bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P303: Time-Varying Healthy Lifestyle Profile and All-Cause Mortality Among the Oldest-Old in China
Authors: He Zhengting , Zou Siyu , Guo Qi , Lee Beomhyeok , Zhang Xian , Li Yaxi , Hu Rundong , Ding Xiong , Li Chaoyun , Guo Xiaoyang , Yan Lijing L
Published: March 2023

Background:
Association between an individual modifiable lifestyle with mortality is well established. However, influences of combined lifestyles on mortality risks remain inconclusive among adults aged 80 years or older (“oldest-old”). We investigated the association of time-varying healthy lifestyle profile (HLP) with mortality among Chinese oldest-old adults.

Methods:
We pooled 36,021 oldest-old adults from first seven waves of the Chinese Longitudinal Healthy Longevity Survey (1998-2014), with follow-up to latest wave (2018) (range 0-21.04 years). Lifestyle information was collected at each wave. Nonsmoking, no regular alcohol intake, regular exercise, and simplified healthy eating index of 11-18 were defined as healthy lifestyle. We assigned a score of 1 for healthy and 0 for nonhealthy lifestyle and summed the four scores to a HLP index ranging 0-5 (representing least to most healthy) to reflect joint lifestyle measurements. We used both a continuous time-to-event data set up with study enrollment as time origin (SE model) and a discrete time-to-event data set up with age 80 as time origin. We used Cox proportional hazard model with time-varying covariates and complementary log-log regression to examine hazard ratios (HRs) of mortality, adjusting for demographics, self-reported diseases, activities of daily living, and cognitive function.

Results:
During 110897.40 person-years of follow-up, 25,511 deaths were recorded. Median death age was 5 years older in most versus least healthy group. In SE model with least healthy group as reference, HRs (95% CIs) for mortality were 0.90 (0.86-0.95), 0.83 (0.79-0.87), 0.74 (0.70-0.78), 0.54 (0.49-0.58), respectively for HLP of 1-4 groups (p-trend<0.001) (
Table
). Dose-response relationships were consistent for HRs of mortality over age since 80.

Conclusion:
Healthier lifestyle profiles were associated with significant reductions in all-cause mortality risks among Chinese oldest-old, suggesting the importance of life-long adherence to HLP into advanced old age.
Abstract P306: Life’s Essential 8 is Associated With All-Cause and Cardiovascular Disease Mortality Among Community Dwelling Older Men and Women in the InCHIANTI Study of Aging (1998-2020)
Authors: Sarma Vivek , Jin Yichen , Bandinelli Stefania , Ferrucci Luigi , Tanaka Toshiko , Talegawkar Sameera
Published: March 2023

Introduction:
The population of individuals aged 65 y and older has increased steeply over the past few years. Health factors including obesity, high cholesterol, blood pressure, and blood glucose levels, as well as adverse health behaviors such as smoking, poor diet, insufficient physical activity, and low sleep quality are risk factors for chronic disease development and mortality. Because both health factors and behaviors are critical for reducing the risk of chronic disease and mortality, we examined a score assessing overall cardiovascular health (CVH) based on American Heart Association’s (AHA) Life’s Essential 8, an update of the AHA’s former Life’s Simple 7 metric. This metric may provide a tenable framework for chronic disease management and prevention.

Hypothesis:
We hypothesized that in a cohort of participants aged 65 y and older, higher CVH scores based on Life’s Essential 8, indicating better CVH, at baseline, is inversely associated with risk of all-cause and CVD mortality.

Methods:
Overall cardiovascular health was assessed using 8 health factors and behaviors, scored 0 to 100, among 928 participants (55% female) aged 65 years and older within the InCHIANTI study of aging. Vitality status was ascertained using registry information. For analysis, CVH was modeled as a 1 Standard Deviation (SD) increase in the score. Cox proportional hazards models, adjusted for age and sex, were used to examine the associations between CVH and all-cause and cardiovascular disease mortality over a median follow-up of 14.6 y.

Results:
A 1 SD increase in the overall CVH score was inversely associated with all-cause (hazard ratio [HR] = 0.80, 95% confidence interval [CI] = [0.738, 0.873]) and CVD mortality (HR = 0.73, 95% CI = [0.632, 0.832]).

Conclusion:
Among older adults, overall CVH - assessed through the lens of the AHA's Life's Essential 8 - is associated with a lower risk of all-cause and CVD mortality. This relationship lends credence to the importance of prioritizing health factors and behaviors in preventing chronic disease development and promoting healthier lives among older individuals.
Abstract P311: Lifestyle Factors Substantially Contributed to Urban-Rural Disparity in All-Cause Mortality Among Chinese Adults 65 or Older
Authors: Ding Xiong , Su Kehan , Guo Qi , Xiong Shangzhi , Li Yaxi , Ling Yikai , He Zhengting , Zhang Xian , Yan Lijing L
Published: March 2023

Background:
Studies on whether lifestyle factors could explain urban-rural differences in mortality risks among Chinese adults 65 years or older are limited. We aim to assess whether and to what extent individual-level lifestyle factors contribute to urban-rural disparity in mortality among older Chinese adults.

Methods:
Our study included a total of 37,083 adults 65 years or older residents (8,522 city, 8,022 urban and 20,539 rural) from seven waves of the Chinese Longitudinal Healthy Longevity Survey (1998-2014), with follow-up to the latest wave (2018). Five lifestyle factors were examined: smoking, drinking, physical activity, diet and leisure activities. All-cause mortality was ascertained through death registry and information from next of kin. We conducted multivariable Cox proportional hazard models to examine mortality risks and used two measures to estimate the contributions to urban-rural mortality disparity from lifestyle factors, PERM (percentage excess risk mediated) calculated by the change of hazard ratio of the different models divided by the hazard ratio of the adjusted demographics model and AUC (area under the receiver-operating curve).

Results:
During a median follow-up of 3.24 years, 23,576 death cases were recorded. Report crude differences (death rates by the 3 groups city, town, rural) before adjusting for any vars. After adjusting for demographics, the hazards for town and rural residents were 8.8% and 17.2% higher than city residents, respectively (Table 1, Model 1). Adjustment for leisure activities made the largest difference in explaining the urban-rural disparities (Model 6). Adjustment for all five lifestyle factors explained 36.6% of city-town and 26.1% of city-rural differences (Model 7). AUCs for all models were > 0.7.

Conclusion:
Lifestyle factors, especially leisure activities, physical activities and diet, contributed substantially to the urban-rural disparity in all-cause mortality of adults aged 65 years or older in China.
Abstract P316: Lower Mortality From Ischemic Heart Disease Associated With Attenuation of Autonomic Dysfunction is Related to Reduction of Sensitivity to Pain at the Chest Bone
Authors: Faber Jens , Selmer Christian , Gyntelberg Finn , Kreimer Svend , Karpatschof Benny , Ballegaard Søren , Hjalmarson Aake , Gjedde Albert
Published: March 2023

Introduction:
Autonomic nervous system dysfunction (ANSD) is associated with negative prognosis of ischemic heart disease (IHD) and has been found also to be related to elevated measures of sensitivity to pain from pressure (PPS) at the sternum. Previously, we found that non-pharmacological intervention by peripheral sensory nerve stimulation, monitored by repeated home-based PPS measurements, consistently was associated with lowered PPS measures. Compared to the general Danish population, the intervention reduced the all-cause mortality in two prospective observations, one of 103 patients with IHD followed for 3 years, and one of 73 patients with stroke followed for 4.5 years. Here, we test if we can reproduce lower all-cause mortality associated with lowered PPS measures in a randomized controlled trial (RCT).

Methods:
Of 361 consecutively followed patients with stable IHD, 65% had elevated PPS, suggestive of ANSD. Of these, 213 participated in a randomized controlled trial (RCT) with active (n=106) or passive intervention (n=107). We compared the 5-year all-cause mortality of both groups with two corresponding subsections of approximately 35.000 members of the general population of Denmark, matching patients for gender, age, and observation period with data from Statistics Denmark, and we compared the 5-year mortality of the two RCT groups. In separate analyses, we pooled mortality data from the active group of the RCT with data from two observational studies. We registered the pooled active intervention mortality of 1.168 person-years, compared to approximately 40 million person-years of the pooled general population.

Results:
We observed fewer than three deaths in the active RCT group (exact number and 95% CI not available according to GDRP rules), compared to eight deaths of passive RCT group members (P=0.035). Based on the predicted mortality from the general population of eight deaths in both groups, the result is consistent with significantly reduced mortality of recipients of active intervention (P=0.011). The separate analyses of pooled data from three consecutive studies demonstrated a mean reduction of the 4.2-year all-cause mortality of 50% (P<0.00005).

Conclusions:
The predicted attenuation of ANSD associated with lowering of elevated PPS matched the lower all-cause mortality of patients with IHD.
Abstract P318: Life’s Essential 8 as a Measure of Cardiovascular Health in the Women’s Health Initiative (WHI)
Authors: Wong Eugenia , Jones Sara , Franceschini Nora , Allison Matthew A , Garcia Lorena , Wise Thomas Sherrie , Shadyab Aladdin H , Rosamond Wayne D
Published: March 2023

Introduction:
In 2022, the American Heart Association (AHA) introduced Life’s Essential 8 (LE8) as an updated definition of cardiovascular health (CVH). Sleep health was added to the original Life’s Simple 7 (LS7), and a new scoring system was developed. We evaluated how LE8 characterizes CVH among women in the WHI.

Hypothesis:
We hypothesized that the average LE8 score would be moderate, with only a small group of WHI participants having high CVH.

Methods:
The WHI recruited 161,808 post-menopausal women from 40 clinical centers in 1993-1998. This analysis included 116,514 women without self-reported CVD, with measured height, weight, and blood pressure, and self-reported smoking history, sleep duration, physical activity, diet, diabetes, and cholesterol at baseline. CVH components were scored from 0-100 based on participants’ achievement of each health factor or behavior. Scores were assigned per AHA guidance with some adaptations made based on data availability. Lacking measured values, glucose and lipid scores were calculated based on history and treatment status of diabetes and high cholesterol. Overall LE8 scores were calculated as the unweighted mean of all components. Scores were further categorized into high (80-100), moderate (50-79), or low (0-49), with higher scores indicating positive CVH.

Results:
The average LE8 score among WHI participants at baseline was 71.5 (standard deviation (SD): 12.5; range 20.6-100) (
Figure
). Overall, sleep scores were high (mean: 86.5, SD 19.1). The lowest scores were found in diet (mean: 39.5, SD 31.3) and physical activity (mean: 47.7, SD: 43.5). LE8 classified 28.1% of WHI participants (32,773/116,514) as having high CVH whereas a prior analysis of LS7 found that 17.7% and 6.1% had ideal levels of 5 and 6-7 CVH components, respectively.

Conclusions:
Based on the new LE8 definition, most women had moderate CVH at study baseline, with approximately a quarter having high CVH. Although sleep health was high, scores for other health behaviors demonstrated considerable room for improvement.
Abstract P320: Adverse Childhood Experiences Are Associated With Greater Adiposity in Midlife Women: Findings From the Prospective Project Viva Cohort
Authors: Bornkamp Nicole , Sidote Melissa N , Zhang Mingyu , Nichols Amy , Rifas-Shiman Sheryl L , Hivert Marie-France , Oken Emily
Published: March 2023

Introduction:
The associations of adverse childhood experiences (ACEs) with adiposity are not well characterized in midlife women, a life stage when cardiometabolic risk increases substantially.

Hypothesis:
More reported adverse childhood experiences are associated with greater body mass index (BMI) and waist circumference (WC).

Methods:
At mean (SD) 51.0 (5.0) years, 432 participants in the Project Viva cohort completed questionnaires and research staff measured height and weight (used to derive BMI) and waist circumference. Women self-reported personal history of ACEs (10 possible types in 3 subdomains: abuse, neglect, and household challenges) prior to 18 years old. We used multivariable linear regression to evaluate associations of ACEs with BMI and waist circumference and adjusted for childhood social factors including parental education, US birth, and race/ethnicity.

Results:
Mean (SD) ACE score was 1.7 (1.9), BMI was 27.4 (6.2) kg/m
2
and WC was 91.8 (15.3) cm. In unadjusted models, each additional ACE was associated with higher BMI (β =0.49kg/m
2
, 95% CI: 0.18, 0.80) and greater waist circumference (β =0.94cm, 95% CI: 0.18, 1.71). Adjusting for childhood social factors reduced associations and 95% CIs included the null (BMI: 0.19kg/m
2
, 95% CI: -0.13, 0.51; WC: 0.35cm, 95% CI: -0.45, 1.14). Associations were stronger for ACEs related to abuse and neglect versus household challenges in unadjusted and adjusted models (Figure). Adjusting for childhood social factors attenuated the associations for neglect and household challenges subdomains, but less so for abuse.

Conclusions:
Adverse childhood experiences are associated with greater adiposity measures in midlife women. The differing associations of ACEs subdomains with adiposity indicate that these outcomes may be more strongly related to the type of ACE someone experiences than solely the number of ACEs experienced.
Abstract P328: Higher Intake of Dietary Cholesterol Was Associated With Increased Risk of Myocardial Infarction in the Million Veteran Program
Authors: Sheikh Shamlan , Nguyen Xuan-Mai , Li Yanping , Ivey Kerry L , Gaziano John M , Djousse Luc
Published: March 2023

Background:
Association of dietary cholesterol with coronary artery disease (CAD) remains inconsistent. We examined the relation of dietary cholesterol with incidence of myocardial infarction (MI), among participants of the Million Veteran Program (MVP).

Methods:
The MVP is a nationally representative, prospective cohort study of Veterans which started in 2011 and by 2020 had over 800,000 enrollees and looked at factors, that could be associated to their chronic conditions. Dietary intake was one of these characteristics and was collected by self-reported semi-quantitative food frequency questionnaire. MI cases were identified by Surrogate-Assisted Feature Extraction (SAFE) method which is an algorithm approach combing ICD codes, natural language processing and medical record review labels. All information regarding MI were reviewed by combining the VA Corporate Data Warehouse (VDW), which consist of VA EHR and Medicaid/Medicare database, and National Death index databases.

Results:
Among the 180,156 Veterans with data on dietary cholesterol, mean age was 62 years, 90% men, and 80% White. Mean follow up was 3.5 years. We observed a linear, dose-response, association between dietary cholesterol intake and the risk of MI (
P
for linear trend =0.003) (Figure 1). When adjusting for age and sex every increase of 100 mg/day of dietary cholesterol was associated with a 9% higher risk of MI (RR: 1.07, 95%CI: 1.06-1.12). Participants with a cholesterol intake ≥300 mg/day had a 15% higher risk of MI compared to participants whose cholesterol intake was no more than 300 mg/day (RR: 1.15, 95%CI: 1.06-1.25).

Conclusion:
In our study, increased intakes of dietary cholesterol were associated with a higher risk of MI among US Veterans.
Abstract P329: Eicosanoids and Heart Failure Risk in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Nguyen Ngoc Quynh , Yang Yueh-Ning , Alotaibi Mona , Wu Huaizhu , Hoogeveen Ron C , Ballantyne Christie M , Shah Amil M , Long Tao , Jain Mohit , Cheng Susan , Yu Bing
Published: March 2023

Introduction:
Eicosanoids play an important role in regulating inflammation response, which influences the development of heart failure (HF). However, the association between eicosanoids and the risk of HF remains unclear.

Hypothesis:
We hypothesize that eicosanoid metabolites are associated with incident HF and may improve HF prediction.

Methods:
We measured plasma eicosanoids via liquid chromatography-mass spectrometry among HF-free participants at visit 2 (1990-1992) from the Atherosclerosis Risk in Communities (ARIC) study. The Cox proportional hazard regression was performed to evaluate the relationship between eicosanoids and incident HF controlling for clinical risk factors. The least absolute shrinkage and selection operator was applied to identify a representative subset of eicosanoids towards constructing an eicosanoid risk score (ERS). We further conducted genome-wide association analyses to examine the genetic determinants for HF related eicosanoids in black and white participants respectively.

Results:
During an average of 21 years of follow up, 2,202 (28.0 % blacks, 50.3% women) out of 9,519 participants developed HF. Out of 200 eicosanoids analyzed, six with hazard ratio between 0.89 to 1.10 were found associated with the risk of HF (FDR <0.05) per SD change, namely 11-dehydro-2,3-dinor-TXB2, 5-hydroperoxyicosa-6,8,11,14,17-pentaenoic acid, 13-hydroperoxyoctadeca-9,11-dienoic acid, eicosapentaenoic acid (EPA) [M-H], and EPA [M-H+Acetate]. Genetic loci were identified for six HF related eicosanoids (p<8.3e-9). One locus, rs6600888, an intronic variant of
UGT2B7
, where its T allele was associated with lower EPA [M-H+Acetate] level while positively affect the risk of HF and systolic blood pressure level. ERS constructed from 52 eicosanoids showed a 39% increase in HF risk per SD increment and twice the risk between the highest and the lowest ERS quartile (p < 0.001). The addition of ERS to the HF 10-years prediction model modestly improved the C-statistics from 0.799 to 0.808, 95%CI
ΔC
: 0.004-0.015.

Conclusion:
We identified a set of eicosanoids that significantly associated with increased risk of HF. The contributing genetic variation of eicosanoids may depict the biological pathways related to HF.
Abstract P331: Higher Allostatic Load Score is Associated With Early Cardiovascular Risk in Young South Africans. The AfricanPREDICT Study
Authors: Wentzel Annemarie , Kruger Ruan , Smith Wayne , Jansen van Vuren Esme , Chowdry Aruba , Wonkamtingang Edmond , Hanchard Niel A , Chung Stephanie T
Published: March 2023

Background:
The Allostatic load score (ALS) is a composite score that measures the cumulative physiological burden of sustained exposure to stress and biological dysregulation. ALS has markers capture risk in 4 domains (neuro-endocrine, metabolic, cardiovascular, and immunological). Higher ALS in adults predict cardiovascular disease (CVD), but it is unknown whether ALS is associated with CVD risk in youth and young adults (YA), and whether the risk and association would differ at such an early age.

Aims:
In youth and YA we compared 1) the total ALS; 2) the cardiovascular profile according to high and low ALS; and 3) the association of ALS with markers of CVD.

Methods:
Participants in the African PRospective study on the Early Detection and Identification of Cardiovascular disease and HyperTension (AfricanPREDICT) were 587 youth<24years (48% Male, 21±2 years) and 579 YA≥24years (49% Male, 27±2 years) were evaluated. The ALS was calculated from fasting biomarkers using the upper quartile population distribution of dehydroepiandrosterone (DHEA), cortisol, interleukin-6 (IL-6), C-reactive protein (hsCRP), BMI, systolic-BP, diastolic-BP, and lower quartile of HDL-cholesterol. The upper quartile of ALS in the whole population was defined as high ALS. Retinal vessel analyses, pulse wave velocity, and echocardiography were obtained and associations with ALS determined by regression analyses adjusted for sex, ethnicity, cotinine, gamma-glutamyl-transferase (GGT) and physical activity.

Results:
ALS median range was 1-8, and a high ALS of >3 was observed in 35% of youth, and 47% YA. In youth with high ALS, ALS associated with narrower retinal arteries (Adj R
2
:0.16, β-coefficient, -1.73, (95%CI), -2.95, -0.94),
P
=0.052), greater pulse wave velocity (Adj R
2
:0.56, 0.75 (0.48, 1.98),
P
=0.021), increased left ventricular mass index (Adj R
2
:0.61, 2.21 (0.43, 8.46)
P
=0.048), lower left ventricular function (global longitudinal strain) (Adj R
2
:0.37, -0.45 (-1.06, -0.06)
P
=0.015). Similarly, in YA with high ALS, ALS associated with narrower retinal arteries (Adj R
2
:0.43, -4.54 (-6.58, -2.50),
P
<0.001), greater pulse wave velocity (Adj R
2
:0.44, 0.62 (0.09, 1.17),
P
=0.043), increased left ventricular mass index (Adj R
2
:0.53, 2.62 (1.52, 5.76)
P
=0.032), lower diastolic function (E/A ratio) (Adj R
2
:0.27, -0.11 (-0.18, -0.04)
P
=0.002).

Conclusion:
Youth and YA with high ALS had a more adverse CVD risk profile and greater association with markers of cardiovascular aging compared to their low ALS counterparts. ALS and allostatic dysregulation should be evaluated in youth and YA, when assessing current and future cardiovascular risk.
Abstract P332: Duration of Diabetes and Risk of Multiple Cardiovascular Disease Outcomes
Authors: Anderson Shannon C , Ndumele Chiadi E , Zhang Sui , Tang Olive , Hamo Carine , Michos Erin D , Ballantyne Christie M , Coresh Josef , Selvin Elizabeth , Echouffo Tcheugui Justin B , Pankow James
Published: March 2023

Introduction:
Diabetes is strongly linked to cardiovascular disease (CVD). However, there is scarce data on the extent of the association of diabetes duration with multiple CVD outcomes (coronary heart disease [CHD], heart failure [HF], and stroke), considered individually and in combination.

Hypothesis:
A longer duration of diabetes is associated with CVD outcomes or death, independent of age, blood glucose control, and other cardiovascular risk factors.

Methods:
We included 9,296 participants (mean age 63 years, 58.2% women, 22% Black adults, 19% with diabetes) at ARIC Visit 4 (1996-1998) without CVD at baseline. We calculated diabetes duration at Visit 4 (baseline), utilizing diabetes status at the first four ARIC visits spaced 3 years apart, and self-reported diagnosis date for those with diabetes diagnosed before Visit 1. We used Cox regression to estimate associations of diabetes duration with incident CHD, HF, stroke, a composite of CVD outcomes, and all-cause mortality, adjusted for risk factors. We performed analyses stratified by age (<65 or ≥65 years), race, sex and glycemic control (HbA
1C
consistently <7%, vs. HbA
1C
≥7%), with tests for interaction.

Results:
Over a maximum of 24 years of follow-up, there were 3109 CVD events and 4095 deaths. Compared to adults without diabetes, the risk of each CVD outcome or death rose progressively with longer diabetes duration, except for stroke (Figure). Participants with a diabetes duration ≥ 15 years were at highest risk of CHD (HR: 2.65, 95%CI: 2.00, 3.51), HF (HR 2.65, 95% CI: 2.00, 3.51), composite CVD (HR: 2.47, 95% CI 2.00, 3.05), and death (HR: 1.95, 95% CI: 1.60, 2.37). Except for stroke, the link of diabetes duration with CVD outcomes was stronger among those <65 years, with HbA
1C
≥7%, women, and Black adults (all
P
interactions <0.05).

Conclusions:
Longer diabetes duration is associated with multiple CVD outcomes and death. Delaying diabetes onset should be a focus of global CVD prevention, and therapies to improve CVD outcomes might target those with long diabetes duration.

Figure:
Associations of diabetes duration with cardiovascular outcomes.

Legend:
HRs were adjusted for age, sex, race-center, smoking, alcohol, body mass index, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, triglycerides and estimated glomerular filtration rate. Diabetes duration (in years) was modeled as a restricted cubic spline with knots located at 0, 2.6, 7.0, and 19.8 years. Dark shaded area along the curve represents the 95% CI. Bar graph reflects the histogram of distribution. No diabetes served as the reference group. Prediabetes was defined as glycosylated hemoglobin of 5.7% to 6.4%. HF: heart failure, CHD: coronary heart disease, CVD: cardiovascular disease (composite of heart failure, coronary heart disease and stroke)
Abstract P333: Asian-Specific BMI Cutoffs as a Predictor for Mortality Risk
Authors: Nguyen Nhan , Sajjadian Amin , Cruanes Gaël , Bacong Adrian , Jamal Armaan , Srinivasan Malathi , Huang Robert J , Kim Gloria S , Palaniappan Latha , Kim Karina , Yang Eugene , Elfassy Tali
Published: March 2023

Introduction:
Prior studies have found a U-shaped association between body mass index (BMI) and mortality. The WHO has recommended Asian-specific BMI guidelines to better screen for BMI-related diseases among Asians. Little is known about patterns between BMI and mortality rates in Asian subgroups. We used Asian-specific BMI cutpoints to determine whether BMI was associated with mortality among disaggregated Asian subgroups.

Methods:
A sample of Asians (n=26,831) was obtained from the 1999-2018 National Health Interview Survey (NHIS) linked to the National Death Index. BMI was calculated with self-reported height and weight. Individuals were grouped into 4 BMI classes by Asian-specific BMI cutpoints: underweight (BMI <18.5), normal (BMI >18.5-22.9), overweight (BMI > 23-24.9), and obese (BMI ≥ 25) categories. Using Poisson models, we calculated the age-standardized mortality rate (ASMR) per 1,000 person years (PY) for All Asian adults and specific sub-groups (Asian Indian, Chinese, Filipino, Other Asian) with normal weight as a reference.

Results:
Our sample was comprised of 20.6% Chinese (n=5517), 22.8% Filipino (n=6111), 19.5% Asian Indian (n=5232), and 37.2% Other Asian (n=9971). Compared to normal BMI, underweight individuals had significantly higher ASMR among all Asians and more specifically among Chinese, Filipinos, and Asian Indians, but not among Other Asians. Compared to normal BMI, risk of mortality was not significantly different among overweight or obese individuals across any Asian subgroup.

Conclusion:
We found that low BMI was consistently associated with increased mortality among all Asian subgroups. In contrast to what has been described in Non-Hispanic White adults, we found that overweight or obesity was not associated with increased mortality among Asian American subgroups utilizing Asian-specific cutpoints.
Abstract P334: N-terminal Pro B-type Natriuretic Peptide Improves Stratification of Cardiovascular Disease and Specifically Stroke Risk in South Asians
Authors: Ahmed Ayesha , Pinto Pereira Snehal , Tillin Therese , Wannamethee Goya
Published: March 2023

Introduction:
N-terminal pro B-type natriuretic peptide (NT-proBNP) has been widely explored as a biomarker for improving cardiovascular disease (CVD) risk stratification in populations of European ancestry. Evidence on whether NT-proBNP adds value to CVD risk prediction in South Asians (SA) is limited.

Hypothesis:
We hypothesized that NT-proBNP would improve CVD and stroke-specific risk stratification in SA.

Methods:
In the London-based multi-ethnic Southall and Brent Revisited study 1710 first generation SA were randomly recruited from primary care lists and workplaces in 1988-91. Of these, 1149 (mean age 51±7y, 85% men) were free of prevalent CVD and had complete data on baseline CVD risk factors and NT-proBNP (median 31pg/ml, 1
st
-3
rd
quartile 19-55pg/ml). Follow-up for mortality and fatal/non-fatal coronary heart disease (CHD) and stroke events was available to 2008-11. We assessed change in discrimination (Harrell’s C-index [95% CI]) and integrated discrimination improvement (IDI) on adding standardized log-NT-proBNP to Cox models containing age, sex, body mass index, cholesterol:HDL ratio, systolic blood pressure, antihypertensive use, smoking, diabetes, chronic kidney disease and social class; for predicting (1) risk of composite-CVD (CHD or stroke) over (a) 10y and (b) maximum follow-up of 22y; and (2) risk of stroke over 22y. Net reclassification improvement (NRI) for events (NRIe) and non-events (NRIne) was calculated across high, intermediate and low-risk categories defined by cut-offs corresponding to observed (Kaplan-Meier) risk and half-the-observed risk of each endpoint: CVD 15% and 7.5% over 10y; 44% and 22% over 22y; and stroke 10% and 5% over 22y.

Results:
Over 10y, 175 SA experienced a first CVD event. NT-proBNP increased C-index from 0.7269 [0.6920-0.7618] to 0.7323 [0.6973-0.7674] with IDI 0.006, NRIe -0.5% and NRIne 3%. Over 22y, 455 participants experienced a first CVD event. NT-proBNP increased C-index from 0.6759 [0.6521-0.6998] to 0.6795 [0.6555-0.7035] with IDI 0.006, NRIe -0.2% and NRIne 2.5%. In both instances, NT-proBNP correctly downgraded 2% of participants without incident CVD from high to intermediate risk with little change in other risk categories. Additionally, 106 participants experienced a first stroke event over 22y. For this model, NT-proBNP increased C-index from 0.7610 [0.7174-0.8046] to 0.7700 [0.7262-0.8138] with IDI 0.018, NRIe 3.8% and NRIne 4.9%. This correctly downgraded 3.5% of participants without incident stroke to low risk. And upgraded 5% of those with incident stroke from intermediate to high risk, while incorrectly downgrading 1% of these participants to low risk.

Conclusions:
In middle-aged SA, NT-proBNP modestly improves 10y and long-term composite-CVD risk prediction but improves to a greater extent long-term stroke risk prediction leading to sizeable reclassifications into more appropriate risk categories.
Abstract P335: Prognostic Cut Point of Fasting Insulin in Apparently Healthy Young Adults for the Development of Future Cardiovascular Disease
Authors: Garza Joshua , Dwivedi Alok , Cistola David P
Published: March 2023

Introduction:
Early metabolic imbalance (EMI) is insidiously prevalent in the U.S., especially among teens and young adults. It includes markers of insulin resistance, inflammation and oxidative stress, but does not meet the criteria for metabolic syndrome. Individuals with EMI have compensatory hyperinsulinemia, an independent risk factor for CVD. Yet, fasting insulin is an underutilized prognostic marker, partly due to a lack of calibrated cut points for this population.

Hypothesis:
The prognostic value of insulin for CVD risk is associated with an optimum cut point, which can be calibrated using a time-dependent receiver operator characteristic (timeROC) analysis of CARDIA: Coronary Artery Risk Development in Young Adults.

Methods:
The parent CARDIA study began in 1985, enrolling 5,114 participants ages 18-30 at baseline, with 35-year follow-up. In our retrospective cohort analysis, the exclusion criteria were hyperglycemia, hypertriglyceridemia, low HDL, pregnancy, diabetes, CVD, or fasting < 8 hours, all at baseline; n=3,292. The primary outcome was time to incident CVD (or censor), defined as fatal/nonfatal MI, coronary revascularization, acute coronary syndrome, CHF, stroke, TIA, carotid or peripheral artery disease. Survival data were analyzed using the ‘timeROC’ package in R v.4.2.1, with/without adjustment for the 2019 ACC/AHA risk factors for CVD. For validation, a conventional ROC (logROC) analysis was performed, with incident CVD as the outcome. For timeROC and logROC, the cut point optimum was determined using minimum distance to the [0, 1] coordinate; predictive accuracy was summarized by area under the curve (AUC). The prognostic value of insulin at its optimum was determined using Cox regression for insulin alone and with risk factors, using Stata v.17.0. Cox results are summarized with hazard ratio (HR) and Harrell’s c-statistic (c).

Results:
The cut point optimum for baseline fasting insulin was 9.1 mIU/L (60.5 percentile), with AUC 0.583 (95% CI: 53.6, 62.9), sensitivity 54.8% and specificity 61.7%. The results were unchanged with/without covariate adjustment in timeROC, and with logROC. Using the optimum, the unadjusted Cox HR for high vs. low insulin was 1.9 (95% CI 1.4, 2.6, p<0.0001); c=0.580. Cox model 2 included a variable with both high insulin and high waist circumference (WC); HR for both vs. neither condition was 2.6 (95% CI 1.8, 3.8, p<0.0001); c=0.606. Cox model 3 added ACC/AHA risk factors to model 2: HR 2.2 (95% CI 1.5, 3.4, p<0.0001) for high insulin and WC vs. neither; c=0.716.

Conclusion:
For young adults in CARDIA without metabolic syndrome or prediabetes, the cut point optimum for fasting insulin is near the top tertile. Insulin has a high prognostic value for CVD, especially when combined with WC. Though useful, insulin suffers from modest sensitivity. Better markers of EMI are needed for assessing hidden CVD risk in apparently healthy young adults.
Abstract P339: The Clinical Application and Ancestral Diversity of Cardiometabolic Polygenic Risk Scores
Authors: Phulka Jobanjit S , Ashraf Mishal , Bajwa Beenu K , Pare Guillaume , Laksman Zachary
Published: March 2023

Introduction:
A polygenic risk score (PRS) is derived from a genome-wide association study (GWAS) and represents an aggregate of thousands of single-nucleotide polymorphisms (SNPs) that provide a baseline estimate of an individual’s genetic risk for a specific disease or trait at birth. Cardiometabolic disease represents a set of disease processes that historically have disproportionally affected underrepresented racial and minority groups. Furthermore, these groups represent a population generally not well captured by traditional risk scores compared to European cohorts. Since the first GWAS studying myocardial infarction was published, PRSs have increasingly been seen as a promising tool to improve risk stratification of non-European populations. However, how PRSs can be best used in clinical practice remains unclear.

Hypothesis:
We provide an overview of the PRSs related to cardiometabolic disease, analyze the ancestral diversity of GWAS cohorts, and discuss the evidence supporting their clinical applications.

Methods:
The Preferred Reporting Items For Systematic Reviews and Meta-analysis extension for Scoping Reviews protocol was used to conduct a scoping review of the MEDLINE, EMBASE, and CENTRAL databases. English studies that published a PRS related to atrial fibrillation (AF), cerebrovascular disease (CVD), coronary artery disease (CAD), dyslipidemia, heart failure, heritable cardiomyopathy, hypertension, and type 2 diabetes were reviewed.

Results:
Across the 4,863 studies screened, 82 articles met the inclusion criteria. The most common PRS related to CAD, followed by hypertension and CVD. Limited ancestral diversity was observed as most studies (56) included only individuals of European ancestry. A smaller proportion of studies (16) published PRSs derived in multi-ancestry cohorts. Only ten studies published a PRS derived solely from a sample population of non-European ancestry (Chinese, East Asian, Japanese, and Korean). The predictive performance of most PRSs was similar to or superior to traditional risk factors. More than half of the included studies (42) reported an integrated risk model combining a PRS with traditional risk factors or a clinical risk tool (FRS, PCE, CHADS2). The integrated risk model consistently improved predictive accuracy, but few studies investigated the performance in a non-European population.

Conclusion:
In conclusion, this scoping review reports strong evidence for the clinical use of PRSs in AF, CAD, CVD, and hypertension. However, most PRSs are derived in cohorts of European ancestry, which contributes to a lack of PRS transferability across different ancestral groups, likely exacerbating health inequities. Future prospective studies should focus on further establishing the clinical utility of PRSs. Additionally, diversity in future GWAS cohorts is essential to ensure that PRSs reflect the multi-ancestry society at large.
Abstract P340: Development and Delivery of an Effective 16-week HealthEYou Program to Mitigate Metabolic Disease Risk Factors
Authors: Geller Talya E , Nepocatych Svetlana , Bailey Elizabeth
Published: March 2023

Introduction:
Metabolic syndrome (MetS) is a growing concern in the U.S and around the world. MetS is a cluster of disease risk factors including hypertension, hyperlipidemia, hyperglycemia, and obesity increasing the risk of cardiometabolic disease development.

Purpose:
The purpose of this study was to assess the efficacy of a 16-week nutrition and physical activity education program (HealthEYou) in mediating metabolic risk factors associated with MetS.

Methods:
This was a two phase study including phase 1) the use of a person-based approach and community needs assessment to develop a nutrition and physical activity education program, and 2) delivery of the 16-week workplace education program and assessment of its effectiveness. In phase 1, a survey and focus groups were used to assess the needs of the target population to develop the 16-week education program. Twenty-six participants (96% female; age: 50.1±9.2 yrs; BMI: 31.2±5.3 kg/m2) enrolled in the HealthEYou program. At baseline, 8- and 16-weeks participants completed assessments including blood pressure, body composition via Dual-energy X-ray absorptiometry (DXA) and waist circumference, 6-minute walk test, handgrip strength test, dietary intake via the Automated Self-Administered 24-hour (ASA-24) dietary assessment tool, and quality of life questionnaire. In addition, blood was drawn to assess metabolic disease risk markers (total cholesterol, glucose and hemoglobin A1c (HbA1c)). The education program consisted of 8-weeks in-person weekly interactive group (60 min) and individual goal setting (15 min) sessions and 8-weeks of weekly newsletters and two individual goal setting sessions.

Results:
Data was analyzed using repeated measures analysis of variance. The prevalence of MetS among the participants decreased significantly from 41.7% at baseline to 15.8% after completion of the program. There was a significant decrease from baseline compared to after 16-weeks in fat mass (36.8±10.5 kg and 34.4 ±10.47 kg, p=0.003) and HbA1c (5.36±0.40% and 5.12±0.37%, p=0.001). In addition, significant improvements in distance walked, handgrip strength, caloric intake and quality of life (p<0.05) were also observed. However, no significant changes (p>0.05) in total cholesterol, fasting blood glucose or systolic and diastolic blood pressure were observed at 16-weeks compared to baseline measures.

Conclusion:
In conclusion, the use of a person-based approach and community needs assessment was beneficial to the development of a 16-week nutrition and physical activity education program. Participants who completed the 16-week program had significant improvements in a number of metabolic risk factors. In addition, the physiological improvements corresponded with improvements in dietary intake and fitness levels, suggesting participants made positive lifestyle changes.
Abstract P342: Periodontal Disease is Associated With Elevated Prediabetes Prevalence and Glucose Levels Among Non-Diabetic Adults. Results From Oral Infections, Glucose Intolerance and Insulin Resistance Study
Authors: Adam Hamdi S , Molinsky Rebecca L , Roy Sumith , Rosenbaum Michael , Paster Bruce , Yuzefpolskaya Melana , Colombo Paolo C , Papapanou Panos N , Desvarieux Moise , Jacobs David R , Demmer Ryan T
Published: March 2023

Background:
Periodontitis (a bacterially-driven, inflammatory disease) is a plausible risk factor for prediabetes and diabetes. We studied the association between clinical attachment loss (CAL – a cumulative measure of tooth-supporting tissues lost due to periodontitis), prediabetes, and glucose levels among non-diabetic younger adults.

Hypothesis:
We hypothesize that greater CAL is associated with higher levels of biomarkers of cardiometabolic risk cross-sectionally.

Methods:
We included n=1071 non-diabetic participants from the Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) who underwent full-mouth periodontal examinations and provided fasting blood at baseline. Baseline enrollment occurred in two waves: Wave 1 (2011-2013; n=293) and Wave 2 (2016-2020; n=778). HbA1c and glucose were measured during clinical exams. Prediabetes was defined as fasting glucose between 100-125 mg/dL or HbA1c between 5.7-6.4% per American Diabetes Association guidelines. We computed prevalence ratios and 95% confidence intervals of prediabetes among 2
nd
and 3
rd
CAL tertiles (vs. 1
st
tertile) via multivariable Poisson regression with robust variance estimation. Multivariable linear regression was used to assess the association between CAL tertiles (independent variable) and estimates of glucose and HbA1c. We adjusted for demographics, health variables, and study wave.

Results:
The mean age(SD) of participants was 32.3(9.6) years and 28% were male. Prediabetes prevalence was 8.7%. Multivariable adjusted prevalence ratios (95%CIs) for prediabetes in tertiles 2 and 3 (vs. 1) were 1.45(0.79,2.67) and 1.91(0.99,3.67), respectively, consistent with p for trend = 0.05 and stronger associations with continuous glucose and HbA1c (see
Table
).

Conclusion:
CAL, a cumulative measure of periodontitis, was cross-sectionally associated with increased prediabetes prevalence, glucose and HbA1c.
Abstract P345: Physical Activity and Cardiorespiratory Fitness Among Adolescents With Type 1 and Type 2 Diabetes: A Systemic Review and Meta-Analysis
Authors: Steiman De Visser Hannah , Fast Isaak D , Arevalo Edward , Askin Nicole , McGavock Jonathan
Published: March 2023

Background:
Physical activity (PA) is a cornerstone in the management of pediatric diabetes, due in part to a dose-response effect on cardiorespiratory fitness (CRF). The extent to which PA and CRF is impaired in children and adolescents with diabetes remains unclear.

Hypothesis:
We hypothesized that PA and CRF would be lower in children and adolescents with type 1 (T1D) and (T2D) compared to controls.

Design and Methods:
To test this hypothesis we conducted a systematic review of observational studies in MEDLINE, Embase, the Cochrane Library, and CINAHL from 2000 to April 2022. Cross sectional studies that reported PA and/or CRF for children and adolescents (0-21 years) with T1D, T2D and controls without diabetes were included in the analysis. We excluded studies in adults and those that did not differentiate diabetes type. The main outcomes of interest were objective or subjective measures of PA and direct or indirect measures of CRF. Co-variates extracted from each manuscript included body mass index, sex, measures of socio-economic status, age and ethnicity. A modified risk of bias tool was used to assess the methodological quality of each study. (Prospero registration: CRD42022329303). We used an inverse variance weighted meta-analysis to estimate effect size and precision effects. A random effects model was used.

Results:
Of 7857 citations retrieved, we included 42 studies with T1D (n=4027 with T1D, n=9699 controls) and 14 studies with T2D (n=581 with T2D, n=1008 controls). 26 and 2 studies included direct and indirect measures of cardiorespiratory fitness respectively. 14 and 26 studies include objective and subjective measures of PA respectively. The standardized mean difference (SMD) was PA [-0.28; 95% CI: -0.46, -0.10; I
2
= 89%] and CRF [-0.30; 95% CI: -0.66, 0.06; I
2
= 92%] were lower children and adolescents with for T1D compared to controls. The SMD for PA [-0.61; 95% CI: -0.98, -0.24; I
2
= 89%] and CRF [-1.20; 95% CI: -1.73, -0.67; I
2
= 91%] were also lower for children and adolescents with T2D compared to controls. The majority of studies were considered a high risk of bias.

Conclusions:
Children and adolescents with T1D display modestly lower daily PA and CRF compared to controls. Deficits in PA and CRF are more profound among children and adolescents with T2D.
Abstract P346: Adherence to the French Dietary Guidelines and Type 2 Diabetes Risk: The E3n-Epic Prospective Cohort Study
Authors: Seck Daouda , Shah Sanam , Gaye Bamba , LAOUALI Nasser
Published: March 2023

Background:
Recently, a dietary index reflecting adherence to the 2017 French food-based dietary guidelines, the
Programme National Nutrition Santé
- guidelines score 2 (PNNS-GS2), has been developed, but evidence on its level of adherence and incident type 2 diabetes (T2D) risk is limited.

Objective:
We aimed to investigate the association between adherence to the simplified PNNS-GS2 (sPNNS-GS2) and the risk of incident T2D in a French cohort of women.

Methods:
Between 1993 and 2014, 71,450 women aged over 18 years were examined, and thereafter followed up for the occurrence of T2D within the E3N-EPIC prospective cohort. Dietary data were collected at baseline via a food frequency questionnaire, and the sPNNS-GS2 was derived for each participant. Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of T2D for continuous and quintile groups of the sPNNS-GS2. Effect modification by body mass index (BMI) and mediation by BMI and waist-hip ratio (WHR) were explored.

Results:
The mean age was 52.9 years (SD 6.7). During a mean follow-up of 19 years, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D risk (P
non-linear
= 0.85). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a 8% decrease risk of T2D [HR (95% CI), 0.92 (0.89, 0.95)]. Compared to those with the lowest adherence (first quintile), the third [HR (95% CI), 0.91 (0.82, 1.00)] up to the fifth quintile group [HR (95% CI), 0.79 (0.71, 0.88)] had a lower T2D risk. There was a sPNNS-GS2 x BMI interaction on T2D risk (P
interaction <
0.01) but not with WHR. The overall association was partly mediated by BMI (18%) and WHR (59%).

Conclusion:
Higher adherence to the 2017 French food-based dietary guidelines was associated with a lower risk of T2D in women. Furthermore, our mediation analysis suggests that the lower risk of T2D in women associated with adherence to the sPNNS-GS2 is partly mediated by obesity measured by BMI or WHR.