Risk Of Recurrent Coronary Events Research Articles

Recurrent events after acute ST-segment elevation myocardial infarction: predictors and features of plaque progression and stent failure.

Patients with acute ST-segment elevation myocardial infarction (STEMI) are at high risk for recurrent coronary events (RCE). Non-culprit plaque progression and stent failure are the main causes of RCEs. We sought to identify the incidence and predictors of RCEs. Eight hundred thirty patients with STEMI were enrolled and followed up for 5 years. All patients underwent blood test analysis at hospital admission, at 1-month and at 12-month follow-up times. Patients were divided into RCE group and control group. RCE group was further categorized into non-culprit plaque progression and stent failure subgroups. Among 830 patients with STEMI, 63 patients had a RCE (7.6%). At hospital admission, HDL was numerically lower in RCE group, while LDL at both 1-month and 12-month follow-up times were significantly higher in RCE group. Both HDL at hospital admission and LDL at 12-month follow-up were independently associated with RCEs (OR 0.90, 95% CI 0.81-0.99 and OR 1.041, 95% CI 1.01-1.07, respectively). RCEs were due to non-culprit plaque progression in 47.6% of cases, while in 36.5% due to stent failure. The mean time frame between pPCI and RCE was significantly greater for non-culprit plaque progression subgroup as compared to stent failure subgroup (27 ± 18 months and 16 ± 14 months, P = 0.032). RCEs still affect patients after pPCI. Low levels of HDL at admission and high levels of LDL at 12 months after pPCI significantly predicted RCEs. A RCE results in non-culprit plaque progression presents much later than an event due to stent failure.

Clinical Features of Acute Coronary Syndrome in Patients with Coronary Heart Disease and Its Correlation with Tumour Necrosis Factor in Cardiology.

Tumour necrosis factor (TNF) levels are higher in patients who have experienced an acute ischemic stroke. Greater levels of TNF may not be linked to an increased risk of recurrent coronary events in the stable phase after myocardial ischemia (MI). Coronary atheroma is connected to endothelial and smooth muscle cells, as well as macrophages that emit the multifunctional cytokine tumour necrosis factor (TNF). Transplanted tumours become more vulnerable when TNF-α was first recognized to have a function in hemorrhagic necrosis. TNF-α has been demonstrated to induce heart failure, pulmonary edoema, and cardiomyopathy in people with advanced heart failure when it is elevated in the bloodstream. It has been postulated that prolonged overexpression of TNF-α after ischemia may contribute to poor cardiac outcomes by increasing TNF-α when the myocardium undergoes both temporary ischemia and reperfusion. A rise in TNF levels has been seen after a myocardial infarction, but it is unclear if these higher levels, found months after the initial event, are associated with an increased risk of subsequent heart attacks. We looked at TNF levels in the blood of 270 patients with coronary heart disease in the Chinese Hypertension League's Cholesterol and Recurrent Events (CARE) experiment to see if this notion held true. Recurrent coronary syndrome and coronary mortality were monitored prospectively in the participants. The min max imbalance normalization can be used to assess a patient's baseline characteristics, including hormone and cholesterol test results. Type 2 stimulant connection to aggregate the TNF-signaling qualities and fuzzy techniques was applied. There may now be enough preliminary evidence from the crucial bundle neural network analysis to identify the risk of coronary heart disease associated with TNF pregeneration studies. The tests were assessed using a variety of methods and performance metrics in a Matlab environment.

Gender differences in cardiovascular risk factor awareness. Results from the ESC EORP EUROASPIRE V registry

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Fonds voor hartchirurgie - Fonds pour la Chirurgie Cardiaque Background Risk factor awareness among coronary patients is related to a decreased risk of recurrent coronary events and hence important in the secondary prevention of coronary heart disease (CHD). Whereas previous studies demonstrated gender differences in disfavour of women with regard to patients’ risk factor control, little is known about gender differences in patients’ risk factor awareness. Purpose The aim of this study was to document potential gender differences across Europe in patients’ risk factor awareness and information provided by healthcare professionals. Methods Analyses were based on data from the most recent ESC EORP EUROASPIRE V survey (European Survey Of Cardiovascular Disease Prevention And Diabetes, 2016-17). Consecutive patients hospitalized for a first or recurrent coronary event or surgical procedure between 18-80 years old at the time of identification were retrospectively identified in 27 countries. Awareness of risk factor levels were defined as patients’ self-reported awareness about their latest weight, waist circumference, blood pressure, total cholesterol, blood glucose levels, and HbA1c levels. Data on risk factor awareness and information provided by healthcare professionals were obtained from patient interviews (6 months to 2 years prior to the date of the study visit). Logistic regression analyses were performed adjusting for age and medical history (stroke, heart failure, and diabetes). Results Information was available on 8,261 patients, including 25.8% women. Women were significantly older (65.4 vs. 63.0 years) and were more likely to have a history of stroke (5.3% vs. 3.7%; P=0.002), heart failure (7.6% vs. 5.9%; P=0.006), and self-reported diabetes (33.1% vs. 28.0%; P<0.001). Overall, no significant gender differences were found regarding the information provided by a healthcare professional on overweight, diabetes, and chronic kidney disease, whereas, a higher proportion of women with hypertension (≥140/80 (≥140/85 if diabetes)) (OR=2.07, 95% CI=4.60-2.68) and women with raised cholesterol levels (LDL-C ≥1.8mmol/L) (OR=1.31, 95% CI=1.14-1.51) were informed about their raised risk factor levels. Furthermore, women with obesity were less aware about their actual weight (OR= 0.66, 95% CI=0.52-0.85) and weight target level (OR= 0.66, 95% CI=0.54-0.81) than men. In contrast, no significant gender differences in awareness of waist circumference levels were found in obese patients neither for fasting blood glucose or HbA1c levels in patients with self-reported diabetes. Women with hypertension and those found with raised LDL-C levels were more aware about their target blood pressure level (OR=1.21, 95% CI=1.01-1.46) and actual cholesterol level (OR=1.18, 95% CI=1.02-1.36). Conclusions Our study reveals only little gender differences in disfavour of women in terms of information provided by healthcare professionals and risk factor awareness.

Gender differences in cardiovascular risk factor awareness: Results from the ESC EORP EUROASPIRE V Registry

BackgroundPatients' risk factor awareness is essential to decrease the risk of recurrent coronary events. The aim of this study was to provide up-to-date evidence on existing gender differences in the patients' knowledge of risk factors and information provided by healthcare professionals. MethodsAnalyses were based on the cross-sectional ESC EORP EUROASPIRE V survey, including data on CHD patients across 27 European countries. Consecutive patients (18–80 years), hospitalized for a coronary event or surgical procedure, were retrospectively identified. Information on risk factor awareness was collected from medical records, medical examination, and structured questionnaires during the study visit (six months to two years after hospitalization). ResultsPatient information was available for 8261 patients, of which 25.8% were women. Although women with obesity were significantly less aware about their actual (OR = 0.66, CI = 0.52–0.85) and target weight levels (OR = 0.66, CI = 0.54–0.81), no significant gender differences in risk factor awareness were found in disfavour of women. Remarkably, women with hypertension and women with raised low-density lipoprotein cholesterol (LDL-C) levels were even more aware about their target blood pressure levels (OR = 1.21, CI = 1.01–1.46) and actual cholesterol levels (OR = 1.18, CI = 1.02–1.36), respectively. Moreover, there is some indication that women were more informed by a healthcare professional if they had raised CHD risk factor levels. ConclusionsOur study showed only few gender differences in disfavour of women in terms of risk factor awareness and information provided by a healthcare professional. Nevertheless, previous EUROASPIRE V findings demonstrated that women still have a poorer risk factor control in secondary CHD prevention.

Effect of Prediabetes on Long-Term Risk of Developing Cardiac Events in Patients Presenting With Acute Coronary Syndrome

Type 2 diabetes is associated with an increased risk of recurrent coronary events compared to individuals without diabetes. However, whether prediabetes confers a similar risk to established diabetes for developing subsequent cardiac events is less clear. This study aims to investigate the long-term risk associated with prediabetes and developing subsequent cardiac events in patients presenting with acute coronary syndrome (ACS) at the University of Ottawa Heart Institute.

Elevated soluble lectin-like oxidised low-density lipoprotein receptor-1 (sLOX-1) associated with increased risk for heart failure and MACE after an acute coronary event

Abstract Background/Introduction The lectin-like oxidised low-density lipoprotein receptor (LOX-1) is involved in atherosclerotic plaque inflammation and vulnerability. Plasma levels of soluble LOX-1 (sLOX-1) have previously been associated with increased risk for recurrent coronary events and mortality in patients with acute coronary syndrome (ACS). Purpose To assess the association of sLOX-1 with the development of heart failure (HF) post-ACS. Methods We measured sLOX-1 in 524 patients with ACS within 24 hours after the acute event. A subgroup of 97 of these patients completed a follow-up echocardiogram after one year. The incidence of HF-related hospitalisation and recurrent major adverse cardiovascular events (MACE), defined as recurrent ACS or cardiovascular death, was followed for a mean period of two years. In a separate cohort of 363 patients with ACS and percutaneous coronary intervention (PCI), we studied the correlations between sLOX-1, coronary flow reserve, left ventricular systolic function and systemic inflammation at two follow-up visits within four weeks and 16 weeks post-ACS, respectively. Results Baseline sLOX-1 was positively associated with the risk of HF and MACE, independently of traditional cardiovascular risk factors, revascularisation and medication. The hazard ratios and 95% confidence intervals were 1.57 (1.10–2.23), p=0.012 for HF and 1.36 (1.08–1.71), p=0.009 for MACE per standard deviation baseline sLOX-1 increase. Elevated sLOX-1 was also negatively associated with lower-left ventricular ejection fraction at one year (r=−0.263, p=0.009). In the second ACS cohort, we found that plasma sLOX-1 measured at the two follow-up visits was negatively associated with coronary flow reserve and left ventricular systolic function, and positively correlated with biomarkers of systemic inflammation and cardiac overload. Conclusion Elevated sLOX-1 is associated with the development of HF and recurrent cardiovascular events in patients with ACS. Although this association study cannot confirm causality, the results suggest LOX-1 as a potential biomarker and treatment target in patients with ACS. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): • Swedish Research Council • The Swedish Heart and Lung foundation• Swedish Foundation for Strategic Research Dnr IRC15-0067 • Marianne and Marcus Wallenberg Foundation • Bundy Academy at Lund University

Long Working Hours and Risk of Recurrent Coronary Events

BackgroundEvidence from prospective studies has suggested that long working hours are associated with incident coronary heart disease (CHD) events. However, no previous study has examined whether long working hours are associated with an increased risk of recurrent CHD events among patients returning to work after a first myocardial infarction (MI). ObjectivesThe purpose of this study was to examine the effect of long working hours on the risk of recurrent CHD events. MethodsThis is a prospective cohort study of 967 men and women age 35 to 59 years who returned to work after a first MI. Patients were recruited from 30 hospitals across the province of Quebec, Canada. The mean follow-up duration was 5.9 years. Long working hours were assessed on average 6 weeks after their return to work. Incident CHD events (fatal or nonfatal MI and unstable angina) occurring during follow-up were determined using patients’ medical files. Hazard ratios were estimated using Cox proportional hazard regression models. Splines and fractional polynomial regressions were used for flexible exposure and time modeling. ResultsRecurrent CHD events occurred among 205 patients. Participants working long hours (≥55 h/week) had a higher risk of recurrent CHD events after controlling for sociodemographics, lifestyle-related risk factors, clinical risk factors, work environment factors, and personality factors (hazard ratio vs. 35 to 40 h/week: 1.67; 95% confidence interval: 1.10 to 2.53). These results showed a linear risk increase after 40 h/week and a stronger effect after the first 4 years of follow-up and when long working hours are combined with job strain. ConclusionsAmong patients returning to work after a first MI, longer working hours per week is associated with an increased risk of recurrent CHD events. Secondary prevention interventions aiming to reduce the number of working hours among these patients may lower the risk of CHD recurrence.

Risk of Recurrent Coronary Events in Patients With Familial Hypercholesterolemia; A 10-Years Prospective Study.

Background and Aim: Real world evidence on long term treatment of patients with familial hypercholesterolemia (FH) is important. We studied the effects of intensive lipid lowering medication (LLM) and optimized lifestyle in the study TTTFH–Treat To Target FH. Materials and Methods: Adults with a first known total cholesterol of mean (95% CI) 9.8 mmol/L (9.5, 10.1) were included consecutively in their routine consultation during 2006. Of the patients 86.4% had a pathogenic FH-mutation and the remaining were clinically diagnosed. We included 357 patients and 279 met for follow-up after median 10.0 (min 8.1, max 12.8) years. Results: Mean (95% CI) low density lipoprotein (LDL-C) was reduced from 3.9 (3.8, 4.1) to 3.0 (2.9, 3.2). More men than women used high intensity statin treatment, 85.2 and 60.8%, respectively. Women (n = 129) had higher LDL-C; 3.3 mmol/L (3.0, 3.5), than men; (n = 144) 2.8 mmol/L (2.6, 3.0), p = 0.004. Add-on PCSK9 inhibitors (n = 25) reduced mean LDL-C to 2.0 (1.4, 2.6) mmol/L. At enrollment 57 patients (20.4%) had established atherosclerotic cardiovascular disease (ASCVD), and 46 (80.4%) of them experienced a new event during the study period. Similarly, 222 (79.6%) patients had no detectable ASCVD at enrollment, and 29 of them (13.1%) experienced a first-time event during the study period. Conclusion: A mean LDL-C of 3.0 mmol/L was achievable in FH, treated intensively at a specialized clinic with few users of PCSK9 inhibitors. LDL-C was higher (0.5 mmol/L) in women than in men. In patients with ASCVD at enrollment, most (80.7%) experienced a new ASCVD event in the study period. The FH patients in primary prevention had more moderate CV risk, 13% in ten years.

5234KAND567, the first selective small molecule CX3CR1 antagonist in clinical development, mediates anti-inflammatory cardioprotective effects in rodent models of atherosclerosis and myocardial infarction

Abstract Background Fractalkine is a chemokine that mediates recruitment and extravasation of CX3CR1-expressing subsets of leukocytes and monocytes and has been implicated in the inflammation-driven pathology of cardiovascular disease. More specifically, fractalkine signaling has been proposed to contribute to increased infarct size and enhanced atherosclerotic plaque vulnerability in patients and experimental models. Blocking fractalkine/CX3CR1 signaling is suggested as a promising anti-inflammatory strategy for the treatment of both acute and chronic cardiovascular disease. KAND567 is a small molecule, selective, non-competitive, allosteric antagonist of the fractalkine receptor CX3CR1, that is under preparation for a clinical phase IIa study in AMI patients. Purpose To explore the therapeutic effects of the short and long term administration of KAND567 in experimental rodent models of acute myocardial infarction and atherosclerosis, respectively. Methods Myocardial infarction was induced in Wistar rats (N=6–8 per group) by ligation of the left anterior descending (LAD) coronary artery for 30 minutes followed by 2 h of reperfusion. The drug or vehicle infusion started either 5 min before or 30 min after start of reperfusion and continued during the remainder of the experiment. Hearts were collected and subjected to triphenyl tetrazolium chlorine (TTC) staining and the infarction area/area at risk of the left ventricle was determined by planimetry and compared against vehicle group. Atherosclerosis-prone LDL-receptor deficient mice on a high-cholesterol diet, (N=15–25 per group) were treated with KAND567 for 15–23 weeks. Atherosclerotic plaque development in the thoracic arch was determined by ultrasound imaging and histology. Immunohistochemistry was used to follow changes in the cellular composition in the atherosclerotic lesions. Results In the acute myocardial infarction study, the infusion of KAND567 before the start of reperfusion significantly reduced infarcted/risk area (by up to 50%) as compared to the vehicle group. However, the infusion had no effect on the infarct size when administration was initiated 30 min after start of reperfusion. In the atherogenesis study, oral treatment with KAND567 significantly reduced vascular macrophage infiltration by 50% and reduced intima media thickness. Furthermore, reduced plaque volume and a more stable plaque phenotype was noted following treatment with KAND567. KAND567 experimental results Conclusion Specific inhibition of fractalkine-driven inflammation by KAND567 provides cardioprotective, anti-atherosclerotic and plaque stabilizing effects via mechanisms related to immune cell infiltration, in rodent models. Further studies should be initiated to test if KAND567 is a potential candidate drug, targeting the excessive inflammatory injury associated with ischemia/reperfusion in myocardial infarction and providing plaque stabilization by reducing inflammatory risk for recurrent coronary events.

Long-term dual antiplatelet therapy: pharmacological and clinical implications.

: Patients experiencing an acute coronary syndrome are exposed to an increased residual risk of recurrent coronary events. Dual antiplatelet therapy (DAPT) is highly effective in preventing atherothrombotic complications in patients with previous myocardial infarction and current guidelines recommend the prescription of DAPT for at least 12 months in all patients experiencing an acute event. However, recent findings demonstrated that long-term DAPT (over 12 months) is related to a better outcome in patients at high risk, suggesting the use of a long-term DAPT to achieve a better clinical outcome. The choice of DAPT duration is still a difficult issue and a personalized approach to the patients is mandatory to manage both the residual ischemic risk and the risk of bleeding events.The aim of this review is to analyze the pharmacological characteristics of available antiplatelet agents and to revise the use of DAPT in clinical practice, focusing on the benefits of a long-term approach.

Ticagrelor for Secondary Prevention of Atherothrombotic Events in Patients With Multivessel Coronary Disease

BackgroundPatients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events. ObjectivesThe authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial. MethodsPatients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months. ResultsA total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HRadj]: 1.24; p = 0.026) and for coronary events (7.67% vs. 5.34%, HRadj: 1.49; p = 0.0005). In patients with MVD, ticagrelor reduced the risk of MACE (7.94% vs. 9.37%, HR: 0.82; p = 0.004) and coronary events (6.02% vs. 7.67%, HR: 0.76; p < 0.0001), including a 36% reduction in coronary death (HR: 0.64; 95% confidence interval: 0.48 to 0.85; p = 0.002). In this subgroup, ticagrelor increased the risk of TIMI major bleeding (2.52% vs. 1.08%, HR: 2.67; p < 0.0001), but not ICH or fatal bleeds. ConclusionsPatients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562)

The role of cytokine gene polymorphism in the development of acute myocardial infarction

The continuous growth of cardiovascular diseases is one of the important challenges facing the modern medicine. They are the primary cause of death both in developed countries and inUkrainein particular. The aim of the study is to perform analysis of modern literary sources related to the role of cytokine gene polymorphism in the development of acute myocardial infarction. The basis for the search for candidate genes was study of individual characteristics and identifying genetic polymorphisms that increase the risk of triggering mechanisms of atherosclerotic lesions of the coronary vessels and the consequent acute myocardial infarction development. Cytokine genes feature a very high level of polymorphisms. The obtained results of the study are quite contradictory, in addition there is no consensus on their application. One of these candidate genes is the gene encoding interleukin-6 production. This is one of the proinflammatory cytokines, elevated levels of which are associated with the development and course of coronary heart disease, as well as with the processes of the atherosclerotic plaque destabilization. Polymorphic marker in interleukin-6 (-174-G/C) gene promoter is associated with IL-6 gene expression level and the level of Interleukin-6 inplasma, and can affect the course of ischemic heart disease. The tumor necrosis factor-α is a multifunctional proinflammatory cytokine which is produced mainly by monocytes and macrophages. Concentration of tumor necrosis factor-α in blood plasma is constantly increased in patients after acute myocardial infarction with an increased risk of recurrent coronary events. These data support the hypothesis that stable patients are at risk of constant inflammatory instability. Increased production of tumor necrosis factor-α is considered an important cause of destabilization of atherosclerotic plaques. The gene cluster of tumor necrosis factor-α is within the region of class III genes of highly polymorphic major histocompatibility complex, located on human chromosome 6 at the position 6p21.1–21.3. Another candidate gene encodes interleukin-10, being an anti-inflammatory cytokine is an inhibitor of inflammation located on chromosome 1 at the position 1q31–q32. The research identified a number of IL-10 gene polymorphisms at positions -592, -627, -1082. Conclusions. Analysis of the above literature allows us to make a conclusion that: first, the concentration of cytokines depends on the genetic characteristics of an individual; secondly, cytokine gene polymorphism may be of importance in regard to the course of coronary heart disease.

Terminalia methanol extracts inhibit the amidolytic activity of human activated factor XII (Hageman factor)

The long‐term goal of this study is to develop the selective inhibitors of FXIIa based on traditional medicine, which might be safe, and effective. There are positive correlations between increased plasma FXIIa levels with coronary heart disease as well as increased risk of recurrent coronary events. Although they maintain a normal hemostasis, FXII knockout mice (FXII−/−) display defective arterial thrombus formation. In addition, FXII−/− mice are protected from development of cerebral ischemia and pulmonary embolism. Thus, inhibition of FXIIa would help prevent cardiovascular diseases. The present study examines the effects of different but related herbal medicines that impact on the plasma blood coagulation FXII. While it initiates the activation of blood coagulation to stop any bleeding, FXII helps the remaining blood clotting factors and platelets to keep certain circulating pathogenic microorganism close to the phagocytes. The negative charge on the microorganism surface or platelet polyphosphate (poly P) binds readily to zymogen FXII, resulting in the activation of FXII. Evidence indicates that poly P containing pathogens promote FXII‐mediated blood coagulation independent of factor XI, reflecting a novel poly P‐induced thrombus formation. The methanol extracts of T. chebula fruit, T. bellirica fruit, T. arjuna fruit, and T. arjuna bark blocked FXIIa activity with IC50 values of 30, 50, 190, 190 and 27 mg/ml, respectively. Two isolated compounds from Terminalia, Arjunoglucoside II and arjunic acid blocked FXIIa activity with IC50 values of 370 and 780 μM, respectively. T. chebula fruit, T. and arjuna fruit extracts at 50 mg/ml did not affect endothelial cells viability. Overall, T. chebula fruit and T. arjuna fruit extracts might be useful to improve symptoms of FXIIa‐dependent inflammation and thrombosis.

SMOKING AS A RISK FACTOR OF CARDIOVASCULAR AND CEREBROVASCULAR DISEASES: PREVALENCE, IMPACT ON PROGNOSIS, POSSIBLE SMOKING CESSATION STRATEGIES AND THEIR EFFECTIVENESS. Part 1. Smoking Prevalence and Impact on Prognosis

The prevalence of smoking in the Russian Federation is 27.7%. Losses of potential years of life in working age associated with premature death due to smoking in Russia on average are 9 years for men, for women – 5.6 years. Tobacco use is a risk factor for 6 of 8 main causes of death in the world: ischemic heart disease (IHD); cerebral circulation disorders; lower respiratory tract infection; chronic obstructive pulmonary disease; tuberculosis; trachea, bronchus, and lung cancer. The risk of developing IHD in smoking patients is increased by 2-4 times in men and women and in any age group. Myocardial infarction occurs in smoking patients at a younger age, and they have a similar risk of coronary events with patients of older age groups. The increased risk of recurrent coronary events persists with the continuation of smoking in the patient after myocardial infarction. Smoking is associated with a double risk of ischemic stroke and a 2-4-fold increase in the risk of subarachnoid hemorrhage. The risk of peripheral arteries diseases in smokers is increased 3-6 times than this in non-smokers. The mechanisms of development of acute cardiovascular events during smoking include the activation of inflammation, platelet aggregation/thrombogenesis, the sympathetic nervous system, and the development of endothelial dysfunction due to exposure to tobacco smoke components.

THE INFLUENCE OF CELL AND PLASMA HEMOSTASIS AND BIOMARKER LEVELS ON CLINICAL OUTCOMES IN PATIENTS WITH UNSTABLE ANGINA AND RESISTANCE TO ANTIPLATELET AGENTS

SUMMARY Objective: to assess the impact of cell plasma hemostasis disorders and the level of biomarkers on clinical outcomes and to develop laboratory diagnostic criteria forecast recurrent coronary events in patients with unstable angina. Material and Methods: the study included 124 patients with unstable angina. All patients were performed: complete blood count, to determine the level for TnI, the determination of inflammatory markers (hs C-reactive protein (CRP)), the level of myeloperoxidase, von Willebrand factor, the level of thrombin, fibrinogen (FG), antithrombin III (AT III), D-dimer, factor Xa), agregatogramm was performed an impedance aggregometer Multiplate and determining platelet activation by flow cytometry. All patients underwent ECG, echocardiogram, 24-hour ECG monitoring, coronary angiography. Results: developed independent predictors of the risk of recurrent coronary events in patients with unstable angina: the threshold values for evaluating platelet aggregation analyzer Multiplate-ASPI-test (AUC) &gt;52 U, ADP-test (AUC) &gt;60 U; the peak concentration of thrombin &gt;294,5 nM, platelet size - MPV &gt;9,6 fl, myeloperoxidase level &gt;316 pmol/l, hsCRP &gt;3.8 g/l, and troponin I &gt;0,07 ng/ml. We created the scale of the prediction of recurrent coronary events after suffering unstable angina. In patients included to the study it was found that 18 patients (14.5%) recorded a decrease of sensitivity to aspirin (ASA)in the standard dose of 75 mg, in 24 patients (19.4%) to clopidogrel 75 mg and in 8 patients (6,5%) - both to ASA and clopidogrel. It was found that the resistance to ASA and/or clopidogrel more than 2.5 [CI, 2.0; 2.8] once increases the relative risk of recurrent ischemic events. Conclusions: developed by independent predictors of the risk of recurrent coronary events in patients with unstable angina: AUC ASPI- test&gt;52 U, AUC ADP- test&gt;60 U; the peak concentration of thrombin&gt;294,5 nM, platelet size - MPV&gt;9,6 fl, myeloperoxidase &gt;316 pmol/l, high-sensitivity CRP &gt;3.8 g/l, the level of troponin I&gt;0,07 ng/ml. Keywords: unstable angina, resistance to ап^рШеШ agents, agregatogramm, cell and plasma hemostasis

Inflammatory markers modify the risk of recurrent coronary events associated with apolipoprotein A-I in postinfarction patients

Laboratory findings have suggested that systemic and vascular inflammation can impair the antiatherogenic function of high-density lipoproteins (HDLs). However, evidence from population studies is sparse. The objective of the study was to assess if blood inflammatory markers modify the risk of recurrent coronary events associated with apolipoprotein A-I (apoA-I) and HDL cholesterol (HDL-C) among postinfarction patients. ApoA-I, HDL-C, and inflammatory markers (C-reactive protein [CRP], serum amyloid A (SAA), fibrinogen, von Willebrand factor [vWF], and D-dimer) were measured from blood samples of 1028 patients drawn 2months after an index myocardial infarction (MI). Patients were followed up for the composite coronary endpoint (nonfatal MI, coronary death, or unstable angina) for an average of 26months. Cox proportional hazard models were used to assess effect modifications for the association of apoA-I and HDL-C with coronary risk by each inflammatory marker. CRP significantly modified the risk of recurrent coronary events associated with apoA-I. Among the entire population, multivariable-adjusted hazard ratios associated with each standard deviation increase in apoA-I for those with low and high CRP levels were 0.89 and 1.35, respectively (P value for interaction=.008). vWF was a significant effect modifier of the apoA-I/coronary risk association only among diabetic patients (hazard ratios were 0.56 and 1.43, for diabetic patients with low and high vWF levels, respectively; P value for interaction=.002). No effect modification was observed for the HDL-C/coronary risk association. Among stable post-MI patients, CRP modified the risk of recurrent coronary events associated with apoA-I. VWF modified this association only among the diabetic subgroup.

LATITUDE-TIMI: is there still hope for anti-inflammatory therapy in acute myocardial infaction?

Inflammation is a crucial feature of atherosclerotic plaque formation as well as post myocardial infarction (MI) remodeling and thus thought to play an essential role in the pathogenesis of ischemic heart disease and its complications (1,2). The regenerative processes after MI involve inflammatory, proliferative and maturation phases that are crucial for wound healing and reparation (3). However, an overactive inflammatory and fibrotic response is associated with maladaptive structural and electrophysiological remodeling, leading to systolic as well as diastolic dysfunction and contributing to the development of an arrhythmogenic substrate (2,4). Moreover, elevated cytokine levels also correlate with increased risk for recurrent coronary events in patients with MI (5).

Insulin resistance predicts the risk for recurrent coronary events in post-infarction patients.

We investigated the risk for recurrent coronary events associated with insulin resistance in post-infarction patients from the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) study. The association between insulin resistance expressed by Homeostatic Model As-sessment 2 for Insulin Resistance (HOMA2-IR) and the risk for recurrent coronary events was investigated in a cohort of 1,032 patients evaluated 2 months after myocardial infarction (MI) with a follow-up of 26 months. The endpoint for the study was recurrent coronary event defined as cardiac death, nonfatal MI, or unstable angina, whichever occurred first. We used time dependent survival analysis and Cox proportional hazards regression method to determine the association between HOMA2 categorized as high > 75th percentile and endpoints after adjustment for relevant clinical covariates and series of thrombogenic and dyslipogenic factors. High HOMA2-IR defined as in fourth quartile (≥ 2.4) was associated with increased risk for recurrent coronary events (HR 1.44; CI 1.03-2.01; p = 0.03) after adjustment for the clinical covariates: age, gender, diabetes, prior MI, pulmonary congestion, coronary artery bypass grafting and percutaneous transluminal coronary angioplasty. The highest risk of cardiac events was observed in non-obese patients (body mass index [BMI] ≤ 30 kg/m2) with high HOMA2-IR (HR 1.5; CI 1.02-2.22; p = 0.038). The plasma level of plasminogen activa-tor inhibitor-1 was associated with higher risk for recurrent coronary events in patients with insulin resistance (HR 1.79; CI 1.05-3.03; p = 0.03, interaction p = 0.018). In conclusion, insulin resistance predicts recurrence of coronary events in post-infarction population. HOMA2-IR is better than BMI in stratifying risk of recurrent coronary events.

On-Statin Resistin, Leptin, and Risk of Recurrent Coronary Events After Hospitalization for an Acute Coronary Syndrome (from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Study)

Resistin is an adipokine secreted by macrophages and inflammatory cells linked to insulin resistance and inflammation. Leptin is an adipokine regulator of appetite and obesity. Although circulating levels of both have been associated with atherosclerosis, few data have reported their relation to coronary events in the context of statin therapy. This study measured on-statin levels of both resistin and leptin through enzyme-linked immunosorbent assay in a nested case-control cohort (n= 176 cases with coronary death, myocardial infarction, or unstable angina pectoris observed in follow-up matched 1:1 to 176 controls) derived from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 study, a randomized controlled trial of atorvastatin 80mg/day versus pravastatin 40mg/day in patients with a recent acute coronary syndrome. Resistin demonstrated a moderate association with high-sensitivity C-reactive protein (hsCRP; Spearman rho= 0.25, p <0.0001). On-statin resistin levels were linked to recurrent coronary events in conditional logistic regression analysis adjusted for additional risk factors including hsCRP and history of diabetes (tertile 3 vs 1 adjusted odds ratio 2.08; 95% confidence interval [CI] 1.04 to 4.19). An additive risk was noted when patients were stratified by resistin and glycated hemoglobin levels. In contrast, leptin levels were associated with obesity, diabetes, triglycerides, and hsCRP (p <0.001 for each) but demonstrated no association with recurrent coronary events (tertile 3 vs 1 adjusted odds ratio 0.72; 95% CI 0.28 to 1.83). In conclusion, on-statin resistin, but not leptin, is an independent marker of residual risk for recurrent coronary events in patients after hospitalization for an acute coronary syndrome.

The Association Between Central Fat Distribution and Recurrent Cardiovascular Disease Events in Female Survivors of Nonfatal Myocardial Infarction

Visceral fat has been shown to be an important predictor of metabolic alterations that lead to increased cardiovascular disease (CVD) risk factors, morbidity, and mortality. The aim of this study was to investigate the association between central fat distribution and the risk of recurrent coronary events among a cohort of female myocardial infarction (MI) survivors. Participants included 356 women (mean ± SD age, 55 ± 8.71 years) discharged alive after an incident MI from hospitals in Erie and Niagara (New York) counties between 1996 and 2004. A recurrent cardiovascular event was any nonfatal or fatal International Classification of Diseases, Ninth Revision-coded diagnosis between 390 and 450. The mean ± SD follow-up time was 4.01 ± 2.6 years. Interviews and self-administered follow-up surveys were used to collect pertinent information, and a search of the National Death Index Plus database was completed. Eighty-five women experienced a recurrent cardiovascular event. Using Cox proportional hazards analyses, the crude model for body mass index suggested that after incident MI, women had a 39% risk of a recurrent CVD event (hazard ratio [HR], 1.39; confidence interval [CI], 0.76-2.54; P = .293), whereas crude models for waist circumference and sagittal abdominal distention showed the risk to be more than twice as high (HR, 2.12; CI, 1.08-4.16; P = .010; and HR, 2.16; CI, 1.09-4.28; P = .037, respectively). Both measures of central fat distribution appeared to be better predictors of recurrent cardiovascular events when compared with body mass index, whereas sagittal abdominal distention was the better predictor compared with waist circumference, even after multivariate adjustment. After adjusting for secondary prevention interventions-statin, aspirin, β-blocker use, and physical activity-the risk of recurrent event was observed to decrease by about 1%. These results suggest that central fat distribution is positively associated with a recurrence of cardiovascular events after incident MI in women. The absence of decreased risk with secondary prevention interventions suggests that more investigation into the association of central abdominal fat and secondary prevention management is warranted.