bluuebunny/crossref_metadata_2025_split huggingface dataset:
P1527The applicability of the dual pathway approach criteria after coronary angiography
Authors: Olesen K K W , Wurtz M , Gyldenkerne C , Thrane P G , Thim T , Kristensen S D , Botker H E , Eikelboom J W , Maeng M 
Published: October 2019

Abstract

Background
The combination of aspirin and low-dose rivaroxaban (dual pathway approach, DPA) has been approved for high-risk patients with stable coronary artery disease (CAD) in the COMPASS trial. Patients with CAD combined with ≥1 DPA criteria, defined as peripheral artery disease, renal failure, heart failure, or diabetes, have been proposed as high-risk patients eligible for DPA.

Purpose
To determine the prevalence of patients meeting the DPA criteria and the association with major adverse cardiovascular events (MACE) in patients with stable CAD after coronary angiography (CAG). Further, to evaluate use of the DPA criteria in CAD patients meeting the inclusion criteria in the COMPASS trial.

Methods
We studied patients included in the Western Denmark Heart Registry after examination by CAD 2004–11. Patients without CAD or myocardial infarction (MI) <1 year before or 30 days after CAG were excluded. Patients were stratified according to 0 or ≥1 DPA criteria and being eligible/ineligible for the COMPASS trial. Event rates and incidence rate ratios (IRRs) of MACE (cardiac death, ischemic stroke, and MI) were estimated.

Results
Of 80,071 patients undergoing CAG, 18,689 (23%) patients had stable CAD. According to the DPA criteria, 7,730 patients (10%) were DPA eligible. Rates of MACE were 1.98 (95% CI 1.86–2.34) events per 100 person-years among DPA ineligible patients and 4.26 (95% CI 4.04–4.50) events per 100 person-years among DPA eligible patients (IRR 2.15, 95% CI 1.98–2.34). When stratifying patients according to eligibility in the COMPASS inclusion criteria, COMPASS eligible patients with 0 DPA criteria and COMPASS ineligible patients with ≥1 DPA criteria were at intermediate risk compared to patients meeting both (high risk) or none (low risk) of these criteria (Figure 1).
Figure 1

Conclusion
In a cohort of consecutive patients undergoing CAG, 1 in 10 patients would be eligible for DPA according to the DPA criteria. Patients with stable CAD and ≥1 DPA criteria had >2-fold higher rate of MACE than CAD patients without any DPA criteria.
P1531The association between plasma choline and acute myocardial infarction is modified by potential markers of endogenous PPAR activation
Authors: Svingen G F T , Lysne V , Ueland P M , Zeisel S , Pedersen E R , Dhar I , Bjornestad E O , Schartum-Hansen H , Tell G S , Nilsen D W , Karaji I , Nygaard O K 
Published: October 2019

Abstract

Background
Choline is related to lipid handling and higher plasma concentrations have been associated with an adverse cardiovascular risk profile. However, previous studies have suggested that the relationship between plasma free choline and later cardiovascular events may differ according to patient phenotypes.

Purpose
To explore the risk association between plasma choline and later acute myocardial infarction (AMI) according to plasma methylmalonic acid (MMA) or dimethylglycine (DMG). The latter two metabolites are suggested markers of endogenous activation of perixosome proliferator-activated receptors (PPARs), which are nuclear receptor proteins involved in lipid metabolism.

Methods
Risk relationships were explored by Cox regression among 2232 patients evaluated for suspected stable angina pectoris in the overall population and according to median plasma MMA and DMG.

Results
Baseline plasma choline was related to several cardiovascular risk factors (Table 1). After median follow-up of 7.3 years, 338 patients were reported with at least one incident AMI. In the overall population, the age and gender adjusted HR (95% CI) for each increment of 1 SD log-transformed plasma choline and AMI was 1.21 (1.08–1.35), P=0.001, and the association persisted in multivariate analyses.
In patients with plasma MMA or DMG≥median, the HRs (95% CIs) were 1.33 (1.16–1.54) and 1.38 (1.20–1.58), respectively, both P<0.0001; however no significant relationships were observed between plasma choline and later AMI among patients with either plasma MMA or DMG < median (P interaction <0.008) (Figure 1).
<MEDIAN (P>
Table 1. Baseline characteristics according to plasma choline quartiles Quartile 1 Quartile 4 P for trend Age, years 58 (52–66) 66 (58–73) <0.0001 Smoking, n (%) 212 (37.9) 153 (27.9) <0.0001 Diabetes, n (%) 61 (10.9) 85 (15.5) 0.12 Previous acute myocardial infarction, n (%) 200 (35.7) 238 (43.4) <0.0001 Estimated glomerular filtration rate, mL/min/1.73m2 96 (87–104) 79 (63–92) <0.0001 Serum hs-troponin T, ng/L 4 (3–8) 9 (4–17) 0.0002 Serum triglycerides, mmol/L 1.35 (1.00–2.03) 1.60 (1.16–2.25) <0.0001 Serum apolipoprotein A1, mg/L 1.29 (1.12–1.51) 1.32 (1.17–1.53) 0.01 Statin therapy, n (%) 384 (68.6) 435 (79.4) 0.01
Figure 1

Conclusion
Among patients with stable angina, plasma choline was related to increased long-term AMI risk among patients with higher plasma MMA or DMG only. This finding potentially reflects increased risk conferred by choline during concomitant endogenous PPAR activation.

Acknowledgement/Funding
None
P1545Predictve factor for major adverse cardiovascular events in health check-up participants
Authors: Takase H , Machii M , Nonaka D , Ohno K , Sugiura T , Ohte N , Dohi Y 
Published: October 2019

Abstract

Background/Introduction
Health check-up has been carried out for individual health management. One of its main objectives is the early detection and prevention of major adverse cardiovascular event (MACE).

Purpose
We investigated predictive factors for MACE among clinical test items in health check-up program.

Methods
A total of 13522 subjects (male=8140, 52.8±12.3 year-old at baseline), who visited our hospital for a health check-up between 2008 and 2015, were enrolled. After the baseline examination, they were followed up until December 2016 (median 1827 days) with the endpoint being the incident of MACE. The outcome was confirmed using a questionnaire at health check-up, medical record, telephone, or letter. Possible association between MACE and clinical test items including gender, age, waist circumference, blood pressure, kidney function, fasting plasma glucose, lipid profile, hemoglobin, electrocardiogram (ECG), smoking habit and alcohol consumption was investigated.

Results
During the follow-up period, MACE occurred in 196 subjects (3.03 per 1000 person-year), with the incidence being more frequent in male than female subjects (4.07 vs. 1.42 per 1000 person-year). Multivariate Cox-hazard analysis demonstrated that male gender (hazard ratio [HR] = 2.457, 95% confidence intervals [CI] = 1.498–4.028), age (HR = 1.056, 95% CI = 1.040–1.071), waist circumference (HR = 1.023, 95% CI = 1.004–1.042), systolic blood pressure (HR = 1.015, 95% CI = 1.005–1.024), hemoglobin (HR = 0.868, 95% CI = 0.758–0.994) and Sokolow–Lyon voltage in the ECG (HR = 1.227, 95% CI = 1.033–1.458) were significant predictors for MACE. However, in a model where B-type natriuretic peptide (BNP) was also added as an independent variable, BNP (HR = 2.593, 95% CI = 1.602–4.196) was the strongest predictor for MACE.

Conclusions
In participants underwent health check-up, systolic blood pressure and hemoglobin as well as age and gender were the risk factors of MACE. Appropriate control of blood pressure and treatment of anemia may be useful for the prevention of MACE. Measurement of BNP may give us additional important information associated with future MACE.
P1553Differential association between vascular and chronological age with cardiovascular outcomes
Authors: Bruno R M , Nilsson P , Engstrom G , Wadstrom B , Empana J P , Boutouyrie P , Laurent S 
Published: October 2019

Abstract

Background/Introduction
Increased pulse wave velocity (PWV), is a reliable marker of early vascular aging (EVA). However, the identification of individuals whose arteries are abnormally healthy in comparison to their age and cardiovascular (CV) risk profile might be of interest, to discover novel pathways of cardioprotection and provide preventive strategies for successful vascular aging.

Purpose
1) to provide a novel calculation for vascular age and examine his determinants; 2) to test the hypothesis that individuals with the largest difference between chronological and vascular age (C-V age) show a lower rate of CV events than their counterparts, and may thus be defined as the supernormal vascular aging group (SUPERNOVA).

Methods
Vascular age was defined as predicted age based on classical CV risk factors and PWV. The best fitting model for vascular age was investigated in the multicenter, European, cross-sectional Reference Values for Arterial stiffness Collaboration Database (n=11406). Continuous variables were modelled as smoothing splines. Thereafter, the risk of fatal and non-fatal CV events associated with C-V age was examined in the longitudinal cohort of the Malmo Diet and Cancer Study (n=2663) using Cox proprotional hazard regression models. C-V age was examined as a continuous variable (natural splines) and as a 3 levels categorical variables based on the best grouping of the deciles of C-V age and corresponding to the EVA (<3.0 years), normal vascular aging (3.0 to 8.8 years) and SUPERNOVA (>8.8 years) respectively.

Results
In the Reference Values Cohort (age range 17–85 years, 52.4% men, 38.1% hypertensives, 3.9% diabetics, average PWV 7.8 m/s), the most significant predictor of vascular age (full model r2 0.598) was PWV. In the Malmo Diet and Cancer Study Cohort (age 61–89 years, 63.6% men, 64.0% hypertensives, 12.9% diabetics, PWV 11.5 m/s), during follow-up (6.6 years on average), 286 individuals developed a first cardiovascular event. In the Cox survival analysis, C-V age was significantly and inversely associated with CV events. Compare to normal vascular aging, participants with SUPERNOVA had lower risk for CV events [HR 0.51 (0.34–0.76)] whereas those with EVA had a higher risk [HR 2.71 (1.80–4.09)]. Instead, there was no significant association with all-cause mortality.

Conclusions
The use of PWV and CV risk factors may be useful to define early and supernormal vascular aging in particular, and to assess its clinical relevance towards the risk of cardiovascular disease and death.
P1560Prognostic predictors of mortality in very elderly patients presenting with NSTEMI
Authors: Cacho C , Cordero Fort A , Gonzalez Ferrero T , Perez Dominguez M , Torrelles Fortuny A , Antunez Muinos P J , Cid Menendez A , Agra Bermejo R M , Rigueiro Veloso P , Iglesias Alvarez D , Alvarez Alvarez B , Gonzalez Juanatey J R , Garcia Acuna J M 
Published: October 2019

Abstract

Background
Elderly patients are usually under-represented in randomized controlled trials, therefore there is less data providing prognostic information for this particular group. NSTEMI clinical practice guidelines indicate that older patients should receive the same therapeutic strategy than younger patients.

Methods
Observational retrospective study including 8771 patients admitted for acute coronary syndrome in two tertiary referral hospitals between 2003 and 2017: 5673 NSTEMI (64.3%) and 3098 STEMI (35.7%). 999 patients presenting with NSTEMI and aged over 75 years were selected and divided into 3 groups: aged 75–80, aged 80–89 and aged over 90. Cox proportional hazard regression analysis was performed in order to determine independent predictors of mortality. Mortality and survival were represented by Kaplan-Meier curves and log rank test was conducted to assess significant differences in survival between groups. Median follow-up period was 48 months.

Results
A significant association between female sex and elder age was observed, also a higher prevalence of hyperlipemia and diabetes. In acute phase, no significant differences were found in between congestive heart failure onset, myocardial re-infarction, acute renal failure, stroke or in-hospital mortality amongst the 3 groups. However, at follow-up period, higher mortality in elder groups was documented. After performing a multivariate analysis, age was identified as an independent predictor of mortality at follow-up (<90 years: HR 1.50 CI 95% 1.23–1.83, p=0.0001, >90 years: HR 1.93 CI 95% 1.27–2.93, p=0.002) as well as GRACE score (HR 1.06, CI 95% 1.02–1.09, p=0.002), CRUSADE score (HR 1.01 CI 95% 1.01–1.02, p=0.0001) and treatment with digoxine (HR 1.38 CI 95% 0.95–2.0, p=0.08). On the other side, beta-blockers (HR 0.71 CI 95% 0.59–0.86, p=0.0001) and complete coronary revascularization (HR 0.48 CI 95% 0.37–0.64, p=0.0001) were found to be protective factors.

Conclusions
In very elderly patients presenting with NSTEMI, prognostic predictors of mild-term mortality are similar to those present in younger patients. Recommendations of clinical practice guidelines, such as beta-blockers' treatment and coronary revascularization, should also be applied in elderly patients.
P1561An elevated risk of heart failure and stroke events in octogenarian Japanese patients with acute myocardial infarction who received percutaneous coronary intervention
Authors: Tsuda K , Kataoka Y , Nishikawa R , Doi T , Nakashima T , Hosoda H , Honda S , Fujino M , Yoneda S , Otsuka F , Nakao K , Tahara Y , Asaumi Y , Noguchi T , Yasuda S 
Published: October 2019

Abstract

Background
The proportion of the octogenarian population is expanding especially in Eastern society. Due to the clustering of risk factors, acute myocardial infarction (AMI) represents a major cardiovascular complication in octogenarian subjects. This suggests the need to further optimize their therapeutic management to prevent future cardiac events after AMI. However, analysis of clinical characteristics and cardiovascular outcomes in octogenarian subjects with AMI who received the current established medical therapies is limited.

Purpose
To investigate clinical features and prognosis in octogenarian AMI subjects treated with percutaneous coronary intervention (PCI).

Methods
We analyzed 1547 AMI subjects underwent PCI between 2007 and 2017. Baseline characteristics and the occurrence of composite major adverse cardiovascular events (cardiac death, non-fatal MI, revascularization, heart failure and stroke) were compared in octogenarian and non-octogenarian subjects.

Results
22.0% (340/1547) of study subjects was octogenarian. They were more likely to have chronic kidney disease (CKD) and a lower level of LDL-C on admission (Table). Moreover, a higher prevalence of severer Killip class and LVEF <30% were observed in octogenarians (Table). However, they were not optimally treated with the established medical therapies at discharge (Table). During the observational period (median=3.1 years), the composite of cardiovascular events more frequently occurred in octogenarian subjects. Of note, they exhibited a 2.15-fold and 3.01-fold increased risk for heart failure and stroke events, respectively (Figure).
Table 1 Non-Octogenarian (n=1207) Octogenarian (n=340) P-value CKD* (%) 33.8 63.2 <0.0001 LVEF <30% (%) 5.7 10.3 0.02 Killip class 1.33±0.03 1.55±0.05 <0.0001 LDL-C (mmol/L) 3.20±0.03 2.80±0.05 <0.0001 Statin (%) 86.3 78.2 0.0006 Beta-blocker (%) 74.0 65.8 0.005 ACE-I/ARB (%) 87.3 76.6 <0.0001 DAPT (%) 86.0 88.6 0.42 *CKD is defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2.
Figure 1

Conclusions
Octogenarian subjects with AMI were high-risk group associated with heart failure and stroke events. Their distinct clinical backgrounds may affect the adoption of optimal medical therapies, potentially resulting in worse cardiovascular outcomes. Further intensified management should be applied to octogenarian subjects with AMI.
P1570Cardiac strain detects subclinical decline of cardiac function after hematopoietic stem cell transplantation in patients with hematologic malignancies
Authors: Oboshi M , Oka T , Yasui T , Shioyama W , Tada Y , Ishikawa J , Fujita M 
Published: October 2019

Abstract

Background
Hematopoietic stem cell transplantation (HSCT) has been established as a treatment of various hematologic malignancies and improved their prognoses. HSCT includes intensive chemotherapy and systemic radiation, which occasionally induces cardiac dysfunction. However, early predictor of cardiac dysfunction associated with HSCT is still elusive. Recently, left ventricular (LV) global longitudinal strain (GLS) has been recognized as an early detector of cardiotoxicity. In this study, we retrospectively analyzed GLS and cardiac parameters in patients with hematologic malignancies before and after HSCT to explore HSCT-induced cardiac dysfunction.

Methods
Thirty-one consecutive patients undergone HSCT were enrolled and reviewed their cardiac comorbidities, medications, chemotherapy, and radiotherapy before HSCT. Transthoracic echocardiographic variables including GLS, cardiac troponin-I, and B-type natriuretic peptide were analyzed prior to and 1 month after HSCT.

Results
The patients were 49.7±13.5 years of age, 61% were male, and 52% had cardiovascular risk factors. Cardiac troponin-I was significantly increased following HSCT from 0.010±0.002 ng/ml to 0.016±0.014 ng/ml (P=0.02), indicating that HSCT should have certain impact on cardiac myocytes. Echocardiographic analyses revealed that LV GLS was significantly decreased after HSCT from −19.4±0.8% to −18.8±0.8% (P<0.001), whereas there was no significant difference in LV ejection fraction between these time points of HSCT (63.6±5.5% vs. 64.7±4.6%; P=0.13). Although there was no correlation between the decline of GLS and the increase of troponin-I in this cohort, these results clearly indicated that GLS, but not LVEF, predicted HSCT-induced early and subclinical cardiac dysfunction at 1 month after the HSCT.

Conclusion
GLS detected early decline of cardiac function after HSCT in the patients with hematologic malignancies. Further follow-up investigations will reveal relationship between GLS, troponin-I and prognosis of cardiac function after HSCT in patients with hematologic malignancies.
P1576Association of colorectal cancer with genetic and epigenetic variation in PEAR1 - a population-based cohort study
Authors: Yang W.-Y , Izzi B , Zhang Z.-Y , Thijs L , Citterio L , Wei F.-F , Salvi E , Delli Carpini S , Manuta P , Kuznetsova T , Cusi D , Hoylaerts M F , Luttun A , Verhamme P , Staessen J A 
Published: October 2019

Abstract

Background
Platelet Endothelial Aggregation Receptor 1 (PEAR1) modulates angiogenesis and platelet contact-induced activation, which play a role in the pathogenesis of colorectal cancer.

Purpose
To study the association of colorectal cancer with genetic and epigenetic variation in PEAR1.

Methods
Among 2532 randomly recruited participants enrolled in the family-based Flemish Study on Environment, Genes and Health Outcomes (51.2% women; mean age 44.8 years), we recorded the incidence of colorectal cancer and genotyped SNP rs12566888 located in intron 1 of the PEAR1 gene. In 929 participants, we also measured the methylation at 16 CpG sites in the PEAR1 promoter. In multivariable-adjusted analyses, we contrasted the risk of colorectal cancer in minor-allele (T) carriers vs. major allele (GG) homozygotes. We applied partial least square discriminant analysis (PLS-DA) to identify methylation sites associated with colorectal cancer.

Results
Over a median follow-up of 18.1 years, 49 patients developed colorectal cancer. While accounting for clustering within families and adjusting for sex, age, body mass index, the total-to-HDL cholesterol ratio, serum creatinine, plasma glucose, smoking and drinking, use of antiplatelet and nonsteroidal anti-inflammatory drug, the hazard ratio contrasting minor allele carriers vs. major allele homozygotes was 2.17 (95% confidence interval, 1.18–3.99; P=0.013). Bootstrapped analyses, from which we randomly excluded from two to nine cancer cases, provided confirmatory results. PLS-DA identified two methylation sites in the PEAR1 promoter associated with higher colorectal cancer risk and two with lower risk. In-silico analysis suggested that methylation of the PEAR1 promoter at these four sites affects binding of the transcription factors p53, PAX5, and E2F-1, thereby modulating gene expression.
Potential pathways

Conclusions
Our findings suggest that genetic and epigenetic variation in PEAR1 modulates the risk of colorectal cancer in white Flemish.

Acknowledgement/Funding
The European Union, the European Research Council, the European Research Area Net for Cardiovascular Diseases, and the Research Foundation Flanders.
P1582Prognostic value of C-reactive protein/albumin ratio for cardiovascular morbidity and mortality in end-stage renal disease patients with incident haemodialysis therapy
Authors: Takahashi H , Ishii H , Kumada Y , Oshima T , Sakakibara T , Ito R , Murohara T , Ozaki Y 
Published: October 2019

Abstract

Background
Hypoalbuminemia, a manifestation of protein-energy wasting or malnutrition, is commonly observed in patients with end-stage renal disease (ESRD), and is associated with chronic inflammation and increasing cardiovascular (CV) risk. Recently, C-reactive protein (CRP)/albumin ratio at discharge is reportedly a well-predictor of mortality in severe sepsis or cancer patients.
We investigated prognostic value of the CRP/albumin ratio at just starting haemodialysis (HD) therapy for CV morbidity and mortality in patients with ESRD.

Methods
A total of 1,548 ESRD patients were enrolled and were divided into quartiles according to CRP/albumin levels at initiation of HD; quartile 1 (Q1): <0.22, Q2: 0.23–0.54, Q3: 0.55–1.83 and Q4: >1.84. They were followed up for 10-year after starting HD therapy. Primary endpoint was CV events defined as hospitalization due to CV events such as cardiac disease, stroke and peripheral artery disease and CV death. We also evaluated the incremental value with C-index when CRP alone, albumin alone and the CRP/albumin ratio were added into a model with established risk factors.

Results
During follow-up period (median: 59 months), 512 cases experienced CV events (33.1%) including 165 cases of CV deaths (10.7%). Kaplan-Meier analysis shows that CV event-free survival rates for 10 years were 63.5%, 53.8%, 47.5% and 31.9% in Q1, Q2, Q3 and Q4, and that CV survival rates were 90.4%, 83.9%, 77.2% and 64.6% in Q1, Q2, Q3 and Q4, respectively (p<0.0001 in both). After adjustment for all baseline variables, elevated CRP/albumin ratio was identified as an independent predictor for CV events [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11–2.07, p=0.0093 for Q2 vs. Q1, HR 1.79, 95% CI 1.33–2.42, p<0.0001 for Q3 vs. Q1and HR 2.27, 95% CI 1.70–3.07, p<0.0001 for Q4 vs. Q1, respectively]. As to CV mortality, similar results were obtained (HR 1.80, 95% CI 0.98–3.44, p=0.056 for Q2 vs. Q1, HR 2.56, 95% CI 1.45–4.71, p=0.0009 for Q3 vs. Q1 and HR 2.66, 95% CI 1.53–4.86, p=0.0004 for Q4 vs. Q1, respectively). Furthermore, adding the CRP/albumin ratio to a baseline model with established risk factors improved the C-index greater than that of CRP alone or albumin alone, respectively (0.715 from 0.692, p=0.0095 and from 0.683, p=0.0019)

Conclusion
The CRP/albumin ratio, which easily available from daily practice, could strongly stratify the risk of future CV morbidity and mortality in ESRD patients who need HD therapy.