bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 20111: High MCV and Low Platelet Count Indicate Higher Risk to Develop Cardiovascular Events in Patients Undergoing Hemodialysis
Authors: Tateno Kaoru , Takeda Yorinobu , Kobayashi Yoshio
Published: March 2022

Patients undergoing hemodialysis (HD) are at high risk of suffering fatal cardiovascular events, and there is a need to specify the most vulnerable cases that should undergo aggressive cardiovascular intervention. Here, we show that routine blood cell count has a prognostic value in HD patients. In a nested case-control study constituted of 167 patients who have had HD on April 2008, we analyzed conventional blood tests at arrival. Primary endpoint was defined as composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and occurrence of critical limb ischemia (CLI). Ten patients met exclusion criteria including renal transplant, and remaining 157 patients were analyzed. We found that those who met the endpoint were older, had higher Ca x P values, higher MCV, lower albumin, or lower platelet counts. Cox hazard analysis revealed that low platelet count was a risk factor independent to other significant factors (age and albumin). Kaplan-Meyer analysis showed that patients in the lowest platelet quartiles had strikingly worse prognosis compared to those with the highest (p<0.05). Sub-analysis showed that occurrence of the endpoint in secondary prevention arm, consisted of 40 patients with history of myocardial infarction, stroke, or healed CLI, were highly influenced by platelet count decrease compared to the remainder 117 patients who were designated as primary prevention arm. On the other hand, in the primary prevention arm, high MCV value was shown to be an independent risk factor. High MCV value had been reported to predict adverse outcome after coronary stenting, and our result expanded this finding to HD patients without any history of vascular diseases. This study also exhibited that low platelet count is an independent risk factor, especially for the secondary prevention arm of HD patients. Importantly, we have reported that platelet count positively correlates with circulating CD34-positive cells in CLI patients, whereas high MCV has been recognized to represent disturbed bone marrow function in various hematologic disorders. These imply that platelet count and MCV values can be surrogate markers of vascular injury and homeostasis, which thereby serve as predictors of adverse cardiovascular events in HD patients.
Abstract 20158: Consequences of Co-isolation of Brain and Heart on the Function of Isolated Cardiac Mitochondria in a Swine Model of Cardiopulmonary Resuscitation
Authors: Matsuura Timothy R , Bartos Jason A , Tsangaris Adamantios , Chandra Shekar Kadambari , Olson Matthew D , Rees Jennifer N , McKnite Scott H , Yannopoulos Demetris
Published: March 2022

Introduction:
Functional testing of isolated mitochondria is a powerful in vitro tool for determining mitochondrial health following an ischemic stress. Successful preservation of intact mitochondria requires an efficient harvest technique under cold conditions. As heart and brain mitochondria are vital to the success of cardiopulmonary resuscitation (CPR), we sought to determine the consequence of co-isolation of these organs on cardiac mitochondrial function in a porcine model of cardiac arrest.

Methods:
After 15 min of ventricular fibrillation, 36 animals were randomized to active compression decompression + impedance threshold device (ACD-ITD) CPR (Control), or ACD-ITD CPR + ischemic postconditioning (IPC) and further randomized to heart-only (Control n=9, IPC n=11) or heart + brain mitochondrial isolation (Control n=8, IPC n=8). IPC consisted of 3 cycles of 20 sec compression / 20 sec pause for the first 2 min of CPR. Cardiac and brain mitochondria were isolated via differential centrifugation 4 min after initiation of CPR. To minimize warm ischemia, brain biopsies were performed while animals were supine with uninterrupted chest compressions. Heart biopsies were subsequently performed via intercostal incision. Respiratory control index (RCI) and calcium retention capacity (CRC) were measured for complex I and II substrates.

Results:
Due to technique, heart isolation was delayed by 100 s in heart + brain vs. heart-only animals. In animals with heart-only isolation, IPC increased complex I and II RCI and complex I CRC compared to Controls. In animals with heart + brain isolation, cardiac complex I and II RCI and complex I CRC decreased within the IPC group but not within the Control group. There were no differences in brain mitochondrial function between IPC and Controls.

Conclusion:
Mitochondrial isolation from multiple organs must consider warm ischemia that may worsen mitochondrial performance. Communication between the brain and heart during biopsy appears to be mediated by a mechanism antagonistic to the beneficial effects of IPC, as isolation of heart and brain resulted in deleterious cardiac mitochondrial performance in IPC but not in Controls. Further investigation is warranted to refine multi-organ mitochondrial isolation.
Abstract 20174: Impact of Entrance Examination on Development of Nonalcoholic Fatty Liver Disease in New University Students
Authors: Konno Tetsuo , Ikeda Michiko , Shimizu Miho , Yoshimuta Tsuyoshi , Yoshikawa Hiroaki , Koizumi Junji , Okada Tohihide , Suzuki Ayako , Yamagishi Masakazu
Published: March 2022

Introduction:
Nonalcoholic fatty liver disease (NAFLD) has emerged as a risk factor for cardiovascular diseases. In Japan, most of high-school graduates who fail to pass the university entrance examinations attend full-time cram schools to devote themselves to preparing for the examinations for another year(s). These full-time cram-school students, called as “Ronin samurais” in Japanese, could be at risk for development of NAFLD because they live sedentary lifestyle under persistent academic stress.

Hypothesis:
We assessed the hypothesis that the Ronin-samurai period before entering university is associated with NAFLD in new university students.

Methods:
This cross-sectional study included 1777 new university students who underwent a group medical check-up immediately after admission into Kanazawa University.

Results:
Of the 1777 students, 319 (18%) went through the Ronin-samurai period before entering university (Ronin-samurai group). The Ronin-samurai group showed significantly higher body mas index, total cholesterol levels, and alanine aminotransferase (ALT) values compared to the non-Ronin group (n = 1458). The estimated mean difference (B) in ALT values between the two groups was 5.6 ± 1.2 IU/L (P <0.0001). The association persisted even after adjusting for age, gender and metabolic risk factors (B = 3.7 ± 1.5, P = 0.014). The follow-up analysis in 94 students with elevated ALT values (≥ 40 IU/L) after medical check-up showed a drastic decrease in mean ALT values in both groups only 9 weeks after entering the university (Figure), although no lifestyle intervention was performed during the time period.

Conclusions:
Spending an extra year(s) preparing for the entrance examination, as Ronin samurais, could contribute to this previously unrecognized “entrance examination-related NAFLD” in new university students.
Abstract 9741: A Novel Mutation Identified in a Large Multi-Generational Family With Long QT Syndrome Reveals Distinct, Disease-Specific Mutation Hot Spots within the
CACNA1C-
Encoded L-type Calcium Channel
Authors: Landstrom Andrew P , Boczek Nicole J , Ye Dan , Allen Hugh D , Ackerman Michael J , Kim Jeffrey J
Published: March 2022

Background:
Mutations in the CACNA1C-encoded L-type calcium channel have been associated with Timothy Syndrome (TS) with severe QT prolongation, cardiac hypertrophy, syndactyly, facial dysmorphisms, developmental delay, and sudden death by impaired channel inactivation and increase peak current. Recently, a small number of patients with CACNA1C mutations with only long QT syndrome (LQTS) have been described.

Objective:
To explore whether CACNA1C mutations associated with TS were mechanistically and clinically distinct from CACNA1C-mediated LQTS.

Methods/Results:
Illumina HiSeq 2000 platform-based whole exome sequencing with variant alignment using HGSC Mercury analysis and Atlas2 revealed a novel variant CACNA1C-L762F that co-segregated with affected patients of a large, multi-generational family with LQTS and sudden death. The proband presented at 3 years of age with out-of-hospital cardiac arrest and demonstrated QTc of 530. The mutation localized to the DII/DIII intracellular linker domain of the channel in a highly conserved region in close proximity to the 6th DI transmembrane domain. Whole cell patch clamp of heterologously expressed CACNA1C-L762F in TSA201 cells demonstrated slower inactivation tau and increased late current indicating its gain-of-function cellular electrophysiological phenotype. Comprehensive review and topological mapping of all described CACNA1C mutations associated with TS or LQTS revealed disease-specific hotspots. TS-associated mutations localized to cytoplasmic aspects of transmembrane domains while LQTS-associated mutations localized to cytoplasmic N- and C-terminal domains and linker regions. Probands hosting TS mutations demonstrated markedly prolonged QTc values compared to LQTS (618 vs 486 ms, p<0.001) and were younger at presentation (2.7 vs 20.1 years, p<0.002). Supporting these associations, the L762F mutation localized closer to the CACNA1C transmembrane domain than any other LQTS mutation and are associated with a QTc and age of diagnosis reflective of TS-associated mutations.

Conclusions:
The CACNA1C-L762F mutation is associated with biochemical and clinical features which highlight a molecular and clinical distinction between TS- and LQTS-associated CACNA1C mutations.
Abstract 9742: Counteractive Effects of Omentin-1 Against Atherogenesis
Authors: Watanabe Kaho , Watanabe Rena , Konii Hanae , Shirai Remina , Sato Kengo , Matsuyama Taka-aki , Ishibashi-Ueda Hatsue , Koba Shinji , Kobayashi Youichi , Hirano Tsutomu , Watanabe Takuya
Published: March 2022

Introduction:
Omentin-1, a novel adipocytokine expressed in visceral fat tissue, is negatively correlated with obesity, insulin resistance, and stable coronary artery disease (CAD). However, there have been no previous reports regarding the effects of omentin-1 on atherogenesis.

Objective and Methods:
We aimed to evaluate the atheroprotective effects of omentin-1 on human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs)
in vitro
, and aortic lesions in apolipoprotein E-deficient (ApoE
-/-
) mice
in vivo
. The histological expression of omentin-1 in coronary artery lesions and epicardial adipose tissues and its plasma levels were compared between CAD and non-CAD patients.

Results:
Omentin-1 was abundantly expressed in human umbilical vein endothelial cells, macrophages, HASMCs, and human coronary artery SMCs
in vitro
. Omentin-1 promoted antiinflammatory M2 phenotype
via
PPAR-γ upregulation and NF-κB downregulation during differentiation of human monocytes into macrophages. Omentin-1 suppressed oxidized LDL-induced foam cell formation associated with downregulation of CD36, scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1 and upregulation of neutral cholesterol ester hydrolase in human macrophages. In HASMCs, omentin-1 suppressed angiotensin II-induced migration and PDGF-BB-induced proliferation, and collagen-1 and collagen-3 expressions
via
ERK1/2 and NF-κB downregulation. Four-week infusion of omentin-1 into ApoE
-/-
mice retarded the development of aortic atherosclerotic lesions with reduced contents of monocytes/macrophages, SMCs, and collagen fibers. In addition, it increased peritoneal M2-activated macrophages, downregulated inflammasomes such as CRP, NF-κB, COX-2, and apoptosis-associated speck-like protein containing a caspase recruitment domain, and lowered plasma total cholesterol levels in ApoE
-/-
mice. Omentin-1 levels were markedly reduced in coronary endothelium and epicardial fat but increased in plasma and atheromatous plaques (macrophages/SMCs) in CAD patients compared with non-CAD patients.

Conclusions:
Our translational research provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD.
Abstract 9776: Association of Early Stress Testing With Outcomes for Emergency Department Evaluation of Suspected Acute Coronary Syndrome
Authors: Sun Benjamin , Laurie Amber , Fu Rongwei , Ferencik Maros , Shapiro Michael , Lindsell Christopher , Diercks Deborah , Hoekstra James , Hollander Judd , Kirk J. Douglas , Peacock W.Frank , Gibler W.Brian , Anantharaman Venkataraman , Pollack Charles
Published: March 2022

Introduction:
The emergency department (ED) evaluation of suspected acute coronary syndrome (ACS) is a common, challenging, and costly task with high clinical stakes. Professional society guidelines recommend early stress testing (within 72 hours of ED visit); however, there are no data to demonstrate improved outcomes with this approach.

Hypotheses:
1.) Early stress testing improves outcomes, and 2.) The association between early stress testing and outcomes is modified by pre-test ACS risk.

Methods:
We analyzed prospectively collected registry data from 9 emergency departments on patients with suspected ACS. The primary outcome was 30-day major adverse cardiovascular events (MACE), including all-cause death, acute myocardial infarction, and urgent revascularization. The exposure variable of interest was early stress testing. We used the HEART score to determine pre-test ACS risk (low, intermediate, high). To mitigate potential confounding by indication, patients with and without early stress testing were matched in a 1:2 ratio using propensity score methods. The propensity score model included over 40 demographic, clinical, biomarker, and ECG covariates.

Results:
The analytic cohort included 946 patients with early stress testing and 1,892 without early stress testing. There were no significant baseline imbalances after propensity score matching (p>0.1 for all covariates). There was no association between early stress testing and 30-day MACE in the overall cohort (OR 1.3; 95%CI 0.8-2.1). There was evidence of effect modification by pre-test ACS risk strata (low: OR 1.2, 95%CI 0.2-5.3; intermediate: 2.1, 95%CI 1.1-4.1; high: 0.4, 95%CI 0.1-1.4). In intermediate risk patients, early stress testing is associated with increased rates of revascularization (OR 2.8, 95%CI 1.3-6.0), but not with death/ acute myocardial infarction (OR 0.9, 95%CI 0.1-4.6).

Conclusions:
Early stress testing does not reduce 30-day MACE in the ED evaluation of suspected ACS. In intermediate-risk patients, early stress testing may result in increased revascularization rates without reduction in the objective outcomes of death or myocardial infarction. These findings challenge existing care guidelines and require confirmation by randomized trials.
Abstract 9796: Transradial versus Transfemoral Approach for Coronary Angiography and Intervention in Elderly: A Systemic Review & Meta-analysis
Authors: Singh Sukhchain , Sethi Ankur , Singh Mukesh , Grewal Navsheen , Khosla Sandeep
Published: March 2022

Background:
Limited information is available about the safety & efficacy of transradial (TR) versus transfemoral (TF) approach for percutaneous coronary angiography & interventions in the elderly.

Objective:
The authors Aimed to conduct first ever comprehensive meta-analysis to evaluate the safety & efficacy of TR versus TF approach in the elderly.

Methods:
The PubMed, Embase & CINAHL were searched for studies evaluating TR versus TF approach in the elderly (age≥75 years). The Stata software package was used to conduct more conservative random effect meta-analysis. Primary end point was access site complications (hematoma, pseudoaneurysm or need for access site surgery).

Results:
Twelves studies (4 randomized & 8 observational) comprising 5636 patients met inclusion criteria for the review (Figure). The primary end point of access site complications was significantly lower in the TR group versus TF group (RR 0.23, 95% CI 0.15-0.34). The secondary end points of bleeding requiring blood transfusion (RR 0.49, 95% CI 0.25-0.94) and any access site bleeding (0.26, 95% 0.17-0.40) were also significantly lower in TR group compared to TF. However, TR group had higher access site cross-over rate requiring alternate access site (RR 4.26, 95% CI 1.59-11.39). Two groups had similar rates of myocardial infarction (RR 0.81, 95% CI 0.54-1.21), stroke (RR 1.21, 95% CI 0.30-4.79), major adverse cardiovascular events (RR 0.84, 95% CI 0.64-1.11), in-hospital mortality (RR 0.75, 95% CI 0.29-1.96) & 30 day mortality (RR 0.79, 95% CI 0.57-1.08). The randomized and observational studies yielded concordant pooled effect estimates.

Conclusions:
Transradial approach, when feasible, significantly reduces the need for blood transfusions and access site complications in the elderly. A careful selection of access site is required due to high cross over rate in the TR approach. The benefit of TR approach may not extend beyond access site complications and bleeding.
Abstract 9885: Exercise Enhances Vascular Protective Effects of HMG-CoA Inhibitor Statins in Mice at Advanced Age
Authors: Cheng Xian Wu , Hu Lina , Jiang Haiying , Inoue Aiko , Wu Hongxian , Piao Limei , Okumura Kenji , Murohara Toyoaki , Kuzuya Masafumi
Published: March 2022

Introduction:
Regulatory T cells (Treg) have been shown to be immune suppressors of inflammatory actions. Given that exercise or 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, protect vascular tissue to stress in young animals and humans, we aimed to clarify the potential effect of swimming training (ST) to enhance the beneficial effects of statins and the cellular mechanism of the effect of statins on vascular actions in response to ischemia in mice at advanced age.

Methods and Results:
Aged (24 months) mice underwent hindlimb ischemic surgery. On operative day 1, the mice were randomly assigned to three groups treated with either vehicle, pitavastatin (PiS: 1 mg/kg/day; given by oral gavage every day), or PiS with swimming training (PiS-ST 1 hour/day) for 14 days. PiS treatment increased the levels of GATA3 and p-GATA6 proteins and interleukin-10 and CD206 (M2 macrophage marker) genes, whereas it suppressed the levels of p-STAT4 and tumor necrosis factor-1α proteins and C-X-C motif chemokine 10, monocyte chemotactic protein-1, gp91phox and CD40 (M1 macrophage marker) genes as well as macrophage infiltration of the ischemic muscles. PiS also reduced circulating numbers of CD4+ and CD8+ T cells and enhanced circulating CD4+/CD25+ T cells and CD31+/c-Kit+ EPCs. Moreover, EC apoptosis of the ischemic muscles ware lower in PiS-treated mice than in that of control mice. PiS improved blood flow recovery and capillary density. Interestingly, ST was found to enhance PiS-mediated beneficial actions.

Conclusion:
The statin-mediated beneficial effects are likely attributable, at least in part, to improvement of Treg-mediated inflammation and immune action and EC apoptosis; in addition, ST appears to enhance the vasculoprotective effects of statins, suggesting that a combination of statin and ST could be effective for the clinical treatment of cardiovascular disease in advanced age.
Abstract 9896: Reassessing Risk Factors for High Defibrillation Threshold: The EF-SAGA Risk Score and Implications for Device Testing
Authors: Shih Michael J , Kakodkar Siddharth , Kaid Yousef , Hassel Jonathan , Yarlagadda Santi , Fogg Louis , Madias Christopher , Krishnan Kousik , Trohman Richard G
Published: March 2022

Background:
Controversy exists over routine defibrillation threshold (DFT) testing during implantable cardioverter-defibrillator (ICD) placement. The aim of this study was to reevaluate risk factors for high DFT and propose a risk assessment tool.

Methods:
We retrospectively analyzed 1642 consecutive patients who received an ICD and underwent DFT testing.

Results:
The incidence of high DFT requiring addition of a subcutaneous array was 2.3%. Five significant independent variables predictive of high DFT were identified including younger age, male gender (hazard ratio 1.99), LV dysfunction, secondary prevention (hazard ratio 2.33), and amiodarone use (hazard ratio 2.39). Each 10 year increase in age was indicative of a 0.35 times lower chance of high DFT. Each 10% increase of LV EF was indicative of a 0.52 times lower chance of high DFT. These five variables form the EF-SAGA risk score (LV EF less than 20%, Secondary prevention ICD indication, Age less than 60 years, male Gender, Amiodarone use). Cumulative risk of high DFT increased incrementally; patients with four or more variables had an 8.9% likelihood of high DFT (Figure 1). Importantly, primary prevention patients with LV EF >20% had a negative predictive value for high DFT of 99.3%.

Conclusions:
In conclusion, we identified five independent predictors of high DFT. We propose the EF-SAGA risk score to help decision making. Primary prevention patients with an LV EF >20% had an exceedingly low incidence of high DFT suggesting that testing could be avoided in these patients. Careful assessment of the risk-benefit ratio of testing is important in high-risk patients.
Abstract 9941: Baseline Vitamin D Levels, Vitamin D Deficiency and Changes in Vitamin D With Statin Therapy Do Not Predict Statin Myalgia
Authors: Taylor Beth , Swales Heather , Lorson Lindsay , White C. Michael , Thompson Paul D
Published: March 2022

Background and Objective:
Low Vitamin D levels have been implicated as contributing to statin myalgia, but studies on the relationship between Vitamin D and statin-associated muscle side effects (SAMS) have produced discrepant results. We examined the influence of baseline and change in Vitamin D levels in patients with self-reported statin myalgia who developed muscle symptoms during a statin-placebo cross-over trial.

Methods:
Statin myalgia was verified in 120 patients with prior statin muscle complaints using an 8-week randomized, double-blind crossover trial of simvastatin (SIMVA) 20 mg/d and placebo. Anthropometrics, medical histories, demographics and serologic data (including 25 (OH)Vitamin D) were measured at each phase of the trial.

Results:
Forty three (35.8%) patients met the study criteria for myalgia, experiencing muscle pain on SIMVA but not placebo. Serum Vitamin D levels (mean ± standard deviation) prior to simvastatin treatment were not different between patients who did (31.7 ±12.1 ng/mL) or did not (31.6 ±10.3 ng/mL) develop myalgia and did not predict SAMS (r
2
= 0.00; p = 0.96). The change in Vitamin D with SIMVA (post-pre treatment) was also not different between myalgic and non-myalgic patients (0.3 ± 5.9 vs. 0.2 ±8.3 ng/mL, respectively) and again did not predict SAMS (r
2
= 0.00; p = 0.96). In addition, the proportion of patients classified as Vitamin D deficient (< 20 ng/mL) did not differ between myalgics and non-myalgics (n=7 vs. n=8; χ
2
=1.45; p = 0.23), nor did the proportion of patients classified as Vitamin D insufficient (< 30 ng/mL) (n=18 vs. n=37; χ
2
< 0.01 and p = 0.94, respectively).

Conclusions:
Our results suggest that baseline levels of Vitamin D, Vitamin D deficiency/insufficiency and changes in Vitamin D with statin therapy do not predict statin myalgia in patients in whom SAMS are verified using a rigorous double-blind, cross-over study design. The failure to verify SAMS in other studies may explain the discordant results on Vitamin D as a risk factor and potential treatment for statin myalgia.

Trial Registration:
NCT01140308
Abstract 9966: Radial versus Femoral Access in Acute Coronary Syndrome: Decrease in Mortality, Major Adverse Cardiac Events and Bleeding - An Updated Meta-Analysis of Randomized Controlled Trials
Authors: Casso Dominguez Abel , El-Hayek Georges , Contreras Elizabeth , Ranjan Pragya , Gongora Carlos , Argulian Edgar
Published: March 2022

Background:
Previous studies have come to inconsistent results about the role of radial access in reducing adverse outcomes in patients with Acute Coronary Syndrome (ACS) undergoing coronary angiography or Percutaneous Coronary Intervention (PCI). A meta-analysis was performed to summarize the up-to-date evidence on this subject.

Methods:
The Pubmed, EMBASE, Scopus and ClinicalTrials.gov databases were searched from inception to April 2015. The results was limited to Randomized Controlled Trials (RCTs) that evaluated the outcomes in patients with ACS undergoing radial versus femoral access for coronary angiography or PCI. Only studies that reported clinical outcomes. The primary end-point was all-cause mortality. Secondary end-points included Non-CABG major bleeds, Major Adverse Cardiac Events (MACE: Composite of death, myocardial infarction, or stroke), recurrent myocardial infarction (MI) and stroke. Pooled risk ratios (RR) and their 95% confidence intervals (CI) were calculated for all the clinical outcomes.

Results:
Sixteen RCT’s (n = 18,947) fulfilled the inclusion criteria. A total of 9,454 (49.9%) subjects were randomized to radial access and 9,493 (50.1%) to femoral access. The allocation to the radial approach was associated with decrease risk of all-cause mortality (1.7% vs. 2.4%; RR 0.72; 95% CI 0.59-0.88; I2 = 0%; P = 0.0010), decrease in non-CABG major bleeding (1.2% vs. 2.2%; RR 0.60; 95% CI 0.48-0.76; I2 = 0%; P < 0.0001), and decrease in MACE (6.2% vs. 7.2%; RR 0.85; 95% CI 0.77-0.95; I2 = 0%; P = 0.004). The rate of recurrent MI (4.0% vs. 4.4%; RR 0.91; 95% CI 0.80-1.04; I2 = 0%; P = 0.18) and stroke was similar with both approaches (0.49% vs. 0.41%; RR 1.19; 95% CI 0.77-1.84; I2 = 0%; P = 0.42).

Conclusions:
The current meta-analysis shows that radial access in patients with ACS undergoing coronary angiography or PCI reduces all-cause mortality, major bleeds and MACE. No substantial difference was found in the rate of recurrent MI or stroke.
Abstract 03: Choice Architecture Increases WIC Fruit and Vegetable Purchases in a Latino Community: Randomized, Controlled Corner Store Intervention
Authors: Thorndike Anne N , Bright Oliver-John M , Dimond Melissa A , Fishman Ronald , Levy Douglas E
Published: March 2022

Background:
In 2009, the Special Supplemental Nutrition program for Women, Infants, and Children (WIC) increased access to healthy foods by providing cash-value vouchers for fruit/vegetables, but improving access alone is not sufficient to reduce disparities in food choices and obesity among low-income families. We hypothesized that making fresh produce more visible and of better quality in corner stores would increase their WIC fruit/vegetable sales.

Methods:
We conducted a randomized, controlled trial of 6 WIC-certified corner stores in a low-income, Latino community. Three stores were assigned to “choice architecture” intervention that increased visibility and quality of fresh fruit/vegetables. Primary outcome was WIC fruit/vegetable voucher (FVV) sales, comparing changes in sales trends from baseline (Dec. 2012-Oct. 2013) to follow-up (Dec. 2013-Apr. 2014) for intervention vs. control stores. Secondary outcomes, from customer exit surveys at all 6 stores (N=575), were changes between baseline and follow-up in self-reported fresh fruit/vegetable purchases by customers on WIC or Supplemental Nutrition Assistance Program (SNAP).

Results:
WIC FVV sales decreased in both intervention and control stores during baseline but increased in the 3 intervention stores after implementing choice architecture (Figure). In exit surveys, 23% of all corner store customers reported using WIC, and 37% used SNAP. Compared to baseline, intervention store customers on SNAP increased purchase of fruit/vegetables at follow-up more than SNAP customers at control stores (6% vs. -15%, p=0.007). For WIC customers, there was a similar but not statistically significant difference between intervention and control (18% vs. -2%, p=0.11).

Conclusion:
A simple choice architecture intervention increased purchases of fruit/vegetables by corner store customers using WIC. Policies that incentivize WIC-certified stores to stock and prominently display good quality fresh produce could improve healthy choices of low-income families.
Abstract 06: Long-term Blood Pressure Variability Throughout Young Adulthood and Mid-life Cerebrovascular Structure and Function: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Yano Yuichiro , Allen Norrina , Erus Guray , Colangelo Laura , Levine Deborah , Sidney Stephen , Bryan R. Nick , Viera Anthony , Reis Jared , Shimbo Daichi , Schreiner Pamela , Ning Hongyan , Tedla Yacob , Liu Kiang , Greenland Philip , Lloyd-Jones Donald , Launer Lenore
Published: March 2022

Introduction:
In addition to average blood pressure (BP) values, BP variability has been suggested to be associated with lower cognitive function. It is unclear how long-term BP variability throughout young adulthood is associated with cerebrovascular structure (e.g., hippocampus) and function in midlife.

Methods:
Using data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which recruited healthy young adults ages 18 to 30 years (mean age 25 years) in 1985-1986, we assessed average BP over visits and visit-to visit BP variability (average real variability [ARV], defined as the absolute differences of BP between successive BP measurements) during 25-year follow-up (8 visits). Normal brain volume, abnormal brain volume, brain integrity assessed by fractional anisotropy, and cerebral blood flow were calculated by 3-Tesla MRI at the Year 25 follow-up (n=557, 52.2 % women, and 34.5 % African Americans).

Results:
For the 557 participants, mean ARV of SBP was 7.8±3.1 mm Hg. Higher ARV of SBP was associated with lower normal total brain volume, gray matter, and hippocampus after adjustment for covariates including intracranial volume and average BP during follow-up (Table). Higher average SBP during follow-up was associated with higher abnormal brain volume and lower integrity in the whole brain and the white matter, and lower blood flow in the hippocampus.

Conclusions:
Long-term visit-to-visit BP variability for 25 years beginning in young adulthood was associated with midlife cerebrovascular structural and functional alterations, independent of average BP during follow-up. Focusing not only on BP values alone but also on visit-to-visit BPV may be important to identify younger adults who may be at risk for developing lower cognitive function later.
Abstract 21: Associations of Nonalcoholic Fatty Liver Disease with Measures of Early Brain Health
Authors: VanWagner Lisa B , Terry James G , Chow Lisa , Alman Amy , Kang Hakmook , Ingram Katherine , Shay Christina , Lewis Cora E , Bryan Robert N , Launer Lenore , Carr J. J
Published: March 2022

Background:
Subclinical liver disease may be a risk factor for cognitive impairment. Obesity is related to metabolic processes that affect brain structures underlying cognitive decline. Nonalcoholic fatty liver disease (NAFLD) is an obesity-related condition with high cardiovascular disease (CVD) morbidity. In a population-based cross-sectional sample of black and white adults free from prevalent liver or cerebrovascular disease, we tested the hypothesis that NAFLD is associated with early measures of brain health independent of BMI or visceral adipose tissue (VAT).

Methods:
Participants from the Coronary Artery Risk Development in Young Adults study (Y25 exam; age 43-55 years) with concurrent CT quantification of liver fat and brain magnetic resonance (MR) images were included. NAFLD was defined after exclusion of other causes of liver fat. 3T brain MR images provided estimates of normal tissue volume (NTV) and total (CBF-tot) and gray matter (CBF-GM) cerebral blood flow. NTV was adjusted for intracranial volume (ICV, brain plus cerebral spinal fluid). CBF was adjusted for total tissue volume (TTV, total brain tissue perfused). Linear regression models tested associations.

Results:
Mean liver attenuation (LA) was 56.9 HU (range 16.6-81.3). NAFLD prevalence was 11%. Lower LA (higher liver fat) was associated with reduced NTV, CBF-tot and CBF-GM after adjusting for ICV, demographics, and health behaviors (p<0.05). LA remained associated with CBF-tot and CBF-GM after adjustment for CVD factors (p<0.05). Only NTV was significant after adjustment for CVD factors and BMI (p=0.02). After adjusting for VAT, the relationship between LA and NTV was attenuated (p=0.06). Findings were similar when using a clinical cutpoint of ≤51 HU for NAFLD (Table 1).

Conclusion:
Increased liver fat and CT-defined NAFLD are negatively associated with early brain health, reflected in MR measures of structure and perfusion. BMI and VAT attenuate the relationship providing insight into the potential role of obesity in brain health and disease.
Abstract 23: Visceral Adiposity is Associated with Persistently High and Less Variable Blood Pressure: Results From the Dallas Heart Study
Authors: Yano Yuichiro , Vongpatanasin Wanpen , Ayers Colby , Turer Aslan , Turer Aslan , Chandra Alvin , Carnethon Mercedes , Greenland Philip , de Lemos James , Neeland Ian
Published: March 2022

Introduction:
Hypertension is strongly linked to obesity. Blood pressure variability (BPV), a novel BP phenotype with potential clinical significance, may also be associated with increased adiposity. We aimed to investigate the relationship between body fat distribution and average BP and BPV in the short- and long-term.

Methods:
Using data from the Dallas Heart Study, we assessed within-visit (short-term) and visit-to-visit (long-term) BPV (average real variability [ARV], defined as the average of absolute differences of BP between successive BP measures) during a 5-month follow-up period (2000-2002). Five BP measures were taken at each of the 3 visits (two in-office and one in-home survey). The associations of visceral (VAT) and abdominal subcutaneous adipose tissue (SAT) quantified by MRI and lower body subcutaneous fat (LBF) by DEXA with BP phenotypes were assessed using multivariable-adjusted linear regression.

Results:
2595 participants with mean age 44 years; 54 % women; 68 % non-White; mean BMI 29 kg/m2, mean SBP 127 mmHg and DBP 79 mmHg were included. The short-term ARV of SBP at home and office, and long-term ARV of SBP over 3 visits were 4.0±2.4 mm Hg, 4.1±2.5 mmHg, and 9.8±7.1 mmHg, respectively. VAT, SAT, and LBF were not associated with short-term ARV of SBP, while higher VAT was associated with lower long-term ARV of SBP (Table). VAT was strongly associated with average SBP in the short- and long-term, while higher LBF was associated with lower average SBP in the short- and long-term.

Conclusions:
Greater VAT is associated with persistently higher short- and long-term average BP with lower variability over visits. The presence of persistently elevated BP, coupled with lower BPV, associated with visceral adiposity may impose higher cardiac workload and consequently increase cardiac hypertrophy and risk for heart failure.
Abstract 34: Effects of the DASH Diet and Sodium Intake on Serum Uric Acid
Authors: Juraschek Stephen P , Gelber Allan C , Appel Lawrence J , Miller Edgar R
Published: March 2022

Background:
Elevated serum uric acid (SUA) is etiologically related to the occurrence of gout and is associated with an increased risk of cardiovascular disease. Dietary recommendations for SUA reduction are largely based on observational studies. In an ancillary study to the DASH-Sodium feeding study conducted at the Johns Hopkins clinical center (N=103), we examined the effects of the DASH diet and of sodium intake on SUA levels.

Methods:
The DASH-Sodium trial was a randomized, crossover feeding trial among adults without cardiovascular disease not using antihypertensive medications. Participants were randomly assigned to either a control diet or the DASH diet; during both diets, participants were fed each of three sodium levels in random order in 4-week periods separated by 5-day breaks. Body weight was held constant. The three sodium levels were: low (50 mmol/d), medium (100 mmol/d), and high (150 mmol/d). SUA was measured at baseline and after each feeding period, allowing for comparisons by diet (DASH vs control) and sodium levels.

Results:
Trial participants were 55% women and 76% black; mean age was 52 years (SD, 10) and mean SUA was 5.0 mg/dL (SD, 1.3). Mean baseline alcohol intake was low at 1.3 g/day. Compared with the control diet, the DASH diet reduced SUA by -0.35 mg/dL (95% CI: -0.65, -0.05; P = 0.02). Among participants with a baseline SUA ≥6 and <7 mg/dL (N=16), the mean effect was -0.8 mg/dL; among participants (N=8) with a baseline SUA ≥7 mg/dL the mean effect was -1.3 mg/dL (P-interaction = 0.04) (Figure). Compared to the low sodium intake, the medium sodium intake lowered SUA by -0.3 mg/dL (95% CI: -0.5, -0.2; P < 0.001) and the high sodium intake lowered SUA by -0.4 mg/dL (95% CI: -0.6, -0.3; P < 0.001). The effects of sodium intake on SUA were greater among participants with high blood pressure at baseline (P-interaction = 0.02, see Figure).

Conclusions:
This study demonstrates that the DASH diet lowers SUA, that this effect differs by sodium level, and that SUA reduction is greatest in those with hyperuricemia at baseline.
Abstract 43: Access to Care, Income, Education and Coronary Heart Disease Outcomes in the Reasons for Geographic and Racial Differences in Stroke Study
Authors: Lewis Marquita W , Khodneva Yulia , Safford Monika M
Published: March 2022

Background:
We have shown that individuals aged <65 years with the combination of low income (INC) and low education (EDU) are at high risk of coronary heart disease (CHD). Access to healthcare is often cited as a major contributor to this relationship, but few studies have examined these relationships for combinations of INC and EDU. We hypothesize that he association between INC+EDU categories and incident CHD is mediated by insurance status, rural residence, and living in a health professional shortage area (HPSA).

Methods:
We used data from 24,666 participants free of CHD at baseline in the national prospective Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort study of black and white participants aged
>
45 years recruited between 2003-2007. Low INC (<$35,000) and low EDU (<high school graduation) were used to define four groups (Table column headings). Cox proportional hazards models examined the mediating effects of having health insurance, rural residence, and HPSA residence on the association between combinations of INC-EDU and CHD, stratified on age 65.

Results:
A total of 1,046 events occurred over mean follow-up 6.4±2.3 years. For those <65, low INC+EDU and low INC+high EDU were associated with higher risk for CHD (Table). In unadjusted models, HPSA residence was not significantly associated with CHD incidence for either younger or older participants, but having health insurance (HR 0.74 [95% CI 0.55-0.99]) and rural residence (HR 1.41 [95% CI 1.14-1.73]) were significantly associated with CHD for younger but not older participants. There was no evidence of mediation by access to care variables (Table).

Conclusion:
Access to care variables did not mediate the relationship between low INC, especially low INC+EDU, and CHD observed in younger REGARDS participants. Access to care as reflected in health insurance or rural or HPSA residence may not play a major role in the higher risk for CHD in middle aged adults living in low socioeconomic circumstances.
Abstract 46: Legacy Effects of STRRIDE Exercise Training Programs on Cardiometabolic Health Observed Ten Years Later
Authors: Kraus William E , Slentz Cris A , Duscha Brian D , Willis Leslie H , Johnson Johanna L
Published: March 2022

Introduction:
STRRIDE Reunion evaluated longitudinal changes in cardiometabolic health 10 years after completion of STRRIDE (Studies Targeting Risk Reduction Interventions through Defined Exercise). Subjects originally were randomized to one of four eight-month interventions: inactive control (IC); low amount moderate, intensity exercise (LAMI); low amount, vigorous intensity (LAVI); high amount, vigorous intensity (HAVI).

Methods:
Of 153 Duke STRRIDE graduates, 28 were lost to followup; 21 declined to participate in the Reunion; 104 were studied. Participants completed medical history and physical activity questionnaires; height, weight, blood pressure, waist circumference, and blood were collected; fitness was assessed on 93. We evaluated change in CMH 10 years after completion relative to assessments taken at the time of original randomization; thus, change scores reflect the original study-related changes plus those persisting over the ensuing ten years (legacy effect).

Results:
Several independent measures suggested group-specific legacy effects. Mean arterial pressure was lower in LAMI. This was different (P<0.05) from all other groups even after controlling for BP meds and baseline values. LAMI also had a lower fasting insulin; this was different (P<0.05) from IC. Peak VO2 decreased 10-11% over ~11 y in IC and LAMI, but decreased < 5% in both vigorous intensity groups (LAVI, HAVI). IC increased 5.3 kg and 5 cm in waist circumference; however, none of the exercise groups changed significantly in these variables. All exercise groups maintained or improved lipids, blood pressure, body weight, fasting insulin; fasting glucose increased substantially in all groups. Physical activity was maintained more in all exercise groups over follow-up.

Conclusions:
We observed group-specific legacy effects from a eight-month exercise training program. Whether this was due to maintained physical activity, it demonstrates the power and value for long-term CMH of even moderate term exercise interventions.
Abstract MP05: Life’s Simple 7 and Incident Heart Failure: The Multi-Ethnic Study of Atherosclerosis
Authors: Ogunmoroti Oluseye , Oni Ebenezer , Allen Norrina B , Spatz Erica S , Rana Jamal S , Virani Salim S , Blankstein Ron , Blumenthal Roger S , Veledar Emir , Szklo Moyses , Blaha Michael J , Nasir Khurram
Published: March 2022

Background:
The concept of Life’s Simple 7 (LS7) metrics was introduced by the American Heart Association to assess and promote cardiovascular health. Individuals with favorable LS7 scores have a lower incidence of cardiovascular disease. In this study, we examined the association between the LS7 metrics and incident heart failure (HF)

Methods:
We analyzed data from the Multi-Ethnic Study of Atherosclerosis, a multicenter cohort study that included 6,814 participants free of established cardiovascular disease, between the ages of 45 and 84. The components of the LS7 metrics (smoking, physical activity, body mass index, diet, blood pressure, total cholesterol and blood glucose) were graded on a scale of 0-2, with 2 indicating “ideal” status, 1 indicating “intermediate” status and 0 indicating “poor” status. These scores were summed for each participant, thus, the LS7 score created ranged from 0 to 14. Hazard ratios and incidence rates of HF per 1000 person-years were calculated

Results:
After exclusion of participants with incomplete data, the final study population was 6,506 (53% female mean age 62 ±10 years). In a median follow up of 10.2 years, 181 (2.8%) participants developed HF. The incidence of HF decreased as the number of ideal LS7 metrics increased 6.5 per 1000 person-years for participants with 0-1 ideal metrics compared to 1.3 per 1000 person-years for those with 5 ideal metrics (Table). No HF event was reported in participants with 6-7 ideal metrics at baseline. In comparison to participants with 0-1 ideal metrics, having 2, 3, 4, and 5 ideal metrics was associated with an 11%, 36%, 59% and 76% lower hazard for HF respectively. In addition, optimal and average LS7 scores were associated with an 80% and 51% lower hazard for HF, respectively

Conclusion:
The American Heart Association LS7 metrics was associated with a lower incidence of HF in a follow up extending up to 10 years. These findings suggest that efforts to achieve ideal cardiovascular health metrics favorably reduce the risk of HF, a major source of morbidity and mortality
Abstract MP101: Infection as a Trigger for Ischemic Stroke: The ARIC Study
Authors: Cowan Logan T , Alonso Alvaro , Pankow James S , Folsom Aaron R , Rosamond Wayne D , Gottesman Rebecca F , Lakshminarayan Kamakshi
Published: March 2022

Background and Purpose:
Acute triggers for ischemic stroke, which may include infection, are poorly understood, as is whether background cardiovascular disease (CVD) risk modifies such triggering. We hypothesized that recent infection increases acute stroke risk, especially among those with low background CVD risk.

Methods:
Hospitalized strokes and infections were identified during follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort of 15,792 men and women aged 45-64 years at baseline (visit 1) in 1987-89 through 2013. A case-crossover design and conditional logistic regression were used to compare acute hospitalized infections among stroke patients (14, 30, 42, and 90 days prior to stroke) with corresponding control periods 1 year and 2 years prior. Background CVD risk was assessed using the ACC/AHA equations at both visit 1 and the visit most proximal to the stroke, with risk dichotomized at the median (10.0% estimated 10-year risk for visit 1 and 15.4% for most recent visit).

Results:
A total of 1,008 adjudicated incident ischemic strokes were included. Compared to control periods 1 and 2 years before stroke, hospitalized infection was more common within 2 weeks before stroke (14 day odds ratio (OR) = 7.7 (95% confidence interval=2.1, 27.3)); the strength of association declined with increasing time in the exposure window before stroke (30 day OR = 5.7 (2.3, 14.3), 42 day OR = 4.5 (2.0, 10.2), and 90 day OR = 3.6 (2.1, 6.5) see Table). Stroke risk was higher among those with low compared with high background CVD risk, with this interaction (between hospitalized infection and CVD risk) reaching statistical significance for some exposure periods.

Conclusions:
These results suggest that hospitalized infection is a trigger of ischemic stroke, and may explain some cryptogenic strokes. Infection control efforts may prevent some strokes. CVD preventive therapies, including antiplatelet agents and statins, may prevent strokes if used in the peri-infection period but clinical trials are needed to evaluate this.