bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 836: Impact of Hypoadiponectinemia on Left Ventricular Remodeling after Primary Coronary Intervention for Acute Myocardial Infarction
Authors: Arita Yukio
Published: July 2021

Left ventricular (LV) remodeling after acute myocardial infarction (AMI) is a precursor of the development of overt heart failure and is an important predictor of mortality. Adiponectin (AN) is an adipose-derived plasma protein that has the cardio-protective role against ischemia-reperfusion injury. Altered activity of matrix metalloproteinase (MMP) family has been implicated in the development of LV remodeling after myocardial infarction. Serum AN levels affect MMPs and tissue inhibitor of MMP (TIMP) levels, and attenuate adverse LV remodeling after AMI. In 88 consecutive patients with AMI successfully treated with primary percutaneous coronary intervention (PCI), serum levels of AN, MMP-2, MMP-9, and TIMP-1 were measured on admission, at day 7, and at 6 months after the onset. LV end-diastolic volume index (EDVI) and ejection fraction (EF) were assessed with
99m−
Tc-tetrofosmin quantitative gated single-photon emission computed tomography within 10 days (early) and six months (chronic) after the onset. Serum AN and MMP-2 levels were decreased and serum MMP-9 and TIMP-1 levels were increased at day 7 compared to those at the onset and 6 months. Chronic/early EDVI ratio was negatively correlated with log AN at day 7 (r= −0.265, p=0.013), log AN at 6 months (r= −0.335, p=0.008), log MMP-2 at day 7 (r= −0.229, p=0.042), and positively correlated with log MMP-9 at day 7 (r= 0.237, p=0.037), log TIMP-1 on admission (r=0.277, p=0.0408). Chronic EF was positively correlated with log AN at day 7 (r=0.225, p=0.0374) and negatively correlated with log TIMP-1 at day 7 (r= −0.281, p=0.0133). Multiple logistic regression analyses revealed that chronic/early EDVI ratio independently correlated with log AN (r= −0.249, p=0.034) at day 7, although Log AN correlated positively log MMP-2, and negatively with log MMP-9 both at day 7 and 6 months. Measurement of AN at subacute phase can predict adverse cardiac remodeling in patients with AMI successfully treated with PCI.
Abstract 2165: Harvesting the Energy of Cardiac Motion to Power a Pacemaker
Authors: Roberts Paul , Stanley Giles , Morgan John M
Published: July 2021

There is significant motion of the heart with each cardiac cycle. We examine the feasibility of harvesting surplus energy (HE) using a catheter-mounted device (CMD) that could be incorporated into a pacemaker/ICD lead and assist powering. The CMD consisted of a pacemaker electrode incorporating a coaxially mounted device with 2 pressure responsive bladders that utilise cardiac pressure (RV/RA) to drive a linear generator. CMD was placed at the RVA of an anesthetized pig (Landrace, 45kg) via the internal jugular vein. Arterial and RV pressure were recorded. The energy generated by the device was continuously monitored using a portable data acquisition system during steady state and then during induced tachycardia (isoproterenol), bradycardia (adenosine) and hypotension (pentobarbital). Placement of the device was uncomplicated. The figure

illustrates the effect of 4 mcg isoproterenol on HE from device. In steady state (80 bpm, BP 100/60) the energy generated by each cardiac cycle was 4.3μJ (variance ± 0.8μJ). Incremental changes in heart rate produced a corresponding increase in HE e.g. 104 to 128 bpm produced 140% increase in HE (10.0μJ). Relative bradycardia/hypotension following adenosine/pentobarbitol administration produced a proportionate decrease in HE. Post mortem examination demonstrated no significant endocardial trauma. This study has demonstrated the feasibility of energy harvesting of cardiac motion. The device produced 17% of the energy required to power a conventional pacemaker. With further material modification it is envisaged that HE will be efficient enough to allow for complete and indefinite powering of pacemakers.
Abstract 2248: Prevalence and Long-term Clinical Significance of Aortic Root Dilatation in Competitive Athletes
Authors: Di Paolo Fernando M , De Blasiis Elvira , Guerra Emanuele , Pisicchio Cataldo , Quattrini Filippo M , Di Giacinto Barbara , Ciardo Roberto , Caselli Stefano , Culasso Franco , Pelliccia Antonio
Published: July 2021

OBJECTIVES: Prevalence, clinical significance, and long-term consequences of aortic root (AoR) dilatation in competitive athletes are not yet investigated. Our aim was to assess the distribution and determinants of AoR size in a large population of competitive athletes.

METHODS: AoR dimension were assessed by echocardiography in 2,361 athletes participating in 48 different sports. Of them, 43 were excluded because aortic structural abnormalities, such as bicuspid aortic valve, Marfan’s Syndrome, aortic prosthesis. The remaining 2,318, including 1,301 (56%) males and 1,017 (44%) females were the study population. Arbitrary cut-off of ≥ 40 mm, according to #36
th
Bethesda Conference, was used as upper normal limits for AoR.

RESULTS: AoR dimension was 32.2 ± 2.7 mm (23 to 44) in males, and 27.5 ± 2.6 mm (20 to 36) in females. AoR dimension exceeded accepted upper limits in only 18 male athletes (0.8%). Figure

. Multivariate regression analysis showed left ventricular (LV) mass and body size explaining majority of AoR variability (R
2
= 0,59). Surprisingly, type of sport was not a determinant for AoR dimension. The 18 athletes with enlarged AoR were periodically followed for 7.0 ± 4.2 years. None developed cardiovascular events or symptoms. Two showed progression of AoR dilatation (from 40 to 48, and 43 to 46 mm, respectively), one had incident myocarditis and one developed moderate aortic regurgitation with enlarged LV cavity.

CONCLUSIONS: Dilated aortic root is an uncommon finding in competitive athletes and do not represent expression of physiologic cardiac remodelling of the athlete’s heart. Therefore, athletes with dilated AoR deserves continued clinical surveillance.
Abstract 2287: Prosthesis-Patient Mismatch is an Independent Predictor of Short-Term Mortality Following Mitral Valve Replacement
Authors: Magne Julien , Mathieu Patrick , Dumesnil Jean G , Charbonneau Eric , Pibarot Philippe
Published: July 2021

Recent studies have shown that prosthesis-patient mismatch (PPM) is associated with an increased incidence of pulmonary hypertension and congestive heart failure and with reduced long-term survival following mitral valve replacement (MVR). The objective of this study was to examine the effect of PPM on operative mortality following MVR. The indexed valve effective orifice area (EOA) was estimated for each type and size of prosthesis being implanted in 1049 consecutive patients undergoing MVR±CABG and used to define PPM as not clinically significant if >1.2 cm
2
/m
2
, as moderate if >0.9 cm
2
/m
2
and ≤1.2 cm
2
/m
2
and as severe if ≤0.9 cm
2
/m
2
. Moderate PPM was present in 56% of patients and severe PPM in 12%. The overall operative mortality (OM) was 7% (n=73) and 84% were from cardiac causes (n=61, 6% of the whole cohort). Patients with severe PPM had higher overall OM (14%, p=0.0003) as well as operative cardiac-related death (CRD) (12%, p=0.007) than patients with moderate (OM: 6%, CRD: 5%) or nonsignificant PPM (OM: 6%, CRD: 4%). On multivariate analysis, severe PPM was an independent predictor of overall OM (Odds-ratio [OR]= 2.6 [95% confidence interval (CI): 1.3– 4.8], p=0.0045) and of operative CRD (OR= 2.3 [95%CI: 1.1– 4.4], p=0.02). Among the subset of 703 patients undergoing isolated MVR (i.e. without concomitant CABG), patients with severe PPM also had higher overall OM (12%, p=0.0025) than patients with moderate (4%) or nonsignificant PPM (3%). Mitral PPM was also a powerful independent predictor of both overall OM (OR=4.8, 95%CI: 1.8 –12.1, p=0.0009) and operative CRD (OR=3.2, 95%CI: 1.03– 8.7, p=0.03) in this subset of patients. Severe PPM is a strong independent predictor of both overall operative mortality and cardiac-related death after MVR. Hence, the projected indexed EOA should be systematically calculated at the time of operation prior to prosthesis implantation and an effort should be made to implant prosthesis with a larger EOA in patients who are identified as being at risk of severe PPM
Abstract 2686: Survival Unchanged Five Months After Implementing The 2005 AHA CPR And ECC Guidelines For Out-of-hospital Cardiac Arrest
Authors: Bigham Blair L , Koprowicz Kent , Kiss Alex , Dorian Paul , Emerson Scott , Zhan Cathy , Rea Thomas D , Aufderheide Tom P , Powell Judy , Cheskes Sheldon , Davis Daniel P , Stouffer John A , Perry Jeff , Lees Martin , Morrison Laurie J
Published: July 2021

Introduction:
To improve survival from out of hospital cardiac arrest (OHCA), the American Heart Association released guidelines in 2005. We examined the effect of these guidelines on survival in the Resuscitation Outcomes Consortium (ROC) Epistry - Cardiac Arrest. We hypothesized that survival would increase after guideline implementation.

Methods:
174 EMS agencies from 8 of 10 ROC sites were surveyed to determine 2005 AHA guideline implementation, or crossover, date. Two sites with 2005 compatible treatment algorithms prior to guideline release were not included. Patients with OHCA secondary to a non cardiac cause, EMS witnessed events, patients <18 years old, and patients with do-not-resuscitate orders were excluded. A linear mixed effects model was applied for survival controlling for time and agency. The “crossover” date was added to the model to determine the effect of the 2005 guidelines.

Results:
Of 174 agencies, 83 contributed cases to both cohorts during the 18 month period between 2005/12/01 and 2007/05/31. Of 7403 cases, 4897 occurred during the 13 month (median) interval before crossover and 2506 occurred in the 5 month (median) interval after crossover. The overall survival rate was 5.9%. Our model estimated an overall increase in survival over time (monthly OR 1.02, 95% CI 0.99, 1.04, p=0.23), a decrease in survival at crossover (OR 0.92, 95% CI 0.66, 1.26, p=0.59), and a further increase in survival over time after crossover (monthly OR 1.005, 95% CI 0.96, 1.05, p=0.84).

Conclusion:
This study found a trend towards increased survival over time and no statistically significant effect of the 2005 guidelines early after implementation. This observed increase in survival over time may be attributed to the Hawthorne effect or participation in ROC or improved quality assurance. A delay in knowledge and skill acquisition amongst EMS providers and the need to rechoreograph their cardiac arrest treatment may explain why no significant increase in survival was observed after implementation. EMS providers may require more time to gain proficiency in the guideline changes before the full potential of the guidelines can be realized. Further longitudinal study is needed to determine the full impact of the guidelines on survival.
Abstract 3084: Bare Metal Stenting versus Percutaneous Pulmonary Valve Implantation for Treatment of Right Ventricular Outflow Tract Obstruction - Utilization of a Catheter/Magnetic Resonance Hybrid Lab for Acute Physiological Comparison
Authors: Lurz Philipp , Nordmeyer Johannes , Khambadkone Sachin , Derrick Graham , Yates Rob , Muthurangu Vivek , Jones Rod , Bonhoeffer Philipp , Taylor Andrew M
Published: July 2021

Background: Treatment of right ventricular outflow tract obstruction (RVOTO) is possible with a bare metal stent (BMS), though this causes pulmonary regurgitation (PR). In this study, we sought to assess the acute physiological effects of BMS vs. percutaneous pulmonary valve implantation (PPVI) using a catheter/ magnetic resonance (MR) hybrid lab (Siemens).

Methods: 12 consecutive children (median age 12.9) with significant RVOTO (echo gradient > 50 mmHg) were included. Patients were initially placed in the MR scanner and the ventricular volumes and great vessel blood flow assessed under general anaesthetic (GA). Patients were then transferred into the bi-plane catheter lab (under the same GA, on a sliding table) and a BMS inserted. Catheters and wires were removed and patients were transferred back to MR for repeat assessment. This whole process was repeated for a PPVI, which was placed into the BMS. MR and pressure data were compared with repeated measures ANOVA and post-hoc testing between the 3 physiological states.

Results (see Table

): BMS placement significantly reduced RV pressures and caused free PR. The increased PR was partially compensated for by a decrease in RV ESV and an increase in RV EF. There was no improvement in effective RV SV after BMS placement. Re-valvulation with PPVI resulted in a significant increase in effective RV SV, with consequent heart rate reduction at maintained cardiac output.

Conclusion: Utilisation of a catheter/MR hybrid lab offers new opportunities for the assessment of acute physiology following percutaneous interventions. Using this method we have demonstrated the superior acute haemodynamic effects of PPVI over BMS in patients with RVOTO.
Abstract 4331: Elevated Albumin Excretion is an Independent Risk Factor in Patients with Chronic Heart Failure. Data from the GISSI-Heart Failure Trial
Authors: Masson Serge , Moretti Luciano , Mazzoni Ospedale , Rossi Maria Grazia , Carbonieri Emanuele , Frisinghelli Anna , Gualco Alessandra , Minneci Sergio , Valisi Massimiliano , Milani Valentina , Maggioni Aldo P , Latini Roberto
Published: July 2021

Elevated albuminuria, a marker of endothelial renal damage, is a risk factor for cardiovascular events in the general population and in patients with diabetes or hypertension. We report here on its association with mortality in a large population of patients with chronic HF. Albuminuria (albumin/creatinine concentration ratio in a morning spot sample, UACR) was determined in 2131 patients with chronic HF enrolled in 77 centers participating to the GISSI-HF trial. Patients were divided according to normal (UACR <30 mg/g) and abnormal urinary excretion of albumin (≥30 mg/g). Association between elevated albuminuria and all-cause mortality was tested by univariable and multivariable analyses. Elevated albuminuria was found in 25.3% of the population (age 67±11 y, 78.9% males, 30.1% NYHA class III-IV, 55.5% hypertension, 26.1% diabetes) and was more frequent in older patients, those with reduced renal function, diabetes or high CRP. Mortality was significantly higher in patients with elevated albuminuria (20.1% at 1000 days) compared to normals (9.0%, p<0.0001). Elevated albuminuria remained an independent risk factor for all-cause mortality (HR [95%CI] 1.47 [1.18 –1.82]) in a Cox model adjusted for clinical risk factors such as age, gender, NYHA class, renal function, diabetes, BMI and blood pressure. About a quarter of the patients enrolled in the GISSI-HF trial had abnormal urinary albumin excretion, a marker for both renal and systemic vascular disease. We show for the first time in a large representative sample that elevated albuminuria is an independent predictor of all-cause mortality in patients with chronic HF.
Abstract 4627: Specifically Enhancing Inward Rectifying Potassium Current (i
K1
) : A New Antiarrhythmic Strategy
Authors: Liu Qinghua , Li Xiaoli , Lin Yuanyuan , Li Yuan , Wu Bowei
Published: July 2021

Background: The inward rectifier K
+
current (I
K1
) plays a significant role in the final repolarization and resting phases of the ventricular action potential. Modulation of I
K1
would likely have a profound effect on cardiac excitability and arrhythmogenesis. However, there has been no I
K1
-specific pharmacologic agent found so far. We identified zacopride, a benzamide derivatives acting on 5-HT
4
receptor, as a specific agonist of I
K1
and effective antiarrhythmic drug.

Methods and results: Part I. The whole-cell patch-clamp technique was used to record effect of zacopride on membrain ionic current I
K1,
I
Ca-L
, I
Na,
I
to
, I
Na/Ca,
I
pump
, and action potential (AP). We found that zacopride in 0.1~10μmol/L had no effects on I
Ca-L
, I
Na,
I
to
, I
Na/Ca,
I
pump
, but enhanced I
K1
concentration-dependently. The optimal concentration appeared in 1~3μmol/L with approximately 30% increase which can be abolished by low concentration of BaCl
2
(1 μmol/L), or 10μmol/L 5-HT
4
-receptor antagonist RS23597. Otherwise, zacopride could increase resting membrane potential from −81.3±0.9 up to −87.5±1.7mv (P < 0.01) with APD
90
slightly shorten. Part II. Langendorff-perfused hearts were subjected to either coronary artery occlusion for 30 minutes, or 15 minutes followed by 15minutes reperfusion. We monitored and compared the rhythm disturbances in experimental vs. placebo-treated hearts (n = 16 in each group). Zacopride in 1μmol/L was supplied 3 minutes before ischemia or reperfusion treatment. Far more dramatic protection was observed during ischemia. Zacopride treatment reduced the incidence of ventricular tachycardia from 100% to 25% (P<0.01) and ventricular fibrillation from 75% to 12.5% (P < 0.01), the number of premature ventricular beats from 173±26 to 9±4 (P< 0.05). Less protection was observed during reperfusion. The incidence of ventricular tachycardia and ventricular fibrillation declined from 100% to 68.8% (P<0.05) and from 75% to 25% (P < 0.05) respectively. The number of premature ventricular beats decreased but without statistical significance. Conclusion: Zacopride in 0.1~10μmol/L specifically enhanced I
K1
. It would be used as the first specific I
K1
agonist and showed a significant antiarrhythmic effect during acute myocardial ischemia and reperfusion.
Abstract 4928: Natural Endothelium Mimicking Self-Assembled Nanomatrix for Drug Eluting Stent Applications
Authors: Jun Ho-Wook , Kushwaha Meenakshi , Anderson Joel , Minor William , Andukuri Adinarayana , Bosworth Charles , Lancaster Jack , Brott Brigitta , Anderson Peter
Published: July 2021

Deployment of stents has been a major therapeutic method for treatment of cardiovascular diseases. However, poor endothelialization and intimal hyperplasia in bare metal stents lead to restenosis. Drug eluting stents (DES) are designed to deliver therapeutic drugs to prevent intimal hyperplasia and have been implanted in about 6 million patients for last three years. However, recent reports suggest that DES have been associated with a higher risk of late thrombosis which may be related to inadequate endothelialization. Therefore, the main goal of this project is to develop the next generation of DES using a natural endothelium mimicking self-assembled nanomatrix which will inhibit both restenosis and thrombosis while enhancing endothelialization from surrounding endothelium and endothelial progenitor cells circulating in the blood stream. The nanomatrix is formed by self-assembly of peptide amphiphiles (PAs) which contain nitric oxide (NO) producing donors and endothelial cell adhesive ligand YIGSR along with enzyme-mediated degradable sites. Successful synthesis of PAs and the self-assembly of the PAs into nanofibers with the diameter of 8 nm forming the nanomatrix were characterized by MALDI-TOF mass spectrometry and transmission electron microscope, respectively. The nanomatrix showed significantly greater attachment and spreading of human umbilical vein endothothelial cells (HUVECs) compared to human aortic smooth muscle cells (AoSMCs). The nanomatrix was reacted with NO solution and NO was released from the nanomatrix rapidly within 24 hours followed by sustained release over period of 5 days. The NO releasing nanomatrix demonstrated a significantly enhanced proliferation of HUVECs (51 ± 3 % to 67 ± 2 %) but reduced proliferation of AoSMCs (35 ± 2 % to 16 ± 3 %) after 48 hrs of incubation. Platelet attachment on the nanomatrix is under investigation. A natural endothelium mimicking nanomatrix was successfully synthesized and supported growth of endothelial cells while inhibiting growth of smooth muscle cells. Therefore this nanomatrix could have a great potential to improve clinical patency of DES as a coating material by enhancing endothelialization but reducing restenosis.
Abstract 019: Oxidized LDL and AGE-LDL in Circulating Immune Complexes Strongly Predict Progression of Carotid IMT in Type 1 Diabetes
Authors: Hunt Kelly J , Baker Nathaniel L , Cleary Patricia , Backlund Jye-Yu , Virella Gabriel , Lopes-Virella Maria F ,   DCCT/EDIC Rsch Group
Published: July 2021

Many studies have demonstrated a relationship between modified LDL and cardiovascular disease. Nonetheless, few studies have examined the relationship between modified LDL immune complexes (IC) and cardiovascular disease, even though the majority of modified LDL in circulation is bound to IC. We report the relationship between circulating concentrations of IC of oxidized LDL (oxLDL-IC), malondialdehyde-LDL (MDA-LDL-IC) and advanced glycation end products-LDL (AGE-LDL-IC) and progression of atherosclerosis over a 12 year period in individuals with type 1 diabetes. OxLDL-IC, AGE-LDL-IC and MDA-LDL-IC levels were measured in a subgroup of 459 patients participating in the Diabetes Control and Complications Trial (DCCT) and it’s follow up study the Epidemiology of Diabetes Interventions and Complications (EDIC). Internal carotid intima-medial thickness (IMT) was measured at EDIC follow-up years 1, 6 and 12. Levels of oxLDL-IC, AGE-LDL-IC and MDA-LDL-IC were moderately correlated with lipid levels [i.e., rho<0.32], but not with age. Modified LDL-IC significantly predicted having elevated internal carotid IMT (i.e., IMT ≥1.00 mm) as well as progression of IMT defined as being in the upper quintile of change from EDIC year 1 to 12 after adjusting for DCCT treatment group [intensive vs. conventional], retinopathy cohort [primary prevention vs. secondary intervention], age, gender, diabetes duration, albumin excretion rate, LDL, HDL, SBP, smoking status and IMT reader (Table). Relative to those in the lowest quartile, individuals in the upper quartile of oxLDL-IC had a 3.7-fold increased odds (CI: 1.72, 7.94) of having IMT ≥ 1.00 mm and had a 6.1-fold increased odds (CI: 2.57, 14.6) of having significant IMT progression. Parallel odds ratios for AGE-LDL-IC were 3.26 (CI: 1.57, 6.79) and 5.31 (CI: 2.23, 12.6), while results for MDA-LDL-IC were not as strong. Our study indicates that high levels of oxLDL-IC and AGE-LDL-IC are important predictors of carotid intima-medial thickening in patients with type 1 diabetes.
Abstract 037: Ace Inhibitor Use by Older Adults is Associated with Improved Functional Responses to Exercise
Authors: Buford Thomas W , Manini Todd M , Hsu Fang-Chi , Cesari Matteo , Anton Stephen D , Nayfield Susan , Stafford Randall S , Church Timothy S , Pahor Marco , Carter Christy S ,   LIFE Rsch Group
Published: July 2021

Introduction:
Functional status, assessed objectively by measures of physical performance, is a strong predictor of cardiovascular events in older adults. Angiotensin converting enzyme (ACE) inhibitors may further enhance the beneficial effects of exercise training on the functional status of older adults, but studies are lacking to confirm. The objective of this study was to assess the association of ACE inhibitor use with exercise-derived improvements in physical function among physically-limited older adults.

Hypothesis:
Older adults who used ACE inhibitors would have larger improvements in physical function in response to exercise than non-users.

Methods:
This study is a secondary analysis of the Lifestyle Interventions and Independence for Elders Pilot (LIFE-P) study. LIFE-P investigated the effects of 12-month interventions consisting of either structured physical activity or health education to promote successful aging on 424 adults aged 70-89 years at risk for becoming physically disabled. This analysis compared change in outcome measures at 6- and 12-months among participants who (1) did not use anti-hypertensive drugs, (2) used ACEi, and (3) used anti-hypertensive drugs excluding ACEi. The primary outcome measures were change in performance on a battery of short-duration mobility tasks (SPPB) and walking speed during a 400 meter test.

Results:
A significant medication by intervention interaction existed for SPPB (p=0.018). PA improved the adjusted SPPB score among ACEi users (p<0.001) and users of other anti-hypertensive drugs (p=0.005) but not among anti-hypertensive non-users (p=0.911). Adjusted SPPB changes at 12 months were 0.95 points among ACEi users, 0.77 points among users of other anti-hypertensive drugs, and -0.08 points among anti-hypertensive non-users. For walking speed, the medication by intervention interaction was not significant (p=0.178), but a trend existed for the medication by intervention by visit interaction (p=0.094). PA significantly improved the adjusted walking speed of ACEi users (p<0.001) but did not improve walking speed among the other two groups across study visits. At 12 months adjusted changes were 0.06 m/sec among ACEi users, 0.05 m/sec among anti-hypertensive non-users, and 0.02 m/sec among users of other anti-hypertensives.

Conclusions:
Among older adults at risk for disability, exercise-derived improvements in physical function were greatest among ACEi users. Future prospective studies are needed to confirm the true efficacy of ACE inhibitors in improving older adults’ functional responses to exercise.
Abstract P055: Diet, Lifestyle And Blood Pressure of Non-alcohol Drinkers and Alcohol Drinkers in The Intermap Study
Authors: Chan Queenie , Stamler Jeremiah , Brown Ian , Daviglus Martha L , Van Horn Linda , Miura Katsuyuki , Zhao Liancheng , Elliott Paul ,   The INTERMAP Cooperative Rsch Group
Published: July 2021

Background:
Non-drinkers and alcohol drinkers differ in social and cultural traits, lifestyle habits (e.g., smoking, exercise, diet) and blood pressure (BP).

Objective:
Assess whether differences in lifestyle traits, particularly food intake, among non-alcohol drinkers, moderate and heavy alcohol drinkers account for higher BP of heavy drinkers.

Methods:
The INTERMAP Study is a cross-sectional epidemiologic investigation of 4,680 men and women ages 40–59 years from 17 population samples in China, Japan, United Kingdom and United States. With standardized quality-controlled methods, four 24-hour dietary recalls, 2 timed 24-hour urine collections, 8 BP measurements and questionnaire data were accrued. Data on lifetime alcohol use and daily alcohol consumption over the previous 7 days were obtained at two visits (14 days total).

Results:
Heavy alcohol drinkers (>26 g alcohol/day for men; >13 g alcohol/day for women) were more likely to be cigarette smokers, and had lower age-sex-sample adjusted mean body mass index (BMI) and higher adjusted total energy intake than moderate and non-alcohol drinkers (P<0.001). Heavy alcohol drinkers had mean systolic and diastolic BP higher by 3.2/2.1 mm Hg (P<0.001) compared to non/moderate drinkers adjusted for sex, population sample, age, years of education, cigarette smoking, physical activity, employment, marital status, family history of hypertension, cardiovascular disease and diabetes mellitus diagnosis, supplement intake, and special diet. With additional adjustment for BMI, the BP differences between non/moderate drinkers and heavy drinkers increased 8% to 3.5 mm Hg for systolic and 2.3 mm Hg for diastolic (P<0.001). Heavy drinkers had significantly lower intakes of pasta and rice, bread, cereals, milk, ice-cream, table spread, vegetable oil, fresh fruits, fruit juices, raw vegetables, cooked vegetables, sweet snacks and non-alcoholic beverages, and higher intakes of meat, fish, shellfish and nuts compared to non-drinkers and moderate drinkers. Of 17 foods with significantly different intakes between heavy drinkers and non/moderate drinkers had little or no influence on the higher BP of heavy drinkers (range from 0.00 to 0.16 mm Hg, 0 to 5% changes). With adjustment for possible confounders and multiple foods, the adjusted mean BP differences between non/moderate drinkers and heavy drinkers were 3.2 mm Hg for systolic (P<0.001) and 2.1 mm Hg for diastolic (P<0.001). Results were similar for men and women analysed separately.

Conclusions:
Differences in food intake did not account for the significantly higher BP among heavy drinkers suggesting that other lifestyle traits may operate, and/or that heavy drinking per se is the responsible trait.
Abstract P260: Active Video Game Participation in U.S. Youth: Findings from the National Youth Physical Activity and Nutrition Survey, 2010
Authors: Fulton Janet E , Song MinKyoung , Carroll Dianna D , Lee Sarah M
Published: July 2021

Objective:
Active video game usage (active gaming) is a viable way to encourage and increase physical activity. Video game technology is perceived as ubiquitous although no current nationally-representative study describes participation in active gaming in U.S. youth. Our study describes the proportion of high school youth who report active gaming and the characteristics associated with active gaming.

Methods:
The National Youth Physical Activity and Nutrition Survey, 2010 provided data for this study. A nationally representative sample of 9,125 U.S. students in grades 9=12 completed a self-administered questionnaire during class in Spring, 2010. The survey response rate was 73%. Active gaming was assessed as the number of days reported participating in active video games [Wii, Dance Dance Revolution] in the past 7 days. Students reporting ≥1 days were classified as active gamers. Characteristics hypothesized to be associated with active gaming [demographic (sex, grade, race/ethnicity), BMI (normal, overweight, obese), sedentary behaviors (watching DVDs and TV), and physical activity (sports and physical education participation, meeting aerobic and muscle strengthening guidelines)] were also obtained from the questionnaire. Statistical software was used to account for complex sampling and to calculate prevalence estimates and 95% confidence intervals (CI). Logistic regression was used to examine the association between active gaming and demographic characteristics, BMI, sedentary behaviors, and physical activity.

Results:
The proportion of U.S. high school students reporting active gaming was 39.9% (95% CI = 37.9, 42.0%). Adjusting for all covariates, the following characteristics were positively associated (p<0.05) with active gaming: 9
th
and 10
th
grades (versus 12
th
grade), African-American race/ethnicity (versus Hispanic), overweight or obese (versus normal weight), watching DVDs >0 hours/day (versus watching DVDs 0 hours/day) and watching TV >0 hours/day (versus watching TV 0 hours/day), and meeting aerobic physical activity and muscle strengthening guidelines (versus not meeting the respective guidelines).

Conclusion:
Four out of 10 U.S. high school students report participating in active gaming. Active gamers are more likely to be younger, African-American, overweight or obese, spend time watching DVDs or TV, and meet physical activity guidelines. Active gaming may be a viable mode for U.S. youth to meet physical activity guidelines.
Abstract MP73: Systolic Blood Pressure Control among Hypertensives and Incident Heart Failure: The Atherosclerosis Risk in Communities Study
Authors: Rodriguez Carlos J , Swett Katrina , Agarwal Sunil K , Folsom Aaron R , Loehr Laura R , Fox Ervin R , Ni Hanyu , Rosamond Wayne D , Chang Patricia P
Published: July 2021

Background:
Studies document a progressive increase in heart disease risk as systolic blood pressure (SBP) rises above 115mmHg, suggesting a benefit of treatment to a SBP <120mmHg. Hypertension is a major risk factor for heart failure (HF) but whether an SBP <120mmHg lowers HF risk is unknown.

Methods:
Hypertensive participants at baseline (SBP/DBP >140/90mmHg, report of hypertension or taking BP medication) from ARIC, a prospective population-based study of black and white men and women from 4 US communities, were included. SBP measured at baseline and at three triennial visits was treated as a time-dependent variable and categorized as: Elevated (SBP >140), Standard (SBP 120-139) and Intensive (SBP <120). Prevalent HF at baseline was excluded. Incident HF was defined from HF hospitalization or a death certificate with an ICD-9 or ICD-10 codes. Multivariable Cox regression models included baseline age, sex, diabetes, BMI, high cholesterol, smoking and alcohol intake.

Results:
After median follow-up of 20.8 years, a total of 1,111 incident HF events occurred in 4,802 hypertensives. Participants with elevated SBP had less HF-free survival compared to those with intensive group (log-rank p<0.001). However, there was no difference in incident HF-free survival among those with standard vs. intensive group (log-rank p=0.08). In adjusted analysis, findings remained similar for elevated SBP (HR: 1.2; 95% CI 1.0-1.5, intensive group as referent); and for standard SBP (HR: 0.9; 95% CI 0.8-1.1, intensive group as referent). There were no differences by race and sex (p for interaction >0.05). Further adjustment for BP medication use at baseline did not significantly affect the results.

Conclusion:
Hypertension control is necessary to prevent HF. Our results suggest that among hypertensives, having elevated SBP carries the highest risk for HF but in this categorical analysis we observed no risk difference between the standard and intensive SBP groups.
Abstract MP84: Incident Sleep-Disordered Breathing is Associated with Higher Blood Pressure and its Reactivity: Penn State Child Cohort
Authors: Bixler Edward O , Liao Duanping , Vgontzas Alexandros N , He Fan , Rodriguez-Colon Sol M , Calhoun Susan , Fernandez-Mendoza Julio
Published: July 2021

Objectives:
To examine the association between incident sleep-disordered breathing (SDB) and blood pressure and blood pressure reactivity in a population based sample of adolescents.

Methods:
The Penn State Child Cohort is a general population based sample of 700 children aged 5-12 years at the baseline examination (2000-2005). Currently, 300 participants have completed their 8-year follow up examination. Blood pressure was assessed at follow up in the evening using an automated device prior to the sleep recording in three positions. Three assessments in the seated position were completed after 5 minutes of rest. This was followed by 3 assessments in the supine position after 5 minutes of rest. The averages of the 2
nd
and 3
rd
readings for both positions are reported. Finally the subject was asked to stand as fast as possible and 2 additional readings were completed immediately upon their foot hitting the floor. These two standing readings were averaged. The difference between standing and supine BP was used as measures of vascular reactivity. The age, gender and height adjusted mean level of BP measures comparing individuals with and without incident SDB (defined as Apnea Hypopnia Index, AHI>5/hr) after excluding individuals with baseline SDB were calculated.

Results:
We observed no significant differences in diastolic blood pressure across the three positions. However, systolic blood pressure across all three positions and vascular reactivity were significantly elevated in those with incident SDB, as summarized in Table 1.

Conclusion:
In an 8-year followup of this population based sample of children, there was no persistence of SDB from baseline. Incident SDB (about 11%) was significantly associated with elevated systolic BP across all three positions. Further, SDB was associated with increased systolic BP reactivity, which has been associated with increased risk of CVD and the development of hypertension in adults.
Abstract P054: Rare Variants in and Near IRS1 are Associated with Fasting Insulin in CHARGE-S Cohorts
Authors: Cornes Belinda K , Brody Jennifer , Morrison Alanna C , Siscovick David , Meigs James B ,   Cohorts for Heart and Aging Rsch in Genomic Epidemiology Sequencing (CHARGE-S) Diabetes WG
Published: July 2021

Introduction:
Common variants in the gene encoding insulin receptor substrate 1 (
IRS1
) and nearby on 2q36.3 have been associated with levels of fasting insulin (FI). We hypothesized that a greater burden of rare variants in these regions is associated with higher FI.

Methods:
CHARGE-S sequenced (average coverage >60x) the
IRS1
and 2q36.6 regions (totaling 185 kb) in 3,539 individuals on the SOLiD platform. FI information among non-diabetics was available in 3 studies: Framingham Heart Study (
N
=811), Cardiovascular Heart Study (
N
=967) and Atherosclerosis Risk in Communities Study (
N
=1761). We analyzed rare variants (MAF < 1%) using a weighted sum test, similar to Madsen-Browning (powerful to detect an association if effects of casual rare variants are in the same direction), and the SKAT test (preferred method if variant effects are in opposite directions). Meta-analyses of weighted rare variants results used the inverse-variance method while SKAT results used a similar approach. For multi-variant tests, the threshold for significance was considered to be α = 0.05. Coding annotation predictions were obtained from the dbNSFP database which includes functional predictions from SIFT, MutationTaster, Polyphen-2, Phylo-P and LRT. Non-coding annotation information (protein binding regions, transcription factor binding sites, DNase hypersensitivity sites, conservation scores) was obtained from ENCODE and ORegAnno databases. From these annotations, we grouped different types of variants together (possible loss of function; possibly regulatory) in order to determine specific variants contributing most to the effect.

Results:
Sequencing found 4,534 variants in two regions, 86.7% of which were rare and novel, not seen in 1000 genomes or dbSNP. Approximately 20% of variants had annotation information available; of these, 34 variants were possibly damaging. We found suggestive association with FI (
p
=0.03) for all rare variants in the meta-analysis of weighted-sum tests at 2q36.3 but not at
IRS1
. At
IRS1
(but not at 2q36.3), SKAT meta-analysis tests showed evidence for all rare variants associated with FI (
p
=0.03). SKAT tests restricted to
N
=365 possibly damaging variants at
IRS1
suggested an association with FI in coding (
p
=0.06) and in non-coding (
p
=0.02) variants.

Conclusion:
Large scale deep sequencing in the
IRS1
and 2q36.3 regions found very large numbers of new, rare variants. Multi-variant tests suggest that rare variation in these regions influence FI levels, with individuals with more and rarer variants having higher FI. Further investigation is warranted to address why weighted sum and SKAT tests provide different levels of evidence for association in the two regions. Also, conditional analyses will test whether new rare variants at
IRS1
or 2q36 explain observed GWAS associations.
Abstract P291: Adipocytokines, Lipoproteins & Obesity Among Black & White Postmenopausal Women from the Women’s Health Initiative
Authors: Mackey Rachel H , McTigue Kathleen M , Barinas-Mitchell Emma , Evans Rhobert W , Tinker Lesley F , Manson JoAnn E , Liu Simin , Howard Barbara V , Robinson Jennifer G , Stefanick Marcia L , Phillips Lawrence S , Allison Matthew A , Rosal Milagros C , Beresford Shirley , Kuller Lewis H
Published: July 2021

Background:
Despite the prevalence of severe obesity, particularly among women and African-American women, there is little data on CV risk factor differences across the BMI spectrum including extreme obesity.

Methods:
Participants were 1200 black and white postmenopausal women sampled from the Women’s Health Initiative Observational Study according to BMI categories and waist circumference tertiles: 300 black and 300 white women with BMI 40-65 kg/m
2
and 75 black and 75 white women in BMI categories 8.5-<25, 25-<30, 30-<35 and 35-<40 kg/m
2
. Using stored baseline serum, total and high molecular-weight (HMW) adiponectin, leptin, ghrelin and insulin were measured by immunoassay; plasma lipoproteins and subclasses were measured by NMR spectroscopy. Race-ethnicity differences were tested in linear regression models adjusted for age, diabetes, BMI, waist, hip, hormone therapy and lipid-lowering medication.

Results:
Compared with white women, black women had lower levels of total and HMW adiponectin and ghrelin, and higher levels of insulin and leptin. Despite similar levels of total LDL particles (LDL-P), black women had lower levels of small LDL-P and higher levels of large LDL-P and larger mean LDL size. Levels of large HDL particles (HDL-P) and small HDL-P were also similar for black and white women, but black women had lower levels of total and medium HDL-P and larger mean HDL particle size. Black women also had lower levels of total, large, medium and small VLDL particles (VLDL-P) which increased little across BMI category, such that mean levels of total or large VLDL-P among black women with BMI≥ 40 kg/m
2
were lower than white women of normal BMI (<25 kg/m
2
) (Figure). Among white, but not black women, total LDL-P was higher and total HDL-P was lower with higher BMI category (Figure).

Conclusions:
Among postmenopausal women of similar BMI and waist circumference, black women have lower levels of ghrelin and total and HMW adiponectin, but better lipoprotein levels that are less related to obesity compared with white women.
Abstract MP54: The Health Burdens Attributable to Suboptimal Diet in the US - a National Comparative Risk Assessment
Authors: Micha Renata , Singh Gitanjali M , Khatibzadeh Shahab , Shi Peilin , Fahimi Saman , Engell Rebecca E , Mokdad Ali , Murray Chris J , Powles John , Ezzati Majid , Mozaffarian Dariush ,   The Global Burden of Diseases Nutrition and Chronic Diseases Expert Group (NutriCoDE)
Published: July 2021

Background:
Suboptimal diet has become the leading cause of death and disability globally and in the US. Yet, the specific contributions of different dietary factors to poor health in the US are not established.

Objective:
To estimate the burdens of 12 key dietary factors on major chronic diseases in the US, overall and by age, sex, and disease.

Methods:
We used a comparative risk assessment framework to develop consistent and comparable methods to identify specific dietary factors with evidence for etiologic effects on coronary heart disease (CHD), stroke, diabetes, and cancers; estimate current national intake levels and their uncertainty, by age and sex; quantify etiologic effects of each diet-disease relationship, by age; and characterize optimal consumption levels of each dietary factor. We combined these inputs with national disease-specific deaths and disability-adjusted life-years (DALYs) to estimate burdens attributable to each dietary factor overall, and by age, sex, and disease. We quantified uncertainty using probabilistic simulation analyses for all our estimates.

Results:
In 2010, the 5 leading dietary causes of chronic disease mortality and morbidity in the US were low fruits, low nuts/seeds, high sodium, low vegetables, and high processed meats (
Figure
). Most dietary factors contributed to CHD burden. Leading causes of cancer mortality were low fruits, high processed meats, low milk, low vegetables, and high red meats. Leading causes of diabetes morbidity were high sugar-sweetened beverages, high processed meats, low whole grains, and high red meats.

Conclusions:
Our findings revealed a major impact of specific dietary factors on poor health in the US. Our study calls for policies and coordinated, multi-stakeholder efforts to improve diet in the US.
Abstract P298: Relationship Of Plasma Asymmetrical Dimethylarginine To Carotid Intima-media Thickness In General Japanese Population: The ERA-JUMP And The SESSA
Authors: Nagasawa Shin-ya , Miura Katsuyuki , Fujiyoshi Akira , Kadota Aya , Ohkubo Takayoshi , Hisamatsu Takashi , Kadowaki Sayaka , Miyagawa Naoko , Torii Sayuki , Zaid Maryam , Masaki Kamal , Barinas-Mitchell Emma J , Bertolet Marrianne H , Evans Rhobert W , El-Saed Aiman , Kuller Lewis H , Sekikawa Akira , Ueshima Hirtsugu ,   the ERA-JUMP and SESSA Rsch Group
Published: July 2021

Objective:
Asymmetrical dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, is known as a mediator of endothelial cell dysfunction. Some clinical studies have found evidence that increased plasma ADMA levels are associated with a higher risk of cerebrovascular events. However, studies on the relationship of plasma ADMA to subclinical atherosclerosis have been scarce.

We evaluated the association of ADMA with carotid intima-media thickness (IMT) in population-based samples in Japan.

Methods:
Population-based Japanese samples composed of 313 men aged 40-49 (40s men) from the ERA-JUMP and 732 men aged 60-79 (60s+70s men) from the SESSA were examined with physical examinations, life-style questionnaires, laboratory assessment and IMT using standardized methods. Plasma samples were stored at -80°C, and concentration of ADMA was determined using a validated high-throughput liquid chromatographic-tandem mass spectrometric assay.

The IMTs of the right and left common carotid arteries, the carotid bulbs, and the internal carotid arteries were examined. Statistical associations were evaluated using multiple linear regression models with adjustment for age, body mass index, systolic blood pressure, LDL-cholesterol, HDL-cholesterol, fasting blood glucose, smoking, alcohol intake, medications for hypertension, hyperlipidemia, or diabetes, and
estimated glomerular filtration rate (eGFR)
.

Results:
The average concentrations and standard deviation (SD) of plasma ADMA in men aged 40-49 and 60-79 were 0.39 ± 0.06 and 0.43 ± 0.06 μmol/L, respectively. The mean and SD of IMT in men aged 40-49 and 60-79 were 0.61 ± 0.07 and 0.91 ± 0.20 mm, respectively. Higher level of ADMA was significantly and positively associated with proportion of current smoking both in 40s and 60s+70s men (correlation coefficient: both p <0.001). It was also significantly and positively associated with eGFR in 60s+70s men (p <0.001) but not associated with eGFR in 40s men (p = 0.429). In full adjusted linear regression models, 1 SD increase in ADMA was associated with 0.14mm increase in IMT in 40s men (p=0.01) but only 0.04mm increase in IMT in 60s+70s men (p=0.26).

Conclusions:
Higher level of ADMA was associated with more IMT independently of traditional risk factors and renal function in young adult men, but not in elderly men.
Abstract P343: Racial Differences In The Progression Of Carotid Intima-media Thickness In Middle-aged Men-the Era Jump Study
Authors: Ahuja Vasudha , Barinas-Mitchell Emma J , Seto Todd B , Evans Rhobert , Kadota Aya , El Khoudary Samar R , Fujiyoshi Akira , Vishnu Abhishek , Miura Katsuyuki , Willcox Bradley J , Ueshima Hirotsugu , Masaki Kamal , Kuller Lewis H , Sekikawa Akira ,   For the ERA JUMP Study Group
Published: July 2021

Introduction:
Intima-media thickness (IMT) of the carotid artery is an independent predictor of future cardiovascular events. A few studies have examined the racial differences in IMT progression. We aimed to study the racial differences in IMT progression over 4-6 years among middle-aged Caucasian, African and Japanese American men.

Methods:
Population-based samples of 393 men (Caucasian=199, African Americans=39, Japanese Americans=155; aged 40-49 years at baseline) free of clinical cardiovascular disease and not on lipid lowering, anti-diabetic or anti-hypertension medications at baseline were examined for IMT at two time points (baseline (2004-07) and follow-up (2008-13). Measurements of IMT were standardized and performed by University of Pittsburgh. Progression of IMT was defined as (follow-up IMT [[Unable to Display Character: –]] baseline IMT)/duration of follow-up (years). Multivariable linear regression analyses were used and models were adjusted for traditional cardiovascular risk factors (Table).

Results:
In the unadjusted analyses, IMT progression was significantly associated with age and race, and marginally significantly associated with systolic blood pressure and diabetes. The progression rate of IMT (mean ± SE) was the highest in Japanese American (16 ± 1.2μm/year) compared with Caucasian (10.3 ± 1.0μm/year; P < 0.01) and African American men (3 ± 2μm/year; P < 0.01). In the adjusted analyses, age and race remained significantly associated with IMT progression. Japanese Americans progressed significantly faster than Caucasians. African Americans progressed slower than Caucasians but this difference was not significant. Diabetes was marginally significantly associated with IMT progression.

Conclusions:
Age and race are the major determinants of IMT progression in these middle-aged men. Racial differences in progression are prominent with fastest progression in Japanese Americans.