COVID-19 and Acute Coronary Syndromes: From Pathophysiology to Clinical Perspectives.

Acute coronary syndromes (ACS) are frequently reported in patients with coronavirus disease 2019 (COVID-19) and may impact patient clinical course and mortality. Although the underlying pathogenesis remains unclear, several potential mechanisms have been hypothesized, including oxygen supply/demand imbalance, direct viral cellular damage, systemic inflammatory response with cytokine-mediated injury, microvascular thrombosis, and endothelial dysfunction. The severe hypoxic state, combined with other conditions frequently reported in COVID-19, namely sepsis, tachyarrhythmias, anemia, hypotension, and shock, can induce a myocardial damage due to the mismatch between oxygen supply and demand and results in type 2 myocardial infarction (MI). In addition, COVID-19 promotes atherosclerotic plaque instability and thrombus formation and may precipitate type 1 MI. Patients with severe disease often show decrease in platelets count, higher levels of d-dimer, ultralarge von Willebrand factor multimers, tissue factor, and prolongation of prothrombin time, which reflects a prothrombotic state. An endothelial dysfunction has been described as a consequence of the direct viral effects and of the hyperinflammatory environment. The expression of tissue factor, von Willebrand factor, thromboxane, and plasminogen activator inhibitor-1 promotes the prothrombotic status. In addition, endothelial cells generate superoxide anions, with enhanced local oxidative stress, and endothelin-1, which affects the vasodilator/vasoconstrictor balance and platelet aggregation. The optimal management of COVID-19 patients is a challenge both for logistic and clinical reasons. A deeper understanding of ACS pathophysiology may yield novel research insights and therapeutic perspectives in higher cardiovascular risk subjects with COVID-19.

International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19.

BACKGROUND: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. OBJECTIVES: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre-COVID-19 cohorts. METHODS: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re-myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre-COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). RESULTS: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001). CONCLUSIONS: In this multicenter international registry, COVID-19-positive ACS patients presented later and had increased in-hospital mortality compared with a pre-COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients.

Sex Differences in Extrahepatic Outcomes After Antiviral Treatment for Hepatitis C.

INTRODUCTION: Despite recognized differences in the rates of cardiovascular and renal disease between men and women in the general population, studies of the downstream effects of antiviral treatment for hepatitis C (HCV) have not investigated differences in outcomes based on sex. We analyzed sex differences in risk of acute coronary syndrome (ACS), end-stage renal disease (ESRD), and ischemic stroke by treatment and response in a large US-based multisite cohort of HCV patients. METHODS: Observation started at the HCV diagnosis date (untreated) or last antiviral treatment start (treated). Treatment selection bias was addressed using an inverse probability-weighting approach. We estimated the effect of treatment on the cumulative incidence of outcomes using the Fine-Gray method (subdistribution hazard ratios [sHR] and 95% confidence intervals [95% CI]). Death was a competing risk. RESULTS: Roughly 40% of 15,295 HCV patients were women. After controlling for other risk factors, sustained virological response (SVR) (interferon-based [IFN] or direct-acting antiviral [DAA]) significantly reduced risk of all outcomes, particularly among female patients. Female patients who achieved SVR after IFN-based treatment had significantly lower risk of ACS compared with male patients with SVR from either treatment type (sHR 0.45 [95% CI 0.35-0.59] vs 0.81 [95% CI 0.69-0.96, for DAA SVR] and sHR 0.72 [95% 0.62, 0.85, for IFN SVR]). Successful treatment seemed to be most protective against ESRD; female patients who achieved SVR were at 66%-68% lower risk than untreated patients (sHR 0.32 [95% CI 0.17-0.60 for DAA SVR] and 0.34 [95% CI 0.20-0.58 for IFN SVR]), whereas men were at 38%-42% lower risk (sHR 0.62 [95% CI 0.46-0.85 for DAA SVR] and 0.58 [95% CI 0.43-0.76 for IFN SVR]). IFN treatment failure significantly increased risk of all outcomes by 50%-100% among female patients. Compared with no treatment, female patients who experienced IFN treatment failure were at 63% increased risk of ACS (sHR 1.63 [95% CI 1.35-1.96]), almost twice the risk of ESRD (sHR 1.95 [95% CI 1.43-2.66]) and 51% increased risk of stroke (sHR 1.49 [95%CI 1.11-2.00]). DISCUSSION: SVR reduced the risk of extrahepatic complications, particularly in females. The significantly increased risk associated with IFN TF in women-a subset who represented roughly 10% of that group-underscores the importance of prioritizing these patients for DAA treatment irrespective of the fibrosis stage.

Management of acute coronary syndrome in the context of coronavirus disease 2019.

ABSTRACT: Coronavirus disease 2019 (COVID-19) is still developing worldwide. The prognosis of the disease will become worse and mortality will be even higher when it is combined with cardiovascular disease. Furthermore, COVID-19 is highly infectious and requires strict isolation measures. For acute coronary syndromes (ACS), a common cardiovascular disease, infection may aggravate the occurrence and development of ACS, making the management of more difficult. It will be an enormous challenge for clinical practice to deal with ACS in this setting of COVID-19.Aim to reduce the mortality of ACS patients during the epidemic of COVID-19 by standardizing procedures as much as possible.Pubmed and other relevant databases were searched to retrieve articles on COVID-19 and articles on ACS management strategies during previous influenza epidemics. The data was described and synthesized to summarize the diagnosis and management strategy of ACS, the preparation of catheter laboratory, and the protection of the medical staff in the context of COVID-19. Ethical approval is not required in this study, because it is a review with no recourse to patient identifiable information.Standardized diagnosis and treatment advice can help reduce the mortality of COVID-19 patients with ACS. In the absence of contraindications, the third generation of thrombolytic drugs should be the first choice for thrombolytic treatment in the isolation ward. For patients who have to receive PCI, this article provides detailed protective measures to avoid nosocomial infection.

Coronavirus disease-19 and cardiovascular disease: A risk factor or a risk marker?

Severe acute respiratory syndrome coronavirus-2 causes the clinical syndrome of coronavirus disease of 2019 (COVID-19) which has become a global pandemic resulting in significant morbidity and mortality. While the virus primarily affects the respiratory system, it also causes a wide variety of complex cardiac manifestations such as acute myopericarditis, acute coronary syndrome, congested heart failure, cardiogenic shock and cardiac arrhythmias. There are numerous proposed mechanisms of cardiac injury, including direct cellular injury, pro-inflammatory cytokine storm, myocardial oxygen-demand mismatch, and systemic inflammation causing multi-organ failure. Additionally, medications commonly used to treat COVID-19 patients have various cardiovascular side effects. We aim to provide a succinct review about the pathophysiology and cardiac manifestations of COVID-19, as well as treatment considerations and the various adaptations made to the current healthcare structure as a result of the pandemic.

Invasive strategy for COVID patients presenting with acute coronary syndrome: The first multicenter Italian experience.

OBJECTIVE: To report our initial experience of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/acute coronary syndrome (ACS) patients undergoing standard of care invasive management. BACKGROUND: The rapid diffusion of the SARS-CoV-2 together with the need for isolation for infected patients might be responsible for a suboptimal treatment for SARS-CoV-2 ACS patients. Recently, the group of Sichuan published a protocol for COVID/ACS infected patients that see the thrombolysis as the gold standard of care. METHODS: We enrolled 31 consecutive patients affected by SARS-COV-2 admitted to our emergencies room for suspected ACS. RESULTS: All patients underwent urgent coronary angiography and percutaneous coronary intervention (PCI) when required except two patients with severe hypoxemia and unstable hemodynamic condition that were conservatively treated. Twenty-one cases presented diffuse ST-segment depression while in the remaining cases anterior and inferior ST-elevation was present in four and six cases, respectively. PCI was performed in all cases expect two that were diagnosed as suspected myocarditis because of the absence of severe coronary disease and three with apical ballooning at ventriculography diagnostic for Tako-Tsubo syndromes. Two patients conservatively treated died. The remaining patients undergoing PCI survived except one that required endotracheal intubation (ETI) and died at Day 6. ETI was required in five more patients while in the remaining cases CPAP was used for respiratory support. CONCLUSIONS: Urgent PCI for ACS is often required in SARS-CoV-2 patients improving the prognosis in all but the most advanced patients. Complete patient history and examination, routine ECG monitoring, echocardiography, and careful evaluation of changes in cardiac enzymes should be part of the regular assessment procedures also in dedicated COVID positive units.

Manejo del síndrome coronario agudo durante pandemia por COVID ­ 19 / Management of acute coronary syndrome during COVID ­ 19 pandemic

INTRODUCTION: Acute Myocardial Infarction is a medical emergency, being his early and adequate treatment highly effective mainly in relation to reperfusion therapy. Unfortunately, COVID ­ 19 pandemic, has brought changes in its management due to availability of conditioned hemodynamic rooms, infection risk of the professionals, patient conditions and availability of critical unit beds. A review of the topic was made aimed to give a guide for the management of these patients with the available tools. MATERIALS AND METHOD: A review of the topic was made using the Medline/ Pubmed platform, in English and Spanish. Further, published articles in journals as The journal of the American college of cardiology and Circulation were included. CONCLUSIONS: The reperfusion strategies must be used according to the clinical context of the patient. In the acute myocardial infarction with ST elevation, fibrinolytic treatment may be chosen in low risk and without hemodynamic instability. In patients with hemodynamic instability, not eligible for fibrinolytic treatment or in whom this therapy fails, percutaneous angioplasty is indicated considering the protection of personnel. In the case of acute myocardial infarction without ST elevation, the treatment by urgent percutaneous angioplasty is considered in cases of hemodynamic instability or malignant arrhythmias.

Incidence and consequences of systemic arterial thrombotic events in COVID-19 patients.

A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients. In addition, small series of patients with coronary, cerebrovascular and peripheral arterial thrombotic events have also been reported, but their true incidence and consequences are not well described, and constitute the objective of this study. From February 1st to April 21st, 2020, 2115 COVID-19 patients were treated at Hospital Universitario Fundación Alcorcón (Madrid, Spain), and 1419 were eventually admitted. Patient characteristics and outcomes were collected by reviewing their electronic medical records. Fourteen patients had a systemic arterial thrombotic event, which represents a 1% incidence in relation to the total number of hospitalized patients. Three patients suffered an acute coronary syndrome, two with persistent ST-segment elevation, one of whom was treated invasively, and one with transient ST-segment elevation. Eight patients had a cerebrovascular event. Six suffered an acute ischemic stroke and two a transient ischemic attack, 50% of them had a Rankin score ≥ 3 at discharge. Three additional patients had a limb thrombotic event, all of them infrapopliteal, and were managed conservatively. All three cases developed necrosis of the toes, two of them with bilateral involvement. The hospitalization death rate of patients with an arterial event was 28.6%. Although COVID-19 may favor the occurrence of thrombotic events, the destabilization and thrombosis of arterial atherosclerotic plaques do not seem to be a frequent mechanism which warrants the need for specific systematic preventive measures.

EAPCI Position Statement on Invasive Management of Acute Coronary Syndromes during the COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) pandemic poses an unprecedented challenge to healthcare worldwide. The infection can be life threatening and require intensive care treatment. The transmission of the disease poses a risk to both patients and healthcare workers. The number of patients requiring hospital admission and intensive care may overwhelm health systems and negatively affect standard care for patients presenting with conditions needing emergency interventions. This position statements aims to assist cardiologists in the invasive management of acute coronary syndrome (ACS) patients in the context of the COVID-19 pandemic. To that end, we assembled a panel of interventional cardiologists and acute cardiac care specialists appointed by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) and from the Acute Cardiovascular Care Association (ACVC) and included the experience from the first and worst affected areas in Europe. Modified diagnostic and treatment algorithms are proposed to adapt evidence-based protocols for this unprecedented challenge. Various clinical scenarios, as well as management algorithms for patients with a diagnosed or suspected COVID-19 infection, presenting with ST- and non-ST-segment elevation ACS are described. In addition, we address the need for re-organization of ACS networks, with redistribution of hub and spoke hospitals, as well as for in-hospital reorganization of emergency rooms and cardiac units, with examples coming from multiple European countries. Furthermore, we provide a guidance to reorganization of catheterization laboratories and, importantly, measures for protection of healthcare providers involved with invasive procedures.

Helicobacter pylori Seropositivity in Patients with Interleukin-1 Polymorphisms Is Significantly Associated with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Helicobacter pylori infection and interleukin-1 polymorphisms are associated with an increased risk of gastric cancer. We examined the prevalence of Helicobacter pylori seropositivity and interleukin-1 polymorphisms between ST-segment elevation myocardial infarction and non-ST-segment elevation acute coronary syndrome patients. METHODS: We recruited consecutive acute coronary syndrome patients, and 101 non-ST-segment elevation acute coronary syndrome patients and 103 ST-segment elevation myocardial infarction patients were enrolled. Interleukin-1 polymorphism analyses were performed for single nucleotide polymorphism in interleukin-1 beta-511 and the variable number of tandem repeats polymorphism in the interleukin-1 receptor antagonist by polymerase chain reaction. Immunoglobulin G antibodies against Helicobacter pylori and high sensitivity C-reactive protein were also measured. RESULTS: The rates of the simultaneous presence of interleukin-1 polymorphisms and Helicobacter pylori-seropositivity between non-ST-segment elevation acute coronary syndrome and ST-segment elevation myocardial infarction groups were 25.7% and 42.7%, respectively (P = 0.012). Helicobacter pylori-seropositive subjects with interleukin-1 polymorphisms showed significantly higher levels of high sensitivity C-reactive protein (0.04-0.12 vs. 0.02-0.05; P<0.001). Multivariate logistic regression analysis revealed that the carriage of Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was significantly associated with ST-segment elevation myocardial infarction (odds ratio, 2.32; 95% confidence interval, 1.23-4.37; P = 0.009). The C-statistic of conventional risk factors was 0.68 (P<0.001) and that including Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was 0.70 (P<0.001); continuous net reclassification improvement was 34% (P = 0.0094) and integrated discrimination improvement was 3.0% (P = 0.014). CONCLUSIONS: The coincidence of Helicobacter pylori-seropositivity and interleukin-1 polymorphisms was significantly associated with higher levels of high sensitivity C-reactive protein and the increased risk of ST-segment elevation myocardial infarction.

Cytomegalovirus-Productive Infection Is Associated With Acute Coronary Syndrome.

BACKGROUND: Although an association between human herpesvirus (HHV) infection and atherosclerosis has been suggested, the data supporting such an association are controversial and, in most cases, are based on serological evidence or on the presence of cell-associated HHV DNA, which do not report about actual viral replication. We quantified the DNA of all 8 types of HHVs in plasma, in which their presence is evidence of viral replication. METHODS AND RESULTS: Using quantitative real-time polymerase chain reaction, we evaluated the presence of HHV DNA in blood samples obtained at the time of hospitalization from 71 patients with acute coronary syndrome, 26 patients with stable coronary artery disease, and 53 healthy volunteers and in atherosclerotic plaques of 22 patients with peripheral artery disease who underwent endarterectomy. HHV-5 (cytomegalovirus [CMV]) was the only HHV with a level that was higher in acute coronary syndrome patients than in the control group and that correlated with the level of high-sensitivity C-reactive protein. The numbers of effector memory T cells positively correlated with the numbers of CMV genome copies in carotid arteries plaques, whereas the numbers of central memory T cells negatively correlated with CMV copy numbers. CONCLUSIONS: Of all HHV levels, only CMV was higher in patients with stable coronary artery disease and acute coronary syndrome than in the healthy group, and its load correlated with the level of high-sensitivity C-reactive protein. The level of CMV in atherosclerotic plaques correlated with the state of immunoactivation of lymphocytes in plaques, suggesting that the reactivation of CMV may contribute to the immune activation associated with the progression of atherosclerosis.

Herpes zoster infection associated with acute coronary syndrome: a population-based retrospective cohort study.

BACKGROUND: Vasculopathy in varicella zoster virus (VZV) infection and a proposed association between herpes virus infection and atherosclerosis suggest a possible link between VZV infection and vascular thrombosis. OBJECTIVES: To determine the risk of acute coronary syndrome (ACS) associated with herpes zoster infection. METHODS: We used the Taiwan National Health Insurance Research Database to identify 57,958 patients newly diagnosed with herpes zoster between 1999 and 2010; 231,832 patients without herpes zoster were examined as the control group. Both cohorts were followed up until the end of 2010 to measure the incidence of ACS. Cox proportional-hazards regression and Kaplan-Meier analyses were used to measure the hazard ratios (HR) and the cumulative incidences of ACS, respectively. RESULTS: The incidence of ACS was 1·24-fold higher in the herpes zoster group than in the control group [36·8 vs. 29·6 per 10,000 person-years, 95% confidence interval (CI) 1·16-1·33]. After adjusting for age, sex and comorbidities, the HR of ACS for the herpes zoster group compared with the control group was 1·15 (95% CI 1·07-1·24). Analysis by the time lag (≤ 3 months, ≤ 1 year, > 1 year) showed that the incidence of ACS remained significantly higher in the herpes zoster group than in the control group, with an adjusted HR of 1·10 (95% CI 1·02-1·19) after the 1-year follow-up period. The Kaplan-Meier survival curve showed that the risk of ACS was significantly higher in the herpes zoster group than in the control group (P < 0·001). CONCLUSION: Herpes zoster infection is associated with an increased risk of ACS.

Cytomegalovirus localization in atherosclerotic plaques is associated with acute coronary syndromes: report of 105 patients.

It has been shown that cytomegalovirus (CMV) is present in coronary atherosclerotic plaques, but the clinical relevance of this presence remains to be elucidated. In this study we sought to examine CMV infection in atherosclerosis patients defined by different methods and to identify the clinical significance of CMV replication in the atherosclerotic plaques. The study included 105 consecutive patients who were admitted to our department and underwent coronary artery bypass grafting (CABG) surgical interventions. Coronary atherosclerotic specimens as well as 53 specimens from the mamillary artery of these same patients were analyzed. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) methods were used for evaluations. The CMV PCR test result was positive for 28 (26.7%) of patients with coronary artery atherosclerosis. After adjusting for other risk factors, coronary artery disease patients with a history of acute coronary syndrome were more likely to be positive for CMV PCR test (P=0.027; odds ratio: 4.2; 95% CI: 1.18-15.0). They were also more likely to have a positive family history for cardiovascular diseases (CVD). This study confirms previous evidence about the replication of CMV virus in the atherosclerotic plaques of coronary arteries and brings clinical significance to this observation by showing a higher prevalence of acute coronary syndromes in those patients with CMV-infected plaques. Our study also suggests a familial vulnerability to CMV replication in the coronary artery walls.

[Enterovirus infection as a risk factor of acute coronary syndrome and its complications].

Antigens of enteroviruses were detected quantitatively in the modified complement-binding reaction in blood samples from 102 of the 208 (49%) patients with ACS, in coronary artery tissues from 23 of 24 and heart from 51 of 94 (54.3%) patients with MI who died from cardiogenic shock and/or cardiac rupture. The relative level of enterovirus antigen (RLEVA) in the blood of patients with MI complicated and uncomplicated by cardiogenic shock and/or cardiac rupture was 0.42 +/- 0.04 and 0.29 +/- 0.02 arbitrary units respectively (p = 0.032) compared with 0.21 +/- 0.07 in patients with unstable angina (UA) (p = 0.0001). RLEVA in patients with UA was significantly lower than in those with uncomplicated MI (p < 0.011). RLEVA in necrotized myocardial areas after death from cardiogenic shock (0.54 +/- 0.18) and/or cardiac rupture (0.46 +/- 0.15) was higher than outside MI zones (0.30 +/- 0.14 and 0.26 +/- 0.10 respectively) (p < 0.01). RLEVA in coronary vessels feeding the necrotic zones of patients with MI complicated by cardiogenic shock (0.44 +/- 0.18) was higher (p = 0.03) than in the vessel feeding tissues outside the MI zone (0.29 +/- 0.19). It is concluded that enterovirus infection is a factor of ACS; it is directly involved in its pathogenesis and promotes the development of cardiogenic shock and/or cardiac rupture.

Impact of intimal pathogen burden in acute coronary syndromes--correlation with inflammation, thrombosis, and autoimmunity.

BACKGROUND: Increasing evidence supports a link between serological evidence of pathogen burden (PB) and the risk for future cardiovascular events. Our study evaluates the intimal presence of 4 pathogens in atheroma, clinically associated with acute coronary syndromes (ACS) and stable angina (SA), and the effect on the expression of intimal C-reactive protein (CRP), tissue factor (TF) and human heat-shock protein 60 (hHSP60). METHODS: Coronary atherectomy specimens retrieved from 60 primary lesions of patients with ACS (n=35) or SA (n=25) were assessed immunohistochemically for the presence of Chlamydia pneumoniae (Cpn), Helicobacter pylori (HP), Cytomegalovirus (CMV) and Epstein­Barr Virus (EBV) and for the expression of CRP, TF, and hHSP60. RESULTS: Analysis revealed eight lesions without, 22 lesions with one, 19 lesions with two, seven lesions with three, and four lesions with four pathogens. Cpn was present in 73%, HP in 31%, CMV in 16%, and EBV in 40%. Mean value of PB in ACS-lesions was significantly increased. Expressions of CRP, TF, and hHSP60 were significantly higher in ACS lesions. The number of infectious pathogens correlated significant with the expressions of CRP, TF, and hHSP60. CONCLUSIONS: Our data demonstrate the impact of PB in plaque instability and suggest local proinflammatory, prothrombotic, and proimmunogenic effects.

Active cytomegalovirus replication in patients with coronary disease.

OBJECTIVES: To study the prevalence of active cytomegalovirus (CMV) infection in patients with stable and unstable conditions of coronary artery disease (CAD). DESIGN: Forty patients with acute coronary syndrome (ACS), 50 patients with stable angina and angiographically verified CAD (SA) and 50 clinically healthy controls were included. Monocytes were isolated from peripheral blood and CMV-RNA expression was determined by a nested RT-PCR assay. CMV IgM and IgG antibodies, interleukin-(IL)-6, IL-10 and CRP were measured in serum. RESULTS: The prevalence of active CMV infection was significantly higher in patients with ACS (15%) and in patients with SA (10%) compared with controls (2%) (p<0.001). The presence of an active CMV infection was associated with increased serum concentrations of IL-6. CONCLUSIONS: Active CMV infection was found to a larger extent in CAD patients than in healthy controls. The data indicate that CAD patients are more susceptible to reactivation of CMV and put new focus on the role of CMV in atherosclerosis.

Effects of atypical pneumonia agents on progression of atherosclerosis and acute coronary syndrome.

BACKGROUND: The aim of this study was to investigate the presence of various atypical pneumonia agents (Chlamydia pneumoniae, cytomegalovirus, Mycoplasma pneumoniae), which are considered to have a role in the ethiopathogenesis of atherosclerosis, in aortic biopsies without macroscopically visible plaque and in internal thoracic artery biopsies. MATERIAL AND METHODS: Thirty-three patients (group 1), who had undergone coronary bypass operation and 10 non-atherosclerotic patients (group 2), were included in the study. Seventy-six tissue biopsies were taken. Biopsies from the patients in group 1 a were obtained from the atheroma plaque-free aortic tissue and 33 biopsies (group Ib) were obtained from their internal thoracic arteries. Following DNA extraction, nested PCR was used to detect Chlamydia pneumoniae DNA, and real time PCR was used to detect cytomegalovirus and Mycoplasma pneumoniae DNA. Blood parameters (lipid profile, CRP, fibrinogen) of the patients and operation characteristics were recorded. RESULTS: Chlamydia pneumoniae DNA was detected in 5 of 33 biopsy samples from coronary bypass patients, whereas none of the control patients (group 1b and group 2) were positive for this agent (P = 0.001). Neither CMV nor Mycoplasma pneumoniae was detected in IMA and aortic biopsies of both bypass and control patients. Elevated total cholesterol levels (P = 0.02) and positive CRP (P = 0.001) was found in C. pneumoniae positive patients. Prevalence of acute coronary syndrome was significantly higher in C. pneumoniae detected patients compared (P = 0.00 1). CONCLUSIONS: Detection of C. pneumoniae DNA in the atheroma free aortic biopsies might indicate that this micro-organism intervened in the progression of atheroma plaque. There was a strong relationship between the detection of this micro-organism in the aortic wall and acute coronary syndrome. The absence of DNA of the corresponding micro-organisms in the IMA wall may show its resistance to infective agents and in turn to atherosclerosis, which is a result of the prevailing endothelial functions of this artery.

[Changes of serum soluble P-selectin and tumor necrotic factor-alpha in patients with CMV induced acute coronary syndrome].

OBJECTIVE: To explore the changes and relationship between serum soluble P-selectin, tumor necrosis factor-alpha (TNF-alpha) in coronary heart disease patients with acute coronary syndrome (ACS) and human cytomegalovirus (HCMV) infection. METHODS: The levels of circulating soluble P-selectin, TNF-alpha, HCMV-IgM and HCMV-IgG were determined by enzyme-linked immunosorbent assay (ELISA) in 79 cases for ACS group, 30 cases for stable angina (SA) group and 30 healthy control cases. RESULTS: (1) The serum positive rate of HCMV-IgM and HCMV-IgG in the ACS, SA and healthy control groups were 30.4% (24/79), 10.0% (3/30) and 6.7% (2/30); 86.1% (68/79), 80.0% (24/30) and 53.3% (16/30), respectively. Positive rate of HCMV-IgM in the ACS was higher than those in SA and healthy control groups (P < 0.01), positive rate of HCMV-IgG in the ACS and SA groups were higher than that of the healthy control group (P < 0.01). (2) Compared with the SA group and healthy control group, the levels of the serum soluble P-selectin and TNF-alpha were significantly higher in patients with ACS [(6437.3 +/- 666.9) pg/ml vs. (1520.0 +/- 112.7) pg/ml and (1481.0 +/- 109.1) pg/ml, (56.2 +/- 18.4) pg/ml vs. (27.3 +/- 13.7) pg/ml and (28.1 +/- 11.3) pg/ml], respectively, P < 0.01). The AMI group, compared with the UA group in the ACS group, had significantly higher levels of the serum soluble P-selectin and TNF-alpha (P < 0.01). Compared with the SA group, the levels of the serum soluble P-selectin and TNF-alpha were not significantly different in healthy control group. (3) The levels of the serum soluble P-selectin and TNF-alpha in HCMV-IgM positive patients were significantly higher than the HCMV-IgM negative patients in the ACS group (P < 0.01). CONCLUSION: The chronic infection with HCMV might injure endothelial cells that subsequently contribute to the formation and progression of atherosclerosis, the acute infection with HCMV may induce increased serum levels of soluble P-selectin and TNF-alpha that might participate in acute coronary events.