Timing of Surgery and Social Determinants of Health Related to Pathologic Complete Response after Total Neoadjuvant Therapy for Rectal Adenocarcinoma: Retrospective Study of National Cancer Database.

Total neoadjuvant therapy (TNT) for rectal adenocarcinoma (RAC) involves multi-agent chemotherapy and radiation before definitive surgery. Previous studies of the rest period (time between radiation and surgery) and pathologic complete response (pCR) have produced mixed results. The objective of this study was to evaluate the relationship between the rest period and pCR. This study utilized the National Cancer Database (NCDB) to retrospectively analyze 5997 stage-appropriate RAC cases treated with TNT from 2016 to 2020. The overall pCR rate was 18.6%, with most patients undergoing induction chemotherapy followed by long-course chemoradiation (81.5%). Multivariable logistic regression models revealed a significant non-linear relationship between the rest period and pCR (p = 0.033), with optimal odds at 14.7-15.9 weeks post radiation (odds ratio: 1.49, 95% confidence interval: 1.13-1.98) when compared to 4.0 weeks. Medicaid, distance to the treatment facility, and community education were associated with decreased odds of pCR. Findings highlight the importance of a 15-16-week post-radiation surgery window for achieving pCR in RAC treated with TNT and socioeconomic factors influencing pCR rates. Findings also emphasize the need for clinical trials to incorporate detailed analyses of the rest period and social determinant of health to better guide clinical practice.

Adipokines and adiposity among postmenopausal women of the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: We investigated whether the associations of serum adiponectin, leptin, and resistin with adiposity differ with menopausal age. METHODS: In this cross-sectional study, we included 751 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis (MESA) who reported their menopausal age (<45, 45-49, 50-54 and ≥55 y) and had anthropometrics, serum adipokines, and abdominal computed tomography measures of visceral and subcutaneous adipose tissue (VAT and SAT) obtained at MESA exam 2 or 3. Linear regression models were used for analysis. RESULTS: The mean ± SD age was 65.1 ± 9.0 years for all participants. The median (interquartile range) values for serum adiponectin, leptin and resistin, VAT, and SAT were 21.9 (14.8-31.7) ng/L, 24.3 (12.5-42.4) pg/L, 15.3 (11.8-19.5) pg/L, 183.9 (130.8-251.1) cm2, and 103.7 (65.6-151.5) cm2, respectively. The mean ± SD values for body mass index, waist circumference, and waist-to-hip ratio were 28.3 ± 5.81 kg/m2, 96.6 ± 15.9 cm, and 0.91 ± 0.078, respectively. Adiponectin was inversely associated with all adiposity measures, with similar patterns across menopausal age categories. Leptin was positively associated with all adiposity measures, and the strength of associations varied across menopausal age categories for body mass index, waist circumference, and SAT (Pinteraction ≤ 0.01 for all). The associations of resistin with adiposity measures were mostly nonsignificant except in the 45- to 49-year menopausal age category. CONCLUSIONS: Menopausal age category had no influence on the association of serum adiponectin with adiposity. The association of serum leptin and resistin differed according to menopausal age category for generalized adiposity but was inconsistent for measures of abdominal adiposity.

Listeria-based vaccination against the pericyte antigen RGS5 elicits anti-vascular effects and colon cancer protection.

Colorectal cancer (CRC) remains a leading cause of cancer-related mortality despite efforts to improve standard interventions. As CRC patients can benefit from immunotherapeutic strategies that incite effector T cell action, cancer vaccines represent a safe and promising therapeutic approach to elicit protective and durable immune responses against components of the tumor microenvironment (TME). In this study, we investigate the pre-clinical potential of a Listeria monocytogenes (Lm)-based vaccine targeting the CRC-associated vasculature. CRC survival and progression are reliant on functioning blood vessels to effectively mediate various metabolic processes and oxygenate underlying tissues. We, therefore, advance the strategy of initiating immunity in syngeneic mouse models against the endogenous pericyte antigen RGS5, which is a critical mediator of pathological vascularization. Overall, Lm-based vaccination safely induced potent anti-tumor effects that consisted of recruiting functional Type-1-associated T cells into the TME and reducing tumor blood vessel content. This study underscores the promising clinical potential of targeting RGS5 against vascularized tumors like CRC.

Targeting the pericyte antigen DLK1 with an alpha type-1 polarized dendritic cell vaccine results in tumor vascular modulation and protection against colon cancer progression.

Despite the availability of various treatment options, colorectal cancer (CRC) remains a significant contributor to cancer-related mortality. Current standard-of-care interventions, including surgery, chemotherapy, and targeted agents like immune checkpoint blockade and anti-angiogenic therapies, have improved short-term patient outcomes depending on disease stage, but survival rates with metastasis remain low. A promising strategy to enhance the clinical experience with CRC involves the use of dendritic cell (DC) vaccines that incite immunity against tumor-derived blood vessels, which are necessary for CRC growth and progression. In this report, we target tumor-derived pericytes expressing DLK1 with a clinically-relevant alpha type-1 polarized DC vaccine (αDC1) in a syngeneic mouse model of colorectal cancer. Our pre-clinical data demonstrate the αDC1 vaccine's ability to induce anti-tumor effects by facilitating cytotoxic T lymphocyte activity and ablating the tumor vasculature. This work, overall, provides a foundation to further interrogate immune-mediated mechanisms of protection in order to help devise efficacious αDC1-based strategies for patients with CRC.

Reduced Risk of All-Cause, Cancer-, and Cardiovascular Disease-Related Mortality among Patients with Primary Malignant Cardiac Tumors Receiving Chemotherapy in the United States.

Primary malignant cardiac tumors (PMCTs) are rare but lethal neoplasms. There are limited evidence-based treatment guidelines for PMCTs. We evaluated the relation of chemotherapy with mortality outcomes in patients with PMCTs in the United States. Data were from patients aged ≥ 20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with PMCTs from 2000 to 2020. Cox regression, competing risk, and propensity score analyses were performed to estimate hazard ratios (HR) and confidence intervals (CI). About 53% of the 563 patients with PMCTs received chemotherapy as the first course of treatment. During a mean follow-up of 24.7 months (median: 10), 458 deaths occurred with 81.7% and 9.4% due to cancer and cardiovascular disease (CVD), respectively. In models adjusted for sociodemographic and clinico-pathophysiological factors including histology, receipt of chemotherapy was associated with low risk for all-cause (HR: 0.56, 95%CI: 0.45-0.69), cancer (HR: 0.63, 95%CI: 0.50-0.80) and CVD mortality (HR: 0.27, 95%CI: 0.12-0.58). Patients who had both chemotherapy and surgery had the lowest risk for all-cause and cancer mortality. This study suggests that the subpopulations of patients with PMCTs who receive chemotherapy may have better prognosis than those who do not receive this therapy regardless of histology.

Factors associated with self-report of polycystic ovary syndrome in the Coronary Artery Risk Development in Young Adults study (CARDIA).

BACKGROUND: Polycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women's report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS. METHODS: We performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, "Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?" at the year 15 examination. Women who answered "yes" were defined as having self-reported PCOS. Women who answered "no or not sure" were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions. RESULTS: Forty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS. CONCLUSIONS: Unrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.

The prospective association of hyperandrogenism, oligomenorrhea and polycystic ovary syndrome with incident gestational diabetes: The coronary artery risk development in young adults women's study.

In this 28-year prospective study of 455 women (mean age: 26 years), polycystic ovary syndrome (PCOS) was associated with a 2.6-fold elevated risk of gestational diabetes (GDM). However, hyperandrogenism or oligomenorrhea in the absence of PCOS was not associated with GDM.

Racial and ethnic disparities in the association of maternal infection during pregnancy and risk of cyanotic congenital heart defects in the United States, 2011-2020.

PURPOSE: The etiology of cyanotic congenital heart defects (CCHD) is not well understood. There are scarce data on racial/ethnic disparities in maternal infection and CCHD. We evaluated the relation of maternal infections during pregnancy and risk of CCHD in the United States, and to assess if this association varies by race/ethnicity. METHODS: Data were from the National Vital Statistics System comprising 35.3 million singleton livebirths among mothers aged 15-49 years from 2011 to 2020. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: After adjustment for sociodemographic and maternal health factors, including prepregnancy body mass index, diabetes, hypertension, and smoking during pregnancy, time to prenatal care was initiated and pregnancy complications, any maternal infection, was associated with elevated odds of CCHD (OR: 1.25, 95% CI: 1.15-1.37). The odds of CCHD were mainly evident for sexually transmitted infections, namely chlamydia and hepatitis-C viral infection. The association was limited to non-Hispanic Black (OR: 1.22, 95% CI: 1.03-1.45), Hispanic (OR: 1.61, 95% CI: 1.33-1.95), and Asian (OR: 2.03, 95% CI: 1.42-2.91) mothers. CONCLUSIONS: In this population-based study, maternal infection during pregnancy was associated with a modest risk of CCHD in offspring, which was the highest in racial/ethnic minority mothers.

Low endogenous estradiol levels are associated with elevated risk of cardiovascular disease mortality in young and middle-aged men in the United States.

BACKGROUND AND AIMS: Evidence for the association of total estradiol (E2) with cardiovascular disease (CVD) in young men is limited. We investigated the association of total E2 or free estradiol (FE2) and CVD mortality in a nationally representative multiracial sample of young and middle-aged men in the United States. METHODS: Data were from 954 men without CVD, cancer, diabetes and not on androgen therapy or taking anabolic steroids, who participated in the National Health and Nutrition Examination Survey (1988-1991), for whom E2 was measured, and were followed for mortality through to 2015. Fasting serum levels of E2 were measured using competitive electrochemiluminescence immunoassays. Free estradiol was estimated from the levels of estradiol, sex hormone binding globulin, and albumin. International Classification of Diseases codes were used to define CVD mortality. Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of participants at baseline was 35.7 ± 11.6 years, with 11% and 6% reporting Black and Hispanic race and ethnicity, respectively. During a median follow-up of 25.2 years, 40 CVD deaths were recorded. Controlling for baseline demographic and CVD risk factors, and total testosterone levels, a 1 standard deviation decrement in log E2 (HR: 2.33, 95%CI: 1.11-5.00) or FE2 (HR: 1.89, 95%CI: 1.01-3.57) was associated with elevated risk of CVD mortality. This elevated risk was largely limited to non-Hispanic White men. CONCLUSIONS: In this study, low levels of E2 or FE2 were associated with elevated risk of CVD mortality.

Anti PD-1/Anti PDL-1 Inhibitors in Advanced Gastroesophageal Cancers: A Systematic Review and Meta-Analysis of Phase 2/3 Randomized Controlled Trials.

Importance: Immune checkpoint inhibitors (ICI) have revolutionized the treatment for gastroesophageal cancers (GEC). It is important to investigate the factors that influence the response to anti-PD-1/PD-L1 ICIs. Objective: To assess the benefits of PD-1/PD-L1 ICIs in advanced GEC and perform subgroup analysis to identify patient populations who would benefit from ICI. Data sources: PubMed, Embase, Scopus, and the Cochrane Library databases were systematically searched from database inception to September 2021 for all relevant articles. We also reviewed abstracts and presentations from all major conference proceedings including relevant meetings of the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO) during the last four years (2018 to 2021) and reviewed citation lists. Study selection, data extraction, and synthesis: Full articles and presentations were further assessed if the information suggested that the study was a phase 2/3 randomized controlled trial (RCT) comparing PD-1/PD-L1 inhibitor either alone, or in combination with standard therapy vs. standard therapy in advanced GEC. The full text of the resulting studies/presentations and extracted data were reviewed independently according to PRISMA guidelines. Main outcomes and measures: The main outcomes were OS, PFS, and treatment-related adverse events (TRAEs). Results: A total of 168 studies were assessed for eligibility, and 17 RCTs with 12,312 patients met the inclusion criteria. There was an OS benefit in the overall population with ICIs (HR 0.78; 95% CI 0.73−0.83 p < 0.001). Immunotherapy showed better OS benefit in males (HR 0.77 95% CI 0.72−0.83; p < 0.001) than females (HR 0.89; 95% CI 0.80−0.99 p < 0.03), esophageal primary tumors (HR 0.70 95% CI 0.64−0.76 p < 0.001) vs. gastric cancer (HR 0.84 95% CI 0.74−0.94 p 0.002) or GEJ cancer (HR 0.84 95% CI 0.72−0.98 p 0.024) and in squamous cell carcinoma (HR 0.71 95% CI 0.66−0.77 p < 0.001) vs. adenocarcinoma (HR 0.85 95% CI 0.78−0.93 p < 0.001). PD-L1 positive patients seemed to benefit more (HR 0.74 95% CI 0.67−0.82 p < 0.001) compared to PD-L1 negative patients (HR 0.86 95% CI 0.74−1.00 p < 0.043), and Asians showed OS benefit (HR 0.76 95% CI 0.67−0.87 p < 0.001) compared to their White counterparts (HR 0.92 95% CI 0.74−1.14; p 0.424). Conclusions and relevance: ICIs improve survival in advanced GEC without significantly increasing the side effects. However, certain subgroups of patients such as males, Asians, and those with esophageal primary, PD-L1 positive tumors and squamous cell carcinoma benefit more from such treatments. Further translational research is needed to understand the mechanistic links and develop new biomarkers.

A Prospective Population-Based Study of Cardiovascular Disease Mortality following Treatment for Breast Cancer among Men in the United States, 2000-2019.

Male breast cancer is rare but its incidence and mortality are increasing in the United States, with racial/ethnic disparities in survival reported. There is limited evidence for cardiotoxicity of cancer treatment among men with breast cancer. We evaluated the relation between breast cancer treatment and cardiovascular disease (CVD) mortality among men and investigated the salient roles that race/ethnicity play on this relation. Data were from 5216 men with breast cancer aged ≥ 40 years from the Surveillance, Epidemiology, and End Results program who were diagnosed from 2000 to 2019 and underwent surgery. Competing risk models were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). During a median follow-up of 5.6 years, 1914 deaths occurred with 25% attributable to CVD. In multivariable-adjusted models, men who received chemotherapy had elevated risk for CVD (HR: 1.55, 95%CI: 1.18-2.04). This risk was higher among Hispanic men (HR: 3.96, 95%CI: 1.31-12.02) than non-Hispanic Black and non-Hispanic White men. There was no significant association between radiotherapy and CVD deaths. In this population-based study, treatment with chemotherapy was associated with elevated risk of CVD mortality in men with breast cancer. Racial/ethnic disparities in the association of chemotherapy and CVD mortality were observed.

The influence of individual and neighborhood-level characteristics on rural-urban disparities in cardiovascular disease mortality among U.S. women diagnosed with breast and gynecologic cancers.

OBJECTIVE: Rural-urban disparities exist in cancer and cardiovascular disease (CVD) mortality. Investigations of CVD mortality among breast and gynecologic cancer (BGC) survivors from rural/urban communities are limited. We evaluated the influence of individual and neighborhood-level factors on rural-urban disparities in CVD mortality among BGC survivors. METHODS: Data were from 1,139,767 women aged ≥20 years from the Surveillance, Epidemiology, and End Results program who were diagnosed with BGC from 2000 to 2016 that was merged with Area Health Resource Files for neighborhood-level factors (smoking, cancer screening, primary care provider density and socioeconomic index). Standardized mortality ratios (SMRs) for CVD mortality were calculated and multilevel Cox models, accounting for competing events, were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). RESULTS: The average age of BGC survivors was 60 years, with 10.3% of them living in rural counties. During a median follow-up of 5.1 years, 47,995 CVD deaths occured. Women with BGC had excess CVD mortality compared to general population women (SMR 6.05; CI: 6.00-6.11). This risk was highest among women aged <50 years (SMR = 27.16; CI: 25.74-28.62). In models adjusted for demographics, cancer stage and cancer therapy, women with BGC in rural communities had higher CVD deaths than those in urban communities (HR = 1.10, CI:1. 05-1.15). Additional adjustment for neighborhood-level characteristics attenuated the relation of rurality with CVD mortality (HR = 1.02, CI: 0.98-1.07). CONCLUSIONS: BGC survivors living in rural communities have elevated risk of CVD mortality. Neighborhood-level characteristics explained the rural-urban disparities in CVD mortality observed among BGC survivors.

The association of skipping breakfast with cancer-related and all-cause mortality in a national cohort of United States adults.

PURPOSE: Many lifestyle and dietary factors have been recognized as risk factors for cancer morbidity and mortality. However, investigations of the association of the frequency of breakfast consumption and cancer are limited. This study aimed to examine the association of skipping breakfast with all-cause and cancer-related mortality in a national cohort of United States men and women. METHODS: Data were from 7,007 adults aged ≥ 40 years who participated in the third National Health and Nutrition Examination Survey (1988-1994) and had follow-up information on mortality up until 31 December 2015. Cox proportional hazards regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The mean age of participants was 55.4 years, with 54.4% and 79% being women and non-Hispanic whites, respectively. Approximately, 16% of participants rarely consumed breakfast, 23.0% consumed breakfast some days, and 61% consumed breakfast every day. During a median follow-up of 22.2 years, 3,573 deaths occurred with 795 being related to cancer. In models adjusting for sociodemographic factors, smoking, physical activity, body mass index, hypertension, diabetes, cholesterol levels, total energy intake and diet quality, persons who rarely consumed breakfast had a higher risk of cancer-related mortality (HR = 1.52; CI:1.06-2.18) and all-cause (HR = 1.69; CI: 1.42-2.02) compared to those who took breakfast every day. CONCLUSION: In this nationally representative sample, skipping breakfast was associated with elevated risks for all-cause and cancer-related mortality. This study provides evidence for the benefits of regular breakfast consumption in reducing the risk of all-cause and cancer mortality.

The Association of Lactation Duration with Visceral and Pericardial Fat Volumes in Parous Women: The CARDIA Study.

BACKGROUND: Lactation is associated with lower risks for cardiovascular disease in women. Organ-related adiposity, which plays significant roles in the development of cardiometabolic diseases, could help explain this observation. We evaluated the association of lactation duration with visceral (VAT) and pericardial (PAT) fat volumes in women. METHODS: Data were obtained from 910 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study (1985-1986) without diabetes prior to pregnancy who had ≥1 birth during 25 years of follow-up and had VAT and PAT measured from computed tomographic scans in 2010-2011. Cumulative lactation duration across all births since baseline was calculated from self-reports collected at periodic exams. RESULTS: At baseline, the average age of women (48% black, 52% white) was 24 ±â€…3.7 years. After controlling for baseline age, race, smoking status, body mass index, fasting glucose, family history of diabetes, fat intake, total cholesterol, physical activity, and follow-up covariates (parity, gestational diabetes), the mean fat volumes across categories of lactation [none (n = 221), 1-5 months (n = 306), 6-11 months (n = 210), and ≥12 months (n = 173)] were 122.0, 113.7 105.0, and 110.1 cm3 for VAT and 52.2, 46.7, 44.5, and 43.4 cm3 for PAT, respectively. Changes in body weight from the first post-baseline birth to the end of follow-up mediated 21% and 18% of the associations of lactation with VAT and PAT, respectively. CONCLUSIONS: In this prospective study, longer cumulative lactation duration was associated with lower VAT and PAT volumes, with weight gain partially mediating these associations.

The Association of Ideal Cardiovascular Health and Ocular Diseases Among US Adults.

BACKGROUND: Globally, about 2.2 billion people have a vision impairment or blindness and approximately half of the cases could have been prevented. Several ocular diseases share common characteristics that overlap with risk factors for cardiovascular diseases. The aim of this study was to evaluate the relation between the American Heart Association's prescription for health called the Life's Simple 7 (LS7) metrics and the occurrence of ocular diseases. METHODS: Data were from 6118 adults ages ≥40 years who participated in the 2005-2008 National Health and Nutrition Examination Survey (NHANES). LS7 metrics consisted of information on smoking, physical activity, body mass index, diet, blood pressure, total cholesterol, and blood glucose. Scores were summed for a maximum of 14 (most ideal cardiovascular health). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The average age of participants was 57 years with 53% of them being women. A 1-unit increase in LS7 scores was associated with reduced odds for age-related macular degeneration (OR: 0.95, 95% CI: 0.90-0.99), diabetic retinopathy (OR: 0.68, 95% CI: 0.64-0.73), cataract (OR: 0.94, 95% CI: 0.90-0.98), and glaucoma (OR: 0.94, 95% CI: 0.88-0.99). After multivariable adjustment, the association was limited to only diabetic retinopathy (OR: 0.69, 95% CI: 0.64-0.74). This association persisted when diabetic retinopathy was limited to only diagnosis by retinal imaging. CONCLUSIONS: In this study, ideal cardiovascular health, which is indicative of a healthy lifestyle, was associated with lower odds for ocular diseases, especially diabetic retinopathy. These findings suggest that interventions to prevent cardiovascular diseases may also hold promise in preventing ocular diseases.

The hepatic lipidome and HNF4α and SHBG expression in human liver.

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

Antimüllerian hormone and F2-isoprostanes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

OBJECTIVE: To examine whether F2-isoprostanes, a marker of systematic oxidative stress, are associated with antimüllerian hormone (AMH), an indicator of ovarian reserve, in a population-based cohort of women of black and white ethnicities. DESIGN: Cross-sectional analysis. SETTING: Not applicable. PATIENTS: The CARDIA Women's Study, a population-based cohort. Black (n = 398) and white (n = 432) late reproductive-aged women (mean age 40 ± 3.6 years) without histories of gynecologic surgery. MAIN OUTCOME MEASURES: Log-transformed serum AMH concentrations. RESULTS: Linear regression models evaluated whether plasma F2-isoprostanes were associated with log-transformed AMH after adjustment for age, race, smoking, body mass index, and oral contraceptive pill use. Higher levels of F2-isoprostanes were associated with lower AMH levels (ß -0.048 per standard deviation, 95% confidence interval -0.087, -0.01). The observed associations were stronger at younger ages (P=.04 for interaction between levels of age and F2-isoprostanes). Indicators of other steps in the oxidative stress pathway (superoxide dismutase, paraoxonase activity, oxidized low-density lipoprotein cholesterol, and carotenoids) were not associated with AMH, although lower phospholipase A2 activity (ß 0.036 per standard deviation, 95% confidence interval 0.001, 0.071) was associated with lower AMH across all ages. CONCLUSION: In a population-based cohort, higher levels of F2-isoprostanes were associated with lower ovarian reserve, particularly at younger ages.

Temporal Changes in Resting Heart Rate, Left Ventricular Dysfunction, Heart Failure and Cardiovascular Disease: CARDIA Study.

BACKGROUND: The prognostic significance of temporal changes in resting heart rate in young adults for premature heart failure and cardiovascular disease is unclear. We investigated the association between temporal changes in resting heart rate in young adults and early adult risk factors, subsequent cardiac function, and the risk of heart failure and cardiovascular by middle age. METHODS: We examined 4343 Coronary Artery Risk Development in Young Adults (CARDIA) study participants (mean [SD] age was 29.9 [3.6] years at the CARDIA Year-5 examination [1990-1991], 49% of participants were men, and 45% were African-American). Adjusted linear regression models were used to assess the association between temporal changes in resting heart rate, early life cardiovascular disease risk factors, and midlife cardiac function. Cox proportional hazard regression models were used to relate temporal changes in resting heart rate to heart failure and cardiovascular disease. Outcomes were followed up until August 31, 2017. RESULTS: Higher alcohol consumption (ß = 0.03, P <0.001), lower physical activity (ß = 0.002, P = 001), smoking (ß = 1.58, P <0.001), men (P <0.001), African Americans (P <0.001), impaired left ventricular relaxation (e´,ß = -0.13, P = 0.002), and worse diastolic function (E/e´, ß = 0.1, P = 0.01) were associated with longitudinal increases in resting heart rate. We observed 268 cardiovascular disease and 74 heart failure events over a median of 26 years. In Cox models, baseline and temporal changes in resting heart rate were associated with higher risk of heart failure (hazard ratio [HR] =1.37 95% confidence interval [CI] [1.05-1.79] and HR = 1.38 95% CI [1.02-1.86]) and a higher risk cardiovascular disease (HR = 1.23 95% CI [1.07-1.42] and HR = 1.23 95% CI [1.05-1.44]). CONCLUSIONS: Baseline and temporal changes in resting heart rate in young adults were associated with incident heart failure and cardiovascular disease by midlife. Contributory factors were associations between temporal increases in resting heart rate and early adult risk factors and subsequent cardiac dysfunction.

Prepregnancy Fitness and Risk of Gestational Diabetes: A Longitudinal Analysis.

PURPOSE: This study aimed to assess the associations of prepregnancy cardiorespiratory fitness, moderate- to vigorous-intensity physical activity (MVPA), and time spent watching television with subsequent development of gestational diabetes mellitus (GDM). METHODS: Participants were 1333 women enrolled in the Coronary Artery Risk Development in Young Adults study who did not have diabetes either at baseline (1985-86) or before births occurring after baseline. Baseline fitness was estimated using a graded symptom-limited maximal exercise treadmill test and expressed in MET units. Baseline MVPA (exercise units per day) was measured using the Coronary Artery Risk Development in Young Adults physical activity history questionnaire, and television viewing (h·d) was assessed by self-report in 1990-1991. Logistic regression analysis was used to derive odds ratios and 95% confidence intervals, adjusting for time from baseline to delivery and baseline study center, age, race, education, parity, family history of diabetes, smoking, alcohol, saturated fat intake, waist circumference, homeostasis model assessment of insulin resistance, and HDL cholesterol. RESULTS: Over 25 yr of follow-up, 164 women developed GDM. The odds of developing GDM were 21% lower for each 1 SD increment in baseline level of fitness (2.3 METs, odds ratio = 0.79, 95% confidence interval = 0.65-0.96). Prepregnancy MVPA and television viewing were not statistically associated with the development of GDM. CONCLUSION: Study findings indicate that objectively assessed prepregnancy fitness, but not self-reported MVPA or television time, is associated with GDM. Clinicians should counsel women on the benefits of improving fitness in the preconception period, particularly among women at greater risk for GDM.

Gamma prime (γ') fibrinogen and carotid intima-media thickness: the Atherosclerosis Risk in Communities study.

: We assessed if γ' fibrinogen, an isoform of fibrinogen, is independently associated with subclinical atherosclerosis beyond total fibrinogen in black and white men and women participating in the Atherosclerosis Risk in Communities study. Fasting γ' fibrinogen was measured in 6847 Atherosclerosis Risk in Communities participants, ages 51-70 years, in 1993-1995. Carotid intima-media far wall thickness (CIMT) was measured by B-mode ultrasonography at the common, internal and bifurcation carotids. The association of γ' fibrinogen tertiles with overall and segment-specific mean CIMT was assessed with linear regression, controlling for fibrinogen as well as cardiovascular risk factors, including high-sensitivity C-reactive protein and D-dimer. γ' Fibrinogen values ranged from 8.0 to 80.3 mg/dl and were positively related to age, female sex, black race, smoking, BMI, lipids and SBP. Crude γ' fibrinogen was directly associated with all CIMT measures except for the internal carotid, but explained less than 1% of the variance in the associations. Adjustment for total fibrinogen eliminated these associations, and total fibrinogen remained an independent predictor of CIMT without explaining additional variance. Adjustment for potential confounding variables did not alter the observed associations, which did not differ by race or sex. In these cross-sectional data, γ' fibrinogen was not independently associated with CIMT when controlling for total fibrinogen. γ' Fibrinogen and total fibrinogen together explained a very small proportion of the variance in CIMT, regardless of the carotid site. If γ' fibrinogen adds to total fibrinogen's ability to predict subclinical atherosclerosis, it may be in younger populations.