bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P216: Relationships of Nativity and Length of Residence in the U.S. with Favorable Cardiovascular Health Among Hispanics/Latinos of Diverse Backgrounds: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Kershaw Kiarri N , Espinoza Giacinto Rebeca , Gonzalez Franklyn , Isasi Carmen R , Salgado Hugo , Stamler Jeremiah , Talavera Gregory A , Tarraf Wassim , Van Horn Linda , Wu Donghong , Daviglus Martha
Published: March 2022

Objectives:
Little is known about the relationship of acculturation and favorable cardiovascular (CV) health (i.e., low CV risk) in the Hispanic/Latino population.

Methods:
Age-adjusted prevalences (weighted for sampling probability and non-response) are reported. Logistic regression was used to examine associations of acculturation (measured using nativity and length of residence: <10 years, ≥10 years, and US-born) with low CV risk (not currently smoking; no diabetes; untreated total cholesterol <200mg/dL; untreated blood pressure <120/<80; body mass index <25 kg/m
2
; and no major ECG abnormalities) in 15,047 HCHS/SOL participants (52.4% women) of Central American, South American, Cuban, Dominican, Mexican, Puerto Rican background, and Hispanic/Latino men and women identifying as other or >1 background group. We also tested whether these associations varied by Hispanic/Latino background.

Results:
Among women, age-adjusted low CV risk prevalence was highest for those living in the US < 10 years (15.4%) and similar for those living in the US ≥ 10 years (9.4%) and born in the US (9.2%). Low CV risk prevalence in was lower in men, but patterns were similar by acculturation (<10 years: 4.5%; ≥ 10 years: 5.6%; US-born: 6.0%). In multivariable-adjusted models (Table), women living in the US<10 years were more likely to be low CV risk than US-born women; these associations did not vary by Hispanic/Latino background (P for interaction=0.72). Findings varied significantly in men (P for interaction <0.001), but there was no strong patterning in low CV risk prevalence by length of residence for most groups.

Conclusions:
These findings highlight the role that acculturation plays in shaping cardiovascular health in Hispanics/Latinos.
Abstract P238: Distribution of Aortic Plaque by Sex and Age Among Community-dwelling Adults: A Framingham Magnetic Resonance Study
Authors: Qazi Saadia , Gona Philimon N , Oyama-Manabe Noriko , Salton Carol J , O’Donnell Christopher J , Manning Warren J , Chuang Michael L
Published: March 2022

Introduction:
Aortic plaque can be seen on noncontrast cardiovascular magnetic resonance (CMR) imaging. We sought to determine the prevalence, distribution and burden, or quantitative amount, of CMR-detected thoracic (TAP) and abdominal (AAP) aortic plaque in a community-dwelling cohort of adults.

Methods:
1794 Framingham Offspring cohort members underwent ECG-gated, fat-suppressed, T2-weighted TSE black blood aortic CMR at 1.5T: 1.03 x 0.64-mm pixels, 5-mm slice thickness. We obtained 12 thoracic (above diaphragm, 1-cm interslice gap) slices and 24 abdominal (below diaphragm/above aortic bifurcation, 5-mm gap) slices. Plaque protruding ≥1mm into the lumen was traced on each slice and summed to determine AAP and TAP burdens. Participants were stratified by sex and 10-year age groups. We tabulated number of persons with prevalent (i.e. >0) AAP and TAP and tested for trend (Cochrane-Armitage) across age groups. Among those with plaque>0, we determined upper 90th percentile (P90) plaque burden, if the sex/age-group had ≥20 persons with prevalent plaque (we felt calculations based on N<20 would be speculative at best).

Results:
Complete aortic studies were available on 1726 adults aged 65±9y (47% men). AAP was more prevalent than TAP: 359/806 (44.5%) men and 430/920 (46.7%) women had AAP, p=0.26; 72/806 (8.9%) men and 65/920 (7.1%) women had TAP, p=0.15. The Table shows sex-specific distributions and burdens of plaque by age-group, where +AAP (+TAP) indicates abdominal (thoracic) aortic plaque is present. Prevalence of both AAP and TAP increased monotonically with age (p<0.0001) in both sexes. Burden of AAP at the P90 level also increased monotonically with age.

Conclusions:
Among middle-aged and older community dwelling adults, AAP is seen on noncontrast CMR in 45.7%, while TAP is less prevalent at 7.9%. Prevalence of aortic plaque did not differ between men and women and increases with age in both sexes. Burden (amount) of AAP also increases with greater age.
Abstract P239: Burden of Adverse Metabolic Factors is Associated with Increased Left Ventricular Concentricity in Adults with Normal-range Body Mass Index: The Framingham Heart Study
Authors: Gona Philimon N , Lee Jane J , Salton Carol J , O’Donnell Christopher J , Manning Warren J , Chuang Michael L
Published: March 2022

Introduction:
Persons with normal-range body mass index (BMI) but adverse metabolic characteristics associated with obesity have been described as metabolically-obese normal weight (MONW). We sought to determine whether adverse metabolic profile is associated with alterations in left ventricular (LV) structure or function among adults with normal BMI.

Methods:
From the 1794 Framingham Offspring cohort adults who underwent cardiac magnetic resonance (CMR), we identified 446 free of non-skin cancer and prevalent clinical cardiovascular disease (CVD) who had 18.5≤BMI<25.0 kg/m2 and complete covariates. We calculated a metabolic score (MS) where 1 point was assigned for each of: a) fasting glucose≥100 mg/dL or diabetes; b) SBP≥140 or DBP≥90 mmHg or antihypertensive treatment; c) TG≥150 or HDL_C <40(M)/<50(W) mg/dL or lipid treatment; d) HOMA-IR≥2.5; e) waist circumference ≥102/88cm for M/W. Participants were stratified as MS0 (no points), MS1 (exactly 1 point), or MS2+ (≥2 points). LV mass (LVM), end-diastolic volume (EDV), ejection fraction (EF), and concentricity (LVM/EDV) were measured from breathhold cine SSFP CMR scans; we calculated LVM/BSA. Linear regression was used to compare MS1 and MS2+ groups to the MS0 group. We also tested for linear trend across metabolic groups. CMR variables were adjusted for sex, age, heart rate (HR) and body size (BSA); LVM/BSA was adjusted for sex, age, HR only.

Results:
LV concentricity increased with worsening metabolic status (see Table); this was driven by lower LV EDV, not increased LVM. LVM did not differ across (trend) or between MS-groups. LVEDV decreased across groups but only MS2 differed significantly from MS0. LVEF increased slightly but significantly across MS-groups.

Conclusions:
In a community-dwelling cohort, among participants who were free of cancer and clinical CVD and had normal BMI, worsening metabolic profile was associated with adverse remodeling of the left ventricle, reflected by greater LV concentricity.
Abstract P247: Trends in Obesity Prevalence and Predictors of Significant Weight Loss in a Large, Diverse Employee Population: The Baptist Health Employee Study
Authors: Osondu Chukwuemeka U , Aneni Ehimen C , Valero-Elizondo Javier , Salami Joseph A , Younus Adnan , Rouseff Maribeth , Das Sankalp , Guzman Henry , Tran Thinh , Khan Gulmeena , Feldman Theodore , Agatston Arthur , Veledar Emir , Nasir Khurram
Published: March 2022

Background:
Obesity has become a significant problem in the workplace, impacting health care costs to employers and employee productivity. As a result, employers have adopted various strategies to improve obesity among their employees. In this study, we examine the changes in obesity distribution in a cohort of employees of a large healthcare organization over a 3-year period and examine characteristics of employees who lost significant weight.

Methods:
Employees of Baptist Health South Florida (BHSF), a large not-for-profit healthcare organization, participated voluntarily in an annual Health Risk Assessment between 2012 and 2014. Only employees who participated in all 3 consecutive years were selected for this study. Height and weight from which body mass index was calculated, as well as other biometric measures were collected. The HRA also assessed current lifestyle behaviors, as well as intentions/ readiness to improve these lifestyle characteristics and behaviors including diet, exercise and weight. Obesity was categorized according to BMI as < 30, 30 - 34.9 and ≥ 35.0 kg/m2.

Results:
A total of 7357 employees (76% females, 56% Hispanic) participated in all 3 years of the HRA under study. Five percent (n=362) of participants shifted to a lower obesity category over 2 years. After 1 year, about 10% (n=703) of participants had a 5% reduction in BMI, while at 2 years, almost 15% (n=1061) achieved a reduction in BMI of at least 5%. Over 20% of participants with a BMI > 35 lost significant weight (≥5% BMI reduction). Participants who lost significant weight were more likely to have reported an intention to lose weight (OR=1.7; 1.5 - 2.0), an intention to improve their diet (OR=1.3; 1.2 - 1.5) or physical activity (OR=1.2; 1.1 - 1.4)

Conclusion:
Our findings suggest that intentions to improve lifestyle may be as important as improving lifestyle itself. It also highlights the need for, and the opportunity to create motivational strategies to encourage individuals to pursue healthier lifestyles.
Abstract P255: Gut Microbiota Diversity and Specific Microbial Genera Associate with Cardiovascular Disease Risk: Findings From the Bogalusa Heart Study
Authors: Kelly Tanika , Ajami Nadim J , Bazzano Lydia A , Zhao Jinying , Petrosino Joseph , He Jiang
Published: March 2022

Recent advances in sequencing technology have made it feasible to characterize human gut microbial communities (or microbiota) and examine their associations with disease outcomes, including cardiovascular disease (CVD) related traits. However, there is a paucity of research examining how the human gut microbiome may influence overall CVD risk in population based studies. The objective of the current study was to identify composite measures of microbiota diversity and specific microbial genera that associate with CVD risk among participants of the Bogalusa Heart Study (BHS). The current BHS cohort includes 1,257 participants who have been screened at least two times in childhood and two times in adulthood for CVD risk factors. For the microbiome study, we selected the 55 participants at highest CVD risk and 57 participants at lowest CVD risk using a z-score based data reduction technique, leveraging longitudinal mean measures of systolic BP, low-density lipoprotein cholesterol, and fasting plasma glucose levels. Next generation 16S rRNA sequencing of the V4 hypervariable region was conducted using genomic bacterial DNA extracted from stool samples of the 112 participants. The Wilcoxon rank sum test was used to examine differences in measures of alpha diversity, including observed operational taxonomic units (OTUs) and the Chao1 index, along with specific microbial taxa between CVD risk groups. Permutation multivariate analysis of variance (PERMANOVA) was used to test compositional differences based on unweighted Unifrac distance as a measure of beta diversity. We observed significantly less alpha diversity in those at high versus those at low CVD risk (P=0.04 and 0.02 for observed OTU and Chao1 index measures, respectively). The PERMANOVA test indicated marginal significance of compositional differences between the two groups (P=0.07). In addition, 10 microbial genera significantly differed between high and low CVD risk participants, including Faecalibacterium (P=0.0014), Subdoligranulum (P=0.01), Turicibacter (P=0.01), Rothia (P=0.01), Lachnospira (P=0.01), Haemophilus (P=0.03), Dialister (P=0.03), Bifidobacterium (P=0.03), Oscillibacter (P=0.04), and Megamonas (P=0.05). In summary, we provide empirical evidence of lower microbial enrichment among BHS participants at high versus those at low CVD risk, along with promising findings of differences in specific microbial genera between CVD risk groups.
Abstract P265: Macrosocial Disparity, Diet, and Cardiovascular Mortality in Global Populations Undergoing Transition
Authors: Singh Gitanjali M , Morrish Kurtis , Masters William , Mozaffarian Dariush
Published: March 2022

Background:
Economic and social disparities are linked to poor health outcomes in diverse countries worldwide. Differences in diet may mediate many of these effects, yet to-date, the impact of social, economic, and demographic inequality on the quality and diversity of diet has not been examined in a comparable manner globally.

Objective:
To comparably quantify the relationships of macroeconomic indicators of disparity with diet quality in 84 countries worldwide, and to assess their associations with CVD mortality.

Methods:
Data on country-specific per-capita GDP, urbanization, income inequality (income Gini coefficient and share of income held by top 1%), education, and educational inequality (educational Gini); on dietary quality and diversity; and on CVD mortality rates were obtained from our Global Dietary Database and other sources (Figure). Relationships between income inequality, diet quality, and CVD mortality were examined through multivariate regression controlling for country-level per-capita GDP, including country-level fixed effects, as well as through non-parametric Loess regression. Analyses were performed separately for 1990, 2010, and for the percent change between 1990 and 2010 for each variable.

Results:
From 1990-2010 income inequality increased by >5% in 51 of 84 countries and decreased by > 5% in 15/84 countries. Of countries with increasing income inequality, 61% had worsening scores for unhealthy diet; of those with decreasing income inequality, only 27% had worsening unhealthy diet scores. CVD mortality increased in 43% of countries with increasing income inequality, primarily in Eastern Europe/Asia; while it declined in ½ of countries with declining income inequality (Figure). Results for educational inequality and urbanization are in progress.

Conclusions:
This first cross-country analysis of macrosocial disparities, diet quality and CVD mortality highlights regional heterogeneity and time variance the impacts of these inequities on diet and subsequent risk of CVD.
Abstract P277: ‘Catalytic’ Doses of Fructose Improve Glycemic Control but Not Insulin Resistance: A Systematic Review and Meta-Analysis of Controlled Feeding Trials
Authors: Noronha Jarvis , Braunstein Catherine , Blanco Mejia Sonia , Cozma Adrian , Glenn Andrea , Sievenpiper John
Published: March 2022

Objective:
Contrary to concerns that fructose may have adverse metabolic effects, an emerging literature has shown that low-dose fructose at a level obtainable from fruit (
<
40-g/day) may benefit glycemic control. This effect appears to be mediated by upregulation of glucokinase, leading to increased hepatic glycogen synthesis. Whether this ‘catalytic’ mechanism of fructose will manifest as an increase in hepatic insulin sensitivity is unclear. To address this question, we synthesized evidence from controlled feeding trials assessing the effect of small ‘catalytic’ fructose doses on HbA1c, fasting blood glucose, and homeostasis model assessment of insulin resistance (HOMA-IR).

Methods:
We searched MEDLINE, EMBASE, and Cochrane Library through October 6, 2015. We included controlled feeding trials of
>
7 days investigating the effect of small ‘catalytic’ fructose doses (
<
40-g/day) in isoenergetic exchange for other carbohydrates. Two independent reviewers extracted relevant data and risk of bias (Cochrane Risk of Bias Tool). Data were pooled using the generic inverse variance method and expressed as mean differences (MD) with 95% confidence intervals (CIs). Heterogeneity was assessed (Cochran Q statistic) and quantified (I
2
statistic).

Results:
Nine trials (n= 153) met the eligibility criteria. ‘Catalytic’ doses of fructose significantly reduced HbA1c (MD= -0.40% [95% CI -0.72 to -0.08%]) and fasting blood glucose (MD= -0.18 mmol/L [95% CI -0.35 to -0.02 mmol/L]). There was no effect on HOMA-IR (MD= 0.04 [95% CI -0.14 to 0.22]).

Limitations:
The available trials were small (median sample size, n= 20) and of short duration (median follow-up, 2 weeks).

Conclusion:
Pooled analyses indicate that small ‘catalytic’ doses of fructose in isoenergetic exchange for other carbohydrates improve aspects of glycemic control, but the effect does not appear to be mediated through an improvement in hepatic insulin sensitivity. There is a need for larger and longer (
>
6 months) high quality randomized trials to confirm these results.
Abstract P286: Macronutrient Intake and Dietary Patterns’ Association with Telomere Length in American Indians: The Strong Heart Study
Authors: Mete Mihriye , Eilat-Adar Sigal , Zeymo Alexander , Zhao Jinying , Fretts Amanda M. , Shara Nawar , Howard Barbara V.
Published: March 2022

Introduction:
Telomeres are repeated DNA sequences and their associated proteins at the ends chromosomes. A slow and gradual loss of telomere length with increasing age in humans has been reported. Substantial variability observed in the rate of telomere shortening
independent of age
has been attributed to environmental and lifestyle factors
.

Hypothesis:
This study examines the association between leukocyte telomere length (LTL) and dietary intake among American Indians (AIs). We hypothesized that diets deemed “unhealthy”, with high content of sugar, saturated and trans fats, and alcohol would be associated with shorter LTL.

Methods:
The current analysis included 2,842 American Indians (AIs) participating in the Strong Heart Family Study (SHFS). LTL was measured by quantitative PCR. Nutrition data were collected via food frequency questionnaire. Four diet patterns were extracted using principal component analysis (Western, Traditional, Healthy and Unhealthy diet patterns). The relationship between LTL and diet was analyzed, separately, by using diet patterns measured in quintiles or by using macronutrient intake in diet including alcohol consumption. The analyses were conducted using multivariate linear mixed models, adjusting for family relatedness, age, diabetes, gender, BMI, physical activity and smoking.

Results:
The mean age was 40 (SD=17), 60% were female. In models examining diet patterns, the traditional diet pattern, which includes traditional foods, dry beans, Mexican foods, stew, (processed) meats, and hydrogenated vegetable fats, was significantly and negatively associated with LTL. Participants who scored higher on the traditional diet had shorter LTL (shorter by 0.005 per one quintile of traditional diet, p<0.01). We observed no significant association between LTL and other three diet patterns. There was no association of macronutrients (i.e., protein, fat components, carbohydrates, simple and added sugars, dietary cholesterol or fiber) with LTL. However, alcohol intake was significantly and negatively related to LTL in the macronutrients model (shorter by 0.03 per 10-percentage point increase, p<0.05).

Conclusions:
Our results suggest that, in addition to known factors such as older age, higher BMI and diabetes, traditional diet pattern may reflect a lifestyle associated with accelerated aging of AIs. Alcohol intake seems to be related to the shortening of LTL with an effect size comparable to that of diabetes.
Abstract P306: Participation in Cardiac Rehabilitation and Survival After Mitral or Aortic Valve Surgery
Authors: Pack Quinn R , Lahr Brian D , Squires Ray W , Lopez-Jimenez Francisco , Greason Kevin , Michelena Hector , Goel Kashish , Thomas Randal J
Published: March 2022

Background:
Cardiac rehabilitation (CR) improves functional capacity after heart valve surgery (HVS), but no survival benefit has yet been described. We hypothesized that attendance at CR after HVS would be associated with improved long-term survival.

Methods:
In 2013, we surveyed all patients (or a close family member if the patient was deceased) who had isolated HVS between 2006 through 2010 at the Mayo Clinic to assess if they attended CR after their HVS. We assessed survey reliability among local patients by comparing self-reported vs. medical-record verified CR attendance with the kappa statistic. We then performed a propensity-adjusted landmark mortality analysis through October 2014 for the association between CR attendance and long-term all-cause mortality conditional upon surviving the first year after HVS.

Results:
Survey response rate was 40% (573/1420), with responders more likely to be older, have longer hospitalizations, more aortic valve disease, but have better survival than non-responders. Among local patients, there was “substantial” agreement between reported attendance and medical-record verified CR attendance (agreement at 84%, kappa = 0.62.) A total of 547 patients (age 70 yrs., 62% male, 59% aortic valve surgery) with valid survey responses were included in the propensity analysis, of whom 296 (54.1%) attended CR. There were 100 deaths during a median follow-up of 5.4 years. For all patients, the propensity-adjusted model suggested no impact of CR on mortality (HR 1.03, 95% CI, 0.66 to 1.62). When stratified by procedure type, results suggested a potentially favorable, but non-significant, effect among patients with mitral valve surgery (HR 0.49, 95% CI 0.15 to 1.56), but not among patients with aortic valve surgery (HR 1.00, 95% CI 0.61 to 1.64.)

Conclusions:
Important improvements in functional capacity from CR have been previously reported after HVS, but, contrary to our hypothesis, we found that CR does not provide long-term survival benefits after HVS. These findings need additional confirmation to better clarify any mortality impact that may exist for CR following HVS, particularly among patients undergoing mitral valve surgery.
Abstract P313: Excessive Daytime Sleepiness in Older British Men: An Early Marker of Heart Failure
Authors: Zonoozi Shahrzad , Ramsay Sheena , Papacosta Olia , Lennon Lucy , Ellins Elizabeth A , Halcox Julian P , Whincup Peter H , Wannamethee Sasiwarang G
Published: March 2022

Background:
Sleep disturbance is common, especially amongst older adults. The association between night-time sleep duration, cardiovascular disease (CVD), metabolic disorders and mortality has been extensively reported, with studies showing a U-shaped association. Less is known about the influence of daytime sleep and attention has more recently turned to excessive daytime sleepiness which has been associated with increased CVD, heart failure and mortality. We aimed to investigate the association between sleep patterns and cardiovascular risk markers in older adults including metabolic risk markers, cardiac markers and early markers of atherosclerosis [arterial stiffness and carotid intima-media thickness (CIMT)] with particular focus on day sleep.

Methods:
Cross sectional study of 1722 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Men with a history of heart attack or heart failure (n = 251) were excluded from the analysis. Self-reported sleep duration (night and day) was based on a questionnaire; insomnia was defined as self-reported difficulty falling asleep. Participants were invited for a physical examination which included non-invasive assessment of vascular measures including CIMT and arterial stiffness (carotid distensibility and pulse wave velocity (PWV)).

Results:
Analysis of the data confirmed previous reports of a U-shaped association between night-time sleep duration and HbA1c, even following adjustment for confounding factors including age, BMI, physical activity and social class. Men who reported insomnia had significantly higher mean triglyceride, glucose and insulin (p = 0.02, 0.04 and 0.01 in the age-adjusted model). Increasing daytime sleep duration was associated with higher fasting glucose and insulin levels which remained significant (p = 0.02 and 0.01 respectively) after adjustment for prevalent diabetes. Compared to those with no daytime sleep, men with daytime sleep > 1 hour had a higher risk of raised N-terminal pro brain natriuretic peptide (NT-proBNP) of ≥400pg/ml, the diagnostic threshold for heart failure [OR (95% CI) = 1.88 (1.15, 3.1)], reduced lung function (forced expiratory volume in 1s) and elevated von Willebrand factor (vWF), a marker of endothelial dysfunction. These patterns were not seen for night-time sleep or insomnia. Sleeping patterns were unrelated to CIMT and arterial stiffness.

Conclusions:
Day sleep of > 1 hour may be an early indicator of heart failure. Clinically, this is important in the assessment of older patients who seek medical advice for excessive daytime sleepiness, in whom indicators of heart failure should be sought and further investigations carried out if necessary.
Abstract P317: Dietary Carbohydrate Quantity and Quality Measures and Risk of Stroke
Authors: Adebamowo Sally N , AlEssa Hala B , Spiegelman Donna , Rexrode Kathryn M , Willett Walter C
Published: March 2022

Background:
Dietary carbohydrates with high glycemic index and low in cereal fiber have been associated with increased risk of diabetes, a risk factor for stroke. Few prospective studies have examined the relation between measures of carbohydrate quality and risk of incident stroke. The relation between carbohydrate to fiber ratio and stroke risk remains unknown.

Methods:
We prospectively examined the associations of dietary carbohydrate quantity and quality measures (total carbohydrate, fiber [total, cereal, fruit and vegetable], glycemic index and load, and carbohydrate/fiber ratio) and risk of incident stroke among 40,689 men in the Health Professionals Follow-up Study, aged 40 to 75 years and free of diagnosed cardiovascular disease and cancer at baseline in 1986. Diet was collected using a validated questionnaire every 4 years. We calculated the hazard ratio of total, ischemic, and hemorrhagic strokes by quintiles of energy-adjusted intake of dietary variables using multivariate Cox proportional hazard models. Multivariate models were adjusted for age, lifestyle (BMI, smoking, alcohol, physical activity, multivitamins and aspirin use), history of diseases (family history of CHD, baseline history of hypertension, diabetes and hypercholesterolemia) and diet (total energy, red meat, magnesium, polyunsaturated fat to saturated fat ratio and trans fat).

Results:
During 24 years of follow-up, 1,530 total stroke events (including 847 ischemic, 178 hemorrhagic and 505 unspecified types) were documented. In multivariate analyses adjusted for age, lifestyle risk factors, history of diseases and total energy intake, carbohydrate (RR=0.74, 95% CI: 0.61 - 0.91, Ptrend 0.008), cereal fiber (RR=0.77, 95% CI: 0.64 - 0.93, Ptrend 0.003) and glycemic load (RR=0.78, 95% CI: 0.64 - 0.95, Ptrend 0.03) were associated with reduced risk of total stroke, comparing the extreme quintiles. With further adjustment for dietary variables, these associations were attenuated to non-significant levels, carbohydrate (RR=0.84, 95% CI: 0.67 - 1.05, Ptrend 0.20), cereal fiber (RR=0.91, 95% CI: 0.73 - 1.14, Ptrend 0.40) and glycemic load (RR=0.84, 95% CI: 0.68 - 1.05, Ptrend 0.26). Vegetable, fruit and total fiber, glycemic index and carbohydrate to fiber ratio were also not significantly associated with incident stroke risk. The results for total stroke were relatively similar to those for ischemic and hemorrhagic stroke types.

Conclusions:
Consumption of high quality carbohydrate foods did not appear to confer protection against incident stroke risk among this population of US men.
Abstract P318: Dietary Sodium to Potassium Ratio and Risk of Stroke in a Multi-ethnic Urban Dwelling Population: The Northern Manhattan Study
Authors: Cespedes Sandino , Willey Joshua Z , Sacco Ralph L , Wright Clinton B , Elkind Mitchell S , Gardener Hannah
Published: March 2022

Background:
There is growing evidence that an increase in dietary sodium increases morbidity and mortality from cardiovascular disease (CVD) at least in part via an increase in blood pressure (BP). Several researchers have identified an association of higher dietary potassium, seen with increased intake of fruits and vegetables, with lower BP. Moreover, there may be a potential interaction of sodium and potassium on CVD health, such that the relative levels of these variables may be more important than their absolute levels. The goal of this study was to determine the association of dietary sodium to potassium ratio (Na:K) with the risk of stroke and CVD in a multi-ethnic urban dwelling population.

Methods:
Stroke-free participants from the Northern Manhattan Study, a population-based cohort study of stroke incidence, were followed prospectively to assess incident stroke, myocardial infarction and vascular death. Baseline food-frequency questionnaires were analyzed for Sodium and Potassium intake based on self-reported food consumption using DIETSYS software (Block Dietary Data System: Dietsys+ analysis software, version 59, 1999). We examined the association of Na:K with incident stroke (ischemic and overall) as well as combined vascular events (CVE)(stroke, myocardial infarction and vascular death) using Cox-proportional Hazards models adjusting for age, sex, race/ethnicity, total daily calories, adherence to a Mediterranean-style diet, smoking, physical activity, BMI, diabetes, hypertension, and hypercholesterolemia.

Results:
2570 participants had dietary data, (mean age 69 ± 10 years, 64% women, 21% white, 53% Hispanic, 24% black); the mean of the Na:K ratio intake was 1.22 with a standard deviation of 0.43. Over a mean follow-up time of 11.9 years (SD=5.4), 274 participants developed stroke (N=232 ischemic) and 745 had a vascular event overall. In adjusted models the Na:K intake ratio was associated with an increased risk for ischemic Stroke (HR=1.5, 95% CI: 1.2-2.0), all stroke (HR=1.5, 95% CI: 1.2-1.9) and CVE (HR=1.2, 95% CI: 1.0-1.4). These results were unchanged in models adjusting for sociodemographic variables only.

Conclusions:
Our findings suggest that Na:K intake may be an important predictor of the risk of ischemic stroke and overall CVE.
Abstract P324: Cardiovascular Risk and Mortality Increase with Progression of Chronic Liver Disease
Authors: An Kyungeh , Kim Cheongtag , Salyer Jeanne , Bruffy Shannon , Sterling Richard
Published: March 2022

Introduction:
Patients with
c
hronic liver disease accounts for 30-45% of the adult population in North America; among them, more die from cardiovascular disease (CVD) than from liver cirrhosis. Reduction of CVD-mortality in this high risk population requires understanding of CVD-risk across the whole spectrum of liver disease progression ranging from mild forms (i.e. nonalcoholic fatty liver disease) to advanced forms (i.e. nonalcoholic- and alcoholic-liver cirrhosis) as well as understanding of the increase of CVD-risks by time.

Hypothesis:
We assessed two hypotheses that (1) CVD-risk and mortality are dependent on type of liver disease; and that (2) CVD-risk and mortality increase in five years in all three types of chronic liver disease. One exploratory hypothesis was (3) the increment of CVD-risk in five years is higher in advanced forms than in a mild form of chronic liver disease.

Methods:
A secondary data analysis was conducted using 2,765 records of patients with nonalcoholic fatty liver disease, nonalcoholic- and alcoholic-liver cirrhosis identified by the International Classification of Disease -9 codes. Framingham risk scores were calculated for each patient based on their sex, age, systolic blood pressure, total cholesterol and high density lipoprotein level or body mass index, smoking status, and the presence of diabetes with five year interval from 2009 to 2014.

Results:
Framingham CVD risk scores were significantly different among patients of nonalcoholic fatty liver disease (21.4%), nonalcoholic- (21.3%) and alcoholic-liver cirrhosis (28.1%) (
F
=5.610,
p=
.004). The all-cause mortality rate was significantly different among nonalcoholic fatty liver disease (5.8%), nonalcoholic- (20.5%) and alcoholic-liver cirrhosis (23.4%) (

[[Unsupported Character - Symbol Font ]]
2

=101.54,
p
=.000). In five years, CVD risk increased from 22.9 to 28.4% (
F
=55.7,
p
=.000) with the greater extent in alcoholic- and nonalcoholic liver cirrhosis (increased by 7.2 and 6.0%, respectively) than in nonalcoholic fatty liver disease (increased by 3.4%) (
F
=5.21,
p
=.023).

Conclusions:
We conclude that cardiovascular risks and mortality increase are dependent on type of liver disease. We also conclude that CVD risk increases in 5 years with the greater extent in advanced forms than in a mild form of chronic liver disease. To prevent CVD mortality, tailored risk reduction in earlier phases of chronic liver disease is crucial and may offer better outcomes.
Abstract 12: Whole Blood DNA Methylation Signatures of a Mediterranean-style Dietary Pattern
Authors: Ma Jiantao , Liu Chunyu , Joehanes Roby , Mendelson Michael M , Liang Liming , Lichtenstein Alice H , Hu Frank B , Levy Daniel
Published: March 2022

Introduction:
Mediterranean-style dietary patterns (MSDPs) have been associated with lower risk of cardiometabolic diseases, but the underlying biological mechanisms are poorly understood. To date, little is known in humans of the relationship between MSDPs and epigenetics. We hypothesized that adherence to a MSDP is associated with DNA methylation, an important epigenetic modification.

Methods:
We conducted a cross-sectional study of 3,563 Framingham Heart Study participants (median age 59 years, 55% women). We excluded participants with heavy alcohol use. Whole-blood derived DNA methylation of 480,000 cytosine-phosphate-guanine dinucleotides (CpGs) was assessed using the Illumina HumanMethylation450 BeadChip. A MSDP score was created based on nine dietary components, including fruits, vegetables, legumes, nuts, whole grains, fish, red meat, alcohol, and ratio of monounsaturated fatty acids to saturated fatty acids. Food intake was assessed by a validated food frequency questionnaire. Our study sample was randomly split into separate discovery/replication groups (n=1,788 and n=1,775) by pedigrees. We tested the association of CpG methylation with the MSDP score using linear mixed model, adjusted for sex, age, and energy intake (as well as family structure, imputed leukocyte composition, and technical variables). CpGs identified in discovery at FDR<0.05 were taken forward for replication. We then tested the significance (Bonferroni corrected α 0.05) of the identified CpGs after additional adjustment for smoking, physical activity, and BMI in whole study sample.

Results:
One CpG, cg05575921 in the
AHRR
gene, was associated with MSDP score in the discovery sample (
P
=3.3x10
-10
) and replicated in the replication sample (
P
=3.6x10
-5
). In whole study sample, higher MSDP score was associated with greater methylation of cg05575921 after adjustment for sex, age, energy intake, smoking, physical activity, and BMI (
P
=4.5x10
-3
). Higher fruit and whole grain intake was also associated with higher methylation level of cg05575921 (
P
=3.8x10
-7
and 5.1x10
-8
, respectively) and legume intake was associated with higher methylation level of cg17333223 (annotated to the
NSA2
gene,
P
=1.3x10
-7
). In contrast, fruit intake was associated with lower methylation of cg07035242 (annotated to the
UBIAD1
gene,
P
=2.0x10
-7
). These patterns persisted in the replication and in whole study sample.

Conclusions:
These data demonstrate a unique whole blood DNA methylation signature of a MSDP score and some of its individual components. The differentially methylated genes may represent therapeutic targets for prevention or treatment of cardiometabolic diseases. Future work is needed to explore the underlying mechanisms.
Abstract 25: The Impact of Excess Body Weight on Cardiovascular Disease Mortality From 1990 to 2015 and Drivers of Change at the State-Level in the United States
Authors: Reitsma Marissa B , Afshin Ashkan ,   GBD 2015 Collaborators
Published: March 2022

Introduction:
Maintaining a healthy weight is a key step toward ideal cardiovascular health and achieving AHA 2020 goals. State-level estimates of excess body weight and its impact on cardiovascular disease (CVD) mortality are necessary to inform interventions and track progress.

Objective:
To systematically quantify CVD deaths attributable to high body mass index (BMI) by age, sex, and state between 1990 and 2015.

Methods:
We synthesized 118 surveys (12,972,378 person-years) to characterize the population distribution of BMI by age, sex, and state from 1990-2015. We used a hierarchical mixed-effects linear regression to quantify and adjust for bias in self-reported height and weight data. Using the Global Burden of Disease analytic framework, we estimated CVD deaths attributable to high BMI in five-year increments from 1990 to 2015. We also quantified the contribution of changes in population structure, background mortality rate, and risk exposure to overall changes in CVD mortality.

Results:
In 2015, 173,180 (95% uncertainty interval: 130,890-218,620) CVD deaths were attributable to high BMI in the US: 70.4% from ischemic heart disease, 11.6% from hypertensive heart disease, 9.7% from hemorrhagic stroke and 8.2% from ischemic stroke. Mississippi had the highest attributable death rate (65.6 per 100,000 [51.6-80.3]), whereas Colorado had the lowest (23.4 [17.1-30.6]) (Figure). While the prevalence of excess body weight increased in all states from 1990-2015, reductions in background mortality rate offset increases in risk exposure (Figure). As a result, over the past 25 years the death rate attributable to high BMI increased in only 3 states (annual percent change: OK [0.53%], AL [0.17%], AK [0.08%]). The 3 states with the greatest annual decrease in attributable death rate were MN (-1.52%), NH (-1.47%), and MA (-1.45%).

Conclusions:
Our results highlight the need for implementation of evidence-based interventions at the state-level to reduce the prevalence and disease burden of high BMI in order to meet AHA 2020 goals.
Abstract 27: Volume and Density of Calcium in the Ascending Thoracic Aorta, When Present, Predict Incident Coronary Heart Disease Beyond Coronary Artery Calcium: the Multi-Ethnic Study of Atherosclerosis
Authors: Thomas Isac C , Forbang Nketi , Allison Matthew , Michos Erin , Post Wendy , McClelland Robyn , Longstreth WT , Wong Nathan , Budoff Matthew , Criqui Michael
Published: March 2022

Introduction:
Coronary artery calcium (CAC) volume and density differentially predict coronary heart disease (CHD) beyond traditional CVD risk factors. Whether similar associations exist for ascending thoracic aortic calcium (ATAC) volume and density are unknown. We hypothesized that ATAC volume and density predict CHD independent of the pooled cohort equations (PCE) and CAC.

Methods:
The Multi-Ethnic Study of Atherosclerosis followed 6,814 participants free of clinical CVD at recruitment. Cardiac CT was performed at baseline. For this analysis, only those with prevalent ATAC were included (necessary for evaluation of density). Cox regression was used to estimate associations of ATAC volume and density with incident CHD (fatal/non-fatal MI and cardiac arrest), with adjustment for the PCE and CAC volume and density. The incremental predictive value of ATAC volume and density was evaluated by area under receiver operating characteristic curves (AUC).

Results:
Of the total cohort, 233 (3.4%) had prevalent ATAC. In these participants, 29 CHD events occurred over 10.3 years. After simultaneous adjustment for the PCE, ATAC and CAC volumes and densities, ATAC alone was associated with CHD, with one standard deviation (SD) higher natural log ATAC volume associated with a 76%
greater
risk [HR 1.76 (95% CI 1.07-2.87)], and one SD lower ATAC density associated with a 57%
lower
risk [0.43 (0.26-0.71)]. The PCE, CAC volume and CAC density were not significantly associated with CHD. A model containing the PCE, CAC volume and density had an AUC of 0.584 (0.467-0.701) for incident CHD prediction. Adding ATAC volume and density to the model improved the AUC to 0.703 (0.588-0.817) (see table).

Conclusions:
ATAC was uncommon in a cohort free of baseline clinical CVD. However, when ATAC was present, both ATAC volume and density were independently associated with incident CHD. Furthermore, in these participants, the PCE and CAC poorly discriminated incident CHD, and ATAC volume and density substantially improved risk prediction.
Abstract 33: Handgrip Strength is Associated With Insulin Resistance in US Adolescents: Experience in NHANES 2011-2014
Authors: Li Shengxu , Zhang Rui , Zheng Liqiang , Chen Wei
Published: March 2022

Background:
Handgrip strength is a measure of muscular strength and body fitness. It has been shown that handgrip strength is associated with cardiometabolic risk in adult population. We hypothesized that handgrip strength is associated with insulin resistance measures in children and adolescents.

Methods:
The sample included 1,023 adolescents (50.4% boys and 49.6% girls) aged 12-19 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 2011-2014 and did not take any antidiabetic medications. The sum of the maximum handgrip strength from both hands, standardized to age- and sex-specific z-scores, was used. Fasting plasma glucose, serum insulin, and calculated Homeostatic model assessment of insulin resistance (HOMA-IR) were used as insulin resistance measures. Serum insulin levels and HOMA-IR were log-transformed before further analyses. General linear models were used for data analyses.

Results:
After adjustment for age, race, sex, and body mass index, handgrip strength was inversely associated with serum insulin levels (P<0.0001) and HOMA-IR (P=0.0002). The associations tended to be stronger in boys than in girls such that the inverse associations of handgrip strength with insulin levels and HOM-IR were significant in boys (P<0.0001 for both) but not in girls (P>0.35), though interaction terms between handgrip strength and sex were not significant (P>0.36). There was no association between handgrip strength and plasma glucose levels (P=0.50).

Conclusion:
These results suggest that handgrip strength is associated with insulin sensitivity in adolescents, which indicates that increasing muscular strength and body fitness may have beneficial effects in early stage prevention of insulin resistance and type 2 diabetes.
Abstract 41: Omega-6 Fatty Acid Biomarkers and Incident Type 2 Diabetes: A Pooled Analysis of 20 Cohort Studies
Authors: Wu Jason H , Marklund Matti , Imamura Fumiaki , Tintle Nathan , Ardisson Korat Andres V , de Goede Janette , Zhou Xia , Yang Wei-Sin , de Oliveira Otto Marcia C , Kroger Janine , Qureshi Waqas , Virtanen Jyrki K , Bassett Julie , Frazier-Wood Alexis C , Lankinen Maria , Murphy Rachel A , Rajaobelina Kalina , Lemaitre Rozenn N , Micha Renata , Mozaffarian Dariush ,   CHARGE Fatty acids and Outcomes Rsch Consortium (FORCE)
Published: March 2022

Background:
Emerging evidence suggests that dietary omega-6 polyunsaturated fatty acids (n-6 PUFA) plays a role in the primary prevention of type 2 diabetes (T2D).

Aims:
To evaluate the relation between blood and adipose tissue levels of n-6 PUFA and incident T2D, including n-6 linoleic acid (LA), the major dietary PUFA abundant in vegetable oils, and n-6 arachidonic acid (AA), a key precursor of endogenous metabolites that modulate glucose metabolism and inflammation.

Methods:
A global consortium of 20 prospective cohort studies identified by February 2016. Each study measured LA and AA at study baseline among adults>18y without prevalent T2D, and assessed the association of n-6 PUFA biomarkers and T2D risk prospectively using individual-level data, using a pre-specified analytic plan and harmonized exposures, covariates, and effect modifiers. Findings were centrally pooled using fixed-effects meta-analysis.

Results:
39,740 men and women from 10 countries were included (range of cohort means, age, 49-76y, and BMI, 25.0-28.1kg/m
2
), with 4,347 incident cases of T2D observed during follow-up. In continuous multivariate-adjusted analyses, higher LA was associated with 36% lower risk of T2D (RR,0.64, 95% CI,0.59-0.71, P<0.001, I
2
=49%,
Figure 1A
) per interquintile range. Similar inverse associations were observed for LA measured in different fractions, and in sensitivity analysis using random effects model. Levels of AA were not associated with T2D risk overall and in studies grouped by different biomarker fractions except total plasma (per interquintile RR=0.74, 95% CI=0.62-0.88, P<0.001,
Figure 1B
). The relations of LA and AA with T2D were not significantly modified by age, BMI, sex, race, aspirin use, n-3 PUFA biomarker, or
FADS
genetic variants (
P
≥ 0.13 for each).

Conclusion:
Higher blood and adipose tissue LA levels, biomarkers of the major dietary PUFA, were associated with lower risk of T2D among free-living populations worldwide. There was little evidence that AA levels were appreciably associated with risk of T2D.
Abstract 43: Association of Severe Hypoglycemia With Cardiovascular Disease and All-cause Mortality in Older Adults With Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lee Alexandra K , Warren Bethany , Lee Clare J , Huang Elbert S , Sharrett A. Richey , Coresh Josef , Selvin Elizabeth
Published: March 2022

Introduction:
There is concern that the strong association of severe hypoglycemia with cardiovascular disease (CVD) and all-cause mortality is confounded by diabetes severity or may not be causal and simply reflects general vulnerability. Our objective was to determine if the association of hypoglycemia with CVD and death withstood rigorous adjustment for likely confounders that prior studies have not adequately accounted for.

Methods:
We included ARIC participants aged 65+ at Visit 4 (1996-1998) with diagnosed diabetes and CMS Part B insurance. Severe hypoglycemia was identified through 2013 with ICD-9 codes from hospitalizations, emergency department visits, and ambulance services. CVD events (coronary heart disease, stroke, or heart failure) and death were assessed through 2013. Hypoglycemia was a time-varying exposure in progressively adjusted Cox models that included demographics, clinical characteristics, comorbidities, cognitive function, and activities of daily living and instrumental activities of daily living.

Results:
Of the 464 eligible participants, hypoglycemic events occurred in 65 participants prior to CVD or censoring and in 94 participants prior to death or censoring. The crude incidence rates of CVD and death were higher in persons with hypoglycemia compared to those without (CVD: 10.6 vs. 5.08 per 100 person-years (PY), p<0.001; death: 14.3 vs. 4.5 per 100 PY, p<0.001). After adjustment for age, sex, and race-center, hypoglycemia was strongly associated with both CVD and death (
Figure
). After additional adjustment for confounders, the hazard ratios (HR) for hypoglycemia were substantially attenuated but remained significant (CVD HR: 1.61 (95%CI 1.06-2.46); death HR: 1.83 (95%CI 1.35-2.84)).

Conclusion:
After adjustment for rigorously measured shared risk factors, hypoglycemia was associated with both CVD and death. These results suggest that severe hypoglycemia may influence CVD risk and death independently of diabetes severity and general vulnerability.