bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 11: Fructosamine and Glycated albumin with Risk of Coronary Heart Disease and Death
Authors: Selvin Elizabeth , Rawlings Andreea M , Lutsey Pamela L , Pankow James S , Kao Linda , Steffes Michael W , Coresh Josef
Published: July 2021

Background:
HbA1c is the standard measure to monitor glucose control and is now used for diagnosis of diabetes. Fructosamine and glycated albumin are markers of short-term glycemic control that may add complementary information to HbA1c. However, the associations of fructosamine and glycated albumin with cardiovascular outcomes are uncharacterized.

Methods:
We measured glycated albumin and fructosamine in 11104 adult participants (792 with a history of diabetes) of the community-based ARIC Study without cardiovascular disease at baseline (1990-1992). We evaluated the associations of fructosamine and glycated albumin with incident coronary heart disease and total mortality. We compared these associations to those for HbA1c.

Results:
Baseline HbA1c was highly correlated with fructosamine (Pearson’s r =0.82) and glycated albumin (Pearson’s r=0.86). During over two decades of follow-up there were 1,032 new cases of coronary heart disease and 2,594 deaths. In Cox proportional hazards models adjusted for traditional cardiovascular risk factors, elevated baseline levels of fructosamine and glycated albumin were significantly associated with coronary heart disease and total mortality (
Figure
). After additional adjustment for HbA1c, the associations were attenuated but remained significant, particularly at diabetic levels of fructosamine and glycated albumin. The associations with death were J-shaped, with an elevation of risk also apparent at the lowest levels of each biomarker, as has been previously observed for HbA1c.

Conclusions:
The acceptance of new measures of hyperglycemia is partly dependent on establishing their association with long-term outcomes. We found that fructosamine and glycated albumin were associated with coronary heart disease and mortality and that these associations were similar to those observed for HbA1c. The elevated risk of death at very low levels of fructosamine, glycated albumin, and HbA1c deserves further examination.
Abstract 15: Obstructive Sleep Apnea is a Risk Factor for Incident Diagnosed Diabetes: The Sleep Heart Health-Atherosclerosis Risk in Communities Study
Authors: Nagayoshi Mako , Punjabi Naresh M , Selvin Elizabeth , Pankow James S , Shahar Eyal , Iso Hiroyasu , Lutsey Pamela L
Published: July 2021

Background:
Sleep apnea has been associated with diabetes in many cross-sectional studies, but prospective data is sparse. Most prior studies defined sleep apnea by self-reported sleep symptoms.

Hypothesis:
Objectively measured obstructive sleep apnea is associated with greater risk of incident diabetes.

Design:
We conducted a prospective cohort study of 1,465 non-diabetic participants of the Sleep Heart Health-Atherosclerosis Risk in Communities Study with in-home polysomnography conducted in 1996-1998 (baseline). Participants were categorized into four groups according to number of events per hour, as defined by the apnea-hypopnea index: <5.0 (normal), 5.0-14.9 (mild sleep apnea), 15.0-29.9 (moderate sleep apnea), and ≥30.0 (severe sleep apnea). Incident diagnosed diabetes or diabetes medication use was ascertained during annual follow-up calls through 2010. Cox proportional hazards models were used to examine the association between sleep apnea severity and incident diagnosed diabetes.

Results:
During a median follow-up of 12 years, there were 279 incident self-reported diabetes cases among the study participants (mean age 63 years, 99% white, 47% male). The risk of diabetes among those with moderate or severe sleep apnea was significantly higher than in those without sleep apnea after adjustment for demographics measures and other confounders. The association persisted among those with severe sleep apnea even after adjustment for body mass index and waist circumference. Across all models there was evidence of a dose-response association between the sleep apnea severity and the risk of incident diabetes (
Table
). There was no evidence for an interaction by sex.

Conclusions:
In this community-based study, persons with objectively measured obstructive severe sleep apnea were at higher risk of diabetes compared to persons without sleep apnea, independent of body mass index and waist circumference. Screening and treatment of sleep apnea may be beneficial for the prevention of diabetes.
Abstract 29: Virtual Small Groups for Weight Management: An innovative delivery mechanism for evidence-based lifestyle interventions
Authors: Azar Kristen M , Aurora Magi , Wang Elsie J , Muzaffar Amy , Pressman Alice , Palaniappan Latha P
Published: July 2021

Background:
Innovative, feasible and effective treatment strategies are urgently needed to address the obesity epidemic. While group interventions for weight loss have been shown to be efficacious, adherence is often low due to participant burden in attending in-person weekly meetings. Technology offers the potential for highly scalable intervention strategies that can be disseminated in diverse settings, and may improve access and adherence. This study assessed the feasibility and effectiveness of using virtual small groups for weight loss treatment.

Methods:
Obese men (BMI ≥30kg/m
2
) age 21-60 years, were recruited within a primary care clinic. We delivered an adapted Group Lifestyle Balance curriculum
,
based on the Diabetes Prevention Program lifestyle intervention, for 3-months using synchronous, encrypted, web-based video conferencing. Each session allowed for 8 participants and 1 facilitator, all attending from their own personal computer. Body weight was remotely monitored weekly using wireless scales. Participants (n= 48) were randomized to receive the intervention immediately following the baseline assessment, or 3-months later, as a delayed intervention control group. The main outcome of mean change in body weight was compared between intervention and control groups using student’s t-test.

Results:
Baseline characteristics did not differ between the intervention (n = 25) and delayed intervention control groups (n = 23). Intervention participants lost more weight than those in the delayed intervention control group, losing on average 4.3% (95% CI: -5.9%, -2.6%,
P
= 0.0004) of their initial body weight. The decrease in body weight was greater among men in the intervention group than in the delayed control group, with a mean difference of -3.9 kg (-5.9kg, -1.9kg,
P
= 0.0003) and mean difference for BMI of-1.2 kg/m
2
(-1.9 kg/m
2
,-0.4 kg/m
2
, P =
0.0021). On average, of the 12 weeks of the intervention, participants transmitted weekly weights 10.2 times (9.1,11.3) and attended 9.0 sessions (7.9, 10.0), or 74.7% (9 of 12) of total sessions offered.

Conclusion:
This pilot study is the first attempt to our knowledge to evaluate the delivery of a group behavior weight loss intervention via video conferencing in a primary care setting. Virtual small groups may be an effective means of healthcare service delivery and allow for face-to-face group interaction, while overcoming some barriers to access that a participant of an in-person program may face.
Abstract 52: Associations of Nonalcoholic Fatty Liver Disease with Subclinical Myocardial Dysfunction: The CARDIA Study
Authors: VanWagner Lisa B , Wilcox Jane E , Colangelo Laura A , Lloyd-Jones Donald M , Carr J J , Lima Joao A , Lewis Cora E , Shah Sanjiv J
Published: July 2021

Background:
Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition with high cardiovascular morbidity. NAFLD patients often have echocardiographic features of left ventricular (LV) diastolic dysfunction. In a large population-based cross-sectional sample of black and white adults free from prevalent liver or heart disease, we tested the hypothesis that NAFLD is associated with subclinical myocardial dysfunction independent of BMI or visceral adipose tissue (VAT).

Methods:
Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and tissue Doppler echocardiography with myocardial strain measured by speckle tracking were included (n=2,572). NAFLD was defined as liver attenuation ≤ 40 Hounsfield units after exclusion of other causes of liver fat (medication/alcohol use). Linear regression models were used to test associations.

Results:
NAFLD prevalence was 9.9%. NAFLD participants were more likely to be male (57.1% vs. 41.5%), white (57.5% vs. 50.6%), and had higher BMI (36.3 vs. 29.8 kg/m2) and VAT (222.4 vs. 120.5 cm3) than non-NAFLD. Those with NAFLD also had lower e’ tissue velocity (10.8 vs. 11.9 cm/s), lower E/A ratio (1.2 vs. 1.3), and higher E/e’ ratio (8.4 vs. 7.7). Increased LV mass, left atrial area, LV relative wall thickness, and cardiac output (CO) were present in NAFLD. Global longitudinal strain was also worse in NAFLD (-14.2% vs. -15.2%, all p<0.05). In multivariable analyses adjusted for demographics, health behaviors and BMI, the associations of NAFLD with markers of subclinical myocardial dysfunction were attenuated but remained significant (Table 1). Only e’ velocity, LV mass and CO remained significant after adjustment for VAT. Effect modification by race and sex was not statistically significant.

Conclusion:
NAFLD is associated with subclinical myocardial dysfunction independent of BMI. Attenuation of the relationship by VAT supports the hypothesis that VAT may be a marker of NAFLD.
Abstract 55: Kidney Measures Beyond Conventional Risk Factors for Predicting Incident Cardiovascular Disease: A Collaborative Meta-Analysis of 16 Cohorts
Authors: Matsushita Kunihiro , Coresh Josef , Sang Yingying , Chalmers John , Fox Caroline , Ishani Areef , Jafar Tazeen , Jassal Simerjot K , Landman Gijs W , Muntner Paul , Roderick Paul , Sairenchi Toshimi , Schöttker Ben , Shankar Anoop , Shlipak Michael , Tonelli Marcello , Townend John , van Zuilen Arjan , Yamagishi Kazumasa , Yamashita Kentaro , Gansevoort Ron , Sarnak Mark , Warnock David G , Woodward Mark , Ärnlöv Johan
Published: July 2021

Introduction:
Despite the high risk of cardiovascular disease (CVD) in those with chronic kidney disease (CKD), there are conflicting data as to whether two key kidney measures, estimated glomerular filtration rate (eGFR) and albuminuria, contribute to better CVD prediction, beyond conventional risk factors, warranting a more comprehensive investigation over a broad range of populations.

Methods:
We studied 127,825 participants without history of CVD from 12 general population, 3 high risk and 1 CKD cohorts with data on eGFR (based on the CKD-EPI creatinine equation) and urinary albumin-creatinine ratio (ACR) and at least 4 years of median follow-up for CVD mortality (4,133 deaths from 15 cohorts), coronary heart disease (CHD) (5,420 events from 9 cohorts), stroke (2,651 events from 9 cohorts), or heart failure (2,507 events from 8 cohorts). To compare eGFR and ACR with conventional predictors independently of the order of modeling, we examined the worsening of 5-year prediction of CVD outcomes by omitting each predictor in turn compared to a full model with all kidney and conventional predictors.

Results:
C-statistics for full models ranged from 0.759-0.836 in general population and high risk cohorts and 0.712-0.796 in the CKD population (Table). All the conventional and kidney measures contributed to better prediction of CVD outcomes. The contribution of ACR was greater than that of any conventional modifiable risk factors except in predicting CHD in both general/high-risk cohorts and CKD population. Although weaker than ACR, eGFR also contributed significantly to better prediction of CVD mortality (especially in CKD populations) and CHD. Largely similar results were observed for categorical net reclassification index.

Conclusion:
The two key kidney measures (particularly albuminuria) contribute as much as some or all of the conventional risk factors to CVD prediction, supporting their use for CVD risk classification in certain circumstances.
Abstract 62: The Role of Physical Activity in the Hypertension Pathway: A longitudinal pathway-based analysis across 18 years in modernizing China
Authors: Howard Annie Green , Gordon-Larsen Penny , Herring Amy , Du Shufa , Popkin Barry
Published: July 2021

Background:
Urbanization is associated with a decline in physical activity and an increase in CVD, particularly hypertension in lower and middle income countries. We investigate the impact of modernization-related declines in physical activity and pathways through body mass to hypertension in Chinese adults.

Methods:
Data come from the China Health and Nutrition Survey (CHNS), a household-based study that covers 9 diverse Chinese provinces from 1991 to 2009 across eight waves of data (n=12,018 adults; aged 18-66). We used detailed activity recall across multiple domains (leisure, work, and home), 3 repeated 24-hour-dietary-recalls, measured anthropometry and blood pressure at each exam. We created a multi-level structural equation model in Mplus to estimate direct pathways from specific domains of physical activity to hypertension and indirect paths through BMI. All pathways, including pathways to physical activity domains, were adjusted for gender, age, socioeconomic factors, urbanicity and region. Hypertension-related dietary factors were included in all pathways to BMI and hypertension.

Results:
The impact of physical activity on hypertension was most notable in the direct pathway to hypertension. Occupational and leisure activity were significantly associated with hypertension (p-value < 0.001), and individuals who were more active were less likely to have hypertension. Estimated from this model, a typical active, highly-educated, high-income middle aged female has a 12% probability of having hypertension, compared to a 43% probability for a similar non-active woman. There was however no direct association between physical activity and BMI.

Conclusions:
In China, declining physical activity over 18 years of modernization is strongly and directly related to increasing hypertension prevalence, with little evidence for effects along the pathway through BMI. Given continued declines in leisure and occupational activity, it is unlikely that hypertension will decline without additional intervention.
Abstract MP08: Bundle Branch Blocks and Risk of Mortality in the Atherosclerosis Risk in Communities Study: Gender and Racial Differences
Authors: Zhang Zhu-ming , Rautaharju Pentti M , Prineas Ronald J , Loehr Laura , Rosamond Wayne , Soliman Elsayed Z
Published: July 2021

Introduction:
Gender and racial differences in the association between different patterns of bundle branch block (BBB) and mortality in the general population are not well established.

Methods:
We used Cox proportional hazard models to evaluate the risk of all-cause mortality associated with left BBB (LBBB) and right BBB (RBBB). The study group, 15,316 participants from the Atherosclerosis Risk in Communities (ARIC) study was stratified by gender and race. We excluded the participants with other BBBs or QRS duration ≥120 ms not classified as complete RBBB or LBBB.

Results:
At baseline in 1987-89, mean age was 54 years, 55.3% were women, and 26.8% blacks. There were 88 LBBB and 202 RBBB. During a mean follow up of 18 years, 3,347 deaths occurred. Compared to No-BBB, LBBB was strongly associated with increased mortality in all subgroups by gender and race (Table). However, RBBB was not significantly associated with all-cause mortality in any of the subgroups in the multivariable adjusted models.

Conclusions:
Prevalent LBBB, but not RBBB, is a predictor of all-cause mortality in women and men as well as in blacks and whites. These findings may help in selecting patients who could benefit from further diagnostic evaluation for possible therapeutic and preventive intervention.
Abstract MP09: Deep Terminal Negativity of the P Wave in V1 is Associated with Sudden Cardiac Death in the Community: The Atherosclerosis Risk in Communities Study
Authors: Tereshchenko Larisa G , Zhang Yiyi , Arking Dan E , Sotoodehnia Nona , Siscovick David S , Deo Rajat , Agarwal Sunil K , Post Wendy S , Berger Ronald , Solomon Scott , Guallar Eliseo , Coresh Josef , Josephson Mark E , Soliman Elsayed Z
Published: July 2021

Background:
Deep terminal negativity of the P wave in V1 (P prime in V1, PPV1) defined as PPV1 ≤ -0.1mV in amplitude and ≥40 ms in duration (one small box on ECG grid) is sign of a left atrium enlargement, and a component in the Romhilt-Estes score of left ventricular hypertrophy (LVH). LVH is known to be associated with the risk of sudden cardiac death (SCD). Deep PPV1 negativity is also associated with atrial fibrillation (AF) and stroke; both have been linked to SCD as well. However, it is unknown whether or not PPV1 negativity is independently associated with SCD.

Method:
Baseline resting digital 12-lead ECGs of 13232 ARIC cohort participants (mean age 53.9±5.7 y; 5760 [43.5%] men; 9747 [73.7%] white) were analyzed. Individuals with prevalent baseline coronary heart disease (CHD), heart failure (HF), or QRS ≥ 120 ms were excluded. The ECGs were analyzed using a 12SL TM algorithm (GE Healthcare, Wauwatosa, WI, USA). Amplitude and duration of PPV1 was automatically measured.

Results:
Deep PPV1 negativity was observed in 97 (0.73%) participants. During a median follow-up of 14 years, 182 participants had SCD. In multivariable competing risks regression analysis, deep PPV1 negativity was significantly associated with SCD after adjustment for baseline risk factors of CHD and SCD (age, sex, race, diabetes, smoking, alcohol consumption, cholesterol, triglycerides, body mass index, serum creatinine, albumin, systolic blood pressure, use of antihypertensive, QT-prolonging medications, level of physical activity, mean heart rate, QTc, QRS duration, ECG-LVH by Cornell product), and incident HF, AF, stroke [subHR 3.8 (95%CI 1.88-7.69); P<0.0001]. Deep PPV1 negativity showed 7% sensitivity and 99% specificity for SCD prediction.

Conclusion:
In apparently CV healthy, middle-aged individuals, deep terminal negativity of P-wave in V1 is associated with about 4-times higher risk of SCD during 14 years of follow-up. Further studies should explore the cardiac substrate underlying presence of this marker and its use for risk stratification.
Abstract MP13: N-Terminal Pro-Brain Natriuretic Peptide (NT-proBNP) and Risk of Hypertension in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bower Julie K , Lazo Mariana , Rubin Jonathan , Matsushita Kunihiro , Hoogeveen Ron C , Ballantyne Christie M , Selvin Elizabeth
Published: July 2021

Introduction:
Increased plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration reflects cardiac overload and is used to diagnose and stage congestive heart failure. While NT-proBNP exhibits beneficial effects on the cardiovascular system via vasodilatation and diuresis, increased amounts of circulating NT-proBNP also promote release of norepinephrine, which is known to affect blood pressure. Cross-sectional studies report positive associations of NT-pro-BNP with blood pressure, but the prospective association of increased NT-proBNP with risk of hypertension is not well characterized. Thus, the study aim was to evaluate the association of NT-proBNP with incident hypertension in the community-based ARIC Study.

Methods:
We conducted a prospective cohort analysis of 3,849 participants aged 53-75 years with measured NT-proBNP at ARIC Visit 4 (1996-98) and normal blood pressure; participants with a history of hypertension (medication use or measured BP ≥140/90 mmHg), cardiovascular disease, or heart failure at baseline were excluded. Incident hypertension was defined based on diagnosis or antihypertensive medication use reported during annual follow-up.

Results:
During a median follow-up of 9 years, there were 2,157 new hypertension cases. There was a significant independent positive association between NT-proBNP levels and risk of hypertension. A 10% increased risk of hypertension was observed per log-unit increase in NT-proBNP (Table). This association was similar among individuals who were normotensive and pre-hypertensive at baseline [HR (95 % CI): 1.08 (1.01-1.15) and 1.11 (1.00-1.24), respectively]. Participants in the highest quartile for NT-proBNP were at 26% increased risk compared to those in the lowest quartile.

Conclusions:
NT-proBNP is positively associated with incident hypertension in this community-based cohort of middle-aged and older adults. In spite of the vasodilatory effects of increased NT-proBNP, elevated levels predict the development of hypertension.
Abstract MP14: Relations of Arterial Stiffness and Incident Heart Failure in the Community
Authors: Tsao Connie W , Lyass Asya , Larson Martin G , Mitchell Gary F , Vasan Ramachandran S
Published: July 2021

Background:
The structure and function of the aorta and left ventricle are closely coupled, but the relations of arterial stiffness, pressure pulsatility, and wave reflection to clinical heart failure (HF) are not well described.

Methods:
We evaluated 2904 Framingham Heart Study participants (mean age 64+11 yrs, 56% F) who were free of clinical HF and myocardial infarction (MI). Carotid-femoral pulse wave velocity (CFPWV), central pulse pressure, forward wave amplitude, and augmentation index were assessed by applanation tonometry. Cox proportional hazards models accounted for competing risk of death and adjusted for age, sex, body mass index, mean arterial pressure, total and HDL cholesterol, use of hypertensive medications, prevalent diabetes, current smoking, and prevalent cardiovascular disease.

Results:
On follow-up (mean 9.2 years, limits 0.04-13 years), 170 participants developed new-onset HF while 106 experienced an MI. The incidence of HF rose across CFPWV tertiles (
Figure
). Each standard deviation (SD) higher CFPWV conferred a 50% (95% CI 1.21-1.85, p=0.0002) and 30% (95% CI 1.02-1.64, p=0.037) increased risk of incident HF in age- and sex-adjusted and multivariable-adjusted analyses, respectively. CFPWV was associated with increased risk of MI (hazards ratio [HR] per SD 1.46, 95% CI 1.01-2.12, p=0.04). The inclusion of interim MI in multivariable models attenuated the association of CFPWV with HF incidence (HR per SD 1.26, 95% CI 0.99-1.60, p=0.061). Central pulse pressure, forward wave amplitude, and augmentation index were not associated with incident HF in multivariable-adjusted models.

Conclusions:
Higher aortic stiffness as assessed by CFPWV is associated with increased risk of incident HF, mediated in part by the increased risk of interim MI associated with vascular stiffness. These findings illustrate the importance of ventricular-vascular coupling, and underscore the need for studies to examine the benefit of therapies that modify aortic stiffness for lowering the population burden of MI and HF.
Abstract MP21: Circulating Biomarkers of Dairy Fat and Incident Type 2 Diabetes in Two US Prospective Cohorts
Authors: Yakoob Mohammad Y , Shi Peilin , Hu Frank B , Campos Hannia , Rexrode Kathryn M , Orav John E , Willett Walter C , Mozaffarian Dariush
Published: July 2021

Background:
Prior observational studies suggest that self-reported consumption of dairy foods is associated with lower risk of type 2 diabetes (DM). Few studies have used circulating biomarkers that provide objective measures of dairy fat consumption.

Aim:
To test the hypothesis that plasma fatty acid biomarkers of dairy fat, 15:0, 17:0, 16:1 n-7t and 14:0, are associated with lower incidence of DM.

Methods:
We used gas-liquid chromatography to measure plasma 15:0, 17:0, 16:1 n-7t and 14:0 biomarkers in 3,347 adults aged 30-75 years and free of prevalent DM at baseline in two separate U.S. prospective cohorts, Nurses’ Health Study (NHS) and Health Professionals’ Follow Up Study (HPFS). Incident DM was identified through 2008 and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Cox proportional hazards regression was used and cohort findings pooled by fixed-effects meta-analysis.

Results:
During mean ± SD follow-up of 14.0 ± 4.9 years, 254 new cases of DM were diagnosed. Correlations with self-reported dairy fat consumption were modest for 17:0 (r=0.19), 16:1 n-7t (r=0.21) and 15:0 (r=0.27), and weaker for 14:0 (r=0.12). In pooled multivariate analyses, comparing highest to lowest quartiles, lower risk of DM was seen for 17:0 [HR=0.57 (95% CI: 0.39 - 0.82), P-trend=0.001] and 16:1 n-7t [HR=0.60 (0.42 - 0.87), P-trend=0.007], while 14:0 was positively associated [HR=1.98 (1.35 - 2.91), P-trend <0.0001] and 15:0 was not associated [HR=1.11 (0.75 - 1.63), P-trend=0.80] (
Table
).

Conclusion:
In separate prospective cohorts, two biomarkers of dairy fat (17:0 and 16:1 n-7t) were associated with lower incidence of DM. 14:0, which is also obtained from beef, and is a marker of de novo lipogenesis, was associated with increased risk. Further research is needed on plausible biological and mechanistic pathways.
Abstract MP23: The Prognostic Value of 1,5-anhydroglucitol
Authors: Selvin Elizabeth , Rawlings Andreea M , Grams Morgan , Pankow James S , Sharrett A. Richey , Steffes Michael , Coresh Josef
Published: July 2021

Background:
1,5-anhydroglucitol (1,5-AG) is inversely related to glucose excursions and is thought to be a useful indicator of short-term (1-2 week) hyperglycemia. A commercial assay for 1,5-AG is approved for use in the USA but the relationship of 1,5-AG to long-term outcomes is unclear.

Methods:
We measured 1,5-AG in stored serum samples from 11,106 participants in the ARIC Study without cardiovascular disease at baseline (1990-1992) and examined prospective associations with clinical outcomes. Cox models were adjusted for demographic, lifestyle, and clinical variables.

Results:
During 20 years of follow-up, there were 2,601 incident cases of diabetes (among the 10,344 persons without diabetes at baseline), 2,928 incident cases of cardiovascular disease, 1,328 incident cases of chronic kidney disease (among the 10,951 persons with normal kidney function at baseline) and 2,595 deaths. There were 137 prevalent cases of retinopathy (among 516 persons with diabetes) identified in 1993-1996 when retinal photographs were taken. Compared to persons with 1,5-AG concentrations ≥10 ug/mL and no history of diabetes, persons with diabetes and 1,5-AG <6.0 ug/mL had significantly higher risks of chronic kidney disease (HR 4.45, 3.69-5.37), coronary heart disease (HR 3.81, 3.04-4.78), ischemic stroke (HR 3.84, 2.91-5.06), heart failure (HR 3.63, 3.01-4.38), and total mortality (HR 2.48, 2.12-2.91). Associations in persons with diabetes were attenuated but remained significant after adjustment for HbA1c. In persons with diabetes, 1,5-AG <6.0 ug/mL was associated with a higher prevalence of retinopathy compared to persons with 1,5-AG ≥10 ug/mL (OR 12.90, 6.74-24.69). In persons without diabetes at baseline, 1,5-AG <10 ug/mL was also associated with incident diabetes (HR 2.24, 1.97-2.54). Multivariable-adjusted spline models show the continuous associations of 1,5-AG with the prospective outcomes (
Figure
).

Conclusions:
1,5-AG provides prognostic information regarding long-term risk of important clinical outcomes.
Abstract MP30: Chronic Kidney Disease Progression and Risk of End-Stage Renal Disease: The Use of Change in Novel Kidney Filtration Markers
Authors: Rebholz Casey M , Matsushita Kunihiro , Selvin Elizabeth , Grams Morgan E , Coresh Josef
Published: July 2021

Introduction:
Chronic kidney disease (CKD) progression assessed by estimated GFR from creatinine (eGFR-Cr) is a risk factor for cardiovascular disease and end-stage renal disease (ESRD) and has been proposed as a surrogate endpoint for clinical trials. It is unclear if CKD progression assessed by change in different filtration markers has similar risk associations with ESRD.

Hypothesis:
We hypothesized that percent change in novel kidney filtration markers (β
2
-microglobulin and cystatin C) over a 6-year period would be independently associated with increased risk of ESRD during 15 years of follow-up, similar to the risk seen with change in eGFR-Cr.

Methods:
We conducted prospective analyses of the ARIC study (N=9,703). β
2
-microglobulin, cystatin C, and creatinine were measured at study visits 1 (1990-92) and 2 (1996-98). Incident ESRD (kidney dialysis or transplant) was defined as entry into the U.S. Renal Data System registry between study visit 2 and September 30, 2011. Cox proportional hazards regression was used to estimate the association between percent change in filtration marker and incident ESRD, adjusting for demographics, kidney disease risk factors, and 1
st
measurement of the filtration marker.

Results:
During a median follow-up of 13.1 years, there were 142 incident ESRD cases. Median eGFR-Cr was 97.3 mL/min/1.73 m
2
at 1
st
measurement and 89.0 mL/min/1.73 m
2
at 2
nd
measurement. Percent change in eGFR-Cr was moderately correlated with percent change in the inverse of β
2
-microglobulin (r = 0.34) and the inverse of cystatin C (r = 0.36). Progression of CKD (10-25% and >25% decline in filtration function) was associated with increased ESRD risk, with novel markers (β
2
-microglobulin, cystatin C) showing an association at least as strong as the creatinine and eGFR-Cr estimates (Table).

Conclusions:
CKD progression assessed using novel filtration markers is independently associated with ESRD risk, suggesting the potential utility of measuring change in β
2
-microglobulin and cystatin C in clinical trials.
Abstract MP47: Contribution of Preventable Risk Factors for Incident Congestive Heart Failure in Older Adults: the Cardiovascular Health Study
Authors: Del Gobbo Liana , Kalantarian Shadi , Imamura Fumiaki , Lemaitre Rozenn , Siscovick David , Mozaffarian Dariush
Published: July 2021

Background:
Heart failure (HF) incurs high morbidity, mortality and health care costs among adults ≥65 years, the most rapidly growing segment of the US population. The relative contribution of lifestyle factors on incident HF, including total dietary pattern, physical activity, smoking, alcohol, and obesity, has not been established.

Methods:
We prospectively investigated the contribution of major preventable risk factors, measured using repeated assessments, on incident HF among 4490 men and women ≥65 years in the Cardiovascular Health Study, a community-based US cohort. Lifestyle factors included four diet patterns (Biologic, DASH, AHEI, AHA 2020), four physical activity metrics (exercise intensity, walking pace, walking distance leisure activity), alcohol intake, smoking, and obesity. Incident HF was adjudicated by a centralized committee using medical records, diagnostic tests, and interviews. Adults with baseline CHF, moderate or severe mitral or aortic regurgitation, or missing lifestyle information were excluded from analysis. Risk associated with each lifestyle factors was assessed using Cox proportional hazards models.

Results:
Over 21-years (51849 person-years), 1380 cases of HF occurred. After multivariable adjustment, no dietary pattern was associated with incident HF (
p
>0.05), although sodium intake was associated with increased risk in secondary analyses. In contrast, walking pace, leisure activity, modest alcohol intake, former or never smoking, and BMI<30kg/m
2
were independently associated with lower risk of HF, with the highest population attributable risks for alcohol intake (18%) and physical activity (18%), followed by BMI (8%) and smoking (5%) (Table).

Conclusion:
Surprisingly, overall dietary patterns were not associated with HF, although sodium intake was associated with increased risk. Key modifiable risk factors to be targeted for HF prevention in older adults include physical activity and alcohol intake, obesity and smoking.
Abstract MP49: Sugar Sweetened and Artificially Sweetened Beverages and risk of Mortality in US adults
Authors: Malik Vasanti S , Pan An , de Koning Lawrence , Schernhammer Eva , Willett Walter C , Hu Frank B
Published: July 2021

Background:
Sugar sweetened beverages (SSBs) are the single largest source of calories and added sugars in the US diet and regular consumption has been associated with weight gain and risk of chronic diseases. Artificially sweetened beverages (ASBs) are often suggested as alternatives to SSB but little is known about their long-term health effects. Whether consumption of SSBs or ASBs is associated with risk of mortality is unknown.

Methods:
We prospectively followed 38,602 men from the Health Professional’s Follow-up study (1986-2010) and 82,592 women from the Nurses’ Health study (1980-2010) who were free from cardiovascular disease (CVD) and cancer at baseline. Diet was assessed using validated food frequency questionnaires every 4 years and Cox Proportional Hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).

Results:
We documented 27,691 deaths (6,631 CVD and 10,447 cancer deaths) during 3.14 million person-years. After adjusting for major dietary and lifestyle risk factors, and BMI, baseline diabetes, hypertension and hypercholesterolemia, consumption of SSBs was associated with an increased risk of total mortality, which was mainly driven by CVD mortality among individuals consuming at least 2 servings per day; pooled HRs (95% CIs) across categories (<1/month, 1-4/month, 2-6/week, 1-<2/day and ≥2/day) were 1.00, 0.95 (0.91, 0.98), 0.96 (0.93, 0.99), 1.02 (0.96, 1.08), and 1.18 (1.04, 1.33), respectively (P-trend= 0.0001) for total mortality, and 1.00, 0.97 (0.90, 1.02), 0.96 (0.90, 1.02), 1.04 (0.93, 1.16) and 1.28 (1.09, 1.51), respectively (P-trend=0.007) for CVD mortality. In contrast, ASBs were not associated with mortality; pooled HR’s (95% CIs) across categories (<1/month, 1-4/month, 2-6/week, 1-<2/day and ≥2/day) were 1.00, 0.92 (0.89, 0.95), 0.91 (0.86, 0.97), 0.91 (0.86, 0.95) and 0.99 (0.85, 1.15), respectively (P-trend=0.50) for total mortality and 1.00, 0.86 (0.80, 0.92), 0.87 (0.81, 0.94), 0.96 (0.88, 1.06) and 0.96 (0.74, 1.25), respectively (P-trend=0.99) for CVD mortality. No associations were observed with cancer mortality for either SSBs or ASBs in multi-variable adjusted models.

Conclusion:
Regular consumption of SSBs is associated with an increased risk of total and CVD mortality, providing additional support for recommendations and policies to limit intake of these beverages.
Abstract MP55: DNA Methylation Mediates The Effects Of Obesity On Insulin Resistance In African American Youth And Young Adults
Authors: Xu Xiaojing , Su Shaoyong , Barnes Vernon , Snieder Harold , Wang Xiaoling
Published: July 2021

Obesity and its related cardiovascular disease and type 2 diabetes have imposed huge burdens on public health worldwide. Insulin resistance is considered one of the key players in the development of obesity related comorbidities. However, the underlying mechanisms are still largely unknown. In this study, we aim to examine whether and to what extent peripheral blood DNA methylation can mediate obesity’s effect on insulin resistance using a genome-wide approach. Illumina 450k data were obtained for 456 black youth and young adults (226 obese cases vs. 230 lean controls) aged 14-34 years with fasting insulin levels available for 293 subjects and genome-wide gene expression data available for 92 subjects. As shown in figure 1, obesity and fasting insulin associated differentially methylated CpG sites were identified separately. Among the overlap of these 2 lists (n=69), 32 CpG sites mapping to 28 genes significantly mediated obesity’s effect on fasting insulin. Principal component analysis found that, in total, these 32 methylation sites explained up to 17.3% of the effect of obesity on insulin. Among these mediators, the top CpG site is located in the promoter region of the LIPA (lipase A) gene, and this single CpG site explained 8.4% of the effect of obesity on insulin. Consistent with the higher methylation levels observed in the obese group, LIPA expression was decreased in the obese group (p=0.038). A significant negative partial correlation was also found between LIPA methylation levels and its expression levels (p=0.01, r=-0.26). Genetic variants in LIPA have been suggested to contribute to the interindividual variability in metabolic traits observed among obese individuals. In summary, we observed that peripheral blood DNA methylation mediates obesity’s effect on insulin resistance in African American youth and young adults, explaining up to 17% of the effect.
Abstract MP66: Cheese Consumption and Blood Lipids; a Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: de Goede Janette , Geleijnse Johanna M , Ding Eric L , Soedamah-Muthu Sabita S.
Published: July 2021

Aims:
Cheese may have a different effect on lipids and lipoproteins than expected from the saturated fat content. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to examine the effect of cheese consumption on blood lipids and lipoproteins in healthy populations.

Methods:
A systematic search in MEDLINE, EMBASE, Scopus, Cababstracts, Cochrane Controlled Trials Register, Clinicaltrials.gov was performed to identify RCTs of cheese supplementation in human adults with total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides as a primary or secondary outcome (published until September 2013). A quantitative meta-analysis was performed if more than four RCTs with a comparable control treatment were available. Within person-differences of lipids with corresponding standard errors caused by the cheese compared to the control treatment were pooled (random effects model, STATA 11.0).

Results:
We identified 15 RCTs, published between 1978 and 2012. We pooled four RCTs comparing the effect of cheese intake to butter with a similar fat content on plasma levels of total cholesterol, LDL-cholesterol, HDL-cholesterol and triglycerides. The amount of cheese used in these trials was rather large, ranging between 120 and 205 g/d. This is approximately equivalent to 3 to 5 cheese servings per day. Intake of cheese (weighted mean difference: 142.6 g/d) reduced total cholesterol significantly by -0.27 mmol/l (95% CI: -0.36 to -0.18), LDL-C by -0.21 mmol/l (95% CI: -0.29 to -0.13), and HDL-C by -0.05 (95% CI: -0.08 to -0.02) compared to butter. The pooled effect on triglycerides was 0.004 (95% CI: -0.058 to 0.065). No heterogeneity was observed (all I
2
=0%). Cheese was also compared with tofu (n=4 RCTs), fat-modified cheese (n=3), CLA-rich cheese (n=3), milk (n=2), fish (n=1), egg white (n=1). Trials that compared cheese with tofu or fat-modified cheese suggest that differential effects of the products can mainly be attributed to the differences in fatty acid content of the diets. Comparisons with CLA-rich cheese were of limited value because those studied the effects of CLA (and not cheese). Too few trials with milk, egg white, and fish were available to draw conclusions.

Conclusions:
Based on a limited number of trials, cheese appears less hypercholesterolemic than butter with a similar fat content. Differences in plasma lipids based on cheese compared with tofu and fat-modified products are likely to be caused by the different fat content of the total diets.
Abstract MP72: Apolipoprotein B and Apolipoprotein B, LDL-C Discordance in Young Adults Are Associated With Coronary Artery Calcification at 25 Year Follow-Up: The Coronary Artery Disease in Young Adults (CARDIA) Study
Authors: Li Ron C , Chan Cheeling , Sniderman Allan , Liu Kiang , Lloyd-Jones Donald , Wilkins John T
Published: July 2021

Introduction:
High ApoB has been shown to predict cardiovascular disease (CVD) in adults even in the context of low LDL-C. It is not known, however, if high ApoB and high ApoB, low LDL-C discordance in young adults are associated with coronary artery calcium (CAC) in mid-life.

Methods:
Data were derived from CARDIA, a multicenter study of the development and determinants of CVD risk factors in young adults recruited at ages 18 to 30. All participants with complete baseline CVD risk factor data, ApoB, and year-25 CAC score were included in this study. Baseline lipid fractions and ApoB were measured by standard assays. Year-25 CAC was assessed using two consecutive CT scans with presence of CAC defined as having a positive, non-zero Agatston score using the average of two scans. Baseline ApoB values were divided into tertiles. Four mutually exclusive concordant/discordant groups were created based on median ApoB and LDL-C. Logistic regression was performed for unadjusted and adjusted models.

Results:
3496 participants were included [mean age=25±3.6, BMI=24.5±5Kg/m2, 44.4% male, and the following mean lipid values (mg/dL): total cholesterol=177.3±33.1, LDL-C=109.9±31.1, HDL-C=53±12.8, ApoB=90.7±24, median triglycerides=61(IQR 46-83)]. Compared with the lowest ApoB tertile, the middle [OR=1.55 (95% CI 1.22-1.95)] and high [OR=2.35 (95% CI 1.87-2.97)] tertiles exhibited increased odds of developing year-25 CAC in traditional risk factor-adjusted models. High ApoB, low LDL-C discordance was also associated with year-25 CAC in adjusted models [OR=1.57 (95% CI 1.12-2.20)].

Conclusions:
These data suggest a dose-response association between ApoB in young adults and presence of mid-life CAC independent of baseline traditional CVD risk factors. High ApoB, low LDL-C discordance was also associated with year-25 CAC, suggesting that ApoB in young adults may help identify individuals with modest LDL-C levels who are at increased risk for subclinical atherosclerosis in mid-life.
Abstract MP74: Understanding the Higher Diabetes Prevalence in South Asians Compared to Four U.S. Racial/Ethnic Groups: The MASALA and MESA Studies
Authors: Kanaya Alka M , Herrrington David , Liu Kiang , Blaha Michael J , Kandula Namratha R
Published: July 2021

Background:
South Asians (SA) have a high prevalence of diabetes (DM) which may be due to differences in insulin resistance (IR) or beta-cell function. We compared the prevalence of DM, IR, and beta cell function between SA and four race/ethnic groups. We also determined whether the association between age and adiposity with IR and beta cell function differed by ethnicty.

Methods:
We conducted a cross-sectional analysis of two cohorts aged 44-84 years without CVD: the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study and the Multi-Ethnic Study of Atherosclerosis (MESA). We compared 799 SA with 2,611 Whites, 1,879 African Americans (AA), 1,493 Latinos and 801 Chinese Americans (CA). DM was classified by fasting plasma glucose ≥126 mg/dL or use of a diabetes medication. Insulin resistance was estimated by the homeostasis model assessment (HOMA)-IR and beta cell function by the HOMA-ß model. Spline curves displayed the effect of age and waist with HOMA-IR and HOMA- ß stratified by ethnic group among those not on diabetes medications.

Results:
SA had significantly higher age-adjusted prevalence of DM (23%) compared to each MESA group (6% Whites; 18% AA; 17% Latino; 13% CA, p<0.001 each compared to SA), which were further enhanced after adjusting for all covariates of DM. Median HOMA-IR was higher and HOMA-β was lower in SA compared to other groups. Patterns of insulin resistance and ß cell function with age and waist circumference differed by ethnic group (Figure). SA had higher HOMA-IR to age 65, and lower HOMA-ß across the all ages compared to other groups. SA had higher HOMA-IR and lower HOMA-β after adjusting for waist circumference compared to other groups.

Conclusions:
There are ethnic differences in IR and beta cell that vary by age and adiposity. South Asians may have lower innate beta cell function and an inability to compensate adequately for high levels of IR with increasing adiposity. Longitudinal follow-up can assess whether IR and beta cell function explain the higher diabetes rates in South Asians.
Abstract MP75: The Influence of Income on Global Dietary Habits by Country, Age, Sex, and Time
Authors: Mozaffarian Dariush , Khatibzadeh Shahab , Micha Renata , Muhammad Andrew
Published: July 2021

Background:
Income may influence diet, especially in low and middle-income countries, and particularly in the setting of relatively high recent food prices and the global financial crisis. Yet, the influence of income on dietary habits in most countries is not well established, nor how this influence varies by age, sex, or time across different countries.

Aim:
To assess the relation of income with dietary habits globally, including from least developed to highly industrialized countries, and by age, sex, and time.

Methods:
We estimated the income elasticities of consumption of 11 food categories in 180 countries using the Global Dietary Database, based on 325 national surveys on individual-level dietary intakes worldwide. Per-capita income by country in real terms and on purchasing power parity basis were obtained from the World Bank. Elasticities were modelled using a modified Working’s expenditure share model by country, age (20-80+ in 5-year intervals), sex, and time (1990, 2005, 2010).

Results:
Significant income elasticities were identified. Food intake in low-income countries was generally more responsive to income than in high-income countries (
Figure
). In addition, income elasticity of dietary intake varied for different items (fruit, fruit juices, vegetables, beans/legumes, nuts/seeds, whole grains, unprocessed red meat, processed meat, milk, sugar sweetened beverages, fish). Additional heterogeneity was evident by age and sex, that also varied by food item.

Conclusions:
Intakes of different foods are variably responsive to income, and diets in low-income countries are more sensitive to income changes than in high-income countries, even after accounting for purchasing power. Additional food-specific patterns of variation in income elasticity were seen by age and sex. These first-ever global findings of dietary income elasticity based on individual-reported dietary intakes and by age and sex inform the relevance and impact of underlying societal determinants of dietary habits across the world.