Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.

BACKGROUND: Atherosclerotic cardiovascular disease (ACVD) is worsened by chronic inflammatory diseases. Interleukin receptor antagonists (IL-RAs) and tumour necrosis factor-alpha (TNF) inhibitors have been studied to see if they can prevent cardiovascular events. OBJECTIVES: The purpose of this study was to assess the clinical benefits and harms of IL-RAs and TNF inhibitors in the primary and secondary prevention of ACVD. SEARCH METHODS: The Cochrane Heart Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE (including In-Process & Other Non-Indexed Citations), Ovid Embase, EBSCO CINAHL plus, and clinical trial registries for ongoing and unpublished studies were searched in February 2024. The reference lists of relevant studies, reviews, meta-analyses and health technology reports were searched to identify additional studies. No limitations on language, date of publication or study type were set. SELECTION CRITERIA: RCTs that recruited people with and without pre-existing ACVD, comparing IL-RAs or TNF inhibitors versus placebo or usual care, were selected. The primary outcomes considered were all-cause mortality, myocardial infarction, unstable angina, and adverse events. DATA COLLECTION AND ANALYSIS: Two or more review authors, working independently at each step, selected studies, extracted data, assessed the risk of bias and used GRADE to judge the certainty of evidence. MAIN RESULTS: We included 58 RCTs (22,053 participants; 21,308 analysed), comparing medication efficacy with placebo or usual care. Thirty-four trials focused on primary prevention and 24 on secondary prevention. The interventions included IL-1 RAs (anakinra, canakinumab), IL-6 RA (tocilizumab), TNF-inhibitors (etanercept, infliximab) compared with placebo or usual care. The certainty of evidence was low to very low due to biases and imprecision; all trials had a high risk of bias. Primary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality(RR 0.33, 95% CI 0.01 to 7.58, 1 trial), myocardial infarction (RR 0.71, 95% CI 0.04 to 12.48, I² = 39%, 2 trials), unstable angina (RR 0.24, 95% CI 0.03 to 2.11, I² = 0%, 2 trials), stroke (RR 2.42, 95% CI 0.12 to 50.15; 1 trial), adverse events (RR 0.85, 95% CI 0.59 to 1.22, I² = 54%, 3 trials), or infection (rate ratio 0.84, 95% 0.55 to 1.29, I² = 0%, 4 trials). Evidence is very uncertain about whether anakinra and cankinumab may reduce heart failure (RR 0.21, 95% CI 0.05 to 0.94, I² = 0%, 3 trials). Peripheral vascular disease (PVD) was not reported as an outcome. IL-6 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.68, 95% CI 0.12 to 3.74, I² = 30%, 3 trials), myocardial infarction (RR 0.27, 95% CI 0.04 to1.68, I² = 0%, 3 trials), heart failure (RR 1.02, 95% CI 0.11 to 9.63, I² = 0%, 2 trials), PVD (RR 2.94, 95% CI 0.12 to 71.47, 1 trial), stroke (RR 0.34, 95% CI 0.01 to 8.14, 1 trial), or any infection (rate ratio 1.10, 95% CI: 0.88 to 1.37, I2 = 18%, 5 trials). Adverse events may increase (RR 1.13, 95% CI 1.04 to 1.23, I² = 33%, 5 trials). No trial assessed unstable angina. TNF inhibitors The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.78, 95% CI 0.63 to 4.99, I² = 10%, 3 trials), myocardial infarction (RR 2.61, 95% CI 0.11 to 62.26, 1 trial), stroke (RR 0.46, 95% CI 0.08 to 2.80, I² = 0%; 3 trials), heart failure (RR 0.85, 95% CI 0.06 to 12.76, 1 trial). Adverse events may increase (RR 1.13, 95% CI 1.01 to 1.25, I² = 51%, 13 trials). No trial assessed unstable angina or PVD. Secondary prevention: IL-1 RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 0.94, 95% CI 0.84 to 1.06, I² = 0%, 8 trials), unstable angina (RR 0.88, 95% CI 0.65 to 1.19, I² = 0%, 3 trials), PVD (RR 0.85, 95% CI 0.19 to 3.73, I² = 38%, 3 trials), stroke (RR 0.94, 95% CI 0.74 to 1.2, I² = 0%; 7 trials), heart failure (RR 0.91, 95% 0.5 to 1.65, I² = 0%; 7 trials), or adverse events (RR 0.92, 95% CI 0.78 to 1.09, I² = 3%, 4 trials). There may be little to no difference between the groups in myocardial infarction (RR 0.88, 95% CI 0.0.75 to 1.04, I² = 0%, 6 trials). IL6-RAs The evidence is very uncertain about the effects of the intervention on all-cause mortality (RR 1.09, 95% CI 0.61 to 1.96, I² = 0%, 2 trials), myocardial infarction (RR 0.46, 95% CI 0.07 to 3.04, I² = 45%, 3 trials), unstable angina (RR 0.33, 95% CI 0.01 to 8.02, 1 trial), stroke (RR 1.03, 95% CI 0.07 to 16.25, 1 trial), adverse events (RR 0.89, 95% CI 0.76 to 1.05, I² = 0%, 2 trials), or any infection (rate ratio 0.66, 95% CI 0.32 to 1.36, I² = 0%, 4 trials). No trial assessed PVD or heart failure. TNF inhibitors The evidence is very uncertain about the effect of the intervention on all-cause mortality (RR 1.16, 95% CI 0.69 to 1.95, I² = 47%, 5 trials), heart failure (RR 0.92, 95% 0.75 to 1.14, I² = 0%, 4 trials), or adverse events (RR 1.15, 95% CI 0.84 to 1.56, I² = 32%, 2 trials). No trial assessed myocardial infarction, unstable angina, PVD or stroke. Adverse events may be underestimated and benefits inflated due to inadequate reporting. AUTHORS' CONCLUSIONS: This Cochrane review assessed the benefits and harms of using interleukin-receptor antagonists and tumour necrosis factor inhibitors for primary and secondary prevention of atherosclerotic diseases compared with placebo or usual care. However, the evidence for the predetermined outcomes was deemed low or very low certainty, so there is still a need to determine whether these interventions provide clinical benefits or cause harm from this perspective. In summary, the different biases and imprecision in the included studies limit their external validity and represent a limitation to determining the effectiveness of the intervention for both primary and secondary prevention of ACVD.

Muscle quality and major adverse cardiovascular events in post-acute myocardial infarction: A prospective cohort study.

BACKGROUND & AIMS: Functional muscle quality, as assessed through the muscle quality index (MQI), represents a contemporary method to measure the capacity to generate force. Despite its potential, the prognostic significance of MQI remains uncertain in various clinical conditions, particularly among patients following acute myocardial infarction (AMI). In light of this, our study sought to evaluate the prognostic relevance of MQI concerning major adverse cardiovascular events (MACE) in patients following AMI. METHODS AND RESULTS: This is a secondary analysis of a prospective cohort study that included subjects aged ≥20 years from a Cardiovascular Unit Hospital. Functional muscle quality was estimated using MQI, defined as the ratio of handgrip strength (HGS) to muscle mass (MM) derived from bioelectrical impedance analysis. The outcomes included prolonged length of hospital stay, new adverse cardiovascular events (AMI, stroke and hospital readmission for unstable angina), and cardiovascular mortality. A composite score comprising all adverse events over the 1-year follow-up was calculated and defined as MACE. This study included 163 patients, with a median age of 61 years (IQ: 54-69 years), and the majority consisted of males (76.1%). Individual components of the functional muscle quality (HGS and MM) were not associated with any of the adverse outcomes. Only MQI was associated mortality over the 1-year follow-up. For each increase in MQI, the hazard of mortality decreases: adjusted HR: 0.08 (95% CI 0.01-0.84). CONCLUSION: Functional muscle quality assessed by the MQI may be a valuable clinical predictor of 1-year cardiovascular mortality in patients hospitalized post-AMI.

Prognostic value of a novel artificial intelligence-based coronary CTA-derived ischemia algorithm among patients with normal or abnormal myocardial perfusion.

BACKGROUND: Among patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CTA), downstream positron emission tomography (PET) perfusion imaging can be performed to assess the presence of myocardial ischemia. A novel artificial-intelligence-guided quantitative computed tomography ischemia algorithm (AI-QCTischemia) aims to predict ischemia directly from coronary CTA images. We aimed to study the prognostic value of AI-QCTischemia among patients with obstructive CAD on coronary CTA and normal or abnormal downstream PET perfusion. METHODS: AI-QCTischemia was calculated by blinded analysts among patients from the retrospective coronary CTA cohort at Turku University Hospital, Finland, with obstructive CAD on initial visual reading (diameter stenosis ≥50%) being referred for downstream 15O-H2O-PET adenosine stress perfusion imaging. All coronary arteries with their side branches were assessed by AI-QCTischemia. Absolute stress myocardial blood flow ≤2.3 â€‹ml/g/min in ≥2 adjacent segments was considered abnormal. The primary endpoint was death, myocardial infarction, or unstable angina pectoris. The median follow-up was 6.2 [IQR 4.4-8.3] years. RESULTS: 662 of 768 (86%) patients had conclusive AI-QCTischemia result. In patients with normal 15O-H2O-PET perfusion, an abnormal AI-QCTischemia result (n â€‹= â€‹147/331) vs. normal AI-QCTischemia result (n â€‹= â€‹184/331) was associated with a significantly higher crude and adjusted rates of the primary endpoint (adjusted HR 2.47, 95% CI 1.17-5.21, p â€‹= â€‹0.018). This did not pertain to patients with abnormal 15O-H2O-PET perfusion (abnormal AI-QCTischemia result (n â€‹= â€‹269/331) vs. normal AI-QCTischemia result (n â€‹= â€‹62/331); adjusted HR 1.09, 95% CI 0.58-2.02, p â€‹= â€‹0.794) (p-interaction â€‹= â€‹0.039). CONCLUSION: Among patients with obstructive CAD on coronary CTA referred for downstream 15O-H2O-PET perfusion imaging, AI-QCTischemia showed incremental prognostic value among patients with preserved perfusion by 15O-H2O-PET imaging, but not among those with reduced perfusion.

High-Risk Percutaneous Coronary Intervention of Native Coronary Arteries Without Mechanical Circulatory Support in Acute Coronary Syndrome Without Cardiogenic Shock.

Widespread utilization of mechanical circulatory support (MCS) for high-risk percutaneous coronary intervention (PCI) remains controversial, with a lack of randomized supporting evidence and associated risk of device-related complications. We investigated whether high-risk PCI of native coronary arteries without elective MCS in patients with acute coronary syndrome (ACS) is safe and feasible. We performed a single-center, retrospective analysis for ACS patients meeting American College of Cardiology high-risk criteria: unprotected left main disease, last remaining conduit, ejection fraction <35%, 3-vessel coronary artery disease, severe aortic stenosis, or severe mitral regurgitation. Patients with cardiogenic shock and those undergoing PCI of the bypass grafts were excluded. Major in-hospital and 30-day cardiovascular outcomes were assessed. From 2003 through 2018, 499 patients (847 lesions) with unstable angina pectoris (UAP), 1218 patients (1807 lesions) with non-ST-elevation myocardial infarction (NSTEMI), and 868 patients (1260 lesions) with ST-segment elevation myocardial infarction (STEMI) underwent high-risk PCI. Procedural success was achieved in 97.2% of UAP, 98.3% of NSTEMI, and 96.6% of STEMI patients. In-hospital and 30-day all-cause mortality were as follows: UAP, 2%; NSTEMI, 2.1%; and STEMI 4.7%. Bailout intra-aortic balloon pump was required in 1.6% of UAP, 3.1% of NSTEMI, and 10.3% of STEMI patients. Major complications for UAP, NSTEMI, and STEMI were, respectively: target lesion revascularization (2.3%, 1.4%, and 1.5%), stroke or transient ischemic attack (0.8%, 0.6%, and 1.3%), acute renal failure (8.2%, 7.2%, and 10.2%), major bleeding (1.6%, 3.1%, and 8.5%). In conclusion, our results show that high-risk PCI without elective MCS is safe and feasible in most ACS patients, challenging professional societies' current recommendations. A randomized trial comparing unprotected versus protected high-risk PCI for non-shock ACS patients is warranted.

Comparison of the effect of ticagrelor combined with tirofiban versus clopidogrel combined with tirofiban on inflammation response and prognosis of patients with unstable angina pectoris in long term follow-up.

To investigate the effect of ticagrelor combined with tirofiban versus clopidogrel combined with tirofiban on inflammation response and prognosis of patients with unstable angina pectoris (UA). The present prospective study included a total of 291 patients who were diagnosed as unstable UA from January 2018 to December 2019. All UA patients were divided into two groups: ticagrelor combined with tirofiban group (n = 159) and clopidogrel combined with tirofiban group (n = 132). Serum levels of C-reactive protein (CRP), interleukin-1ß, interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9 were measured using commercially available enzyme-linked immunosorbent assay kits. Kaplan-Meier (K-M) curve was performed for analysis of cumulative incidences of major adverse cardiovascular events (MACEs). Both ticagrelor combined with tirofiban and clopidogrel combined with tirofiban significantly decreased the serum levels of inflammatory factors in UA patients. Compared to clopidogrel combined with the tirofiban group, ticagrelor combined with the tirofiban group had a lower platelet aggregation rate and improved cardiac function of UA patients. Besides, ticagrelor combined with tirofiban group had a better prognosis and the K-M curve showed that UA patients treated by ticagrelor and tirofiban had lower incidences of MACEs in one-year follow-up. The treatment of ticagrelor combined with tirofiban significantly attenuated inflammation response and improved the prognosis of UA patients.

Derivation and validation of a clinical model to predict death or cardiac hospitalizations while on the cardiac surgery waitlist.

BACKGROUND: Waitlist management is a global challenge. For patients with severe cardiovascular diseases awaiting cardiac surgery, prolonged wait times are associated with unplanned hospitalizations. To facilitate evidence-based resource allocation, we derived and validated a clinical risk model to predict the composite outcome of death and cardiac hospitalization of patients on the waitlist for cardiac surgery. METHODS: We used the CorHealth Ontario Registry and linked ICES health care administrative databases, which have information on all Ontario residents. We included patients 18 years or older who waited at home for coronary artery bypass grafting, valvular or thoracic aorta surgeries between 2008 and 2019. The primary outcome was death or an unplanned cardiac hospitalizaton, defined as nonelective admission for heart failure, myocardial infarction, unstable angina or endocarditis. We randomly divided two-thirds of these patients into derivation and one-third into validation data sets. We derived the model using a multivariable Cox proportional hazard model with backward stepwise variable selection. RESULTS: Among 62 375 patients, 41 729 patients were part of the derivation data set and 20 583 were part of the validation data set. Of the total, 3033 (4.9%) died or had an unplanned cardiac hospitalization while waiting for surgery. The area under the curve of our model at 15, 30, 60 and 89 days was 0.85, 0.82, 0.81 and 0.80, respectively, in the derivation cohort and 0.83, 0.80, 0.78 and 0.78, respctively, in the validation cohort. The model calibrated well at all time points. INTERPRETATION: We derived and validated a clinical risk model that provides accurate prediction of the risk of death and unplanned cardiac hospitalization for patients on the cardiac surgery waitlist. Our model could be used for quality benchmarking and data-driven decision support for managing access to cardiac surgery.

A prognostic nomogram for long-term major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

BACKGROUND: Accurate prediction of major adverse cardiovascular events (MACEs) is very important for the management of acute coronary syndrome (ACS) patients. We aimed to construct an effective prognostic nomogram for individualized risk estimates of MACEs for patients with ACS after percutaneous coronary intervention (PCI). METHODS: This was a prospective study of patients with ACS after PCI from January 2013 to July 2019 (n = 2465). After removing patients with incomplete clinical information, a total of 1986 patients were randomly divided into evaluation (n = 1324) and validation (n = 662) groups. Predictors included in the nomogram were determined by a multivariate Cox proportional hazards regression model based on the training set. Receiver operating characteristic (ROC) curves and calibration curves were used to assess the discrimination and predictive accuracy of the nomogram, which were then compared with those of the classic models. The clinical utility of the nomogram was assessed by X-tile analysis and Kaplan-Meier curve analysis. RESULTS: Independent prognostic factors, including lactate level, age, left anterior descending branch stenosis, right coronary artery stenosis, brain natriuretic peptide level, and left ventricular ejection fraction, were determined and contained in the nomogram. The nomogram achieved good areas under the ROC curve of 0.712-0.762 in the training set and 0.724-0.818 in the validation set and well-fitted calibration curves. In addition, participants could be divided into two risk groups (low and high) according to this model. CONCLUSIONS: A simple-to-use nomogram incorporating lactate level effectively predicted 6-month, 1-year, and 4-year MACE incidence among patients with ACS after PCI.

Long-Term Prognosis in Young Patients with Acute Coronary Syndrome Treated with Percutaneous Coronary Intervention.

BACKGROUND: Acute coronary syndrome (ACS) at a young age is uncommon. Limited data regarding the long-term follow-up and prognosis in this population are available. Our objectives were to evaluate the long-term clinical outcomes of patients presenting with ACS at a young age and to assess factors that predict long-term prognosis. METHODS: A retrospective analysis of consecutive young patients (male below 40 and female below 50 years old) that were admitted with ACS and underwent percutaneous coronary intervention (PCI) between the years 1997 and 2009. Demographics, clinical characteristics, and clinical outcomes including major cardiovascular (CV) events and mortality were analyzed. Multivariable cox proportional hazard model was performed to identify predictors of long-term prognosis. RESULTS: One-hundred sixty-five patients were included with a mean follow-up of 9.1±4.6 years. Most patients were men (88%), and mean age (years) was 36.8±4.2. During follow-up, 15 (9.1%) died, 98 (59.4%) patients had at least one major CV event, 22 (13.3%) patients had more than two CV events, and the mean number of recurrent CV events was 1.4±1.48 events per patient. In multivariate analysis, the strongest predictors of major CV events and/or mortality were coronary intervention without stent insertion (HR1.77; 95% CI 1.09-2.9), LAD artery involvement (HR 1.59; 95% CI 1.04-2.44) and hypertension (HR 1.6; 95% CI 1.0-2.6). CONCLUSION: Patients with ACS in young age are at high risk for major CV and/or mortality in long-term follow-up with a high rate of recurrent CV events. Close follow-up and risk factor management for secondary prevention have a major role, particularly in this population.

Prognostic Impact of Nonobstructive Coronary Artery Disease Detected by Coronary Computed Tomographic Angiography.

Coronary computed tomographic angiography (CCTA) is a promising technique for ruling out coronary artery disease (CAD) in patients with chest pain. We aimed to investigate the prognostic impact of nonobstructive CAD on CCTA. We retrospectively reviewed patients who underwent CCTA between 2010 and 2016 at our institution. We divided them into 3 groups: (1) patients with no CAD, (2) patients with nonobstructive CAD, and (3) patients with obstructive CAD. We investigated the incidence of the primary outcome (combination of death, nonfatal myocardial infarction, unstable angina, and late revascularization). A total of 989 patients were included: 540 patients had CAD, which was obstructive (≥50% stenosis) in 256 cases. During the follow-up period, 99 events occurred (32 [7%] in patients without CAD, 26 [9%] in patients with nonobstructive CAD, and 41 [16%] in patients with obstructive CAD; P < .001). The presence of nonobstructive and obstructive CAD was an independent predictor of events (HR: 2.33 [1.15-4.69], P < .001; and 4.02 [1.98-8.13], P = .019, respectively) compared with no CAD. Nonobstructive CAD on CCTA is associated with a 2-fold increase in risk of coronary events compared with patients with no CAD.

Pathways leading to prevention of fatal and non-fatal cardiovascular disease: An interaction model on 15 years population-based cohort study.

BACKGROUND: A comprehensive study on the interaction of cardiovascular disease (CVD) risk factors is critical to prevent cardiovascular events. The main focus of this study is thus to understand direct and indirect relationships between different CVD risk factors. METHODS: A longitudinal data on adults aged ≥35 years, who were free of CVD at baseline, were used in this study. The endpoints were CVD events, whereas their measurements were demographic, lifestyle components, socio-economics, anthropometric measures, laboratory findings, quality of life status, and psychological factors. A Bayesian structural equation modelling was used to determine the relationships among 21 relevant factors associated with total CVD, stroke, acute coronary syndrome (ACS), and fatal CVDs. RESULTS: In this study, a total of 3161 individuals with complete information were involved in the study. A total of 407 CVD events, with an average age of 54.77(10.66) years, occurred during follow-up. The causal associations between six latent variables were identified in the causal network for fatal and non-fatal CVDs. Lipid profile, with the coefficient of 0.26 (0.01), influenced the occurrence of CVD events as the most critical factor, while it was indirectly mediated through risky behaviours and comorbidities. Lipid profile at baseline was influenced by a wide range of other protective factors, such as quality of life and healthy lifestyle components. CONCLUSIONS: Analysing a causal network of risk factors revealed the flow of information in direct and indirect paths. It also determined predictors and demonstrated the utility of integrating multi-factor data in a complex framework to identify novel preventable pathways to reduce the risk of CVDs.

Routine Revascularization Versus Initial Medical Therapy for Stable Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Revascularization is often performed in patients with stable ischemic heart disease. However, whether revascularization reduces death and other cardiovascular outcomes is uncertain. METHODS: We conducted PUBMED/EMBASE/Cochrane Central Register of Controlled Trials searches for randomized trials comparing routine revascularization versus an initial conservative strategy in patients with stable ischemic heart disease. The primary outcome was death. Secondary outcomes were cardiovascular death, myocardial infarction (MI), heart failure, stroke, unstable angina, and freedom from angina. Trials were stratified by percent stent use and by percent statin use to evaluate outcomes in contemporary trials. RESULTS: Fourteen randomized clinical trials that enrolled 14 877 patients followed up for a weighted mean of 4.5 years with 64 678 patient-years of follow-up fulfilled our inclusion criteria. Most trials enrolled patients with preserved left ventricular systolic function and low symptom burden, and excluded patients with left main disease. Revascularization compared with medical therapy alone was not associated with a reduced risk of death (relative risk [RR], 0.99 [95% CI, 0.90-1.09]). Trial sequential analysis showed that the cumulative z-curve crossed the futility boundary, indicating firm evidence for lack of a 10% or greater reduction in death. Revascularization was associated with a reduced nonprocedural MI (RR, 0.76 [95% CI, 0.67-0.85]) but also with increased procedural MI (RR, 2.48 [95% CI, 1.86-3.31]) with no difference in overall MI (RR, 0.93 [95% CI, 0.83-1.03]). A significant reduction in unstable angina (RR, 0.64 [95% CI, 0.45-0.92]) and increase in freedom from angina (RR, 1.10 [95% CI, 1.05-1.15]) was also observed with revascularization. There were no treatment-related differences in the risk of heart failure or stroke. CONCLUSIONS: In patients with stable ischemic heart disease, routine revascularization was not associated with improved survival but was associated with a lower risk of nonprocedural MI and unstable angina with greater freedom from angina at the expense of higher rates of procedural MI. Longer-term follow-up of trials is needed to assess whether reduction in these nonfatal spontaneous events improves long-term survival.

Mannose-Binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study.

OBJECTIVE: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease (CVD) in diabetes, but the nature of the association is unclear. We investigated the association between MBL and the risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS: In a cohort study of 7,588 patients with type 2 diabetes, we measured serum MBL in 7,305 patients and performed MBL expression genotyping in 3,043 patients. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, or cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. RESULTS: Serum MBL and CVE showed a U-shaped association. Compared with the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI 1.34-2.46) for the low-MBL category and 1.48 (95% CI 1.14-1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared with the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI 0.87-2.25) for the low-expression genotype and 1.44 (95% CI 1.01-2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. CONCLUSIONS: Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for CVD in this population.

Prognostic Significance of Serum Albumin in Patients With Acute Coronary Syndrome.

In patients with unstable angina pectoris (UAP) or non-ST elevation myocardial infarction (NSTEMI), long-term mortality remains high despite improvements in the diagnosis and treatment. In this study, we investigated whether serum albumin level is a useful predictor of long-term mortality in patients with UAP/NSTEMI. Consecutive patients (n = 403) who were hospitalized with a diagnosis of UAP/NSTEMI were included in the study. Patients were divided into 2 groups based on the presence of hypoalbuminemia and the relationship between hypoalbuminemia and mortality was analyzed. Hypoalbuminemia was detected in 34% of the patients. The median follow-up period was 35 months (up to 45 months). Long-term mortality rate was 32% in the hypoalbuminemia group and 8.6% in the group with normal serum albumin levels (P < .001). On multivariate analysis, hypoalbuminemia, decreased left ventricular ejection fraction, and increased age were found to be independent predictors of mortality (P < .05). The cutoff value of 3.10 g/dL for serum albumin predicted mortality with a sensitivity of 74% and specificity of 67% (receiver-operating characteristic area under curve: 0.753, 95% CI: 0.685-0.822). All-cause long-term mortality rates were significantly increased in patients with hypoalbuminemia. On-admission albumin level was an independent predictor of mortality in patients with UAP/NSTEMI.

Patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris randomised to an invasive versus conservative strategy: angiographic and procedural results from the After Eighty study.

OBJECTIVES: We aimed to report the angiographic and procedural results of the After Eighty study (ClinicalTrials.gov, NCT01255540), and to identify independent predictors of revascularisation. METHODS: Patients of ≥80 years old with non-ST-elevation myocardial infarction and unstable angina pectoris were randomised to an invasive or conservative strategy. Angiographic and procedural results were recorded. Univariate and multivariate analyses were performed to explore variables predicting revascularisation. RESULTS: Among 229 patients in the invasive group, 220 underwent immediate coronary angiography (90% performed via the radial artery). Of these patients, 48% had three-vessel disease or left main stenosis, 18% two-vessel disease, 16% one-vessel disease, 17% minor coronary vessel wall changes and two patients had normal coronary arteries. Six patients (3%) underwent coronary artery bypass graft. Percutaneous coronary intervention (PCI) was performed in 107 patients (49%), with 57% treated with bare metal stents, 37% drug-eluting stents and 6% balloon angioplasty. On average, 1.7 lesions were treated and 2 stents delivered per patient. Complications included 1 major PCI-related bleeding (successfully treated), 2 minor access site-related bleedings, 3 side branch occlusions during PCI and 11 periprocedural myocardial infarctions (considered end points). Sex, bundle branch block and smoking were independent predictors of revascularisation. CONCLUSIONS: PCI was performed in approximately half of the patients, similar to findings in younger populations. Procedural success was high, with few complications. TRIAL REGISTRATION NUMBER: NCT01255540.

Effect of invasive strategy on long-term mortality in elderly patients presenting with acute coronary syndrome.

OBJECTIVE: The elderly have the highest incidence of cardiovascular disease and frequently present with acute coronary syndrome (ACS). In this study, our aim was to evaluate the effect of an invasive strategy on long-term mortality in patients of 80 years and older presenting with ACS. METHODS: Patients who were admitted to hospital with ACS were recruited using appropriate ICD codes in the computerised hospital data system. After exclusion of patients below 80 years old, the remaining 156 patients were involved in the final analyses. Ninety-four of 156 patients (60.3%) underwent coronary angiography and they constituted the invasive-strategy group, whereas the remaining 62 (39.7%) patients were treated medically and they constituted the conservative-strategy group. RESULTS: Median follow-up duration of patients was 8.5 (0-61) months. Total mortality at the end of the follow-up period was 24 (25.5%) patients in the invasive-strategy group and 30 (48.4%) in the conservative-strategy group (p = 0.006). According to Cox regression analysis, the invasive strategy (OR: 0.26, 95% CI: 0.12-0.56, p = 0.001), presentation with ST-segment elevation myocardial infarction (OR: 7.76, 95% CI: 1.74-34.57, p = 0.002), low ejection fraction below 40% (OR: 3.11, 95% CI: 1.43-6.76, p = 0.004), heart rate (OR: 0.98, 95% CI: 0.96-0.99, p = 0.013) and GRACE risk score between 150 and 170 (OR: 7.76, 95% CI: 1.74-34.57, p = 0.002) were related to long-term mortality. CONCLUSIONS: Our results show the benefit of the invasive strategy on mortality rate in elderly patients over 80 years old and presenting with ACS.

An Upfront Two-Stent Strategy for True Coronary Bifurcation Lesions with A Large Side Branch in Acute Coronary Syndrome: A Two-Year Follow-Up Study.

Background and Objectives: Little is known about the upfront two-stent strategy (U2SS) for true coronary bifurcation lesions (CBLs) in acute coronary syndrome (ACS). We aimed to present our two-year follow-up results on the U2SS by using different two-stent techniques for the true CBL with a large side branch (SB) in ACS patients, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI), and to identify independent predictors of the presence of major adverse cardiac events (MACEs) after intervention. Materials and Methods: The study included 201 consecutive ACS patients with true CBLs who underwent percutaneous coronary intervention (PCI) using U2SS from October 2015 to March 2018. Clinical outcomes at follow-up were assessed. MACE was defined as a composite of cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). Results: 31.3% of the patients had an UA, 46.3% had an NSTEMI, and 22.4% had an STEMI. CBL was most frequently located in the left anterior descending (LAD)/diagonal artery (59.2%). In total, 71.1% of the patients had a Medina classification (1,1,1). Overall, 62.2% of cases were treated with mini-crush stenting. Clopidogrel was given in 23.9% of the patients; 71.1% of the patients received everolimus eluting stent (EES); and 11.9% received a sirolimus eluting stent (SES). Final kissing balloon inflation was carried out in all patients, with an unsatisfactory rate of 5%. A proximal optimization technique sequence was successfully carried out in all patients. The MACE incidence was 16.9% with a median follow-up period of 2.1 years. There were seven cardiac deaths (3.5%). The TLR rate was 13.4% (n = 27), with PCI treatment in 16 patients, and coronary artery bypass grafting treatment in 11 patients. After multivariate penalized logistic regression analysis (Firth logistic regression), clopidogrel use (odds ratio (OR): 2.19; 95% confidence interval (CI): 0.41-2.51; p = 0.007) and SES use (OR: 1.86; 95% CI: 0.31-2.64; p = 0.014) were independent predictors of the presence of MACE. Conclusion: U2SS is feasible and safe for the true CBLs with large and diseased SB in ACS patients, and is related to a relatively low incidence of MACE. Clopidogrel use and SES use may predict the MACE development in ACS patients treated using U2SS.

Temporal trends in incidence and outcome of acute coronary syndrome.

BACKGROUND: We aimed to investigate changes of incidence, outcome and related interventions of patients with acute coronary syndrome (ACS) over the past decade in Germany. METHODS: Data on the international statistical classification of diseases and procedural codes from the Federal Bureau of Statistics in Germany was used. This included all ACS cases in Germany in the years 2005-2015. Analyses were performed separately for the diagnoses of overall ACS, ST-elevation myocardial infarction (MI), non-ST-elevation MI and unstable angina pectoris. Procedures including coronary angiography and percutaneous coronary intervention and the endpoint in-hospital mortality were assessed. RESULTS: Between 2005 and 2015 a total of 3797,546 cases of ACS were recorded. The mean age was 69 years and 36% were females. In-hospital mortality was 6.3%, 62% underwent coronary angiography and 42% received percutaneous coronary intervention. In-hospital mortality was highest for patients with ST-elevation MI (12.0%) and lowest for patients with unstable angina pectoris (0.6%). From 2005 to 2015 the incidence rates of ACS, ST-elevation MI and unstable angina pectoris decreased, while the incidence rate of non-ST-elevation MI increased. The percentages of performed coronary angiographies and percutaneous coronary interventions increased from 52 to 70% and 34 to 50%, respectively. The adjusted incidence rate of in-hospital mortality decreased from 64.9 cases per 1000 person-years to 54.8 cases. CONCLUSION: In a large dataset including more than 3.7 million cases, we report an increase in coronary procedures and a reduction of ACS incidence and related mortality in the past decade in Germany.

Incidence and Outcomes of Acute Coronary Syndrome After Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to address a knowledge gap by examining the incidence, timing, and predictors of acute coronary syndrome (ACS) after transcatheter aortic valve replacement (TAVR) in Medicare beneficiaries. BACKGROUND: Evidence about incidence and outcomes of ACS after TAVR is scarce. METHODS: We identified Medicare patients who underwent TAVR from 2012 to 2017 and were admitted with ACS during follow-up. We compared outcomes based on the type of ACS: ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina. In patients with non-ST-segment elevation ACS, we compared outcomes based on the treatment strategy (invasive vs. conservative) using inverse probability weighting analysis. RESULTS: Out of 142,845 patients with TAVR, 6,741 patients (4.7%) were admitted with ACS after a median time of 297 days (interquartile range: 85 to 662 days), with 48% of admissions occurring within 6 months. The most common presentation was NSTEMI. Predictors of ACS were history of coronary artery disease, prior revascularization, diabetes, valve-in-TAVR, and acute kidney injury. STEMI was associated with higher 30-day and 1-year mortality compared with NSTEMI (31.4% vs. 15.5% and 51.2% vs. 41.3%, respectively; p < 0.01). Overall, 30.3% of patients with non-ST-segment elevation ACS were treated with invasive approach. On inverse probability weighting analysis, invasive approach was associated with lower adjusted long-term mortality (adjusted hazard ratio: 0.69; 95% confidence interval: 0.66 to 0.73; p < 0.01) and higher risk of repeat revascularization (adjusted hazard ratio: 1.29; 95% confidence interval: 1.16 to 1.43; p < 0.001). CONCLUSIONS: After TAVR, ACS is infrequent (<5%), and the most common presentation is NSTEMI. Occurrence of STEMI after TAVR is associated with a high mortality with nearly one-third of patients dying within 30 days. Optimization of care is needed for post-TAVR ACS patients and if feasible, invasive approach should be considered in these high-risk patients.

Superiority of high sensitivity cardiac troponin T vs. I for long-term prognostic value in patients with chest pain; data from the Akershus cardiac Examination (ACE) 3 study.

BACKGROUND: Cardiac troponins (cTn) are essential in the diagnostic assessment of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Elevated concentrations of cTnT and cTnI predict cardiovascular events in non-acute settings, but the individual troponin isotype association with long-term mortality in patients with suspected unstable angina pectoris (UAP) is less clear. METHODS: Patients hospitalized with chest pain between June 2009 and December 2010 were included in the Akershus Cardiac Examination 3 Study and followed for median 6.6 (IQR 6.2-7.1) years. The index diagnosis was adjudicated by an independent committee as NSTE-myocardial infarction (NSTEMI), UAP or non-ACS. Blood samples were collected within 24 h of admission and analyzed with high sensitivity assays for cTnT (hs-cTnT, Roche) and cTnI (hs-cTnI, Singulex). RESULTS: Of 402 patients included, 74 (18%) were classified as NSTEMI, 88 (22%) UAP and 240 (60%) non-ACS. hs-cTnI concentrations were detectable in all patients (median 3 [IQR 1-11] ng/L), while hs-cTnT concentrations were above the level of blank in 205 (51%) (median 3 [IQR 3-16] ng/L). In patients with UAP, both log2-transformed hs-cTnT and hs-cTnI were associated with all-cause mortality in analyses that adjusted for other risk factors: HR 2.40 [95% CI 1.75-3.30], p < 0.001 and HR 1.44 [1.14-1.81], p = 0.002. There were no significant sex-dependent differences in the association between hs-cTnT or hs-cTnI and outcome. Time dependent receiver-operating characteristics area under the curve was 0.85 (95% CI 0.79-0.92) for hs-cTnT and 0.74 (0.64-0.84) for hs-cTnI, p = 0.008 for difference between values. CONCLUSIONS: Higher concentrations of hs-cTnT and hs-cTnI were both associated with all-cause mortality in patients with UAP, but the association with outcome was stronger for hs-cTnT than for hs-cTnI.