bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P171: The “Hub and Spoke” Model of Heart Function Care Achieves Quality Index Markers
Authors: Hinton Stephanie , Geukers Karen , Heckman George , Suskin Neville , Hartley Tim , Harkness Karen , Lonn Eva , McKelvie Robert
Published: July 2021

Introduction:
Heart failure (HF) affects approximately 2% of the population with major effects on morbidity and mortality. Over 80% of existing Heart Function Clinics (HFC) are located within a hospital setting. The CoHealth (Ontario) “hub-and-spoke” model encourages community-based HFCs for patients who are less complex or relatively stable while more complex/unstable patients receive care in a hospital-based HFC. The purpose of this project was to explore patient populations and achievement of established quality indicators (QIs) within a specialist-supported community-based HFC in a Family Health Team (FHT-HFC) and a HFC in a tertiary hospital (H-HFC) over 12 months.

Methods:
Retrospective standardized chart reviews were conducted from all 60 patients enrolled in the FHT-HFC since its inception in 2010 to 2015, and 100 patients followed in the H-HFC in 2013. QIs were measured and compared at enrollment, 6 months and 12 months.

Results:
Patients attending the H-HFC vs FHT-HFC had no difference in age, sex or etiology of HF. However, patients at the H-HFC were significantly more likely to have reduced LV function, have marked HF symptoms, and more likely to have a recent hospital admission. Both cohorts had multiple comorbidities, with greater frequencies of MI, ICD/CRT/pacemaker, smoking and respiratory disease in the H-HFC group. By 6 months’ post enrollment, the number of patients with a HF with a reduced ejection fraction (HFrEF) in the H-HFC (n=65) who were on an ACEi/ARB, beta-blocker, and MRA increased from 75% to 82%, 86% to 88%, and 29% to 34% (vs 99% to 99%, 77% to 89% and 33% to 39%, respectively in the FHT-HFC (n=28)). Over the 12 months following enrollment in a HFC the proportion of patients with NYHA class III symptoms decreased from 67% to 38% (H-HFC) vs 47% to 14% (FHT-HFC) (p < 0.05) and HF hospital admissions were reduced by 31% (H-HFC) vs 68% (FHT-HFC) (p < 0.05). At 12 months 34% (H-HFC) vs 20% (FHT-HFC) (p=0.07) of patients were enrolled in a cardiac rehabilitation program.

Conclusion:
While the H-HFC and FHT-HFC patients had similar demographics and comorbidities, H-HFC patients tended to more frequently have HFrEF, were more symptomatic and more likely to have been recently hospitalized. Participation in either the H-HFC or FHT-HFC was associated with medication optimization, decreased symptoms and fewer hospitalizations compared to the previous year. In conclusion, this retrospective study shows that the “hub and spoke” HFC model may have merit but needs further evaluation on a wider, more formal scale.
Abstract P177: Potential Value of Intensive Blood-Pressure Treatment Based on Predicted Lifetime Cardiovascular Disease at Age 40: Computer Simulation Study
Authors: Thanataveerat Anusorn , Singh Sonia , Kohli-Lynch Ciaran , Zhang Yiyi , Vittinghoff Eric , Pletcher Mark , Moran Andrew E
Published: July 2021

Introduction:
In the SPRINT trial, intensive blood pressure (BP) treatment saved lives and was cost-effective in high-risk older adults. It is unclear if intensive BP treatment should be extended to high-risk adults aged 40-49 years.

Objectives:
We used individual patient computer simulation to assess the incremental value of extending intensive BP treatment to adults as young as age 40 with high cardiovascular disease (CVD) risk. We selected patients aged <60 years with high lifetime risk because few have high ten-year risk.

Methods:
Male and female cohorts of 100,000 individuals were assembled from NHANES surveys 1999-2010 using sampling weights. BP and other risk factor trajectories were projected for ages 40 to 69 years based on Framingham Offspring Cohort analyses. The “standard of care” treatment scenario simulated treating BP <140/90 mmHg in all patients ≥140/90 mmHg. Two alternative scenarios were simulated: add intensive treatment (goal <130/90 mmHg) from age 40-69 or from age 50-59 in patients with high lifetime risk. The lifetime risk thresholds (Table 1) were chosen in order to capture patients with forecasted ten-year CVD risk ≥ 10% at age 60. Costs included added treatment and side-effect costs and avoided CVD costs; indexed to 2016. Incremental cost-effectiveness ratios (ICERs) assessed changes in costs and quality-adjusted life years due to adding intensive BP goals.

Results:
Over a 30-year time horizon, adding intensive treatment in high lifetime risk patients at age 40 would prevent 2,880 additional CVD events in males and 2,958 in females compared to treating only BP <140/90 mmHg. Intensive treatment in high lifetime risk patients before age 60 appeared generally cost-effective except in females aged 40 years (ICER $59,000).

Conclusion:
Our results suggest that over the long term, intensive BP treatment may be cost-effective in high-risk men as young as 40 and high-risk women as young as 50. Lifetime cardiovascular disease risk might be used to select high risk middle-aged adults for intensive BP treatment.
Abstract P178: Trends in Antihypertensive Medication Nonadherence Among US Adults With Commercial Health Insurance Initiating Treatment Between 2007 and 2014
Authors: Tajeu Gabriel , Kent Shia T , Huang Lei , Shimbo Daichi , Krousel-Wood Marie , Kronish Ian M , Bress Adam P , Cuffee Yendelela , Halpern Michael T , Muntner Paul
Published: July 2021

Introduction:
Nonadherence to antihypertensive medication is common and associated with cardiovascular disease events. A previous study reported improvements in antihypertensive medication adherence among adults ≥65 years of age. It is unclear if this trend has also occurred among younger adults.

Methods:
Changes in antihypertensive medication nonadherence were calculated among commercially-insured US adults <65 years of age initiating treatment from 2007 to 2014 using MarketScan claims data. We required beneficiaries have ≥2 diagnoses for hypertension (ICD-9, 401.xx) and insurance coverage for 365 days prior to and following antihypertensive medication initiation. Initiation was defined by a pharmacy claim for antihypertensive medication with no claims for medication within the previous 365 days. During the 365 days after initiation, nonadherence was defined as having a proportion of days covered <80%.

Results:
The percentage of patients who were nonadherent to their antihypertensive medication was 55.6% in 2007 and 54.1% in 2014 (p-trend<0.001) (
Table
). After multivariable adjustment, the relative risk (RR) of nonadherence in 2014 compared with 2007 was 0.98 (95% CI 0.96-0.99). Risk for nonadherence was lower at older age (RR 0.73, 95% CI 0.71-0.74 comparing adults 55-64 to <25 years of age). Nonadherence was more common among adults that were female versus male (RR 1.05; 95% CI 1.05-1.06), initiated treatment with a loop diuretic (RR 1.26; 95% CI 1.24-1.28), had diabetes (RR 1.11; 95% CI 1.10-1.12), or experienced a serious fall injury after medication initiation (RR 1.10; 95% CI 1.06-1.15), and less common among adults initiating treatment with an angiotensin receptor blocker (RR 0.96; 95% CI 0.95-0.96), multiclass regimen (RR 0.89; 95% CI 0.88-0.90), receiving 90-day fills (RR 0.73; 95% CI 0.73-0.74), or medications by mail (RR 0.92; 95% CI 0.91-0.93).

Conclusion:
Among adults <65 years of age, nonadherence to antihypertensive medication did not meaningfully decrease between 2007 and 2014.
Abstract P182: Low Diastolic Blood Pressure is Associated With Subclinical Myocardial Disease and Cardiac Events in Patients With Coronary Artery Disease
Authors: Topel Matthew L , Sandesara Pratik B , Stahl Eric P , Ko Yi-An , Tahhan Ayman S , Hayek Salim S , Quyyumi Arshed A
Published: July 2021

Introduction:
Clinical trials have shown increased survival at lower blood pressures, but low diastolic blood pressure (DBP) is associated with increased cardiovascular (CV) events and mortality. The suggested mechanism in patients with coronary artery disease (CAD) is limitation in coronary blood flow; however, evidence is lacking. We investigated the association between DBP, biomarkers of myocardial injury, and incident events in patients with CAD.

Methods:
We assessed 2448 individuals (aged 65±12 years, 68% male, median follow-up 4.5 years) with stable CAD undergoing cardiac catheterization. Those with acute coronary syndromes or heart failure with reduced ejection fraction were excluded. DBP was categorized into 10 mm Hg increments. Biomarkers of myocardial damage (high sensitivity cardiac troponin-I [hs-cTnI] and soluble urokinase plasminogen activating receptor [suPAR]) were dichotomized at their median values. DBP 80-89 mmHg was used as the referent group and individuals were followed for MACE (CV death or non-fatal myocardial infarction) and all-cause mortality.

Results:
After adjusting for relevant demographic and clinical covariates, individuals with DBP < 60 mm Hg had increased odds of elevated hs-cTnI (OR = 1.75; 95% CI = 1.05, 2.90) and suPAR (OR = 1.73; 95% CI = 1.09, 2.76) compared to the referent group. Additionally, DBP < 60 mm Hg was associated with increased risk of MACE (HR = 2.01; 95% CI = 1.24, 3.25) and all-cause mortality (HR = 2.18; 95% CI = 1.50, 3.19). Adding hs-cTnI and suPAR into the Cox proportional hazards model attenuated the association between DBP < 60 mmHg and MACE (HR =1.63, 95% CI 0.91, 2.91), but not all-cause mortality (HR = 1.67, 95% CI = 1.06, 2.63).

Conclusion:
In patients with CAD, low DBP is associated with biomarkers of myocardial injury and incident events. Aggressive blood pressure control may be harmful in these patients, and further investigation is warranted to determine appropriate blood pressure targets in patients with CAD.
Abstract P184: Meat Cooking Methods and Risk of Hypertension: Results From Three Prospective Cohort Studies
Authors: Liu Gang
Published: July 2021

Background:
The role of open-flame and/or high-temperature cooking (grilling/barbequing, broiling, or roasting) and doneness preferences (rare, medium, or well-done) in the association between meat consumption and risk of hypertension remains unknown. This study aimed to examine cooking methods for meats (red meats, chicken, or fish) in relation to hypertension risk among men and women who consumed meat regularly (≥2 servings/week).

Methods:
Study population consisted of 32,925 women from the Nurses’ Health Study (NHS 1996-2012), 53,852 women from the NHSII (2001-2013), and 17,104 men from the Health Professionals Follow-Up Study (HPFS 1996-2012), who were free of hypertension, diabetes, cardiovascular disease, and cancer at baseline.

Results:
We documented 37,123 incident hypertension cases during 1.06 million person-years of follow-up. After multivariate adjustments of covariates including total consumption of red meats, chicken, and fish, a higher frequency of open-flame and/or high-temperature cooking and a preference for higher meat doneness level were both independently associated with an increased hypertension risk. When comparing open-flame and/or high-temperature cooking >15 times/month with <4 times/month, the pooled hazard ratio (HR) and 95% confidence interval (CI) of hypertension was 1.17 (1.12, 1.21;
P
trend <0.001). When comparing the extreme quartiles of meat doneness level score, the pooled HR (95% CI) of hypertension was 1.15 (1.12, 1.19;
P
trend <0.001). The associations persisted when data were analyzed by individual meat groups: comparing extreme groups, for red meats, the pooled HR (95% CI) of hypertension was 1.18 (1.13, 1.23;
P
trend <0.001) for open-flame and/or high-temperature cooking and 1.15 (1.12, 1.19;
P
trend <0.001) for high meat doneness level; for white meats (chicken and fish), the pooled HR (95% CI) of hypertension was 1.12 (1.08, 1.16;
P
trend <0.001) for open-flame and/or high-temperature cooking and 1.10 (1.07, 1.14;
P
trend <0.001) for high meat doneness level. Moreover, levels of estimated intake of heterocyclic aromatic amines (HAAs) were also independently associated with an increased risk of hypertension. Comparing extreme quintiles of HAAs, the pooled HR (95% CI) of hypertension was 1.16 (1.13, 1.21;
P
trend <0.001). These associations were attenuated but remained significant when further adjusting for baseline body mass index.

Conclusions:
Our results suggest that, independent of the amount of meat consumption, open-flame and/or high-temperature cooking and high doneness level for both red meats and white meats are associated with an increased risk of hypertension.
Abstract P187: Increasing CVD and CVD Risk Among PLWHA in Louisiana 2002-2012
Authors: Ferguson Tekeda F , Wang Xinnan , Dyer Lauren , Straif-Bourgeois Susanne , Rojas Dayana , Maloney Patrick , Fang Zhide , Besch Lynn
Published: July 2021

Introduction:
While effective HIV treatments have decreased the likelihood of AIDS-defining illnesses among people aging with HIV, HIV-associated non-AIDS conditions are more common in individuals with long-standing HIV infection, including cardiovascular disease (CVD), hypertension, diabetes mellitus, and renal failure among others. It has been estimated that 30% of deaths among those with well-controlled viral load has been attributed to CVD, compared to 23.5% in the general US population. The purpose of this study was to determine the prevalence trends of CVD in people living with HIV/AIDS (PLWHA) in South Louisiana.

Methods:
A ten-year retrospective cohort study was conducted using data abstracted from the Louisiana State University (LSU) Health Care Services Division, Disease Management Evaluation Database (DMED) that included patients who received care within the LSU Medical System 7 state facilities. Inclusion criteria included 18 years of age or above, a positive HIV lab test, and a HIV diagnose code. Total sample size for the analysis was 9,374. The presence of CVD was established using ICD9 Diagnosis codes, patient vitals, and lab results. CVD outcomes evaluated included myocardial infarction, coronary artery disease, hypertension, heart failure, and stroke. All analyses were conducted in SAS 9.4.

Results:
The racial distribution was 24% white, 67% black, 2% other, and 7% unknown; distribution by sex remained stabled over the ten-year period approximately 58% male and 42% female. The mean age of the clinic population increased from 39.24±10.17 to 45.09±10.46 over the ten year period. There has been a positive trend in CVD among the HIV Clinic population, from 23.0% to 50.7% prevalence. There was an increase in hypertension, heart failure, stroke, and coronary artery disease among PLWHA. Hypertension showed the largest increase in prevalence from 19.4% to 44.8%. A positive trend and in increased Framingham Risk score was also observed (p< 0.05).

Conclusion:
As PLWHA continue to increase in age, mortality and hospital admissions attributed to CVD has the potential to continue to increase. Data from this project has the potential to guide additional screening recommendations and practices, ultimately resulting in more timely detection of disease, which improves outcomes for patients.
Abstract P189: Factors Associated With Stenosis on Invasive Coronary Angiography for Persons Living With Human Immunodeficiency Virus (PLWH): The HIV Electronic Comprehensive Cohort of CVD Complications (HIVE-4CVD)
Authors: Furman Andrew , Riestenberg Robert , Pawlowski Anna , Schneider Daniel , Lloyd-Jones Donald M , Feinstein Matthew J
Published: July 2021

Background:
Persons living with HIV (PLWH) have greater risks for atherosclerotic cardiovascular disease (ASCVD) than uninfected persons. However, data are sparse regarding HIV-specific factors associated with coronary atherosclerosis.

Methods:
HIVE-4CVD is an electronic data repository of demographic and clinical data collected during the routine clinical care of 5041 PLWH and 10082 uninfected controls frequency matched on age, sex, race, zip code, and clinic location receiving care at Northwestern Medicine from 1/1/2000 to 5/17/2017. Using validated natural language extraction algorithms, we analyzed data on coronary stenosis severity for the 286 PLWH and 266 uninfected controls in HIVE-4CVD who underwent coronary angiography. Stenosis severity was recorded as the highest percentage of stenosis noted for each patient in each artery (LAD, LCx, RCA). Multivariable logistic regression models adjusted for demographics and CVD risk factors were used to evaluate odds of significant (≥50%) coronary stenosis (1) for PLWH versus uninfected controls and (2) across different levels of HIV viremia and immune suppression among PLWH.

Results:
Of the 286 PLWH and 266 uninfected controls undergoing coronary angiography, 205 (55.4%) PLWH vs. 165 (44.6%) uninfected controls had diagnoses of myocardial infarction (p=0.02). The location and severity of coronary stenoses did not differ significantly for PLWH vs. uninfected controls; mean maximal overall stenosis and mean maximal LAD, RCA, and LCx stenoses were 52.3% vs. 50.2% (p=0.52), 44.5% vs. 42.3% (p=0.48), 37.0% vs. 36.1% (p=0.78) and 31.4% vs. 31.6% (p=0.95) respectively. There was no significant difference in odds of having significant coronary stenosis for PLWH vs. uninfected controls (multivariable-adjusted OR 1.15, 95% CI 0.79-1.70). Among PLWH, peak HIV viral load was associated with borderline significantly greater odds of ≥50% coronary stenosis after adjustment for demographics, CVD risk factors, and HIV therapies (OR 1.07 per 10-fold greater peak HIV viral load, 95% CI 1.00-1.14, p=0.04), but lower Nadir CD4+ T cell count (<200 vs. ≥200 cells/mm
3
) was not (OR 1.05, 95% CI 0.74-1.48, p=0.79).

Conclusions:
There was no consistent or significant difference in severity of coronary artery stenosis among PLWH and uninfected controls undergoing invasive coronary angiography in the course of routine clinical care. Higher peak HIV viral load is associated with borderline significantly greater odds of having significant coronary stenosis among PLWH undergoing invasive coronary angiography.
Abstract P193: High Density Lipoprotein is Superior to Triglyceride as a Biomarker of Physiologic Stress in African Immigrants: The Africans in America Study
Authors: Baker Rafeal L , Utumatwishima Jean N , Chung Stephanie T , Sumner Anne E
Published: July 2021

Introduction:
For Africans living in the United States, the extent to which stress-induced physiologic dysfunction varies by reason for immigration is unknown. Allostatic load score (ALS) is used to assess physiologic stress. ALS has biomarkers in 3 domains: cardiovascular, metabolic and immune. However, there are many ALS equations and the number of biomarkers in each domain varies. In the cardiac domain of ALS, equations use either triglyceride (TG) or high density lipoprotein (HDL). A specific problem for African descent populations is that HDL may be superior to TG as a marker of insulin resistance and cardiac risk.

Objective:
Our primary goal in 95 African immigrants (71% male, age 42±10, (mean±SD), range 22-62y) was to determine if ALS varied by reason for immigration. Our secondary goal was to evaluate 4 different ALS equations to determine if there was a difference in ALS performance depending on whether HDL or TG was the included biomarker.

Methods and Results:
For all 4 equations, the reasons for immigration from lowest to highest ALS were: family reunification, lottery for self and immediate family, marriage, asylum, work and study (Figure 1). As the first 3 reasons for immigration promoted family unity, they were grouped together (Group 1). The Africans who came for other reasons were grouped together (Group 2). Equations 1 and 2 included HDL as a biomarker. For these equations, ALS in Group 1 vs. Group 2 were: 1.7±1.3 vs. 2.8±1.7,
P
<0.01 and 1.4±1.2 vs. 2.3±1.7,
P
<0.01 resp. Equations 3 and 4 used TG. For these two equations ALS in Group 1 vs. Group 2 were: 2.2±1.6 vs. 2.9±2.0,
P
=0.08 and 2.1±1.4 vs. 2.9±2.0,
P
=0.03 resp. In Equations 1 and 2, when HDL was replaced by TG, the significant difference in ALS between groups declined. In Equations 3 and 4, when TG was replaced by HDL, the significant difference in ALS between groups increased.

Conclusions:
ALS varies by reason for immigration and is easier to detect in ALS equations which use HDL rather than TG.
Abstract P195: High-density Lipoprotein Subfractions Are Associated With Low-grade Inflammation, Insulin Resistance and Metabolic Syndrome Components: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Generoso Giuliano , Bensenor Isabela J , Santos Raul D , Santos Itamar S , Goulart Alessandra C , Jones Steven R , Kulkarni Krishnaji R , Blaha Michael J , Toth Peter P , Lotufo Paulo A , Bittencourt Marcio S
Published: July 2021

Background:
HDL cholesterol (HDL-C) can be divided into subfractions, which may have variable association with atherogenic process. There are mixed results about the association between HDL-C subfractions and risk factors for cardiovascular disease.

Hypothesis:
HDL-C subfractions have different associations with metabolic syndrome, low-grade inflammation and insulin resistance.

Methods:
4,532 individuals between 35 and 74 years without previous cardiovascular disease not in use of fibrates were enrolled. HDL-C subfractions were separated by vertical ultracentrifugation (Vertical Auto Profile - in mg/dl) in HDL
2
-C and HDL
3
-C. HDL
2
-C/HDL
3
-C ratio, insulin resistance (HOMA-IR) and high-sensitivity C-reactive protein (CRP) were also included in the analysis.

Results:
The mean age was 51 ± 9 years, and 54.8% were women. In univariate analysis, HDL-C, HDL
2
-C, and HDL
3
-C were all inversely associated with each of the MetS defining factors, HOMA-IR values, and serum CRP. It was also observed a negative association between HDL
2
-C/HDL
3
-C ratio with the variables mentioned above even after adjusting for smoking, alcohol use, physical activity, and HDL-C levels (p <0.01).

Conclusion:
HDL-C and both subfractions are inversely associated with all the factors that define MetS, insulin resistance and low-grade inflammation. Additionally, the HDL
2
-C/HDL
3
-C subfractions ratio assessed by VAP is also significantly associated with the former factors even after further adjustment for total HDL-C and other confounding variables.
Abstract P198: Diabetes Alters the Association Between High-density Lipoprotein Subfractions and Carotid Intima-media Thickness: The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)
Authors: Generoso Giuliano , Bensenor Isabela J , Santos Itamar S , Santos Raul D , Goulart Alessandra C , Jones Steven R , Kulkarni Krishnaji R , Blaha Michael J , Toth Peter P , Lotufo Paulo A , Bittencourt Marcio S
Published: July 2021

Background:
Although HDL-C is inversely associated with cardiovascular risk, no causal relationship has been demonstrated. Since HDL comprises a group of heterogeneous subfractions, they might have different effects on atherosclerosis, and its effects may be modified by the presence of diabetes mellitus.

Hypothesis:
HDL-C subfractions exert different effects on subclinical carotid atherosclerosis, and diabetes modifies these effects.

Methods:
We evaluated 3,930 individuals between 35 and 74 years (45.6% men) without previous cardiovascular disease not using lipid-lowering drugs. HDL
2
-C and HDL
3
-C were obtained by zonal ultracentrifugation. The relationships between each HDL-C subfraction and cIMT were analyzed by multiple linear regression models.

Results:
The mean cIMT was 0.796±0.195 mm, the mean total HDL-C was 55.1±14.4 mg/dl, HDL
2
-C was 14.9±6.7, and HDL
3
was 40.1±8.4 mg/dl. Total HDL-C and subfractions, as well as HDL
2
-C/HDL
3
-C ratio were negatively associated with cIMT after adjustment for race/ethnicity, age, and sex (all p<0.001) and further for smoking status, alcohol use, physical activity, LDL-C, systolic blood pressure, waist circumference, fasting serum glucose, body mass index, triglycerides and antihypertensive use (HDL-C: p = 0.003, HDL
2
-C: p = 0.01; HDL
3
-C: p = 0.003; HDL
2
-C/HDL
3
-C ratio: p = 0.02). When stratified by diabetes status, both HDL
2
-C (p=0.03) and HDL
2
-C/HDL
3
-C ratio (p= 0.01) showed a negative association with cIMT in people with diabetes (n=531) after adjusting for confounding variables. These associations were not observed in individuals without diabetes (p = 0.11 and p = 0.30, respectively).

Conclusion:
HDL
2
-C and HDL
3
-C subfractions, as well as the HDL
2
/HDL
3
-C ratio, are inversely associated with cIMT after adjustment for traditional risk factors. This association of HDL
2
-C/HDL
3
-C ratio and HDL
2
-C is modified by the presence of diabetes, where it is more pronounced.
Abstract P199: Alcohol Consumption Modified the Effect of Leptin on Blood Lipids: A Mendelian Randomization Study
Authors: Shen Luqi , Cordero Jose , Wang Jia-Sheng , Shen Ye , Li Changwei
Published: July 2021

Objective:
The current study aimed to evaluate the relation between leptin and serum lipids, and to explore whether alcohol consumption modifies the effect of leptin on lipids.

Method:
We conducted a Mendelian randomization analysis to the baseline data for 3,780 participants of the Framingham Heart Study Generation III cohort. A genetic risk score (GRS) for leptin was generated by summing leptin increasing alleles of 3 single-nucleotide polymorphisms, weighted by their corresponding effect sizes on leptin reported by Kilpelainen et al. For those taking lipid lowering medications, total cholesterol (TC) was adjusted as TC/0.8, and low density lipoprotein (LDL) was imputed by replacing the adjusted TC into the Friedewald equation. Leptin and triglycerides (TG) were log transformed. Associations between the GRS and leptin, leptin and imputed lipids, and GRS and imputed lipids were assessed, respectively, by multivariate linear regression models, controlling for age and sex in basic model and additionally controlling for education, smoking, drinking, and physical activity in the fully adjusted model. Interactions between the GRS and alcohol drinking was evaluated by adding an interaction term, GRS*drinking, in the fully adjusted model. Sensitivity analyses were performed among those not taking lipid or glucose lowering medications.

Result:
In univariate analyses, the GRS was significantly associated with leptin (Beta=1.44,
P
=4.55E-4), but not with age (
P
=0.33), sex (
P
=0.62), education (
P
=0.37), smoking (
P
=0.59), drinking (
P
=0.42), or physical activity (
P
=0.80). Leptin was significantly associated with age and sex adjusted LDL (Beta=7.29,
P
=5.95E-38), high density lipoprotein (HDL) (Beta=-4.30,
P
=4.35E-62), TG (Beta=0.22,
P
=1.05E-119), and TC (Beta=8.06,
P
=1.72E-36). The GRS for leptin was associated with HDL (Beta=-16.72,
P
=0.01), but not LDL (Beta=2.64,
P
=0.85), TG (Beta=-0.35,
P
=0.16), or TC (Beta=-23.34,
P
=0.15), in partially adjusted model. In the fully adjusted model, association between the GRS and HDL was still significant (Beta=-16.70,
P
=0.01). When stratified by drinking status, the GRS for leptin was significantly associated with reduced LDL (Beta=-99.26,
P
=0.02), TG (Beta=-2.4,
P
=0.002), and TC (Beta=-156.10,
P
=0.001) among non-current drinkers, and reduced HDL (Beta=-19.98,
P
=0.005) among current drinkers, adjusting for age and sex. After further adjustment, these associations were still significant. In the fully adjusted model, significant interactions between the GRS and alcohol drinking were identified for LDL (
P
=0.02), TG (
P
=0.005), and TC (
P
=0.008). Sensitivity analyses among those not taking lipid or glucose lowering medications revealed similar associations.

Conclusion:
Out study provided evidence for a causal relationship between leptin and lipids, and an interaction effect of alcohol drinking on leptin and lipids associations.
Abstract P202: Non-targeted Metabolomics Study Identify Multiple Metabolites Associated With Body Mass Index
Authors: Li Shengxu , Li Changwei , Kelly Tanika N , Gu Xiaoying , Sun Xiao , Bazzano Lydia , Chen Wei , Whelton Paul K , He Jiang
Published: July 2021

Background:
Non-targeted metabolomics technology provides a powerful tool to examine the complex etiology of obesity and the underlying mechanisms for its health consequences. The current study aimed to examine the associations of metabolites, quantified by non-targeted metabolomics technology, with body mass index (BMI) in the Bogalusa Heart Study.

Methods:
The study included 1,261 participants (825 White and 436 Blacks) aged 34-58 years. General linear models were used to examine the associations of BMI with the 1,202 metabolites that passed rigorous quality control measures, adjusted for age, sex, smoking, drinking, education, and total physical activity in Blacks and Whites, separately. Weighted correlation network analysis (WGCNA) was used to build metabolites modules according to pair-wise correlations (signed positive correlation and unsigned correlation regardless of correlation direction) among all metabolites; partial correlation was used to assess the link between each module and BMI.

Results:
Six-eight metabolites showed Bonferroni-corrected (P < 4.16E-5) associations with BMI in both Blacks and Whites. The most significant metabolite was glutamate (P = 1.52E-12 in Blacks and P = 1.47E-37 in Whites). Among the 46 significant metabolites with known identities, a majority were involved in pathways of lipids (22 metabolites) and amino acids (13 metabolites). Fifteen unsigned metabolites modules were identified and six of the modules showed significant correlation with BMI (absolute r = 0.11-0.14); ten signed metabolites modules were identified and five of them were significantly correlated with BMI (absolute r = 0.14-0.31).

Conclusion:
We have identified multiple metabolites robustly associated with BMI, which have novel biological implications for obesity and its health consequences.
Abstract P204: Growth and Moderators of Pulse Wave Velocity From Childhood to Adulthood
Authors: Liang Xiaohua , Su Shaoyong , Hao Guang , Snieder Harold , Treiber Frank , Kapuku Gaston , Wang Xiaoling
Published: July 2021

Background:
Increased arterial stiffness measured by pulse wave velocity (PWV) has been shown to be an important parameter in the assessment of cardiovascular risk. However little is known about its longitudinal development from childhood to adulthood and its possible sociodemographic, anthropometric, hemodynamic and behavioral moderators.

Methods and Results:
Individual growth curves of carotid-distal PWV across age were created for 559 African American and European American males and females with a maximum of 5 assessments over a 13-year period (age, 13.7-37.3). African Americans and males had significantly higher PWV than did European Americans and females (Ps<0.01), respectively. A 3-way interaction (P<0.01) between age, gender and ethnicity was observed with African American males displaying a larger rate of increase in PWV with age than the other 3 ethnic and gender groups. The ethnicity and gender effects on PWV persisted when controlling for other moderators. Waist circumstance was the strongest anthropometric predictor but its effect on PWV was only significant in females. Mean arterial pressure was the strongest hemodynamic predictor, marital status of parents was the strongest socioeconomic predictor, and illegal drug use was the strongest behavioral predictor of PWV. The best-fitting full model explained in total 61.6% of the between-subject variance in PWVwith ethnicity, genderand age explaining25%.

Conclusion:
We observed significant ethnic and gender differences in longitudinal trajectories of PWV in youth and young adults. Apart from these ethnicity and gender effects, individual differences in PWV growth can largely be explained by mean arterial pressure, waist circumstance, marital status and illegal drug use.
Abstract P212: Combined Analysis of Longitudinal Cohorts With Case-only Sample Sets for Detecting Genetic Effects on Venous Thromboembolism in Topmed
Authors: Seyerle Amanda A , Coombes Brandon , Laurie Cecelia A , Sofer Tamar , Smith Nicholas L , Tang Weihong , de Andrade Mariza , Kooperberg Charles , Pankow James , Rice Ken , McKnight Barbara , Laurie Cathy C
Published: July 2021

Background:
The Trans-Omics for Precision Medicine (TOPMed) program is performing whole-genome sequencing across multiple studies, including longitudinal cohorts, case-control, and case-only sample sets. Detecting the effects of low frequency variants requires large sample sizes, which can only be achieved by combining data across diverse study designs, including matching of case-only sample sets with controls from other studies. Here we present a strategy for combined analysis of venous thromboembolism (VTE) case status in 3 longitudinal cohorts and 3 case-only sample sets, in the context of whole-genome association studies.

Methods:
For each cohort study, we sampled ‘pure’ controls (without replacement) from the risk set of each incident case, within strata defined by sex, ancestry and birth-cohort. Pure controls had no event throughout their period of observation. A case’s risk set was defined as controls with no prior VTE history and under observation through an age at least as old as the case. For case-only sample sets, controls for each case were sampled from a cohort study, using the same risk set definition. Because of limited overlap in birth years between the cohort studies and the case-only sample sets, this matching was done within strata defined only by sex and ancestry group. Mixed model logistic regression will be used to account for relatedness as a random effect. Although conditional logistic regression is not practical for whole-genome association studies, case-control matching is implicitly recognized by a fixed effect for age-at-event for each matched set (1 case and >=1 matched controls). Additional fixed effects will include sample set and sex. We will also adjust for variations in case-control ratio among the matched sets.

Results:
In two cohort studies, we matched 1,231 cases to 4,820 controls (overall ratio = 1:3.9); only 500 controls and 5 cases could not be matched. For the case-only sample sets we matched 2,141 cases to 2,780 controls from one cohort study (overall ratio = 1:1.3); zero controls and only 14 cases could not be matched.

Conclusions:
We were successfully able to match nearly all cases to controls, and more than 90% of controls were also matched. By matching controls to cases based on age at event, we can account for the different risk of VTE by age clusters. Although this strategy does not provide an asymptotically unbiased estimated of the hazard ratio, compared to classical risk set sampling, it uses a large portion of the available data, it provides odds ratio estimates yielding the correct sign of association, and it reduces the potential influence of resampling subjects with rare variants. This strategy also enables combined analysis of multiple studies with different designs.
Abstract P220: Elevated De Novo Lipogenesis Fatty Acids and Lower Omega-6 Fatty Acids Are Associated With Markers of Insulin Resistance and Respond to Changes in Dietary Carbohydrate Intake in Overweight Individuals on Weight Loss Diets
Authors: Jackson Kristina H , Harris William S , Gardner Christopher D
Published: July 2021

Background:
High blood levels of certain fatty acids (FAs) in the de novo lipogenesis pathway (DNL; i.e., 16:0, cis-16:1n7) and low levels of omega-6 FAs (n-6 FA; i.e., 18:2n6) have been related to increased risk for type 2 diabetes. We hypothesized that individuals with insulin resistance (IR) would have higher DNL and lower n-6 FA plasma levels than insulin sensitive (IS) individuals, and that DNL FA levels would decrease on a low-carbohydrate (LC) diet and not change on a low-fat (LF) diet.

Methods:
Plasma FAs were measured as a % of total FA in subjects (n=61) with varying degrees of obesity and IR before and after 6 months of LF or LC weight loss diets. IR metrics were calculated pre- and post from oral glucose tolerance tests and fasting blood samples. FA medians (Interquartile Range), Spearman correlations (R) and Mann-Whitney test results are presented.

Results:
All differences shown are significant at P<0.05 unless reported as not significant (NS). Compared to the IS group, IR individuals had higher 16:0 (IR: 22.9% [22.2, 24.3] vs IS: 21.7% [20.2, 22.5]) and 16:1n7 (IR: 1.8% [1.4, 2.2] vs IS: 1.3% [1.1, 1.6]), and lower 18:2n6 (IR: 30.8% [27.8, 31.6] vs IS: 32.5% [30.0, 34.6]) levels at baseline. 16:0 and 16:1n7 were directly related to BMI (0.40, 0.28), fasting insulin (0.40, 0.33), HOMA-IR (0.40, 0.43), TG:HDL (0.38, NS) and indirectly to Matsuda Index (-0.35, -0.34). 18:2n6 was directly related to the Matsuda Index (0.35) and indirectly to HOMA-IR (-0.37) and TG:HDL (-0.45). Diet x IR status analyses were not significant, thus FA changes on LC and LF diets were compared. 16:1n7 decreased on the LC diet and did not change on the LF diet (LC: -0.5% [-0.7, -0.3] vs LF: -0.1% [-0.3, 0.2]). 18:2n6 levels increased on the LC diet and decreased on the LF diet (LC: 0.9% [-0.3, 2.7] vs LF: -0.5% [-2.4, 0.6]). Changes in dietary carbohydrate (% of calories) correlated with changes in 16:1n7 directly (0.38) and 18:2n6 indirectly (-0.37). Changes in 16:1n7 were directly related to changes in weight (0.55) and TG:HDL (0.65), and changes in 18:2n6 were indirectly related to TG:HDL changes (-0.51).

Conclusions:
Elevated plasma DNL FA and lower 18:2n6 were evident in IR vs. IS individuals, and individual markers of IR were related to FA levels accordingly. DNL and 18:2n-6 responded to changes in carbohydrate intake. FA patterns may be a useful tool to identify IR individuals and track carbohydrate consumption.
Abstract P222: Consumption of Sugar-Sweetened Beverages, but Not 100% Fruit Juice, is Associated With Fasting High-density Lipoprotein and Triglyceride Concentrations in U.S. Adults
Authors: Haslam Danielle E , Herman Mark A , Dupuis Josée , Lichtenstein Alice H , Peloso Gina M , Smith Caren E , McKeown Nicola M
Published: July 2021

Introduction:
Dyslipidemia, characterized by high triglyceride (TG) and low HDL concentrations, is a risk factor for cardiovascular disease (CVD). Decreasing dietary sugar consumption is one dietary modification that may influence dyslipidemia risk to reduce the risk for CVD. Two major sources of dietary sugar in the US are sugar-sweetened beverages (SSB) and 100% fruit juices, and both can contribute to excess caloric intake. Based on current observational data, there is limited evidence linking these dietary exposures to lipid levels in population-based studies.

Hypothesis:
We hypothesize that SSB and 100% fruit juices may differentially associate with TG and HDL concentrations in adults due to differences in both beverage consumption patterns and nutrient content.

Methods:
We conducted a cross-sectional analysis of data from the Framingham Heart Study (1998-2005; n=6,802). Fasting plasma TG and HDL concentrations were measured using standard assays. Consumption of SSB (sodas and fruit drinks; 1 serving = 12 oz.) and 100% fruit juice (1 serving = 8 oz.) was estimated using the Harvard-Food Frequency Questionnaire. Participants were grouped by category of intake. Using mixed-effect linear regression models accounting for family structure, we examined the associations between SSB intake and 100% fruit juice intake with TG and HDL concentrations, adjusting for potential confounding factors related to demographics, lifestyle, and diet.

Results:
After multivariate adjustment for potential confounding factors, SSB intake was positively associated with TG concentrations [ β ± SE: 0.12 ± 0.03 [ln] mg/dl comparing the highest category of intake (median = 8.5 servings/week) with the lowest category (median = 0 servings/day); p for trend < 0.0001] and inversely associated with HDL concentrations ( β ± SE: -2.90 ± 0.69 mg/dl comparing the highest category of intake with the lowest category; p for trend < 0.0001). Fruit juice intake was not significantly associated with TG concentrations [ β ± SE: 0.04 ± 0.02 [ln] mg/dl comparing highest category of intake (median = 11 servings/week) with the lowest category (median = 0 servings/day); p for trend = 0.15] or HDL concentrations ( β ± SE: -0.18 ± 0.60 mg/dl comparing the highest category of intake with the lowest category; p for trend = 0.73).

Conclusions:
Higher intakes of SSB are significantly associated with lower HDL and higher TG concentrations, which supports dietary recommendations to limit SSB intake. Fruit juice consumption patterns, up to 1.5 servings/day, were not significantly associated with TG and HDL concentrations in this study.
Abstract P225: The Associations of Dietary and Biomarkers of Linoleic Acid Intake and All-cause and Cardiovascular Mortality: A Systematic Review and Meta-analysis
Authors: Li Jun , Guasch-Ferré Marta , Li Yanping , Hu Frank
Published: July 2021

Background:
Previous studies on intake of linoleic acid (LA), a predominant n-6 fatty acid, and risk of mortality from all-cause and cardiovascular disease (CVD) have generated inconsistent results. We performed a systematic review and meta-analysis of prospective cohort studies to summarize the evidence regarding the relation of LA and all-cause and CVD mortality.

Methods:
We searched MEDLINE and EMBASE databases through June 2017 for prospective cohort studies reporting association of LA (assessed by dietary survey or biomarker in blood or adipose tissue) with all-cause and CVD mortality. In addition, unpublished data from pooling projects were included. We pooled the multivariate-adjusted Hazards ratios (HRs) using random-effect meta-analysis, which allowed for between-study heterogeneity.

Results:
27 studies covering 37 prospective cohorts were identified; these included 274,565 individuals with dietary assessment (34,597 all-cause and 10,636 CVD deaths) and 54,794 individuals with biomarker measurements (6,767 all-cause and 5,311 CVD deaths). Comparing the highest category with the lowest, dietary LA intake was associated with a 14% lower risk of all-cause mortality (95% confidence interval [CI], 2%-25%,

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2

=71%) and a 20% lower risk of CVD mortality (95% CI, 13%-26%,

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=0). Baseline health status (i.e. general population, CVD/high risk for CVD, or cancer) might be a main source of heterogeneity for the association of dietary LA intake with all-cause mortality. As for biomarkers, 1 SD increment in LA was associated with a 9% lower risk of all-cause mortality (95% CI, 4%-14%,

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=61%) and a 10% lower risk of CVD mortality (95% CI, 5%-14%,

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=13%). Heterogeneity was presented across tissue types and between genders.

Conclusions:
In prospective cohort studies, LA intake, assessed by either dietary survey or biomarkers, was inversely associated with all-cause and CVD mortality in a dose-response manner. These data support the current recommendations on polyunsaturated fat intake for prevention of CVD and early death.
Abstract P226: HEalth Nutritional Index (HENI): A Health Burden Based Tool for Food and Diet Nutritional Evaluation
Authors: Stylianou Katerina , Fulgoni Victor L , Jolliet Olivier
Published: July 2021

Introduction:
The role of diets on human health is crucial and depends on the quality of the food we eat. A number of indexes help rank food items and evaluate diets based on their nutrient profiling and meeting dietary guidelines, respectively. Existing nutritional indexes fail to quantify the varying effects of major food groups and nutrients on human health. We introduce the HEalth Nutritional Index (HENI), a health burden-based scoring system in disability adjusted life years (DALYs) that uses epidemiological evidence from the Global Burden of Disease (GBD) to rank and evaluate food items and diets.

Methods:
HENI accounts for the health effects of 8 major food groups (nuts and seeds, whole grains, fruits, vegetables, milk, sugar-sweetened beverages, red meat, and processed meat) and 6 nutrients (omega-3, calcium, fiber, polyunsaturated fatty acids, trans fat, and sodium), identified by the GBD as dietary risk factors. The HENI factors are estimated by coupling age- and gender-adjusted outcome-specific incidence rates with risk ratios (RR) and severity factors, measuring positive or detrimental effects in avoided μDALY/g. We determine the food group and nutrient profile for each of the 5000+ consumed food items in the What We Eat in America 2009-2014 dataset, using multiple databases such as the Food Patterns Equivalents Database (FPED), the Food and Nutrient Database for Dietary Studies (FNDDS), and the USDA National Nutrient Database for Standard Reference (SR). We then derive the HENI scores for 100 kcal, 100 grams or 1 serving of each food item by multiplying the food group and nutrient composition by their respective HENI factors.

Results:
HENI factors for food group and nutrient range between -8 μDALY/g for sodium, up to 57 μDALY/g for omega-3 from fish and seafood. HENI score typically ranges from -30 avoided μDALY/100kcal for e.g. soft drinks, up to +50 avoided μDALY/100kcal, for beneficial food items such as fish, fruits, vegetables, and nuts. The majority of the health effect is associated with cardiovascular diseases, with some food items affecting certain cancers (e.g. health benefit for colorectal cancer with milk). Absolute HENI scores and ranking of food items vary substantially when using 100 kcal, 100 grams or 1 serving as a basis for comparison. In a sensitivity study, we consider the indirect effect of saturated fat via total blood cholesterol is considered which can play an important role for animal-based food items, requiring further investigation. The HENI factors are applicable under the assumption that the overall dietary intake of each GBD food group and nutrient is within the effective intake range, below the theoretical risk level limit.

Conclusion:
The proposed HENI index enables to quantify the human health impact of thousands of food items, bringing on the same scale different nutritional impacts, allowing for a comprehensive assessment of food items and diets.