bluuebunny/crossref_metadata_2025 huggingface dataset:
P6206Death, debility, and destitution following recurrent myocardial infarction in older adults
Authors: Levitan E , Poudel B , Zhao H , Bittner V , Safford M M , Jackson E , Monda K L , Muntner P
Published: October 2019

Background

Most prior research on outcomes among older adults with established cardiovascular diseases focuses on recurrent events and hospitalizations. However, older adults value financial security and functional independence in addition to these disease-focused metrics. Recurrent cardiovascular events may increase risk of long-term nursing home residence and financial strain.

Purpose

To compare the risk for death, debility (long-term residence in a nursing home), and destitution (eligibility for health insurance programs for impoverished individuals) among older adults with recurrent myocardial infarction (MI) and controls.

Methods

We conducted a retrospective cohort study using administrative data from the United States Medicare program, a health insurance program for older adults. Among all patients who experienced a first overnight hospitalization with a discharge diagnosis of MI between 1 January 2007 and 30 June 2016, we identified patients with a recurrent MI hospitalization. Additionally, we selected controls from the same population of patients with MI, matched on calendar year of the initial MI and days since the initial MI. We included 194,481 patients aged 66 years and older with recurrent MI hospitalizations and 777,924 controls. Patients were followed for death, debility, and destitution until 31 December 2016. We used Kaplan-Meier curves and Cox proportional hazards models adjusted for sociodemographic factors, comorbidities, and healthcare utilization to compare patients with recurrent MI and matched controls.

Results

The average age of the population was 80.0 (standard deviation 8.3) years and 56.7% were women. Patients with recurrent MI were more likely to have a history of diabetes, chronic kidney disease, heart failure and peripheral artery disease than controls. The cumulative incidence of death, debility, and destitution were all higher among patients with recurrent MI than their matched controls (Figure). Comparing patients with recurrent MI to controls, the hazard ratios (95% confidence intervals) were 2.11 (2.09–2.13) for death, 0.92 (0.89–0.94) for debility, and 1.34 (1.29–1.39) for destitution after multivariable adjustment.

Death, debility, and destitution

Conclusion

Preventing recurrent MIs has the potential to reduce not only mortality but also destitution.

Acknowledgement/Funding

Amgen, Inc
P6208VEgetaRian Diet in patients with Ischemic heart disease (VERDI): an open-label, randomized, prospective, cross-over study
Authors: Djekic D , Carlsson F , Landberg R , Sarnqvist C , Cao Y , Tremaroli V , Backhed F , Frobert O
Published: October 2019

Background

A vegetarian diet (VD) in patients diagnosed with ischemic heart disease (IHD) may reduce future cardiovascular risk.

Purpose

The study hypothesis was that patients diagnosed with IHD can benefit from a VD assessed by multiple risk markers for this type of disease.

Methods

In a crossover study patients diagnosed with IHD, treated by percutaneous coronary intervention and on optimal medical therapy were randomly allocated to a 4-week intervention with ready-made (lunch and dinner) isocaloric VD or meat diet (MD). The primary outcome was change in oxidized low-density lipoprotein cholesterol (LDL-C) levels. Secondary outcomes were difference in changes of blood lipids, weight, body mass index (BMI), blood pressure, heart rate, glycated haemoglobin (HbA1c), number of participants reaching guideline target values, quality of life, gut microbiota, and trimethylamine N-oxide between the two interventions.

Results

31 participants were recruited (median age: 67 years, male sex: 93.5%). Significant between-intervention differences (VD vs MD) were found in oxidized LDL-C (−2.73 U/L; p=0.015), total cholesterol (TC) (−0.13 mmol/L, p=0.01), LDL-C (−0.10 mmol/L; p=0.02), weight (−0.67 kg, p=0.008) and BMI (−0.21 kg/m2, p=0.009). After VD, numerically more subjects reached guideline LDL-C target values (87% vs 77%) but this did not reach statistical significance (p=0.07). During VD intervention the diet led to a significant reduction in oxidized LDL-C, TC, LDL-C, HDL-C, ApoB, and ApoB/ApoA1 ratio.

Conclusions

Our results suggest that in patients with IHD a VD compared to a MD, lowers oxidative stress, improves lipid profile and lowers BMI.

Acknowledgement/Funding

This study is partially funded by ALF and the Swedish Heart and Lung Foundation.
P6210Pathway of care and life course of patients with recurrent ST-elevation myocardial infarction
Authors: Fraticelli L , Kleitz O , Claustre C , Eydoux N , Peiretti A , Bonnefoy-Cudraz E , El Khoury C
Published: October 2019

Background

We hypothesized that patients having experienced one coronary event in their life must present differences in their pathway of care in the acute phase and within 12-month life course.

Purpose

This study aimed to compare pathways between current and recurrent Myocardial Infarction.

Methods

All patients from the OSCAR registry with ST Elevation Myocardial Infarction (STEMI) as final diagnosis from 2013 to 2016 were included. We defined recurrent STEMI as a reinfarction occurring within 12-month post-current-STEMI and STEMI with prior MI occurred before the inclusion date.

Results

Recurrent STEMI called more often the medical dispatch center (71.32% vs 62.36%, p<0.0001) and benefited from out-of-hospital medical care by Emergency Mobile Services (67.07% vs 59.70%, p=0.0007). The hospital management delays did not differ but the delay symptom-ECG tended to be 26 minutes longer for recurrent STEMI admitted directly to the emergency department (182 [109; 314] vs 156 [89; 291], p=0.0510). They also underwent less percutaneous coronary interventions (PCI) (90,24% vs 95,07%, p<0.0001). At 12 months post-discharge, we observed a better adherence to BASIC-treatment (Beta-blockers, Anti-platelet medications [aspirin, clopidogrel, prasugrel], Statins and Converting Enzyme Inhibitor Combination-treatment) for recurrent STEMI (64,06% vs 52,98%, p=0.0062) but the key lifestyle interventions were less applied.

Conclusion

Comparison of care and life course of current and recurrent STEMI highlighted a different use of pre-hospital care and hospital resources. They also showed better adherence to BASIC-treatment during recurrent events compared to current STEMI.

Acknowledgement/Funding

The RESCUe Network is funded by the Regional Agency for Health from Auvergne-Rhône-Alpes region (Agence Régionale de Santé Auvergne-Rhône-Alpes).
P6221Salt consumption as a predictor of cardiovascular events among hypertensive patients: a 5-year follow-up study
Authors: Kasiakogias A , Tsioufis C , Konstantinidis D , Leontsinis I , Iliakis P , Koumelli A , Konstantinou K , Liatakis I , Siafi E , Tousoulis D
Published: October 2019

Background/Introduction

Salt intake is linked to hypertension but data on its association with incident cardiovascular events, especially among hypertensives, is limited.

Purpose

To examine the prospective association of different salt consumption levels with cardiovascular morbidity in a hypertensive population.

Methods

We followed 2130 hypertensive patients (age 57±12 years, 11.2% untreated) without a history of cardiovascular disease for a mean period of 5.3±3.3 years. At the baseline examination, salt intake was evaluated by a structured validated questionnaire. Accordingly, the study population was divided into three groups: hypertensives with a low (1079 patients, 51% of the population), a moderate (895 patients, 42%) and a high salt consumption (146 patients, 7%). During follow-up, patients underwent clinic visits at least yearly for management of hypertension and risk factors. The outcome studied was the composite of non-fatal cardiovascular events.

Results

The composite endpoint (19 strokes and 65 cases of coronary artery disease) occurred in 84 patients (3.9%). At baseline, increasing salt consumption was significantly associated with age, body mass index, office blood pressure and renal function. Unadjusted Cox regression analysis showed that, compared to the reference group, the risk for cardiovascular morbidity was similar in patients with moderate salt consumption (HR: 1.1, 95% CI: 0.71–1.77) but significantly higher in patients with high salt consumption (HR: 2.12, 95% CI: 1.09–4.38). This pattern was clearly sustained after adjusting for multiple risk factors including baseline blood pressure levels.

Conclusions

Among hypertensive patients, heavy salt consumption is associated with an increased cardiovascular risk, while moderate consumption does not affect patient outcome.
P6224The combined influence of waist and hip circumference on mortality risk in a large cohort of European and Australian adults: moving beyond BMI, Waist and WHR as measures of obesity
Authors: Soderberg S
Published: October 2019

Background

Previous research has demonstrated that waist circumference (WC) and hip circumference (HC) are both important predictors of mortality, independent of established risk factors. Their combined influence on risk, and whether they are superior to established obesity measures, has not been thoroughly examined in large cohorts.

Purpose

We investigated whether WC and HC are better joint predictors of all-cause and cardiovascular disease (CVD) mortality than individual measures of obesity: WC, HC, waist hip ratio (WHR), waist-to-height ratio (WHtR), a body shape index (ABSI), and body mass index (BMI).

Methods

We used data from 90,487 males and females, 25–74 years of age with no prior history of CVD, from the MOnica Risk, Genetics, Archiving and Monogram (MORGAM) project. Hazard mortality ratios (HR) were estimated using sex-specific Cox models stratified by cohort/country, with age as the time scale. Obesity measures were categorized based on sex specific sample means and standard deviations (SD). All final fully adjusted models included baseline age, total and HDL cholesterol, systolic blood pressure,antihypertensive drugs, current smoker and diabetes.

Results

During a mean follow-up of 11 years, 9105 all-cause and 2577 CVD deaths were recorded. All obesity measures were found to be associated with all-cause and CVD death after taking account of known CVD risk factors, with the strongest statistical evidence of associations seen for WC and HC combined and ABSI. J- or U-shaped associations with mortality were observed for BMI, WC, HC and WHtR for both males and females, and WHR and ABSI for males. Monotonic associations with mortality were observed for WHR and ABSI for females. For WC and HC combined, HC was an important predictor of death among those with smaller WC (≤1 SD above the mean: below 99cm in women and 106cm in men), with larger HCs associated with reduced risk. No additional increase in mortality risk was found to be associated with HC for those with a WC >1SD above the mean. Of those who would not have been identified as being at higher risk based on their WC alone, 55.7% (n=8350) of females and 30.6% (n=4510) of males are identified as being at higher risk when their smaller HC is taken into consideration.

Conclusion

The use of single measurements of obesity such as BMI, WC or WHR does not capture the complex relationship between body shape and risk of premature death. Both WC and HC, but not as a ratio, should be used by clinicians to help identify those at increased risk of premature death.

Acknowledgement/Funding

Individual grants to included cohorts
P6226Association of functional iron deficiency with incident cardiovascular diseases and mortality in the general population
Authors: Schrage B , Ruebsamen N , Thorand B , Koenig W , Soederberg S , Wahlin A , Mathiesen E , Njolstad I , Kee F , Linneberg A , Kuulasmaa K , Salomaa V , Blankenberg S , Zeller T , Karakas M
Published: October 2019

Background

Functional iron deficiency (FID) has been established as a risk factor in patients with cardiovascular diseases (CVD). As opposed to absolute iron deficiency, it reflects stored iron as well as utilized iron and allows for a more accurate evaluation of individual iron status. However, evidence is scant on the relevance of FID to the incidence of CVD in the general population.

Aim

This study aimed to evaluate the association of FID with incident cardiovascular diseases and mortality endpoints in a large population-based cohort.

Methods

FID was defined as either ferritin below 100 μg/L or ferritin between 100 and 299 μg/L and transferrin saturation below 20%. Only individuals free of CVD at baseline from three population-based European cohorts were included. Multivariable-adjusted sex- and cohort-stratified Cox regression analyses were performed to evaluate the association of functional iron deficiency with incident cardiovascular diseases (coronary heart disease, cerebral infarction, heart failure and atrial fibrillation) as well as with all-cause and cardiovascular mortality. Adjustments were performed for sex (as strata), age (as time scale), smoking, total cholesterol, systolic blood pressure, diabetes, body mass index and high-sensitive C-reactive protein.

Results

In total, N=12146 individuals were included in the analysis with a median age of 59.0 years (25thpercentile 45.0, 75thpercentile 68.0), and 45.2% men. Incidence of FID was 64.3%. Median follow-up times were 12.3 to 21.8 years, with an all-cause mortality rate of 18.2% and a cardiovascular mortality rate of 6.2%. Incident coronary heart disease, cerebral infarction, heart failure and atrial fibrillation were observed in 8.7%, 6.5%, 5.9% and 11.7%, respectively.

FID was significantly associated with all-cause mortality (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.01–1.24, p=0.034), cardiovascular death (HR 1.26, 95% CI 1.03–1.54, p=0.027) and incident coronary heart disease (HR 1.23, 95% CI 1.06–1.43, p<0.01). There was no significant association with the other tested endpoints.

Conclusion

In our analysis of population-based cohorts, FID showed a significant positive association with all-cause as well as cardiovascular mortality and incident coronary heart disease. Further research is needed to validate the role of FID as a cardiovascular risk factor in the general population and to evaluate the impact of iron supplementation on gender and outcome.
P6233The association between ideal cardiovascular health behavior and long-term risk profile and outcomes
Authors: Benderly M , Abu-Saad K , Kalter-Leibovici O
Published: October 2019

Background

Health behaviors are important contributors to cardiovascular health (CVH) across populations. Little data exist regarding the association between attaining health behavior goals and long-term health outcomes.

Methods

Ideal CVH behaviors (no tobacco smoking, normal body mass index, engagement in leisure physical activity and healthy dietary habits) based on the American Heart Association definition, were evaluated in a random Israeli population sample (N=1079) stratified by sex, ethnicity (Arabs and Jews) and age (range: 25–74 years). Negative binomial models were used for testing associations with health service utilization counts and the Cox proportional hazard models for the associations with major adverse cardiovascular events (MACE) and mortality. Median follow-up was 15.6 years (interquartile [IQ] rage: 12.9–16.1) for mortality and 9.7 (IQ range: 7.7–10.2) otherwise.

Results

None of the participants had all four ideal health behaviors at baseline, 68 (6%) had three, 308 (28%) had two, 547 (51%) had one, and 156 (14%) had none. Mean [standard deviation; SD] participant age was 49 [12], 51 [14], 52 [15] and 47 [15] for participants with 0, 1, 2 and 3 ideal health behaviors, respectively. With each additional ideal health behavior, the prevalence of male (range: 83% of subjects with no ideal behaviors to 40% of subjects with three), Arab (61% to 21%) and married (92% to 65%) participants decreased, and the prevalence of participants with higher socioeconomic determinants increased. A higher number of ideal health behavior was associated with lower baseline diastolic blood pressure (mean [SD]: 82 [9] mmHg for none, to 76 [9] mmHg for three ideal behaviors), and a more favorable baseline lipid profile. Adjusting for age, sex, ethnicity, marital status, education years, professional prestige and comorbidities (Charlson index), each additional ideal health behavior was associated with reduced risk of developing diabetes (Hazard Ratio [HR]: 0.73, 95% confidence interval [CI]: 0.58–0.91), hypertension (HR: 0.86, 95% CI: 0.71–1.03) and dyslipidemia (HR: 0.85, 95% CI: 0.74–0.98). Controlling for the same variables, the addition of one ideal health behavior was associated with fewer hospitalizations (rate ratio [RR]: 0.80; 95% CI: 0.69–0.93), and cardiology clinic visits (RR: 0.88; 95% CI: 0.75–1.03). The hazard ratio was 0.84 (95% CI: 0.62–1.14) for MACE and 0.82 (95% CI: 0.66–1.03) for all-cause mortality.

Conclusion

Attainment of all four cardiovascular health behaviors goals is rare across the population. A higher number of ideal health behaviors is associated with a lower risk of long-term diabetes, hypertension and dyslipidemia, fewer health service utilizations and a lower MACE and mortality risk.
P6238International cardiovascular disease risk calculators do not identify high risk in young hodgkin lymphoma survivors
Authors: Piddock K , Britton F , Goode V , White E , Greenstein A , Linton K M , Radford J
Published: October 2019

Background

Cardiotoxic therapy causes significant morbidity and mortality in patients (pts) treated for Hodgkin lymphoma (HL). Cardiovascular (CVS) risk calculators do not include cancer therapy despite epidemiological data demonstrating increased risk. We have assessed modifiable CVS risk factors and predicted risk of CVS disease in a cohort of HL survivors.

Hypothesis

Cardiovascular risk calculators will not identify high risk in young HL survivors.

Methods

Pts now aged ≤50 treated with doxorubicin and/or radiotherapy (RT) to cardiac tissue for HL >5 years ago were identified. Telephone review of CVS risk factors was offered to pts taking statins or already diagnosed with cerebrovascular or CVS disease. Remaining pts were offered clinical review to assess BMI, blood pressure, cholesterol and HbA1c. Carotid-radial pulse wave velocity (PWV) was measured if available. CVS risk was predicted using international risk calculators (European SCORE, QRISK3, Framingham).

Results

160 eligible pts were identified. Median age was 43 years (26–50) and 52% were female. Median time since treatment was 182 months (61–367). Pts received doxorubicin (n=150), with RT (n=97) or RT alone (n=10). Pts were excluded from study due to severe medical condition (n=8), recurrence (n=1), relocation (n=3) or death (n=1). Data were gathered at clinical review (n=70) or telephone review (n=26). Existing cardiovascular diagnoses included hypertension (n=5), transient ischaemic attack (n=2), valvular disease (n=3), heart failure (n=1), atrial fibrillation (n=2), complete heart block (n=1) and coronary artery disease (n=1).

At clinical review 51% pts had 3 or more modifiable risk factors with a median of 3 (0–5) per pt. Total cholesterol was >5.0 mmol/L in 58% of patients with a median of 5.2 mmol/L (3.2–8.6). Median systolic blood pressure was 125.5 mmHg (103–164). Median body mass index was 26.3 kg/m-2 (18.6–56.1) with 60% of patients classed as overweight or obese.Advice was offered to all smokers (9%), pts that drank alcohol above UK recommended levels (20%) or exercised below the recommended amount (60%). Risk calculators classified 1.4% (QRISK3) and 10% (Framingham) of pts at high risk of CVS disease and 0% (European SCORE) at high risk of CVS mortality. Pulse wave velocity measured in 34 pts was elevated (>8 m/s) in 76% of cases with a median 10.2 m/s (2.3–16.8).

Conclusions

Numerous modifiable CVS risk factors were identified in an HL survivor population known from epidemiological studies to be at high risk of CVS morbidity/mortality. None of the CVS risk calculators identified this high risk. Intriguing data indicate PWV may represent an accessible early indicator of CVS dysfunction. These data prompt comprehensive assessment and management of CVS risk factors in cancer survivors and review of the use of risk calculators in this population.

Acknowledgement/Funding

The Christie NHS Foundation Trust
P6241Two-year clinical outcomes of biodegradable polymer versus durable polymer drug-eluting stent implantation in hemodialysis patients after percutaneous coronary intervention
Authors: Okuno S , Ishihara T , Iida O , Asai M , Masuda M , Okamoto S , Nanto K , Kanda T , Tsujimura T , Matsuda Y , Hata Y , Uematsu H , Sato Y , Mano T
Published: October 2019

Background

Biodegradable polymer drug-eluting stent (BP-DES) has been developed to improve clinical outcomes after percutaneous coronary intervention (PCI) for patients presenting coronary artery disease (CAD). Although BP-DES showed non-inferior safety and efficacy to durable polymer DES (DP-DES) in several randomized clinical trials, hemodialysis (HD) patients, who have been well known as high risk population for adverse events, were excluded in the most of trials. Therefore, there are limited data comparing the clinical outcomes between BP-DES and DP-DES in HD patients with CAD after PCI.

Purpose

The purpose of this study was to investigate clinical outcomes in HD patients after BP-DES implantation compared with those after DP-DES implantation.

Methods

We retrospectively analyzed 234 HD patients (male 74%, mean age 71±10 years) undergoing PCI for 404 lesions with 472 DESs (71 patients for 138 lesions with 170 BP-DESs [91 Ultimaster and 79 Synergy] and 163 HD patients for 266 lesions with 302 DP-DESs [219 Xience, 53 Promus and 30 Resolute]) from 2011 to 2017. Two-year clinical outcomes were compared between BP-DES group and DP-DES group. The primary outcome measure was the incidence of target lesion revascularization (TLR), while the secondary outcome measures were the occurrence of cardiac death (CD), stent thrombosis (ST), myocardial infraction (MI), target vessel revascularization (TVR), non-TVR and major adverse cardiac event (MACE) defined as a composite of CD, MI, and TVR. Outcome measures were estimated by the Kaplan-Meier method and the differences between BP-DES group and DP-DES group were assessed by the log-rank test. We also conducted Cox's proportional hazard model to identify predictors for TLR occurrence.

Results

Baseline patient and lesion characteristics were similar between the two groups. The two-year incidence of TLR was not significantly different between BP-DES group and DP-DES group (14.1% vs. 22.2%, p=0.391). The two-year incidences of CD (17.3% vs. 17.5%, p=0.381), ST (0% vs. 3.9%, p=0.133), MI (4.2% vs. 5.8%, p=0.965), TVR (21.3% vs. 27.5%, p=0.586), non-TVR (26.1% vs. 31.3%, p=0.439) and MACE (41.1% vs. 42.6%, p=0.526) were also not different between the two groups. After multivariate analysis, diabetes mellitus (hazard ratio 1.97; 95% confidence interval 1.03–3.78, p=0.004) was independently associated with TLR occurrence in HD patients.

Two-year clinical outcomes of HD patient

Conclusions

At two-year follow-up after PCI, BP-DES had comparable safety and efficacy profiles to DP-DES in HD patients presenting CAD.

Acknowledgement/Funding

None
P6242Left ventricular global longitudinal strain to predict pulmonary edema in chronic kidney disease patients on haemodialysis
Authors: Meenakshi K , Rameshwar R
Published: October 2019

The left ventricular (LV) function remains preserved in the majority patients with chronic kidney disease (CKD). Despite this, Pulmonary edema can still occur in CKD patients with preserved ejection fraction during or after haemodialysis.

The aim of our study was to determine whether assessment of Left ventricular global longitudinal strain (LV GLS) in CKD patients, could be used to detect sub clinical LV dysfunction and hence the propensity to develop pulmonary edema during or post hemodialysis.

Our study cohort consisted of 105 CKD patients with normal Ejection fraction by transthoracic Echocardiography (TTE) and undergoing haemodialysis. There were 38 females and 67 males, ages ranging from 23 to 63yrs. They underwent detailed evaluation and assessment of risk factor profile, particularly the presence of hypertension and Diabetes. The Ejection fraction, presence of left ventricular hypertrophy (LVH), Left ventricular diastolic dysfunction (LVDD) and the LV GLS were assessed by TTE. Based on the findings, the male and female patients were divided into 3 groups. Group A with a GLS <−15, Group with a GLS between −15 and −18 and group C with GLS >−18. In group A, 81.1% of the males and 86.7% of the females developed pulmonary edema in contrast to 13% and 21.1% and 14.3% and 0% in groups B and C respectively. When LVDD was compared to the LV GLS it was found that in Group A, 80% of the males, and 88.2% of the females with LVDD developed pulmonary edema in contrast to 7% and 20% in group B and 0% and 0% in Group c respectively who had LVDD and developed pulmonary edema. In spite of having a normal LV diastolic function 100% of the males in group A developed pulmonary edema. Further, 92.8% of the males and 80% of the females in group B did not develop pulmonary edema despite having LVDD. So from our study, a cut of LV GLS value of −15 could predict pulmonary edema in CKD patients undergoing hemodialysis and although the majority were associated with LVDD, it could occur even in the absence of diastolic dysfunction. Further at LV GLS values >−15, the incidence of pulmonary edema was statistically significantly less despite having LVDD.

Conclusion

Left ventricular GLS appears to be a more reliable method than LVDD for predicting the occurrence of pulmonary edema during or post haemodialysis in CKD patients with normal LV Function, A LV GLS <15 would indicate the necessity for the implementation of appropriate precautions to prevent the occurrence of the same during dialysis. It can also be used in the long term follow up of patients.
P6247Comparative analysis for the implication of serum cardiac troponin measurements by conventional versus high-sensitivity assays in patients with traumatic brain injury
Authors: El-Menyar A , Al-Thani H
Published: October 2019

Background

Stress-induced myocardial injury is not well-studied in patients with head injury.

Objective

To assess the prognostic implication of positive (+ve) Troponins (Tn) measurements by conventional (CTn) versus High-Sensitivity (HsTnT) assay in patients with traumatic brain injury (TBI).

Methods

A retrospective analysis was conducted for patients who were admitted with TBI between 2010 and 2014. Patient demographics, clinical presentation, troponin assay results, TBI lesions, and hospital outcomes were analyzed and compared based on troponin assay (CTn versus HsTnT).

Results

Across the study period, 946 patients withTBI were admitted; of them 654 had troponin levels measured within 24 h post-injury (CTn=252 and HsTnT=402). The mean age was 31 years and 46% had positive troponins. There were 147 deaths (22.5%); of them 54% had +ve HsTnT, 23% had +ve CTn, 16% had –ve CTn and 7% had –ve HsTnT). When the troponin was tested ≤4h post-injury, the mortality was 10.2% in patients with –ve CTn and 4% in patients with –ve HsTnT. There was no documented obvious direct cardiac injury. Overall, patients with positive troponins had lower Glasgow Coma Scale (GCS), higher Injury Severity Scores and higher rates of brain edema (p=0.001), pneumonia and sepsis (p=0.001) than those with negative troponin results. In two different models, multivariate regression analysis showed that +ve CTn and +ve HsTnT were independent predictors of mortality (OR 3.94, 95% CI: 1.65–9.42) and (OR 3.39; 95% CI 1.39–8.36); respectively, after adjusting for age, injury severity scores, GCS, TBI type, neurosurgical intervention, sepsis, and chest injury.

Conclusion

Stress-induced myocyte injury is high in TBI. Positive serum troponins, irrespective of the assay type, are associated with poor outcomes post-TBI. Positive HsTnT could be used for early risk stratification and prognosis in brain injury. Further studies are needed to support our findings.
P6258Direct oral anticoagulants in non-valvular atrial fibrillation: accuracy of traditional bleeding scores in the elderly
Authors: Novello S , Graceffa A , Ninivaggi C , Greco G I , Bonfante F , Di Stasio F , Zambotti E , Zorzi A , Tavian T , Sartori M , Occhipinti G , Granziera S , Nante G , Sergi G , Manzato E
Published: October 2019

Background

Due to the fear of increased risk of bleeding, anticoagulation treatment is underutilized in the prevention of stroke in elderly patients with non-valvular atrial fibrillation (NVAF). Although direct oral anticoagulants (DOAC) are safer than VKA, still little is known about the risk factors associated with bleeding in elderly patients treated with DOAC. Furthermore, it is still uncertain whether the risk scores that are currently used can serve to effectively identify higher bleeding risk in elderly subjects.

Purpose

The aim of this study was to identify predictors of bleeding in a cohort of elderly people affected by NVAF treated with DOAC, and to evaluate the accuracy of risk scores for bleeding used at present.

Methods

Data on outpatients aged ≥75 years, naïve for DOAC therapy, who started therapy with Dabigatran, Rivaroxaban, Apixaban or Edoxaban for the prevention of thromboembolism during FANV were analyzed. HASBLED, ATRIA, OBRI and ORBIT scores were calculated for each patient. Patients had follow-up for 12 months during which deaths, therapy discontinuation and adverse events such as thromboembolism and bleeding were reported. Potential predictors of bleeding and the predictive value of each bleeding score were tested using univariate Cox regression; testing accuracy was evaluated using ROC curves.

Results

A total of 291 patients (52.9% female, mean age 82.85±5.18 years) had a median follow-up time of 11 (10–12) months. The incidence rate of major bleeding was 4.7 per 100 patient-years, the rate of intracranial bleeding was 0.4 per 100 patient-years. Patients who had major bleeding were more often affected by heart failure (63.6% vs 25%; p=0.009) and thrombocytopenia (36.4% vs 7.4%; p=0,009). However in the multivariate analysis only heart failure remained statistically associated with major bleeding (HR 3.83, 95% CI 1.06–13.85; p=0.041). None of tested bleeding risk scores was able to predict major bleeding in our cohort. HASBLED and ORBIT scores were able to predict major and non-major clinically relevant bleeding (HR 1.32; 95% CI 1.01–1.71; p=0.042 and HR 1.20; 95% CI 1.00- 1.43; p=0.046); only the ORBIT score was found to be statistically significant, but with weak discriminatory power at ROC curves (AUC 0.59; 95% CI 0.51–0.68; p=0.041).

Conclusions

In our cohort of elderly patients aged 75 or older, anticoagulated for NVAF, heart failure history was the only effective predictor of major bleeding risk during DOAC treatment. None of the bleeding risk scores used currently have demonstrated a good discriminatory power in our cohort. As predictive factors of bleedings in DOAC-treated patients may not be the same as those for VKA-treated patients and those in elderly may also be differ in younger people, it calls for more investigation on the topic.
P6259Unfavourable vascular risk profile of smokers with testosterone deficiency
Authors: Ioakeimidis N , Vlachopoulos C , Georgakopoulos C , Angelis A , Terentes-Printzios D , Sigala E , Rokkas K , Katsi V , Tousoulis D
Published: October 2019

Purpose

Testosterone deficiency and cigarette smoking are both associated with increased cardiovascular (CV) mortality risk. We examined whether vascular function and structure parameters are significantly impaired in smokers with low testosterone levels.

Methods

Carotid intima media thickness (cIMT) and aortic pulse wave velocity (aPWV) were measured in a total of 690 patients (mean 58±7 yrs) without manifest CV/atherosclerotic disease. All patients underwent exercise stress test (and coronary angiography) to reveal coronary artery disease (CAD). Plasma total testosterone (TT) levels were measured in all patients.

Results

Participants were divided into four subgroups according to smoking (yes/no) and measured low or normal TT levels (low TT<3.5 ng/ml). The subgroups had similar prevalence of hypertension and smoking and comparable LDL-C levels. The mean age of patients with low TT was greater than that of subjects with normal TT (P<0.05). Aortic PWV was significantly higher in smokers with low TT compared to smokers with normal TT (P=0.01) and non-smokers with either low TT (P=0.005) or normal TT (P<0.001) (left plot). Similarly, cIMT was significantly higher in smokers with low TT compared to smokers with normal TT (P=0.01) and non-smokers with either low TT (P=0.005) or normal TT (P<0.001) (right plot). All associations remained statistically significant after adjustment for age. Among smokers with low TT both aPWV and cIMT significantly increased with increasing cigarette smoking intensity (all P<0.05), whereas the associations between smoking intensity and either aPWV or cIMT were not significant among smokers with normal TT concentration (all P=NS). Interestingly, the prevalence of angiographically documented CAD was significantly higher among smokers with low TT (18%) compared to the CAD prevalence of the three other subgroups (overall P<0.001).

TT level, smoking and vascular profile

Conclusions

Carotid IMT and aortic PWV are significantly increased and the prevalence of angiographically documented CAD is greater in smokers with testosterone deficiency. Further studies should be conducted to evaluate how much of the unfavorable effect of both cigarette smoking and testosterone deficiency on coronary atherosclerotic burden is mediated by their associations with function and structure changes in the vascular wall.
P6263Results of percutaneous coronary intervention of unprotected left main coronary disease in octogenarian patients
Authors: Romero Reyes M J , Moya Martin A , Gonzalez Alemany N , Sanchez Burguillos F J , Perez Santigosa P , Rufian Andujar S , Molano Casimiro F J
Published: October 2019

Introduction

Conservative treatment unprotected left main coronary (uLMCA) disease has a high mortality rate (50% at 3 years). Since octogenarian patients are often dismissed for surgical treatment, they tend to adopt a more conservative attitude in this population.

Purpose

We report medium and long-term outcomes of percutaneous coronary intervention (PCI) for uLCMA stenosis in elderly patients.

Methods

Retrospective cohort study of consecutive patients ≥80 years with uLMCA stenosis, treated with PCI at a single center between June 2005 and February 2017.

Results

A total of 100 patients were included in the study. 58% were male, with a mean age of 83.8±3 years. There were 86% hypertensive, 63% diabetic and 68% dyslipidemic. 14% of the patients had an LVEF ≤35%. Unstable angina (45%) and acute coronary syndromes withouth ST-segment elevation (44%) were the most common presentation. In 9% of the cases, cardiogenic shock was the initial presentation form. The distal left main coronary was the most frequent localitation of the lesion (46%) followed by the ostium (33%). In 63% of the cases, a multivessel coronary disease was detected and in 47% the revascularization was incomplete.

The survival rate after a year follow up was 79% and after three years follow up was 65%. However, in most of the cases the cause of death was due to other comorbidities, with cardiac death being 10% per year and 13% at 3 years of follow-up. The rate of non-fatal acute myocardial infarction was 13% per year, increasing to 20% at 3 years of follow-up. There was a 9% stent restenosis implanted at 3 years. The presence of severe left ventricular systolic dysfunction was the main predictor of mortality in long-term follow-up (OR 1.39 [95% CI 1.10–1.752], p<0.001). Incomplete revascularization was not associated with a higher mortality rate.

Conclusion

PCI is a safety option for revascularization in uLMCA stenosis in elderly patientes with excellent short-term results, as well as acceptable long-term results. Age should not be a handicap to consider uLMCA revascularization in this population.
P6273Inhibitory phosphorylation of RIP1 at Ser320 induces nuclear translocation of TFEB, leading to suppression of necroptosis in cardiomyocytes
Authors: Abe K , Yano T , Sato T , Kouzu H , Kuno A , Tanno M , Miki T , Miura T
Published: October 2019

Background

Necroptosis, a form of programmed necrosis, has been shown to contribute to the pathogenesis of various diseases including ischemia/reperfusion injury and heart failure. We recently reported that necroptotic signals suppresses autophagy in cardiomyocytes and that rapamycin, an mTORC1 inhibitor, not only promotes autophagy but also protect the cells from necroptosis.

Purpose

We examined the mechanism by which rapamycin suppresses necroptosis of cardiomyocytes, focusing on regulation of RIP1 activity and autophagic flux.

Methods and results

In H9c2 cardiomyoblasts, necroptosis was induced by treatment with TNF and z-VAD-fmk (zVAD) for 24 h, and cell death was determined by LDH release (as % of total). The treatment with TNF/zVAD increased LDH release from 3.4±1.3% to 46.1±2.3%, and LDH release was suppressed by necrostatin-1 (5.9±0.9%), a RIP1 inhibitor, and by rapamycin (23.5±1.4%). The protective effect of rapamycin was mimicked by Ku-0063794, an mTORC1/2 inhibitor. TNF/zVAD induced RIP1-RIP3 complex formation, together with suppression of TNF-induced RIP1 cleavage, which was mitigated by rapamycin. In addition, rapamycin not only suppressed TNF/zVAD-induced phosphorylation of RIP1-Ser166, an index of RIP1 activation, but also increased phosphorylation of RIP1-Ser320, an inhibitory phosphorylation site. In cells transfected with RIP1-S320A, which lack Ser320 for inhibitory phosphorylation, rapamycin failed to suppress TNF/zVAD-induced RIP1-RIP3 binding and cell death. Immunoblot analyses showed that TNF/zVAD significantly increased level of LC3-II. The accumulation of LC3-II protein was not further increased by bafilomycin A1 (100 nM), an inhibitor of lysosomal protein degradation, indicating that accumulation of LC3-II by TNF/zVAD reflected suppression of autophagic flux. Inhibition of RIP1 by necrostatin-1 attenuated TNF/zVAD-induced accumulation of LC3 II. The restoration of autophagic flux in TNF/zVAD-treated cells by necrostatin-1 was confirmed by monitoring tandem RFP-GFP-LC3 transfected cells; necrostatin-1 increased a ratio of RFP-LC3-puncta (autolysosomes) to RFP-GFP-LC3-puncta (autophagosomes) in TNF/zVAD-treated cells. In addition, necrostatin-1 and rapamycin induced nuclear translocation of TFEB, a regulator of lysosome biogenesis, which was associated with upregulation of MCOLN1 mRNA, a downstream target of TFEB. Restoration of autophagic flux in TNF/zVAD-treated cells by necrostatin-1 was inhibited by siRNA-mediated knockdown of TFEB.

Conclusion

Activation of TFEB by inhibitiory phosphorylation of RIP1-Ser320 is a primary mechanism of cytoprotection afforded by mTORC1 inhibition against necroptosis.
P6276Impact of the cardiac specific deletion of AMPKalpha2 on the contractile and metabolic phenotype of the heart in male and female mice
Authors: Grimbert L , Sanz M N , Rucker-Martin C , Novotova M , Gressette M , Gomez S , Solgadi A , Dumont F , Ventura-Clapier R , Veksler V , Piquereau J , Garnier A
Published: October 2019

Introduction

Mitochondrial dysfunction plays a major role in the Heart Failure (HF) pathophysiology.The AMP activated protein kinase (AMPK) is activated by a high AMP-ADP/ATP ratio and regulates a number of metabolic pathways. Many studies have highlighted a protective role of AMPK in HF, but its relevance to cardiac tissue, its metabolic part and its sex specificity are not well established.

Purpose

Then, the aim of this study is to determine the role of AMPK in the healthy and failing heart in male and female mice.

Methods

We developed and validated a mouse strain with an adult-inducible cardiac-specific deletion of AMPKα2, the major cardiac isoform, using the Cre-Lox system (40mg/kg tamoxifen injection on two consecutive days at adult age). At four months after the deletion, cardiac contractility, morphology and metabolism were studied in control and KO mice from both sexes.

Results

We observed only in male KO mice a decrease of left ventricular ejection fraction (−10%), an increase of the total fibrosis (+64%) and defects in mitochondrial structures. Male KO mice also showed a reduced (−28%) mitochondrial respiration via complex I associated with a different cardiolipin species distribution.

Conclusion

Our results reveal in adult healthy hearts, a sex-specificity in the effects of AMPKα2 deletion, leading to impaired contractile function related to metabolic and non-metabolic alterations only in male mice.
P6281Over expression of HINT2 preserves the mitochondria function of cardiomyocytes via regulating the NAD+ homeostasis
Authors: Mengkang F , Qian Q J Y
Published: October 2019

Background

HINT2, a member of the histidine triad proteins family, has been proved to positively regulate mitochondrial function and energy metabolism.However, its effect in cardiomyocytes is largely unknown.

Purpose

To explore the effects of HINT2 on mitochondrial function and ascertain the underlying mechanism in cardiomyocytes

Methods

The neonatal mouse cardiomyocytes was isolated and cultured for subsequent research. Hypoxia as a adverse factor was used to stimulate the cardiomyocytes for 12 hours. The expression of HINT2 in neonatal mouse cardiomyocytes was determined by real-time quantitative polymerase chain reaction and immunoblotting. We used adenovirus vector to over express or knock down HINT2 in cardiomyocytes.Cell viability were assayed using CCK-8 kit. The mitochondria function was evaluated via detection of oxygen consumption rates and mitochondrial membrane potential. The mitochondrial membrane potential was observed using confocal microscopy after TMRM fluorescence probe labeling. The OCR were measured with a Seahorse Extracellular Flux (XF)-96 Bioanalyzer. The NAD+,as a hydrogen carrier for oxidation respiratory chain, was measured by colorimetric kit.The crystal structure data of HINT2 protein and NAD+ were subjected to rigid body molecular docking using AUTODOCK4.

Results

The expression of HINT2 was down-regulated in cardiomyocytes after hypoxic stimulus for 12 hours. Over expression of HINT2 protected the cardiomyocytes from hypoxia induced reduced cell viability. Moreover,the mitochondrial membrane potential was higher and the basal, ATP-linked and maximum OCR were increased in HINT2 overexpressing cells under hypoxic stimulus. Conversely,the mitochondrial membrane potential, the basal, ATP-linked and maximum OCR were decreased in cell with HINT2 under expression in normoxia condition. Furthermore,the NAD+ levels was increased in HINT2 overexpressing cells and decreased in cells with knock-down expression of HINT2. Besides,The beneficial effects of HINT2 overexpression can be blocked by nicotinamide phosphoribosyltransferase inhibitor. Moclecular docking results showed that HINT2, as a nucleotide binding protein could docking with NAD+, and the conformation with the strongest binding force has 2 hydrogen bonds which was at ARG99:HH21 and GLN102:HE22 in HINT2.

Conclusions

Our results suggest that overexpression of HINT2 preserve the mitochondrial function in cardiomyocytes via maintaining NAD+ homeostasis.

Acknowledgement/Funding

Natural Science Foundation of China
P6283Downregulation of Tim44 exacerbates oxidative stress-induced ROS production and cardiomyocytes death by reducing mitochondrial SOD2
Authors: Ikeda S , Matsushima S , Okabe K , Ishikita A , Tadokoro T , Enzan N , Yamamoto T , Sada M , Deguchi H , Ikeda M , Ide T , Tsutsui H
Published: October 2019

Background

Mitochondrial dysfunction has been highlighted as a critical driver of cardiac remodeling and failure. Mitochondria contains about 1500 proteins, 99% of which are encoded in the nuclear genome. Therefore, protein import into mitochondria is essential to maintain mitochondrial function. Previous reports suggest that nuclear-encoded mitochondrial precursor proteins import into mitochondria by multiple complex; translocase of outer membrane (TOM), translocase of inner membrane (TIM), and protein associated motor (PAM). However, the role of these protein import machineries of mitochondria in cardiac remodeling remains to be elucidated.

Objective

The purpose of this study was to elucidate the role of TOM, TIM, and PAM complex in cardiac remodeling and cardiomyocyte death.

Methods and results

C57BL/6J mice were subjected to myocardial infarction (MI) by permanent ligation of left anterior descending artery. Four weeks after operation, MI-mice demonstrated left ventricular (LV) dilation (LV end-diastolic dimension: 3.91 vs. 5.54 mm, n=8–11, p<0.05) and dysfunction (LV fractional shortening: 33.3 vs. 7.7%, n=8–11, p<0.05). Tim44 protein levels, a component of PAM complex, in mitochondrial fraction from non-infarcted left ventricle were significantly decreased compared with those in the heart from sham-operated mice by 39% (p<0.05), whereas other proteins related to TOM, TIM and PAM complex such as Tom20, Tom22, Tom40, Tom70, Tim22, Tim23 and mtHSP70 were not altered between MI-mice and sham-mice. In addition, blue-native polyacrylamide gel electrophoresis revealed that a protein complex associated to Tim44 was significantly decreased in non-infarcted LV by 40% (p<0.05). Superoxide dismutase 2 (SOD2), a mitochondrial matrix protein, was decreased in mitochondrial fraction from non-infarcted LV by 20% (p<0.05), accompanied by enhancing protein carbonylation, a marker of oxidative stress, by 40% (p<0.05). To assess the role of Tim44, it was downregulated by small interfering RNA in cultured neonatal rat ventricular myocytes (NRVMs). Knockdown of Tim44 significantly decreased SOD2 protein levels in mitochondrial fractionation (22%, p<0.05), with no significant changes in its mRNA levels. Furthermore, knockdown of Tim44 significantly increased protein carbonylation (20%, p<0.05) and cleaved caspase 3 (47%, p<0.05) and decreased cell viability (69%, p<0.05), assessed by cell titer assay, in H2O2-treatred NRVMs.

Conclusions

Downregulation of Tim44 exacerbates oxidative stress-induced ROS production and cardiomyocytes death, which is associated with a decrease in mitochondrial SOD2. Endogenous Tim44 might play a protective role in cardiac remodeling by attenuating oxidative stress and cardiomyocyte death via SOD2 import into mitochondria.