bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between psychosocial burden and prognostic biomarkers in patients with stable coronary heart disease – a STABILITY substudy
Authors: Wassberg C , Batra G , Hadziosmanovic N , Hagstrom E , White H , Stewart R , Siegbahn A , Wallentin L , Held C 
Published: November 2020

Abstract

Background
Psychosocial burden is associated with increased risk of cardiovascular (CV) events in patients with stable coronary heart disease (CHD). The underlying mechanisms linking psychosocial burden and CHD are unclear and might be explained by studying biomarkers known to be associated with CV risk.

Methods
15,608 patients in the STABILITY trial completed a questionnaire on to what extent they were feeling down, had loss of interest, experienced financial stress and if they were living alone. Levels of high-sensitivity (hs) C-reactive protein (hs-CRP), interleukin-6 (IL-6), hs-troponin T (hs-TnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) were assessed at baseline. Associations between levels of psychosocial burden (sometimes, often/always vs. never/rarely) and biomarkers were evaluated in a linear model where geometric mean ratio of the log-transformed biomarker were calculated.

Results
Adjusted associations (age, gender and established CV risk factors) are presented in the table.

Conclusion
Psychosocial burden in patients with stable CHD was independently associated with elevated biomarkers. The underlying association is likely to be complex and involve multiple pathways.

Funding Acknowledgement
Type of funding source: Private company. Main funding source(s): The STABILITY study was funded by GlaxoSmithKline. Roche Diagnostics, Rotkreuz, Switzerland, supported the research by providing the GDF-15 assay free of charge.
Diabetes, coronary artery disease, and risk of dementia – a cohort study from Western Denmark
Authors: Olesen K.K.W , Thrane P.G , Gyldenkerne C , Thim T , Maeng M 
Published: November 2020

Abstract

Background
Diabetes patients have a higher risk of both ischemic stroke and dementia compared to non-diabetes patients. Coronary artery disease (CAD) is associated with an increased risk of ischemic stroke. We hypothesized that diabetes and CAD are independent, and additive, risk factors for ischemic stroke and dementia.

Purpose
We examined the risk of dementia and ischemic stroke in diabetes and non-diabetes patients with and without CAD by coronary angiography.

Methods
We conducted a cohort study of all patients ≥65 years, who underwent coronary angiography between 2003–2016 in Western Denmark. Patients diagnosed with dementia or early cognitive decline at the time of CAG were excluded. Patients were stratified by diabetes and CAD. Outcomes were dementia and ischemic stroke. We estimated the cumulative incidence of a combined endpoint of dementia and ischemic stroke accounting for the competing risk of death. Follow-up was capped at the 75th percentile of overall follow-up (9.2 years). We estimated adjusted hazard ratios (aHRs) using patients without diabetes and CAD as reference. We also examined the association between extent of CAD and dementia in subgroup analysis of diabetes patients.

Results
A total of 62,372 patients were included, of whom 10,417 (16.7%) had diabetes and 43,023 (69.0%) had obstructive CAD. Median follow-up was 5.8 years. Patients with both diabetes and CAD had the highest risk of dementia (aHR 1.47, 95% CI 1.27–1.71), including Alzheimer's dementia (aHR 1.26, 95% CI 1.01–1.56) and vascular dementia (aHR 2.60, 95% CI 1.78–3.80), as well as ischemic stroke (aHR 2.02, 95% CI 1.77–2.32). Patients with either diabetes or CAD were at intermediate risk of dementia and ischemic stroke (Figure). We did not find a significant trend between the extent of CAD and risk of dementia in diabetes patients (p for trend=0.0687).

Conclusions
Both diabetes and CAD were independent risk factors of dementia and ischemic stroke in patients ≥65 years after angiography. Patients with combined diabetes and CAD had a particularly high risk of cognitive impairment and ischemic stroke.
Figure 1

Funding Acknowledgement
Type of funding source: Public hospital(s). Main funding source(s): Department of Cardiology, Aarhus University Hospital
Evaluation of two classical contrast-induced nephropathy definitions for predicting long-term mortality in patients undergoing elective percutaneous coronary intervention
Authors: Lin K , You Z , Chen H , He C , Chen X , Guo Y , Zhu P 
Published: November 2020

Abstract

Background
Contrast-induced nephropathy (CIN) is a frequent complication after percutaneous coronary intervention (PCI), and is associated with poor outcome. However, the optimal definition of CIN has been debated because of its different incidence and influence on prognosis. At present, there are limited data regarding th impact of different CIN definitions on long-term mortality in patients undergoing elective PCI.

Purpose
To explore the influence of two classical CIN definitions on long-term mortality and identify which definition was more suitable for predicting long-term mortality in patients undergoing elective PCI..

Methods
We prospectively observed 5600 consenting patients undergoing PCI from January 2012 to December 2018. Two classical CIN definitions include those defined by ESUR[Contrast-media-induced nephrotoxicity (CMN)] and AKIN[contrast induced acute kidney injury (CI-AKI)]. CMN was defined as an increase in serum creatinine (SCr) ≥25% or 0.5 mg/dLabove thebaseline level within 3 days,while CI-AKI wasdefined as an increase in SCr ≥50% or 0.3 mg/dL within 48hs after contrast medium exposure.The association of CIN with long-term mortality was investigated by Cox regression analysis.Interaction analyses were performed for long-term mortality across subgroups.

Results
The incidence of CIN according to ESUR (CMN) and AKIN (CI-AKI) definition were18.3% (n=1023) and 6.1% (n=342), respectively. During a median follow-up of 2 years, after adjusting other potential risk factors, multivariable cox regression analysis revealed CIN was a risk factor for long-term mortality [hazard ratio (HR): 2.021, 95% confidence interval (CI): 1.389–2.938, P&lt;0.0001] according to AKIN definition, but not for ESUR definition (HR: 1.344, 95% CI: 0.982–1.838, P&gt;0.05). Further interaction analysis showed that there was a significant interaction between age &gt;75ys and CMN for long-term mortality (P=0.042) while no such association was observed between age &gt;75ys and CI-AKI (P=0.806).

Conclusions
CIN defined by AKIN may be more suitable for predicting long-term mortality in patients undergoing elective PCI. However, in elderly patients, CIN defined by ESUR could also be used for predicting long-term mortality.
Association Between CIN and mortality

Funding Acknowledgement
Type of funding source: None
Beta-amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease
Authors: Ikonomidis I , Katogiannis K , Kyriakou E , Taichert M , Katsimaglis G , Tsoumani M , Andreadou I , Lambadiari V , Maratou I , Kousathana F , Varlamos C , Plotas P , Alexopoulos D , Dimitriadis G , Tsantes A.E 
Published: November 2020

Abstract

Background and aims
Increased b-amyloid and decreased Mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization.

Patients and methods
In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: a). maximum platelet aggregation to adenosine diphosphate (ADP) by Light Transmission Aggregometry (LTAmax), b) Malondialdehyde (MDA), as oxidative stress marker, c) MOTS-c, d) b-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up.

Results
Out of 121 patients, 32 showed HPR (LTAmax &gt;48%,). At baseline, HPR was associated with b-amyloid &gt;51 pg/ml (p=0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, b-amyloid &gt;51 pg/ml and MOTS-c&lt;167 ng/ml were predictors of MACE (relative risk 3.1, 3.5 and 3.8 respectively, p&lt;0.05) after adjusting for confounders and medication. There was significant interaction between HPR and b-amyloid or MOTS-c for the prediction of MACE (p&lt;0.05). Patients with HPR and b-amyloid&gt;51mg/dl or HPR and MOTS-c concentration&lt;167 ng/ml had a 4-fold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p&lt;0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD.

Conclusions
Increased b-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow- up.

Funding Acknowledgement
Type of funding source: None
Spontaneous coronary artery dissection (SCAD) in men: an observational study
Authors: Wood A , Adlam D 
Published: November 2020

Abstract

Background/Introduction
SCAD is a rare cause of acute coronary syndrome. Approximately 90% of SCAD patients are women, and factors such as the hormonal changes of the menstrual cycle are thought to be relevant. It is therefore interesting to consider why patients without such hormonal exposure may be affected. SCAD in men remains poorly understood.

Purpose
To study the clinical features and natural history of SCAD in men and to see how it differs from SCAD in women.

Methods
Patients with SCAD were recruited by self-referral and clinician referral from across the UK. Angiograms are reviewed by two experienced cardiologists and other data is obtained from patient questionnaires and from medical records.

Results
53 male SCAD patients were identified from the registry. Mean age at SCAD was 47±5.4 (SD). 1 presented with cardiac arrest, 2 as chronic dissections without a clear acute event, 15 as STEMI and 32 as NSTEMI; admission ECGs were not available for 3 patients. The vessel affected was the circumflex in 15 patients, RCA in 4, LAD in 27 and multi vessel in 7. SCAD type was 1 in seven patients, 2a in 21, 2b in 16, 3 in 7 and 4 in 2. LV function post SCAD was normal in 37 out of 50 patients with data available and mean EF was 52.4%. Of 37 with cardiac MRI data, 11 had no visible late gadolinium enhancement. 23 patients had been screened for fibromuscular dysplasia and only 1/23 had this diagnosis. 2 other patients had a non-FMD aortopathy (dilated ascending aorta) and 1 had a very small cerebral aneurysm that was not thought to represent FMD. Mean follow up from the first SCAD event was 3 years (SD 2 years); over this time period 10/51 patients had recurrent SCAD (2 patients presented as chronic dissections on elective angiography and it was not possible to date the index event).

Conclusions
This is the largest study so far reported of SCAD in men. The mean age was similar to that seen in women, though with a narrower age range, and the proportions of STEMI and NSTEMI are also similar. The most frequently affected vessel was the LAD. Type 2 SCAD was by far the commonest angiographic appearance. The majority of patients had preserved LV systolic function and a significant proportion had no measurable scar. These findings suggest that the presenting features of SCAD in men are very similar to those in women. The incidence of FMD appears to be far lower than in women, however; studies in female SCAD patients suggest that FMD is present in 11–86% (depending on methods used for screening). Finally, rate of recurrent SCAD in men appears significant. The largest series so far reported in SCAD (327 patients, 90.5% women, followed prospectively) showed a recurrence rate of 10.4% over 3 years. We saw a recurrence rate of 19.6%. This may simply represent the play of chance in a small population, or recruitment bias as our study is primarily retrospective, however it is an intriguing observation worthy of further investigation.

Funding Acknowledgement
Type of funding source: Other. Main funding source(s): BeatSCAD
Higher level of high sensitivity C-reactive protein is associated with more fibrocalcific plaque and longer lesion in patients with acute coronary syndrome
Authors: Katamine M , Minami Y , Asakura K , Kato A , Katsura A , Sato T , Muramatsu Y , Hashimoto T , Kameda R , Meguro K , Shimohama T , Ako J 
Published: November 2020

Abstract

Background
The association between the level of high sensitivity C-reactive protein (hsCRP) and coronary plaque characteristics in patients with acute coronary syndrome (ACS) remains to be elucidated.

Purpose
To clarify the morphological characteristics of culprit lesion in patients with ACS according to the hsCRP levels using optical coherence tomography (OCT).

Methods
A total of 215 consecutive patients with ACS, who underwent OCT imaging of culprit lesions were included. The patients were classified into either the higher hsCRP group (hsCRP ≥0.14 mg/dL, n=108) or the lower hsCRP group (hsCRP &lt;0.14 mg/dL, n=107) according to the median preprocedural hsCRP level. The morphological characteristics of culprit lesion assessed by OCT were compared between the two groups.

Results
The higher hsCRP group had higher prevalence of insulin therapy (14 vs. 6%, p=0.037) and current smoker than the lower hsCRP group (37 vs. 18%, p=0.002). The prevalence of long lesion (≥25 mm, 67 vs. 53%, p=0.041) and fibrocalcific plaque (53 vs. 33%, p=0.003) was significantly higher in the higher hsCRP group than in the lower hsCRP group (Figure). On the other hand, the prevalence of plaque rupture (36 vs. 46%, p=0.174) and lipid-rich plaque (47 vs. 64%, p=0.011) was rather lower in the higher hsCRP group than in the lower hsCRP group (Figure). In a multivariate analysis, fibrocalcific plaque (odds ratio [OR]: 2.098, 95% confidence interval [CI]: 1.125–3.913, p=0.019), lesion length (mm, OR: 1.036, 95% CI: 1.010–1.061, p=0.004) and current smoker (OR: 2.757, 95% CI: 1.388–5.476, p=0.003) was independently associated with higher hsCRP level.

Conclusions
ACS patients with high hsCRP levels had more fibrocalcific plaque and longer lesion than those with low hsCRP levels. The association between high hsCRP levels and vulnerable characteristics of culprit plaque was not demonstrated.

Funding Acknowledgement
Type of funding source: None
Prognostic impact of elevated baseline CRP levels in primary PCI-treated patients with residual cholesterol risk
Authors: Zobenica V , Milasinovic D , Jelic D , Mehmedbegovic Z , Zaharijev S , Radomirovic M , Djurosev I , Pavlovic A , Dudic J , Dedovic V , Asanin M , Vukcevic V , Stankovic G 
Published: November 2020

Abstract

Background
Recent large randomized studies have indicated the potential of anti-inflammatory therapies to reduce adverse cardiovascular events in patients with myocardial infarction, with the most pronounced benefit in patients with baseline elevated C-reactive protein (CRP).

Purpose
Our aim was to assess the association of CRP levels with 30-day and 1-year mortality in patients with acute myocardial infarction treated with primary PCI and with residual cholesterol risk.

Methods
The study included 1531 patients admitted for primary PCI, with the residual cholesterol risk, i.e. low-density lipoprotein cholesterol (LDL-C) levels of &gt;1.80 mmol/l (70 mg/dl), from a prospectively kept electronic registry of a high-volume tertiary center, for whom in-hospital CRP measurements were available. Elevated CRP was defined as ≥5 mg/l (local laboratory cut off value), measured during index hospitalization. Cox regression models were constructed to assess the impact of elevated CRP on 30-day and 1-year mortality.

Results
72% of the included patients with LDL-C &gt;1.80 mmol/l had elevated in-hospital CRP (n=1107). Compared with patients with CRP levels within reference limit, elevated CRP was associated with older age (62 vs. 60, p&lt;0.001), higher rates of diabetes (25.8% vs. 18.5%, p=0.002), renal failure (6.4% vs. 2.1%, p&lt;0.001) and Killip class &gt;1 at presentation (22.5% vs. 12.3%, p&lt;0.001), as well as lower EF (44% vs. 48%, p&lt;0.001) and lower haemoglobin on admission (13.9 g/dl vs. 14.2 g/dl, p&lt;0.001). Crude mortality rates were increased in patients with CRP ≥5mg/l at both 30 days (6.0% vs. 2.4%, p=0.003) and 1 year (13.2% vs. 6.3%, p&lt;0.001) (Figure). After adjusting for the observed baseline differences, CRP ≥5mg/l remained an independent predictor of mortality at 1 year (HR 1.691, 95% CI: 1.050–2.724, p=0.03), but not at 30 days (HR 1.690, 95% CI: 0.859–3.324, p=0.13).

Conclusion
In primary PCI-treated patients with residual cholesterol risk, elevated in-hospital CRP was independently associated with 1-year mortality. Our findings may thus suggest a potential window of opportunity, for anti-inflammatory therapies to improve outcomes beyond the acute phase.
Figure 1

Funding Acknowledgement
Type of funding source: None
Iron deficiency is associated with larger infarcts and with adverse remodeling in STEMI patients and reduces myocardial tolerance to ischemia/reperfusion by inhibiting the eNOS/sGC/PKG pathway in mice
Authors: Barrabes J.A , Aluja D , Castellote L , Rodriguez A , Otaegi I , Pineda V , Mila A , Baneras J , Lidon R.M , Sambola A , Rodriguez-Palomares J , Valente F , Beneitez D , Ferreira-Gonzalez I , Inserte J 
Published: November 2020

Abstract

Background
Iron deficiency (ID) interferes with the cardioprotective pathway endothelial nitric oxide synthase/soluble guanylate cyclase/protein kinase G (eNOS/sGC/PKG), but its role in acute myocardial infarction remains unclear.

Methods
Patients (n=125) with a first anterior STEMI treated with PCI underwent magnetic resonance imaging in the acute phase and at 6 months. We assessed whether ID (ferritin level &lt;100 μg/L or &lt;300 μg/L if transferrin saturation was &lt;20%) was associated with infarct size acutely or with adverse left ventricular (LV) remodeling (LV end-diastolic volume increase at 6 months &gt;20%, n=105). C57BL6/N mice were fed with standard diet or iron-deficient diet for 4 weeks before undergoing 45-min coronary occlusion/24-h reperfusion.

Results
Patients with ID (43.2%) had larger infarcts (22.8±10.2 vs 16.8±9.8% of LV mass, P=0.002) and more frequent microvascular obstruction (70.0 vs 43.3%, P=0.004) in the initial exam than the rest. They also developed adverse LV remodeling more often (38.6 vs 14.8%, P=0.005), even after adjusting by infarct size and final TIMI flow grade (OR 3.1, 95% CI 1.1–8.6, P=0.027). In mice, ID diet reduced myocardial iron content, serum ferritin and hemoglobin levels without reaching anemic values and without inducing echocardiographic alterations. ID diet reduced myocardial eNOS protein content, its dimeric form, and nitrites/nitrates and cGMP levels. eNOS decrease was associated with reduced HSP90 levels and increased eNOS ubiquitination in correlation with oxidative and nitrosative stress. Weekly iv administration of iron sucrose effectively reverted the ID-diet effects. Infarct size was larger in the ID group than in controls (58.8±3.0 vs. 40.3±3.6%, P=0.03) but was not increased in ID-diet animals treated with iron sucrose (36.3±4.0%) or receiving the sGC activator ataciguat before ischemia (31.0±2.5%).

Conclusions
ID is associated with larger infarcts and with more frequent adverse LV remodeling in patients with STEMI and reduces myocardial tolerance to ischemia/reperfusion in mice by attenuating eNOS/sGC/PKG pathway activity. Iron sucrose treatment and sGC activation reverted these deleterious effects of ID in mice. Iron supplementation might be beneficial in STEMI patients with ID.

Funding Acknowledgement
Type of funding source: Public grant(s) – National budget only. Main funding source(s): CIBER-CV. Instituto de Salud Carlos III (PI16/00232), co-financed by the ERDF
Prognostic impact of severe anemia (hemoglobin &lt;10g/dL) during treatment with dual antiplatelet therapy after hospital discharge for acute coronary syndrome
Authors: Campos I , Oliveira C , Pires C , Medeiros P , Flores R , Mane F , Braga C , Gaspar A 
Published: November 2020

Abstract

Introduction
In recent years, the use of invasive strategies has become the generalized approach in the management of patients with acute coronary syndrome (ACS), justified by the associated prognostic benefit due to reduced mortality and the evolution of percutaneous coronary intervention (PCI). However, the benefits of an invasive approach in ACS are unclear in the population with significant anemia, as anemia is strongly associated with increased risk of morbidity and mortality in these patients.

Aim
To determine the ischaemic vs. bleeding risks from patients with severe anemia (hemoglobin &lt;10 g/dL) during treatment with Dual Antiplatelet Therapy (DAPT) after an ACS undergoing PCI.

Methods
From a national multicentre registry, we analyzed 17 370 ACS pts. Pts were divided into two groups: group 1 - pts with severe anemia (hemoglobin &lt;10g/dL) (n=557, 3.2%); group 2 - pts without severe anemia (hemoglobin 10g/dL) (n=16813, 96.8%). Primary endpoint was the occurrence of a composite of death and adverse cardiovascular events (stroke, reinfarction, and rehospitalization of cardiovascular etiology) at 1 year.

Results
The sample consisted in 73.4% men and 26.6% women, with mean age of 66±14 years. The incidence of severe anemia was 3.2%. Group 1 pts were older (75±12 vs 66±14, p&lt;0.001), had a higher proportion of women (47.6% vs 25.9%, p&lt;0.001), diabetes (55% vs 30.6%, p&lt;0.001), hypertension (81.8% vs 68.2%, p&lt;0.001) and chronic kidney disease (29.2% vs 5.2%, p&lt;0.001). During hospitalization, group 1 had more heart failure (35.3% vs 15.1%, p&lt;0.001), worst LVEF (27.3% vs 17.3%, p&lt;0,001), bleeding (7.6%% vs 1.3%, p&lt;0.001) and transfusion (23.4% vs 1%, p&lt;0.001). During hospitalization, group 2 pts were more likely to undergo revascularization (82.9% vs 89.4%, p&lt;0.001) and double antiaggregation (82.5% vs 95%, p&lt;0.001). A multivariate analysis identified age [OR 1.48, 95% CI 1.32 to 1.89; p&lt;0.001] and feminine sex [OR 2.21, 95% CI 1.89 to 3.61; p&lt;0.001] as independent predictors of severe anemia during hospitalization. Patients with severe anemia had longer hospital stay (9 days vs 6 days; p&lt;0.001), and higher 6-month mortality (8.7% vs. 2.9%; p&lt;0.001). In multivariate analysis and after adjusting for different baseline characteristics, pts with severe anemia had higher occurrence of a composite of death and adverse cardiovascular events at 1-year compared to those without severe anemia [OR 3.04, 95% CI 1.21 to 5.04; p=0.029].

Conclusion
We objected a low prevalence of ACS patients with severe anemia undergoing PCI (52.2%) but the incidence of ICP in these complex patients has increased in recent years, mainly due to the evolution of PCI over the last 40 years. Severe anemia was strongly associated with increased risk of morbidity and mortality in ACS pts.

Funding Acknowledgement
Type of funding source: None