between plasma L-carnitine levels and mitochondrial DNA copy number(Springer Nature, 2023-12-11) Li, Mingyue; Yang, Keming; De Vivo, Immaculata; Eliassen, A. Heather; Qureshi, Abrar A.; Nan, Hongmei; Han, Jiali; Epidemiology, Richard M. Fairbanks School of Public HealthMitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy number (mtDNAcn) is considered a biomarker for both mitochondrial quantity and function as well as cellular oxidative stress level. Previous epidemiologic findings revealed that weight gain, higher body mass index (BMI), smoking, and high insulinemic potential of lifestyle were associated with lower leukocyte mtDNAcn. Carnitines are a group of compounds that play a critical role in energy production. We quantified the associations of plasma L-carnitine levels with leukocyte mtDNAcn. We then examined the association between mtDNAcn and L-carnitine (HMDB0000062) in 538 U.S. men without cancers, diabetes, or cardiovascular disease at blood collection from the Health Professionals Follow-Up Study (HPFS). We found a significant inverse association between L-carnitine and mtDNAcn (ρ = −0.1, P = 0.02). This implies that the carnitine metabolic pathway may be associated with mitochondrial function and oxidative stress.Item Body Mass Index Trajectories, Weight Gain, and Risks of Liver and Biliary Tract Cancers(Oxford University Press, 2022-08-12) Yang, Wanshui; Zeng, Xufen; Petrick, Jessica L.; Danford, Christopher J.; Florio, Andrea A.; Lu, Bing; Nan, Hongmei; Ma, Jiantao; Wang, Liang; Zeng, Hongmei; Sudenga, Staci L.; Campbell, Peter T.; Giovannucci, Edward; McGlynn, Katherine A.; Zhang, Xuehong; Epidemiology, Richard M. Fairbanks School of Public HealthBackground: Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). Methods: We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). BMI was self-reported at ages 20, 50, and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a median follow-up of 15.9 years among 138,922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI does not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 had increased risks of liver cancer (HR = 2.03, 95% CI: 1.26-3.28) and BTC (HR = 1.99, 95% CI: 1.16-3.39). Compared to participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI: 1.55-4.04) and BTC (HR = 1.83, 95% CI: 1.03-3.22). Compared to adults with stable weight (+/-5kg) between age 20 to 50 years, weight gain ≥20 kg between ages 20 to 50 years had higher HRs of 2.24 (95%CI: 1.40-3.58) for liver cancer and 1.86 (95% CI: 1.12-3.09) for BTC. Conclusions: Being overweight/obese at age 20, and BMI trajectories that result in being overweight and/or obese, may increase risk for both liver cancer and BTC.Item Cardiovascular risk assessment in the resource limited setting of Western Honduras: An epidemiological perspective(Elsevier, 2020-02-04) Montalvan Sanchez, Eleazar Enrique; Urrutia, Samuel Alejandro; Rodriguez, Aida Argentina; Duarte, Gabriela; Murillo, Axel; Rivera, Ricardo; Paredes Henriquez, Andrea Alejandra; Montalvan Sanchez, Daniela Maria; Ordoñez, Eva; Norwood, Dalton Argean; Dominguez, Lucia Belem; Dominguez, Ricardo Leonel; Torres, Karla; Reyes Fajardo, Esmelia Michell; Godoy, Carlos Amilcar; Medicine, School of MedicineCardiovascular Disease (CVD) epidemiology varies significantly among Low and Middle-Income Countries. Honduras is the Central American country with the highest Ischemic Heart Disease and CVD mortality rates. The aim of this study was to assess the individual CVD risk factors and calculate Cardiovascular Risk Assessment Scores (CVRAS) from the population. Methods: A cross-sectional study in western Honduras. Estimation of CV risk was performed using Framingham, MESA, ACC/AHA-PCEs and ESC SCORE calculators. Results: 38% were male. For men and women respectively; 49% and 48% had self-reported hypertension (HTN), on measured blood pressure only 18% and 30% had normal readings. Diabetes Mellitus was reported in 19% and 22%. Tobacco use was 14% and 3%. Self-reported regular exercise was 39.9% and 25%. Obesity was diagnosed in 24% and 24%. Lipid profile; total cholesterol was ≥200 mg/dl in 63% of subjects. LDL-C was elevated (>100 mg/dl) in 74% of participants, 9% had LDL-C levels higher than 190 mg/dl. Triglycerides were high (>160 mg/dl) in 60%, of these subjects 22% were taking lipid-lowering medications. 52% reported family-history of CVD. The risk calculation for men and women respectively for each CVRAS were; AHA/ACC-PCEs high risk (score ≥ 7.5%) in 62% and 30%, FRS high risk (score ≥ 20%) 46% and 15%, MESA high risk (Score ≥ 7.5%) in 70.6% and 17.7%, ESC SCORE high risk (score ≥ 5% in 32.4% and 11.8%). Conclusions: CV risk calculations revealed higher than rates than expected with consequently reflected on higher than estimated CVRAS. This represents the first report of its kind in Honduras.Item Changes in Care during the COVID-19 Pandemic for People with Cystic Fibrosis(American Thoracic Society, 2022) Sanders, Don B.; Wu, Runyu; O’Neil, Tom; Elbert, Alexander; Petren, Kris; Jain, Raksha; Ren, Clement L.; Pediatrics, School of MedicineRationale: Cystic fibrosis (CF) centers transitioned to telemedicine during the spring 2020 peak of the coronavirus disease (COVID-19) pandemic. Objectives: We hypothesized that people with CF (pwCF) with more severe disease would be more likely to be seen in-person. Methods: We used paired t tests to compare within-subject changes in body mass index (BMI) and percentage predicted forced expiratory volume in one second (FEV1) and calculated relative risk (RR) to compare pulmonary exacerbations (PEx) between pwCF enrolled in the CF Foundation Patient Registry with at least one in-person clinic visit after March 15 in both 2019 and 2020. Results: Overall, the proportion of clinical encounters that were in-person clinic visits decreased from 91% in 2019 to a low of 9% in April 2020. Among pwCF seen after March 15 in both 2019 and 2020, the mean (95% confidence interval [CI]) FEV1 percentage predicted was 1.3% (0.1-2.4) predicted higher in 2020 for children 6 to <12 years of age, and 7.5% (7.1-7.9) predicted higher in 2020 among pwCF ⩾12 years of age eligible for the highly effective CF transmembrane conductance regulator modulator, elexacaftor-tezacaftor-ivacaftor (ETI). There was no difference in FEV1 percentage predicted for pwCF ⩾12 years of age who were not eligible for ETI. Similarly, the mean (95% CI) BMI was 2.4 (2.0-2.8) percentile higher in 2020 for children 6 to <12 years of age and 5.2 (4.8-5.7) percentile higher in 2020 among children 12 to <18 years of age eligible for ETI. Mean (95% CI) BMI was 1.2 (1.2-1.3) (kg/m2) higher for pwCF ⩾18 years of age eligible for ETI, and 0.2 (0.1-0.3) (kg/m2) higher for pwCF ⩾18 years of age not eligible for ETI. The proportion of in-person clinic visits where any PEx was present was lower in 2020 compared with 2019, 25% compared with 38%, RR 0.82 (0.79-0.86). Conclusions: The care of pwCF was substantially changed during the spring 2020 peak of the COVID-19 pandemic. Among pwCF seen in-person in both 2019 and 2020 after the spring peak of the COVID-19 pandemic, lung function and BMI were higher in 2020 for children 6 to <12 years of age and pwCF eligible for ETI.Item Depressive Disorder Subtypes as Predictors of Incident Obesity in US Adults: Moderation by Race/Ethnicity(Oxford, 2017-05-01) Polanka, Brittanny M.; Vrany, Elizabeth A.; Patel, Jay; Stewart, Jesse C.; Psychology, School of ScienceWe compared the relative importance of atypical major depressive disorder (MDD), nonatypical MDD, and dysthymic disorder in predicting 3-year obesity incidence and change in body mass index and determined whether race/ethnicity moderated these relationships. We examined data from 17,787 initially nonobese adults in the National Epidemiologic Survey on Alcohol and Related Conditions waves 1 (2001-2002) and 2 (2004-2005) who were representative of the US population. Lifetime subtypes of depressive disorders were determined using a structured interview, and obesity outcomes were computed from self-reported height and weight. Atypical MDD (odds ratio (OR) = 1.68, 95% confidence interval (CI): 1.43, 1.97; P < 0.001) and dysthymic disorder (OR = 1.66, 95% CI: 1.29, 2.12; P < 0.001) were stronger predictors of incident obesity than were nonatypical MDD (OR = 1.11, 95% CI: 1.01, 1.22; P = 0.027) and no history of depressive disorder. Atypical MDD (B = 0.41 (standard error, 0.15); P = 0.007) was a stronger predictor of increases in body mass index than were dysthymic disorder (B = -0.31 (standard error, 0.21); P = 0.142), nonatypical MDD (B = 0.007 (standard error, 0.06); P = 0.911), and no history of depressive disorder. Race/ethnicity was a moderator; atypical MDD was a stronger predictor of incident obesity in Hispanics/Latinos (OR = 1.97, 95% CI: 1.73, 2.24; P < 0.001) than in non-Hispanic whites (OR = 1.54, 95% CI: 1.25, 1.91; P < 0.001) and blacks (OR = 1.72, 95% CI: 1.31, 2.26; P < 0.001). US adults with atypical MDD are at particularly high risk of weight gain and obesity, and Hispanics/Latinos may be especially vulnerable to the obesogenic consequences of depressions.Item Dietary Fat and Fatty Acid Intake in Nulliparous Women: Associations with Preterm Birth and Distinctions by Maternal BMI(Oxford University Press, 2021-05-08) Robinson, Daniel T.; Van Horn, Linda; Balmert, Lauren; Silver, Robert M.; Parry, Samuel; Haas, David M.; Wing, Deborah A.; Grobman, William A.; Obstetrics and Gynecology, School of MedicineBackground: Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited. Objective: The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n-3 (ɷ-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI. Methods: We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (<37 wk). Adjusted regression models controlled for maternal factors relevant to PTB and evaluated associations with PUFAs. Interaction terms estimated effect modification of BMI. A false discovery rate (FDR) correction accounted for multiple comparisons. Results: Median daily intake of combined EPA+DHA in 7365 women was 70 mg (IQR: 32, 145 mg). A significant interaction term indicated the effects of EPA+DHA on odds of PTB were different for different BMI categories (P < 0.01). Specifically, higher intake of combined EPA+DHA was nominally associated with reduced odds of PTB in women with underweight (OR: 0.67; 95% CI: 0.46-0.98) and normal BMI (OR: 0.87; 95% CI: 0.78-0.96), yet was associated with increased odds of overweight BMI (OR: 1.21; 95% CI: 1.02-1.44). Associations remained significant after FDR correction. Conclusions: Based on a cohort of US women designed to identify predictors of adverse pregnancy outcomes, dietary intake of combined EPA+DHA was considerably lower than recommended. Associations between intake of these recommended n-3 fatty acids and risk of PTB differ by maternal BMI.Item Genetic Influence Underlying Brain Connectivity Phenotype: A Study on Two Age-Specific Cohorts(Frontiers Media, 2022-02-07) Cong, Shan; Yao, Xiaohui; Xie, Linhui; Yan, Jingwen; Shen, Li; Alzheimer’s Disease Neuroimaging Initiative; Biomedical Engineering and Informatics, Luddy School of Informatics, Computing, and EngineerinBackground: Human brain structural connectivity is an important imaging quantitative trait for brain development and aging. Mapping the network connectivity to the phenotypic variation provides fundamental insights in understanding the relationship between detailed brain topological architecture, function, and dysfunction. However, the underlying neurobiological mechanism from gene to brain connectome, and to phenotypic outcomes, and whether this mechanism changes over time, remain unclear. Methods: This study analyzes diffusion-weighted imaging data from two age-specific neuroimaging cohorts, extracts structural connectome topological network measures, performs genome-wide association studies of the measures, and examines the causality of genetic influences on phenotypic outcomes mediated via connectivity measures. Results: Our empirical study has yielded several significant findings: 1) It identified genetic makeup underlying structural connectivity changes in the human brain connectome for both age groups. Specifically, it revealed a novel association between the minor allele (G) of rs7937515 and the decreased network segregation measures of the left middle temporal gyrus across young and elderly adults, indicating a consistent genetic effect on brain connectivity across the lifespan. 2) It revealed rs7937515 as a genetic marker for body mass index in young adults but not in elderly adults. 3) It discovered brain network segregation alterations as a potential neuroimaging biomarker for obesity. 4) It demonstrated the hemispheric asymmetry of structural network organization in genetic association analyses and outcome-relevant studies. Discussion: These imaging genetic findings underlying brain connectome warrant further investigation for exploring their potential influences on brain-related complex diseases, given the significant involvement of altered connectivity in neurological, psychiatric and physical disorders.Item High early pregnancy body mass index is associated with alterations in first- and second-trimester angiogenic biomarkers(Elsevier, 2022) Beck, Celeste; Allshouse, Amanda; Silver, Robert M.; Grobman, William A.; Simhan, Hyagriv; Haas, David; Reddy, Uma M.; Blue, Nathan R.; Obstetrics and Gynecology, School of MedicineBackground: Obesity is associated with various placenta-mediated adverse pregnancy outcomes, including preeclampsia, preterm birth, and stillbirth. Mechanisms linking obesity with placental dysfunction are not completely understood. Objective: This study aimed to examine the relationship between early pregnancy body mass index and placental angiogenic biomarkers soluble fms-like tyrosine kinase-1, placental growth factor, and the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio. Study design: We conducted secondary analyses of an existing substudy within a multisite, prospective observational cohort study of nulliparous pregnant women in the United States. First- and second-trimester maternal blood samples, first-trimester body mass index, and demographic, lifestyle, and pregnancy outcomes data were collected. Soluble fms-like tyrosine kinase-1 and placental growth factor concentrations were measured at 6 to 13 and 16 to 22 weeks of gestation for women (cases) who experienced one of several adverse pregnancy outcomes (delivery at <37 weeks of gestation, preeclampsia or eclampsia, birthweight for gestational age <5th percentile, or stillbirth) and for those who had none of those outcomes (controls). We used multivariable mixed-effects linear regression models to estimate the association of body mass index with angiogenic biomarkers at both time points. We evaluated mean change between first- and second-trimester biomarker concentrations using multivariable linear regression models. Lastly, we used logistic regression models to estimate the risk of a high second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratio, using clinically established cutoffs for risk prediction. Results: Angiogenic biomarker and early pregnancy body mass index data were available for 2363 women (1467 with adverse pregnancy outcomes and 896 controls). High early pregnancy body mass index was associated with consistently lower soluble fms-like tyrosine kinase-1 concentrations across the first and second trimesters of pregnancy. We found lower first-trimester placental growth factor concentrations in the group with class II or III obesity (P<.001) and lower second-trimester placental growth factor concentrations among groups who were overweight, with class I obesity, and class II or III obesity (P<.001). For every unit increase in early pregnancy body mass index, there was a -4.4 pg/mL (95% confidence interval, -3.6 to -5.2) smaller mean increase in placental growth factor concentrations between the first and second trimesters of pregnancy. These differences resulted in significantly lower mean first-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratios among groups who were overweight, with class I obesity, and class II or III obesity (P<.05) and in a significantly higher second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratio among the group with class II or III obesity (P<.001), compared with the group with normal body mass index. Each unit of increase in body mass index was associated with a 0.5 (95% confidence interval, 0.3-0.7) greater mean increase in the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio between the first and second trimesters of pregnancy. In stratified analyses, associations between body mass index and angiogenic biomarkers soluble fms-like tyrosine kinase-1 and placental growth factor were similar in nonadverse pregnancy outcome and adverse pregnancy outcome subgroups, whereas associations between body mass index and the soluble fms-like tyrosine kinase-1-to-placental growth factor ratio were attenuated in the subgroups. Participants in the group with class II or III obesity were 3.13 (95% confidence interval, 1.15-8.49) times more likely than participants with normal weight to have a second-trimester ratio of ≥38 in univariate analysis. Conclusion: High early pregnancy body mass index was associated with lower soluble fms-like tyrosine kinase-1 and placental growth factor concentrations across early pregnancy. Maternal body mass was inversely associated with first-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratios and positively associated with second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratios, driven by a diminished rise in placental growth factor between the first and second trimesters of pregnancy. Women with class II or III obesity have an increased risk of a high second-trimester soluble fms-like tyrosine kinase-1-to-placental growth factor ratio associated with placental dysfunction.