bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 94: Closed Loop Compression Depth Optimization in a Pig Model
Authors: Aelen Paul , Ordelman Simone , Woerlee Pierre , Noordergraaf Gerrit-Jan
Published: July 2021

Introduction:
CPR success depends on blood flow generated by it, affected among others by compression depth. AHA guidelines advise the same small range of depths for all patients, while their individual optimum may vary widely. Therefore, an individual patient may have an increased chance of survival if CPR is performed at this optimum depth. We investigated the feasibility of an automated compression depth tuning algorithm.

Methods:
In five Yorkshire pigs (about 31 kg) aortic and right atrial pressure were measured with Millar catheters. CPP and aortic diastolic blood pressure (DBP) were calculated in real-time. DBP was used as CPR quality indicator (QI), i.e. as a surrogate for myocardial blood flow. After VF induction, CPR was performed at 100 cpm for 10 min with a proprietary automated CPR device. Compression depth was tuned automatically every 2 min by first decreasing depth by 0.5 cm, followed by increasing depth by 1 cm, both for 20 seconds. The depth at the highest QI was used as new depth in the next cycle (Fig. 1). It was determined whether the QI reflected CPP. Tuning step size (cm) and duration (s) were studied to see if these resulted in clinical relevant QI changes.

Results:
The mean correlation coefficient between the QI and the CPP was 0.7. The mean QI change per depth change was 2.3 mmHg (about 10% change). The algorithm had a bias towards lower depths as the depth increase first had to overcome the QI change of the preceding decrease which did not result in a steady state QI within 20 seconds. The algorithm tuned to a compression depth between 2.5 and 4.5 cm for these animals.

Conclusion:
DBP can be used as a CPR quality indicator as its correlation with CPP is high. A step size of 0.5 cm is a viable choice for a tuning algorithm as it resulted in clinical relevant changes of QI within 20 seconds. A bias to a certain compression depth should be prevented by either lengthening the duration of the depth change or by performing the increase and decrease at non-consecutive time intervals.
Abstract 9406: ST-Segment Elevation in Lead AVR Strongly Predicts Long-Term Adverse Outcomes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Tsukahara Kengo , Iwahashi Noriaki , Maejima Nobuhiko , Akiyama Eiichi , Umemura Satoshi , Kimura Kazuo
Published: July 2021

Introduction:
In non-ST-segment elevation acute coronary syndrome (NSTE-ACS), ST-elevation in lead aVR (ST↑aVR) on admission ECG has been shown to be associated with severe coronary artery disease, but its impact on long-term clinical outcomes is unclear.

Methods:
We studied 454 patients with NSTE-ACS who underwent coronary angiography during initial hospitalization. Patients were divided into the 3 groups according to the degree of ST↑aVR on admission ECG: no ST↑aVR (n=301, G-A); ST↑aVR <1.0 mm (n=82, G-B); and ST↑aVR ≥1.0 mm (n=71, G-C). Troponin T (TnT), hemoglobin (Hb), estimated glomerular filtration rate (eGFR), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), TIMI risk score, and summed ST-segment depression in other leads were also measured on admission.

Results:
There were no differences in sex or coronary risk factors except for diabetes mellitus in the 3 groups. In G-A, G-B, and G-C, age was 66±11, 68±11, and 70±11 years; the rates of diabetes mellitus were 30%, 48%, and 51%; Killip class ≥2 was 7%, 20%, and 34%; positive TnT was 30%, 46%, and 56%; TIMI risk score was 2.8±1.4, 3.6±1.3, and 3.8±1.2; the levels of Hb were 13.4±1.9, 13.2±1.9, and 12.2±2.3 g/dl; eGFR was 65±24, 59±27, and 53±28 ml/min/1.73 m2; BNP was 155±249, 386±338, and 455±507 pg/ml; hsCRP was 0.339±1.499, 0.654±1.899, and 0.842±1.788 mg/dl; summed ST-segment depression was 2.0±2.6, 5.6±3.5, and 13.0±6.6 mm; the rates of left main or 3-vessel disease were 9%, 44%, and 75%; and major adverse events (death, [re]infarction, urgent revascularization, or heart failure requiring hospitalization) at 5 years were 19%, 43%, and 58%, respectively (all p<0.01). After adjusting for baseline characteristics, multivariate analysis showed that as compared with no ST↑aVR, the hazard ratios (95% CI) for 5-year adverse events associated with ST↑aVR <1.0 mm and ST↑aVR ≥1.0 mm were 2.16 (1.10-5.59; p=0.019) and 3.90 (1.44-9.76; p=0.001), respectively.

Conclusions:
In patients with NSTE-ACS, greater ST↑aVR on admission ECG strongly predicted 5-year adverse outcomes, even after adjusting for traditional risk factors, biomarker profiles, and ST-segment depression in other leads. Our findings suggest the importance of ST↑aVR in risk stratification for NSTE-ACS.
Abstract 9409: Aging Inhibits Angiogenic Response in a Rat Model of Hindlimb Ischemia: A HUR-VEGF Dependent Mechanism
Authors: Hao Chang-Ning , Huang Jing-Juan , Shi Yi-Qin , Li Rui-Lin , Duan Jun-Li
Published: July 2021

Introduction:
Human antigen R (HUR) is a RNA stablilizer and its expression decressed in aging organism, however, its downstream signal pathways remain modest clarified. Here, we examined whether HUR plays a role in angiogenic response using an aging rat model of hindlimb ischemia.

Methods and Results:
Male Sprague-Dawley rats were divided into 2 groups: the young group (12 week-old) and the aging group (96 week-old). The left femoral artery of all rats were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 2 weeks. At postoperative day 14, aging rats exhibited impaired angiogenic action (skin temperature, capillary density and angiography) and decreased angiogenic factor expressions (vascular endothelial growth factor [VEGF], hypoxic inducible factor-1α and nitric oxide [NO]) in ischemic muscles. The protein expression of HUR as well as endothelial nitric oxide synthetase (eNOS) phosphorylation were significantly inhibited in aging rats as well. In vitro, we applied anti-HUR small interfering RNA to transfect human umbilical vein endothelial cells (HUVECs). The results showed that transfected HUVECs exhibited decreased the capacities of VEGF/NO production, tube formation and apoptotic resistence compared with control.

Conclusions:
Our results domenstrated that the down-regulation of HUR plays a key role in aging-related poor angiogenic response.
Abstract 9440: Prognostic Value of Stress Echocardiography in Patients With Low (<10%)-Intermediate (10-20%) Framingham Risk Score (Short-Term) versus Low (<39%) or High (≥39%) Lifetime Predicted Risk of Cardiovascular Disease
Authors: Yao Siu-Sun , Supariwala Azhar , Yao Amanda , Sreenija Sai , Chaudhry Farooq A
Published: July 2021

Background:
The ideal risk assessment and management of patients with low-intermediate or high Framingham risk score (FRS, short-term) versus low or high lifetime cardiovascular (CV) risk is unclear. The purpose of this study was to evaluate the prognostic value of stress echocardiography (SE) in defined FRS and lifetime risk groups.

Methods:
We evaluated 4566 patients (60±13 years; 46% male) undergoing SE (41% treadmill, 59% dobutamine) with low-intermediate FRS (<20%) divided into: low (<39%, n=368) or high lifetime (≥39%, n=661) CV risk and third group with high FRS (≥20%, n=3537). Follow-up (3.2±1.5 years) for non-fatal myocardial infarction (n=102) and cardiac death (n=140) were obtained.

Results:
By univariate analysis, age (p<0.001), ejection fraction (p<0.001) and ≥3 ischemic wall motion abnormalities (WMA) (p<0.001) were significant predictors of cardiac events. Cumulative survival in patients with low or intermediate short term risk groups were significantly worse in patients with ≥3 WMA vs. <3 WMA in low-intermediate FRS and low (3.3%/year vs. 0.3%/year, p<0.001) or high lifetime CV risk (2.0%/year vs. 0%/year, p<0.001) and high FRS group (3.5%/year vs. 1.0%/year, p<0.001). Multivariate Cox proportional hazards analysis identified ≥3 new ischemic wall motion abnormalities as the strongest predictor of cardiac events (HR 3.2, 95% CI 2.2-4.6, p <0.001).

Conclusion:
Stress echocardiography results (absence or presence of ≥3 ischemic segments) can equally and effectively risk stratify low-intermediate or high FRS versus low or high lifetime cardiovascular risk patients. Event rate with normal SE is highest in patients with high FRS.
Abstract 9483: High Mobility Group Box 1 Promotes Angiogenesis From Bone Marrow-Derived Endothelial Progenitor Cells After Myocardial Infarction
Authors: Nakamura Yuichi , Suzuki Satoshi , Shimizu Takeshi , Miyata Makiko , Shishido Tetsuro , Ikeda Kazuhiko , Saitoh Shu-ichi , Kubota Isao , Takeishi Yasuchika
Published: July 2021

Background:
High mobility group box 1 (HMGB1) is a DNA-binding protein secreted into extracellular space from necrotic cells and acts as a cytokine. We have reported that HMGB1 attenuates cardiac damage and restores cardiac function by enhancing angiogenesis after myocardial infarction (MI). We examined the role of HMGB1 in angiogenesis from bone marrow (BM) -derived cells in the heart, using transgenic mice with cardiac-specific overexpression of HMGB1 (HMGB1-TG).

Methods and Results:
HMGB1-TG mice and wild-type littermate (WT) mice were lethally irradiated and injected with BM cells from green fluorescent protein (GFP) mice through the tail vein. Two weeks after BM transplantation, the left anterior descending artery was ligated to create MI. In flow cytometry analysis, GFP-positive cells were identified as donor BM cells-derived endothelial progenitor cells (EPC) if they were positive for both CD34 and CD144 in granulocyte differentiation antigen-1-negative fraction. Circulating EPC mobilized from BM was increased at 1 week after MI in HMGB1-TG mice compared with WT mice (41.9% vs. 24.5%, P < 0.01). Histological examination showed the size of MI was smaller in HMGB1-TG mice than in WT mice (42.9% vs. 59.1%, P < 0.01) at 4 weeks after MI. In myocardial immunofluorescence staining, GFP and CD31 double-positive cells were BM-derived cells engrafted within myocardial tissue as vascular endothelial cells of new capillaries or arterioles. The ratio of these double positive cells to all cardiac cells was significantly higher in the HMGB1-TG mice than in the WT mice (8.3% vs. 2.9%, P < 0.01). Enzyme-linked immunosorbent assay revealed that the levels of cardiac vascular endothelial growth factor at 1 week after MI were higher in HMGB1-TG mice than in WT mice (642.1 vs. 390.7 pg/dl, P < 0.05).

Conclusions:
The present study demonstrated the direct in vivo evidence that HMGB1 promoted angiogenesis and reduced MI size by enhancing mobilization and differentiation of BM cells to EPC, migration to the border zone of MI, and engraftment as vascular endothelial cells of new capillaries or arterioles in the infarcted heart.
Abstract 9487: Implantation of Scaffold-Free Tubular Tissue Using a Bio-3D Printer Augments Vascular Remodeling and Endothelialization
Authors: Itoh Manabu , Nakayama Koichi , Noguchi Ryo , Kamohara Keiji , Furukawa Kojirou , Uchihashi Kazuyoshi , Toda Shuji , Oyama Jun-ichi , Node Koichi , Morita Shigeki
Published: July 2021

Introduction:
Small caliber synthetic vascular grafts are not clinically available. We developed a novel method to create scaffold-free tubular tissue from multicellular spheroids (MCS) using a “Bio-3D printer”-based system, which enables the creation of various three-dimensional structures pre-designed using a computer system. With this system, we created a tubular structure (Fig. 1), and studied its biological features.

Methods:
We made 1.5 mm in diameter scaffold-free tubular tissues from MCS (1.25 x 10[[Unable to Display Character: ⁷]] cells) composed of human umbilical vein endothelial cells (40%), human aortic smooth muscle cells (10%) and normal human dermal fibroblasts (50%) using a Bio-3D printer. The vessels were cultured in a perfusion system. We implanted grafts into the abdominal aortas of F344 nude rats, and assessed the flow by ultrasonography and performed histological examinations on the second (N=5) and fifth (N=5) days after implantation.

Results:
All grafts were patent. Remodeling of the vessel (enlargement of the lumen area and thinning of the wall) was observed (Fig. 2). A layer of endothelial cells was developed after implantation of the graft (Fig. 3).

Conclusions:
The scaffold-free vascular grafts made of MCS using a Bio-3D printer showed biological features comparable to native vessels. Further studies are warranted toward the clinical application of this novel technology.
Abstract 99: A Multidimensional Bundle Intervention Effectively Enhances Delivery of Dispatcher-Assisted Cardiopulmonary Resuscitation
Authors: Chong Kah-Meng , Hsieh Ming-Ju , Liu Sot Shih-Hung , Wang Hui-Chih , Jin Cedric Guan-Cheng , Chiang Wen-Chu , Ma Matthew Huei-Ming , Ko Patrick Chow-In
Published: July 2021

Objective:
The better detection of OHCA through EMS calls by dispatchers may influence the performance of online dispatcher-assisted cardiopulmonary resuscitation (DA-CPR). In an EMS system with a bystander CPR rate around 20%, we launch a bundle intervention for better recognition of OHCA by EMS dispatchers and assess its impact on DA-CPR.

Design:
The EMS authority implements a multidimensional bundle for calls recognition of OHCA and DA-CPR, including 1) a simpler protocol prioritizing patient breathe identification, 2) post-hoc auditing the call audio records for confirmed OHCA cases upon paramedics contact, 3) feedback the audit results to each dispatcher, and a written response from dispatcher is demanded, 4) modifying the computer-aided dispatch (CAD) system to highlight the dialog of “breath not normally” instead of “no breath”, and 5) to add an icon for dispatcher to reassure the call case is unnecessary for DA-CPR before case close in CAD, 6) a leadership commitment for bundle, and 7) a steering team composed with both medical and fire administrative personnel for bundle execution.

Settings:
A centralized CAD system in a metropolitan EMS is studied. Routinely in system the call to ambulance dispatch time should be within 60 seconds.

Methods:
Through audio records evaluation, the proportions of calls recognition and DA-CPR for OHCA patients six months after the intervention are compared with that for the same month period in the prior year as the control group, using regression analysis for statistics.

Results:
A total of 717 calls after the intervention are compared with the 749 calls in control. The proportion of call recognition of OHCA after the intervention is significantly higher than the control (74.8% vs 57.7%, adjusted odds ratio: 2.2, 95% CI: 1.5-3.1). The proportion of dispatcher-assisted bystander chest compressions after the bundle is significantly higher than the control (28.2% vs 18.9%, adjusted odds ratio: 1.7, 95% CI: 1.1-2.5).

Conclusions:
We demonstrate a multidimensional bundle including simpler protocol, call records auditing, feedback, CAD with emphasizing patient breath status and reassuring assessment, leadership, and a joint steering team may effectively enhance EMS calls recognition and delivery of DA-CPR for OHCA.
Abstract 9902: Serum FGF23 Concentration is Associated With Cardiac Hypertrophy and Decreased Systolic Function Among Both CKD and Non-CKD Cardiac Patients
Authors: Morita Hideaki , Fujita Shuichi , Ito Takahide , Sohmiya Koichi , Hoshiga Masaaki , Ishizaka Nobukazu
Published: July 2021

Introduction:
Purpose: Serum concentrations of fibroblast growth factor-23 (FGF23) are increased in response to elevated serum phosphate levels among patients with renal dysfunction. Besides regulating circulating phosphate levels, FGF23 may induce cardiac hypertrophy; thus, enhanced FGF23 excretion may underlie the heart failure observed among patients with chronic kidney disease (CKD). Here we examined whether FGF23 concentrations are associated with cardiac hypertrophy among cardiac patients regardless of the presence or absence of CKD.

Methods:
The present study enrolled 480 cardiac patients admitted to our cardiology department between January 2012 and December 2012. Serum FGF23 level was measured by an ELISA method. Left ventricular mass index (LVMI) was used as a marker of cardiac hypertrophy.

Results:
Of the 480 patients, 132 (27.5%) had an estimated glomerular filtration rate (eGFR) of <60 mL/min/m2 (no-CKD group) and the remaining 348 (72.5%) had an eGFR of 60 or greater (CKD group). FGF23 was correlated with eGFR in the CKD group, but not in the no-CKD group. Stepwise multivariate linear regression analysis was performed using LVMI as a dependent variable, and sex, age, eGFR, serum calcium and phosphate, and log(FGF23) as independent variables. Log(FGF23) was selected as an independent variable that had a significant association with LVMI with a standardized correlation coefficient of 0.26 in the no-CKD group (P<0.01) and 0.25 in the CKD group (P<0.01). When left ventricular ejection fraction was used as an independent variable in this model, log(FGF23) was selected as significant predictor with a standardized correlation coefficient of -0.20 in the no-CKD group (P<0.05) and -0.18 in the CKD group (P<0.01).

Conclusions:
Among cardiac patients, serum FGF23 concentration was associated positively with left ventricular mass and negatively with left ventricular ejection fraction not only in patients with CKD, but also in those without CKD.
Abstract 01: The Role of Renin-Angiotensin-Aldosterone System Genes in the Progression of Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Kelly Tanika N , Raj Dominic , Rahman Mahboob , Kretzler Matthias , Kallem Radhakrishna R , Ricardo Ana C , Rosas Sylvia E , Tao Kaixiang , Xie Daiwei , Hamm L. Lee , He Jiang
Published: July 2021

Background:
We conducted single-marker, gene-based and pathway-based analyses to examine the association between renin-angiotensin-aldosterone system (RAAS) variants and chronic kidney disease (CKD) progression among Chronic Renal Insufficiency Cohort (CRIC) study participants.

Methods:
A total of 1,523 white and 1,490 black subjects were genotyped for 490 SNPs in 12 RAAS genes as part of the ITMAT-Broad-CARe array. CKD progression phenotypes included decline in estimated glomerular filtration rate (eGFR) over time and the occurrence of a renal disease event, defined as incident end stage renal disease or halving of eGFR from baseline. Mixed-effects models were used to examine SNP associations with eGFR decline, while Cox proportional hazards models tested SNP associations with renal events. Gene and pathway-based analyses were conducted using the truncated product method. All analyses were stratified by race, and a Bonferroni correction was applied to adjust for multiple testing.

Results:
Among white and black participants, eGFR declined an average of 1.2 and 2.3 ml/min/1.73m
2
per year, respectively, while renal events occurred in a respective 11.5% and 24.9% of participants. We identified strong gene and pathway-based associations with CKD progression. The
AGT
and
RENBP
genes were consistently associated with risk of renal events in separate analyses of white and black participants (all
P
<1.00х10
-6
). Driven by the significant gene-based findings, the entire RAAS pathway was also associated with renal events in both groups (both
P
<1.00х10
-6
). No single-marker associations with CKD progression were observed.

Conclusions:
The current study provides strong evidence for a role of the RAAS in CKD progression.
Abstract 05: Assessing Population Impact of Statin Treatment for Primary Prevention of Atherosclerotic Cardiovascular Diseases in US
Authors: Yang Quanhe , Zhong Yuna , Gillespie Catheen , Merritt Robert , Bowman Barbara , George Mary , Flanders Dana
Published: July 2021

Introduction:
American College of Cardiology/American Heart Association (ACC/AHA) new cholesterol treatment guidelines recommend consideration of statin treatment for a larger proportion of population for the primary prevention of atherosclerotic cardiovascular disease (ASCVD). It is important to assess the population impact of statin treatment under these new guidelines.

Hypothesis:
We assessed the hypothesis that increased statin use for the primary prevention of ASCVD might be accompanied by adverse effects among population.

Methods:
We used 2010 US Census, Multiple Cause Mortality, Third National Health and Nutrition Examination Survey Linked Mortality File (NHANES III 1988-2006, n=7095) and NHANES 2005-2010 (n=3178) participants 40-75 years of age to estimate prevalence of statin use, annual ASCVD deaths prevented and excess adverse effects by age, sex, and race/ethnicity if everyone followed updated guidelines.

Results:
Among 33.0 million adults aged 40-75 years meeting new guidelines for primary prevention of ASCVD (12.4 million with diabetes and 20.6 without diabetes but with a predicted 10-year ASCVD risk ≥7.5% and 70 ≤ low-density lipoprotein (LDL) ≤189 mg/dL), 26.9% (8.8 million) were on statins, indicating an additional 24.2 million potentially eligible for statin treatment (7.7 million with diabetes and 16.5 million without). Among the 7.7 million with diabetes, assuming 100% statin use, expected annual ASCVD deaths prevented were 2,514 (95% CI 592-4,142) and number-needed-to-treat (NNT) was 3,063 (1,860-13,017). The additional cases of myopathy based on estimates from randomized clinical trials (RCT) was 482 (0-2239) and number-needed-to-harm (NNH) was 15,992 (3,440-∞), and was 11,801 (9,251-14,916) and NNH 653 (516-833) based on estimates from population-based studies. Among 16.5 million without diabetes, ASCVD deaths prevented were 5,425 (1,276-8,935) with NNT 3,039 (1,845-12,914). The additional diabetes cases were 16,406 (4,922-26,250) with NNH 1,005 (628-3,349). Additional cases of myopathy was 1,030 (0-4,791) with NNH 15,996 3,441-∞) based on RCT estimates, and 24,302 (19,363-30,292) with NNH 678 (544-851) for population-based studies. ASCVD deaths prevented increased with age and >70% of ASCVD deaths prevented would occur among adults aged ≥60 years.

Conclusions:
Under ACC/AHA new guidelines for primary prevention of ASCVD by statin, assuming all those eligible took a statin, up to 12.6% of annual ASCVD deaths could be prevented, but could be accompanied by additional cases of diabetes and myopathy.
Abstract 18: Changes in Diet Quality Scores and Risk of Cardiovascular Disease Among Us Men and Women
Authors: Sotos-Prieto Mercedes , Bhupathiraju Shilpa N , Mattei Josiemer , Fung Teresa T , Li Yanping , Pan An , Willett Walter C , Rimm Eric B , Hu Frank B
Published: July 2021

Background:
While adherence to several diet quality scores, including the Alternative Healthy Eating Index (AHEI), Alternative Mediterranean diet score (AMED), and Dietary Approach to Stop Hypertension (DASH), has been associated with lower risk of cardiovascular disease (CVD), little is known about how changes in these scores over time influence subsequent CVD risk.

Objective:
To evaluate the association between 4-y changes in three diet quality scores (AHEI, AMED and DASH) and subsequent risk of CVD among women and men in the Nurses’ Health Study I and Health Professionals Follow-up Study.

Methods:
We followed up 50,195 women in the Nurses’ Health Study (1986-2010) and 29,547 men in the Health Professionals Follow-up Study (1986-2010). AHEI, AMED and DASH were defined using data obtained from validated food frequency questionnaires updated every 4-y. Time-dependent and baseline Cox proportional hazards regression models were used to calculate hazard ratios (HR) with adjustment for age, family history of CVD, race, baseline diet quality, changes in smoking status, and initial and changes in other lifestyle factors (physical activity, alcohol intake, total energy intake). Outcome was defined as the number of confirmed incident cases of CVD (total coronary heart disease and stroke). Results across cohorts were pooled by an inverse variance-weighted, random-effect meta-analysis.

Results:
During 1,397,871 person-years of follow-up, we documented 11,542 incident CVD cases. Compared with individuals whose diet quality remained relatively stable (no change) in each 4-y period, those with the greatest improvements (11-22%) in diet quality had a 7-8% lower risk of CVD in the subsequent 4-y period [pooled HR (95% CI): AHEI: 0.92(0.87, 0.99); AMED: 0.93 (0.85, 1.02); DASH: 0.93, (0.87, 0.99); all P-trend<0.05]. A 20 % increase in diet scores was associated with 3-9% lower risk of CVD (AHEI: 0.91 (0.86, 0.97); AMED: 0.97 (0.94, 0.99); DASH: 0.94 (0.90, 0.98). Increasing the diet scores (12-22%) from baseline to the first 4-y follow-up was associated with a lower risk of CVD during the next 20 years of follow-up [7% (1%, 12%) for AHEI and 9% (3%, 14%) for AMED]. On the other hand, a decrease in DASH score (16%) was associated with 8% (2%, 15%) higher risk of CVD over 20 years.

Conclusions:
Improving adherence to diet quality scores over time is associated with significantly lower risk of CVD, both in the short-term and long-term. Our results provide novel evidence that modest improvement in diet quality over time confers benefits for CVD prevention.
Abstract 20: Carbohydrate Quality, Measured Using Multiple Carbohydrate Quality Metrics, is Negatively Associated with Risk of Type 2 Diabetes in US Women
Authors: AlEssa Hala , Bhupathiraju Shilpa , Malik Vasanti , Wedick Nicole , Campos Hannia , Rosner Bernard , Willett Walter , Hu Frank B
Published: July 2021

Background:
Carbohydrate quality may be an important determinant of type 2 diabetes (T2D), however, the relationships between various carbohydrate quality metrics and T2D risk have not been systematically investigated.

Objective:
To prospectively examine the association between carbohydrate, starch, fiber, and different combinations of these nutrients in relation to the risk of T2D in US women.

Methods:
We prospectively collected information on diet and lifestyle behaviors among 70,041 women from the Nurses Health Study every 2-4 years, after baseline in 1984. These participants were free of diagnosed cardiovascular disease, cancer, or diabetes at baseline. We used Cox proportional hazards regression models to assess the association between dietary factors of interest and incidence of T2D.

Results:
With 24 years of follow-up we ascertained 6,934 incident cases of T2D during 1,484, 213 person years of follow-up. After adjusting for age, lifestyle and dietary variables, total carbohydrate intake was not associated with T2D (RR=0.98, 95% CI: 0.89 - 1.08, p for trend=0.84), while starch was positively associated with T2D (RR=1.23, 95%CI: 1.12 - 1.35), p for trend <0.0001), comparing the highest to lowest quintile. Total fiber (RR= 0.80, 95%CI: 0.72 - 0.89, p for trend < 0.0001), cereal fiber (RR= 0.71, 95%CI: 0.65 - 0.78, p for trend < 0.0001) and fruit fiber (RR= 0.80, 95%CI: 0.73 - 0.88, p for trend < 0.0001) were all inversely associated with T2D, comparing extreme quintiles. . There was a borderline significant positive association between the ratio of carbohydrate to total fiber intake and risk of T2D (RR= 1.09, 95%CI: 1.00 - 1.20, p for trend = 0.039), and stronger positive associations between the ratios of carbohydrate to cereal fiber (RR= 1.28, 95%CI: 1.17 - 1.39, p for trend < 0.0001), starch to total fiber (RR= 1.12, 95%CI: 1.02 - 1.23, p for trend = 0.030) and starch to cereal fiber (RR= 1.39, 95%CI: 1.27 - 1.53, p for trend < 0.0001) with T2D, comparing extreme quintiles..

Conclusion:
Diets with high starch, low fiber and high starch to cereal fiber ratio were associated with increased risk of T2D. Using the starch to cereal fiber ratio of the overall diet is a potentially useful way of assessing carbohydrate quality in relation to T2D.
Abstract 22: Visit-to-Visit Variability in Blood Pressure is Related to Late-Life Cognitive Decline
Authors: Qin Bo , Viera Anthony J , Adair Linda S , Plassman Brenda L , Edwards Lloyd J , Popkin Barry M , Mendez Michelle A
Published: July 2021

Introduction:
Recent studies suggest higher visit-to-visit variability of blood pressure (BP) is associated with worse cognitive function, but evidence based on longitudinal cognitive testing has not been reported.

Hypothesis:
We assessed the hypothesis that higher visit-to-visit variability in BP, but not mean BP, would be associated with faster decline in cognitive function among community-dwelling older adults.

Methods:
This prospective cohort study comprised 1213 adults who had two or more waves of BP measurements as part of the China Health and Nutrition Survey from 1991, up to their first cognitive tests, and completed a cognitive screening test at two or more waves in 1997, 2000 or 2004. Mean (SD) age at first cognitive test was 64 (6) y. Outcomes were repeated measures of global cognitive scores (baseline mean ± SD: 19 ± 6 points), standardized composite cognitive and verbal memory scores (standardized units [SU]). Visit-to visit BP variability was expressed as the standard deviation [SD] or as the variation independent of mean (SD/mean^x, with x derived from curve fitting) in BP measures obtained at a mean interval of 3.6 years. Multivariable-adjusted linear mixed-effects models were used to determine the association of changes in cognitive scores with visit-to visit BP variability.

Results:
Higher visit-to-visit variability in systolic BP, but not mean systolic BP, was associated with a faster decline of cognitive function (adjusted mean difference [95% CI] for high vs. low tertile of SD in variability (Figure): global score -0.23 points/y [-0.41 to -0.04], composite scores -0.029 SU/y [-0.056 to -0.002] and verbal memory -0.044 SU/y [-0.075 to -0.012]). Higher visit-to-visit variability in diastolic BP was associated with a faster decline of global cognitive function only among adults 55-64 years, independent of mean diastolic BP.

Conclusion:
Higher long-term BP visit-to-visit variability predicted a faster rate of cognitive decline among older adults.
Abstract 48: Long-Term Patterns in the Development of Multiple Cardiovascular Diseases: The Framingham Heart Study
Authors: Allen Norrina B , Ning Hongyan , Wilkins John , Levy Daniel , Lloyd-Jones Donald
Published: July 2021

Background:
Having a first CVD event increases the risk for subsequent events; however, the long-term patterns in the development and sequence of multiple CVDs, including stroke, myocardial infarction (MI) and chronic heart failure (CHF) are unknown. The aim of this study was to identify distinct long-term patterns in the order and timing of MI, stroke and CHF occurrence.

Methods:
We used publicly available data from the Framingham Heart Study (FHS). The occurrence of fatal/non-fatal MI, stroke and CHF were examined separately using discrete mixture modeling implemented in SAS (Proc Traj) to identify trajectory groups for the risk of each CVD event starting at age 30. We included both first and subsequent events. Clusters of disease specific trajectory groups were examined. Baseline demographics and risk factors were compared across clusters.

Results:
Among 5,079 participants (ppts) in FHS, we identified 8 unique patterns in the development of CVDs (see figure). The majority, 72.5%, of Framingham ppts experienced average age- related increases in the yearly risk for all three endpoints of MI, stroke and heart failure (Average Risk group) other groups experienced early or higher risks for specific CVDs including the High CHF Risk group (6% of ppts), Early CHF group (2%), High Stroke Risk group (9%), High CHF and Stroke Risk group (1%), High MI Risk group (4%), High MI and CHF Risk group (1%), Early CHF and MI Risk group (1%). Groups in which stroke and/or HF risk was elevated had higher prevalence of smoking and greater baseline BP levels; those groups at elevated risk of MI had higher total cholesterol levels and higher BMI.

Conclusions:
We identified distinct patterns in development and ordering of MI, stroke and CHF associated with diverse risk factor profiles. By understanding the life-course and likely sequence of CVD events related to distinct risk factor profiles, clinicians may be able to consider personalized prevention strategies with the highest likelihood of preventing first CVD events and reducing the overall burden of CVD.
Abstract MP03: All-Cause Mortality and Cardiorespiratory Fitness Among Patients with a Family History of CHD - The FIT Project
Authors: Patel Jaideep , Al Rifai Mahmoud , Hung Rupert K , Nasir Khurram , Keteyian Steve J , Brawner Clinton A , Al-Mallah Mouaz H , Blaha Michael J
Published: July 2021

BACKGROUND:
The extent to which cardiorespiratory fitness (CRF) provides meaningful risk stratification among those with a family history (FH) of coronary heart disease (CHD) is yet to be defined. We compare all-cause mortality in individuals with a FH of CHD to those without.

METHODS:
We retrospectively studied 68,947 patients without history of CHD (n=7,980) or heart failure (n=1,564) who underwent physician-referred treadmill stress testing between 1991 and 2009. FH of CHD was defined as a self-reported compatible history of CHD in a first-degree relative. CRF was based on peak estimated metabolic equivalents (METS) and categorized into 4 groups: <6, 6 to 10, 10 to 12, and ≥12 METS. Multivariable-adjusted Cox proportional hazards models were used to study the association between increasing METS categories and risk of mortality using the lowest METS category as the reference. Adjusted mortality rates were calculated using direct standardization. Multiplicative interaction testing was performed for FH and METS categories.

RESULTS:
Overall, 50% (n=34,532) of patients (mean age 53.5±12 years, 49% males) reported a FH of CHD. Compared to those without a FH, those with a FH were more likely to abuse tobacco (43% vs 40%) and have hyperlipidemia (47% vs 42%), but less likely to be diabetic (18% vs 22%). FH was significantly associated with mortality after adjusting for traditional risk factors, however an association was not observed with the addition of METS [HR(95%CI)]: 0.92(0.88-0.97) and 0.96(0.91-1.01), respectively. Adjusted mortality rates were lower with increasing METS categories (43%,19%,10% and 7% in those without a FH vs 34%,15%,8% and 5%, respectively, in those with a FH). In fully adjusted models, increasing METS categories were associated with a lower risk of mortality (figure), without effect modification by FH of CHD (P=0.37).

CONCLUSION:
CRF limited an independent mortality association with FH. Higher levels of CRF were associated with similar reductions in mortality risk in those with and without a FH of CHD.
Abstract MP08: Evaluating the Influence of Bloomberg Era Policy on New York City Cardiovascular Disease Mortality Rates
Authors: Ong Paulina , Lovasi Gina , Demmer Ryan
Published: July 2021

Background:
Since 2002, under the Bloomberg administration, New York City (NYC) has aggressively pursued and implemented a broad set of public health policies to reduce chronic disease. Limited research exists evaluating secular trends in cardiovascular disease (CVD) mortality against the backdrop of these policy initiatives.

Hypothesis:
We hypothesized that CVD mortality trends declined more rapidly during the years 2002-2011 compared with the previous decade.

Methods:
Using individual death certificates of NYC residents during 1990-2011, all-cause mortality rates were calculated in addition to the following cause-specific mortality rates: any CVD, atherosclerotic CVD (ACVD), coronary artery disease (CAD), stroke, ischemic stroke. Mortality rates were age and sex standardized to the NYC year 2000 population. Joinpoint regression identified years in which mortality trends changed after excluding 116,285 deaths (10% of all deaths) occurring in 9 NYC hospitals (due to their participation in a cause of death reporting quality improvement training in 2009, sponsored by NYC Department of Health & Mental Hygiene (DOHMH)).

Results:
1,149,217 deaths occurred to NYC residents from 1990-2011, 566,181 among women and 583,036 among men. The annual percent change (APC) in all-cause mortality rates for women and men were -2.6% and -7.1% between 1994 and 1998, while rates were approximately -2.5% for both sexes from 1998-2011. CVD accounted 49.5% and 37.5% of deaths among women and men, respectively in 1990; in 2011 these proportions were 40.4% and 35.3%. Age standardized CVD mortality rates (per 100,000) for women and men were 391.0 and 357.8 in 1990 vs. 197.2 and 166.2 in 2011. Overall CVD mortality rates increased in women and men by 1.7% and 0.05% from 1990-1993 and began to decline in 1993 with APCs of -3.8% and -4.0% during 1993-2011. In contrast, the decline in atherosclerotic CVD mortality accelerated during 2002-2011 (APC=-4.7%) vs. 1990-2002 (APC=-2.4%) among men. Among women, atherosclerotic CVD rates began to decline more rapidly in 1993 (APC=-3.2%) and again in 2006 (APC=-6.6%) vs. 1990-1993 (APC=1.9%). Similar trends were evident for CAD mortality. Ischemic stroke mortality rates declined steadily from 1990-2011 in both sexes and there was no evidence of change in these trends. Results were generally consistent when all hospitals were included with the exception of rates for overall CVD mortality, which began to show more rapid decline in 2009 - immediately following DOHMH cause-of-death training efforts.

Conclusion:
Overall, CVD mortality rates in NYC did not accelerate during the 2002-2011 period after accounting for changes in cause of death reporting. However, atherosclerotic CVD rates did appear to change in slope (shift to declining more rapidly) during this period, with possible differences in timing between men and women.
Abstract MP44: Leukocyte Telomere Length and Risks of Incident Coronary Heart Disease and Mortality in a Racially Diverse Population
Authors: Carty Cara L , Liu Jingmin , Kooperberg Charles , Skinner Herndon Megan , LaCroix Andrea , Aviv Abraham , Reiner Alexander P
Published: July 2021

Background:
Telomeres are nucleotide repeat regions at the ends of chromosomes that maintain chromosomal structural integrity and genomic stability. Telomeres from circulating leukocytes can be readily measured; mean leukocyte telomere length (LTL) tends to decrease with age, vary by race/ ethnicity and is a putative marker of cellular aging. In studies of mainly white populations, shorter LTL has been associated with cardio-metabolic risk factors and increased risks of mortality and coronary heart disease (CHD), yet it is not clear whether these findings extend to other race/ethnicity groups. We sought to assess the relationship of LTL with risks of incident CHD and total mortality in a racially diverse population of post-menopausal women.

Methods:
Using a nested case-cohort design, African American (AA) and white women with incident CHD or mortality during a maximal follow-up of 19.4 years were randomly selected from the Women’s Health Initiative. LTL from baseline blood samples was assayed by Southern blotting. Race-stratified and risk factor-adjusted Cox proportional hazards models, weighted to account for the sampling scheme, were used to estimate the hazard of CHD or mortality.

Results:
A total of 1,525 women (858 whites and 667 AA) were included in the analyses. In whites, there were 367 incident CHD (292 mortality) events, while AA experienced 269 incident CHD (265 mortality) events. Cross-sectional LTL associations (p<0.05) with age, current smoking, and US recruitment region were observed in AA, whereas in whites, LTL was associated with age, current smoking and HDL cholesterol. Whites with longer LTL at baseline were less likely to have incident CHD, HR=0.58 (95%CI: 0.40-0.84), p=0.004, yet no significant association was observed in AA, HR=1.07 (95%CI: 0.71-1.61), p=0.74. This LTL-CHD association varied significantly by race/ethnicity, p=0.028. Similar trends were observed for total mortality, with longer LTL associated with reduced hazard in whites, HR=0.70 (95%CI: 0.46-1.06), but a slightly increased hazard in AA, HR=1.10 (95%CI: 0.80-1.53), though neither association was significant. In exploratory analyses of cause-specific mortality, increased LTL was associated with an increased, but non-significant hazard of cancer mortality in both AA and whites, p=0.17 and 0.28 respectively.

Conclusion:
We describe LTL associations with incident mortality, CHD and cardiovascular risk factors in post-menopausal women; these findings appear to vary by race/ethnicity. As a marker of chronic inflammation and cellular stress, LTL is robustly associated with CHD in whites, even after adjustment for cardio-metabolic risk factors including C-reactive protein, yet it does not appear to be associated with CHD in AA. Future studies exploring these race-specific differences may be warranted.
Abstract MP66: AREST Lifestyle: Adherence Effects of a Comprehensive Reminder System on Exercise Adherence in Post-Myocardial Infarction Patients
Authors: Pandey Avinash , Choudhry Niteesh K
Published: July 2021

Background:
The risk of recurrent cardiac events can be reduced by 30-50% through regular, structured exercise; however, there remains a high rate of inactivity in post myocardial infarction (MI) patients. Forgetting to exercise may be a contributor to inactivity. This study assessed the hypothesis that text message reminders may be an effective strategy to reduce forgetfulness and inactivity.

Methods:
In this one year, single center study, we recruited 50 cardiac rehabilitation patients within 2 weeks of their MI. Participants were randomized to usual care or to receive text message reminders 4 times daily which stated "Please remember to exercise 45 minutes today". The outcomes measured were the frequency and total duration of exercise (assessed by log books) and physical endurance/ aerobic fitness (assessed by exercise stress testing at months 1, 3 and 12).

Results:
Intervention and control patients had similar baseline characteristics with an average age of 64. In the control group, monthly duration of exercise fell from an average of 683 minutes over 17 days at month 1 to 416 minutes over 11 days at month 12. Patients randomized to text message reminders exercised 772 minutes over 18 days at month 1 and 794 minutes over 18 days in month 12 (p<0.01 for duration of exercise, control versus intervention, month 12). Baseline aerobic fitness and cardiac endurance was similar between control and intervention groups. However, there was a significant improvement in aerobic fitness and cardiac endurance at month 12 with text reminders (7.4 versus 6.1 METS achieved month 12, p<0.01). In all sub-groups analyzed this intervention significantly improved exercise adherence and fitness.

Conclusions:
In summary, this system improved frequency and duration of exercise, and objective measures of cardiac endurance and aerobic fitness. While this study was not designed to assess clinical outcomes, this text message reminder system represents a simple and scalable method for improving adherence to exercise regimens among post-MI patients.
Abstract MP70: Habitual Sleep Variability, Mediated by Energy Intake, is Associated with Abdominal Obesity in Adolescents
Authors: He Fan , Bixler Edward O , Liao Jiangang , Berg Arthur , Imamura Kawasawa Yuka , Fernandez-Mendoza Julio , Vgontzas Alexandros N , Liao Duanping
Published: July 2021

Introduction:
Although self-reported sleep duration has been associated with obesity, study of the association between objectively-measured habitual sleep pattern and the more metabolically relevant abdominal obesity, and the mediation factors for such an association, is limited.
Hypothesis:
We assessed the hypothesis that objectively-measured variability, mediated by excessive energy intake, is associated with abdominal obesity in adolescents.

Methods:
We used data from 421 adolescents in the Penn State Child Cohort follow-up examination. Actigraphy was used for 7 consecutive nights to calculate each participant’s mean sleep duration as habitual sleep duration (HSD) and the standard deviation of the mean as habitual sleep variability (HSV). Abdominal obesity was assessed by dual-energy x-ray absorptiometry as
Android/Gynoid Fat Ratio
and
visceral fat area
. Youth/Adolescents Food Frequency Questionnaire was used to obtain daily caloric, fat, carbohydrate, and protein intakes one year prior to the study. The R-based
Mediation Effect Models
were used to assess the association between sleep pattern and abdominal obesity, and quantitatively estimate the mediation effects of caloric intake and of other factors not analyzed in this report.

Results:
As shown in the table, after controlling for major confounders and BMI percentile, HSV was significantly and consistently associated with both abdominal obesity measures. The Mediation analysis consistently indicated a significant mediation effect of caloric intake, especially carbohydrate intake. For example, 20% of the association between HSV and visceral fat could be attributed to carbohydrate intake, while 80% by other factors not analyzed. HSD was not associated with abdominal obesity.

Conclusions:
Higher HSV, not HSD, is associated with abdominal obesity, which can be partially explained by increased caloric intake, especially from carbohydrate, in adolescents. More studies are needed to identify other mediation factors in the association.
Abstract MP80: Psychosocial Factors and Risk of Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ogilvie Rachel P , Everson-Rose Susan , Rodriguez Carlos , Longstreth W.T. , Albert Michelle , Diez-Roux Ana , Lutsey Pamela L
Published: July 2021

Background:
Heart failure is a major source of morbidity and mortality in the United States. Psychosocial factors have frequently been studied as risk factors for coronary heart disease, but not for heart failure.

Methods:
We examined the relationship between psychological status and incident heart failure among 6,782 individuals from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of cardiovascular disease at baseline. Anger, anxiety, chronic burden, depression, and hostility were measured using validated scales and were modeled categorically. Physician reviewers adjudicated incident heart failure events. Cox proportional hazards models were used to generate hazard ratios (HR) and 95% confidence intervals (CI) and adjusted for relevant demographic, behavioral, and physiological covariates. In exploratory analyses, we evaluated interactions between self-rated health and each psychosocial factor, and then stratified by baseline self-rated health (fair/poor and good/very good/excellent).

Results:
During a mean follow up of 9.3 years, 242 participants developed incident heart failure. Compared to participants in the lowest level, hazard ratios for those categorized in the highest level of anger [HR=1.14 (95%CI: 0.81-1.60)], anxiety [HR=0.74 (95%CI: 0.51-1.07), chronic burden [HR=1.25 (95%CI: 0.90-1.72), depression [HR=1.19 (95%CI: 0.76-1.85), and hostility [HR=0.95 (95%CI: 0.62-1.42) revealed no association with incident heart failure. In the exploratory analysis, interactions between the psychosocial factors and self-rated health were only statistically significant for hostility, but stratified models differed according to baseline health status. Compared to the lowest level, hazard ratios for those categorized in the highest level of anxiety [HR=2.11 (95%CI: 1.00-4.47)], chronic burden [HR=2.25 (95%CI: 1.08-4.67)], and depression [HR=2.15 (95%CI: 0.98-4.68)] revealed a positive association with incident heart failure among participants self-rated poor health at baseline, but there was no association for those with good self-rated health at baseline. For hostility, HRs for the highest versus lowest categorization were larger among those with good self-rated health and for anger, associations were similar regardless of self-rated health status.

Conclusions:
Overall these five psychosocial factors were not significantly associated with incident heart failure. However, for participants reporting poor health at baseline, anxiety, chronic burden, and depression were associated with an increased risk of heart failure. Future research with greater statistical power is necessary to confirm these findings and seek explanations.