bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract MP78: Relationship Between Casual Urinary Sodium/potassium Ratio And 24-h Urinary Sodium/potassium Ratio: The Intersalt Study
Authors: Iwahori Toshiyuki , Miura Katsuyuki , Ueshima Hirotsugu , Chan Queenie , Dyer Alan R , Elliott Paul , Stamler Jeremiah
Published: July 2021

Objective:
High dietary sodium (Na) and low dietary potassium (K) intakes are associated with adverse blood pressure levels and excess risks of cardiovascular diseases. The Sodium/potassium (Na/K) ratio is a composite index of Na and K. Recently, we found Na/K ratio of casual urine is useful for estimating 24-h urinary Na/K ratio in healthy Japanese participants. However, this finding has not been validated in different ethnic groups. Our aim was to assess the utility across and within populations of casual (spot) urine specimens to estimate 24-h urinary Na/K ratio using data from the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT).

Methods:
The INTERSALT study collected standardized data on casual urinary Na and K concentrations, and also on timed 24-h urinary Na and K excretion for 10,079 men and women ages 20-59 years from 52 population samples in 32 countries. Pearson correlation coefficients and agreement quality analysis (by the Bland-Altman method) were computed for Na/K ratio of casual urine against 24-h urinary Na/K ratio.

Results:
Overall mean value of Na/K ratio in 24-h urine collections was 3.24. 24-h urinary Na/K ratio and Na/K ratio of casual urine across the 52 population samples were highly correlated: r=0.96 (overall), r=0.96 (men), r=0.95 (women), r=0.94 (ages 20-29), r=0.94 (ages 30-39), r=0.95 (ages 40-49) and r=0.95 (ages 50-59). 24-hour urinary Na/K ratio and Na/K of casual urine across the 10,079 individuals had moderately strong correlations: r=0.69 (overall), r=0.70 (men), r=0.68 (women), r=0.58 (white), r=0.47 (black), r=0.81 (Amerindian), r=0.70 (Asian Indian), r=0.64 (east-Asian), r=0.70 (other ethnicities), r=0.58 (with anti-hypertensive medication use) and r=0.72 (without anti-hypertensive medication use). The bias estimate with the Bland-Altman method, defined as the difference between Na/K of 24-h urine collection and casual urine, was approximately 0.4 across both populations and individuals, independent of age, gender and anti-hypertensive medication use across the 52 population samples. Bias estimates across population samples were 0.39 (overall), 0.42 (men), 0.36 (women), 0.32 (ages 20-29), 0.41 (ages 30-39), 0.37 (ages 40-49) and 0.46 (ages 50-59). Bias estimates for the 10,079 individuals were 0.40 (overall), 0.42 (men), 0.37 (women), 0.33 (white), 0.69 (black), 0.04 (Amerindian), 0.22 (Asian Indian), 0.65 (east-Asian), 0.31 (other ethnicities), 0.45 (with anti-hypertensive medication use) and 0.38 (without anti-hypertensive medication use).

Conclusions:
These findings indicate that casual urine Na/K ratio is a useful, low-burden, low-cost method alternative to 24-h urine collection for estimation of urinary Na/K ratio across populations of various ethnicities. It is also applicable to individual urinary Na/K ratio.
Abstract MP79: Physical Activity Patterns by Data-driven Model-based Clustering Improve Association with Cardiovascular Risk Factors in a Multiethnic Cohort: The Northern Manhattan Study
Authors: Cheung Ken , Willey Joshua Z , Yu Gary , Gervasi-Franklin Palma , Wall Melanie M , Sacco Ralph L , Elkind Mitchell S
Published: July 2021

Background:
Physical activity is a complex modifiable risk factor (RF) for cardiovascular disease (CVD). Current methods to measure physical activity are limited by the use of summary scores such as total metabolic equivalents score (METS).

Hypothesis:
Physical activity patterns derived by a data-driven clustering method are associated with CVD RFs independently of METS.

Methods:
The Northern Manhattan Study is a prospective cohort of older, urban-dwelling, multiethnic, stroke-free individuals. Questionnaires were used to capture multi-dimensions of leisure-time physical activity, which was summarized with METS (total activity minutes х intensity in MET). Participants were grouped into previously defined METS categories (less than 1, greater than 14, and 1-14), and also into clusters by multivariate finite mixture modeling based on activity frequency, duration, energy expenditure, and number of activity types. Bayesian information criterion was used to decide number of clusters. Associations between model-based clusters and 4 RFs (diabetes, hypertension, obesity, high waist circumference) were assessed in the entire cohort and in each METS category; associations between METS and RFs were assessed in each cluster. Chi-squared test was used.

Results:
Physical activity data were available in 3293, with mean age 69 years, 63% women, and 52% Hispanic. Six clusters were identified and labeled I-VI (Table 1). Model-based clusters were associated with all four RFs (all p≤0.01), with clusters V and VI having lower RFs prevalence than the others: the association with obesity prevailed among those with 1≤METS≤14 (p<0.01); and with hypertension among those with METS>14 (p=0.03). METS categories were associated with all four RFs in the entire cohort (all p≤0.04); METS and RFs became no longer significantly associated within clusters.

Conclusions:
A data-driven clustering method for depicting physical activity data is a principled, generalizable approach to form subgroups associated with CVD RFs independently of METS.
Abstract P011: ST2 As A Risk Predictor For Cardiovascular Disease, Heart Failure And Mortality In The Prospective Finrisk97 Population Cohort
Authors: Hughes Maria F , Appelbaum Sebastian , Havulinna Aki S , Jagodzinski Annika , Ojeda Francisco , Zeller Tanja , Blankenberg Stefan , Salomaa Veikko
Published: July 2021

Introduction:
ST2 is a receptor for the inflammatory cytokine IL33. The ST2-IL33 pathway has been associated with development of atherosclerosis and coronary artery disease in humans although the mechanism is not fully established. Increased ST2 levels have been associated with heart failure and death in patients with acute myocardial infarction and in the general population where it has also been associated with diabetes. We hypothesized that ST2 levels can identify people in the general population with elevated risk of subsequent cardiovascular disease (CVD) and add to existing risk prediction algorithms.

Methods:
We measured high sensitivity soluble ST2 (Presage) in 7,551 men and women (25-74 years) from the FINRISK97 prospective population cohort. Cox proportional hazards modeling using age as the time scale evaluated the ability of sST2 to predict cardiovascular endpoints including fatal and non-fatal cardiovascular disease (coronary heart disease, stroke, heart failure), incident diabetes and death over 14 years follow up. Missing data (~10%) was multiply imputed and participants with prevalent disease at baseline were excluded for corresponding endpoints of disease. Discrimination and reclassification statistics (c-index, NRI) for 10 year absolute risks were calculated with internal (10-fold) cross validation to compare the ability of ST2 to improve upon Framingham risk factors, N-terminal pro-brain natriuretic peptide (NTProBNP) and renal function (eGFR), established markers of CVD risk.

Results:
sST2 concentrations significantly predicted all-cause death (hazard ratio (HR) comparing the highest quartile with the lowest was 1.28 95% confidence interval (C.I.) 1.04-1.57 (1024 events), major adverse cardiac events (MACE) (HR 1.22 (95% C.I. 1.001-1.49) (1068 events) and stroke (1.44 (95% C.I. 0.99-2.1) (370 events) after adjustment for Framingham risk factors, NTProBNP and eGFR. sST2 showed suggestive but non-significant association with heart failure (HR 1.21 (95% C.I. 0.92-1.58) (577 events) after similar adjustment. Similarly, sST2 showed a trend toward elevated but non-significant risk for diabetes (HR 1.14 (95% C.I. 0.87-1.49) (377 events) after adjustment for age, area, sex, smoking, systolic blood pressure, antihypertensive medication, glucose and prevalent CVD. No improvement in the c-index was observed for models adding sST2 to Framingham and other risk factors. Clinical NRI was improved in fully adjusted models for death 9% (
p
=1x10
-6
) and stroke 4% (
p
=0.028) with reclassification benefit mainly for non-cases. IDI was improved for MACE (
p
=0.02) and stroke (
p
=0.02).

Conclusions:
In a healthy general population from Finland (FINRISK97), sST2 improves prediction of death, MACE and stroke beyond Framingham covariates, NTProBNP and eGFR but does not improve prediction of heart failure.
Abstract P015: Fibroblast Growth Factor 23 and Echocardiographic Measures of Cardiac Structure and Function among African Americans: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Misialek Jeffrey R , Alonso Alvaro , Michos Erin D , Solomon Scott D , Shah Amil M , Konety Suma , Agarwal Sunil K , Selvin Elizabeth , Lutsey Pamela L
Published: July 2021

Introduction:
Fibroblast growth factor 23 (FGF23), an endocrine hormone, induced left ventricular (LV) hypertrophy through direct action in experimental animal models. The association of FGF23 with echocardiographic measures in humans is relatively uncharacterized.

Hypothesis:
Higher levels of FGF23 will be cross-sectionally associated with more adverse echocardiographic measures of LV structure and function.

Methods:
We conducted a cross-sectional analysis of 2086 African-American adults (66% female, median age 55) from a subset of the ARIC Study, a community-based cohort in the United States. Intact active FGF23 was assessed in blood samples collected at ARIC visit two (1990-1992). Echocardiography was performed at visit three (1993-1995) in participants recruited at the Jackson field center only. We used multivariable linear regression to evaluate the associations of FGF23 (per 15 pg/mL change) with echocardiographic measures after adjustment for traditional cardiovascular risk factors assessed at visit two. We also examined differences in observed associations by age and sex using interaction terms.

Results:
FGF23 was significantly associated with greater left atrial diameter and LV mass index (Table). A significant sex interaction was identified for LV diameter (p-interaction = 0.005). No association was observed in men while a positive association was observed among women. An adverse, decreasing trend in percent fractional shortening of the LV diameter at higher levels of FGF was stronger in individuals aged >55 (p-interaction = 0.03). No linear association was found between FGF23 and E/A ratio.

Conclusion:
FGF23 was associated with higher LV mass, larger LV size, and lower LV systolic function. These findings are consistent with results from experimental animal studies and provide evidence suggesting that cardiac structure and function may be influenced by FGF23 in humans. Prospective studies are needed to evaluate whether FGF23 is associated with change in markers of cardiac structure and function.
Abstract P017: Serum N-Carboxymethyl-Lysine and Risk of Mortality in Older Adults
Authors: Biggs Mary Lou , Benkeser David , Ix Joachim , Kizer Jorge , Djousse Luc , Siscovick David , Fitzpatrick Annette , Tracy Russell , Mukamal Kenneth
Published: July 2021

Advanced glycation end products (AGEs) are compounds formed by the non-enzymatic glycation of proteins, lipids, and nucleic acids, and are thought to play a role in the pathogenesis of diseases across multiple organ systems. Carboxymethyl-lysine (CML) is a dominant AGE found in tissue proteins and in the circulation, and a commonly used AGE biomarker. Only a few epidemiological studies have evaluated the association between circulating CML and mortality risk, and none have evaluated the association between CML and cause-specific non-CVD mortality.

We measured CML by ELISA on serum specimens collected from 3,373 Cardiovascular Health Study participants in 1996. Participants were followed for death through 2010, and cause of death was classified using death certificates, medical records, and proxy interview. We used Cox regression to estimate the relative risk of total and cause-specific mortality associated with circulating CML, adjusting for confounders (Models 1 & 2) and estimated glomerular filtration rate (eGFR) as a potential mediator (Model 3). We tested whether sex or diabetes modified the association between CML and mortality.

The mean age among participants was 78 years and 60% were women. The mean CML level among participants was 629 ng/mL. Over median follow-up of 10 years, 2,322 deaths occurred (73.4 per 1,000 person-years). After adjustment for confounders (Models 1 & 2), CML was associated with an increased risk of death from CVD, dementia, infection, fracture/trauma, and renal failure (Table). Aside from renal failure, adjustment for eGFR attenuated the HR estimates modestly. There was no evidence for effect modification of the association of CML and all-cause mortality risk by sex or diabetes.

In a cohort of community-dwelling older individuals, elevated circulating CML was associated with increased risk of mortality from cardiovascular causes, dementia, infection, fracture/trauma, and renal failure. A portion of the increased risk may be mediated through decreased renal function.
Abstract P022: Chocolate Intake and Incidence of Heart Failure: Findings from the Cohort of Swedish Men (COSM)
Authors: Steinhaus Daniel , Mostofsky Elizabeth , Levitan Emily B , Wolk Alicja , Håkansson Niclas , Mittleman Murray A
Published: July 2021

Background:
Several observational studies have found that moderate chocolate consumption is associated with a lower risk of incidence of stroke and myocardial infarction and beneficial effects on lipid metabolism and endothelial function. Randomized clinical trials have shown that chocolate reduces systolic and diastolic blood pressure. One study showed that moderate chocolate consumption is associated with a lower rate of heart failure (HF) in women, but there have been no studies to evaluate the association between chocolate intake and incidence of HF in men.

Methods and Results:
We conducted a prospective cohort study of 33,028 men 45-79 years old with no history of myocardial infarction, diabetes, or HF at baseline who were participants in the population-based Cohort of Swedish Men (COSM) study. Chocolate consumption was assessed through a self-administrated food frequency questionnaire. Participants were followed for HF hospitalization or mortality from January 1, 1998 to December 31, 2011 using record linkage to the Swedish inpatient and cause-of-death registries. During 14 years of follow up, 1350 men were hospitalized (n = 1256) or died from incident HF (n = 192). We used Cox proportional hazards models to compute multivariable-adjusted rate ratios accounting for age, total caloric intake, education, BMI, physical activity, cigarette smoking, alcohol consumption, family history of myocardial infarction, self-reported history of hypertension, and self-reported history of high cholesterol. Compared with subjects who reported no chocolate intake, the multivariable-adjusted rate ratio of HF was 0.90 (95% CI 0.75 - 1.08) for those consuming 1-3 servings per month, 0.88 (95% CI 0.72 - 1.08) for those consuming 1-2 servings per week, 0.69 (95% CI 0.51 - 0.93) for those consuming 3-6 servings per week, and 1.14 (95% CI 0.77 - 1.69) for those consuming and ≥1 servings per day (P for quadratic trend=0.02).

Conclusions:
In this large prospective cohort study, there was a J-shaped relationship between chocolate consumption and HF incidence. Moderate chocolate consumption was associated with a lower rate of HF hospitalization or death, but the protective association was not observed among individuals consuming one or more servings per day.
Abstract P023: Risk Factors Associated with Progression of Subclinical Diastolic Dysfunction in a Multiethnic Population
Authors: Zhang Lili , Shan Jian , Taub Cynthia
Published: July 2021

Background:
Subclinical diastolic dysfunction is defined as echocardiographic evidence of left ventricular diastolic dysfunction and normal ejection fraction (EF) without congestive heart failure (HF) symptoms/diagnosis. Our study, for the first time, sought to examine risk factors associated with progression from subclinical diastolic dysfunction to overt HF in a large multiethnic population.

Methods:
The study population included patients with asymptomatic diastolic dysfunction and EF ≥ 50% assessed by transthoracic echocardiogram between 2003 and 2008 at Montefiore Medical Center, Bronx, NY. Patients with preexisting HF, valvular heart disease or atrial fibrillation prior were excluded. The end point was the development of HF by September 1, 2013. Multivariable adjusted Cox proportional hazards models, determined by stepwise selection method, were performed to examine risk factors associated with the development of HF. All analyses were also performed with adjustment and stratification of race.

Results:
A total of 7,879 patients, with 21% European Americans (EA), 36% African Americans (AA), 31% Hispanics, and 12% others or unknown, were included in the analysis. Mean follow up time was 6.3 years. Mean age of the cohort was 68±12, with 63% women. The overall cumulative probability of development of HF was 17% (19% in EA, 17% in AA, 19% in Hispanic patients) during the follow up period. In multivariable Cox proportional hazard regression analysis, renal disease (hazard ratio (HR)=1.6, 95% confidence interval (CI) 1.3-2.0, P<0.001) and hemoglobin levels (HR=0.9, 95% CI 0.9-1.0, P=0.001) were significantly associated with the development of HF in overall population. In stratification analysis, age (P=0.012) and hypertension (P=0.007) were independent risk factors for HF in Hispanic patients, but not in EA and AA.

Conclusions:
In a large multiethnic population with subclinical diastolic dysfunction, renal disease and hemoglobin levels were independently associated with development of HF in overall population.. Age and hypertension were significant risk factors for HF only in Hispanic patients. These results may have important implications in preventing the development of HF from subclinical stage.
Abstract P052: History of High Cholesterol and Incidence of Dementia: The 90+ Study
Authors: Evans Marcella A , Kawas Claudia H , Corrada Maria M
Published: July 2021

Background:
Hypercholesterolemia at midlife has been associated with increased dementia risk. However, some studies suggest that this relationship may change with age. It is not known if an association between cholesterol and dementia incidence persists in the oldest-old (people aged 90+) [[Unable to Display Character: –]] the most rapidly growing segment of the population. We examined whether a history of high cholesterol is associated with dementia incidence in
The 90+ Study,
a longitudinal population-based study of the oldest-old.

Methods:
We analyzed data from 569 participants who were non-demented at baseline, had one or more follow-up visits, and provided self-reported history of high cholesterol. Participants were evaluated every six months, with dementia diagnosis (DSM-IV criteria) at follow-up determined in a hierarchal manner from: neurological exam, Mini-Mental Status Exam, informant questionnaires, and the Cognitive Abilities Screening Instrument (telephone short form). We used Cox regression to estimate the association between history of high cholesterol and incident dementia, using age as the time scale and adjusting for gender and education.

Results:
Participants had a mean age of 93.3 years (range 90-103) at baseline and were primarily Caucasian (99%), women (69%), and with at least some college education (77%). 200 participants (35%) reported a history of high cholesterol. After a mean follow-up of 3.3 years (range 0.1-9.0), 224 individuals (39%) were diagnosed with dementia (68% from neurological exam). People who reported a history of high cholesterol at baseline were less likely to develop dementia compared to people without a history of high cholesterol (HR=0.76, 95% CI 0.57[[Unable to Display Character: –]]1.02, p=0.072).

Conclusions:
Contrary to findings in younger ages, high cholesterol appears to be associated with lower dementia risk in the oldest-old. A potential mechanism could be that with advanced age a compensatory increase in cholesterol synthesis or uptake occurs in order to preserve function of the aging brain, as the cholesterol molecule has a variety of biological roles related to brain health. Further research is needed to analyze direct measurements of serum cholesterol, as well as to examine the effects of a variety of factors (such as use and duration of cholesterol-lowering medications, low cholesterol as a proxy for poor health and frailty, and duration of hypercholesterolemia) on the observed association. Our results imply that target cholesterol levels in the oldest-old may be different from those recommended in younger populations, at least in regards to cognitive health.
Abstract P063: A Systematic Review of Current Dietary Policies for Reducing Cardiometabolic Diseases in the Middle East
Authors: Afshin Ashkan , Shangguan Siyi , Nomura-Baba Marik , Abu Awad Yara , Reich Michael , Mozaffarian Dariush
Published: July 2021

Background:
Cardiometabolic diseases such as CVD and diabetes are rising rapidly in many regions, especially the Middle East. Governments could reduce these burdens by targeting suboptimal diets, but little is known about national dietary policies in this region.

Objective:
To systematically investigate, summarize, and identify gaps in national dietary policies in 22 Middle Eastern nations.

Methods:
Using PRISMA and MOOSE guidelines, we systematically searched PubMed, Econ Lit, PAIS, Cochrane library, AGRIS, Web of Science, CABI, and CINAHL for original studies, reviews, and organizational reports on national dietary policies adopted in these countries; Google searches are ongoing. We searched for dietary policies in 6 categories: media/education, labeling/consumer info, taxes/subsidies, school programs, workplace approaches, and direct bans/mandates. We evaluated 13 dietary targets of interest (Figure). Studies were excluded if published prior to 1980, described only local (subnational) policies, or only provided data on policies for food safety, micronutrient deficiency, hunger, or other issues without at least one focus on cardiometabolic risk.

Results:
From 3866 identified studies, 17 met inclusion criteria. We found 4 types of dietary policies (media/education, labeling/consumer information, taxation/subsidies, direct bans/mandates) in 9 countries of the region (Bahrain, Djibouti, Egypt, Iran, Jordan, Kuwait, Pakistan, Sudan, United Arab Emirates) that targeted 7 dietary factors (fruits, vegetables, whole grains, unprocessed red meat, trans fats, sodium, dietary fiber) . Details of these policies will be presented, as well as current gaps (Figure).

Conclusions:
Our findings highlight existing national dietary policies that have been adopted to reduce cardiometabolic diseases in the Middle East, as well as remaining major policy gaps, thereby identifying current progress and opportunities for policy innovation.
Abstract P067: Nut Consumption is Associated with a Lower Risk of Death among US Male Physicians
Authors: Djousse Luc , Petrone Andrew , Gaziano John
Published: July 2021

Background:
Previous studies have suggested that nut consumption, a good source of unsaturated fatty acids, magnesium, potassium, fiber, antioxidants, and vitamins is associated with a lower risk of coronary heart disease, type 2 diabetes, and sudden cardiac death. However, limited data are available on the association between nut intake and all-cause mortality.

Objective:
To test the hypothesis that nut consumption is inversely associated with the risk of all-cause mortality.

Methods:
A prospective cohort study of 20,742 male physicians from the Physicians’ Health Study. Nut intake was assessed between 1999 and 2002 using a food frequency questionnaire and deaths were ascertained by an endpoint committee. We used Cox regression to estimate multivariable adjusted relative risk of death according to nut consumption. In secondary analyses, we evaluated associations of nut consumption with cause-specific mortality (coronary heart disease, stroke, and cancer deaths).

Results:
During a median follow-up of 9.5 years, there were 2,732 deaths. The mean age at baseline was 66.6 ± 9.3 years. Median intake of nuts was 1 time per week. Multivariable adjusted hazard ratios (95% CI) were: 1.0 (ref), 0.91 (0.83-1.00), 0.85 (0.76-0.95), 0.86 (0.75-0.98), and 0.74 (0.63-0.87) for nut consumption of never, 1-3/month, 1/week, 2-4/week, and 5+/week, respectively (p for linear trend <0.0001), after adjustment for age, body mass index, alcohol use, smoking, exercise, energy intake, saturated fat, fruit and vegetables, red meat intake, and prevalent diabetes and hypertension. In a secondary analysis, nut intake was inversely related to CVD death; however, only a suggestive and non-statistically significant relation was seen for cancer mortality (Table).

Conclusions:
Our data are consistent with an inverse association between nut consumption and risk of all-cause mortality in US male physicians.
Abstract P080: Fructose Acutely Increases Size of Very Low Density Lipoprotein In Adolescents With Hepatic Steatosis
Authors: Vos Mirian , Jin Ran , Welsh Jean , Le Ngoc-Anh
Published: July 2021

Introduction:
Cardiovascular complications are a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). Fructose has been reported to be associated with dyslipidemia and increased cardiovascular risk in adults but its impact on adolescents with NAFLD is not well understood. We previously demonstrated that fructose disproportionately increased postprandial hypertriglyceridemia in pediatric NAFLD as compared to healthy children. However, the mechanism remains unclear.

Hypothesis:
We hypothesized that fructose would contribute to hypertriglyceridemia in pediatric NAFLD by increasing the size of VLDL particles.

Methods:
We examined the acute response to a single dose of fructose beverage in 50 Hispanic-American obese adolescents with varying degrees of hepatic steatosis. Those with hepatic fat >5% on MRI imaging were designated as presumed NAFLD. Subjects consumed a 12oz drink containing 33g of fructose and plasma samples were collected at baseline and 30, 60, and 90 minutes afterwards. Plasma lipoproteins were measured using NMR (Liposcience, Raleigh, NC).

Results:
In response to acute fructose load, subjects without NAFLD increased the total number of TG rich lipoprotein particles (p = 0.047). However, this increase was not observed in subjects with NAFLD; instead, they increased the subpopulation of large VLDL particles (p = 0.008) and the mean size of VLDL particles (p = 0.004) (Figure 1). In line with this finding, TG-to-apoB ratio significantly increased in subjects with NAFLD (2.25 ± 0.26 to 2.37 ± 0.25, p = 0.031) but not in non-NAFLD.

Conclusions:
These findings demonstrate that adolescents with NAFLD have more atherogenic, large VLDL in response to fructose compared to obese adolescents without NAFLD. Dietary fructose restriction may be a critical component in the treatment of NAFLD associated cardiovascular disease and should be tested further.
Abstract P098: Maternal Insulin/Glycemic Regulation, Leptin, and Adiposity Levels are Associated with Newborn Adiposity
Authors: Patenaude Julie , Allard Catherine , Lacroix Marilyn , Guillemette Laeticia , Battista Marie-Claude , Doyon Myriam , Moreau Julie , Perron Patrice , Hivert Marie-France
Published: July 2021

Introduction:
Leptin is a hormone secreted by adipocytes that circulates in proportion to body fat. Placenta also produces leptin suggesting a specific role during pregnancy, maybe contributing to pregnancy-induced insulin resistance.

Objective:
To determine the associations between maternal levels of leptin, glucose and insulin and weight/adiposity measures in newborns.

Methods:
A population-based cohort of pregnant women in the region of Sherbrooke, Canada was recruited in early pregnancy (n=1040 at 1
st
trimester). Maternal anthropometry was measured and blood samples were collected at the 1
st
and 2
nd
trimesters to measure glucose (hexokinase), leptin and insulin (ELISA Luminex, Millipore Canada). Birth weights were recorded from the medical records in 783 newborns (full term >36 weeks). We measured skinfolds in 199 newborns within 72h after birth, using a standardized caliper. We measured triceps, biceps, subscapular and supra-iliac skinfolds and the sum of skinfolds was used for analysis representing overall neonatal adiposity. Correlations and linear regression analyses were performed to evaluate the associations between maternal metabolic characteristics and neonatal weight/adiposity measures.

Results:
Birth weight was associated with maternal body mass index (BMI; r=0.18 and r=0.20 at 1st and 2
nd
trimesters respectively; both
P
<0.001), percent body fat (%bf; r=0.25;
P
<0.001), weight gain over pregnancy (r=0.14;
P
<0.001), and fasting leptin (r=0.15,
P
<0.001). Surprisingly, crude birth weight was not associated with maternal glycemic or insulin levels at 1
st
or 2
nd
trimesters (all
P
>0.05). In contrast, sum of skinfolds was associated with maternal fasting glucose (r=0.17,
P
=0.01) and fasting insulin (r=0.24,
P
=0.001), in addition to fasting leptin (r=0.18,
P
=0.01) at 2
nd
trimester. Sum of skinfolds was also associated with maternal BMI (r=0.18,
P
=0.008 at 1
st
and r=0.21,
P
=0.003 at 2
nd
trimester) and %bf (r=0.19;
P
=0.005). After adjustments for maternal BMI or %bf, sum of skinfolds remained significantly associated with maternal fasting insulin (all
P
<0.05), but not with maternal leptin levels (
P
=0.16 to 0.35)

Conclusion:
These results suggest that maternal insulin/glycemic regulation has a greater impact on neonatal adiposity than overall crude birth weight. Birth weight and neonatal adiposity are both associated with maternal leptin levels, likely representing maternal own adiposity levels that might influence neonatal outcomes directly or indirectly.
Abstract P103: Patterns of Childhood Obesity and Relation to Middle-Age Sleep Apnea Risk: The Bogalusa Heart Study
Authors: HU TIAN , Bertisch Suzanne , Chen Wei , Gustat Jeanette , Webber Larry , Li Shengxu , Pak Kirk , Srinivasan Sathanur , Berenson Gerald , Bazzano Lydia
Published: July 2021

Background:
Patients with obesity have high risk of obstructive sleep apnea (OSA); however, the relationship between childhood obesity and later OSA risk is unknown.

Methods:
We prospectively examined the association between changes in overweight/obesity status in childhood and subsequent OSA in 823 middle-aged adults free of cardiovascular diseases at baseline and who had at least 2 measures of body mass index (BMI) between 4 and 18 yrs old (1974-) and responded to the Berlin Questionnaire in 2010. Childhood overweight/obesity was defined as age and gender specific BMI ≥85
th
percentile based on 2000 CDC Growth Charts. Four groups were generated based on change in obesity status from the earliest to most recent visit in childhood: persistent normal weight, incident overweight (from normal to overweight), weight loss (from overweight to normal), and persistent overweight. Based on Berlin Questionnaire, high-risk OSA was defined as any 2 of the following: obesity or hypertension, persistent snoring symptoms, and persistent daytime sleepiness. Persistent snoring was defined as snoring on ≥3 nights/week, snoring louder than talking or very loud, and breathing pauses on ≥3 nights/week; and persistent daytime sleepiness was defined as feeling tired ≥3 days/week after sleeping, feeling tired during time awake ≥3 days/week, and falling asleep while driving.

Results:
Mean age was 42 yrs and mean BMI was 31.0 kg/m
2
in adulthood. Of the total, 43% were male, and 34% were African-American. There were 604, 68, 39, and 112 persons in the persistent normal weight, incident overweight, weight loss, and persistent overweight groups, respectively. Median time between measures of BMI in childhood was 5 yrs (IQR: 5 yrs) across the 4 groups. Over an average of 35 years follow-up from childhood to adulthood (IQR: 1 yr), 326 (38%) participants had high-risk of OSA. In multivariate log-linear regression models, compared to participants in persistent normal weight group, those in persistent overweight, incident overweight, and weight loss groups had 1.80 (95% CI: 1.48, 2.19), 1.61 (1.22, 2.12), and 1.28 (0.89, 1.87) times higher risk of OSA, after adjustment for age, gender, race, educational level, leisure-time physical activity, regular drinking, and current smoking. The persistent overweight group had significantly higher risk of persistent snoring symptoms than persistent normal group (RR: 1.39; 95% CI: 1.12, 1.73). Results were not statistically significant for persistent daytime sleepiness among the groups.

Conclusions:
Persistent overweight or change from normal weight to overweight in childhood was associated with a higher risk of OSA in middle age, while weight loss during childhood did not have higher risk of OSA in adulthood compared to their counterparts in the persistent normal weight group.
Abstract P107: Are Sleep Disturbances Associated with the Development of Gestational Diabetes? A Systematic Review and Meta-analysis.
Authors: Miller Michelle A , Saravanan Ponnusamy , Vatish Manu , Cappuccio Francesco P
Published: July 2021

Introduction and objectives:
Physiological and hormonal changes occurring in pregnancy increase the risk of sleep disordered breathing (SDB), which, along with short sleep (SS) duration, may be associated with an increased risk of gestational diabetes mellitus (GDM). Exposure to GDM in the mother increases her lifetime risk of type-2 diabetes (T2D) as well as the risk of obesity, metabolic syndrome and, in later life, T2D of her children. The aim of this study was to systematically review the collective published evidence of associations between snoring/sleep-disordered breathing or sleep duration and increased risk of GDM.

Hypothesis:
We assessed the hypotheses that sleep disturbances, and/or short sleep during pregnancy may be associated with an increased risk of GDM.

Materials and Methods:
We performed systematic searches using MEDLINE, EMBASE, the Cochrane library and PsycINFO to assess the effect of snoring/sleep disordered breathing (SDB) or short sleep (SS) on the development of gestational diabetes (GDM) and impaired glucose tolerance in pregnancy. Prospective studies with measures of sleep disturbances at baseline and outcome measures of GDM or levels of glucose 1hr post GCT were included in a meta-analysis. We extracted odds ratios (OR) or relative risks (RR) and 95% confidence intervals (CI) and pooled them using a random effect model.

Results:
Overall, 7 studies met the inclusion criteria. They included 4,292 participants with 311 cases of GDM. In the pooled analysis, snoring/SDB and SS were both associated with a greater risk of GDM (RR: 2·27; 95% CI 1·65 to 3·12; P < 0· 00001) and (3·19 [1·56 to 6·54]; P < 0·002), respectively. There was no evidence of heterogeneity but there was evidence of publication bias and not all studies adjusted for obesity. Sensitivity analyses did not influence the pooled risk estimates.

Conclusions:
In conclusion, sleep disturbances may represent a risk factor for the development of GDM. Further studies are required to address the issues of publication bias and potential confounding, and to extend these observations to high-risk groups like women of ethnic minority groups whose risk of GDM is the greatest. Prevention, detection and treatment strategies need to be explored.
Abstract P108: Habitual Short Sleep Duration Associated with Self-Reported and Objectively-Determined Cardiovascular and Metabolic Disease Risk Factors: Data from NHANES
Authors: Grandner Michael A , Chakravorty Subhajit , Perlis Michael , Oliver Linden , Gurubhagavatula Indira
Published: July 2021

Background:
Self-reported short and long sleep duration have been associated with adverse cardiometabolic health outcomes in laboratory and epidemiologic studies, but interpretation of such data has been limited by methodological issues.

Methods:
We analyzed adult 2007-2008 US National Health and Nutrition Examination Survey (NHANES) data (N=5,649). Average self-reported nightly sleep duration was reported and categorized as either very short (<5h), short (5-6h), normal (7-8h), or long (≥9h). Self-reported as well as objective evidence of obesity, diabetes, hypertension, and hyperlipidemia were recorded. Univariate comparisons were conducted across sleep duration categories for all variables. Binary logistic regression analyses were performed using cardiometabolic factor as the outcome variable, and sleep duration category as the predictor variable, before and after adjusting for age, sex, race/ethnicity, acculturation, education, access to insurance, food security, home ownership, smoking, and caffeine use.

Results:
See table. In adjusted analyses, very short sleep was associated with self-reported hypertension, self-reported hyperlipidemia, objective hyperlipidemia, self-reported diabetes, and objective obesity. Regarding short sleep (5-6hrs), in adjusted analyses, elevated risk was seen for self-reported hypertension self-reported obesity and objective obesity. Regarding long sleep (≥9hrs), no elevated risk was found for any outcomes.

Conclusions:
Very short and short sleep duration are associated with self-reported and objectively-determined adverse cardiometabolic outcomes, even after adjustment for covariates.

Table 1.
Unadjusted and Adjusted Odds Ratios (OR) and 95% Confidence Intervals (95%CI) of Associations between Sleep Duration and Cardiometabolic Disease Outcomes

*Adjusted analyses include age, sex, race/ethnicity, acculturation, education, insurance, home ownership, food security, smoking, and caffeine
Abstract P114: Low Prevalence of Ideal Cardiovascular Health Metrics among African Americans: The Jackson Heart Study
Authors: Djousse Luc , Petrone Andrew , Blackshear Chad , Griswold Michael , Harman Jane , Clark Cheryl , Talegawkar Sameera , Liu Jiankang , Hickson DeMarc , Gaziano J , Dubbert Patricia , Correa Adolfo , Tucker Katherine , Taylor Herman
Published: July 2021

Background:
While the prevalence of cardiovascular health metrics or Life’s Simple Seven (LSS) has been shown to be far from optimal in the US, such information has been predominantly reported in Caucasians. The burden of cardiovascular disease among African Americans underscores the need to evaluate the prevalence and secular trends of LSS in other ethnic groups.

Objective:
To test the hypothesis that the prevalence of the LSS is far from ideal among participants of the Jackson Heart Study.

Methods:
We analyzed LSS with 3,500 African Americans from the Jackson Heart Study, using data from their first clinic visit (2000-2004). Standard methods were used to measure blood pressure, glucose, body mass index (BMI), and cholesterol. Information on physical activity, smoking, and diet was collected with interviewer-administered questionnaires. Each of the LSS metrics (smoking status, diet, physical activity, BMI, fasting blood glucose, total cholesterol, and blood pressure) was categorized as poor, intermediate, or ideal, as defined by the AHA guidelines.

Results:
The mean age at baseline was 56.9 ± 12.2 years and 2,350 participants (67%) were women. Among men, the prevalence of having 0, 1, 2, 3, 4, 5, 6, and 7 ideal cardiovascular health metrics was 6.6%, 25.8%, 32.7%, 21.6%, 10.6%, 2.3%, 0.4%, and 0%, respectively. Corresponding values for women were 3.2%, 28.1%, 32.9%, 22.3%, 10.1%, 2.9%, 0.38%, and 0%. While about two-thirds of men and women reported ideal smoking status, almost none reported ideal diet quality, and few met recommendations for BMI and blood pressure (
Figure)
.

Conclusions:
Our data are consistent with less than optimal prevalence of cardiovascular health metrics in both men and women from the Jackson Heart Study. The lower prevalence of meeting ideal recommendations for diet, physical activity, BMI, and blood pressure underscores the need for targeted interventions to improve these modifiable lifestyle factors in order to reduce the burden of cardiovascular disease among African-Americans.
Abstract P120: Omega-3 Fatty Acid Supplementation in Middle-Aged Adults Reduces Cardiometabolic Risk in Men but not Women
Authors: Newlon Claire , Muldoon Matthew , Sereika Susan , Kuan Dora
Published: July 2021

Background:
Greater consumption of omega-3 fatty acids has been associated with lower cardiovascular disease risk. Randomized controlled trials indicate direct, albeit small, beneficial effects of omega-3 fatty acids on plasma triglycerides and blood pressure, yet few studies have tested their impact on insulin resistance and the clustered risk factors comprising the metabolic syndrome.

Hypothesis:
Short-term supplementation with marine omega-3 polyunsaturated fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) will improve aggregated cardiometabolic risk (CMR) in healthy middle-aged adults

Methods:
We conducted a double-blind, placebo-controlled, parallel group clinical trial. Subjects were 30-54 year-old adults free of atherosclerotic disease and diabetes whose intake of EPA and DHA totaled <300 mg/day. Each was randomly assigned to daily fish oil supplements (2g/day containing 1000 mg EPA and 400mg DHA) or matching soybean oil placebo for 18 weeks. Aggregate CMR at baseline and post-intervention was calculated as the standardized sum of standardized distributions of blood pressure, BMI, and fasting serum triglycerides, glucose, and HDL (reverse scored). Missing data due to dropouts (n=17) and outliers (1-6 per variable) were replaced by multivariate imputation. Outcome analyses were conducted with linear regressions of all randomized subjects based on intention-to-treat.

Results:
Participants were 272 healthy adult (57% (154 out of 272) women; 17% (47 out of 272) minority; mean age 42) Pittsburgh-area residents. At baseline, demographics, health parameters, physical activity and EPA and DHA consumption did not differ significantly between treatment groups. No overall treatment effect was found, whereas gender moderated the effects of treatment on CMR risk (gender, p=.001 and gender*treatment interaction term p=.011). In gender-specific analyses, supplementation lowered CMR risk relative to placebo in men(p=.036, effect size=.629, standard error (SE) =.282) but not women (p=.168, effect size .261, SE=.222). Of the individual CMR variables, only HDL-cholesterol in men revealed a significant improvement (p=.012). In men receiving placebo, HDL-cholesterol fell by 1.1 mg/dl, whereas in those receiving fish oil, HDL rose by 1.7 mg/dl. As has been noted in other samples, compared to women men had greater CMR and lower HDL-cholesterol.

Conclusions:
Increased intake of n-3 fatty acids over 4 months reduced CMR in healthy, mid-life men but not women. This finding may be due to poorer baseline CMR and HDL characteristic of men, or to gender differences in fatty acid metabolism. Further study of gender differences in cardiometabolic risk and fatty acid metabolism may lead to gender-tailored preventive interventions.
Abstract P140: Glycemic Index, Glycemic Load, and Risk of Type 2 Diabetes: Results from 3 Large US Cohorts and an Updated Meta-analysis
Authors: Bhupathiraju Shilpa N , Tobias Deidre K , Malik Vasanti S , Pan An , Hruby Adela , Manson JoAnn E , Willett Walter C , Hu Frank B
Published: July 2021

Epidemiologic evidence for the role of glycemic index (GI) and glycemic load (GL) in the prevention of type 2 diabetes (T2D) has been mixed. The American Diabetes Association’s nutrition recommendations for T2D prevention state that there is not sufficient, consistent evidence to conclude that low GL diets reduce T2D risk but acknowledge the role of low GI foods rich in fiber in preventing T2D. Therefore, our objectives were to 1) prospectively examine the association of dietary GI and GL with T2D in 3 US cohorts, and 2) conduct an updated meta-analysis of the previous literature including results from our 3 cohorts. We prospectively followed 74,248 women from the Nurses’ Health Study (1984-2008), 86,484 women from the Nurses’ Health Study II (1991-2009), and 40,525 men from the Health Professionals Follow-up Study (1986-2008) who were free of diabetes, cardiovascular disease, and cancer at baseline. Diet was assessed every 4 years using a validated questionnaire. During 3,738,507 person-years of follow-up, we documented 14,482 T2D cases. In pooled multivariable analyses, after adjusting for dietary and non-dietary covariates including body mass index, those in the highest quintile of energy-adjusted GI had a 34% higher risk (95% CI: 27-43%) of T2D. Participants in the highest quintile of energy-adjusted GL had a 13% higher risk (95% CI: 5-22%) for T2D. Participants in the highest tertile of GI/GL and lowest tertile of cereal fiber had about a 50% (GI, RR=1.59, 95% CI:1.47-1.73; GL, RR=1.47, 95% CI:1.32-1.63) higher risk for T2D compared to those in the lowest tertile of GI/GL and highest tertile of cereal fiber. In the updated meta-analysis (675,767 participants and 45,570 T2D cases), the summary RRs (95% CIs) comparing the highest versus lowest categories of GI and GL were 1.19 (1.15-1.24) and 1.13 (1.09-1.18), respectively (Figure 1A and 1B). Our findings provide further evidence that a high GI/GL diet is associated with a higher T2D risk. Public health recommendations for T2D prevention should incorporate GI and GL in meal planning.