bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 018: Association of the Change in Physical Activity and Cardiovascular Disease Outcomes in the Look AHEAD Trial
Authors: Jakicic John M , Fulton Janet E , Lang Wei , Walkup Michael P
Published: July 2021

Introduction:
The Look AHEAD trial examined cardiovascular disease incidence in adults with type 2 diabetes randomly assigned to an intensive lifestyle intervention compared to those randomly assigned to diabetes support and education (control). In a substudy, physical activity was assessed using accelerometry, which provides an opportunity to examine whether the incidence of cardiovascular disease varied by the measured change in physical activity.

Hypothesis:
There is a beneficial association between the 1- and 4-year change in physical activity and the pre-specified primary and secondary outcomes in participants in the Look AHEAD trial.

Methods:
Adults (N=1,978; 59.1±6.8 kg; 102.8±19.0 kg) with type 2 diabetes at 8 study sites, who completed physical activity was assessment using accelerometry for 1 week at 0, 1, and 4 years. MET-minutes per week of moderate-to-vigorous physical activity (MVPA) performed in bouts of at least 10 minutes was identified from the accelerometry data. The 1- and 4-year change in MVPA was computed as the difference from baseline. The primary outcome was pre-defined as non-fatal myocardial infarction, stroke, hospitalized angina, and cardiovascular disease death. The first secondary outcome was pre-defined as non-fatal myocardial infarction, stroke, hospitalized angina, CABG/PTCA, hospitalized congestive heart failure, carotid endarterectomy, peripheral vascular disease, and total mortality. The relationships between 1- and 4-year change in physical activity and the primary and secondary outcomes were examined using Cox proportional hazards models with data collapses across the two treatment groups. Hazard ratios (HR) were adjusted for age, sex, history of cardiovascular disease, duration of diabetes, diabetes medication use, baseline weight, change in weight, and baseline physical activity.

Results:
MVPA [Median (25
th
, 75
th
percentile)] was 167.6 (0,545.5), 205.4 (0, 700.2), and 91.3 (0, 418.9) MET-minutes per week at 0, 1 and 4 years, respectively. Change in MVPA at 1-year was not significantly associated with the primary outcome [HR per 100 MET-minutes per week = 1.001 (95% CI: 0.985, 1.017)] or secondary outcome [HR per 100 MET-minutes per week = 0.989 (95% CI: 0.966, 1.013)] assessed across 8.8±2.4 years of follow-up. Change in MVPA at 4-years was significantly associated with a reduction in the primary [HR per 100 MET-minutes per week = 0.949 (95% CI: 0.912, 0.987)] and the secondary outcome [HR per 100 MET-minutes per week = 0.897 (95% CI: 0.843, 0.954)] assessed across 9.2±1.8 years of follow-up.

Conclusions:
Change in physical activity at 4-years is associated with a reduction in incidence of cardiovascular disease in adults with type 2 diabetes. These findings suggest improvements in physical activity may need to be sustained for a relatively long period (4 years) to elicit a beneficial effect on incidence of cardiovascular disease.
Abstract 020: Heartbreaking Careers in Old Age: Retirement Sequences as a Non-Traditional Risk Factor for Cardiovascular Diseases
Authors: Diaz-Toro Felipe , Madero-Cabib Ignacio , Calvo Esteban , Staudinger Ursula
Published: July 2021

Background:
Traditional factors leave substantial risk for incident cardiovascular disease (CVD) unexplained. Recent literature addressing this limitation identifies non-traditional risk factors, such as depression and clinical biomarkers. This study explored retirement sequences as a new non-traditional risk factor for CVD among older Americans.

Methods:
Heart disease and stroke incidence were measured for 7,880 Health and Retirement Study participants age 70 and over. Non-parametric survival curves and time-discrete survival models were used to compare the succeeding incidence of CVD across the retirement sequences that individuals followed between ages 60-61 and 70-71. We employed six holistic types of retirement sequences: (i)
early
for individuals who completely retired at or before age 62; (ii)
complete
for the conventional normative model of retirement by which people who are working in full-time jobs completely retire at the legally established age; (iii)
ambiguous
for people out of the labor force who shifted into retirement; (iv)
partial
for subjects with full-time jobs that claimed partial pension benefits in their early 60s; (v)
compact
for individuals moving from part-time positions into partial retirement; and (vi)
late
for individuals with full-time employments until their late 60s. These sequences were measured as longitudinal pathways of labor-force statuses and transitions measured in two-year intervals between the ages 60-61 to 70-71 years. Models were fitted for the whole sample, as well as males and females separately, adjusting for the probability of dying before CVD onset, sociodemographics, traditional risk factors, and clinical characteristics.

Results:
Out of all participants, 78.1% (6154/7880) reported at least one adverse cardiovascular event after age 70. Individuals following retirement sequences characterized by a progression from full-time jobs to either early retirement (heart disease, HR 3.07 CI95% 2.89-3.26 p<.001; stroke, HR:2.75 CI95% 2.53-2.96 p<.001) or retirement at the state pension age (heart disease, HR:3.73 CI95% 3.52-3.93 p<.001; stroke, HR:2.30 CI95% 2.07-2.54 p<.001), as well as people out of the labor force who move into retirement (heart disease, HR:2.36 CI95% 2.12-2.60 p<.001; stroke, HR:2.72 CI95% 2.44-3.01 p<.001) experienced a higher risk for heart disease and stroke relative to individuals who kept on working past the retirement age. However, the effects are stronger for heart disease among women and stroke among men.

Conclusions:
Retirement sequences may indeed be regarded as a non-traditional risk factor for CVD in aging populations.

Keywords:
Retirement-Heart disease-Stroke-Work
Abstract 022: Cost-Effectiveness of Financial Incentives and Disincentives for Improving Diet and Health Through the Supplemental Nutrition Assistance Program
Authors: Liu Junxiu , Mozaffarian Dariush , Sy Stephen , Huang Yue , Lee Yujin , Wilde Parke , Abrahams-Gessel Shafika , de Souza Veiga Jardim Thiago , Gaziano Tom , Micha Renata
Published: July 2021

Introduction:
The 2018 Farm Bill represents a major opportunity to reduce disparities in diet and health. The largest component is the Supplemental Nutrition Assistance Program (SNAP), feeding 1 in 6 Americans. Potential options include subsidizing fruits & vegetables (F&V), restricting sugar-sweetened beverages (SSBs), or implementing a broader food incentive/disincentive framework that preserves choice. Their comparative health impacts and cost-effectiveness are not established.

Methods:
Using a validated microsimulation model (CVD PREDICT), we estimated changes in CVD events, quality-adjusted life-years (QALYs), costs, and cost-effectiveness of 3 policy scenarios in SNAP adults: 1) 30% subsidy on F&V; 2) 30% F&V subsidy + SSB restriction; and 3) 30% subsidy on F&V, whole grains, nuts/seeds, seafood, plant-based oils, and 30% disincentive on SSBs, junk food, and processed meats. Model inputs included national data from NHANES (2009-2014), policy effects from SNAP pilots and food pricing meta-analyses, diet-disease effects from meta-analyses, and policy, food subsidy, and healthcare costs.

Results:
From a societal perspective, all 3 scenarios were cost-savings at 5, 10, 20 y and lifetime (
Table
). At 5 y, a F&V subsidy would prevent 32,218 CVD events, gain 18,072 QALYs, and save $1.04B ($6.05B lifetime). Corresponding values for a F&V subsidy + SSB restriction were 63,898, 45,772, and $4.47B ($38.83B); and for a broader incentive/disincentive framework that preserved choice, 65,078, 26,663, and $3.98B ($29.90B). Government affordability varied by program duration and by whether subsidy costs for SNAP adults or all SNAP participants were included. Scenario 3 was generally most cost-effective or -saving, followed by scenario 2 and then scenario 1; all were cost-effective over a lifetime from a government affordability perspective.

Conclusions:
Financial incentives/disincentives through SNAP could generate substantial health benefits and be cost-effective or cost savings.
Abstract 023: Left Ventricular Hypertrophy and Elevated Biomarkers of Chronic Myocardial Injury May Identify African Americans With a Very High Risk for Heart Failure Development: Findings From The Jackson Heart Study
Authors: PANDEY Ambarish , Keshvani Neil , Ayers Colby , Correa Adolfo , Drazner Mark , Rodriguez Carlos , Hall Michael , Mentz Robert , de Lemos James , Berry Jarett
Published: July 2021

Introduction:
African Americans (AA) have a disproportionate greater burden of risk factors and higher risk of HF than Whites. However, the factors underlying the transition from at-risk to clinical HF in AA is not well understood. We aimed to examine the independent and joint effects of subclinical myocardial injury, as measured by highly sensitive assays for cardiac troponin (hs-TnI) and left ventricular hypertrophy (LVH), on risk of HF in AA.

Methods:
Participants from the Jackson Heart Study, a prospective study of AA adults, without prevalent HF at baseline (2000-2004) were stratified into categories based on elevation in hs-cTnI (>6 ng/L) and presence of LVH (LV mass > 96 g/m
2
in women and > 116 g/m
2
in men). The risk of incident HF across different LVH and hs-cTnI groups was assessed using adjusted Cox models.

Results:
We included 3,796 participants (54 y, 64% women, 17.2% with elevated hs-TnI & 6.1% with LVH) with median follow up of 9.8 y and 285 incident HF events. In adjusted analyses, LVH and higher hs-TnI at baseline were independently associated with risk of HF [HR (95% CI): LVH (vs. no LVH) = 2.2(1.6 - 2.9); Log hs-cTnI (per unit higher)=1.6(1.5 - 1.8)]. A significant interaction was observed between LVH and hs-TnI for the risk of HF (p-int < 0.0001) with the highest risk among individuals with both LVH and elevated hs-TnI [43% incidence, HR (95% CI): 5.7(3.9 - 8.2)]. In contrast, LVH in absence of hs-TnI elevation was not associated with HF risk [
Figure
]. Among 2,367 participants with repeat assessment of hs-TnI at 5 year follow-up, increase in hs-TnI levels on follow-up was also associated with significantly higher risk of HF [HR (95% CI) per 1 unit increase = 1.03 (1.02 - 1.06)]

Conclusions:
The combination of LVH and elevated hs-TnI levels identifies a malignant preclinical HF phenotype in AAs with a remarkably high absolute risk of HF over a 10-year f/u period. Longitudinal increase in hs-TnI levels is also associated with significant risk of HF. Targeting these high-risk subsets may be an important strategy to mitigate HF risk in blacks.
Abstract 024: Plasma Free Fatty Acids and Risk of Dementia: The Cardiovascular Health Study
Authors: Jensen Majken K , Buzkova Petra , Fitzpatrick Annette L , Longstreth W. T. , Kuller Lewis H , Lopez Oscar L , Siscovick David S , Kizer Jorge R , Ix Joachim H , Djoussé Luc , Mukamal Kenneth J
Published: July 2021

Background:
Plasma free fatty acids (FFAs) are a byproduct of lipolysis largely derived from adipose tissue. High plasma FFA levels have toxic effects on a variety of organs central to cardiometabolic disease. Whether FFAs associates with cognitive decline or dementia remains unknown.

Objective:
To assess the association of plasma FFAs with risk of cognitive decline and dementia.

Methods:
Plasma FFAs were measured in participant samples from the 1992-1993 study visit of the Cardiovascular Health Study (CHS) (mean age 74 yrs; 59% female; 14% African American [AA]; 24% APOE4 carriers). A total of 3,242 non-demented participants were followed with adjudication for dementia through 1998-1999 (n=456 cases). In addition, cognitive decline was assessed annually among all CHS participants using the 100-point modified Mini-Mental State examination (3MSE; n=4,417) and the Digital Symbol Substitution Test (DSST; n=4,254).

Results:
Higher plasma FFAs levels were positively associated with risk of dementia
(Figure:
Log-rank p-value=0.04). In Cox regression analysis adjusted for demographics, FFAs remained associated with risk of dementia (HR per SD [0.20 mEq/L] =1.10; 95% CI, 1.00-1.22). In fully adjusted models that included lifestyle factors, medical history, C-reactive protein, LDL-C, HDL-C, and 3MSE at baseline, the hazard ratio per SD was 1.13 (1.01-1.26), with a particularly strong association observed among AA participants (HR=1.49 [1.10-2.01], p interaction=0.08). FFA levels did not differ by APOE genotype, and adjustment for genotype did not influence results. FFA levels from the baseline visit were also associated with a decline in both cognitive assessments over 6 years of follow-up, with significant time x FFA interactions (p=0.04 for 3MSE and p=0.002 for DSST). We observed no interactions with APOE genotype or race for cognitive outcomes.

Conclusions:
In non-demented older men and women, higher plasma FFA levels are associated with faster cognitive decline and higher risk of dementia over the subsequent years.
Abstract 026: Eicosapentaenoic Acid is a Strong Predictor of Risk for Heart Failure in the Multi-ethnic Study of Atherosclerosis
Authors: Block Robert C , Liu Linxi , Tsai Michael Y , O'Connell Timothy D , Shearer Gregory C
Published: July 2021

Introduction:
In animal models of afterload stress, eicosapentaenoic acid (EPA) prevents interstitial myocardial fibrosis and preserves diastolic dysfunction.

Hypothesis:
We hypothesized that EPA is similarly protective in humans.

Methods:
In the Multi-Ethnic Study of Atherosclerosis, we tested for an effect of plasma phospholipid EPA percent of total fatty acids on primary heart failure incidence across heart failure types including, heart failure with reduced ejection fraction (HFrEF; <45% EF), and with preserved ejection fraction (HFpEF) using Cox proportional hazards modeling in 6566 subjects. Results are mean [95% CI].

Results:
A total of 6566 subjects had measured baseline EPA, including 1797 black, 794 Chinese, 1444 Hispanic, and 2531 white participants; 52% were female. Over a median follow-up of 13.0 years, 293 heart failure events occurred in subjects with measured EPA: 129 had HFrEF, 110 had HFpEF, and the remaining 54 had unknown ejection fraction status. Mean EPA in HF-free subjects was 0.77% (0.76 - 0.79), and was lower in heart failure subjects 0.70% (0.65 - 0.74), p=0.002. EPA was associated with lower incidence of HF, having a hazard ratio of 0.73 (0.60 - 0.89) per unit change in percentage of total fatty acids, p=0.001. Adjusting for age, sex, race, BMI, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, and albuminuria did not change this relationship. Sensitivity analysis showed no dependence on heart failure type. Adjusting for other fatty acids with clustering did not change hazards. In animals, >2.5% EPA is required for prevention of HF, between 2.5% and 1% is marginal, and <1% EPA is insufficient. Most subjects had insufficient EPA levels (n=4794), fewer had marginal levels (n=1471), and fewer still had sufficient levels (n=301). Subjects with sufficient EPA levels were at 0.40 (0.15 - 0.81) fold risk compared to insufficient EPA (p=0.008).

Conclusion:
High abundance of EPA is robustly associated with reduced risk for heart failure, independent of established risk factors and regardless of ejection fraction status.
Abstract 029: Age-Related Blood Pressure Changes at the Incipient Stages of Westernization in Yanomami and Yekwana Tribes
Authors: Mueller Noel T , Noya-Alarcon Oscar , Contreras Monica , Appel Lawrence J , Dominguez-Bello Maria Gloria
Published: July 2021

Introduction:
Studies of isolated hunter-gatherers have found little evidence of the age-related rise in blood pressure (BP) that is common to Western societies, but none of these studies have included children or, for comparison, neighboring tribes exposed to Western culture. We tested the hypothesis that BP does not rise with age in isolated, hunter-gatherer Yanomami, and the age-BP slope is greater in neighboring Yekwana tribes that have some Western exposure.

Methods:
In the Upper Caura basin, a remote area of the Venezuelan Amazon, we sampled 438 participants from 5 isolated Yanomami-Sanema villages, accessible only by foot or canoe, and 3 Yekwana villages, 1 of which had a grass landing strip for small-engine planes, allowing for delivery of medicine and aspects of Western lifestyle, including salt. Trained researchers measured ausculatory sitting BP in triplicate per standard protocols, and height and weight to determine BMI (kg/m
2
). We used ANCOVA to compare the age-BP slope between the Yanomami and Yekwana.

Results:
154 participants (83 Yekwana; 71 Yanomami) ages 2-60 y (53% female) had data on age and sitting systolic BP (SBP). Age-SBP slopes were significantly different (p=0.02): in Yekwana, a 1-y age increment was associated with a 0.25±0.08 mmHg (p=0.003) increase in SBP (
Figure
), whereas in Yanomami age was not associated with SBP (1-y increment: 0.00±0.07mmHg; p=0.98). These results indicate that at age 10 y, mean sitting SBP was, on average, 5.8 mmHg lower for Yanomami compared to Yekwana, and that the average difference increased to 15.9 mmHg by age 50 y. BP differences between Yanomami and Yekwana remained after control for BMI.

Conclusion:
In isolated Yanomami with hunter-gatherer-grower lifestyles, BP does not increase with age over ages 2 to 60 y. Yet, among the Yekwana—the closest geographic neighbors of the Yanomami in whom Westernization is at the incipient stages—age is positively associated with BP, suggesting that the rise in BP with age may result in part from cumulative exposure to Western lifestyle.
Abstract 033: Associations of Smoke-Free Policies With Blood Pressure Changes in the Coronary Artery Risk Development in Young Adults Study
Authors: Mayne Stephanie , Schreiner Pamela , Widome Rachel , Jacobs David , Gordon-Larsen Penny , Kershaw Kiarri
Published: July 2021

Introduction:
Laws banning smoking in indoor public places have been associated with reductions in second-hand smoke exposure and cardiovascular disease among non-smokers. Second-hand smoke exposure has been associated with hypertension in prior studies. However, it is unknown whether smoke-free policies are associated with changes in blood pressure.

Hypothesis:
We tested the hypothesis that living in an area with a smoke-free policy banning smoking in restaurants, bars, and/or other workplaces is associated with reductions in systolic and diastolic blood pressure among non-smokers.

Methods:
Longitudinal data from 2,896 non-smoking participants of the Coronary Artery Risk Development in Young Adults (CARDIA) Study (aged 18-30 at enrollment, 1985-2011, 14,193 person-exam-years) were linked to state, county, and local 100% smoke-free policies in bars, restaurants, and/or non-hospitality workplaces based on participants’ census tract of residence at each exam. Fixed-effects linear regression estimated associations of each type of smoke-free policy (restaurant, bar, workplace) with within-person changes in systolic and diastolic blood pressure (SBP and DBP). Models adjusted for time-varying covariates: exam year (categorical), socio-demographic (education, income, marital status), health-related (body mass index, total physical activity, alcohol use), and policy (state cigarette tax, self-reported ban on smoking in their workplace) covariates, and interactions of baseline covariates (age, sex, race, field center) with exam year to account for differences in blood pressure patterns that were associated with these characteristics (p<0.05 for all interactions). Blood pressure values were adjusted to reflect antihypertensive medication use (+10 mmHg for SBP, +5 mmHg for DBP for those on medication).

Results:
At baseline, mean SBP was 110.5 mmHg and mean DBP was 69.3 mmHg. By year 25, a majority of participants were exposed to smoke-free policies in restaurants (1,759 of 2,264, 78%), bars (1,536 of 2,264, 68%), and other workplaces (1,518 of 2,264, 67%). Smoke-free policies were associated with within-person reductions in SBP and DBP in fully adjusted models (expressed as average change between exams in mmHg). Mean reductions in SBP were -0.77 (95% CI: -1.51, -0.02) for restaurant policies, -0.73 (95% CI: -1.54, 0.08) for bar policies, and -0.79 (95% CI: -1.51, -0.08) for workplace policies. Mean reductions in DBP were -0.67 (95% CI: -1.27, -0.06) for restaurant policies, -0.54 (95% CI: -1.20, 0.11) for bar policies, and -0.86 (95% CI: -1.44, -0.28) for workplace policies.

Conclusions:
Smoke-free policies in restaurants and other workplace are associated with within-person reductions in systolic and diastolic blood pressure among non-smokers. These results suggest an additional health benefit of these policies beyond those previously described in the literature.
Abstract 037: Cost-effectiveness of Financial Incentives for Improving Diet Through Medicare and Medicaid
Authors: Lee Yujin , Mozaffarian Dariush , Huang Yue , Liu Junxiu , Sy Stephen , Wilde Parke E , Abrahams-Gessel Shafika , Jardim Thiago V , Gaziano Thomas A , Micha Renata
Published: July 2021

Background:
While economic incentives through health insurance are being considered to promote healthy behaviors, little is known about health or financial impacts of incentivizing diet, a leading risk factor for CVD. We estimated health and economic impacts of programs to incentivize healthful foods through Medicare and Medicaid over a 5, 10, and 20 y horizon.

Methods:
A validated microsimulation model, CVD PREDICT, was used to estimate reductions in CVD events, gains in quality-adjusted life-years (QALYs), costs, and cost-effectiveness of two policy scenarios within Medicare and Medicaid: (1) 20% subsidy on fruits and vegetables (F&V), and (2) 20% subsidy on broader healthful foods including F&V, whole grains, nuts/seeds, seafood and plant-based oils. Model inputs included national demographic and dietary data from NHANES 2009-2014, policy effects from pricing meta-analyses, diet-disease effects from meta-analyses, and policy costs including program and healthcare costs, inflated to constant 2017 US dollars and discounted at 3% annually. Productivity gains were conservatively excluded.

Results:
Both incentive programs were cost-effective from a healthcare (government affordability) perspective (
Table
). Over 20 y, a 20% F&V subsidy could prevent 1.24M CVD events; while a broader 20% healthful food subsidy could prevent 1.91M CVD events. Incremental cost-effectiveness ratios for the F&V program ranged from $19,773/QALY for dual eligible to $26,862/QALY for Medicaid beneficiaries; and for the broader healthful food program, from $9,020/QALY for dual eligible to $13,484/QALY for Medicare beneficiaries. Findings were robust to a range of sensitivity analyses; within Medicare, the incentive program was more cost-effective among individuals with lower income. These incentive programs were also cost-effective at 5 and 10 y (not shown).

Conclusions:
Economic incentives for healthier foods through either Medicare or Medicaid could generate substantial health gains and healthcare cost savings.
Abstract 038: 30-year Risk of Cardiovascular Disease in Adolescents With Severe Obesity: Benefit of Bariatric Surgery (Teen-LABS)
Authors: Ryder Justin R , Xu Peixin , Xie Changchun , Jenkins Todd M , Inge Thomas H , Kelly Aaron S , Urbina Elaine M
Published: July 2021

Severe obesity in youth is associated with accentuated risks of chronic health problems. However, quantifying risk of cardiovascular disease (CVD) events later in life is challenged by long latent periods between risk factor development and overt disease outcomes. A 30-year CVD event risk score has been developed in the Framingham Offspring cohort to address this problem. The 30-year CVD event risks were estimated for adolescents with severe obesity prior to and up to 5 years after undergoing bariatric surgery. We hypothesized that adolescents with severe obesity would be at high risk for full CVD events within 30-years and that bariatric surgery would reduce that risk. Adolescents (n=215; mean age pre-op = 17 years; mean body mass index (BMI) = 53 kg/m
2
) from the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) were used in this analysis. Data collected preoperatively and annually to 5 years were analyzed. A 30-year composite risk score (CVD event risk) was examined which included the following hard endpoints: coronary death, myocardial infarction, and stroke (fatal and nonfatal), coronary insufficiency, angina pectoralis, transient ischemic attack, intermittent claudication, and congestive heart failure. CVD event risk score requires the following risk factors for calculation: Sex, age, systolic blood pressure, antihypertensive treatment, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, and BMI. Data are presented as mean (SD) with differences between time-points examined using linear mixed-models. Preoperatively, the likelihood of CVD events was 7.9 (6.7)%. Preoperatively, 52.6% of the cohort presented with >5% risk of CVD events, 22.3% with >10% risk of event, and 10.7% with >15% risk of event. At 1-year post-surgery a significant reduction in CVD events (7.9 [6.7]% to 4.0 [3.4]%, p<0.0001) was estimated. A reduction in proportion with >5% (52.6% to 22.1%), >10% (22.3% to 4.4%), and >15% (10.7% to 1.7%) risk of CVD events was observed. These predicted benefits for full CVD events were sustained at 2 years (4.0 [2.9]%), 3 years (4.2 [3.8]%), 4 years (4.3 [3.1]%), and 5 years (4.8 [3.8]%) post-surgery, with similar >5%, >10%, and >15% risks noted (p<0.0001 for all years versus baseline). These data suggest that prior to bariatric surgery, the risk of CVD event within 30-years is pronounced. However, following bariatric surgery, risk of hard endpoints is substantially reduced for up to 5 years following surgery.
Abstract 039: Adherence to a Healthy Lifestyle in Relation to Cardiovascular Disease Incidence and Mortality Among Adults With Type 2 Diabetes
Authors: Liu Gang , Li Yanping , Hu Yang , Zong Geng , Li Shanshan , Rimm Eric B , Hu Frank B , Manson JoAnn E , Rexrode Kathryn M , Shin Hyun Joon , Sun Qi
Published: July 2021

Objective:
To examine the associations of individual and combined low-risk lifestyle practices, including non-smoking, engaging in moderate to vigorous intensity physical activity (≥150 min/week), drinking alcohol in moderation (5-15 g/day for women and 5-30 g/day for men), and eating a high quality diet (top two fifths of Alternative Healthy Eating Index), with the risk of subsequent cardiovascular events among adults with incident diabetes.

Methods:
The prospective study included 11,527 participants with diabetes diagnosed during follow-up (8,970 women from the Nurses’ Health Study and 2,557 men from the Health Professionals Follow-Up Study), who were free of cardiovascular disease (CVD) and cancer at the time of diabetes diagnosis. Diet and lifestyle factors after diabetes diagnosis were repeatedly assessed every 2-4 years. Multivariable Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of total CVD, coronary heart disease (CHD), and stroke incidence, and CVD mortality.

Results:
There were 2,311 incident CVD cases (including 498 stroke cases) and 858 CVD deaths during an average of 13.3 years of follow-up. After multivariate adjustment including medication use, the individual low-risk lifestyle factors after diabetes diagnosis were each significantly associated with a lower risk of CVD incidence and mortality. The multivariate-adjusted HR (95% CI) for participants with three or more low-risk lifestyle factors compared with zero was 0.48 (0.40-0.59) for total CVD incidence, 0.53 (0.42-0.66) for CHD incidence, 0.33 (0.21-0.51) for stroke incidence, and 0.32 (0.22-0.47) for CVD mortality (all
P
trend<0.001). The population-attributable-risk for poor adherence to low-risk lifestyle was 42.6% (26.7%-55.1%) for CVD mortality. In addition, greater improvements in lifestyle factors from pre- to post-diabetes diagnosis were also significantly associated with a lower risk of CVD incidence and mortality. For per one number increment in low-risk lifestyle factors, there was a 16% reduced risk of incident total CVD, a 12% reduced risk of CHD, a 21% reduced risk of stroke, and a 30% reduced risk of CVD mortality (all
P
<0.001). Similar results were observed when analyses were stratified by diabetes duration, sex/cohort, body mass index at diabetes diagnosis, smoking status, and lifestyle factors before diabetes diagnosis.

Conclusions:
Greater adherence to an overall healthy lifestyle is associated with a substantially lower risk of CVD incidence and mortality among adults with type 2 diabetes. These findings further support the tremendous benefits of adopting a healthy lifestyle in reducing the subsequent burden of cardiovascular complications in diabetic patients.
Abstract 041: Smoking Cessation and Subsequent Risk of Type 2 Diabetes in Three Large Prospective Cohort Studies of Americans
Authors: Hu Yang , Zong Geng , Liu Gang , Wang Molin , Pan An , Willett Walter C , Manson JoAnn E , Hu Frank B , Sun Qi
Published: July 2021

Background:
The inter-relationships between smoking cessation, subsequent weight change, and type 2 diabetes (T2D) risk remain to be characterized.

Methods:
We prospectively followed 153,123 U.S. men and women from the Health Professionals Follow-up Study (1988-2012), Nurses’ Health Study (NHS, 1984-2012), and NHS II (1991-2013). Participants were followed biennially for smoking status, weight change, and diabetes risk. Self-reported T2D was confirmed using a validated supplementary questionnaire.

Results:
Compared with current smokers, T2D risk among quitters significantly increased and peaked after 5-7 years of quitting, and gradually decreased along extended durations. With a mean quitting duration of 9.9 years, the multivariate-adjusted hazard ratio (HR; 95% confidence intervals [95% CI]) of T2D was 1.26 (1.14, 1.39) for recent quitters (≤6 consecutive years) and1.04 (0.95, 1.14) for longer-term quitters in three cohorts. The T2D risk approached that of never smokers after 30 years of quitting among older nurses. There was, on average, 5.5 kg weight gain within 6 years of smoking cessation whereas 2.2 kg was gained in the same period among current smokers. The weight change significantly modified the association of smoking cessation with T2D risk (
p
for interaction = 0.04): for quitters without weight gain (≤0 kg), 0-5 kg weight gain, and ≥5 kg weight gain within 6 years of smoking cessation, the HRs (95% CIs) of T2D were 0.92(0.73, 1.14), 1.27(1.10, 1.46) and 1.47(1.29, 1.67), respectively, compared with current smokers. We estimated that for quitters who did not gain weight within the first 6 years, their T2D risk approached that of never smokers after 5 years of quitting. Weight change within 6 years of quitting explained 22% (14.8%, 30.1%) of the elevated risk of T2D.

Conclusions:
Weight gain after quitting smoking may significantly attenuate the benefits of smoking cessation by increasing T2D risk. Our findings underscore the importance of weight control after quitting in maximizing the benefits of smoking cessation.
Abstract 046: Cardiorespiratory Fitness, Physical Activity, and Television Viewing Before Pregnancy and Risk of Gestational Diabetes: A Longitudinal Analysis From the CARDIA Study
Authors: Whitaker Kara M , Ingram Katherine H , Appiah Duke , Nicholson Wanda K , Bennett Wendy L , Lewis Cora E , Reis Jared P , Schreiner Pamela J , Gunderson Erica P
Published: July 2021

Introduction:
Low levels of cardiorespiratory fitness, moderate-to-vigorous-intensity physical activity (MVPA), and excess sedentary behaviors are associated with a greater risk of type 2 diabetes. Less is known about the role of fitness, MVPA, and sedentary behaviors before pregnancy with subsequent development of gestational diabetes mellitus (GDM), a strong risk factor for future diabetes and cardiovascular disease.

Objective:
To assess the associations of pre-pregnancy fitness, MVPA, and time spent watching television (a surrogate for sedentary behavior) with risk of GDM.

Methods:
Participants were 1,333 women enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study who did not have diabetes at baseline (1985-86) or before post-baseline births. Baseline fitness was estimated using a graded symptom-limited maximal treadmill test and expressed in metabolic equivalent units (METS). Baseline MVPA (exercise units/day) was measured using the CARDIA physical activity history questionnaire, and television viewing (hours/day) was assessed by self-report in 1990-91. Logistic regression analysis was used to calculate odds ratios and 95% confidence intervals, adjusting for study center, baseline age, race, parity, education, family history of diabetes, smoking, alcohol, dietary fat, pre-pregnancy body mass index, HOMA-IR, HDL-cholesterol, and time from baseline to delivery.

Results:
Over 25 years of follow up, 164 women developed GDM. As shown in the
Table
, the odds of developing GDM were 22% lower for each 1 standard deviation increment in baseline fitness after adjustment (2.3 METS; OR 0.78, 95% CI: 0.65, 0.95, p=0.013). MVPA and television viewing were not statistically significantly associated with developing GDM.

Conclusions:
This is one of the first studies to report an inverse association between objectively measured pre-pregnancy fitness and subsequent development of GDM. Improved pre-conception fitness may benefit women at risk for GDM.
Abstract 054: Diet Beverage Intake is Positively Associated With Incident Coronary Heart Disease in People With Type 2 Diabetes
Authors: Odegaard Andrew O , Steffen Lyn M , Jacobs David R , Tucker Katherine L , Mukamal Kenneth J , Pereira Mark A
Published: July 2021

Introduction:
Diet beverages are calorie free beverages sweetened with non-nutritive sweeteners. People with diabetes are the highest per-capita consumers of diet beverages, tending to consume them as a replacement for dietary sources of sugar, especially in place of sugar sweetened beverages. This behavior is endorsed by dietetic and scientific organizations and diet beverages are marketed synonymously with better health, weight loss, and thus, are considered advantageous for diabetes control. The underlying public health concern is the lack of data to support or refute this concept.

Hypothesis:
Higher diet beverage intake is positively associated with incident Coronary Heart Disease (CHD)

Methods:
We pooled the data sets of the Atherosclerosis Risk in Communities (ARIC) study (1987-2014), Cardiovascular Health Study (CHS) (1989-2014), Framingham Offspring Study (FOS) (1995-2014), Jackson Heart Study (JHS) (2000-2012), and Multi-Ethnic Study of Atherosclerosis (MESA (2000-2013) to conduct a prospective examination of the association of diet beverage intake with the incidence of CHD among participants with clinically ascertained type 2 diabetes (T2D) without prevalent CHD and with valid dietary data (N=3,947). We carried out a 2-step meta-analysis using individual level, cohort-specific Cox regression analyses with identical adjustment for demographic, lifestyle, overall diet quality and clinical risk factors to generate effect estimates that were pooled together using fixed and random effects meta-analysis.

Results:
1,046 participants developed adjudicated CHD during follow-up. There was a positive, graded association between diet beverage intake and risk of incident CHD (Table). Results were consistent by sex, race and age.

Conclusions:
Diet beverage intake is associated with increased risk of developing CHD in a population with T2D. These results suggest the need to further evaluate dietary recommendations related to diet beverages and consider their role in this high risk population.
Abstract 055: Adherence to a DASH (Dietary Approaches to Stop Hypertension) Dietary Pattern and Risk of Abdominal Aortic Aneurysm
Authors: Haring Bernhard , Selvin Elizabeth , He Xintong , Coresh Josef , Steffen Lyn M , Folsom Aaron R , Tang Weihong , Rebholz Casey M
Published: July 2021

Background:
Abdominal aortic aneurysms (AAAs) develop in up to 8% of men and 6% of women over a lifetime. Although they typically remain asymptomatic, rupture of an AAA carries high mortality. Smoking and hypertension have been identified as modifiable risk factors for developing an AAA. The role of diet, however, is yet unclear.

Objective:
To evaluate the relationship between adherence to a DASH-style dietary pattern and the risk of incident AAA in a large, community-based cohort of middle-aged adults.

Methods:
Dietary intake was assessed via a 66-item FFQ at two visits in 14,322 participants enrolled in the ARIC study (Atherosclerosis Risk in Communities) without clinical AAA, incomplete dietary/covariate information or extreme energy intake at baseline. Adherence to a DASH-style dietary pattern was assessed using a previously developed dietary scoring index. Participants were followed for incident clinical AAAs using hospital discharge diagnoses, Medicare outpatient diagnoses, or death certificates through December 31, 2011. Cox proportional hazards models with covariate adjustment were used to estimate hazard ratios (HR) with 95% confidence intervals (CIs).

Results:
During a median follow-up of 23 years, there were 539 incident AAA cases. Participants with a DASH diet score in the highest quintile had a 39% lower risk to develop AAAs than those in the lowest score quintile (HRQ5 vs. Q1: 0.61; 95% CI 0.45, 0.84; ptrend =0.004) after adjusting for sociodemographics, total caloric intake, smoking, physical activity, BMI, abdominal obesity, diabetes, hypertension, hypercholesterolemia and cardiovascular disease. Higher intake of fruits, vegetables, whole grains, low-fat dairy, and nuts and legumes was related to a decreased risk for AAA.

Conclusions:
Greater adherence to a DASH-style dietary pattern was found to be associated with lower incidence of AAA. Higher consumption of fruits, vegetables, whole grains, low-fat dairy as well as nuts and legumes may help to decrease the burden of AAA in U.S. adults.
Abstract MP02: N-Terminal Pro-B-type Natriuretic Peptide and Risk of Stroke in Those With and Without Cerebrovascular Disease: The REGARDS Cohort
Authors: Landry Kara , Judd Suzanne , Kleindorfer Dawn , Howard George , Howard Virginia , Zakai Neil , Cushman Mary
Published: July 2021

Background:
N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), a commonly used marker of cardiac function, is associated with presence of stroke symptoms and is a strong risk factor for future atrial fibrillation, stroke and mortality. Little data are available on the association between NT-pro-BNP levels and stroke recurrence.

Objective:
We studied the relationship between NT-proBNP with the risk of future ischemic stroke across a spectrum of pre-existing cerebrovascular conditions, ranging from history of stroke symptoms, to prior transient ischemic attack (TIA), to prior stroke.

Methods:
The Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort enrolled 30 239 black and white Americans age 45 years and older in 2003-14. Among a case-cohort study sample including 1109 stroke cases and a 4311-person cohort random sample, we calculated hazard ratios of future ischemic stroke by baseline NT-proBNP stratified by presence of prior cerebrovascular conditions.

Results:
In the cohort sample, there were 3056 participants without any history of cerebrovascular disease, 738 with prior stroke symptoms, 196 with history of TIA and 338 with history of prior stroke. In a fully adjusted model, elevated NT-proBNP was associated with risk of stroke in participants without a pre-existing cerebrovascular condition (HR 2.32, 95% CI 1.84, 2.94), and in participants with a history of stroke symptoms (HR 1.67 95% CI 1.01, 2.78) or TIA (HR 2.66, 95% CI 1.00, 7.04), but not among those with prior stroke (HR 1.26, 95% CI 0.71, 2.21).

Conclusions:
These findings further support the potential for NT-proBNP testing to identify patients who are at highest risk for future stroke, although not in those with prior stroke.
Abstract MP04: Sex Hormones and 10 Year Progression of Coronary Artery Calcium Among Post-Menopausal Women in the Multi-Ethnic Study of Atherosclerosis
Authors: Subramanya Vinita , Zhao Di , Ouyang Pamela , Ying Wendy , Vaidya Dhananjay , Guallar Eliseo , Ndumele Chiadi E , Heckbert Susan R , Budoff Matthew J , Post Wendy S , Michos Erin D
Published: July 2021

Background:
Cardiovascular disease (CVD) is the leading cause of death in women. Sex differences in risk factors, prevalence and mortality suggest the involvement of sex hormones in disease processes. Coronary artery calcium (CAC) is a marker of subclinical atherosclerosis and its progression. CAC is prognostic of CVD risk, independent of traditional risk factors, even among low-risk women. We hypothesized that a more androgenic hormone pattern will predict CAC progression over 10 years in post-menopausal women.

Methods:
We studied 2759 post-menopausal women, aged 45-84 years, participating in MESA who underwent serum sex hormone measurement and a cardiac CT scan for CAC at baseline (2000-2002). Among these, 2427 women had up to 3 follow-up cardiac CT scans at subsequent visits spanning 10 years. CAC was assessed by Agatson units. CAC and sex hormones were log-transformed for analysis. Using multivariable-adjusted Poisson and linear mixed effects models, we tested the longitudinal associations of testosterone (T), free T, dehydroepiandrosterone (DHEA), estradiol (E2), and sex hormone binding globulin (SHBG) with prevalent CAC and progression of CAC over 10 years.

Results:
At baseline, average age was 65 years, 46% had prevalent CAC and 32% were using hormone therapy (HT). Cross-sectionally, there were no associations between sex hormones and prevalent CAC. After adjustment for demographics, lifestyle factors and use of HT, higher levels of free T and lower levels of SHBG were associated with an increase in CAC progression over 10 years (
Table,
Model 2). These associations remained statistically significant after adjusting for potential mediating cardiovascular risk factors (Model 3) and in sensitivity analyses excluding women on HT.

Conclusion:
A more androgenic hormone profile of higher free T and lower SHBG is associated with a greater CAC progression over 10 years in post-menopausal women. Sex hormone levels may help identify women at increased CVD risk who may benefit from other risk reduction strategies.
Abstract MP09: Geographic Disparities in Rates of End-Stage Renal Disease and Organ Supply in Gulf States Compared to Non-Gulf States
Authors: Reed Rhiannon D , Shelton Brittany A , McWilliams Deanna M , Mustian Margaux N , MacLennan Paul A , Sawinski Deirdre , Locke Jayme E
Published: July 2021

Background:
Organ Procurement Organizations are responsible for procuring and allocating organs for transplantation from deceased donors in Donation Service Areas (DSAs). The Final Rule prohibits geographic disparities in access to organs, but the current kidney allocation system does not account for potential supply variations based on disease burden and other population characteristics within DSAs. As such, regions with traditionally high rates of comorbid disease, such as the Gulf States region, may be disadvantaged if local supply is limited.

Methods:
Using data from the 2016 Robert Wood Johnson Foundation County Health Rankings, the Scientific Registry of Transplant Recipients public reports, and the United States Renal Data System, we compared comorbid disease prevalence, rates of end-stage renal disease (ESRD), and expected organ donation rates by Gulf States location.

Results:
Prevalence of African American ethnicity, diabetes, fair/poor self-rated health, physical inactivity, food insecurity, and uninsurance were higher among DSAs in the Gulf States region vs. non-Gulf States (Table). Conversely, the prevalence of non-Hispanic White ethnicity, college education, and median household income were higher among non-Gulf States. The rate of ESRD varied by DSA, ranging from < 162 cases per 100,000 to > 225 cases per 100,000 (Figure). Median rate of ESRD was 214.4 per 100,000 among DSAs in the Gulf States, vs. 187.1 per 100,000 in the non-Gulf States (p=0.003). Expected rate of organ donation per 100 eligible deaths was 71.1 in Gulf States and 75.4 in non-Gulf States (p=0.01).

Conclusion:
Higher rates of ESRD were observed in the Gulf States region, suggesting a greater need for organs than non-Gulf States. However, fewer donors were estimated in Gulf States, likely due to high comorbid disease burden, compared to non-Gulf States. These data suggest the need to examine allocation policy to prevent geographic disparities in access to deceased donor transplantation.
Abstract MP17: Galectin-3 and Subsequent Risk of Lower-extremity Peripheral Artery Disease: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Matsushita Kunihiro , Yang Chao , Ballew Shoshana H , McEvoy John W , Salameh Maya , Aguilar David , Hoogeveen Ron C , Nambi Vigay , Selvin Elizabeth , Folsom Aaron R , Heiss Gerardo , Coresh Josef , Ballantyne Christie M
Published: July 2021

Background:
Galectin-3 is involved in the regulation of inflammation and the formation of fibrosis and has been liked to atherosclerosis. However, there are no studies investigating prospective associations of galectin-3 with incidence of lower-extremity peripheral artery disease (PAD).

Methods:
Among 9,827 ARIC participants without a history of PAD, we investigated whether galectin-3 (measured at visit 4 [1996-98]) was associated with incident clinical PAD through 2013, defined as hospitalizations with PAD diagnosis or leg revascularization. We defined PAD cases with rest pain or tissue loss as critical limb ischemia (CLI). We constructed Cox models with galectin-3 modeled categorically (quartiles) and continuously (log transformed).

Results:
During a median follow-up of 15.8 years, 287 participants developed PAD (105 incident CLI cases). In demographically adjusted models, galectin-3 demonstrated a dose-response association with incident PAD: hazard ratios (HRs) 2.55 (95% CI 1.80-3.61) and 1.69 (1.18-2.41) for the highest and second highest quartiles, as compared to the lowest quartile (Table; Model 1). Additional adjustment for traditional cardiovascular risk factors attenuated the associations, although the highest quartile remained borderline significant (HR 1.44 [0.99-2.07], p=0.051, Table: Model 2) and galectin-3 as a continuous variable remained significant (1.15 [1.02-1.29]). Similar results were observed for the association of galectin-3 with CLI.

Conclusions:
Galectin-3 was modestly associated with future risk of clinical PAD events in a community-based cohort, supporting the involvement of inflammation and fibrosis in the development of clinical PAD.