2nd Quartiles Research Articles

A Prospective Study of Arsenic and Manganese Exposure and Maternal Blood Pressure During Gestation

BACKGROUND AND AIM: Pregnancy is a sensitive time for maternal cardiovascular functioning. This study examines the associations between arsenic and manganese exposures to maternal blood pressure (BP) measured during pregnancy. METHODS: Pregnant women (N=1,522) were recruited for a prospective cohort in Bangladesh (2008-2011). Drinking water arsenic and manganese were measured at 16 weeks gestation and toenail measurements were made one-month post-partum. BP (systolic and diastolic) levels were measured during monthly home visits. Linear mixed models estimated the associations between repeated BP measurements, arsenic, and manganese. RESULTS:Drinking water and toenail arsenic showed a positive dose-response association with maternal BP. Each natural log increase in drinking water arsenic was associated with 1.27 mmHg systolic (95% CI: 1.20 – 1.34) and 1.16 mmHg diastolic (95% CI: 1.11-1.20) increase in BP per month of gestation after adjusting for covariates. Each natural log increase in toenail arsenic levels was associated with a 1.28 mmHg systolic (95% CI: 1.15 – 1.44) and 1.14 mmHg diastolic (95% CI: 1.05 – 1.23) increase in BP per month of gestation after adjusting for covariates. Drinking water manganese exposure had a non-linear association with maternal BP. Drinking water manganese in the 2nd quartile (160-589 µg/L) was associated with a 1.70 mmHg increase in systolic (95% CI: 1.21-2.38) and 1.39 mmHg in diastolic (95% CI: 1.09-1.76) BP per month of gestation after adjusting for covariates. Each natural log increase of toenail manganese was associated with a 1.21 mmHg of systolic and 1.54 mmHg of diastolic increase in BP over gestation (systolic 95% CI: 1.06-1.37, diastolic 95% CI: 1.15-2.05), after adjusting for covariates. CONCLUSIONS:Arsenic and manganese exposure during pregnancy was associated with increases in maternal systolic and diastolic BP. Elevated gestational BP can increase risks of adverse birth outcomes and CVD later in life for the mother. KEYWORDS: Cardiovascular diseases, Pregnancy outcomes, Water quality, Heavy metals, Environmental Epidemiology

Prenatal exposure to solar radiation and hypertensive disorders of pregnancy.

To examine the association between prenatal exposure to solar radiation and hypertensive disorders of pregnancy (HDP). A multicentre retrospective study. 19 hospitals in the USA. 205 888 women with singleton gestation from the Consortium on Safe Labor (2002-2008). Gestational hypertension, pre-eclampsia/eclampsia, and pre-eclampsia superimposed on chronic hypertension. Medical records of the participants were linked to solar radiation obtained from the National Solar Radiation Database. Average daily solar radiation of each woman was estimated over the entire pregnancy period and over three trimesters during pregnancy according to hospital sites. Generalised estimated equation was applied to investigate the relationship between quartiles of average daily solar radiation and HDP. Restricted cubic spline was applied to assess the nonlinear associations. Higher average solar radiation during the entire pregnancy was associated with reduced risks of HDP. Compared with the 1st quartile of solar radiation during the entire pregnancy, odds ratios (ORs) of the 2nd, 3rd and 4th quartiles were respectively 0.80 (95% CI 0.72-0.90), 0.63 (95% CI 0.55-0.73), 0.65 (95% CI 0.54-0.78) for gestational hypertension; 0.66 (95% CI 0.57-0.76), 0.61 (95% CI 0.51-0.73), 0.77 (95% CI 0.62-0.95) for pre-eclampsia, and 0.44 (95% CI 0.36-0.55), 0.42 (95% CI 0.35-0.49), 0.60 (95% CI 0.46-0.78) for superimposed pre-eclampsia. Exposure to higher daily solar radiation during pregnancy is associated with a decreased risk of HDP. The protective effect was stronger for superimposed pre-eclampsia than for pre-eclampsia or gestational hypertension. Exposure to higher daily solar radiation during pregnancy is associated with a decreased risk of HDP.

Land use and semen quality: A fertility center cohort study.

This study explored the association between built environment and semen parameters among men who sought fertility evaluation. We used a data of 5,886 men living in the Seoul capital area whose semen was tested at a single fertility center during 2016-2018. Distance to fresh water, the coast, major roadways, and neighborhood greenness measured by Normalized Difference Vegetation Index (NDVI) were evaluated. Outcome indicators were semen volume, sperm concentration, percentage of progressive motility, vitality, normal morphology, and total motile sperm count. Linear regression models were fitted to standardized values of six semen indicators. Majority of men were white-collar, clerical, and service workers. Linear associations between built environment features and semen quality indicators were not evident except for NDVI within 500 m and sperm vitality (β = 0.05; 95% confidence interval (CI): 0.01, 0.09). The 2nd quartile of distance to fresh water was associated with lower progressive motility compared to the 1st quartile (β = -0.10; 95% CI: -0.17, -0.03). Proportion of vitality was higher among men in the 2nd quartile of distance to roadways than those in the 1st quartile (0.08; 95% CI: 0.01, 0.15). Men in the 2nd quartile of NDVI had higher total motile sperm count (0.09; 95% CI: 0.01, 0.17). In the multi-exposure model, the positive association between NDVI and vitality remained (0.03; 95% CI: 0.00, 0.06). We observed potential evidence regarding the impact of built environment on male fertility, specifically a positive association between residential greenness and sperm vitality among men with a history of infertility.

Community daytime noise pollution and socioeconomic differences in Chicago, IL.

Environmental noise may affect hearing and a variety of non-auditory disease processes. There is some evidence that, like other environmental hazards, noise may be differentially distributed across communities based on socioeconomic status. We aimed to a) predict daytime noise pollution levels and b) assess disparities in daytime noise exposure in Chicago, Illinois. We measured 5-minute daytime noise levels (Leq, 5-min) at 75 randomly selected sites in Chicago in March, 2019. Geographically-based variables thought to be associated with noise were obtained, and used to fit a noise land-use regression model to estimate the daytime environmental noise level at the centroid of the census blocks. Demographic and socioeconomic data were obtained from the City of Chicago for the 77 community areas, and associations with daytime noise levels were assessed using spatial autoregressive models. Mean sampled noise level (Leq, 5-min) was 60.6 dBA. The adjusted R2 and root mean square error of the noise land use regression model and the validation model were 0.60 and 4.67 dBA and 0.51 and 5.90 dBA, respectively. Nearly 75% of city blocks and 85% of city communities have predicted daytime noise level higher than 55 dBA. Of the socioeconomic variables explored, only community per capita income was associated with mean community predicted noise levels, and was highest for communities with incomes in the 2nd quartile. Both the noise measurements and land-use regression modeling demonstrate that Chicago has levels of environmental noise likely contributing to the total burden of environmental stressors. Noise is not uniformly distributed across Chicago; it is associated with proximity to roads and public transportation, and is higher among communities with mid-to-low incomes per capita, which highlights how socially and economically disadvantaged communities may be disproportionately impacted by this environmental exposure.

Impact of Plasmatic Progesterone on the Day of Frozen Embryo Transfer in Hormone-induced Cycles.

To establish a relationship between serum progesterone values on the day of frozen blastocyst transfer in hormone-replaced cycles with the probability of pregnancy, miscarriage or delivery. This was an ambispective observational study including all frozen-thawed embryo transfer cycles performed at our department following in vitro fecundation from May 2018 to June 2019. The outcomes evaluated were β human chorionic gonadotropin (β-hCG)-positive pregnancy and delivery. Groups were compared according to the level of serum progesterone on the day of embryo transfer: the 1st quartile of progesterone was compared against the other quartiles and then the 2nd and 3rd quartiles against the 4th quartile. A total of 140 transfers were included in the analysis: 87 with β-HCG > 10 IU/L (62%), of which 50 (36%) delivered and 37 had a miscarriage (42%). Women with lower progesterone levels (< 10.7ng/mL) had a trend toward higher β-HCG-positive (72 versus 59%; p > 0.05), lower delivery (26 versus 39%; p > 0.05) and higher miscarriage rates (64 versus 33%; p < 0.01). Comparing the middle quartiles (P25-50) with those above percentiles 75, the rate of pregnancy was similar (60 versus 57%; p > 0.05), although there was a trend toward a higher number of deliveries (43 versus 31%; p > 0.05) and a lower number of miscarriages (28 versus 45%; p > 0.05). These differences were not statistically significant. There were no differences in pregnancy and delivery rates related with the progesterone level when measured in the transfer day. The miscarriage rate was higher in the 1st quartile group.

Whole-blood magnesium and blood lipids are individually and jointly associated with an elevated likelihood of youngsters being overweight or obese: A matched case-control study using the propensity score

ObjectivesYoungsters who are overweight or obese (YOO) have become an important global health concern. Some micronutrients may be modifiable influential factors. This study aimed to investigate the individual and joint association of whole-blood magnesium (WBMg) and total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), or high-density lipoprotein cholesterol (HDL-C) in YOO. MethodsThis is a propensity score matching-based case-control study. YOO was defined depending on age- and sex-specific body mass index z-score, calculated with SAS macros (%group_standard and %WHO2007) from the World Health Organization website. WBMg, blood lipids, and covariates were carefully measured by trained technicians using a whole-blood, five-element, basic analyzer and atomic absorption spectrometer or automatic biochemical analyzer. Locally weighted scattered plot smoothing and multivariable conditional logistic regression models were applied to estimate the associations of WBMg and blood lipids in YOO. ResultsWBMg was positively associated with YOO. The adjusted likelihood of YOO significantly increased by 21% (odds ratio: 1.21; 95% confidence interval [CI], 1.10–1.33) with per-interquartile range elevation of WBMg. Compared with the 1st quartile, adjusted odds ratios among youngsters in the 2nd, 3rd, and 4th quartiles of WBMg were 1.11 (95% CI, 0.92–1.35), 1.29 (95% CI, 1.06–1.57), and 1.47 (95% CI, 1.18–1.83), respectively. Furthermore, the relationship between WBMg and YOO was moderated by lipid profiles. Compared with those having lower (< median) WBMg and TC, TG, LDL-C, or higher (≥ median) HDL-C, youngsters with both higher WBMg and TC, TG, LDL-C, or lower HDL-C had higher YOO odds, which averagely increased by 188%, 250%, 339%, and 369%, respectively. ConclusionsWBMg was an independent risk factor of YOO, and the associations were stronger among those with unhealthy blood lipids. Our findings can help to guide clinical and public health policies on the relevance of magnesium nutritional status.

Longitudinal change in lung function and subsequent risks of cardiovascular events: evidence from four prospective cohort studies

BackgroundLung function is constantly changing over the life course. Although the relation of cross-sectional lung function measure and adverse outcomes has been reported, data on longitudinal change and subsequent cardiovascular (CV) events risks are scarce. Therefore, this study is to determine the association of longitudinal change in lung function and subsequent cardiovascular risks.MethodsThis study analyzed the data from four prospective cohorts. Subjects with at least two lung function tests were included. We calculated the rate of forced respiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decline for each subject and categorized them into quartiles. The primary outcome was CV events, defined as a composite of coronary heart disease (CHD), chronic heart failure (CHF), stroke, and any CV death. Cox proportional hazards regression and restricted cubic spline models were applied.ResultsThe final sample comprised 12,899 participants (mean age 48.58 years; 43.61% male). Following an average of 14.79 (10.69) years, 3950 CV events occurred. Compared with the highest FEV1 quartile (Q4), the multivariable HRs for the lowest (Q1), 2nd (Q2), and 3rd quartiles (Q3) were 1.33 (95%CI 1.19, 1.49), 1.30 (1.16, 1.46), and 1.07 (0.95, 1.21), respectively. Likewise, compared with the reference quartile (Q4), the group that experienced a faster decline in FVC had higher HRs for CV events (1.06 [95%CI 0.94–1.20] for Q3, 1.15 [1.02–1.30] for Q2, and 1.28 [1.14–1.44] for Q1). The association remained robust across a series of sensitivity analyses and nearly all subgroups but was more evident in subjects < 60 years.ConclusionsWe observed a monotonic increase in risks of CV events with a faster decline in FEV1 and FVC. These findings emphasize the value of periodic evaluation of lung function and open new opportunities for disease prevention.

Association of serum uric acid with biventricular myocardial dysfunction in patients with type 2 diabetes mellitus

Background and aimsIncreased serum uric acid (SUA) is common in type 2 diabetes mellitus (T2DM) and is associated with left ventricular (LV) myocardial dysfunction. Nonetheless the association of SUA with right ventricular (RV) function in T2DM has not been studied. This study aimed to investigate the association of SUA with biventricular myocardial function in patients with T2DM. Methods and resultsA total of 560 patients with T2DM were enrolled and divided into four groups according to sex-specific quartiles of SUA. Transthoracic echocardiography was performed and two-dimensional speckle tracking was used to measure biventricular myocardial strain, including LV global longitudinal strain (GLS), circumferential strain (CS), radial strain (RS), and RV free wall longitudinal strain (RV-FWLS). The absolute value of all biventricular strain parameters showed a stepwise decrease across SUA quartiles (all P < 0.01). In particular, LV assessment by GLS, CS and RS demonstrated that those in the 4th quartile were impaired compared with the other quartiles (all P < 0.05). Similarly, RV-FWLS of the 4th quartile was significantly impaired compared with the 1st and 2nd quartiles (all P < 0.05). The same reduction in biventricular strain across SUA quartiles was observed in patients with estimated glomerular filtration rate < or ≥60 ml/min/1.73 m2, and glycated hemoglobin < or ≥7.0% (all P < 0.05). Multivariable linear regression analysis demonstrated that higher quartile of SUA was independently associated with impaired biventricular myocardial strain (all P < 0.05). ConclusionsSUA was independently associated with biventricular myocardial dysfunction in asymptomatic T2DM patients, regardless of renal function or diabetic control.

Association between Pb, Cd, and Hg Exposure and Liver Injury among Korean Adults.

Background: Exposure to lead (Pb), cadmium (Cd), and mercury (Hg) has been reported to be associated with liver-related diseases. However, studies examining the association between heavy metal exposure and liver injury in a large population are scant and characterized by inconsistent results. This study aimed to evaluate the association between levels of heavy metal exposure and liver injury in the general population. Methods: Data for 2953 participants aged 19 years or more obtained from the Korean National Environmental Health Survey (KoNEHS) Cycle 3 (2015–2017) were used. The associations between levels of blood or urine heavy metals (Pb, Cd, and Hg) and liver function biomarkers [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT)] were evaluated using multiple linear regression analysis. Results: Regarding the blood Pb (BPb), AST was higher in those of the 4th quartile, ALT was higher in those of the 2nd and 4th quartiles, and GGT was higher in those of the 3rd and 4th quartiles than in the 1st quartile. For urinary Cd (UCd), AST was higher in those of the 4th quartile; ALT was higher in those of the 2nd, 3rd, and 4th quartiles; and GGT was higher in the 4th quartile than in the 1st quartile. For the blood Hg (BHg), AST was higher in those of the 2nd and 4th quartile, ALT was higher in those of the 2nd, 3rd, and 4th quartiles; and GGT was higher in those of the 3rd and 4th quartiles than in the 1st quartile. There was no significant difference between urinary Hg (UHg) and liver function markers. Conclusion: Heavy metal exposure showed an association with liver injury among the general adult population in Korea. Further studies are required to clarify the relationship between heavy metals and liver injury.

432-P: Sodium Intake and Incidence of Diabetes Retinopathy in Elderly Patients with Type 2 Diabetes: Analysis of Data from the Japanese Elderly Diabetes Intervention Study (J-EDIT)

Though excessive sodium intake is regarded as a crucial factor related to developing and worsening of diabetes complications, data on this topic in elderly patients with diabetes are sparse. We investigated the associations between sodium intake and diabetes complications in a nationwide cohort of elderly Japanese patients with type 2 diabetes aged 65 - 85 years. The present analysis was conducted among Japanese patients with type 2 diabetes from outpatient clinics in 39 university and general hospitals in Japan. Data were analyzed on 912 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcomes were times to diabetic retinopathy, overt nephropathy, cardiovascular disease, and all-cause mortality during 6 years. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders Mean sodium intake in quartiles ranged from 2498 mg to 5910 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (&amp;lt; 2300 mg/day). After adjustment for confounders, HRs for complications in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and complications. Among patients whose vegetable intake was less than the average of 268.7 g, HRs for diabetic retinopathy in patients in the 2nd, 3rd, and 4th quartiles of sodium intake compared with the 1st quartile were 0.87 (95% CI, 0.31-2.41), 2.61 (1.00-6.83), and 3.70 (1.37-10.02), respectively. Findings indicated that high sodium intake under conditions of low vegetable intake is associated with elevated incidence of diabetic retinopathy in elderly patients with type 2 diabetes. Disclosure C. Horikawa: None. T. Moriya: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. A. Araki: None. R. Aida: None. S. Tanaka: None. C. Kamada: None. S. Tanaka: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. R. Kawasaki: None. Funding Japan Society for the Promotion of Science (19H04028)

371-P: Impact of Sodium Intake on the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: Analysis of Data from the Japan Diabetes Complications Study and the Japanese Elderly Diabetes Intervention Trial

Excessive sodium intake is regarded as a crucial factor related to developing and worsening of cardiovascular disease (CVD). However, epidemiological studies on this topic in patients with type 2 diabetes are sparse. We investigated the associations between sodium intake and CVD risk in Japanese patients with type 2 diabetes from the analysis of pooled data from two nation-wide prospective longitudinal studies. Data were analyzed on 2428 individuals whose dietary intake at baseline was assessed by the Food Frequency Questionnaire based on food groups. Primary outcome was the 6-year risk of a CVD event. Cox regression analyses estimated hazard ratios (HRs) for dietary intake adjusted for age, gender, body mass index, HbA1c, smoking, energy intake, and other confounders. Mean sodium intake in quartiles ranged from 2494 mg to 6166 mg/day and more than three-quarters of participants had sodium intake more than the recommended dietary allowance by American Diabetes Association (&amp;lt; 2300 mg/day). After adjustment for confounders, HRs for CVD in patients with sodium intake in the 2nd, 3rd, and 4th quartiles compared with sodium intake in the 1st quartile were analyzed, and no significant differences were shown between sodium intake and CVD [Q2: 0.77 (95%CI, 0.48-1.23); Q3: 1.03 (0.65-1.63); and Q4: 1.31 (0.80-2.14), trend p = 0.131]. Results of subgroup analysis according to age showed that patients aged 39 through 59 years in the higher quartiles of sodium intake compared with the 1st quartile had a significantly higher incidence of CVD [Q2: 1.37 (0.57-3.33); Q3: 1.68 (0.70-4.03); and Q4: 4.16 (1.63-10.58), trend p = 0.004]. However, no significant association between sodium intake and CVD in participants aged over 60 years. Findings indicated that high sodium intake is associated with elevated incidence of CVD in younger patients with type 2 diabetes. Disclosure C. Horikawa: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. R. Aida: None. S. Tanaka: None. C. Kamada: None. Y. Yoshimura: None. R. Kodera: None. K. Fujihara: None. T. Moriya: None. A. Araki: None. Funding Japan Society for the Promotion of Science (19H04028)

Impact of segmental hypertrophy on global and regional left ventricular deformation in hypertrophic cardiomyopathy A 3D speckle tracking imaging study

To assess left ventricular (LV) myocardial deformation with 3D echocardiography in hypertrophic cardiomyopathy (HCM) and study the impact of hypertrophy on global and regional systolic deformation. Forty HCM and 114 control patients with comprehensive 2D and 3D resting echocardiography (GE Vivid 9). Secondary HCM excluded classification of segments in relation to wall thickness in 2D short-axis views (30 patients) [as first quartile (< 10.5 mm, n = 104), third quartile (13.0–16.5ϖsecond quartile (10.5–13.0 mm, n = 103) mm, n = 101) and fourth quartile (> 16.5 mm, n = 106)]. All 3D strain value significantly decreased from 2nd to 4th quartile of myocardial thickness. Compared to control subjects, strain values were significantly lower: – in all quartiles of myocardial thickness for 3DGLS and 3DGAS, – in 3rd and 4th quartiles for 3DGRS, – 3DGCS in absolute value was increased for non hypertrophic segments (1st and 2nd quartiles) and decreased for 4th quartile. In addition, post-systolic shortening is frequent with higher values in 4th quartile of myocardial thickness ( Fig. 1 ). 3D echocardiography is a useful tool in HCM patients, allowing the analysis of all global and regional deformation parameters in one acquisition. Hypertrophy has an impact on the global mechanics of LV and on regional deformation of hypertrophic segments. Whatever the myocardial thickness, longitudinal strain absolute value is decreased. On another hand, circumferential strain is increased in non hypertrophic segments (1st and 2nd quartiles). Conversely, severely hypertrophic segments exhibits altered values for all strain components and higher value of post systolic index.

Features Of The Influence Of The Initial Level Of Physiological Indicator On The Following Stages Of Development

Early school age is a “nodal” age period when the most intensive functional restructuring of organs and systems occurs. Therefore, the period of ontogenesis, which coincides with the beginning of schooling, is the most important social stage in the development of a child. The purpose of our work was to study the significance of the initial level of the indicator, i.e. the level of this indicator at the beginning of the first academic year, for subsequent periods of development. We examined 86 pupils of the secondary school in Cheboksary. The study of the significance of the initial level was carried out by means of a separate study of the dynamics of physiological indicators for individual subgroups, formed on the basis of the levels of these indicators at the beginning of the first grade. The surveyed contingent of schoolchildren was divided into subgroups based on the results of calculating the quartiles of the distribution: 1 quartile - pupils with heart rate values below 80 beats / min at the beginning of the first academic year; quartile 2 - pupils with heart rate values in the range of 80-86 beats / min; 3rd quartile - pupils with heart rate values within 87-92 beats / min; 4th quartile - pupils with heart rate values above 92 beats / min. In pupils of the 1st quartile, by the end of the study period compared to the beginning of the study, there is a slight increase in the mean population and individual mean heart rate (p> 0.05). Schoolchildren of the 2nd quartile and schoolchildren of the 3rd quartile have a slight increase in the studied indicator in the middle and at the end of the first year, then the highest average heart rate is observed at the beginning of the second year of study, and already during the subsequent time, there is a gradual decrease in the average heart rate. The pupils of the 4th quartile had a difference in the dynamics of the average heart rate values as compared with the children of the other three quartiles. In children of the 4th quartile, in contrast to other groups, during the first year of schooling, the studied indicator gradually decreases. During the training period in this group, there is a tendency to decrease the average population and individual average heart rate. Based on the corresponding age physiological norms, the studied contingent of children according to the values of systolic blood pressure (SBP) and diasystolic blood pressure (DBP) was divided into two groups: pupils with SBP and DBP values within the normal range; pupils with SBP and DBP values at the level of the lower limit of the norm. For children with relatively low SBP values at the beginning of the first academic year, significant statistically significant fluctuations in the indicator level were revealed during the entire observation period (p < 0.05). In children with SBP values within the normal range at the beginning of the first academic year, the intra-year dynamics was less pronounced. Thus, the study of the significance of the level of functioning of physiological systems at the beginning of school education made it possible to establish the significance of this level for subsequent individual development.

FGF21 Serum Levels in the Early Second Trimester Are Positively Correlated With the Risk of Subsequent Gestational Diabetes Mellitus: A Propensity-Matched Nested Case-Control Study

BackgroundAs an important endocrine hormone regulating glucose metabolism, fibroblast growth factor 21 (FGF21) is increased in individuals with gestational diabetes mellitus (GDM) after 24 gestational weeks. However, it is unknown whether the increase in FGF21 precedes the diagnosis of GDM.MethodsIn this nested case-control study, 133 pregnant women with GDM and 133 pregnant women with normal glucose tolerance (NGT) were identified through propensity score matching, and serum FGF21 levels were measured at 14 to 21 gestational weeks, before GDM is routinely identified. The differences in FGF21 levels were compared. The association between FGF21 and the occurrence of GDM was evaluated using logistic regression models with adjustment for confounders.ResultsThe serum FGF21 levels of the GDM group at 14 to 21 gestational weeks were significantly higher than those of the NGT group overall (P < 0.001), with similar results observed between the corresponding BMI subgroups (P < 0.05). The 2nd (OR 1.224, 95% CI 0.603–2.485), 3rd (OR 2.478, 1.229–5.000), and 4th (OR 3.419, 95% CI 1.626–7.188) FGF21 quartiles were associated with greater odds of GDM occurrence than the 1st quartile after multivariable adjustments.ConclusionsThe serum FGF21 levels in GDM groups increased in the early second trimester, regardless of whether participants were stratified according to BMI. After adjusting for confounding factors, the FGF21 levels in the highest quartile were associated with more than three times higher probability of the diagnosis of GDM in the pregnancy as compared to levels in the first quartile.

Dietary creatine and cognitive function in U.S. adults aged 60years and over.

Recent clinical trials suggested a potential benefit of dietary creatine on cognitive function for aging individuals. However, the association between creatine consumption from food and cognitive function in the older adults remained undetermined at the populational level. The present study quantified the amount of creatine consumed through a regular diet among U.S. adults aged 60years and over, and evaluated the link between dietary creatine and cognitive function using data from the 2001-2002 National Health and Nutrition Examination Survey (NHANES). NHANES 2001-2002 round included a total of 1340 older adults (51.8% women; age 71.4 ± 7.8years) who provided valid dietary information and cognitive testing measures. Dietary intake information was obtained from the NHANES Dietary Data component through a 24-h in-person dietary recall interview. Cognitive function was assessed using the WAIS III Digit Symbol Substitution Test (DSS) conducted during the household interview. A bivariate model revealed a significant positive correlation between DSS scores and creatine intake across the whole sample (τb = 0.043; P = 0.02). The partial models demonstrated a significant correlation between creatine consumption and DSS score when adjusted for sociodemographic variables (r = 0.062; P = 0.039), and nutritional variables (r = 0.055; P = 0.049). The participants who consumed more than 0.95g of creatine per day (3rd and 4th quartiles of creatine intake) were found to have higher scores on the cognitive functioning test as compared to their peers with lower creatine intake (1st and 2nd quartiles) (P < 0.05). Our findings suggest that creatine from food might be protective against reduced cognitive performance in the older population. Further research is highly warranted to investigate the role of dietary creatine amount in cognitive function in the older adults.

Air pollution and meteorological conditions during gestation and type 1 diabetes in offspring

BackgroundGrowing evidence indicates that air pollution is capable of disrupting the immune system and therefore, might be associated with an onset of Type 1 diabetes (T1D). ObjectivesWe explored possible links of T1D with ambient exposures in the population of southern Israel, characterized by hot and dry climate and frequent dust storms. MethodsWe conducted a matched nested case-control study where exposure to environmental pollutants during gestation in T1D cases was compared to that of healthy children. Up to 10 controls were matched to every case by age, gender and ethnicity, in all 362 cases and 3512 controls. Measurements of pollutants' concentrations, nitrogen dioxide (NO2), sulphur dioxide (SO2), ozone (O3) and particulate matter of size less than 10 and 2.5 μm in diameter (PM10 and PM2.5), as well as the mean daily measurements of meteorological conditions were obtained from the local monitoring stations. The association between T1D and pollution, solar radiation (SR), temperature and relative humidity was adjusted for socioeconomic status, temperature, maternal age and pre-gestational maternal DM, using conditional logistic regression. The environmental exposures were presented as indicators of quartiles averaged over whole pregnancy and by trimesters. ResultsExposure to ozone and solar radiation during gestation were both associated with the T1D in offspring, although at borderline significance. Compared to the lowest quartile, the odds ratio (OR) for exposure to 3rd and 4th quartile of O3 was equal 1.61 (95%CI: 0.95; 2.73) and 1.45 (95%CI: 0.83; 2.53), respectively. Likewise, the ORs for exposure to SR were equal 1.83 (95%CI: 0.92; 3.64), 2.54 (95%CI: 1.21; 5.29) and 2.06 (95%CI: 0.95; 4.45) for to 2nd, 3rd and 4th quartiles, respectively. Exposure to SO2 followed a dose-response pattern, but was not statistically significant. Other environmental factors were not independently related to T1D. Analysis of exposures one year prior to the disease onset indicated a positive association between T1D and SR. ConclusionsWe showed that exposure to high ozone levels and solar radiation during gestation might be related to the T1D. More scientific evidence needs to accumulate to support the study findings.

CAROTID VASCULAR RESISTANCE ASSOCIATED WITH COGNITIVE FUNCTION AMONG MIDDLE-AGE ADULTS

Objective: Carotid flow velocity and peripheral blood pressure were independently associated with cognitive function among the elderly population, but unknown among middle-aged adults. We aimed to investigate the association between carotid hemodynamics and cognitive performance among the middle-age population. Design and method: A total of 490 middle-age adults (between 30 and 60 years) participated in the ongoing survey (2017–2020) of the Cardiovascular Disease Risk Factors two-Township study and received the Montreal Cognitive Assessment (MOCA) to evaluate the global cognitive function. Carotid-formal pulse wave velocity (cf-PWV) was measured using carotid and femoral arterial tonometry. Carotid vascular resistance was calculated by mean carotid pressure divided into mean carotid volume flow. Results: MOCA levels were similar between men and women (27.1 vs. 27.2, p = 0.6036). Age(r = -0.22, P &lt; 0.001), and education(r = 0.39, p &lt; 0.001) were associated with MOCA. Controlled for age, gender and education, peak systolic velocity (r = 0.077 @left; r = 0.012@Right, all p &gt; 0.05), end diastolic velocity (r = 0.029, r = -0.062, all p &gt; 0.05), mean flow (r = 0.060; r = -0.038, all p &gt; 0.05), carotid resistive index (r = 0.020, r = 0.05, all p &gt; 0.05), carotid pulsatility(r = 0.015; r = 0.058; p &gt; 0.05), diameter(r = 0.060; r = -0.008, all p &gt; 0.05) at both sides were not associated with MOCA. Only carotid vascular resistance (CVR) at left side was associated with MOCA (r = -0.158, p = 0.0010), but not at right carotid artery (r = -0.030, p = 0.5369). CVR@Left (standard beta = -0.144; p = 0.0022) remains associated with MOCA in the multivariable with further controlling glucose, low density lipoprotein and carotid-formal pulse wave velocity. Those with top, 2nd and 3th quartile of CVR@left had 2.4-fold [Odds Ratio = 2.40; 95% confidence intervals = 1.14–5.04], 1.95-fold(1.95;0.93–4.07) and 0.99-fold (0.99;0.45–2.17) risk for poor cognitive performance (MOCA &lt; 26), compared to those with lowest quartile of CVR@left in the multivariable model. Conclusions: Carotid vascular resistance is a marker of cerebrovascular resistance and associated with cognitive performance in middle-aged adults.

Services and payer mix of Black-serving hospitals and related severe maternal morbidity

Black-serving hospitals are associated with increased maternal risk. However, prior administrative data research on maternal disparities has generally included limited hospital factors. More detailed evaluation of hospital factors related to obstetric outcomes may be important in understanding disparities. To examine detailed characteristics of Black-serving hospitals and how these characteristics are associated with risk for severe maternal morbidity (SMM). This serial cross-sectional study linked the 2010-2011 Nationwide Inpatient Sample and the 2013 American Hospital Association Annual Survey Databases. Delivery hospitalizations occurring to women 15-54 years of age were identified. The proportions ofnon-Hispanic Black patients within a hospital was categorized intoquartiles, and hospital factors such as specialized medical, surgical and safety-net services as well as payer mix were compared across these quartiles. A series of models was performed evaluating risk for SMM with Black-serving hospital quartile as the primary exposure. Log linear regression models with a Poisson distribution (and robust variance) were performed with unadjusted and adjusted risk ratios (aRR) with 95% confidence intervals (CIs) as measures of effect. Overall 965,202 deliveries from 430 hospitals met inclusion criteria and were included in the analysis. By quartile, non-Hispanic Black patients accounted for 1.3%, 5.4%, 13.4%, and 33.8% of patients. Many services were significantly less common in the lowest compared to the highest Black-serving hospital quartile including cardiac intensive care (48.9% versus 74.5%), neonatal intensive care (28.9% versus 64.9%), pediatric intensive care (20.0% versus 45.7%), pediatric cardiology (29.6% versus 44.7%), and HIV/AIDS services (36.3% versus 71.3%) (p≤0.01 for all). Indigent care clinics, crisis prevention, and enabling services (p≤0.01 for all) were more common at Black-serving hospitals as was Medicaid payer. Following adjustments for detailed hospital factors, the lowest Black serving hospital quartile carried the lowest risk for SMM. However, SMM risks were similar across the 2nd (aRR 1.31, 95% CI 1.08, 1.59), 3rd (aRR 1.27, 95% 1.05, 1.55), and 4th (aRR 1.29, 95% CI 1.07, 1.55) quartiles. Black-serving hospitals were more likely to provide a range of specialized medical, surgical, and safety-net services and to have a higher Medicaid burden. Payer mix and unmeasured confounding may account for some of the maternal risk associated with Black-serving hospitals.

Analysis of causes of death in patients with implanted defibrillators.

Implantable cardioverter defibrillators (ICDs) are used for primary or secondary prevention of sudden cardiac death. We sought to clarify prognosis and causes of death after ICD implantation. A total of 2743 patients with ICDs implanted during 1990-2020 were analyzed. Median age was 68.5 (59.6-74.6) years; 21% women, median left ventricular ejection fraction (LVEF) was 30 (23-35), 52% had an ischemic etiology and 77% had a primary preventive indication. Mortality rate after 10years was 22, 44, 55, and 72% in the 1st, 2nd, 3rd, and 4th age quartile, respectively. The calculated median sex and age adjusted loss of life years compared to the average German population was 9.7 (6.1-14.0) years. Prognosis was independently related to sex, age, LVEF, and glomerular filtration rate. 713 out of 852 deaths could be classified to a specific cause. Congestive heart failure (CHF) accounted for death in 214 (30%) and sudden death (SD) for 144 patients (20%). Postmortem interrogation of devices in 74 patients revealed VT/VF in 39 and no episodes in 35 patients. Cancer was identified as the cause of death in 121 patients (17% of cases), of which 36 were bronchial carcinomas. 73 (10%) of patients died due to infection. 67 patients (9%) died within 24h of procedures. Compared to other causes, significantly more life years were lost associated with procedures and SD: 9.3 (5.7-12.9) versus 12.1 (7.4-15.2) and 11.9 (7.6-17.8) years. Life expectancy of ICD patients is lower than for the general population. Mortality is predominantly due to CHF, but there is still a considerable rate of SD. The occurrence of cancers, most importantly bronchial carcinomas, and infections, warrants protective measures. Some deaths during procedures are possibly preventable. Patients with ICDs comprise a vulnerable cohort, and treatment has to be optimized in many directions to improve prognosis.

Abstract PD6-05: Subtype-specific MRI models to guide selection of candidates for de-escalation of neoadjuvant therapy

Abstract Background: MRI measured functional tumor volume (FTV) can predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) as early as 3 weeks after treatment initiation (1), indicating the potential of using MRI to guide treatment de-escalation. We developed MRI based, subtype-specific models for predicting pCR, to be used as part of a de-escalation strategy combining MRI and inter-regimen core biopsy pathology in I-SPY 2. Methods: I-SPY 2 patients underwent MRI exams at pre-treatment, early treatment (3 wks), inter-regimen (12 wks), and pre-surgery. pCR was assessed at surgery. FTV was calculated semi-automatically for every MRI (2). Subtype-specific FTV-based MRI prediction models were trained using FTV measurements at baseline, early treatment and inter-regimen timepoints for patients enrolled in I-SPY 2 between May 2010 and November 2016. Breast cancer subtype was defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The MRI prediction model was then used to predict probability of achieving pCR for each patient at inter-regimen, based on their subtype. The therapy de-escalation strategy focuses on achieving high positive predictive value (PPV, correct identification of patients with pCR) while maximizing sensitivity (proportion of patients with pCR identified by the test). Predicted probability above a specified threshold was considered a positive test for pCR. This study investigated the tradeoff between PPV and sensitivity within subtype groups defined by HR and HER2, and held to constraints set by probability thresholds at the 1st, 2nd (median) and 3rd quartile. Results: A total of 814 patients were included in the analysis. Median age was 49 (range: 24 - 77) years. The pCR rate was 36% (289/814). Table 1 shows patient number and pCR rate by HR/HER2 subtype. The subtype-specific MRI models consist of the predictors: change of FTV (dFTV) at inter-regimen for HR+/HER2- and HR-/HER2+; dFTV at early treatment for HR+/HER2+; pre-treatment FTV and dFTV at inter-regimen for triple negatives. The highest probability varied by subtype: 0.24 for HR+/HER2-, 0.61 for HR+/HER2+, 0.73 for HR-/HER2+, 0.68 for triple negatives. The maximum PPV was 67% for HR+/HER2- and 100% for all other subtypes. Table 1 shows the tradeoff between PPV and sensitivity by subtype using the 1st, median, and 3rd quartile thresholds. Conclusions: Our data demonstrate that PPV and sensitivity vary by breast cancer subtype when the probability threshold generated by MRI model increases from low to high quartile. Results from this study suggest that the probability threshold for recommending treatment de-escalation should be selected carefully based on breast cancer subtype. Imaging results will be combined with core biopsy information obtained at the 12-week timepoint to further improve overall accuracy. Table 1 Tradeoff between positive predictive value (PPV) and sensitivity at different levels of PPVCohortNpCR rateProbability thresholdPPV (%)Sensitivity (%)HR+/HER2-32820% (64/328)1st quartile0.1824912nd quartile0.2128773rd quartile0.233552HR+/HER2+13239% (51/132)1st quartile0.2744862nd quartile0.4053693rd quartile0.515837HR-/HER2+7166% (47/71)1st quartile0.6775852nd quartile0.7181623rd quartile0.728934Triple negative(HR-/HER2-)28345% (127/283)1st quartile0.3454912nd quartile0.5262703rd quartile0.607341 Citation Format: Wen Li, David C Newitt, Jessica Gibbs, Lisa J Wilmes, Ella F Jones, Natsuko Onishi, Bonnie N Joe, Elissa Price, John Kornak, Christina Yau, Denise M Wolf, Barbara LeStage, Susan Samson, the I-SPY 2 Imaging Working Group, the I-SPY 2 Consortium, Laura J Esserman, Nola M Hylton. Subtype-specific MRI models to guide selection of candidates for de-escalation of neoadjuvant therapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD6-05.