bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P027: Obesity Treatment-Induced Weight Loss Improves Resting Blood Pressure and Reduces Progression from Prehypertension to Hypertension in Overweight/Obese Adults
Authors: Gupta Alok K , Church Timothy , Day Wesley W
Published: July 2021

Background:
Obesity is associated with increased risk of hypertension (HTN). Weight loss can reduce blood pressure (BP) and prevent progression to HTN. In the CONQUER trial, overweight/obese subjects with ≥2 weight-related comorbidities had significant weight loss over 56 weeks with phentermine plus topiramate extended-release (PHEN/TPM ER) vs placebo when used in combination with a program of lifestyle modifications.

Methods:
This post hoc analysis of CONQUER evaluated the effects of PHEN/TPM ER on weight, BP, and HTN status over 56 weeks (intent-to-treat population with last observation carried forward). Overweight/obese subjects with normotension (systolic BP/diastolic BP<120/80 mm Hg; 8.7%; n=212), preHTN (120-139/80-89 mm Hg; 19.0%; n=465: both without antiHTN medication use), and HTN (≥140/90 or antiHTN medication use; 72.3%; n=1770) were randomized to placebo, PHEN 7.5 mg/TPM ER 46 mg (7.5/46), or PHEN 15 mg/TPM ER 92 mg (15/92).

Results:
At week 56, PHEN/TPM ER-treated subjects in all categories (normotension, preHTN, HTN) achieved significant weight loss vs placebo (percentage and absolute; all
P
<.0001). Systolic BP was improved vs placebo in all categories in subjects receiving PHEN/TPM ER (significant vs placebo in 15/92 group; Table). Fewer subjects with normotension at baseline receiving PHEN/TPM ER progressed to preHTN, and fewer with preHTN at baseline progressed to HTN, vs placebo (Table). A greater percentage of PHEN/TPM ER-treated subjects with preHTN and HTN achieved normotension vs placebo. Most common adverse events in subjects with preHTN and HTN were constipation, dry mouth, and paraesthesia, and in those with normotension were upper respiratory tract infection, dry mouth, and paraesthesia.

Conclusion:
Overweight/obese subjects treated with PHEN/TPM ER plus lifestyle intervention lost more body weight vs placebo over 56 weeks. This weight loss occurred along with improvements in BP in subjects with normotension, preHTN, and HTN, potentially improving cardiovascular risk.
Abstract P064: Weight Loss Induced by Healthy Diets Reduces Atherogenic Lipoproteins that Contain ApoC-III Independent of Dietary Macronutrient Content
Authors: Furtado Jeremy , Carey Vincent , Bray George , Sacks Frank
Published: July 2021

Background:
Weight-loss improves lipid risk factors for cardiovascular disease risk. However, the effect of weight loss on VLDL, LDL and HDL subtypes that contain apoC-III, newly emerging as important predictors of CVD, is not known. Further, the effects of dietary macronutrient composition on changes in apoC-III-containing lipoproteins in the presence of weight loss have not been studied.

Methods:
The Pounds Lost Trial randomized 811 overweight and obese subjects to four healthful diets that varied in emphasis of unsaturated fat, protein, and carbohydrate for 24 months. A random 50% subsample was selected for analysis of lipoprotein subfractions (~100 per study diet). Plasma samples were collected at baseline and after 24 months and stored at -80C to await analysis. Whole plasma was fractionated first by apoC-III content and then by density (VLDL, IDL+LDL, HDL) to produce 6 subfractions: VLDL with apoC-III, VLDL without apoC-III, IDL+LDL with apoC-III, IDL+LDL without apoC-III, HDL with apoC-III, HDL without apoC-III. Apolipoprotein and lipid concentrations were measured in these subfractions. The primary aim was to determine whether macronutrient content of diets for weight loss influenced changes after weight loss in concentrations and compositions of the 6 lipoprotein subfractions. A secondary analysis determined the relation between amount of weight-loss and change in the lipoproteins, adjusted for baseline BMI, age, race, and sex.

Results:
On average, the study population had lost 5% of their body weight at 2 years regardless of randomized diet group. Changes in lipoprotein subfractions from baseline to 2 years were similar among the 4 diet groups. Multiple regression analysis determined that degree of weight loss significantly predicted reductions in apoC-III in VLDL, LDL and HDL. For example, a 5% weight loss corresponded to reductions in apoC-III in VLDL of 14% (95% CI: 8.0%, 19.8%), LDL of 5.5% (0.3%, 8.6%), and HDL of 2.2% (0.1%, 4.4%). Weight loss notably predicted a decrease in the apoB concentration of LDL with apoC-III. The concentration of LDL with apoC-III was the strongest predictor of CVD in several cohorts. In contrast, weight loss predicted increases in apoE in VLDL and LDL. ApoE increases the clearance from plasma of VLDL and LDL and reduces the formation of LDL from VLDL.

Conclusion:
Weight loss achieved through healthful diets reduces apoC-III and atherogenic LDL with apoC-III but increases apoE in apoB-lipoproteins regardless of macronutrient emphasis. These effects on lipoprotein subfractions represent a novel mechanism by which weight loss may reduce cardiovascular disease risk.
Abstract P072: Who Becomes Weak on Statins? Effect Modification Exposed in a RCT by Risk Factor Compounding
Authors: Golomb Beatrice A , Koperski Sabrina
Published: July 2021

Background:
Some patients develop muscle weakness (
MW
) on statins but MW has not been affirmed in RCTs. Existing evidence suggests muscle problems may arise more commonly in those who are older, female, have a history of muscle problems, or exercise more. We assessed whether statin effects on MW can be unmasked by attending to effect modification, assessing if pairing of known risk factors (
RFs
) may amplify and expose MW in subgroups.

Method:
In a double blind RCT, 1016 adults (68% men) without DM or CVD were randomized equally to simvastatin 20mg, pravastatin 40mg or placebo for 6 months. MW was rated at baseline (0-10) and as change from baseline (-2 to +2). T-tests of difference in self-rated change in MW compared placebo to each statin arm, examining hypothesized vulnerable subgroups based on a) paired age/sex vulnerability (female + age >65); and paired weakness+exercise vulnerability (baseline weakness rated >0, + regular exercise >5x/week).

Results:
Statins vs placebo did not increase MW in the full sample. Trends were not significant in those with individual RFs. Statins significantly increased MW in both risk-factor pairings (
Table
). In older women, mean MW increase on statins rose as age advanced further, from 0.19 (age >65) to 0.26 (>70), 0.37 (>75), and 1 (>80), while MW on placebo remained unchanged or improved. Statins also increased MW in subjects with any baseline MW (rated >0) who engaged in regular exercise: Effects were larger, but the subgroup smaller.

Discussion:
In subgroups suggested by coupling of RFs in existing literature, analysis identifies significantly increased MW with statins vs placebo, providing, to our knowledge, the first RCT evidence of MW on statins. Older women represent an important group in whom MW increased. In those with any baseline MW who exercise regularly (as may be recommended), MW worsened with statins. Findings were consistent across statin randomization arms. This may offer an approach to better unmask adverse effects in RCTs.
Abstract P105: Dietary Acid Load of a Low Versus a High Protein Diet and Its Effect on Blood Pressure: A Fully Controlled Dietary Intervention Trial
Authors: Engberink Marielle F , Altorf-van der Kuil Wieke , Brink Elizabeth J , Bakker Stephan J , van Baak Marleen A , Geleijnse Johanna M
Published: July 2021

Background:
Mild metabolic acidosis may result in elevated blood pressure (BP). Several formulas to estimate dietary acid load have been developed. However, studies in which these formulas have been validated are limited.

Objectives:
To validate and/or improve existing formulas for dietary acid load and to examine the association between dietary protein, acid load and BP.

Methods:
We performed a randomized 14d crossover dietary intervention involving 37 healthy subjects (age: 21±2 y) who consumed individualized, isocaloric diets that were either low or high in protein (0.5 versus 2.0 g protein/kg BW/d). Duplicate portions of the provided diets were collected and analysed for energy and nutrients. We used two measures to characterize dietary acid load (i.e. PRAL and NEAP). Urinary Net Acid Excretion (NAE; i.e. titratable acid + ammonium - bicarbonate) was analysed. BP was measured according to standardized procedures.

Results:
Mean dietary intakes significantly differed between the low and high protein diet, resulting in significantly different acid load values (Table 1, all p<0.001). The correlation between PRAL and NAE was 0.08 in the low protein diet and 0.62 in the high protein diet. For NEAP the correlations were 0.27 and 0.32. PRAL explained 69% of the variance of NAE, which could not be improved by adding other variables to the formula. Systolic BP was 108.4±7.5 and 109.5±8.0 mmHg on the low and high protein diet respectively (p=0.25).

Conclusion:
PRAL predicts NAE reasonably well in healthy adults for normal to high protein intake. PRAL can be influenced by diet, but this cannot be clearly attributed to protein intake alone. PRAL does not seem to influence short-term BP in healthy adults with normal BP.
Abstract P262: Comparison of Contemporary, Highly-sensitive and Supersensitive Troponin Assays as Predictors of Incident Cardiovascular Events - A Prospective Analysis of the Finrisk 1997 Cohort
Authors: Neumann Johannes T , Havulinna Aki S , Zeller Tanja , Appelbaum Sebastian , Jousilahti Pekka , Blankenberg Stefan , Sydow Karsten , Salomaa Veikko
Published: July 2021

Introduction:
Besides the role in diagnosis of acute cardiac events, troponins seem to be powerful biomarkers in terms of risk stratification in the general population. The objective of our study was to compare the performance of three troponin assays with different sensitivities in cardiovascular disease (CVD) risk prediction in a population-based cohort without a history of CVD events. We hypothesized that troponins may predict future CVD events even in healthy individuals and that the predictive power may depend on the sensitivity of the assay.

Methods:
Troponin I concentrations were measured using a contemporary sensitive (Abbott TnI), a highly sensitive (Abbott hsTnI), and a supersensitive assay (Singulex) in participants aged 25-74 years of the FINRISK 1997 cohort, followed up for 14 years. Individuals with a history of major adverse cardiovascular event (MACE, n=470) and pregnant women (n=76) were excluded and 7,899 persons were included in the analysis. Study endpoints were defined as incident myocardial infarction (MI), coronary heart disease (CHD), CVD (including all of the above plus ischemic stroke), incident heart failure (HF) and MACE (including all of the above). We used Cox proportional hazards regression to determine relative risks per one standard deviation increment in troponin, followed by measures of discrimination and reclassification using 10-fold cross-validation to control for overoptimism.

Results:
During follow-up, we observed 1,074 incident MACE, which included 277 MI events, 529 CHD events, 770 CVD events, and 505 cases of HF. We observed significantly (p<0.001) increased hazard ratios (HR) for the supersensitive troponin assay for incident MI (HR 1.24 [95% confidence interval (CI) 1.11-1.39]), and CVD (HR 1.15 [CI 1.07-1.24]). For HF and MACE, both highly sensitive and supersensitive troponin showed significantly increased HR (HF: 1.19 [CI 1.1-1.3] and 1.28 [CI 1.18-1.39]; MACE 1.12 [CI 1.05-1.19] and 1.18 [CI 1.11-1.25]), respectively. There was no overall improvement in net reclassification (NRI). Focusing on the clinical NRI, which determines reclassification in individuals with an intermediate risk according to the Framingham risk score, the NRI was significantly improved for HF (NRI 10.2%, p<0.001), and MACE (NRI 5.1%, p<0.001), when using the supersensitive troponin assay.

Conclusions:
In our large population-based cohort high-sensitivity troponin assays improved risk prediction for cardiovascular endpoints. The use of a supersensitive troponin assay led to an improvement of the clinical NRI for MACE, HF, and CHD.
Abstract P335: Salt Sensitivity and Incidence of Hypertension: The GenSalt Study
Authors: He Jiang , Gu Dongfeng , Chen Jing , Chen Jichun , Zhao Qi , Huang Jianfeng , Li Jianxin , Cao Jie , Rice Treva , Mills Katherine , Chen Chung-Shiuan , Hamm Lee
Published: July 2021

It is well known that blood pressure (BP) responses to dietary sodium and potassium intakes vary among individuals (salt- and potassium-sensitivity). However, it is unknown whether salt- and/or potassium-sensitivity predict the risk of hypertension. We conducted a dietary sodium and potassium intervention study among 1,906 Han Chinese in 2003-05 and followed the study participants in 2008-09 and 2011-12. The dietary intervention included a 7-day low sodium-feeding (51.3 mmol/day), a 7-day high sodium-feeding (307.8 mmol/day), and a 7-day high sodium-feeding with an oral potassium supplementation (60 mmol/day). Three BP measurements were obtained on each of the last 3 days of each intervention period at the baseline and each of the 3 days of follow-up examinations. Systolic BP responses (mean ± SD) to dietary intervention were -5.5±7.0 for low-sodium, 4.9±6.0 for high-sodium, and -3.5±5.5 for potassium-supplementation. Over an average of 7.4 years of follow-up, we identified 455 incidence hypertension cases (systolic BP≥140 mmHg and/or diastolic BP ≥90 mmHg and/or use of antihypertensive medication). The age-adjusted cumulative incidences of hypertension by the quartiles of systolic BP responses to dietary intervention were showed in the following table. These associations remained after adjustment for multiple covariates. These data indicate that BP responses to dietary sodium and potassium intervention are related to the subsequent risk of hypertension. Furthermore, our study suggests that individuals who are more sensitive to dietary sodium and potassium intake are at an increased risk for hypertension and should be target for dietary intervention.
Abstract P338: Age and Gender Differences in Response to Repeat Blood Pressure Measurement after Brief Patient Rest Period
Authors: Karumbaiah Keerthana , Omar Bassam A
Published: July 2021

Background:
Office-based blood pressure (BP) measurement is a snapshot of a patient’s ambulatory BP, and is subject to variations which may influence management.

Objective:
To assess the effect of age and gender on repeat BP measurement after a brief rest period in an outpatient cardiology clinic.

Methods:
Patient charts reviewed in University-based cardiology clinic identified 170 encounters which contained BP re-measurement data due to elevated initial BP of > 130/80 mmHg. BP was measured initially by a nurse, with the patient in a sitting position and the arm resting at the level of the heart. If BP was > 130/80 mmHg, it was repeated by physician after resting the patient for 15 minutes. There were 86 males (51%) and 84 females (49%); 113 (66%) elderly patients ≥ 60 years of age and 57 (34%) younger patients < 60 years of age.

Results:
Among all encounters, after a brief rest period, initial systolic BP (SBP) of 153 ± 27 mmHg decreased to 145 ± 27 mmHg (decrease of 8 mmHg; P = 0.003), and initial diastolic BP (DBP) of 87 ± 16 mmHg decreased to 83 ± 15 mmHg (decrease of 4 mmHg; P = 0.04). SBP decreased by 8 mmHg in both males (from 156 ± 30 to 148 ± 27 mmHg) and females (from 151 ± 23 to 143 ± 14) (NS, males versus females). DBP decreased by 5 mmHg in males (from 91 ± 18 to 86 ± 18 mmHg) and by 2 mmHg in females (from 83 ± 12 to 81 ± 12 mmHg) (P = 0.04, males versus females). SBP decreased by 11 mmHg in elderly (from 154 ± 23 to 143 ± 15 mmHg) and 2 mmHg in the young (from 153 ± 33 to 151 ± 30 mmHg) (P=0.02, old versus young). DBP decreased by 3 mmHg in elderly (from 82 ± 12 to 79 ± 12 mmHg) and 4 mmHg in the young (from 97 ± 18 to 93 ± 17 mmHg) (NS, old versus young).

Discussion:
Hypertension is a challenging public health problem. JNC 7 guidelines recommend that prior to BP measurement, patient should be seated quietly for at least 5 minutes in a chair, with feet on the floor, and arm supported at heart level. This resulted in a significant decrease in BP in our patients. In this study we show that while males and females decrease their systolic BP to the same extent after a brief rest period, males have a greater drop in their diastolic BP than females. Moreover, after the rest period, patients ≥ 60 years of age drop their systolic BP greater than patients < 60 years of age, while there was no significant difference in the drop of their diastolic BP. Given the high reported prevalence of White-coat hypertension in the elderly, between 15% and 25%, this is a clinically significant observation that reinforces that physicians should remeasure the blood pressure, especially the subset of males and the elderly, in whom a bigger decrement may be detected in blood pressure measurement after a brief rest period.
Abstract 11002: Anemia Plays a Role in Pre-Clinical Myocardial Damage and Cardiovascular Mortality in General Population
Authors: Honda Yuki , Watanabe Tetsu , Takahashi Tetsuya , Kinoshita Daisuke , Yokoyama Miyuki , Kadowaki Shinpei , Narumi Taro , Nishiyama Satoshi , Takahashi Hiroki , Arimoto Takanori , Shishido Tetsuro , Miyamoto Takuya , Kubota Isao
Published: July 2021

Background:
Anemia is an independent risk factor for morbidity and mortality in patients with cardiovascular disease. However, the impact of anemia on pre-clinical cardiac damage has not yet fully determined in apparently healthy subjects. The aim of the present study was to investigate whether anemia is associated with pre-clinical cardiac damage and cardiovascular mortality in general population.

Methods and Results:
A cohort study was conducted with subjects who participated in a community-based annual health check in Takahata, Japan, from 2004 through 2006. We examined blood count, serum levels of brain-type natriuretic peptide (BNP) and heart-type fatty acid binding protein (H-FABP) in participants and prospectively followed them (n = 3,509). Anemia was defined as hemoglobin < 13 g/dl for men; < 12 g/dl for women. Four hundred subjects (11.4%) had anemia. In both gender, BNP levels were higher in subjects with anemia than in those without. H-FABP levels were also higher in male subjects with anemia than in those without, while anemia was not associated with H-FABP levels in female subjects. During follow-up period of 7 years, 40 subjects died of cardiovascular diseases. Kaplan-Meier analysis demonstrated that subjects with anemia had higher cardiovascular mortality than those without. Further, subjects those with macrocytic anemia, defined as anemia with mean corpuscular volume (MCV) ≥ 100 fl, had the highest levels of BNP and H-FABP and the highest event rate among subjects with anemia. Multivariate Cox proportional hazard analysis revealed that anemia was an independent predictor of cardiovascular diseases after adjusting age, gender, smoking index, estimated glomerular filtration rate, and BNP (HR: 2.307; 95% CI, 1.032 - 4.808).

Conclusions:
Anemia, especially macrocytic anemia, was associated with pre-clinical myocardial damage and cardiovascular mortality in general population.
Abstract 11242: Impact of Peripheral Artery Disease on Prognosis in Heart Failure Patients
Authors: Nakamura Yuichi , Yoshihisa Akiomi , Kunii Hiroyuki , Takiguchi Mai , Shimizu Takeshi , Yamauchi Hiroyuki , Owada Takashi , Abe Satoshi , Suzuki Satoshi , Sugimoto Koichi , Yamaki Takayoshi , Nakazato Kazuhiko , Suzuki Hitoshi , Saitoh Shu-ichi , Takeishi Yasuchika
Published: July 2021

Background:
A history of peripheral artery disease (PAD) is an independent predictor of cardiac mortality in patients with ischemic heart disease. However, it still remains unclear whether PAD predicts worsening heart failure (HF), cardiac and all-cause mortality in HF patients.

Methods and Results:
Consecutive 388 HF patients admitted to our hospital for the treatment of decompensated HF were divided into 2 groups based on the presence of PAD: HF with PAD (PAD group, n = 103) and HF without PAD (non-PAD group, n = 285). We compared echocardiographic and laboratory findings, and followed the event of worsening HF, cardiac death, non-cardiac death, and all-cause mortality between the two groups. The PAD group, as compared to non-PAD group, had 1) higher age (69.2 vs. 64.5 years old, P=0.001), 2) higher incidence of New York Heart Association functional class III or IV (56.3% vs. 37.2%, P = 0.001), 3) lower levels of hemoglobin (12.3 vs. 12.9 g/dl, P = 0.020), 4) higher levels of B-type natriuretic peptide (591.0 vs. 256.9 pg/ml, P = 0.017), 5) lower estimated glomerular filtration rate (GFR) (46.2 vs. 58.9 ml/min/1.73m
2
, P < 0.001), and 6) lower left ventricular ejection fraction (42.0 vs. 48.7%, P < 0.001). In the follow-up period (mean 765.6 days), Kaplan-Meier analyses (Figure) showed that the event-free survival from worsening HF, cardiac death, non-cardiac death and all-cause death was significantly higher in non-PAD group than in PAD group (P = 0.017, P < 0.001, P = 0.001 and P = 0.005, respectively, by a log-rank test). In the Cox proportional hazard analyses after adjusting for age, gender, ejection fraction, estimated GFR, and the presence of ischemic heart disease, PAD was an independent predictor of cardiac death (hazard ratio (HR) 2.09, P = 0.019) and all-cause mortality (HR 2.16, P = 0.002) in HF patients.

Conclusions:
PAD is an independent predictor of cardiac mortality and all-cause mortality in HF patients.
Abstract 11414: Temporary Right Ventricular Mechanical Support in Addition to a Left Ventricular Assist Device: When is It Required and When is Its Removal Feasible?
Authors: Dandel Michael , Potapov Evgenij , Krabatsch Thomas , Jurmann Beate , Knosalla Christoph , Hetzer Roland
Published: July 2021

Background:
Right ventricular failure (RVF) before, during and after left ventricular assist device (LVAD) insertion is associated with high mortality. Thus, preoperative (preop) distinction between impaired RVs with and without the potential for recovery during RV afterload reduction by an LVAD is paramount. During biventricular support, RV recovery allowing RVAD removal can occur after unloading by a temporary device but preop prediction of recovery, its postoperative (postop) assessment and the timing of RVAD removal are challenging.

We analyzed these issues to improve preop decision making.

Methods:
To assess the predictability of RV recovery during LVAD or LVAD+RVAD support allowing RVF free outcome without RVAD, prospectively gathered data on preop RV size, shape and function, tricuspid regurgitation and pulmonary hemodynamics were tested for relationship with postop RV function. Right heart catheterization and echo variables collected during short stops of the RV pump were used to test the predictability of weaning success from RV support.

Results:
Of 283 evaluated pts (preop RVEF ≤ 30%), 235 received an LVAD (group A) and 48 LVAD+RVAD (group B). We compared in group A the preop data from pts with and without postop RVF and in group B those from pts with and without RV recovery during biventricular support. We found less altered RV size and shape, higher velocity of RV systolic wall motion and myocardial shortening and higher systolic pressure gradients between RV and right atrium in pts with no RVF during LVAD support and also in those with RVAD-promoted RV recovery (p < 0.01). Combined assessment of myocardial velocity of shortening and RV size and geometry in relation to RV load showed the highest predictive values (83-97%) for preop distinction between impaired RVs with and without the potential to remain free from RVF after LVAD insertion or the potential to recover during RVAD support, and also for postop distinction between unloading promoted RV recovery with and without the potential to remain stable after RVAD removal.

Conclusions:
Preoperative assessment of RV ability to improve during LVAD ± temporary RVAD support and prediction of weaning results before RVAD removal can be improved by evaluation of RV size, shape and function in relation to RV load.
Abstract 11526: Intraprocedural Thrombotic Events During PCI for ACS Are Associated With Increased Adverse Ischemic Events at 30 Days: A Meta-Analysis of Randomized Trials
Authors: Nairooz Ramez , Sardar Partha , Chatterjee Saurav , Ahmed Zubair , Feldman Dmitriy N
Published: July 2021

Background:
Data regarding intraprocedural thrombotic events (IPTE) including slow reflow or no reflow, distal embolization, intraprocedural stent thrombosis and abrupt vessel closure during PCI for acute coronary syndrome (ACS) are scarce. Their association with subsequent adverse ischemic events needs further investigation.

Aim:
To evaluate effect of IPTE on in-hospital and at 30-days clinical outcomes after PCI for ACS.

Hypothesis:
IPTE during PCI are associated with adverse ischemic events while in-hospital and at 30 days.

Methods:
We performed a literature search of all published full-length articles of randomized trials that reported data on patients with IPTE compared with no IPTE during PCI for patients with ACS. We calculated odd ratios via random effects model for in-hospital ischemic outcomes and 30 day outcomes.

Results:
Our literature search yielded 3 randomized trials reporting clinical outcomes with IPTE and no IPTE for ACS patients undergoing PCI: ACUITY, HORIZONS-AMI and EARLY-ACS trials. We report clinical outcomes (in-hospital and at 30 days) in 8,043 patients in total, of those 673 had IPTE. At 30 days, patients with IPTE had more major adverse cardiovascular events (MACE) (Odds ratio (OR) 3.97, 95% Confidence interval (CI) [1.81-8.69]; p=0.0006), mortality (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003), myocardial infarction (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003), repeat revascularization (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003), total stent thrombosis (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003) and non-CABG related major bleeding (OR 4.54, 95% CI [1.99, 10.39]; p=0.0003) than those with no IPTE. Similarly, in-hospital clinical outcomes were all significantly higher in patients with IPTE than those without.

Conclusion:
IPTE during PCI is associated with more adverse ischemic events, including mortality, both in-hospital and at 30 days.
Abstract 11600: Long Sleep Duration and Low-Grade Inflammation: New Indicators of Arterial Stiffness in the Japanese at High-risk of Cardiovascular Disease
Authors: Niijima Satoshi , Nagai Michiaki , Hoshide Satoshi , Takahashi Mami , Shimpo Masahisa , Kario Kazuomi
Published: July 2021

Background:
Recently, several studies have reported that long sleep duration was independently associated with increased aortic stiffness. On the other hand, high-sensitive C-reactive protein (hs-CRP) was associated with increased aortic stiffness. In this study, the relationships among self-reported sleep duration, hs-CRP and pulse wave velocity (PWV) were investigated in the Japanese at high-risk of cardiovascular disease. In addition, we investigated whether antihypertensive treatment moderated these relationships or not.

Methods:
Among 4310 patients with one or more cardiovascular risks recruited for the Japan Morning Surge-Home Blood Pressure Study, brachial-ankle PWV and hs-CRP measurement were performed in the 2304 patients (64.7 years old, male 49.6%). A self-administered questionnaire included items on daily sleep duration was used.

Results:
According to the sleep duration (6h or less,6h to 8h,8h or more per night), significant associations of sleep duration were observed with PWV (1594 vs 1644 vs 1763 cm/s, p<0.0001).In the multiple regression analysis adjustment for confounders including age body mass index, total cholesterol, HbA1c and clinic systolic blood pressure (SBP), long sleep duration (8h or more per night) (B: 29, 95%CI: 1.0-56, p<0.05) and log hs-CRP (B: 25, 95%CI: 3.1-48, p<0.05) were significantly positively associated with PWV. A significant interaction was found between long sleep duration and antihypertensive agent non-use for PWV (p<0.05). Especially, in the group without calcium channel blockers (CCBs), long sleep duration was significantly associated with PWV (p<0.01), while a marginal significant synergetic relationship was observed between long sleep duration and log hs-CRP for PWV (p=0.07). On the other hand, there were no significant interactions between long sleep duration and angiotensin receptor blockers non-use.

Conclusions:
Long sleep duration and hs-CRP were significant indicators of increased PVW in the high-risk Japanese population. In those without CCBs, long sleep duration served as a strong determinant for arterial stiffness, marginally interacted by low-grade inflammation. CCBs use might be important not to aggravate artery remodeling caused by long sleep duration.
Abstract 11605: Proteinase-Activated Receptor-2 is Responsible for Amplified Function of Transient Receptor Potential Channel A1 in Skeletal Muscle Sensory Neurons of Rats With Peripheral Artery Disease
Authors: Xing Jihong , Lu Jian , Li Jianhua
Published: July 2021

Background:
Limb ischemia occurs in peripheral artery disease (PAD). Sympathetic nerve activity that regulates blood flow directed to the limbs is augmented during exercise in this disease and transient receptor potential channel A1 (TRPA1) in thin-fiber muscle afferents contributes to the amplified sympathetic responses. The objective of this study was to determine the role played by proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function.

Methods:
A rat model of femoral artery ligation was employed to study PAD. Dorsal root ganglion (DRG) tissues of control limbs and limbs with 24 hours of femoral occlusion were obtained to examine the protein levels of PAR2 using western blot analysis. Also, current responses induced by activation of TRPA1 in skeletal muscle DRG neurons of control limbs and ligated limbs were characterized using whole-cell patch clamp methods. All data are presented as mean ± SE.

Results:
Femoral occlusion significantly increased expression of PAR2 in DRG (optical density: 1.06±0.03 in control
vs.
1.45±0.04 after occlusion,
P<
0.05;
n
= 6 in each group). In addition, femoral occlusion amplified the amplitude of DRG current responses evoked by stimulation of TRPA1 with AITC (a TRPA1 agonist, 100 μM). The peak amplitude of TRPA1 currents was 0.28±0.03 nA in control and 0.41±0.04 nA (
P<
0.05
vs.
control;
n
= 12 in each group) after occlusion, respectively. Activation of PAR2 with SL-NH2 (a PAR2 agonist, 100 μM) increased the TRPA1 currents by 78±10% in DRG neurons of control limb and by 125±10% in DRG neurons of ligated limb (
P<
0.05
vs.
control;
n
= 8 in each group). Moreover, the potentiating effects of PAR2 activation were significantly inhibited by application of phospholipase C (PLC) inhibitors or phosphatidylinositol-4,5-bisphosphate (PIP2).

Conclusions:
A functional interaction in PAR2 and TRPA1 in muscle sensory nerves likely contributes to the amplified sympathetic responsiveness observed in PAD and that the PLC/PIP2 is engaged in sensitization mechanism of TRPA1. These findings provide a pathophysiological basis for autonomic responses during exercise activity in this disease, which may further help to aim at a potential therapeutic approach for improvement of blood flow in PAD patients.
Abstract 11740: Fetal and Neonatal Markers of Neurodevelopmental Outcome in Congenital Heart Disease
Authors: Williams Ismee A , Andrews Howard , Myers Michael M , Fifer William
Published: July 2021

Objectives:
Children with congenital heart disease (CHD) are at risk for abnormal neurodevelopment (ND). We evaluated associations between fetal Doppler and biometry measures, neonatal electroencephalogram (EEG) and 18-month ND.

Methods:
Fetuses with hypoplastic left heart syndrome (HLHS), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF) had middle cerebral (MCA) and umbilical artery (UA) Doppler velocities, as well as biometry such as head (HC) and abdominal circumference (AC), prospectively recorded at 20-25 (F1), 26-32 (F2), and 33-39 (F3) wks gestational age (GA). Pulsatility indices (PI) with GA-derived z-scores and cerebral-to-placental resistance (CPR) ratios were calculated. Neonatal high-density EEG was preformed preoperatively and the Bayley Scales of Infant Development-III were assessed at 18-months. Factor analysis was used to reduce the number of EEG predictors used in regression analysis.

Results:
Among 56 CHD fetuses (N=19 HLHS, N=16 TGA, N=21 TOF) who underwent preoperative EEG, ND scores are available for 33 to date. Cardiac subtype was highly associated with EEG and was considered in all models. Cognition scores were predicted by CPR< 1 ever (B=-15.7, P=0.002) and HC/AC at F2 (B=-130, P=0.013, R
2
=0.42). Language scores were predicted by UA PI z-score at F1 (B=-9.6, P=0.005, R
2
=0.27). Motor scores were predicted by UA PI z-score at F1 (B=-3.9, P=0.085), HLHS (B=-15, P<0.001), EFW%ile (B=0.374, P=0.007), and delta band right parietal and right temporal log power in active sleep (B=3.9, P=0.045, R
2
=0.61).

Conclusion:
Lower umbilical artery pulsatility at 20-25 wks GA was associated with higher 18-month Language and Motor scores. A diagnosis of HLHS predicted poorer Motor scores. Increased EEG power in the parietal and temporal region of the right brain predicted higher Motor scores. A larger abdomen relative to head at 26-32 wks was associated with improved cognition while diminished cerebrovascular compared with placental resistance predicted poorer cognition, similar to what has been observed in the growth restricted fetus. Further investigation is needed to confirm these hypothesis-generating findings.
Abstract 11882: Comprehensive Hemodynamic Analysis of Coronary Arterial Responses to Acetylcholine Provocation Test in Patients With Coronary Vasospastic Angina
Authors: Yamanaga Kenshi , Tsujita Kenichi , Komura Naohiro , Sakamoto Kenji , Ishii Masanobu , Tabata Noriaki , Miyazaki Takashi , Akasaka Tomonori , Arima Yuichiro , Ono Takamichi , Kojima Sunao , Tayama Shinji , Kaikita Koichi , Hokimoto Seiji , Nakamura Sunao , Ogawa Hisao
Published: July 2021

Introduction:
Whereas our prior study showed diffuse coronary intimal thickening in pts with coronary vasospastic angina (VSA), coronary
epicardial
and
microvascular
(MV) hemodynamic and vessel response during coronary vasospasm has not been well studied.

Hypothesis:
We hypothesized that coronary pathogenic abnormalities responsible for coronary vasospasm may not be confined to coronary
epicardial
spastic segments, but the hemodynamic abnormalities may exist in the
entire
coronary bed.

Methods:
According to acetylcholine (ACh) provocation tests, excluding pts with atherosclerotic coronary obstruction (stenosis >50% diameter) and possible heart failure (left ventricular ejection fraction <50%), 41 pts were divided into 2 groups; VSA group (n=20) and non-VSA group (n=21). To evaluate hemodynamic parameters comprehensively, average peak velocity (APV), coronary blood flow (CBF: π (APV/2)(vessel diameter/2)
2
), hyperemic MV resistance (hMR), coronary vascular resistance (CVR: Pd/CBF) and coronary distal pressure (Pd) were measured continuously utilizing a dual-sensor (Doppler velocity and pressure)-equipped guidewire (Combowire, Volcano Therapeutics, Inc.) during ACh provocation test.

Results:
There were no differences between the 2 groups in baseline characteristics. In spite of absence of between-group differences at baseline in CBF (55±26 vs. 51±29, p=0.5) and CVR (2.4±1.5 vs. 2.6±1.4, p=0.7), intracoronary ACh 100μg provocation significantly increased CVR (2.1±2.2 vs. 0.8±0.7; p=0.001), and then attenuated CBF (77±54 vs. 188±129, p=0.001) in VSA group than in non-VSA group. Furthermore, although coronary flow reserve was identical between the groups (2.2±0.9 [VSA] vs. 2.4±0.9 [non-VSA], p=0.5), hMR was significantly augmented in VSA group (2.0±0.7 vs. 1.6±0.6, p=0.046). Also, there was significantly negative correlation between hMR and estimated glomerular filtration rate, which presumably reflect the integrity of renal MV bed (r=-0.522; p=0.0009).

Conclusions:
Compared with non-VSA pts, coronary and systemic MV function was impaired in pts with VSA.
In vivo
assessment using Combowire clarified dynamic
entire
coronary alteration during ACh provocation test, including coronary MV dysfunction, in pts with VSA.
Abstract 12083: Lymphatic Vasculature Mediates Cardiac Progenitor Cell Trafficking After Myocardial Infarction
Authors: Cimini Maria , Troncone Luca , Di Rocco Antonio , Signore Sergio , Cannata Antonio , Anversa Piero , Rota Marcello , leri Annarosa , Goichberg Polina
Published: July 2021

Myocardial infarction (MI) and post-MI heart failure are major causes of morbidity and mortality. Cardiac progenitor cells (CPC) regenerate injured myocardium, due to their ability to migrate and engraft in the wounded area. Yet, the mechanisms governing CPC trafficking in the diseased myocardium are largely unknown. We examined a hitherto unaddressed role of cardiac lymphatic microvessels (LMV) in CPC mobilization to the site of infarction. We detected that in acute and chronic MI, mouse CPC accumulated in the infarct border zone in proximity of LMV and traversed their wall. We showed that human CPC actively intravasated into the lumen of three-dimensional LMV formed by human lymphatic endothelial cells (LEC) in vitro. The binding of CPC to LEC was hindered in the presence of N-cadherin inhibitory peptide or E-selectin neutralizing antibody. CPC displayed unique pattern of interactions with LEC. Specifically, the propensity of CPC to adhere to LEC at basal conditions and after pre-stimulation with an inflammatory mediator TNFα was higher comparing to human cardiac microvascular endothelial cells (CMEC). Trans-migration of CPC through LEC but not CMEC monolayer was enhanced following treatment with TNFα. Interference with the SDF-1/CXCR4 pathway diminished CPC intravasation via LEC but did not affect the CPC ability to traverse CMEC. Intriguingly, we found that the bioactive lipid S1P, secreted by endothelial cells, had a significant impact on CPC migration. S1P binds to 5 different S1P receptors (S1P1-5). We established that the expression of S1P3 was enriched in CPC. Although exposure to S1P mitigated CPC motility, an S1P3-selective agonist evoked strong chemotaxis of CPC, whereas down-regulation of S1P3 blocked CPC translocation. Accordingly, CPC activation with S1P3 agonist reduced their contacts with the extracellular matrix, while S1P ligand induced the organization of adhesion complexes containing β1-integrin subunit. The direct role of S1P3 in CPC trafficking in vivo is supported by our observations that S1P3 expression was increased in the cardiac cells associated with LMV after MI. In conclusion, we provide evidence that specific interactions with LMV may promote CPC trafficking in the infarcted heart facilitating myocardial repair.
Abstract 12140: Prognostic Value of Multiple Biomarkers on Mortality in Adults Congenital Heart Disease: Comparison of Single- and Two-Ventricle Physiology
Authors: Miyamoto Kenji , Takeuchi Daiji , Inai Kei , Shinohara Tokuko , Nakanishi Toshio
Published: July 2021

Introduction:
Although many biomarkers are associated with heart failure, limited data is available on their prognostic predictive value in adults with congenital heart disease (ACHD). We investigate the potential of various biomarkers to predict ACHD mortality.

Methods and Results:
This is a single-center, retrospective cohort study. Blood levels of neurohormones (endothelin-1 [ET1], norepinephrine [NE], aldosterone, and plasma renin activity [PRA]); inflammatory biomarkers (high sensitivity C-reactive protein [hs-CRP], high sensitivity tumor necrosis factor [hs-TNF]-α, soluble TNF receptor type I and II [sTNF-RI and sTNF-RII], and interleukin-6 [IL-6]); and brain natriuretic peptide (BNP) were measured in 115 ACHD (mean age, 30 ± 10 years). NYHA class was I/ II in 86% and III/IV in 14%. The subjects were divided into two groups: patients with single-ventricle (SV group, n = 65) and with two-ventricle physiology (TV group, n = 50). We retrospectively analyzed the relationship between levels of biomarkers and cardiovascular death. During a mean follow-up period of 4.6 years, 17 (14%) cardiovascular deaths occurred, including 7 in the SV group. Univariate cox regression analysis in all subjects showed strong association between elevated levels of ET1, NE, RPA, hs-CRP, sTNF-RI and II, IL-6, and BNP and cardiovascular death (p< 0.05). In the SV group, using multivariate cox regression model, BNP and sTNF-RI were the most powerful predictors in these biomarkers (adjusted hazard ratio [aHR] of BNP: 14.84; 95%CI: 2.21-99.36 per 1 SD increase, p = 0.005) (aHR of sTNF-RI: 2.30; 95%CI: 1.91-4.55 per 1 SD increase, p = 0.017). The optimal cut-off values of BNP and sTNF-RI for mortality were 196 pg/mL and 1.26 ng/mL, respectively. Conversely, in the TV group, only IL-6 was an independent predictor of mortality (aHR: 3.24; 95%CI: 1.57-6.68 per 1 SD increase, p = 0.001), while BNP was not strongly associated with outcomes. The optimal cut-off value of IL-6 for mortality was 2.3 pg/mL.

Conclusion:
Various biomarkers, including sTNF-R, BNP, and IL-6, are associated with prognosis in overall ACHD. The most prominent mortality predictors might differ, due to differences in SV or TV physiology.
Abstract 12450: Myocardial Fibrosis Burden Predicts Left Ventricular Ejection Fraction and is Modified by Age and Steroid Treatment Duration in Duchenne Muscular Dystrophy
Authors: Tandon Animesh , Villa Chet R , Hor Kan N , Jefferies John L , Gao Zhiqian , Towbin Jeffrey A , Wong Brenda L , Mazur Wojciech , Fleck Robert J , Sticka Joshua J , Benson Dudley W , Taylor Michael D
Published: July 2021

Background:
Patients with Duchenne muscular dystrophy (DMD) typically exhibit progressive cardiac and skeletal muscle dysfunction, and are commonly treated with corticosteroids to prolong ambulation. Myocardial fibrosis and steroid treatment may modulate the progression of cardiac dysfunction in DMD patients. We aimed to longitudinally characterize the impact of myocardial fibrosis and steroid treatment on the progression of cardiac dysfunction using cardiac magnetic resonance (CMR) in a large DMD cohort.

Methods:
Serial CMR studies performed on DMD patients were reviewed for LVEF and late gadolinium enhancement (LGE) status, a marker for myocardial fibrosis. LVEF was modeled by examining effects of patient age, steroid treatment duration, LGE status, and myocardial fibrosis burden, as assessed by the number of LGE positive (LGE+) LV segments.

Results:
We analyzed 469 CMR studies from 99 DMD patients with ≥4 CMRs. Patient age at time of CMR ranged from 6.6 to 29.4 (median 12.3) years. There were 146 (31.1%) LGE+ studies and 59 studies (12.6%) that demonstrated depressed LVEF (LVEF<55%). An age-only model demonstrated that LVEF declined 0.58±0.10%/yr (p<0.0001, r
2
=0.067). Univariate modeling showed significant associations between LVEF and steroid treatment duration, presence of LGE, and number of LGE+ LV segments; multivariate modeling showed that LVEF declined by 0.93±0.09% for each LGE+ LV segment (p<0.0001, r
2
=0.171), while age and steroid treatment duration were no longer significant. The number of LGE+ LV segments increased with age by 1.2 segments/year (95% confidence interval 1.1-1.2), and steroid treatment partially mitigated this increase (interaction term β=-0.01±0.005, p=0.010).

Conclusions:
Progressive myocardial fibrosis, as imaged by LGE on CMR, is a strong marker for the decline in LVEF in DMD patients. Steroid treatment partially attenuates the age-related increase in myocardial fibrosis burden.
Abstract 12535: Decreased Six-Minute Walk Distance at Hospital Discharge, Its Cut-off Value of 370 Meters, is an Independent Predictor for Poor Activities of Daily Living After Discharge in Elderly Patients With Chronic Heart Failure
Authors: Nozaki Kohei , Masuda Takashi , Kamiya Kentaro , Hamazaki Nobuaki , Matsuzawa Ryota , Tanaka Shinya , Kawano Mari , Iwamura Takami , Aoyama Akihiro , Shimizu Ryosuke , Maekawa Emi , Ako Junya
Published: July 2021

Background:
Elderly patients with chronic heart failure (CHF) is well known to have poor activities of daily living (ADL) after hospital discharge because of their prolonged hospital stays and subsequent physical deconditioning. Although many studies demonstrated that decreased six-minute walk distance (6MWD) was an independent predictor of rehospitalization and mortality in them, the relationship between decreased 6MWD and poor ADL is not thoroughly evaluated. The purpose of this study was to investigate whether decreased 6MWD measured at hospital discharge reflected poor ADL after discharge in elderly patients with CHF.

Methods:
We recruited 290 patients, 179 males and 111 females, who were 65 years or more and admitted to our hospital because of first heart failure. We excluded the patients who had needed assistance with ADL or walking aid before admission. Plasma brain natriuretic peptide, left ventricular ejection fraction, 6MWD and motor functions including isometric quadriceps strength and one-leg standing time were measured at hospital discharge. ADL was evaluated using the performance measure for ADL-8 (PMADL-8) 3 months after discharge, while PMADL-8 score of 20 or more indicated poor ADL. To determine significant predictors affecting poor ADL and their cut-off values, a multivariate logistic regression analysis and the area under the receiver operating characteristics (ROC) curve were performed.

Results:
Patients’ mean age was 75.4 ± 6.4 years old and their mean PMADL-8 and 6MWD were 18.9 ± 5.9 points and 379 ± 109 meters, respectively. The univariate logistic regression analysis showed that age, 6MWD, quadriceps strength, one-leg standing time were significant predictors for PMADL-8 of ≥20 points (P<0.05, respectively). The multivariate logistic regression analysis detected only 6MWD as a significant and independent predictor for PMADL-8 of ≥20 points (P<0.001). The odds ratio of poor ADL was 1.16 (95% confidence interval: 1.10-1.25, P<0.001) with each 10-meter decrease of 6MWD. The ROC curve showed 370 meters as a cut-off value of 6MWD.

Conclusions:
Decreased 6MWD at hospital discharge was identified as an independent strong predictor for poor ADL after discharge in elderly patients with CHF, and its cut-off value was 370 meters.