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BACKGROUND - The determinants of pulmonary artery systolic pressure (PASP) are not fully understood. It is unknown whether racial differences in PASP exist or if other population characteristics are associated with pulmonary pressure in humans. We examined echocardiographically estimated PASP in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a middle-aged, biracial community-based cohort.
METHODS AND RESULTS - At the CARDIA year-25 examination, 3469 participants underwent echocardiography, including measurement of tricuspid regurgitant jet velocity to estimate PASP. Clinical features, laboratory values, pulmonary function tests, and measurement of adipose depot volume were analyzed for association with PASP. PASP was estimated in 1311 individuals (61% female, 51% white). Older age, higher blood pressure, and higher body mass index were associated with higher PASP. Black race was associated with higher PASP after adjustment for demographics and left and right ventricular function (β 0.94, 95% CI 0.24-1.64; =0.009), but this association was no longer significant after further adjustment for lung volume (β 0.42, 95% CI -0.68 to 0.96; =0.74). Insulin resistance, inflammation (C-reactive protein and interleukin-6), and visceral adipose volume were independently associated with higher PASP after adjustment for relevant covariates. PASP rose with worsening diastolic function (ratio of early transmitral Doppler velocity to average mitral annular tissue Doppler velocity [E/e'] and left atrial volume index).
CONCLUSIONS - In a large biracial cohort of middle-aged adults, we identified associations among black race, insulin resistance, and diastolic dysfunction with higher echocardiographically estimated PASP. Further studies are needed to examine racial differences in PASP and whether insulin resistance directly contributes to pulmonary vascular disease in humans.
© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.
OBJECTIVES - This study sought to assess whether body mass index (BMI) was associated with subclinical left ventricular (LV) systolic dysfunction in African-American individuals.
BACKGROUND - Higher BMI is a risk factor for cardiovascular disease, including heart failure. Obesity disproportionately affects African Americans; however, the association between higher BMI and LV function in African Americans is not well understood.
METHODS - Peak systolic circumferential strain (ECC) was measured by tagged cardiac magnetic resonance in 1,652 adult African-American participants of the Jackson Heart Study between 2008 and 2012. We evaluated the association between BMI and ECC in multivariate linear regression and restricted cubic spline analyses adjusted for prevalent cardiovascular disease, conventional cardiovascular risk factors, LV mass, and ejection fraction. In exploratory analyses, we also examined whether inflammation, insulin resistance, or volume of visceral adipose tissue altered the association between BMI and ECC.
RESULTS - The proportions of female, nonsmokers, diabetic, and hypertensive participants rose with increase in BMI. In multivariate-adjusted models, higher BMI was associated with worse ECC (β = 0.052; 95% confidence interval: 0.028 to 0.075), even in the setting of preserved LV ejection fraction. Higher BMI was also associated with worse ECC when accounting for markers of inflammation (C-reactive protein, E-selection, and P-selectin), insulin resistance, and volume of visceral adipose tissue.
CONCLUSIONS - Higher BMI is significantly associated with subclinical LV dysfunction in African Americans, even in the setting of preserved LV ejection fraction.
Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
BACKGROUND - Studies evaluating the association between obesity and pelvic organ prolapse report estimates that range from negative to positive associations. Heterogeneous definitions for pelvic organ prolapse and variable choices for categorizing obesity measures have made it challenging to conduct meta-analysis.
OBJECTIVE - We systematically evaluated evidence to provide quantitative summaries of association between degrees of obesity and pelvic organ prolapse, and identify sources of heterogeneity.
STUDY DESIGN - We searched for all indexed publications relevant to pelvic organ prolapse up until June 18, 2015, in PubMed/MEDLINE to identify analytical observational studies published in English that reported risk ratios (relative risk, odds ratio, or hazard ratio) for body mass index categories in relation to pelvic organ prolapse. Random effects meta-analyses were conducted to report associations with pelvic organ prolapse for overweight and obese body mass index categories compared with women in the normal-weight category (referent: body mass index <25 kg/m).
RESULTS - Of the 70 studies that reported evidence on obesity and pelvic organ prolapse, 22 eligible studies provided effect estimates for meta-analysis of the overweight and obese body mass index categories. Compared with the referent category, women in the overweight and obese categories had meta-analysis risk ratios of at least 1.36 (95% confidence interval, 1.20-1.53) and at least 1.47 (95% confidence interval, 1.35-1.59), respectively. Subgroup analyses showed effect estimates for objectively measured clinically significant pelvic organ prolapse were higher than for self-reported pelvic organ prolapse. Other potential sources of heterogeneity included proportion of postmenopausal women in study and reported study design.
CONCLUSION - Overweight and obese women are more likely to have pelvic organ prolapse compared with women with body mass index in the normal range. The finding that the associations for obesity measures were strongest for objectively measured, clinically significant pelvic organ prolapse further strengthens this evidence. However, prospective investigations evaluating obesity and pelvic organ prolapse are few.
Copyright © 2017 Elsevier Inc. All rights reserved.
The association of obesity on survival among patients with colorectal cancer (CRC) has not been well characterized. We investigated the association of prediagnostic body mass index (BMI)/waist-hip ratio (WHR) and total/cause-specific mortality in CRC patients. Our study included 1,452 patients who participated in two large cohort studies and were diagnosed with CRC during follow-up period. Participants were measured for anthropometrics and interviewed to collect relevant information at baseline, prior to any cancer diagnosis. Data on site-specific cancer incidence and cause-specific mortality were obtained via in-person surveys and annual record linkage with cancer and vital statistics registries. Cox proportional hazard models were used to evaluate the associations of BMI and WHR with survival. A total of 547 participants died during the follow-up period, including 499 who died of CRC. Relative to normal BMI (18.5 to <25.0 kg/m ), obesity (BMI ≥ 30 kg/m ) was associated with increased mortality resulting from all causes [hazard ratio (HR) = 1.5, 95% confidence interval (CI): 1.1-2.1] and CRC (HR = 1.5, 95% CI: 1.1-2.1). Elevated risk of death was also found among underweight patients (BMI < 18.5 kg/m ), although not all risk estimates were statistically significant. Overweight BMI (25.0 to <30.0 kg/m ) was not associated with risk of death among CRC patients, nor was WHR. In conclusion, prediagnostic BMI was associated with survival among CRC patients following a U-shape pattern; obesity was associated with high mortality after CRC diagnosis. These findings provide support for maintaining healthy weight to improve the survival of CRC patients.
© 2016 UICC.
CONTEXT - Sildenafil increases insulin sensitivity in mice. In humans, phosphodiesterase 5 inhibition improves disposition index, but the mechanism of this effect has not been elucidated and may depend on duration. In addition, increasing cyclic GMP without increasing nitric oxide could have beneficial effects on fibrinolytic balance.
OBJECTIVE - The objective was to test the hypothesis that chronic phosphodiesterase 5 inhibition with sildenafil improves insulin sensitivity and secretion without diminishing fibrinolytic function.
DESIGN - This was a randomized, double-blind, placebo-controlled study.
SETTING - This trial was conducted at Vanderbilt Clinical Research Center.
PARTICIPANTS - Participants included overweight individuals with prediabetes.
INTERVENTIONS - Subjects were randomized to treatment with sildenafil 25 mg three times a day or matching placebo for 3 months. Subjects underwent a hyperglycemic clamp prior to and at the end of treatment.
MAIN OUTCOME MEASURES - The primary outcomes of the study were insulin sensitivity and glucose-stimulated insulin secretion.
RESULT - Twenty-one subjects completed each treatment arm. After 3 months, the insulin sensitivity index was significantly greater in the sildenafil group compared to the placebo group by 1.84 mg/kg/min per μU/mL*100 (95% confidence interval, 0.01 to 3.67 mg/kg/min per μU/mL*100; P = .049), after adjusting for baseline insulin sensitivity index and body mass index. In contrast, there was no effect of 3-month treatment with sildenafil on acute- or late-phase glucose-stimulated insulin secretion (P > .30). Sildenafil decreased plasminogen activator inhibitor-1 (P = .01), without altering tissue-plasminogen activator. In contrast to placebo, sildenafil also decreased the urine albumin-to-creatinine ratio from 12.67 ± 14.67 to 6.84 ± 4.86 μg/mg Cr. This effect persisted 3 months after sildenafil discontinuation.
CONCLUSIONS - Three-month phosphodiesterase 5 inhibition enhances insulin sensitivity and improves markers of endothelial function.
This study aimed to provide data on the impact of known risk factors on endometrial cancer burden. Using data on 1199 endometrial cancer cases and 1212 frequency matched controls from a population-based case-control study carried out in urban Shanghai, China from 1997 to 2003, multivariable adjusted odds ratios were obtained from unconditional logistic regression analyses. Partial population-attributable risks were calculated and corresponding 95% confidence intervals were estimated using a bootstrap method. An estimated 16.94% of endometrial cancer cases were attributed to overweight or obesity; 8.39% to meat intake; 5.45% to nonregular tea drinking; 5.23% to physical inactivity; and 1.77% to family history of endometrial, breast, or colorectal cancers. Overall, these risk factors accounted for 36.01% (95% confidence interval: 28.55-43.11%) of total endometrial cancer cases. Similar results were observed when analysis was restricted to postmenopausal women. Among modifiable lifestyle factors, overweight and obesity accounted for the largest proportion of endometrial cancer in the study population. Lifestyle alterations, such as maintenance of healthy weight, regular exercise, consumption of less meat, and tea drinking, could potentially reduce endometrial cancer by more than one-third.
We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m(2)) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P < 0.01-0.0001), and endothelial function was decreased (P < 0.0005) during euinsulinemia-hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers.
Copyright © 2015 the American Physiological Society.
Although much research has been conducted on the role adult body mass index (BMI) plays in mortality, there have been fewer studies that evaluated the associations of BMI in young adulthood and adult weight trajectory with mortality, and it remains uncertain whether associations differ by race or sex. We prospectively examined the relationships of BMI in young adulthood (21 years of age) and adult obesity trajectory with later-life mortality rates among 75,881 men and women in the Southern Community Cohort Study. Study participants were enrolled between 2002 and 2009 at ages 40-79 years and were followed through December, 2011. Multivariable Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. There were 7,301 deaths in the 474,970 person-years of follow-up. Participants who reported being overweight or obese as young adults had mortality rates that were 19% (95% confidence interval: 12, 27) and 64% (95% confidence interval: 52, 78) higher, respectively, than those of their normal weight counterparts. The results did not significantly differ by race or sex. Participants who reported being obese in young adulthood only or in both young and middle adulthood experienced mortality rates that were 40%-90% higher than those of participants who were nonobese at either time. These results suggest that obesity in young adulthood is associated with higher mortality risk regardless of race, sex, and obesity status in later life.
© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: email@example.com.
The main purpose of this study was to examine whether the Supplemental Nutrition Program for Women, Infants and Children (WIC) helped mothers of overweight/obese preschool children to cut down on dietary fat and sugar intake for their families. Data from the Children Eating Well for Health (CHEW) Nutrition Survey, a probability sample of 150 (50 each White, Black and Hispanic) families with preschoolers participating in the WIC program in Nashville/Davidson County, Tennessee, were analyzed using logistic regression modeling. Mothers who reported that the WIC program helped them reduce fat intake were 2.5 times more likely to have an overweight/obese child and 2.1 times more likely to be obese themselves. No significant effects were found for adding sugar. These results suggest that the mothers in this sample were applying WIC nutritional counseling to use food preparation techniques that cut down on added fats for themselves and their children who were at risk due to weight status.