Unstable Angina Risk Stratification Using High-Sensitivity Cardiac Troponin and Coronary Angiography.

Patients formerly diagnosed with unstable angina (UA) are being reclassified as non-ST-elevation myocardial infarction with the widespread adoption of high-sensitivity troponin (hsTn) assays, leading to significant changes in the incidence and prognosis of UA. This study aimed to evaluate the value of hsTn and the presence of significant obstructive coronary artery disease (CAD) in the risk stratification of patients with UA. We conducted a retrospective, single-center study of 742 patients hospitalized for UA between 2016 and 2021. The primary end point of this study was all-cause mortality. The secondary outcome (major adverse cardiac events [MACEs]) was defined as a composite of nonfatal myocardial infarction (MI), hospitalization for heart failure (hHF), and repeated coronary angiography because of recurring UA (rUA) after the index event. The outcomes were assessed within 1 month, 1 year, and up to 5 years of follow-up. The average follow-up duration was 45 ± 24 months, and 37.2% (n = 276) of patients completed a 5-year follow-up. No in-hospital death was observed, and 6.9% of patients died during follow-up, which was more commonly a late event (>12 months). The composite secondary end point (MI+hHF+rUA) was observed in 16.7% of the patients. There were 3.2% nonfatal MI, 2.3% hHF, and 11.6% rUA during follow-up. We developed a risk model (UA mortality risk) using variables with the highest discriminatory power: age, hsTn, and ST-segment deviation. Our model performed well against the Global Registry of Acute Coronary Events and Thrombolysis in Myocardial Infarction risk scores in predicting death during follow-up. Obstructive CAD on coronary angiography was the only independent predictor of MACEs during follow-up. In conclusion, a contemporary cohort of patients with UA presented with favorable prognosis, particularly, within the first year after the index event. Nonsignificant increases in hsTn levels add to the risk stratification of patients with UA, and the presence of obstructive CAD was the only independent predictor of MACEs, highlighting the potential importance of assessing coronary anatomy.

Effects of Serum LDL-C, CysC, and D-D in Patients with Coronary Atherosclerotic Heart Disease.

Objective: To investigate the effects of low-density lipoprotein cholesterol (LDL-C) and serum cystatin C (CysC) combined with D-dimer (D-D) on patients with coronary atherosclerotic heart disease (CHD). Methods: 90 patients with CHD who were admitted to our hospital and diagnosed by coronary angiography (CAG) from February 2020 to June 2021 were selected as the study subjects. 90 patients were grouped according to different types and branches of coronary lesions, and 30 patients with outpatient health check-ups at the same period were selected as the control group, and the differences in serum LDL-C, CysC, and D-D levels between the groups were compared. The logistic regression model was built to explore risk factors affecting the occurrence of CHD. Also, receiver operating characteristic (ROC) curves were drawn to analyze the diagnostic value of LDL-C, CysC, and D-D in CHD. Results: In the comparison of LDL-C, CysC, and D-D levels, CHD group > control group (P < 0.05); stable angina (SAP) group > unstable angina (UAP) group > acute myocardial infarction (AMI) group (P < 0.05); three-branch group > two-branch group > single-branch group (P < 0.05). The logistic regression model showed that high expression levels of LDL-C, CysC, and D-D, male gender, and combined hypertension were risk factors for CHD. The area under the curve (AUC) of the combination of LDL-C, CysC, and D-D was 0.868, and the sensitivity and specificity were 88.89% and 73.33%, respectively, which are higher than those in single diagnosis (P < 0.05). Conclusions: LDL-C, CysC, and D-D are highly expressed in CHD samples, and the combination of the three is beneficial to enhance the diagnostic accuracy of clinical CHD.

Diagnostic performance and predictive value of D-dimer testing in patients referred to the emergency department for suspected myocardial infarction.

PURPOSE: The study sought to assess the performance of D-dimer testing for the diagnosis of acute coronary syndrome (ACS) and prediction of outcomes in patients admitted for suspected myocardial infarction (MI). RESULTS: A total of 3,557 patients with suspected ACS presenting to a single center with a broad range of symptoms including atypical chest pain were retrospectively recruited between 02/2012-01/2019. Of the study cohort, 435 patients had unstable angina (UA), 420 non-ST-segment elevation myocardial infarction (NSTEMI), 22 ST-segment elevation myocardial infarction (STEMI), and 2,680 non-coronary chest pain. Plasma D-dimer concentrations in patients with hs-cTnT > 14 ng/L differed significantly from those with hs-cTnT < 14 ng/L (1.5 ± 3.6 mg/L vs. 0.5 ± 0.8 mg/L; p < 0.0001). Positive predictive value for a final diagnosis of ACS increased proportionally to rising D-dimer concentrations. The area under the curve (AUC) to discriminate STEMI from non-coronary chest pain (AUC 0.729, 95% confidence interval [CI] 0.71-0.75) was moderate and differed not significantly to UA (AUC 0.595, 95% CI 0.58-0.61; p = 0.0653). During a median follow-up of 29 months, higher D-dimer was associated with a significantly increased risk of recurrent MI (quartile 4 vs. 1: hazard ratio [HR], 6.9 [95% CI 1.2-39.9]; p < 0.0001) and higher all-cause mortality (HR, 17.4 [95% CI 4.3-69.9]; p < 0.0001). D-dimer was an independent predictor of all-cause mortality (p < 0.0001) and subsequent MI events (p = 0.0333). CONCLUSIONS: D-dimer testing revealed great potential to provide independent prognostic information on recurrent MI and all-cause mortality. However, D-dimers do not improve the diagnostic performance except if values exceed the 95th percentile.

High-Density Lipoprotein Cholesterol and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Statins: An Observation from the REAL-CAD Study.

AIM: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients. METHODS: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively. RESULTS: During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months. CONCLUSIONS: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.

Investigation on Risk Stratification and the Prognostic Value of hs-TnT Combined with MMP-2 in Patients with Acute Coronary Syndrome.

OBJECTIVE: The aim of this study was at investigating the risk stratification and prognostic value of hypersensitive troponin T (hs-TnT) combined with matrix metalloproteinase 2 (MMP-2) in patients with acute coronary syndrome (ACS). METHODS: 80 patients with coronary syndrome admitted to our hospital from January 2019 to January 2020 and 40 healthy people (control group) in the same period were selected. According to different types of diseases, the patients were divided into an acute group (n = 40) and stable group (n = 40). Besides, they all were monitored by the hs-TnT value, serum MMP-2, and coronary angiography at admission and the comparative analysis was carried out. The patients in both groups were followed up for 30 days, and the incidence of adverse cardiovascular events in the patients during this period was recorded. RESULTS: Compared with those in the control group, the MMP-2 and hs-TnT levels in the acute group and the stable group were significantly higher and the MMP-2 and hs-TnT levels in the acute group were significantly higher than those in the stable group, with statistically significant differences (P < 0.05). The 30-day follow-up results showed that the incidence of adverse cardiovascular events in the acute group was significantly higher than that in the stable group, with statistically significant differences (P < 0.05). The hs-TnT and MMP-2 levels in the acute myocardial infarction (AMI) group were significantly higher than those in the unstable angina pectoris (UAP) group, with statistically significant differences (P < 0.01). The hs-TnT and MMP-2 levels in the non-single-vessel group were significantly higher than those in the single-vessel group, with statistically significant differences (P < 0.01). CONCLUSION: The hs-TnT and MMP-2 high expression levels are closely associated with myocardial injury, and they can effectively predict the severity of patients' disease. In addition, the hs-TnT and MMP-2 elevated levels can be considered as an important index to judge the short-term treatment efficacy and the risk stratification of early ACS, playing an important role in clinical treatment and rehabilitation in the later stage.

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.

The Relationship between Serum and Gene Expression Levels of RANK, RANKL and Osteoprotegerin Inflammatory Pathway with Unstable Angina: A Case-control Study.

 Osteoprotegerin (OPG), receptor activator of nuclear factor-kappa B (RANK) and receptor activator of nuclear factor-kappa B ligand (RANKL), the members of the tumor necrosis factor (TNF) family, have multiple effects on bone metabolism, endocrine functions and, as an inflammatory pathway, in the immune system. This study tried to determine the association of the OPG/RANKL/RANK axis with the severity of unstable angina (UA) as an inflammatory condition. Our study involved 50 patients with UA and 50 healthy people. Serum and peripheral blood mononuclear cells were isolated from all participants. Serum levels and gene expression of OPG, RANKL, and RANK in mononuclear cells were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (RT-PCR), respectively. For each patient with UA, the thrombolysis in myocardial infarction (TIMI) and the global registry of acute coronary events (GRACE) scores were determined to evaluate the severity of the disease. Then we analyzed the relation of OPG, RANKL, and RANK levels with TIMI and GRACE scores in patients with UA. Discriminate analysis was used to predict the combinational models of such factors on the prediction of UA. Serum levels of OPG and RANKL (p<0.001) and gene expression of RANKL (p<0.001) were significantly more in patients than those in healthy ones. No relation was seen between the OPG/RANKL/RANK axis and the severity of UA according to TIMI and GRACE scores. Our study shows that serum level, as well as gene expression of OPG/RANKL/RANK axis neither, predicts the occurrence of UA nor shows any relationship with its severity.

Cholesterol Control for Subclinical Coronary Atherosclerosis in Subjects Without Indication for Statin Therapy.

Low-risk individuals still experience adverse cardiac events. We sought to evaluate long-term cardiac events and predictors for subclinical coronary atherosclerosis in subjects without indication for statin therapy. We analyzed 3,272 individuals without indication for statin therapy who voluntarily underwent coronary computed tomography angiography as part of a general health examination. A cardiac event was defined as a composite of cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, or late coronary revascularization. The prevalence of normal coronary arteries, nonobstructive coronary artery disease (CAD) (diameter stenosis < 50%), and obstructive CAD (diameter stenosis ≥50%) was 2,338 (71.5%), 809 (24.7%), and 125 (3.8%), respectively. During the follow-up period (median 5.3 [interquartile range, 4.3-6.3] years), the 6-year event-free survival rates were 99.2%±0.2% in subjects with normal coronary arteries, 98.2%±0.6% in those with nonobstructive CAD, and 90.2%±2.7% in those with obstructive CAD (log-rank p < 0.001). Multivariable regression analysis showed that low-density lipoprotein cholesterol (LDL-C, odds ratio [OR]: 1.012; 95% confidence interval (CI): 1.005-1.019) and high-density lipoprotein cholesterol (HDL-C, OR: 0.968; 95% CI: 0.952-0.984) levels were associated with subclinical obstructive CAD, together with age (OR: 1.080; 95% CI: 1.040-1.121) and male sex (OR: 3.102; 95% CI: 1.866-5.155) (all p < 0.05). In conclusion, LDL-C and HDL-C are significantly associated with the presence of subclinical obstructive CAD with a worse prognosis in subjects without indication for statin therapy. These findings suggest that stricter control of LDL-C and HDL-C levels may be necessary for primary prevention even in a relatively low-risk population.

Could Serum Copeptin Level Be an Indicator of Coronary Artery Disease Severity in Patients with Unstable Angina?

This study aimed to identify the serum copeptin levels in patients diagnosed with unstable angina (UA) and evaluate the relationship between the patients' copeptin levels and angiographic severity.A total of 200 patients who were diagnosed with UA and underwent coronary angiography were included in the study. Clinical, electrocardiographic, echocardiographic, and laboratory data (high-sensitivity cardiac troponin T and copeptin levels) as well as The Global Registry of Acute Coronary Events (GRACE) 1.0 risk score were recorded upon admission. Moreover, the Synergy Between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery (SYNTAX) score was calculated following coronary angiography.We isolated and defined two subgroups within our study population: group 1 included patients with non-significant coronary artery disease (CAD) (< 50% diameter stenosis, n = 105); group 2 included patients with significant CAD (≥ 50% diameter stenosis, n = 95). The number of cases with a GRACE score higher than 140 was significantly higher in group 2 than in group 1 (P < 0.001). The SYNTAX scores and copeptin levels were significantly higher in group 2 than in group 1 (P < 0.001 for both). A positive correlation was observed between the copeptin levels and SYNTAX scores (r = 0.683; P < 0.001), and the cut-off level of copeptin was 18.3 pmol/L (sensitivity of 74.7%, specificity of 83.8%, and area under the curve of 0.795).This study suggests that it may be beneficial to use conventional scoring systems and serum copeptin levels when identifying high-risk UA patients.

Trace element, immune and opioid biomarkers of unstable angina, increased atherogenicity and insulin resistance: Results of machine learning.

BACKGROUND: Aberrations in endothelial cells, immune and oxidative pathways are associated with atherosclerosis (ATS) and unstable angina (UA). The role of trace elements, minerals, and the endogenous opioid system (EOS) in UA are less well established. METHODS: We measured lipid, insulin resistance (IR), and immune, trace element (copper and zinc), mineral (magnesium, calcium), EOS (ß-endorphin and mu-opioid receptor (MOR)) and antioxidant (vitamin D3) biomarkers in patients with ATS (n = 60) and UA (n = 60) and healthy controls (n = 58). RESULTS: ATS patients showed increased atherogenic and IR indices, IL-6, IL-10, ß-endorphin, copper and magnesium, and lower zinc than healthy controls. Logistic regression showed that UA was significantly discriminated from ATS without UA with an accuracy of 85.5 % using calcium, IL-10, ß-endorphin, MOR, triglycerides, IR (all positively), and copper and vitamin D3 (inversely). Neural networks showed that UA was discriminated from ATS without UA with an area under the ROC curve of 0.942 using MOR, ß-endorphin, calcium, insulin resistance, vitamin D3 and copper as input variables. We found that 50.0 % of the variance in IR was explained by the regression on copper, IL-10, IL-6 (all positively), and zinc (inversely), while 32.9 % of the variance in the atherogenic index of plasma was explained by copper, IL-10 (both positively), and magnesium (inversely). CONCLUSION: UA is not only mediated by insulin resistance, atherogenicity, and immune disorders, but also by aberrations in the endogenous opioid system and trace elements as well as lowered antioxidant levels. Copper appears to play a key role in IR and atherogenicity.

Association Between Plasma ADAMTS-9 Levels and Severity of Coronary Artery Disease.

Genome-wide association studies have shown that a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS-9) is associated with the development of atherosclerosis. We assessed the level of ADAMTS-9 in patients with coronary artery disease (CAD) and its severity and prognosis. We selected 666 participants who underwent coronary angiography in our hospital and met the inclusion and exclusion criteria; participants included non-CAD patients, patients with stable angina pectoris (SAP), unstable angina, non-ST-segment elevation myocardial infarction, or ST-segment elevation myocardial infarction. The serum level of ADAMTS-9 was higher in patients with CAD than in non-CAD patients (37.53 ± 8.55 ng/mL vs 12.04 ± 7.02 ng/mL, P < .001) and was an independent predictor for CAD (odds ratio = 1.871, 95% CI: 1.533-2.283, P < .001). Subgroup analysis showed that compared with the SAP group, the acute coronary syndrome groups had higher serum levels of ADAMTS-9. In addition, the level of ADAMTS-9 was related to the SYNTAX score (r = 0.523, P < .001). Patients with acute myocardial infarction (AMI) with elevated levels of ADAMTS-9 had a higher risk of major adverse cardiovascular events (MACE) within 12 months than those with lower levels (log-rank = 4.490, P = .034). Plasma ADAMTS-9 levels may be useful for the diagnosis of CAD and as predictors of MACE in AMI patients.

Long-Term Bleeding Risk Prediction with Dual Antiplatelet Therapy After Acute Coronary Syndromes Treated Without Revascularization.

BACKGROUND: Longitudinal bleeding risk scores have been validated in patients treated with dual antiplatelet therapy (DAPT) following percutaneous coronary intervention. How these scores apply to the population of patients with acute coronary syndrome (ACS) treated without revascularization remains unknown. The objective was to evaluate and compare the performances of the PRECISE-DAPT, PARIS, and DAPT (bleeding component) bleeding risk scores in the medically managed patients with ACS treated with DAPT. METHODS AND RESULTS: TRILOGY ACS (Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes) was a double-blind, placebo-controlled randomized trial conducted from 2008 to 2012 over a median follow-up of 17.0 months in 966 sites (52 countries). High-risk patients with unstable angina or non-ST-segment-elevation myocardial infarction who did not undergo revascularization were randomized to prasugrel or clopidogrel. The PRECISE-DAPT, PARIS, and DAPT (bleeding component) risk scores were applied in the TRILOGY ACS population to evaluate their performance to predict adjudicated non-coronary artery bypass grafting-related GUSTO (Global Use of Strategies to Open Occluded Coronary Arteries) severe/life-threatening/moderate and TIMI (Thrombolysis in Myocardial Infarction) major/minor bleeding with time-dependent c-indices. Among the 9326 participants, median age was 66 years (interquartile range, 59-74 years), and 3650 were females (39.1%). A total of 158 (1.69%) GUSTO severe/life-threatening/moderate and 174 (1.87%) TIMI major/minor non-coronary artery bypass grafting bleeding events occurred. The c-indices (95% CI) of the PRECISE-DAPT, PARIS, and DAPT (bleeding component) scores through 12 months were 0.716 (0.677-0.758), 0.693 (0.658-0.733), and 0.674 (0.637-0.713), respectively, for GUSTO bleeding and 0.624 (0.582-0.666), 0.612 (0.578-0.651), and 0.608 (0.571-0.649), respectively, for TIMI bleeding. There was no significant difference in the c-indices of each score based upon pairwise comparisons. CONCLUSIONS: Among medically managed patients with ACS treated with DAPT, the performances of the PRECISE-DAPT, PARIS, and DAPT (bleeding component) scores were reasonable and similar to their performances in the derivation percutaneous coronary intervention populations. Bleeding risk scores may be used to predict longitudinal bleeding risk in patients with ACS treated with DAPT without revascularization and help support shared decision making. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00699998.

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.

Thrombin generation's role in predicting coronary disease severity.

BACKGROUND: Thrombin, a key enzyme of the clotting system, is involved in thrombus formation, platelet activation, and atherosclerosis, thereby possessing a central role in the pathogenesis of ischemic heart disease. Studies have shown an association between thrombin generation (TG) and cardiovascular morbidity and mortality, but results have been equivocal. Our aim was to study the predictive ability of TG assay in evaluating coronary stenosis severity. METHODS: In this prospective study we recruited patients with acute coronary syndrome (ACS) or acute chest pain (without evidence of myocardial injury) planned for coronary angiography. Thrombin generation was evaluated by Calibrated Automated Thrombogram (CAT) prior to angiography. Primary end points were significant coronary stenosis and the Syntax I score evaluated by coronary angiography. RESULTS: From April 2018 through September 2019, we recruited 128 patients. In the primary analysis there was no significant association between TG and significant coronary stenosis nor between TG and syntax I score, however, there was a positive correlation between peak height and troponin peak (Spearman correlation coefficient 0.194, P-value = 0.035). In sub-group analysis, the chest pain group bare no association between TG and coronary stenosis. In unstable angina group there was an association between peak height and significant coronary stenosis (P-value = 0.029), and in non ST-elevation myocardial infarction group, TG values possessed a relatively good predictive ability of significant coronary stenosis (area under the receiver operating characteristic curve of ~65%) and a positive correlation between both lag time and ttpeak with the syntax I score was noticed (Spearman correlation coefficient 0.31, P-value = 0.099 and Spearman correlation coefficient 0.37, P-value = 0.045 respectively). CONCLUSION: In patients with acute chest pain, TG values, evaluated by CAT, do not predict severity of coronary stenosis, nor do they possess prognostic value. Yet, in ACS patients, TG may have the ability to predict coronary disease severity.

Extracellular Vesicle cystatin c is associated with unstable angina in troponin negative patients with acute chest pain.

BACKGROUND: Despite the use of high-sensitive cardiac troponin there remains a group of high-sensitive cardiac troponin negative patients with unstable angina with a non-neglectable risk for future adverse cardiovascular events, emphasising the need for additional risk stratification. Plasma extracellular vesicles are small bilayer membrane vesicles known for their potential role as biomarker source. Their role in unstable angina remains unexplored. We investigate if extracellular vesicle proteins are associated with unstable angina in patients with chest pain and low high-sensitive cardiac troponin. METHODS: The MINERVA study included patients presenting with acute chest pain but no acute coronary syndrome. We performed an exploratory retrospective case-control analysis among 269 patients. Cases were defined as patients with low high-sensitive cardiac troponin and proven ischemia. Patients without ischemia were selected as controls. Blood samples were fractionated to analyse the EV proteins in three plasma-subfractions: TEX, HDL and LDL. Protein levels were quantified using electrochemiluminescence immunoassay. RESULTS: Lower levels of (adjusted) EV cystatin c in the TEX subfraction were associated with having unstable angina (OR 0.93 95% CI 0.88-0.99). CONCLUSION: In patients with acute chest pain but low high-sensitive cardiac troponin, lower levels of plasma extracellular vesicle cystatin c are associated with having unstable angina. This finding is hypothesis generating only considering the small sample size and needs to be confirmed in larger cohort studies, but still identifies extracellular vesicle proteins as source for additional risk stratification.

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.

Intracoronary and peripheral blood levels of TNF-like Cytokine 1A (TL1A) in patients with acute coronary syndrome.

BACKGROUND: TNF-like cytokine 1A (TL1A) is a subgroup of the tumor necrosis factor superfamily that exerts pleiotropic effects on cell proliferation, inflammation, activation, and differentiation of immune cells. The purpose of the current study is to investigate the clinical significance of TL1A expression in coronary and peripheral blood of patients with acute coronary syndrome (ACS) to determine if TL1A levels can serve as an accurate prognostic indicator. METHODS: A total of 141 patients undergoing coronary angiography were divided into 4 groups: Control (n = 35), Unstable Angina (UA) (n = 35), acute non-ST segment elevation myocardial infarction (NSTEMI) (n = 37), and acute ST segment elevation myocardial infarction (STEMI) (n = 34). The levels of TL1A, MPO, hs-CRP, and IL-10 were detected in coronary and peripheral blood using enzyme linked immunosorbent assay (ELISA), and the MACE incidence rates were compared during 26.3 months of follow-up. RESULTS: TL1A levels were not significantly different between the UA group and control group. In the UA group, TL1A levels were not significantly different between coronary blood and peripheral blood. However, TL1A levels were higher in the STEMI and NSTEMI groups than in the control group (P < .05). Moreover, TL1A levels in the coronary blood of the STEMI and NSTEMI groups were higher than in the peripheral blood (P < .05). The expression of TL1A in the coronary blood was the highest in the STEMI group. In addition, TL1A level in the coronary blood was highly correlated with levels in the peripheral blood (correlation coefficient: 0.899, P < .001). The hs-CRP and MPO levels in the coronary and peripheral blood of all the UA, NSTEMI, and STEMI groups were higher than the control group. Plasma IL-10 levels in all the UA, NSTEMI and STEMI groups were lower than those in the control group. Plasma TL1A level was positively correlated with the cTnI level, degree of coronary thrombus burden, occurrence of slow coronary flow / no coronary reflow and MACE, but negatively correlated with the IL-10 level or non-correlated with the Syntax score. CONCLUSION: Plasma TL1A concentration levels can be used as a predictor of inflammatory response and prognosis in patients with ACS. TRIAL REGISTRATION: ClinicalTrials.gov, number: NCT02430025; Unique Protocol ID: FJPH20150101; Brief Title: Fujian Province Cardiovascular Diseases Study (FJCVD).

Short-term prognosis of unstable angina in the era of high-sensitivity cardiac troponin: insights for early rule-out strategies.

BACKGROUND: It is unclear if strategies to rule-out myocardial infarction (MI) based on a single high-sensitivity troponin T (hsTnT) measurement at the emergency department (ED) presentation may also exclude unstable angina. METHODS: We measured hsTnT ex-post on the admission frozen blood sample of 644 subjects with Braunwald IIIB CK-MB-negative unstable angina. This analysis included the 240 patients with hsTnT value ≤99th percentile reference limit (UA). We evaluated the clinical outcome of UA patients and the applicability of two rule-out strategies based on the combination of a non-ischemic ECG with (1) a single hsTnT value below the Limit-of-Detection (LoD), (2) a TIMI risk score ≤1. RESULTS: UA patients with hsTnT ≤99th percentile reference limit had a favorable 30-day outcome [0.8% MI, 0% cardiovascular death (CVD)], but the rate of CVD/MI at 180-day was 4.7%. Sensitivities for UA were 94.6% according to the 'TIMI ≤1-strategy' and 75.4% according to 'hsTnT-below-LoD-strategy', accounting for 5.4 and 24.6% missed diagnoses, respectively. A prognostic risk stratification to guide appropriate outpatient assessment in potential discharged unrecognized UA patients was developed: a risk score based on the combination of age >60 years and C-reactive protein >4.5 mg/L effectively stratified the 180-day CVD/MI occurrence: 0, 2.5 and 12.7% for score 0, 1 and 2 (log-rank = 0.001, C-statistic = 0.776). CONCLUSION: Single measurement hsTnT strategies, successfully tested to rule-out MI, may allow safe ED discharge of patients with a suspected acute coronary syndrome: even if UA may not be excluded, its short-term prognosis is favorable. UA patients with a C-reactive protein >4.5 mg/L and older than 60 years have a substantial medium-term cardiovascular risk and may benefit from a timely outpatient diagnostic assessment.

Serum Levels of Cystatin C, N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP), and Cardiac Function in Patients with Unstable Angina Pectoris.

BACKGROUND This study aimed to investigate the association between serum levels of cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac function in patients with unstable angina pectoris (UAP). MATERIAL AND METHODS A cross-sectional observational study was conducted at a single center and recruited 300 patients (214 men and 86 women), who were diagnosed with UAP between June 2018 to December 2018. The patients had serum levels of NT-ProBNP measured and were divided into four groups according to the serum levels of cystatin C: Q1, 0.49-0.83 mg/L; Q2, 0.84-1.04 mg/L; Q3, 1.05-1.38 mg/L; Q4, 1.39-4.21 mg/L. Cardiac function was graded according to the New York Heart Association (NYHA) class I to IV criteria. RESULTS In the 300 patients with UAP, there were significant differences in cardiac function and NT-ProBNP levels between the four study groups (Q1 to Q4) (p<0.05). Univariate analysis showed that body weight, heart rate, treatment with aspirin, ticagrelor, angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker (ACE/ARB), diuretic use, uric acid level, and serum cystatin C levels were significantly associated with increased levels of NT-ProBNP. After adjusting for confounding factors screened in univariate analysis, multivariate regression analysis showed that increased serum cystatin C levels were significantly associated with increased levels of NT-ProBNP. CONCLUSIONS Increased serum levels of cystatin C were associated with poor cardiac function and increased levels of NT-ProBNP in patients with UAP.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population.

INTRODUCTION: Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran. MATERIAL AND METHODS: This prospective cohort study comprised a population of 8698 men and women aged 35-65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence. RESULTS: After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19-2; P-value< 0.01; HR: 1.53; 95% CI: 1.18-1.98; P < 0.01; HR: 1.57; 95% CI: 1.27-2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12-6.57; P-value< 0.05). CONCLUSION: In the present study, TC baseline level was significantly associated with the risk of MI among men.