bluuebunny/crossref_metadata_2025_split huggingface dataset:
P620The prognostic value of the ratio of transmitral early filling velocity to early diastolic strain rate in type 1 diabetes patients
Authors: Lassen M H , Biering-Soerensen T B S , Joergensen P G J , Andersen H U A , Rossing P R , Jensen M T J 
Published: October 2019

Abstract

Background
Cardiovascular disease is one of the main causes of morbidity and mortality in patients suffering from type 1 diabetes mellitus. It is of great importance to identify early signs of cardiac pathology such as elevated left ventricular (LV) filling pressure. The ratio of transmitral early filling velocity to early diastolic strain rate (E/e'sr) has in recent studies proved to be an accurate measure of left ventricular (LV) filling pressure. Furthermore, E/e'sr has demonstrated strong prognostic value across different study populations.

Purpose
The aim of this study was to assess the prognostic value of E/e'sr in a large cohort of patients with type 1 diabetes mellitus in relation to cardiovascular morbidity and mortality.

Methods
In this prospective study, 1082 patients with type 1 diabetes mellitus (mean age 50±15 years, 53% male, mean duration of diabetes 26 years) underwent a comprehensive echocardiographic examination including both conventional measurements and two-dimensional speckle tracking in which E/e'sr along with other echocardiographic measurements were obtained. The primary outcome was defined as a major cardiac event (heart failure, stroke, myocardial infarction or cardiovascular death).

Results
During follow-up (median: 6.2 years, IQR: 5.7, 6.9) 144 (13.3%) met the composite outcome. E/e'sr was significantly associated with the composite outcome (E/e'sr: HR 1.36 95% CI [1.25–1.47], p<0.001, per 0.10m increase) (figure). E/e'sr remained an independent predictor after multivariable adjustment for age, gender, duration of diabetes, BMI, HbA1c, smoking status, level of physical activity, systolic blood pressure, cholesterol level, eGFR, albuminuria, LV ejection fraction, LV dimensions and left atrial volume index (E/e'sr: HR 1.16 95% CI [1.04–1.28], p=0.006, per 0.10m increase). Interestingly, E/e'sr was especially good as a prognosticator in female patients (p for interaction = 0.008) in a univariable model: (female: HR 1.53 95% CI [1.37–1.71], p<0.001, per 0.10m increase) (male: HR 1.23 95% CI [1.10–1.38], p<0.001, per 0.10m increase). In the same multivariable model as before, E/e'sr remained an independent predictor of the outcome in female patients whereas the same was not true for male patients (female: HR 1.39 95% CI [1.18–1.66], p<0.001, per 0.10m increase) vs (male: HR 1.05 95% CI [0.92–1.21], p=0.46, per 0.10m increase).

Conclusion
In patients with type 1 diabetes, E/e'sr provides independent prognostic information regarding cardiovascular morbidity and mortality. Furthermore, E/e'sr seems to have stronger prognostic value in female patients with type 1 diabetes.
P627Patterns of physical activity over 22 years and mortality: the HUNT Study, Norway
Authors: Moholdt T , Moe B , Nilsen T I L 
Published: October 2019

Abstract

Background
The majority of studies relating physical activity (PA) to mortality have assessed PA using one baseline measure. Important questions in a preventive perspective are whether you can compensate for prior physical inactivity by taking up PA at a later stage in life and whether being physically active earlier in life can confer benefits even if you become inactive later. We investigated how patterns of PA over 22 years associated with all-cause and cardiovascular disease (CVD) mortality.

Methods
We used data from the prospective population-based HUNT Study in Norway, including 10,491 men and 12,655 women aged ≥20 years who participated at HUNT in 1984–86 and 2006–08. PA was categorised into inactive, <2 h/week or ≥2 h/week, making nine categories of patterns of PA over 22 years. All-cause and CVD mortality were assessed from the national Cause of Death Registry, with follow-up until the end of 2013. We used Cox regression to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and CVD mortality within categories of PA patterns, compared to the reference category of individuals who reported ≥2 h/week at both examinations. Estimates were adjusted for baseline age, sex, body mass index, smoking, education level and blood pressure.

Results
Individuals who were inactive in both 1984–86 and in 2006–08 had increased risk of all-cause mortality (HR 1.99, 95% CI 1.48–2.67) and CVD mortality (HR 2.68, 95% 1.47–4.86) compared to those who were physically active ≥2 h/week at both examination. The HRs for all-cause and CVD mortality were 1.60 (1.22–2.15) and 1.90 (1.06–3.42), respectively, for those who reported PA of <2h/week at both examinations. Individuals who went from being physically active in 1984–86 to inactive in 2006–08, had a comparable risk of all-cause and CVD mortality as those who were inactive at both examinations. Overall, the mortality risk was still increased in those who took up PA between the two examinations, compared to the reference category.
Physical activity & all-cause mortality.

Discussion
Individuals who remained physically inactive or who decreased their PA over 22 years had substantially increased all-cause and CVD mortality risk. Taking up PA only attenuated the risk but a high level of sustained PA was associated with the lowest risk.

Acknowledgement/Funding
Funded by the Norwegian Health Association
P634Motivation for physical activity predicts effect of cardiac rehabilitation in an elderly cardiac population
Authors: Mikkelsen N , Dall C , Holdgaard A , Frederiksen M , Rasmusen H , Prescott E 
Published: October 2019

Abstract

Background
Motivation for physical activity is a psychological parameter that is sparsely described in secondary prevention, and it is plausible that motivation contributes to differential effect of CR.

Purpose
To investigate if motivation, measured using the behavioural regulation in exercise questionnaire (BREQ-2), predicts VO2peak in elderly cardiac patients before and after CR.

Methods
Prospective cohort study (Danish cohort from the EU-CaRE study) of elderly patients with ischemic or valvular disease enrolled in CR. Motivation for physical activity was measured using the BREQ-2 questionnaire at baseline, which measures five constructs of motivation and a summed score. VO2peak was measured before and after CR by a cardiopulmonary exercise test (CPET). The impact of motivation on VO2peak was examined using standardized multiple regression analyses.

Results
203 patients performed the baseline tests. 182 (90%) completed CR and had full data available. Dropout was not associated with motivation. VO2peak at baseline was 18 ml/kg/min (SD±5.1) and was associated with motivation score: for each SD increase in motivation VO2peak was 1.05 (0.43–1.69) ml/kg/min higher (p<0.01). Mean improvement was 2.3 (12%) ml/kg/min (SD±4.3). Higher motivation was positively associated with VO2peak (0.78 (0.33–1.24) pr. SD improvement (p=0.01) after adjusting for age, sex, depression, comorbidities and baseline VO2peak (Table). Subscales of the BREQ2 indicate that internal but not external motivation drives this positive association.
Predictors of change in VO2peak Age and sex adjusted Multiple adjusted model Motivation (RAI pr. SD) 0.57 (0.12 to 1.01)* 0.78 (0.33 to 1.24)** Baseline VO2peak (pr. SD) −0.56 (−1.16 to 0.21) −1.30 (−1.94 to −0.66)*** Age (pr. SD) −0.84 (−1.85 to 0.18) −1.00 (−2.01 to −0.01)* Sex (male) −0.18 (−1.21 to 0.85) 0.74 (−0.28 to 1.76) Previous smoker −0.23 (−1.22 to 0.77) −0.37 (−1.34 to 0.59) Current smoker −1.43 (−3.00 to 0.14) −1.89 (−3.36 to −0.40)* Diabetes (Yes) −1.37 (−2.50 to −0.24)* −1.62 (−2.78 to −0.48)** Kidney disease (Yes) −0.98 (−2.37 to 0.42) −1.45 (−2.84 to −0.06)* PHQ-9 (pr. SD) 0.22 (−0.24 to 0.69) 0.21 (−0.24 to 0.66)

Conclusion
In elderly cardiac patients, level of motivation is important to achieve benefits of CR. Future studies should address if motivation measured with BREQ-2 can be applied as a screening tool for elderly patients to provide more personalized intervention.
P664Impact of dynamic change in the status of metabolic syndrome associated with the risk of atrial fibrillation: a nationwide population-based study
Authors: Lee S , Choi E K , Lee S R , Han K , Cha M J , Oh S 
Published: October 2019

Abstract

Background/Introduction
Metabolic syndrome (MetS) is a well-known risk factor for new-onset atrial fibrillation (AF). However, there is a paucity of information on whether the change of MetS status has an impact on the risk of new-onset AF.

Objective
We aimed to evaluate the risk of AF according to the change of MetS status and to find whether components of metabolic syndrome control may affect AF risk.

Methods
A total of 7,565,531 subjects (≥20-year-old, mean age 47.2±13.7 years, male 55.6%) without prevalent AF who underwent 2 times of serial health checkup were identified from the Korean National Health Insurance Service. MetS was defined as having ≥3 of the following risk factors: increased waist circumference (ethnicity-specific, in Asian, ≥80 cm in women or ≥90 cm in men), increased triglycerides (≥150 mg/dL), decreased high-density lipoprotein-cholesterol level (<40 mg/dL in males, <50 mg/dL in females), increased blood pressure (≥130/85 mmHg), and increased fasting glucose level (≥100 mg/dL). Subjects stratified into four groups according to the change of MetS status during the follow-up period: 1,388,850 patients persistent MetS in the serial checkup (MM group), 608,158 in previous healthy but newly diagnosed MetS at 2nd checkup (HM group), 798,555 in the previous MetS but became healthy in 2nd checkup (MH group), and 4,769,968 patients without MetS in both (HH group). Incident AF was followed up till December 2017.

Results
Among those with MetS, 798,555 patients had improved to be healthy (10.6%). In those previous without MetS, 608,158 patients had newly diagnosed as MetS (8.0%) in 2nd checkup. During a mean follow-up of 7.9±0.9 years, incident AF was diagnosed in 135,600 patients (2.3 per 1000 person-year). MM, MH, and HM groups showed an increased risk of AF compared to HH group (Figure). Also, MH group showed a lower risk of AF compared to those with MM group. Regardless of the type of component that meets the MetS criteria, the risk of AF became different according to changing the number of MetS components. The risk of AF increased as the number of MetS components increased, whereas the risk of AF decreased as the number of MetS components decreased.
Risk of AF according to change of MetS

Conclusion
The risk of AF showed association with the dynamic change of MetS status and the variation in the number of MetS components. AF risk was reduced by the improvement in metabolic syndrome and each of MetS components.
P666Anti-platelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: randomised controlled proof of concept trial (APPLE COPD-ICON 2)
Authors: Kunadian V , Wilson N , Stocken D , Ali H , McColl E , Burns G , Howe N , Fisher A , De Soyza A 
Published: October 2019

Abstract

The APPLE COPD-ICON2 trial is a prospective 2x2 factorial, double blinded proof of concept randomised controlled trial targeting patients with chronic obstructive pulmonary disease (COPD) at high risk of cardiovascular disease. The primary goal was to investigate if antiplatelet therapy (APT) will produce the predefined cut-off of platelet inhibition measured using the Multiplate test. We also assessed inflammatory biomarkers in serum.
Patients were randomised to Aspirin plus placebo, ticagrelor plus placebo, Aspirin plus ticagrelor or placebo only for 6 months. The primary outcome is inhibition of arachidonic acid (ASPI-test, cut-off <40) and adenosine diphosphate (ADP-test, cut-off <46) induced platelet aggregation at 6 months based on intention to treat (ITT) and sensitivity per protocol (PP) analyses. Safety outcomes included rates of major/minor bleeding.
Of 543 patients screened, 120 were recruited (mean age of 67.5 years). The ITT response rate to Aspirin was 48.3% (95% confidence interval [CI] 35.8–61.0%) according to ASPI-test and the response rate to ticagrelor was 41.4% (95% CI 29.3–54.6%) according to ADP-test. The PP ASPI-test response rate to Aspirin was 68.3% (95% CI 52.3–80.9%) and the PP ADP-test response rate to ticagrelor was 68.8% (95% CI 50.4–82.6%). There were no differences between the groups in the changes in Quality of Life using questionnaires (EQ5D 5L, St. George's COPD-C), inflammatory markers, carotid intima media thickness and vascular stiffness from baseline to 6-months. There were 5 type 1 bleeds according to the BARC criteria recorded in this study; 2 in the placebo arm, 2 in the Aspirin arm, and 1 in the ticagrelor arm. The MRC Dyspnoea score, FEV1 and FVC was similar across the groups.
Primary outcome measures Aspirin No Aspirin Ticagrelor No Ticagrelor ITT analysis set* n 60 60 58 62   Baseline No. of responders 1 6 4 1 % (95% CI) 1.7 (0.2, 11.3) 10 (4.5, 20.8) 6.9 (2.6, 17.3) 1.6 (0.2, 10.9)   6 months No. of responders 29 7 24 2 % (95% CI) 48.3 (35.8, 61) 11.7 (5.6, 22.8) 41.4 (29.3, 54.6) 3.2 (0.8, 12.3) PP analysis set** n 41 45 32 54   6 months No. of responders 28 7 22 2 % (95% CI) 68.3 (52.3, 80.9) 15.6 (7.5, 29.6) 68.8 (50.4, 82.6) 3.7 (0.9, 14.0) *Descriptive statistics for the primary outcome of response for the comparative groups at baseline and 6 months for the ITT analysis set and **PP analysis set. Note that response is ASPI response in the Aspirin and No Aspirin columns and ADP response in the ticagrelor and No ticagrelor columns.
Primary outcome measure
Nearly one third of COPD patients did not have a platelet response to antiplatelet therapy with Aspirin and ticagrelor. These findings support the high pro-thrombotic milieu and the need for further research in COPD patients.

Acknowledgement/Funding
Astra Zeneca (Funder reference number ISSBRIL0303)
P692Chemoradiation therapy to patients with lung cancer exacerbates thoracic aortic calcification
Authors: Miki T , Miyoshi T , Ichikawa K , Miyauchi S , Soh J , Toyooka S , Nakamura K , Morita H , Ito H 
Published: October 2019

Abstract

Introduction
Development of chemoradiation therapy (CRT) has improved mortality in patients with cancer. Whereas, it is emerging problem that cancer-survivors suffer from cardiovascular diseases, and the association between modern CRT and the increase in future cardiovascular events is suggested. Meanwhile, previous studies showed that thoracic aortic calcification (TAC) detected by computed tomography (CT), a marker of atherosclerosis, was associated with all-cause mortality and cardiovascular events. However, the influence of CRT on TAC progression remains unclear.

Purpose
The purpose of this study was to evaluate whether CRT would exacerbate TAC.

Methods
A total of 68 patients who treated lung cancer at our hospital between 2011 and 2015 were retrospectively analyzed (mean 62 year-old, male 78%): 35 patients underwent surgical treatment after induction CRT (CRT group) and 33 patients underwent surgical treatment alone (control group), extracted by propensity score matching by age, sex, smoking status, and diseased side. The volume of TAC between 2nd and 12th thoracic vertebrae was quantitatively measured with CT imaging, at baseline and at 1 year follow-up. The annual percent change in TAC was compared between the CRT and the control group. Moreover, the independent relationship between implementation of CRT and the progression of TAC was assessed by multivariate logistic regression analysis, adjusting for age, gender, conventional atherosclerotic risk factors and baseline aortic calcification volume.

Results
Patients in the CRT group received radiation (mean 47.3±4.0 Gy) and chemotherapy: 2 courses of cisplatin with docetaxel (34 cases) or vinorelbine (1 case). The prevalence of dyslipidemia, taking statins and diabetes drugs were significantly higher in the control groups (17% vs. 39%; p=0.041, 11% vs. 33%; p=0.029, 3% vs. 18%; p=0.044, respectively). Baseline C-reactive protein level was significantly higher in the CRT group (0.255 vs. 0.115; p=0.034). In univariate analysis, the annual percent change in TAC volume was significantly increased in the CRT group compared with the control group (37.6% vs. 23.3%; p=0.006). Multivariate logistic regression analysis demonstrated that CRT was an independent factor associated with the progression of TAC volume, even after adjustment for baseline calcification volume and coronary risk factors (OR, 3.90; 95% CI, 1.32–11.47; p=0.014).

Conclusion
CRT to patients with lung cancer exacerbates thoracic aortic calcification, which may result in future cardiovascular events.
P712Non-neuronal cholinergic system prevents coronary vascular dysfunction in diabetic heart
Authors: Saw E , Tsuchimochi H , Pearson J T , Yoshihiko K , Schwenke D O , Fronius M , Katare R 
Published: October 2019

Abstract

Background
Diabetic individuals suffer extensive myocardial damage during ischemia due to impaired ATP production and coronary vascular dysfunction. The cardiomyocytes possess a non-neuronal cholinergic system (NNCS) as it has choline acetyltransferase (ChAT) to synthesize acetylcholine (ACh). ACh released from cardiomyocytes activates hypoxia-inducible factor-1 pathway in an auto/paracrine manner under non-hypoxic condition. Activation of this pathway via NNCS promotes angiogenesis and is a promising mechanism to target ischemia in diabetes.

Aim
To investigate if activation of NNCS could improve the coronary vasculature in diabetic heart.

Methods
Type-2 diabetic db/db mice with ventricle-specific ChAT transgene (db/db-ChAT-tg) and control db/db mice of 12- and 24-weeks old were used. Catheterization of the jugular vein and carotid artery was performed in combination with synchrotron radiation microangiography to visualize the in-vivo coronary circulation. Changes of the coronary circulation to ACh (10μg/kg/min) and sodium nitroprusside (SNP, 10μg/kg/min) were assessed. Immunofluorescence analysis was performed to measure the density of arterioles and capillaries ex-vivo.

Results
In comparison to db/db mice, the number of second and third order vessels was higher in the db/db-ChAT-tg mice of 12- and 24-weeks old under baseline condition. In response to ACh and SNP, number of third order vessels were further increased in the db/db-ChAT-tg mice of both ages. However, the magnitude of the diameter changes in db/db-ChAT-tg mice was comparable to that in db/db mice of both ages. Besides, the db/db-ChAT-tg mice had increased density of arterioles and capillaries compared to the db/db mice of both ages.

Conclusion
NNCS-induced angiogenesis prevents coronary vascular dysfunction in diabetic heart.
P7142-AG impacts on endothelial cell activation and endothelial cell viability in vitro and impairs endothelial repair in vivo
Authors: Jehle J , Danisch M , Bagheri S , Avraamidou E , Tiyerili V , Pfeifer P , Bindila L , Lutz B , Zimmer A , Nickenig G 
Published: October 2019

Abstract

Background
The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation and few studies have addressed its influence on myeloid cells in the context of atherogenesis. However, the impact of 2-AG on endothelial cell function has not been studied before.

Methods
Endothelial repair was studied in two treatment groups of wildtype mice following electrical denudation of the common carotid artery at a length of 3000 μm. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184 [5 mg/kg i.p.], which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received vehicle. The residual endothelial gap at five days in either group was visualized by Evan's blue staining. In vitro, the effect of 2-AG on human coronary artery endothelial cell (HCAEC) viability was assessed by an XTT-based assay. Endothelial activation was studied by an adhesion assay of THP-1 monocytes to 2-AG-preconditioned HCAEC. HCAEC migration, ROS-production, expression of NADPH oxidases, and secretion of inflammatory cytokines were assessed by Boyden chamber, qPCR, and colorimetric assays.

Results
Treatment with JZL184 produced a significant increase in 2-AG levels and impaired reendothelialisation in wildtype mice following electrical injury of the common carotid artery. The residual denudation at 5 days yielded 2291±286 μm in JZL184-treated animals vs. 1505±223 μm in vehicle treated controls (n=18–19; p<0.05). In vitro, JZL184 significantly reduced viability of HCAEC at 24 hours (0.31±0.10 vs. 1.00±0.08; n=3; p<0.01). Finally, 2-AG promoted HCAEC activation resulting in a significant increase in THP-1 monocyte adhesion to HCAEC following pre-treatment of HCAEC with 2-AG (0.17±0.03 THP-1 cells per HCAEC vs. 0.07±0.01 THP-1 cells per HCAEC; n=3; p<0.05). Besides, HCAEC migration, ROS-production, expression of NADPH oxidases and secretion of inflammatory cytokines were unaffected by 2-AG.

Conclusion
Elevated 2-AG levels appear to hamper endothelial repair and to promote HCAEC activation and cell death. Our data suggest that besides its influence on myeloid cells, 2-AG is also adverse to endothelial integrity which might promote early atherosclerotic lesion formation. Thus, decreasing vascular 2-AG levels might represent a promising therapeutic strategy for the prevention of atherosclerosis and coronary heart disease.