Cox Regression Model Research Articles

Mortality and patient stratification 30 days after Staphylococcus aureus bacteraemia in patients with cardiac implantable electronic devices - a Danish nationwide cohort study

Abstract Background Staphylococcus aureus bacteraemia (SAB) is a high-risk condition with a reported 30-day mortality of up to 25% even with timely and correct treatment. Patients with cardiac implantable electronic devices (CIEDs) are at increased risk of a complicated course of disease due to the risk of device infection. Purpose We aimed to estimate the 30-day mortality rate following SAB among adult Danish patients with a de novo CIED. Furthermore, we aimed to identify patients with low, intermediate, and high mortality risk following SAB. Methods Using The National Danish Staphylococcus Aureus Bacteriemia Database and The Danish Pacemaker and ICD Register, we identified all Danish patients aged 18 to 99 years with a de novo CIED implantation between 2000 and 2020, and subsequently positive Staphylococcus aureus blood culture. The primary outcome was 30-day all-cause mortality from date of SAB. Clinical variables significantly associated with increased 30-day mortality following SAB were identified (p<0.05 and 95% CI not including 1) using adjusted multivariable Cox regression modelling. We tested variables related to age, sex, calendar year of SAB, device type, timing of infection, previous SAB, concomitant medication, and clinically relevant pre-existing co-morbidities including valvular replacement, recent surgery, and renal dialysis. Patients were awarded 1 point for each of the significant variables present, and the sum was used to stratify into low-, intermediate-, and high-risk groups. The cut-offs between the groups were set at 0 and 2 points (0 points = low risk, 1-2 points = intermediate risk, ≥3 = high risk). Results We identified 1,393 patients with de novo CIED (pacemaker: n=983, implantable cardioverter defibrillator: n=230, cardiac resynchronization therapy w/wo defibrillator capacity: n=180) and subsequent SAB (median time to SAB from CIED implantation: 679 days [IQR 168-1,525]). Median age at the time of SAB diagnosis was 77 years [IQR 68-84] with 72.4% being males. In total, 469 patients died within the first 30 days from SAB, equivalent to an overall 30-day mortality rate of 33.7% (95% CI 31.2-36.2). We identified high age, left sided valvular disease, use of systemic corticosteroids, and SAB occurring >6 months from CIED implantation to be associated with an increased hazard of 30-day mortality following the SAB diagnosis (Fig. 1). The median total sum obtained from the stratification model was 2 points [IQR 1-2]. 30-day all-cause mortality was estimated to 16.2%, 31.6% and 54.9% for the low-, intermediate- and high-risk groups, respectively (Fig. 2). Conclusions In patients with a de novo cardiac implantable electronic device and subsequent Staphylococcus aureus bacteraemia the overall 30-day mortality from date of SAB was 33.7%. Patients with high age, recent surgery, left sided valvular disease, and use of systemic corticosteroids were particularly at risk.Fig. 1.Simplified stratification modelFig. 2.30-day mortality following SAB

Permanent pacemaker implantation is associated with an increased risk of heart failure hospitalization in transcatheter aortic valve implantation patients with reduced systolic function

Abstract Background The impact of permanent pacemaker implantation (PPI) on outcome of patients following transcatheter aortic valve implantation (TAVI) is not fully understood. Purpose This study aimed to assess the impact of PPI on risk of two-year mortality and hospitalization due to heart failure (HF) in TAVI patients. Methods A total of 1275 consecutive patients who underwent TAVI at our hospital between 2009 and 2021 were enrolled in this study (mean age 81.4±5.6 years, 51.8% male). The primary endpoint was defined as two-year all-cause death after TAVI. The second endpoints included cardiovascular (CV) death and HF related hospitalization after TAVI. Results Among the 1275 patients following TAVI, 297 (23.3%) patients received PPI, with 134 receiving PPI before TAVI and 163 receiving PPI after TAVI. The patients were categorized into two groups: no PPI group (n=978) and PPI group (n=297). Compared to patients without PPI, patients who received PPI were more likely to be male (60.9% vs. 49.1%, P<0.001), higher prevalence of atrial fibrillation (51.2% vs. 43.3%, P=0.016), coronary artery disease (61.6% vs. 53.8%, P=0.017), use aldosterone receptor antagonists (MRAs, 25.3% vs. 15.2%, P<0.001), and lower left ventricular ejection fraction (LVEF, 54.9±13.1% vs. 57.5±11.4%, P<0.001). There were no significant differences in all-cause mortality (16.6% vs. 18.5%), CV mortality (11.3% vs. 13.5%), as well as HF hospitalization rate (18.5% vs, 21.2%) between the two groups (P>0.05). In this cohort, 1012 (79.4%) TAVI patients had a preserved LVEF (≥50%), 122 (9.6%) had a mildly reduced LVEF (41-49%), and 141 (11.1%) had reduced LVEF (≤40%). Their primary and secondary outcomes were similar among LVEF subgroups (all P>0.05). In the subgroup of reduced LVEF, the HF related hospitalization rate after TAVI was significantly higher in TAVI patients with PPI compared to those without PPI (30.6% vs. 13.0%, P=0.003). Multivariable Cox regression models demonstrated a 3-fold increased risk of HF related hospitalization in TAVI patients with PPI in comparison to those without PPI in the subgroup of LVEF≤40% (HR 3.057, 95% CI 1.311-7.130, P=0.010) after adjusting for age, sex, TAVI approach, atrial fibrillation, coronary artery disease, and the use of MRAs. Conclusion All-cause mortality and CV mortality are similar between TAVI patients with and without PPI. However, in the subset of TAVI patients with reduced LVEF (≤40%), PPI is associated with an increased risk of HF hospitalization. Efforts are thus needed to reduce the risk of HF hospitalization in these patients.

Double product derived from exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) in patients with a history of breast cancer and radiotherapy (RXT) exposure and MACE

Abstract Background Breast cancer survivorship has markedly improved in the last two decades due to improved therapies. Among these, adjuvant chest radiotherapy stands out as an integral part of the current treatment. Chest radiotherapy can trigger accelerated atherosclerosis, which, coupled with cardiovascular (CV) risk factors common to this population, can lead to increased rates of coronary artery disease (CAD). ESC 2022 guidelines have established both Exercise Stress Echocardiography (ESE) and Dobutamine Stress Echocardiography (DSE) as cost-efficient and reliable tools for screening this patient population. Recommendations include ESE or DSE 5 years after radiotherapy as a screening tool. Double product (DP), an index common to both tests, parallels myocardial oxygen consumption. It has been used to predict major adverse cardiovascular events (MACE) in other cohorts. Purpose We sought to evaluate if DP could be used as a prognostic indicator for MACE (myocardial infarction, stroke, cardiovascular death, and heart failure) in this population. Methods Breast cancer patients treated with adjuvant radiotherapy from 2000 to 2022 were included. ESE or DSE was done after a mean of 5.4 years (1Q-2.2, 3Q-7.5) post-radiotherapy. Uni and multivariable adjusted Cox regression models were performed to evaluate the association between DP quartiles achieved and the risk of MACE in DSE and ESE groups. MACE-free survival among different quartiles was plotted with the Kaplan Meier method. Results 696 patients were included, with a mean age of 65 (SD 10.0) and 72 (SD 9.4) in ESE and DSE respectively. 61% of patients had ESE. In ESE, we observed increased rates of MACE in the 1st quartile when compared to the other quartiles (Figure 1a). On the other hand, univariate and multivariate Cox models established that for every increase of 1000 units of DP achieved during ESE, there is a risk-reduction of 9% [HR=0.91 (0.86-0.95); p=<0.01] in the future incidence of MACE, thus establishing DP as a protective marker. Additionally, advanced age was shown to be a major risk factor as well [HR=4.58 (1.91-10.9); p=<0.01]. In the DSE cohort however, the development of MACE was equally distributed across DP quartiles even after adjusting for existing comorbidities (Figure 1b). Cox analysis did not establish DP as a prognostic tool in this cohort (Table 1). Conclusion DP is established as an excellent prognostic tool for the detection of MACE in patients who underwent ESE. Patients who achieve higher DP quartiles during these tests have lower future rates of MACE. Regarding DSE, DP is not a good prognostic tool. This could be explained by higher burden of cardiovascular risk factors in this patient population. ESE should be recommended when possible.

Stroke-Heart syndrome: a population-based cohort study and cluster analysis

Abstract Background The onset of acute cardiovascular complications following a stroke, also known as "Stroke-Heart Syndrome", can occur in up to 20% of patients following a stroke. The syndrome remains under-investigated and limited data exists related to the occurrence and impact of the Stroke-Heart Syndrome in an Asian population. Objectives We aimed to investigate the potential impact of the Stroke-Heart Syndrome and its associations in a retrospective population based-cohort study. Methods The analysis included patients with new-onset ischaemic stroke (IS) June 2006 and May 2022 with 5 years’ follow-up. Patients who developed acute cardiovascular complications within 28 days of their index stroke were compared to patients who did not. The association between acute cardiovascular complications and longer term outcomes were evaluated using multivariate Fine-Grey analyses to adjust for competing risk of mortality, and a Cox regression model for all-cause mortality. Inverse probability of treatment weighting was applied prior to analysis. Furthermore, a hierarchical cluster analysis was performed in the cohort of stroke patients with "Stroke-Heart Syndrome", to further evaluate associations between the identified clusters and (i) longer term outcomes, as well as (ii) the development of acute cardiovascular complications. Results A total of 141,118 patients (median age 72.4 (IQR 62.6 to80.8) years; 45.4% female) were included in the analysis, 6,457 of who developed acute cardiovascular complications, and 134,661 of whom did not. At 5 years follow-up, acute cardiovascular complications were associated with a higher risk of developing recurrent ischaemic stroke (Sub-distribution Hazard Ratio [SHR]: 1.20, 95% Confidence Interval [CI]: 0. 1.12-1.28, p= <0.001), haemorrhagic stroke (SHR: 1.15, 95%CI: 1.03-1.28, p=0.014), myocardial infarction (SHR: 1.53, 95%CI: 1.39-1.69, p=<0.001), and cardiovascular death (SHR: 1.57, 95%CI: 1.45-1.71, p=<0.001) as well as all-cause mortality (HR: 1.07, 95%CI: 1.07-1.07, p=<0.001). A total of 4 clusters were identified in the cluster analysis. Compared to Cluster 3, the other Clusters were associated with increased 5-year risk of myocardial infarction, cardiovascular death and all-cause mortality (p=<0.001). In this cohort, compared to Cluster 2, the other clusters had an increased risk of developing acute cardiovascular complications, in particular acute ischaemic heart disease and acute heart failure (p=<0.001). Cluster 3 tended to be younger with fewer comorbidities and prescribed medications. Over 90% of the patients in Cluster 2 were aged over 75 (with 43% aged 85 years or over). Conclusion Stroke-Heart Syndrome was associated with long-term adverse cardiovascular events in this Asian cohort of ischaemic stroke patients.

Long-term outcomes among out-of-hospital cardiac arrest survivors with reversible vs. non-reversible causes.

A reversible cause of out-of-hospital cardiac arrest (OHCA) is vaguely defined in international guidelines as an identifiable transient or potentially correctable condition. However, studies evaluating long-term outcomes of patients experiencing OHCA due to reversible and non-reversible causes are lacking. We aimed to determine differences in long-term outcomes in OHCA survivors according to different aetiology. From the British Columbia Cardiac Arrest registry, adults with non-traumatic OHCA (2009-2016) surviving to hospital discharge were identified. Patients were categorized by OHCA aetiology combining reversibility and underlying ischaemic aetiology. The primary outcome was a composite of all-cause mortality, recurrent OHCA, or re-hospitalization for sudden cardiac arrest or ventricular arrhythmias. Using the Kaplan-Meier method and multivariable Cox regression models, we compared the risk of the composite outcome according to different OHCA aetiology. Of 1325 OHCA hospital-discharge survivors (median age 62.8 years, 77.9% male), 431 (32.5%) had reversible ischaemic, 415 (31.3%), non-reversible ischaemic, 99 (7.5%), reversible non-ischaemic, and 380 (28.7%), non-reversible non-ischaemic aetiologies. At 3 years post discharge, the Kaplan-Meier event-free rate was highest in patients with a reversible ischaemic aetiology [91%, 95% confidence interval (CI) 87-94%], and lowest in those with a reversible non-ischaemic aetiology (62%, 95% CI 51-72%). In multivariate analyses, compared with non-reversible non-ischaemic cause, reversible ischaemic cause was associated with a significantly lower hazard ratio (HR; 0.52, 95% CI 0.33-0.81), reversible non-ischaemic cause with a significantly higher HR (1.53, 95% CI 1.03-2.32), and non-reversible ischaemic cause with a non-significant HR (0.92, 95% CI 0.64-1.33) for the composite outcome. Compared to other aetiologies, the presence of a reversible ischaemic cause is associated with improved long-term OHCA outcomes.

Remnant cholesterol predicts major cardiovascular events in coronary artery disease patients with NAFLD

Abstract Remnant cholesterol has attracted interest as a marker of cardiovascular event risk. The power of remnant cholesterol to predict major cardiovascular events (MACE) in patients with non-alcoholic fatty liver disease (NAFLD) is unclear and is addressed in the present study. We enrolled a high-risk cohort of 913 patients with coronary artery disease (CAD). NAFLD was diagnosed using the validated fatty liver index (FLI). Prospectively, MACE including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a mean follow-up period of 9.5±5.2 years. At baseline, remnant cholesterol was significantly higher in patients with NAFLD (n=419) than in patients who did not have NAFLD (30±28 mg/dl vs. 18±17 mg/dl; p<0.001). During follow-up, 379 of our patients suffered MACE. Remnant cholesterol in Cox regression models adjusting for age, sex, hypertension, smoking, diabetes mellitus, body mass index and LDL cholesterol independently predicted MACE in the total study population (standardized adjusted HR 1.18 [1.08-1.30], p<0.001), and both in patients with NAFLD as well as in those who did not have NAFLD (standardized adjusted HRs 1.19 [1.05-1.35], p=0.006 and 1.24 [1.03-1.49], p=0.023, respectively). From our data we conclude that remnant cholesterol is a predictor of MACE in patients with CAD with and without NAFLD.

Percutaneous coronary intervention of in-stent restenosis: A three-arm analysis from SWEDEHEART

Abstract Background During the last decades, there have been substantial improvements in treatment techniques for percutaneous coronary intervention (PCI). Yet, in-stent restenosis (ISR) continues to pose significant challenges as they account for 10% of all PCI cases and are associated with worse outcome compared to de-novo lesions. When assessing ISR with PCI, balloon angioplasty with drug-coated balloons (DCB) is frequently used. Purpose Despite frequent use of DCB, there is a lack of long-term data ensuring the safety of DCB for ISR as no randomized trial has extended beyond a 3-year follow-up. We aimed to study the long-term outcome and conducted a nationwide three-arm investigation on the outcome of ISR, comparing DCB with drug-eluting stents (DES) or plain old balloon angioplasty (POBA) within a 5-year follow-up. Methods We conducted a nationwide analysis using the SWEDEHEART (Swedish Web System for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry. The SWEDEHEART registry was used to include any ISR undergoing coronary angiography between June 11, 2013, and December 31, 2020. Target lesion revascularization (TLR) was the primary outcome. Secondary outcomes included all-cause mortality, myocardial infarction, and any PCI. The outcomes were analysed using a multivariable Cox regression model. Results A total of 9304 segments from 7987 patients were eligible. Compared to POBA, the use of DCB was associated with lower rates of TLR, hazard ratio (HR) 0.62 (95% confidence interval [CI]: 0.50-0.78), all-cause mortality, HR 0.60 (95% CI: 0.50-0.72), and any PCI, HR 0.78 (95% CI: 0.66-0.93). No difference was observed for myocardial infarction. Compared to DES, the use of DCB was associated with higher rates of TLR, HR 1.24 (95% CI: 1.08-1.42). No difference was observed for all-cause mortality, cardiovascular mortality, myocardial infarction, or any PCI. Conclusions In this nationwide analysis including any ISR undergoing PCI, the use of DCB showed superior outcomes compared to POBA within 5 years but higher rates of repeat revascularizations compared to DES. While DES demonstrated lower TLR rates than DCB, the lack of mortality differences indicates that DCB is a viable option, particularly for patients where DES might not be suitable, but that DES should be considered as the first line strategy.Table 1.5-year outcomeFigure 1.Kaplan-Meier curves

Incidence of acute cardiovascular hospitalizations and association with hemodynamic biomarkers in cancer patients treated with Immune Checkpoint Inhibitor therapy

Abstract Background/Introduction Immune checkpoint inhibitors (ICI) have significantly improved outcomes for several malignancies. Despite these benefits, patients with cancer face an increased risk for the development of cardiovascular disease due to mutual risk factors, similar biological mechanisms, as well as cardiotoxic side effects of therapy. Therefore, there is a pressing need for effective risk stratification strategies. Purpose This study aimed to explore the association between NT-proBNP levels and the risk of acute cardiovascular hospitalizations and death in patients who receive ICI. Methods We used electronic health records of patients treated with ICI who had available baseline NT-proBNP levels at our hospital, a tertiary academic center, between January 2017 and July 2022. The primary outcome of interest was the composite of acute cardiovascular hospitalization or death. The associations between NT-proBNP and outcomes were analyzed using cox regression models adjusted for age, sex, serum creatinine, diabetes, HF, CAD, hypertension, AF, LDL-C, and CRP. Results In total, 550 patients (35% female, median age 65 yrs) were included in the study. The median NT-proBNP levels were 272 pg/mL (IQR 102-742 pg/mL) and 388 (71%) patients had NT-proBNP levels ≥125 pg/mL. During a median FU of 67 weeks, 190 patients (35%) died, and 103 CV hospitalizations occurred in 76 patients (14%). Compared with patients with NT-proBNP concentrations <125, those with NT-proBNP concentrations ≥125 pg/ml had significantly higher event rates of the combined endpoint (12-Month KM event rates: 38% vs 21%, P<0.001). After multivariable adjustment, NT-proBNP remained independently associated with an increased risk of cardiovascular hospitalization and death (Adjusted HR for 1-SD increase in log-transformed biomarker 1.64, 95% CI 1.24 to 2.14; Figure). Conclusion These data highlight NT-proBNP levels as a valuable marker for identifying patients at increased risk of cardiovascular complications during ICI therapy.

Relapse of infective endocarditis after cardiac implantable electronic device removal compared to a conservative strategy

Abstract Background According to current guidelines, complete removal of cardiac implantable electronic device (CIED) should be considered in patients with valvular infective endocarditis (IE), accounting for the identified pathogen and need for valve surgery (Class IIa recommendation). Unselected longitudinal data are needed to assess this strategy. Purpose To examine IE readmission after IE discharge according to status of CIED removal in patients with conservatively treated IE. Methods Using Danish nationwide registries, we identified patients aged ≥18 years with first-time IE from 2010-2021. We included patients with conservatively treated IE and a CIED, who were alive at IE discharge. Patients who underwent CIED removal during IE admission were compared to those without removal, examining the study outcome of IE readmission within six months after IE discharge. An initial blanking period of 14 days was applied after IE discharge. The Aalen-Johanson estimator and multivariable Cox regression models were used to determine cumulative incidences and adjusted hazard ratios (HRs) of IE readmission according to status of CIED removal, respectively. Results Among 6,843 patients with first-time IE, 5,731 (83.7%) were conservatively treated. Of these, 1,201 (21.0%) had a CIED, of which 205 (17.1%) died during IE admission. Thus, the final study population comprised 996 patients alive at IE discharge. The median age of the study population was 75.5 years (interquartile range [IQR]: 67.9-82.0), and 753 (75.6%) were males. In total, 574 (57.6%) patients underwent CIED removal during IE admission. Patients who underwent CIED removal were younger, compared to patients without CIED removal, 73.1 years (IQR: 65.7-79.1) versus 79.0 years (IQR: 71.3-85.1), respectively. The six-month cumulative incidence of IE readmission was 2.0% (95% confidence interval [CI]: 1.1-3.5%) in patients who underwent CIED removal versus 6.1% (95% CI: 4.0-8.9%) in patients without CIED removal (P-value=0.001) (Figure 1). CIED removal was associated with a significantly lower six-month rate of IE readmission, compared to no CIED removal (HR: 0.36 [95% CI: 0.17-0.77]). Relapse bacteraemia (including IE) with the same microorganism as first-time IE occurred in 2.2% of patients who underwent CIED removal and in 5.4% of patients without CIED removal. Staphylococcus aureus was the most common microorganism in 33.3% of patients with relapse bacteraemia who underwent CIED removal. Conclusions In this nationwide study, the six-month rate of infective endocarditis (IE) readmission was three-fold lower in patients who underwent cardiac implantable electronic device (CIED) removal, compared to patients without CIED removal. The current findings suggest that CIED removal is associated with lower risk of relapse of IE in patients with conservatively treated IE. These results are in line with current guideline recommendations. However, more randomized clinical trial data are needed.

Body weight variability as a predictor of cardiovascular outcomes in type 1 diabetes: A nationwide cohort study.

Intraindividual body weight variability (BWV), that is, the degree of weight fluctuations over time, is associated with an increased risk of cardiovascular diseases (CVDs) in multiple settings. The impact of BWV on cardiovascular risk in type 1 diabetes (T1D) remains unclear, despite the issues relative to weight management in individuals with this condition. Using data from the Swedish National Diabetes Register, we identified individuals with T1D and without CVD at baseline with at least three measurements of body weight taken over three consecutive years. We estimated BWV as quartiles of the standard deviation of weight measures and explored its longitudinal association with the incidence of CVD during a 12.7 ± 4.6 year follow-up through adjusted Cox regression models. The primary endpoint was the composite of nonfatal myocardial infarction, nonfatal stroke and all-cause mortality. We modelled the function of risk in relation to the magnitude of BWV, testing also whether weight trends, that is, increasing, stable or decreasing, age, sex and glycaemic control modified the association between BWV and the outcome. Among the 36 333 individuals with T1D in the register, we identified 19 373 individuals with at least three measures of body weight and without CVD at baseline. Participants with the highest BWV had a 42% increased risk of reaching the primary endpoint compared to those with the lowest BWV (hazard ratio [HR] = 1.42, 95% confidence interval [CI]: 1.24-1.62). In addition, high BWV was significantly associated with a 51% increased risk of all-cause mortality (HR = 1.51, 95% CI: 1.28-1.78), a 37% increased risk of peripheral artery disease (HR = 1.37, 95% CI: 1.06-1.77) and a 55% increased risk of hospitalization for heart failure (HR = 1.55, 95% CI: 1.20-2.01). BWV showed a quasi-linear association with the primary endpoint. No interaction was observed when comparing subgroups for weight trends, sex or degree of glycaemic control. In the subgroup of elderly individuals, the association of BWV with the primary endpoint was no longer significant. High BWV is associated with an increased risk of CVD and all-cause mortality in individuals with T1D, independently of canonical risk factors. Weight trends, sex and glycaemic control do not modify such association while older age attenuates it.

Application of anticoagulants in the perioperative period of pci for patients with a history of atrial fibrillation and NSTEMI: a real-world, large multicenter retrospective clinical study

Abstract Backgrounds The optimal management for patients with atrial fibrillation (AF) and concomitant coronary artery disease (CAD) remains unclear, particularly regarding anticoagulants use and ischemia-bleeding balance risks. This study aims to investigate the impact of perioperative anticoagulant use on patients with AF and acute non-ST-segment elevation myocardial infarction (NSTEMI). Methods Data for this study were obtained from a retrospective cohort of patients admitted to and discharged from 72 secondary and tertiary hospitals from 2010 to 2023. A total of 150,530 patients were enrolled, including 74,373 NSTEMI patients. Patients were divided into anticoagulants and non-anticoagulants groups. A total of 1,358 patients were included in the non-anticoagulant group, and 3,541 patients were included in the anticoagulant group. Patients in each group were one-to-one matched based on propensity scores using the nearest available pair matching (PSM) method with a caliper width equal to 0.01. The primary endpoints were major adverse cardiovascular and cerebrovascular adverse events (MACCE), including cardiovascular death, recurrent myocardial infarction, and stroke. Secondary endpoints included cardiovascular death, recurrent myocardial infarction, BARC type 3 bleeding, and cerebral hemorrhage. Follow-up time points were set at 1 month,3 months, and 6 months. Multivariate Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Results After PSM matching, each group consisted of 809 patients. The anticoagulant group had a higher proportion of males, a higher prevalence of patients with a history of Percutaneous Coronary Intervention, and hyperlipidemia, while proportions of patients with Killips classification of III/IV and history of chronic kidney disease were lower. Anticoagulant use during the perioperative period significantly reduced the occurrence of MACCE at the primary endpoint at 1 month (aHR 0.57; P < 0.001), 3 months (aHR 0.57; P = 0.023), and 6 months (aHR 0.57; P < 0.001). At the secondary endpoint, anticoagulants use was associated with a lower incidence of cardiogenic death at 1 month,3 months, and 6 months (aHR 0.55; P <0.001), (aHR 0.55; P <0.001), (aHR 0.56; P <0.001), lower risk of myocardial infarction recurrence at 3 months and 6 months (aHR 0.47; P = 0.02), (aHR 0.44; P <0.001), without increasing the risk of bleeding events, including BARC type 3 bleeding and cerebral hemorrhage. Conclusion Perioperative anticoagulant use during PCI can reduce the occurrence of cardiac death, myocardial infarction, and stroke recurrence within 6 months post-surgery without increasing bleeding events in AF and NSTEMI patients. Therefore, for patients with AF, it is recommended to consider combining anticoagulant therapy with dual antiplatelet therapy during the perioperative period, if no contraindications.

Octogenarians, nonagenarians and centenarians with myocardial infarction over time in Sweden

Abstract Background The aim of this study was to evaluate temporal changes in baseline characteristics, in-hospital management and medication at discharge in very elderly with myocardial infarction (MI). Methods Between 2003 and 2016, we included all consecutive patients 80 years or-older, with a MI, included in the nationwide SWEDEHEART registry. The study period was divided into seven equal admission periods. Outcomes included major adverse cardiac and cerebrovascular events (MACCE, including death, MI or stroke) and net adverse cardiac and cerebrovascular events (NACCE, including MACCE and bleeding). All patients had complete 1-year follow up. To evaluate any potential associations between in-hospital management/medications at discharge and clinical outcomes, we adjusted for baseline characteristics and clinical presentation using multivariable Cox regression models. Results We included 85,054 patients. Over time, the proportion of patients with comorbidities such as hypertension, diabetes mellitus, prior percutaneous coronary intervention and a previous bleeding significantly increased but patients were less likely to have a prior MI and previous heart failure (HF). On arrival, the proportion of patients with acute HF declined. Invasive management significantly increased over time as well as prescription of evidence-based medication at discharge. At 1 year, the cumulative rate of MACCE and NACCE significantly decreased. We found a significantly lower risk for death, MI and stroke and a higher risk for bleeding. The observed differences remained significant after adjustment. We found no significant interaction between infarct type and outcomes. Conclusion During the study period, the prognosis in very elderly patients with MI substantially improved. In a population that has been excluded from randomised control trials, implementation of evidence-based management for patients with a MI, seemed to be associated with the lower risk for MACCE and NACCE over time.Cumulative rate of MACCE

The gut-microbiome derived phenylacetylglutamine predicts adverse events in patients with acute coronary syndromes

Abstract Background and Introduction The gut microbiota-derived metabolite phenylacetylglutamine (PAG) is associated with incident cardiovascular events(1). Acute coronary syndromes (ACS) present a major health challenge, especially as population ages(2). Data from our group show increased PAG levels during aging in humans. However, the predictive potential of PAG for mortality and major adverse cardiovascular events (MACE) in patients (pts) with ACS is unknown. Purpose Here, we investigated the potential of PAG to predict ischemic and fatal events in pts with acute coronary syndromes (ACS). We also compared the predictive potential of PAG to another relevant gut-microbiota derived metabolite involved in CVD, namely Trimethylaminoxyde, (TMAO), and we evaluated their cumulative risk potential. Methods A total of 1’848 patients were enrolled in Cohort I of the SPUM-ACS study – a multi-center prospective ACS cohort study from Switzerland. Overall survival and incident MACE after 1 year follow-up were analyzed using Kaplan-Meier (KM) estimates and compared by log-rank test after patient stratification into PAG tertiles. Uni- and multivariable Cox-regression models were fit to calculate the hazard ratios for 1-year MACE in a crude model and adjusted model (adjusted for established confounders). Healthy controls served as additional controls. PAG plasma levels were quantified using LC-HRMS. Results The median PAG plasma level in the healthy control group was 1.76µM, whereas for the whole ACS patient population it was 1.92µM (Table 1). Pts in the third PAG tertile had a two times higher MACE rate and a four times higher mortality rate compared to pts in the first PAG tertile (p<0.001). (Table 2). PAG levels were significantly higher in pts who presented with MACE (2.63µM) or died (3.1µM) within the 1-year follow-up compared to the healthy control subjects (p<0.0001) (Figure 1A). Spearman correlation analysis revealed that plasma PAG levels were positively associated with age (r=0.43, p<0.0001), while a negative association with eGFR was observed (r=-0.51, p<0.0001) (Figure 1B). KM estimates indicated that pts in the highest PAG tertile had significantly higher 1-year MACE risk relative to those with low levels (Figure 1C; p<0.001 log rank). Following multivariable adjustment, PAG remained an independent predictor for MACE at 1-year follow-up with a hazard ratio (HR) of 1.8 (95% CI, 1.1–3.2, p=0.048) (Figure 1D). KM estimates of both, high levels of PAG and high levels of TMAO together, indicate that the combination of these two detrimental metabolites leads to an even higher risk of 1-year MACE relative to lower levels (Figure 1E). Conclusion PAG is a novel and independent predictor of adverse outcomes in patients with ACS. This study indicates the role of the gut-microbiome and its metabolites in predicting ischemic and fatal outcomes of pts with established CVD.

Prognostic value of circulating glypican-4 in patients with chronic heart failure with reduced ejection fraction

Abstract Background Chronic heart failure is one of the leading causes of hospitalization and mortality worldwide, with an ever-increasing prevalence. Glypican-4 (GPC4) is a cell surface protein part of the endothelial glycocalyx which is actively released into the circulation in the context of ischemia, inflammation, neurohumoral activity, and shear stress. The current literature on the association between circulating GPC4 and heart failure is limited and its prognostic value on top of established risk markers in chronic heart failure is unknown. Purpose In the present study, we aim to investigate the prognostic value of circulating GPC4 on clinical outcomes in a contemporary cohort of patients with stable chronic heart failure with reduced ejection fraction (HFrEF). Methods Symptomatic outpatients with stable chronic HFrEF were consecutively enrolled in a prospective cohort study. Circulating serum GPC4 levels were assessed using an enzyme-linked immunosorbent at baseline. Patient outcomes were retrieved from medical and health insurance records. Results We enrolled 205 patients with a median (interquartile range) age of 66 (59-74) years, with 22% females. Median left ventricular ejection fraction (LVEF) was 37 (30-43)%, median estimated glomerular filtration rate (eGFR) was 64 (48-80) ml/min/1,73 m2, median N-terminal pro-brain natriuretic peptide (NT-proBNP) was 964 (336-2173) pg/ml, median interleukin 6 (IL6) was 4.7 (3.2-7.9) pg/ml, and median GPC4 was 1553 (1034-1950) pg/ml. During a median follow-up of 4.7 (4.0-5.3) years, 46 patients (22%) were hospitalized due to worsening heart failure (WHF), 18 patients (9%) died of cardiovascular (CV) cause, and 58 patients (28%) died of any cause. In univariate Cox-regression, serum GPC4 levels predicted WHF (HR 1.57, 95%CI 1.29-1.92, p<0.001), CV death (HR 2.07, 95%CI 1.56-2.74, p<0.001), and all-cause mortality (HR 1.93, 95%CI 1.59-2.34, p<0.001). The association between serum GPC4 levels and both, CV death (HR 1.69, 95%CI 1.04-2.86, p=0.048) and all-cause mortality (HR 1.56, 95%CI 1.14-2.14, p=0.006) remained significant in a multivariable Cox-regression model adjusted for age, sex, eGFR, IL6, NT-proBNP, and LVEF. Conclusion In patients with stable chronic HFrEF, circulating GPC4 is significantly associated with cardiovascular outcome and is an independent predictor of all-cause mortality. The potential prognostic value in clinical routine of GPC4 should be addressed in prospective studies.

Difference in long-term mortality after takotsubo syndrome. The role of gender, socioeconomic profile, and psychological distress

Abstract Background While Takotsubo Syndrome is less common in men, their mortality rates surpass those of women. The influence of socioeconomic factors and psychological distress, remains unexplored in this context. The aim of the study was: 1) to investigate gender differences in socioeconomic profile, and psychological distress in patients with incident Takotsubo Syndrome. And 2) to investigate gender differences in survival in patients discharged alive after incident takotsubo syndrome when taking into account differences in socioeconomic profile and psychological distress. Method A nationwide cohort study using the Danish national registers was performed. All patients discharged alive from Danish hospitals with an incident Takotsubo Syndrome diagnosis between 2008 and 2018 were eligible. Socioeconomic factors covering marital status, cohabitation status, labour market attachment, highest formal education and family income, and psychological distress was explored, and compared. Multivariable Cox-regression models were performed to assess the mortality risk. Results A total of 662 patients with Takotsubo Syndrome were discharged alive from Danish hospitals. Of those, 79 (11.9%) were men with a median age of 67 years (IQR 62-77). Men with Takotsubo Syndrome were socioeconomically disadvantaged compared to their women counterparts, and this disparity was also reflected in mortality rates. Secondly, mortality within three years after an incident Takotsubo Syndrome diagnose was higher among men than women, HR 2.19, 95%CI 1.04-4.61, most pronounced among men with a low family income, HR 2.08, 95% CI 1.03-4.18, and increase in comorbidity score, HR 1.23, 95% CI 1.06-1.43. Conclusion Results unveiled notable gender differences in the socioeconomic profile of individuals diagnosed with TS. Furthermore, the identified gender disparities in mortality can be attributed to socioeconomic and sociodemographic factors, the use of psychiatric medication as an indicator of psychological distress, and a greater comorbidity burden.Survival according to socioeconomy

Association between weight-adjusted waist index with incident stroke in the elderly with hypertension: a cohort study

The objective of this study was to ascertain the relationship between the weight-adjusted waist index (WWI) and the risk of stroke in an elderly hypertensive population, a relationship that has not been previously elucidated. The Cox regression model was employed to assess the correlation between baseline WWI measurements and the incidence of stroke. To further elucidate the shape of the association between baseline WWI and stroke, restricted cubic splines were employed. Furthermore, subgroup analyses and interaction tests were carried out to investigate potential heterogeneities. Our study cohort comprised 4962 hypertensive individuals aged 60 years or older with no prior history of stroke. Over a median follow-up of 3.2 years, we found 547 new-onset stroke cases. After adjusting for confounding variables, the Cox regression analysis revealed a positive association between baseline WWI and the risk of stroke, with hazard ratios (HRs) escalating progressively as WWI values increased. When compared to the lowest quartile of WWI, the highest quartile demonstrated an HR of 1.87 (95% CI, 1.44–2.42) for stroke. Subgroup analyses confirmed the consistency of this relationship across different demographic and clinical strata. The study findings indicate that an elevated WWI is significantly related with a higher risk of new-onset stroke among elderly patients with hypertension. These results underscore the importance of WWI as a potential risk stratification tool. To confirm these results and explore the causal mechanisms behind the observed correlation, more study is necessary.

Preoperative Briganti Nomogram Score and Risk of Prostate Cancer Progression After Robotic Surgery Beyond EAU Risk Categories

Background and Objectives: We sought to investigate whether the 2012 Briganti nomogram may represent a potential prognostic factor of prostate cancer (PCa) progression after surgical treatment beyond European Association of Urology (EAU) risk categories. Materials and Methods: From January 2013 to December 2021, data on PCa patients treated with robot-assisted radical prostatectomy at a single tertiary referral center were extracted. The 2012 version of the Briganti nomogram assessing the risk of pelvic lymph node invasion was used. Here, the nomogram score was evaluated both as a continuous and a categorical variable. The association between variables and disease progression after surgery was evaluated through Cox regression models. Results: Overall, 1047 patients were identified. According to the EAU classification system, 297 (28.4%) patients were low-risk, 527 (50.3%) intermediate-risk, and 223 (21.3%) high-risk. The median (interquartile range) 2012 Briganti nomogram score within the investigated population was 3% (2–8%). Median (95% Confidence Interval [CI]) follow-up was 95 (91.9–112.4) months. Disease progression occurred in 237 (22.6%) patients, who were more likely to have an increasing 2012 Briganti nomogram score (Hazard Ratio [HR]: 1.03; 95%CI: 1.01–1.81; p = 0.015), independently of unfavorable issues at clinical presentation. Moreover, the nomogram score stratified according to tertiles (<3% vs. 3–8% vs. ≥8%) hold significance beyond EAU risk categories: accordingly, the risk of disease progression increased as the score increased from the first (reference) to the second (HR: 1.50; 95%CI: 1.67–3.72; p < 0.001) up to the third (HR: 3.26; 95%CI: 2.26–4.72; p < 0.001) tertile. Conclusions: Beyond EAU risk categories, the 2012 Briganti nomogram represented an independent predictor of PCa progression after surgery. Likewise, as the nomogram score increased so patients were more likely to experience disease progression. Accordingly, it may allow further stratification of patients within each risk category to modulate appropriate treatment paradigms.

Delivery mode and subsequent birth rate: A nationwide register-based analysis in Finland.

The study aimed to calculate the subsequent birth rate for different delivery modes, comparing them with spontaneous vaginal deliveries, using a comprehensive nationwide high-quality registry. Data from the National Medical Birth Register (MBR) were used to evaluate the birth rate after different delivery modes. All first deliveries for a mother during the years 2004 to 2016 were included. For these women, all second pregnancies from the MBR during the years 2004 to 2018 were retrieved and combined with the data of the first deliveries. A Cox regression model was used to evaluate the risk for the second pregnancy after giving birth the first time. The results were interpreted with adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). A total of 375 619 women with a first and second pregnancy leading to birth were included in this study. Of these, a total of 50 579 women underwent assisted vaginal delivery, 50 429 had an unplanned cesarean section (CS), 22 021 had elective CS, and 252 593 had spontaneous vaginal delivery as a mode of delivery in their first pregnancy. Women with assisted vaginal delivery (aHR, 1.23 [CI, 1.21-1.24]) and unplanned CS (aHR, 1.03 [CI, 1.02-1.05]) had higher birth rates after the first birth, and women with elective CS as a mode of delivery had lower birth rates (aHR, 0.86 [CI, 0.84-0.88]) when compared with women who had spontaneous vaginal delivery. The findings of this study indicate that the CS operation itself is not the only cause of the observed lower birth rate; rather, there are underlying factors that have a greater impact on birth rates.

Identification of lncRNA dual targeting PD-L1 and PD-L2 as a novel prognostic predictor for gastric cancer.

Although breakthroughs have been achieved in gastric cancer (GC) therapy with immune checkpoint inhibitors (ICIs) targeting programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1), the acquisition of high response rate remains a huge challenge for clinicians. It is imperative to identify novel biomarkers for predicting response to immunotherapy and explore alternative therapeutic strategy for GC. The transcriptomic profiles and clinical information of GC patients from The Cancer Genome Atlas (TCGA)-stomach adenocarcinoma (STAD) database was used to screen differentially expressed lncRNAs between the tumor specimens and the paracancerous tissues. The TargetScan, miRDB and miRcode database were then utilized to construct competing endogenous RNA (ceRNA) networks and identify pivotal lncRNAs. An independent dataset from GEO (GSE70880) and 23 pairs of GC specimens of our cohort were subsequently performed for external validity. The relationship between clinical variables and gene expression were evaluated by Kruskal-wallis test and Wilcoxon signed-rank. The prognostic value of the candidate genes was assessed using Kaplan-Meier analysis and Cox regression models. CIBERSORT and Gene set enrichment analysis (GSEA) were used to determine immune cell infiltration. Gastric adenocarcinoma AGS cells and human embryonic kidney 293T (HEK293T) cells with knockdown of LINC01094 were generated by siRNA transfection, followed by detecting the alteration of the target miRNA and PD-L1/PD-L2 by RT-qPCR. Besides, the interaction between lncRNA and the miRNA-PD-L1/PD-L2 axis were verified by dual luciferase reporter assay. Twenty-two intersecting lncRNAs were identified to be PD-L1/PD-L2-related lncRNAs and LINC01094-miR-17-5p-PD-L1/PD-L2 was constructed as a potential ceRNA network. LINC01094 was increased in tumor specimens than adjacent normal samples and was positively associated with advanced tumor stages and EBV and MSI status. Furthermore, LINC01094 expression was an independent risk factor for poor overall survival (OS) in GC patients. CD8+ T cell exhaustion-related genes were enriched in high-LINC01094 tissues and high-PD-L2 group. A strong positive association of LINC01094 expression was established with M2 macrophages, IL-10+ TAM, as well as PD-L1 and PD-L2 levels, therefore a LINC01094-miR-17-5p-IL-10 network was proposed in macrophages. Using the exoRBase database, LINC01094 was assumed in blood exosomes of GC patients The results of knockdown experiments and luciferase reporter assays revealed that LINC01094 interacted with miR-17-5p and served as a miRNA sponge to regulate the expression of PD-L1 and PD-L2. LINC01094 dually regulates the expression of PD-L1 and PD-L2 and shapes the immunosuppressive tumor microenvironment via sponging miR-17-5p. LINC01094 may serve as a potential prognostic predictor and therapeutic target in GC.

Prognostic nomograms for young breast cancer: A retrospective study based on the SEER and METABRIC databases.

Young breast cancer (YBC) is a subset of breast cancer that is often more aggressive, but less is known about its prognosis. In this study, we aimed to generate nomograms to predict the overall survival (OS) and breast cancer-specific survival (BCSS) of YBC patients. Data of women diagnosed with YBC between 2010 and 2020 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The patients were randomly allocated into a training cohort (n = 15,227) and internal validation cohort (n = 6,526) at a 7:3 ratio. With the Cox regression models, significant prognostic factors were identified and used to construct 3-, 5-, and 10-year nomograms of OS and BCSS. Data from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database were used as an external validation cohort (n = 90). We constructed nomograms incorporating 10 prognostic factors for OS and BCSS. These nomograms demonstrated strong predictive accuracy for OS and BCSS in the training cohort, with C-indexes of 0.806 and 0.813, respectively. The calibration curves verified that the nomograms have good prediction accuracy. Decision curve analysis demonstrated their practical clinical value for predicting YBC patient survival rates. Additionally, we provided dynamic nomograms to improve the operability of the results. The risk stratification ability assessment also showed that the OS and BCSS rates of the low-risk group were significantly better than those of the high-risk group. Here, we generated and validated more comprehensive and accurate OS and BCSS nomograms than models previously developed for YBC. These nomograms can help clinicians evaluate patient prognosis and make clinical decisions.