bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P346: Modeling Novel Biomarkers with Individual Risk Factors and an “Improved” Bayes Approach are Preferred Strategies for Assessing Predictive Utility of Biomarkers
Authors: Xanthakis Vanessa , Pencina Michael J , Sullivan Lisa M
Published: July 2021

Given the rapid growth of new prognostic biomarkers, it is critical to assess their incremental utility for risk prediction while considering standard risk factors. This assessment may be influenced by the approach used to model new biomarkers. We hypothesized that the performance of a putative biomarker is best assessed by adding it to a model that includes standard risk factors as individual variables, as compared to adding it to a composite risk score (based on standard risk factors) estimated from the current study or to a composite risk score from a published study. We also compared 3 approaches of adjusting the prior absolute risk of an event using the information from a new biomarker, when data regarding prior risk are limited, hypothesizing that conditioning the biomarker residuals on prior risk (Improved Bayes approach) or adjusting the intercept of a model that includes the prior risk estimate are superior to the Naïve Bayes approach. Incremental performance was evaluated by comparing measures of improvement in discrimination. Using 1000 simulated datasets, similar incremental performance was observed when a putative biomarker was added to a model with the individual risk factors as compared to adding it to a model with a risk score estimated from the current study. Including a biomarker in a model with a published risk score resulted in an overestimation of its contribution (
Table
).These findings were supported by Framingham Heart Study data predicting incident atrial fibrillation using CRP and BNP.The Improved Bayes approach was a better strategy for updating the prior risk estimate as compared to the Naïve Bayes approach, using information from a new biomarker (Table). Our theoretical and empirical results identified that adding a new biomarker into a multivariable prediction model that includes the individual risk factors is the preferred strategy for assessing the incremental yield of a novel biomarker, and using the Naive Bayes approach (when information on the prior absolute risk of an event is scarce) is suboptimal.
Abstract P352: Results of a Randomised trial of Selenium Supplementation and Type-2 Diabetes Risk, as Assessed by Plasma Adiponectin
Authors: Rayman Margaret P , Blundell-Pound Gabrielle , Pastor-Barriuso Roberto , Guallar Eliseo , Stranges Saverio
Published: July 2021

Evidence that selenium (Se) affects the risk of type-2 diabetes (T2D) is conflicting with observational studies showing both lower and higher risk or prevalence linked to higher Se status. Importantly, however, a
post-hoc
analysis of the NPC trial carried out in the US showed a significantly increased risk of T2D in those supplemented with Se (200 &956;g/day as Se-yeast), the increased risk being driven by those in the highest tertile of plasma selenium at baseline (>121.6 &956;g/L). Stored plasma samples from the UK PRECISE Pilot study, in which 501 elderly volunteers were randomly assigned to a six-month treatment with 100, 200 or 300 µg Se/d as high-Se or placebo yeast, provided an opportunity to investigate the impact of Se supplementation on the risk of T2D in a lower-Se population. Plasma adiponectin concentration, a recognised independent predictor of T2D risk, was the biomarker chosen as the plasma samples were non-fasted, precluding the measurement of glucose or insulin. Adiponectin concentration was measured at baseline and at the six-month follow-up by ELISA in 473 participants who had one or both plasma samples available. Mean plasma Se increased significantly from baseline in all Se-supplemented groups. Multivariable linear regression based on log-transformed adiponectin data showed a cross-sectional inverse association between plasma Se and adiponectin concentration at baseline. However, results from linear mixed models on untransformed and log-transformed adiponectin concentrations, adjusted for study centre, showed no effect of Se supplementation on adiponectin concentration. Study limitations were the high variability in baseline adiponectin concentrations in the population, the short duration of supplementation and the narrow age range of the participants (60-74 yr). In conclusion, these findings are reassuring as they suggest absence of harm of selenium supplementation in terms of diabetes risk in a lower-Se population.
Abstract P373: Changes in Adipokines with Weight Loss and Regain in a 24-Month Behavioral Weight Loss Study: The SMART Trial
Authors: Burke Lora E , Ambeba Erica , Ye Lei , Styn Mindi , Acharya Sushama , Sereika Susan , Kuller Lewis
Published: July 2021

Background:
Weight regain commonly occurs in many adults who intentionally lose weight. Failure to maintain weight loss can lead to an increased risk for chronic diseases, such as type 2 diabetes and atherosclerosis. A potential mechanism behind the increased risk includes the increased secretion of pro-inflammatory adipokines (TNF-α and IL-6) and the decreased secretion of anti-inflammatory adipokines (adiponectin and IL-10).

Objectives:
We conducted an ancillary study to a 24-month behavioral weight loss trial. The purpose of the study was to examine the association between weight loss and regain and changes in body fat from baseline to 24 months and changes in TNF-α, IL-6, IL-10, and adiponectin.

Methods:
The analysis included a subsample of participants (n=67) from the SMART Trial who lost and regained at least 10 lbs during the 24-month trial. All participants received standard behavioral treatment for weight loss in group sessions during the first 18 months beginning with weekly sessions, which decreased in frequency over time. Linear mixed modeling was used to examine the association of percent changes in weight and body fat with percent changes in adipokines.

Results:
The sample was 81% female and 87% White with a mean (±SD) age of 48.4±7.34 years. At entry into study the mean weight was 96.4±15.6 kg and mean BMI was 34.5±4.35 kg/m
2
. Percent body fat was on average 42.1±6.13%. Mean weight change from baseline to six months was -10.7±5.19% and from baseline to 24 months was -3.34±6.66% while mean change in percent body fat was -8.07±11.6% from baseline to six months and -3.03±9.57% from baseline to 24 months. Weight loss over time was significantly associated with an increase in adiponectin [b(se)=-1.7(0.34), p<.0001] and a decrease in IL-6 [b(se)=1.26(0.49), p=0.01]. A similar pattern of associations was observed for reduction in body fat over time with an increase for adiponectin [b(se)=-0.76(0.19), p<.0001] and a decrease for IL-6 [b(se)=0.68(0.25), p=.006]. There were no significant associations found for either weight loss or change in percent body fat with change in IL-10 [weight: b(se)=0.51(0.54), p=.35; body fat: b(se)=0.43(0.28), p=.12] and TNF-alpha [weight: b(se)=0.35(0.44), p=.43; body fat: b(se)=0.19(0.24), p=.43] over 24-months.

Conclusion:
Weight loss and reduction in body fat were significantly associated with improvements in two of the adipokines. However, by 24 months, when weight regain occurred, those changes were attenuated. Implementing strategies that support healthy behaviors and sustained weight loss can help prevent a state of chronic systemic inflammation and prevent adverse health outcomes.
Abstract P382: Visceral Adiposity is a Stronger Correlate of Plasma C-Reactive Protein Levels than Liver Fat in the INSPIRE ME IAA Study.
Authors: Smith Jessica D , Nazare Julie-Anne , Borel Anne-Laure , Haffner Steven M , Balkau Beverley , Ross Robert , Massien Christine , Alméras Natalie , Després Jean-Pierre
Published: July 2021

Although it is well established than plasma C-reactive protein (CRP) levels predicts cardiovascular events beyond traditional risk factors, the main drivers of elevated CRP in the population are still under investigation. Among those, obesity and body fat distribution have been suggested to be important correlates of circulating CRP concentrations. The present analysis explored the correlates of CRP in the INSPIRE ME IAA cohort, a large CT imaging cardiometabolic risk study involving 2262 men and 2093 women for whom complete CT imaging and cardiometabolic, as well as CRP data, were available. CRP>10mg/l were excluded (N= 327). Both visceral adiposity (Men r=0.41 p<0.0001; Women r=0.50 p<0.0001) and liver attenuation, inversely related to liver fat, (Men r=-0.24 p<0.0001; Women r=-0.27 p<0.0001) were significantly correlated with plasma CRP levels. When both liver fat and visceral adiposity were placed in a multivariate model including age, region and physician’s specialty, we found that visceral adiposity (Men: partial R2=17.4 p<0.0001; Women: partial R2=24.1 p<0.0001) was more strongly related to CRP level than liver attenuation (Men: partial R2=0.3 p<0.0001; Women: partial R2=2.0 p<0.0001). Further adjustment for BMI, smoking status and statin use yielded similar results. We then divided patients into six groups according to tertiles of visceral fat (VAT) and the median of liver fat (LF): 1) lowVAT-lowLF, 2) lowVAT-highLF, 3) midVAT-lowLF, 4) midVAT-highLF, 5) highVAT-lowLF, 6) highVAT-highLF. In both men and women, CRP levels were higher in the midVAT and highVAT groups compared to the lowVAT group; yet, there was no difference between low and high LF within each respective VAT tertile after adjustment for age, BMI, region and specialty. This pattern was similar when statin use, smoking status, and the presence/absence of type 2 diabetes or cardiovascular disease (CVD) or metabolic syndrome were included. Our results show that CRP is strongly related to visceral adiposity, independent of several other covariates including liver fat. Due to the role of CRP in the prediction and prognosis of CVD, the assessment/management of visceral adiposity, by its surrogate marker waist circumference, will provide clinicians and patients with valuable information regarding an important correlate of this key inflammation marker.
Abstract P385: General and Regional Adiposity and Hypertension Risk in a Multi-ethnic Community Cohort of Men and Women: The Take Off the Pressure Study (TOPS)
Authors: McAuley Paul A , Little-Greene Denisha , Piatt Eva , Celma Dailen , Kavas F. A
Published: July 2021

Background:
Although several studies have reported associations of general and regional adiposity with hypertension risk, limited data are available in multi-ethnic cohorts.

Methods:
Cross-sectional associations of body mass index (BMI), waist circumference (WC), and peripheral circumference measures (neck [NC], arm [AC], hips [HC], and thigh [TC]) with hypertension risk was examined in a cohort of 504 multi-ethnic men and women (mean age, 46 years; 76% women; 23% Caucasian, 31% African-American, and 46% Hispanic). Patients were recruited from a community free clinic (Forsyth County, NC) to participate in the Take Off the Pressure Study (TOPS) during April to September, 2011. Associations of adiposity measures with hypertension risk by ethnicity were assessed using logistic regression after adjusting for age and sex.

Results:
Overall, 49% of participants (51%, 76%, and 29% of Caucasians, African-Americans, and Hispanics, respectively) had hypertension (BP >140/90 or previous diagnosis). Positive associations with hypertension risk were observed for BMI, WC, AC, HC and NC among Caucasians, and for WC among Hispanics (
Table
). In other words, Caucasians with higher BMI, and larger waist, arm, hip, and neck circumferences, and Hispanics with a larger waist circumference, were more likely to have hypertension. Notably, each 1-inch increase in arm and neck circumference was associated with 30% and 56% higher risks of hypertension, respectively among whites. However, no significant associations between any adiposity measure and hypertension risk were observed among African-Americans.

Conclusion:
Hypertension was highly prevalent in this cohort, particularly among African-Americans. However, adiposity markers used to assess hypertension risk in Caucasians may not apply to individuals of other ethnicities.

Table.

Age- and sex-adjusted odds ratios (95% CI) for hypertension by adiposity indicator/ethnicity

Caucasian (n = 117)
African-American (n = 156)
Hispanic (n = 231)

BMI (per kg/m
2
)

1.09 (1.03-1.15)
1.03 (0.99-1.08)
1.03 (0.97-1.08)

Waist circ (per in)
1.11 (1.04-1.18)
1.05 (0.99-1.11)
1.06 (1.00-1.11)

Arm circ (per in)
1.30 (1.05-1.62)
1.11 (0.94-1.31)
1.11 (0.93-1.33)

Thigh circ (per in)
1.06 (0.93-1.20)
1.09 (0.97-1.21)
0.98 (0.87-1.10)

Hip circ (per in)
1.09 (1.02-1.17)
1.04 (0.99-1.10)
1.03 (0.97-1.10)

Neck circ (per in)
1.56 (1.19-2.03)
1.15 (0.90-1.47)
1.14 (0.91-1.44)
Abstract P391: Temporal Trends in Medical Therapies for Hospitalized ST- and Non-ST Elevation Myocardial Infarction: The Atherosclerosis Risk in Communities (ARIC) Study Community Surveillance
Authors: O'Brien Emily C , Baggett Chris D , Alonso Alvaro , Rosamond Wayne D
Published: July 2021

Background:
Reports from large studies using administrative datasets and event registries have characterized recent temporal trends and treatment patterns for AMI. However, few are population based and fewer have examined differences in patterns of treatment for patients presenting with ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). We examined 21-year trends in the use of 10 medical therapies and procedures by STEMI and NSTEMI classification in the ARIC Community Surveillance Study.

Methods:
We analyzed data from an estimated 30,986 definite or probable MIs between 1987 and 2008 among residents 35-74 years of age in the four geographically defined US communities of the ARIC Study. Data on medical therapies was obtained through detailed abstraction of the medical records. Classification of STEMI and NSTEMI was based on independent Minnesota coding of electrocardiograms. We used weighted Poisson regression to estimate annual proportions of patients receiving each medication or procedure and age-standardized these estimates to the 2000 U.S. Census population. We then used weighted multivariable Poisson regression controlling for sex, race/center classification, age, and PREDICT mortality risk score to estimate average annual percent changes in medical therapy use over the study period.

Results:
From 1987 – 2008, 6106 (19.7%) hospitalized events were classified as STEMI, and 20302 (65.5%) were classified as NSTEMI. Among STEMI patients, increases (%; 95% CI) were noted in the use of ACE inhibitors (6.4; 5.7, 7.2), non-aspirin anti-platelets (5.0; 4.0, 6.0), lipid-lowering medications (4.5; 3.1, 5.8), beta blockers (2.7; 2.4, 3.0), aspirin (1.2; 1.0, 1.3), and heparin (0.8; 0.4, 1.3). Among NSTEMI patients, the use of ACE inhibitors (5.5; 5.0, 6.1), non-aspirin anti-platelets (3.7; 2.7, 4.7), lipid-lowering medications (3.0; 1.9, 4.1), beta blockers (4.2; 3.9, 4.4), aspirin (1.9, 1.6; 2.1), and heparin (1.7; 1.3, 2.1) increased. Calcium channel blocker use decreased for both STEMI (−8.8%;−9.6,−8.0) and NSTEMI (−5.6; −6.1,−5.1) patients over the study period. Among STEMI patients, we observed decreases in the use of thrombolytics (−7.2; −7.9, −6.6) and CABG (−2.4%; −3.6, −1.2). We noted similar decreases in the use of thrombolytics (−9.8; −10.7, −8.8) and CABG (−2.5; −3.3, −1.6) among NSTEMI patients. PCI use increased for both STEMI (6.4; 5.8, 7.0) and NSTEMI (5.1; 4.5, 5.7) patients. Increases in the use of stents were documented for both STEMI (4.5; 2.7, 6.2) and NSTEMI patients (1.3; −0.5, 3.2).

Conclusion:
We found trends of increasing use of evidence-based medicine for both STEMI and NSTEMI patients over the past 21 years. Future research should examine the broader public health impact of increasing adherence to clinical therapy guidelines.
Abstract P396: Thirty Years of Cardiovascular Mortality in Quebec, is the Decline Slowing in the Younger Population?
Authors: Blais Claudia , Hamel Denis
Published: July 2021

Background:
It has been demonstrated in many countries that cardiovascular mortality has decreased over recent decades and the decline was accelerating for people aged 35 years and older and slowing in the younger population. Coronary heart disease (CHD) and stroke were the major causes responsible of this decline. We hypothesized that this fall and deceleration of the decline has occurred also in Quebec, Canada and looked if other diseases, such as heart failure (HF) and high blood pressure (HBP) presented a similar decline.

Methods:
Age-adjusted and specific mortality rates were obtained with the Quebec registry of death for each year of 1978–2007 period for all cardiovascular diseases and divided into CHD, stroke, HF and HBP for people aged ≥35 years and for each 10 year-age groups respectively. Joinpoint regressions on these mortality rates were used to estimate the annual percentage change (APC) and to detect points in time at which significant changes in the trends occurred. Several methods of forecasting were compared to predict age-adjusted mortality rates for the next decade (2008–2017).

Results:
There were 542,712 cardiovascular deaths. All CHD age-adjusted mortality rates for both sexes combined declined with a marked acceleration in 1997 (APC 1978–1997 and 1997–2007 of −3.05 and −5.99 respectively) while stroke presented with a lower decline between years 1988 and 1997 and reaccelerated thereafter (APC 1978–1988: −4.72, 1988–1997: −2.22 and 1997–2007: −5.39). HF presented an increase between years 1978 and 1981 (APC: 6.28) followed by a decline (APC 1981–2007: −3.58). Death due to HBP in the same group showed a deceleration of the decline in 1992 (APC 1978–1992: −7.46 and APC 1992–2007: −1.97). In the group aged 35–44 years, when both sexes were combined, only HF presented an increase in the mortality rate (APC 1978–1992: −7.76 and 1992–2007: 4.97). CHD and stroke presented constant declines for this age group (APC 1978-2007: −5.17 and −4.73, respectively) while HBP had no mortality at all. CHD mortality for all ages is projected to decrease to an adjusted rate of 100 per 100,000 person-year in 2017 (−38% from 2007).

Conclusions:
Death due to HBP was the only cause responsible of a slowing of the decline in people aged 35 years and older. However, when looking at the younger population, HF is presenting not only a slowing of the decline but, more importantly, an increase in the mortality rate. The forecasting of cardiovascular deaths seems to get a constant decline for the principal cause, CHD.
Abstract P397: Twenty-year Trends of Treatment and Control for Elevated Serum Cholesterol among Minnesota and U.S. Adults
Authors: Steffen Lyn M , Zhou Xia , Jacobs David R , Blackburn Henry , Luepker Russell V
Published: July 2021

Background:
We recently reported lower CHD mortality rates and risk factor levels between 1980 and 2000 in Minnesotans compared to the general US population. Here we report the trends for treatment and control of elevated serum total cholesterol (TC).

Methods:
Cross-sectional surveys were conducted in men and women aged 25-74 years in the Minnesota Heart Survey (MHS) from 1990 to 2009 and in the National Health and Nutrition Examination survey (NH) from 1988 to 2008, in which height, weight, and medication use were obtained and TC measured. A single generalized linear mixed model was used to estimate age-adjusted and gender-specific linear trends of TC and of treatment and control of high TC in MHS and NH taking into account the complex sampling strategy as random effects, (i.e., neighborhood or strata and primary sampling unit pairings). Differences (pdiff) were calculated for slope and TC between surveys.

Results:
Between 1990 and 2008-09, percent obese increased. TC declined at the same rate in MHS and NH men and women, but TC levels were lower in MHS (pdiff0.05). TC was generally lower in MHS men and women compared to NH for each treatment and control category.

Conclusion:
Although TC levels have declined over the past several decades in both regional and national populations, the prevalence for untreated and treated but uncontrolled high TC remains high at 38% in MHS and 46% in NH. Findings were more favorable for Minnesotans than nationally. 20-Year Trends of Serum Cholesterol Treatment and Control in Men and Women: MHS vs. NHANES

Untreated/ Controlled (%)
Untreated/ Uncontrolled (%)
Treated/ Controlled (%)
Treated/ Uncontrolled (%)

Year
*

MHS
NH
MHS
NH
MHS
NH
MHS
NH

Men

1991
41.9
40.7
35.4
36.9
6.0
3.8
16.8
18.5

1996
**

39.1
38.3
36.0
35.7
6.3
8.1
18.6
17.8

2001
38.4
40.3
31.4
31.9
12.2
8.8
18.0
19.0

2008
40.6
39.1
21.2
30.7
22.0
16.3
16.1
13.9

Ptrend
0.32
0.36
<=0.001
0.001
<0.001
<0.001
0.56
0.03

Pdiff
p=0.90
p=0.001
p=0.005
p=0.20

Women

1991
48.7
42.9
30.1
34.8
4.2
3.4
17.0
18.9

1996
45.9
39.3
30.7
34.3
5.9
5.6
17.5
20.8

2001
47.0
43.9
27.7
32.8
6.8
5.9
18.4
17.5

2008
48.1
40.9
23.9
27.9
12.8
12.7
15.2
18.5

ptrend
0.86
0.25
<0.001
<0.001
<0.001
<0.001
0.21
0.73

pdiff
p=0.45
p=0.86
p=0.91
p=0.52

Controlled total cholesterol=less than 200 mg/dL, Uncontrolled total cholesterol= greater than or equal to 200 mg/dL

MHS=Minnesota Heart survey; NH=NHANES

*

Midpoint of survey time period

**

Survey year for NHANES was 1999
Abstract P400: Potential Barriers to Cardiovascular Disease Risk Assessment Among Deaf Young Adults
Authors: David Tamala , Tuttle Jane , Barnett Steven , Kitzman Harriett J
Published: July 2021

Objective:
To address a potential barrier to preventing cardiovascular disease (CVD) among people deaf since childhood; the lack of validated health surveys that might be used for risk assessment.

Background:
CVD impacts the lives of many Americans, including socially or linguistically marginalized persons like those deaf since childhood. CVD risk assessment among young adults, including those who are deaf, is essential for early identification of CVD risk factors and establishment of risk-reduction interventions. Health surveillance approaches like the National College Health Assessment (NCHA) are useful for risk assessment, but young adults must be able to report health information using survey instruments. English literacy among deaf young adults is reportedly poor, and barriers to health surveillance with this group are ill-defined, so risk assessment via health surveillance can be problematic with this group.

Methods:
The survey response patterns of 191 deaf/hard of hearing (HOH) and 541 hearing college freshmen who completed a written health survey were examined. The survey was adapted from the NCHA and other surveys for use by deaf young adults, and it comprised 71 items covering 10 subject areas including tobacco use, weight, diet, and exercise. Language and literacy were examined as factors associated with students’ response patterns. Measures of reading skill were based on students’ California Achievement Tests and measures of survey readability were based on Flesch/ Flesch-Kincaid readability tests. Students’ responses were tallied to create continuous variables, such as “inconsistent response” scores, “don’t know response” scores, and “non-response” scores. Chi-Square was used to examine response patterns involving categorical variables and t-tests were used to examine patterns involving continuous variables.

Results:
Fewer deaf/HOH students (42%, n = 75) reported English, versus sign language, as their best language than hearing students (99%, n = 507). Deaf/HOH students who did report English, versus sign language, as their best language were significantly more likely (p = .027) to have estimated reading skills above the 8
th
grade level. Thirty-one percent (n = 22) of the survey items had estimated readability above the 5
th
grade level; remaining items were at or below 5
th
grade. Deaf/HOH students were more likely to have inconsistent responses to related survey items and “don’t know” responses to survey items than hearing students (p < .000 and p < .000, respectively).

Conclusion:
Study results suggest that language and literacy are potential barriers to CVD assessment among deaf young adults, even high academic achievers like college students. Thus, for health surveillance, the readability of survey instruments and the language and literacy skills of deaf persons must be considered and alternatives to written surveys must be explored.
Abstract 003: Effects of Saturated, Polyunsaturated, and Monounsaturated Fat on Blood Glucose, Insulin Sensitivity, and
2
Cell Function: A Systematic Review and Meta-analysis of 84 Randomized Controlled Feeding Trials
Authors: Imamura Fumiaki , Micha Renata , Wu Jason H , de Oliveira Otto Marcia C , Otite Fadar O , Abioye Ajibola I , Mozaffarian Dariush
Published: July 2021

Background:
Effects of saturated fat (SFA), monounsaturated fat (MUFA), and polyunsaturated fat (PUFA) on blood glucose, insulin sensitivity (IS), and β cell function are not well established.

Aim:
To systematically quantify the effects of dietary fats on glucose homeostasis in randomized controlled feeding trials (RCTs).

Methods:
Using PRISMA guidelines, we systematically searched 11 databases for RCTs testing effects of isocaloric diets of varying dietary fat composition on glucose-insulin metrics in adults. We excluded RCTs of supplements or diet advice rather than provision of diets. Data were extracted independently and in duplicate. Using multivariate meta-regression, we estimated dose-response effects of isocaloric exchange of major macronutrients (SFA, MUFA, PUFA, carbohydrate [CHO]), adjusting for protein and fiber, and assessed heterogeneity (α=0.001 adjusted for multiple testing) by prespecified factors.

Results:
Of 3,661 identified abstracts, 84 RCTs met inclusion criteria, comprising 195 diet arms in 4,837 adults (19-74 y). Replacing CHO with SFA raised fasting glucose (FG), while MUFA and PUFA lowered FG (
Table
). Findings were concordant for HbA1C. Effects on FG were strongest in diabetics and Asians (P interaction<0.001 each); interactions for HbA1c were not statistically significant. Significant effects were not seen on IS or β cell indices by intravenous tests, although fewer RCTs evaluated such tests.

Conclusions:
SFA raises, while MUFA and PUFA reduce FG and HbA1c. Effects are stronger in diabetics and Asians. Our meta-analysis provides robust quantitative evidence on effects of major dietary fats on glucose-insulin metrics, directing further research and dietary guidelines.
Abstract 013: High Prevalence and Rapid Increase of Cardiovascular Disease Risk Factors in Youth with Type 2 Diabetes: The TODAY Study Group
Authors: Bacha Fida , Gidding Samuel S , Caprio Sonia , Weinstock Ruth , Lynch Jane , Hirst Kathryn
Published: July 2021

Background
The natural history of type 2 diabetes (T2D) in youth appears to differ from that in adults in that almost half of T2D youth in the “Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY)” study had a rapid decline in beta cell function. The rate of change in risk for cardiovascular disease (CVD) in youth with T2D is not known. We tested the hypothesis that CVD risk factors are highly prevalent and rapidly progress over time in youth with T2D using longitudinal assessments of hypertension (HT), microalbuminuria (MA) and dyslipidemia obtained during the TODAY clinical trial of adolescents with recent onset T2D.

Methods
A cohort of 699 adolescents, aged 10-17 years, <2 years duration of T2D, body mass index (BMI) ≥85th percentile, Hemoglobin A1c (A1c) ≤8% on metformin therapy were randomized to metformin alone, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention and followed over an average of 3.9 years. (range 2-6.5 years). Primary outcome was loss of glycemic control. Quarterly BP and annual MA were monitored with initiation and titration of therapy (ACE inhibitor) to maintain BP <130/80 or <95th percentile for age, gender, and height and MA <30 mcg/mg. Statin drugs were begun for LDL cholesterol (LDLC) ≥130 mg/dL or triglycerides ≥300 mg/dL. Change in the prevalence of CVD risk factors was examined accounting for the effect of treatment group, time, glycemic control, gender, and race-ethnicity.

Results
In this cohort, 319 (45•6%) reached primary glycemic outcome. HTN was observed in 11•6% of subjects at baseline and 33•8% by end of study (average follow-up 3•9 years). MA was found in 6•3% at baseline and rose to 16•6% at study end. Participants with LDLC ≥130 mg/dL or statin use increased from 4.5% to 10.7%. Male gender and higher BMI significantly increased the risk for HTN. Higher levels of hemoglobin A1c correlated with the risk of developing MA and dyslipidemia.

Conclusion
The prevalence of CVD risk factors increased rapidly among adolescents with T2D regardless of diabetes treatment. The greatest risk for HTN was male gender and higher BMI. The risk for microalbuminuria and worsening of dyslipidemia was related to glycemic control. Measures to address CVD risk are needed early in the disease course in this high risk population.
Abstract 020: NT-proBNP, hs-Troponin T and Incident Venous Thromboembolism: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lutsey Pamela L , Nambi Vijay , Cushman Mary , Heckbert Susan R , DeFilippi Christopher R , Ballantyne Christie , Folsom Aaron R
Published: July 2021

Background:
NT-pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (TnT) are important biomarkers for CHD and HF risk, but whether they are related to incidence of venous thromboembolism (VTE) is unknown. NT-proBNP is a marker of volume overload; volume overload may contribute to VTE risk via increased stasis and thrombogenesis. TnT might relate to VTE indirectly, as a marker of vascular inflammation or endothelial dysfunction.

Hypotheses:
NT-proBNP and TnT are associated positively with risk of incident VTE.

Methods:
Data from visit 4 (1996-1998) of the prospective population-based Atherosclerosis Risk in Communities study (n = 10,735; 53-74 yrs) were used. VTE events through 2005 were identified and validated by medical record review. Cox proportional hazards regression was used to explore the relation between the biomarkers and VTE. Model 1 adjusted for age, sex, and race. Model 2 additionally adjusted for HRT use, diabetes status, BMI, eGFR, CRP, aPTT and factor VIII.

Results:
A total of 227 incident VTE cases accrued over a median follow-up of 8.0 yrs. Relative to participants in the lowest quintile of NT-proBNP (≤26.7 pg/mL), those in the highest quintile (≥151.3 pg/mL) were at 2.28 (95% CI: 1.47-3.54) times greater risk of incident VTE (p-trend = 0.0002), adjusted via Model 1. This association was only slightly attenuated after adjustment in Model 2 [HR: 1.98 (95% CI: 1.25, 3.13); p-trend = 0.003]. The general trend was present for both unprovoked [HR: 1.62 (95% CI: 0.70, 3.75)] and provoked VTE [HR: 2.22 (95% CI: 1.28, 3.84)] in the fully-adjusted models, though power was low when stratifying by VTE type. Participants in the highest category (≥0.014 ug/L) of TnT were also at modestly greater risk of incident VTE in Model 1 [HR: 1.99 (95% CI: 1.23, 3.21); p-trend = 0.0002] and Model 2 [HR: 1.52 (95% CI: 0.89, 2.60); p-trend = 0.03], relative to those with undetectable TnT. The association was, however, present for only provoked VTE, with no evidence of a relation for unprovoked VTE.

Discussion:
In this large prospective cohort, both NT-proBNP and TnT were positively associated with risk of incident VTE. For NT-proBNP, the general trend was present for both provoked and unprovoked events, while for TnT the relation was isolated to provoked VTE events. Additional research is warranted to evaluate whether NT-proBNP and TnT are related to risk of VTE, or if the associations observed were the result of uncontrolled confounding.
Abstract 027: Skeletal Muscle Adipose Tissue Infiltration is Associated with Mortality in Older Men
Authors: Miljkovic Iva , Prasad Tanushree , Cauley Jane , Lee Christine , Kristine Kristine , Cawthon Peggy , Hoffman Andrew , Zmuda Joseph
Published: July 2021

Background:
Emerging evidence suggests that myosteatosis (adipose tissue (AT) infiltration within skeletal muscle (intra-muscular AT) and within the fascia surrounding skeletal muscle (inter-muscular, visible AT), increases with aging, and is positively associated with cardiovascular disease (CVD) risk factors independent of overall adiposity. Studies examining this important fat depot and mortality are lacking.

Methods:
We evaluated the association of mortality (all-cause, CVD, and non-CVD) with BMI, peripheral quantitative computed tomography (QCT) measured components of lower leg skeletal muscle adiposity (total, subcutaneous, and intermuscular AT, and muscle attenuation), and dual-energy X-ray absorptiometry (DXA) measured total body and trunk fat in 1155 community-dwelling older men (mean age 77.2 ± 5.1 years). Date and cause of death from death certificates were reviewed by a central physician adjudicator, with cause of death classified by ICD9 codes. Cox proportional hazards models were used to estimate the risk of mortality. Stepwise regression was used to select significant covariates for multivariable models. We tested the following covariates: age, race, study site, lifestyle risk factors, DXA total body fat, skeletal muscle area, height, diabetes, hypertension, stroke, myocardial infarction, renal disease, cancer, lipids, and medications that may influence metabolism.

Results:
During a mean follow-up of 5.9 years (2005-2012), 246 participants died. Among these, 74 participants died from CVD, and 159 died from non-CVD causes (cancer and other causes). After adjustment for significant covariates, lower intra-muscular AT infiltration, as reflected by greater skeletal muscle attenuation, was associated with decreased all-cause mortality, decreased CVD mortality, and decreased non-CVD mortality (Hazard ratio [95% CI] per SD increase in skeletal muscle attenuation: 0.77 [0.67, 0.90], 0.72 [0.55, 0.94], and 0.81 [0.67, 0.97], respectively; all P-values <0.02). No other measures of peripheral QCT and DXA measured adiposity or generalized obesity (BMI) were associated with mortality, regardless of the degree of adjustment.

Conclusion:
Our study revealed a previously unreported, independent association between myosteatosis and mortality among older men. Further studies are needed to establish if the association of myosteatosis with mortality is independent of inflammation, insulin resistance, visceral and other ectopic fat depots, and to identify possible biological mechanisms underlying this relationship.
Abstract 037: The Association of Early Menarche and Changes in LDL-C During Adolescence for African-American and White Girls
Authors: Dreyfus Jill G , Jacobs David R , Demerath Ellen W
Published: July 2021

Introduction:
LDL cholesterol transiently decreases during puberty, and then increases again in late adolescence. However, the association of earlier pubertal development and LDL-C changes among adolescents is not well established, especially among African-American girls.

Objective:
To examine race-specific associations of early menarche and change in LDL-C during adolescence.

Methods:
The National Growth and Health Study (NGHS) was a 10-year prospective study of 2,379 girls, aged 9-10 at baseline, from four areas of the United States. Girls with missing age at menarche (n=22) or clinic (n=1) information were excluded from analyses. We used mixed effects regression models to test the association of early menarche, defined as less than median age at menarche for race in NHANES III (<12.1 for African-American, and <12.6 years for white girls) and serial measures of LDL-C, adjusted for age, study center, parental education, and percent body fat at each visit. Time was defined as follow-up year 1 (mean age 10) through year 10 (mean age 19), and included as a quadratic term in all models.

Results:
The analytic sample included 2,356 girls (1,200 African-American; 1,156 white). Early (vs. later) menarche (-1.90 mg/dl, p=0.05) and African American race (-1.72 mg/dl, p =0.08) were associated with lower average LDL-C over the 10-year time period. LDL-C increased less during late adolescence in African-American than in white girls (β
race*time
2
= -0.11 mg/dl; p-interaction=0.01), and further, the relationship of menarche to the shape of the LDL-C curve differed by race, as indicated by different quadratic time terms (race*menarche*time
2
; p-interaction=0.02).

Conclusion:
LDL-C was lower among girls with early vs. later menarche during adolescence. By late adolescence, white girls with early menarche tended to experience faster gains in LDL-C compared with later maturing white girls. Additional research is needed to determine if this pattern continues into adulthood.
Abstract 047: Trajectories of Maintaining Recommended Amounts of Physical Activity in Young Adulthood and Associations with Abdominal Adiposity in Middle Age: The Cardia Study
Authors: Shay Christina M , Colangelo Laura , Carnethon Mercedes R , Liu Kiang , Allen Norrina B , Lewis Cora E , Reis Jared P , Jacobs David R , Terry J G , Carr J J
Published: July 2021

Background:
Greater abdominal adiposity is associated with insulin resistance and obesity-related vascular disease. Physical activity (PA) is inversely associated with abdominal adiposity yet associations between trends in adherence to PA recommendations through young adulthood and abdominal adiposity in middle age is unclear.

Objective:
To identify common trajectories of maintaining recommended levels of PA through young adulthood and to examine associations between trajectories and abdominal adiposity at middle age.

Methods:
The Coronary Artery Risk Development in Young Adults (CARDIA) study is a population-based, prospective, observational study of black and white men and women. PA was assessed at 8 exams across 25 years of follow-up. PA trajectories were identified by group-based modeling (PROC TRAJ) based on likelihood of maintaining recommended PA levels across exams. Visceral, subcutaneous, and abdominal intermuscular adipose tissue volumes (cm3) were assessed by computed tomography at the year 25 exam (43-55 yrs, n=3180).

Results:
Four major PA trajectories were identified: highly active (27.3%), declining activity (18.2%), modestly active (20.7%) and always sedentary (33.8%). Abdominal adipose tissue volumes by PA trajectory, race, and sex are displayed in Figure 1. Among white men and women, abdominal adiposity was lowest in always active adults and highest in those always sedentary; higher abdominal adiposity was observed with declining activity compared to modest activity. In black women, highest levels of abdominal adiposity were observed with declining activity. Black men exhibited no differences in abdominal adiposity across PA trajectory groups.

Conclusions:
Maintaining recommended physical activity levels through young adulthood is associated with lower abdominal adiposity at middle age. Highly active adults who exhibit declining physical activity towards middle age exhibit higher abdominal adiposity compared to adults with consistent modest activity throughout adulthood.
Abstract MP13: Circulating Long-chain Monounsaturated Fatty Acids and Cardiac Structure and Function
Authors: Imamura Fumiaki , Lemaitre Rozenn N , Song Xiaoling , Gottdiener John S , Siscovick David S , Mozaffarian Dariush
Published: July 2021

Background:
We previously observed a prospective association of higher levels of plasma phospholipid long-chain monounsaturated fatty acids (LCMUFA, 22:1 and 24:1 fatty acids) with higher risk of incident congestive heart failure (CHF) in two independent cohorts: the Cardiovascular Health Study (CHS) and Atherosclerosis Risk in Communities Study. This is consistent with decades-old animal experiments demonstrating cardiotoxicity of LCMUFA, including cardiac lipid accumulation and dysfunction. However, relationships of LCMUFA to cardiac structure and function in humans are unknown.

Aim:
to evaluate associations of circulating LCMUFA with indices of cardiac structure and function including left-ventricular mass (LVM), LV hypertrophy (LVH), LV wall thickness, and systolic and diastolic function.

Methods:
We evaluated 2,220 CHS participants (age=74.6±5.0) in whom plasma phospholipid LCMUFA were measured in 1992 and M-mode echocardiography was performed in 1996. Primary outcomes were LVM index (LVM / height to the 2.7th power), LVH (LVM / height, >143 g/m for men and >102 g/m for women), LV wall thickness (average of posterior and septal wall thickness), systolic function (% fractional shortening), and diastolic function (ratio of early to atrial ventricular filling velocities, E/A ratio). Adjusting for sociodemographics, lifestyle factors, dietary factors, and prevalent cardiovascular diseases, we performed linear regression analyses to examine associations of 22:1 and 24:1 levels with each continuous outcome. For LVH (a common binary outcome), Poisson regression analysis was performed.

Results:
Mean±SD plasma phospholipid levels of 22:1 and 24:1 were 0.03±0.01 and 1.96±0.44 percent of total fatty acids. Across the interdecile range, higher levels of 22:1 and 24:1 were each associated with lower fractional shortening by 1.2% (95% confidence interval=0.1-2.3%, p=0.03) and 1.4% (0.2-2.7%, p=0.02), respectively. Higher levels of 22:1 and 24:1 were also associated with higher risk of LVH by 27% (0-62%, p=0.05) and 40% (5-86%, p=0.02), respectively. LCMUFA were not associated with LVM index, LV wall thickness, or E/A ratio (p>0.1 each). Findings were similar after excluding 410 adults with prevalent coronary heart disease or CHF.

Conclusions:
Higher circulating levels of plasma phospholipid 22:1 and 24:1 were associated with two indices of lower systolic function and greater risk of LVH, but not with other indices. These findings, if replicated, suggest mechanistic pathways whereby LCMFUA exposure may increase CHF risk and potentially inform future prevention efforts.
Abstract MP16: Prevalence of Dyslipidemia Patterns among US Hispanics: Results from the Hispanic Community Health Study / Study of Latinos
Authors: Rodriguez Carlos J , Swett Katrina , Wassertheil-Smoller Sylvia , Daviglus Martha , Kaplan Robert , Gallo Linda C , Giachello Aida L , Gonzalez Hector M , Schneiderman Neil , Talavera Gregory A
Published: July 2021

Background:
Prevalence and determinants of dyslipidemia among Hispanics/Latinos are not well known.

Methods:
Lipid and lipoprotein data from the HCHS/SOL -- a population-based cohort study of 16,415 US Hispanic/Latino participants, ages 18-74, from Cuban, Dominican, Mexican, Puerto Rican, and Central and South American backgrounds -- were used. Criteria for dyslipidemia are based on National Cholesterol Education Program Adult Treatment Panel III guidelines as low density lipoprotein-cholesterol (LDL-C) >130 mg/dl, triglycerides (TG) >200 mg/dl, non-high density lipoprotein (non-HDL-C) >160 mg/dl, or low HDL-C (<40 mg/dl for men and <50 mg/dl for women). Differences across Hispanic/Latino groups were tested using Mantel- Haenszel Chi-square and analysis of variance for categorical and continuous variables, respectively. Demographics, anthropometric measurements, lifestyle factors, dietary and metabolic profiles in those with abnormal vs. normal lipid components were compared using multivariable logistic regression models.

Results:
Mean age was 40.7 years (SE 0.23) and 48.3% are male. The overall prevalence of any dyslipidemia was 65.1%; prevalence of elevated LDL-C was 35.5%, and highest among Cubans (44.5%; p<0.001). Low HDL-C was present in 41.9% overall, Central Americans had the highest prevalence (44.1%) but not significantly different from other groups (p=0.09). High TGs were seen in 14.9% overall, most commonly among Cubans (17.5%; p<0.001). Elevated non-HDL-C was seen in 34.3% of the sample, and highest among Cubans (43.2%). Dominicans had the lowest prevalence of all four types of dyslipidemia. Multivariate analyses, across all Hispanics, show that prevalence of any dyslipidemia was significantly associated with increasing body mass index and diabetes diagnosis. Higher age was associated with a significantly lower prevalence of low HDL but a higher prevalence of all other dyslipidemia types. Female sex was associated with higher prevalence of low HDL-C but a lower prevalence of elevated TGs, non-HDL-C or LDL-C. Low physical activity was significantly associated with elevated TGs and low HDL-C. Alcohol use was associated with a lower prevalence of low HDL-C only.

Conclusion:
Dyslipidemia is very common among Hispanics/Latinos; Cubans seem particularly at risk. Low HDL-C and elevated LDL-C are most commonly seen. Across all Hispanics, determinants of dyslipidemia varied depending on the type of dyslipidemia. To prevent dyslipidemias, effective public health measures among the Hispanic/Latino population are needed.
Abstract MP28: Life’s Simple 7 and Incident Cognitive Impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study
Authors: Thacker Evan L , Gillett Sarah R , Wadley Virginia G , Unverzagt Frederick W , Judd Suzanne E , McClure Leslie A , Howard Virginia J , Cushman Mary
Published: July 2021

HYPOTHESIS.
We hypothesized that higher scores on Life’s Simple 7 (LS7), a composite measure of cardiovascular health, are associated with lower incidence of cognitive impairment in the absence of stroke, and that this association differs by race and geographic region.

METHODS.
We included REGARDS participants aged 45+ who at baseline were cognitively normal by the Six-Item Screener (SIS) and free of stroke. We censored participants at incident stroke. We calculated baseline LS7 score, ranging from 0 points (worst) to 14 points (best), from smoking, BMI, physical activity, diet, cholesterol, blood pressure, and fasting glucose. We defined incident cognitive impairment as (1) scoring ≤4 of 6 points on the most recent follow-up SIS, or (2) scoring ≥1.5 standard deviations below age, sex, race, and education-adjusted means on the most recent of at least 2 of 3 domain-specific cognitive tests. We calculated age, sex, race, and education-standardized percentages of participants with incident impairment by LS7 score tertiles, and age, sex, race, education, and region-adjusted odds ratios by tertiles and per 1 point higher LS7 score. We repeated analyses by race (black/white) and region (southeastern US stroke belt/nonbelt).

RESULTS.
The distribution of LS7 scores was higher in whites than blacks and outside the stroke belt than within the stroke belt. Incidence of cognitive impairment was lower at higher LS7 scores (Table). This inverse association was stronger for cognitive domain testing than for SIS. For SIS, we observed an inverse association among whites and outside the stroke belt, but not among blacks or within the stroke belt. For cognitive domain testing, the inverse association was similar across race and region.

CONCLUSIONS.
Favorable LS7 scores are associated with lower incidence of cognitive impairment, particularly as assessed by cognitive domain testing. Racial and regional differences in cardiovascular health and its association with cognitive impairment may contribute to cognitive impairment disparities.