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1.  Analysis of C-Reactive Protein and Biochemical Parameters in Pericardial Fluid 
Yonsei Medical Journal  2006;47(3):372-376.
This study was designed to examine the relationship between pericardial fluid and plasma CRP levels, and to alterations in other biochemical parameters in patients undergoing Coronary Artery Bypass Grafting (CABG). The study group consisted of 96 Coronary Artery Disease (CAD) patients who were referred to our clinic for a CABG procedure and from whom sufficient amount of pericardial fluid could be collected. The patients were classified into 3 groups: Stable Angina Pectoris (SAP) (n = 27), Unstable Angina Pectoris (USAP) (n = 36), and Post-Myocardial Infarction (PMI) (n = 33). Levels of CRP, glucose, albumin, total protein, Creatine Kinase (CK), Creatine Kinase-MB (CK-MB), and Lactate Dehydrogenase (LDH) were determined in pericardial fluid samples and in simultaneously collected blood samples from radial artery. The pericardial CRP and LDH levels in the PMI group were higher than in the SAP (p = 0.015 and p = 0.000, respectively) and USAP (p = 0.011, p = 0.047) groups. Serum CRP levels in USAP (p = 0.014) and PMI (p = 0.000) groups were higher than those in the SAP group. Pericardial albumin levels in the PMI group were higher than in the USAP group (p = 0.038). In all groups, the pericardial fluid/serum protein ratio was > 0.5, the LDL ratio was > 0.6, and pericardial fluid LDH concentrations were > 300 mg/dl. CRP level of pericardial fluid was significantly higher in the PMI group than in other groups. However, pericardial fluid LDH levels were higher than blood LDH levels in this group and were also higher than pericardial fluid LDH levels of other groups.
PMCID: PMC2688157  PMID: 16807987
Pericardial fluid; CRP; pericardial CK-MB; pericardial LDH
2.  Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation 
Heart  1998;80(1):19-22.
Background—Unstable angina is a heterogeneous clinical syndrome. The diverse clinical presentations of unstable angina may reflect different pathogenic mechanisms within the plaque.
Objective—To investigate the cellular constituents of culprit coronary atheromatous plaques in patients with stable angina pectoris and patients with diverse clinical presentations of unstable angina.
Methods—48 patients who underwent coronary atherectomy for management of ischaemic heart disease: 23 had stable angina and 25 had unstable angina. Of the latter, 11 patients were classified as Braunwald's IIB and 14 as Braunwald's IIIB unstable angina. The presence of thrombus, cholesterol clefts, and smooth muscle cell proliferation was assessed in atherectomy samples using standard histological techniques. Monoclonal antibodies were used to identify smooth muscle cells and macrophages within atherosclerotic plaque fragments.
Results—Fresh thrombus was more frequently found in patients with Braunwald's IIIB unstable angina (64%) than in patients with stable angina (22%) or IIB unstable angina (27%) (p < 0.0006). A pattern of smooth muscle cell proliferation ("accelerated progression pattern") was observed which was also associated with coronary thrombus. This pattern was present in 30% of patients with stable angina, 64% of patients with IIIB unstable angina, and in all patients (100%) with IIB unstable angina. Atherosclerotic plaques with thrombus, cholesterol clefts, and macrophages were more common in patients with unstable angina than in stable angina patients.
Conclusion—The presence of a specific smooth muscle cell proliferation (accelerated progression) pattern in patients with unstable angina, particularly in those with Braunwald's IIB unstable angina, suggests that episodic plaque disruption and subsequent healing may be an important mechanism underlying angina symptoms in these patients.

 Keywords: angina pectoris;  atherosclerosis;  unstable angina;  accelerated progression pattern
PMCID: PMC1728764  PMID: 9764053
3.  Plasma osteopontin levels are elevated in non-ST-segment elevation acute coronary syndromes. 
BACKGROUND: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD). METHODS: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups. RESULTS: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis. CONCLUSIONS: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.
PMCID: PMC2569782  PMID: 17128682
4.  Acute and convalescent changes in plasma homocysteine concentrations in acute coronary syndromes 
Heart  2001;85(4):380-384.
BACKGROUND—Raised plasma homocysteine is a risk factor for coronary artery disease. Patients with myocardial infarction or unstable angina show greater activation of coagulation, greater troponin release, and a worse outcome.
OBJECTIVE—To examine variations in plasma homocysteine concentration in relation to C reactive protein (CRP) in patients presenting with acute coronary syndromes.
METHODS—Consecutive patients presenting with acute myocardial infarction (22) and unstable angina pectoris (12) were studied. Plasma samples were obtained on admission (before clinical intervention), on days 2, 7, and 28, and again six months after admission. Plasma homocysteine, assayed by high performance liquid chromatography, and CRP were both determined at the same time points. Changes were assessed by analysis of variance.
RESULTS—CRP concentrations showed a classical rise on day 2, followed by a gradual decline to normal values taken at six months from admission in both myocardial infarction (p < 0.0001) and unstable angina (p = 0.02). Homocysteine concentrations in myocardial infarction (median, 25th to 75th interquartile range) were: 11.9 (10.7 to 12.6), 11.5 (9.1 to 13.4), 12.1 (11.4 to 14.1), 12.4 (11.1 to 14.4), and 12.1 (11.2 to 14.0) µmol/l, for days 1, 2, 7, 28, and 180, respectively (p = 0.02). Significant differences were observed only between day 2 and day 7 (p < 0.05). The final homocysteine measurement was not different from the admission level. Homocysteine concentrations in unstable angina did not differ between admission and convalescence (12.5 (9.1 to 14.5) µmol/l and 12.3 (7.7 to 14.9) µmol/l, respectively).
CONCLUSIONS—Plasma homocysteine concentrations are minimally influenced by acute phase variations with reliable measurements obtained on admission in patients with myocardial infarction and unstable angina.

Keywords: myocardial infarction; unstable angina; homocysteine; sample timing
PMCID: PMC1729690  PMID: 11250957
5.  Relationship Between MMP-1, MMP-9, TIMP-1, IL-6 and Risk Factors, Clinical Presentation, Extent and Severity of Atherosclerotic Coronary Artery Disease 
Matrix metalloproteinases (MMPs) and Tissue Inhibitor of Matrix Metalloproteinases (TIMPs) may be associated with atherogenesis and plaque rupture. We evaluated the relationship between MMP-1, MMP-9, TIMP-1 and IL-6 levels and risk factors, presentation, extent and severity of atherosclerotic coronary artery disease (CAD).
Consecutive patients who underwent coronary angiography were randomly included. The serum concentrations of MMP-1, MMP-9, TIMP-1 and IL-6 were analyzed with ELISA method in 134 patients. Participants were divided into 5 groups; stable angina pectoris (SAP; n= 34), unstable angina pectoris (USAP; n=29), non-ST elevation myocardial infarction (NSTEMI; n=16), acute ST elevation myocardial infarction (STEMI; n=25) and controls (n=30). Coronary angiographic Gensini score was calculated.
MMP-1 levels were higher in STEMI and NSTEMI groups compared with USAP, SAP and control groups (STEMI vs USAP p=0.005; STEMI vs SAP p=0.001; STEMI vs control p<0.001; NSTEMI vs USAP p=0.02; NSTEMI vs SAP p=0.027; NSTEMI vs control p<0.001). In STEMI group, MMP-9 levels were higher than USAP and control groups (p=0.002; p<0,001). TIMP-1 levels were not significantly different within all 5 groups. MMP-1 levels were found to be elevated in diabetic patients (p=0.020); whereas MMP-9 levels were higher in smokers (p=0.043). Higher MMP-1, MMP-9 and IL-6 levels were correlated with severe Left Anterior Descending artery (LAD) stenosis and higher angiographic Gensini Score (for severe LAD stenosis; r = 0.671, 0.363, 0.509 p<0.001; for Gensini score; r = 0.717, 0.371, 0.578 p<0.001).
Serum levels of MMP-1, MMP-9, and IL-6 are elevated in patients with CAD; more so in acute coronary syndromes. MMP-1, MMP-9 and IL-6 are associated with more extensive and severe CAD (as represented by Gensini score).
PMCID: PMC3136999  PMID: 21772929
Matrix metalloproteinase; Interleukin-6; coronary artery disease; Gensini score.
6.  Relationship between resistin level in serum and acute coronary syndrome or stable angina pectoris*  
Objective: To investigate the relationship between serum resistin level and acute coronary syndrome (ACS) or stable angina pectoris (SAP). Methods: Sixty-five patients, with coronary artery disease, were enrolled and divided into three subgroups: acute myocardial infarction (AMI), unstable angina pectoris (UAP) and SAP, and 26 healthy people were recruited as controls in the cross-sectional study. Serum resistin levels were determined by ELISA (enzyme-linked immunosorbent assay), and WBC (white blood cell count), hsCRP (high sensitive C-reaction protein), CKmax (maximum of creatinkinase), CK-MBmax (maximum of isozyme of creatinkinase) and cTnImax (maximum of troponin) were measured by standard laboratory methods. Results: The serum resistin levels were 4 folds higher in AMI patients, 2.43 folds in UAP patients and 1.12 folds in SAP patients than in the healthy controls (P<0.05). The resistin levels were also significantly different between AMI [(8.16±0.79) ng/ml], UAP [(5.59±0.75) ng/ml] and SAP [(3.45±0.56) ng/ml] groups (P<0.01); WBC, hsCRP, CKmax, CK-MBmax and cTnImax were significantly increased in AMI patients over UAP and SAP patients. Spearman analysis showed that serum resistin levels were positively correlated with WBC (r=0.412, P=0.046), hsCRP (r=0.427, P=0.037), CKmax, CK-MBmax and cTnImax (r=0.731, 0.678, 0.656; P<0.01). Conclusion: Serum resistin levels increased with inflammatory factors and myocardial impairment. The results suggest that human resistin might play an important role in the pathogenesis of atherosclerosis and AMI as an inflammatory factor.
PMCID: PMC2100158  PMID: 18257120
Resistin; Acute coronary syndrome (ACS); Stable angina pectoris (SAP)
7.  Leukocyte Counts, Myeloperoxidase, and Pregnancy-Associated Plasma Protein A as Biomarkers for Cardiovascular Disease: Towards a Multi-Biomarker Approach 
We evaluated leukocyte counts and levels of CRP, fibrinogen, MPO, and PAPP-A in patients with stable and unstable angina pectoris, acute myocardial infarction, and healthy controls. All biomarkers were analyzed again after 6 months. Leukocyte counts and concentrations of fibrinogen, CRP, MPO, and PAPP-A were significantly increased in patients with acute myocardial infarction. Leukocyte counts and concentrations of MPO were significantly increased in patients with unstable angina pectoris compared with controls. After 6 months, leukocyte counts and MPO concentrations were still increased in patients with acute myocardial infarction when compared to controls. Discriminant analysis showed that leukocyte counts, MPO, and PAPP-A concentrations classified study group designation for acute coronary events correctly in 83% of the cases. In conclusion, combined assessment of leukocyte counts, MPO, and PAPP-A was able to correctly classify acute coronary events, suggesting that this could be a promising panel for a multibiomarker approach to assess cardiovascular risk.
PMCID: PMC3003971  PMID: 21188207
8.  Anaemia predicts cardiovascular events in patients with stable coronary artery disease 
Netherlands Heart Journal  2005;13(7-8):254-258.
Anaemia is an independent risk factor for cardiovascular (CV) events in patients with heart failure and patients with chronic kidney disease. The effect of anaemia on CV outcomes in patients with coronary artery disease (CAD) remains unclear. Therefore, we investigated the prognostic value of anaemia in this group of patients.
Patients with stable angina pectoris, referred for a first diagnostic coronary angiography, were eligible for this study. Only subjects with significant coronary artery disease (>50% luminal narrowing) were used for analysis (n=143). Cardiovascular events were defined as cardiovascular death, acute myocardial infarction and hospitalisation for unstable angina pectoris. Anaemia was defined according to WHO criteria as haemoglobin level ≤8 mmol/l in men and ≤7.5 mmol/l in women.
The mean age of the population was 61.5±9.4 years. During follow-up (44±19 months), 19 CV events occurred. The diagnosis of anaemia predicted CV events, even when adjusted for other risk factors (hazard ratio 5.73, 95% confidence interval 1.49-22.13, p=0.01). In univariate analysis, serum erythropoietin levels predicted CV outcomes (p<0.05); however, this association was lost when adjusted for haemoglobin concentration.
Anaemia is associated with worse outcome in patients with established CAD and could be used as a prognostic indicator in this group of patients.
PMCID: PMC2497247
anaemia; coronary artery disease; prognostic factors
9.  Spontaneous coronary artery dissection diagnosed by multislice computed tomography 
Spontaneous coronary artery dissection is a rare cause of acute coronary syndrome. Spontaneous coronary artery dissection can cause stable angina pectoris, unstable angina pectoris, acute myocardial infarction, cardiogenic shock and sudden cardiac death. It usually occurs in young to middle aged women. Atherosclerosis, peripartum period, and structural and inflammatory diseases affecting the artery wall are predisposing factors. It shows similar clinical presentation to coronary artery disease. Diagnosis and early treatment decrease mortality. Treatment options are medical treatment, percutaneous coronary intervention and surgery. The treatment decision is made according to the clinical presentation of the patient, the affected coronary artery and the length of the dissected segment. Diagnosis of the disease is usually made by coronary angiography. We present a patient who consulted our clinic with atypical chest pain and was diagnosed with spontaneous left anterior descending dissection by coronary computed tomography angiography.
PMCID: PMC3915952  PMID: 24570701
spontaneous coronary artery dissection; computed tomography; angiography
10.  Coronary artery disease: arterial remodelling and clinical presentation 
Heart  1999;82(4):461-464.
OBJECTIVE—To investigate the hypothesis that in coronary artery disease large plaques in compensatorily enlarged segments are associated with acute coronary syndromes, whereas smaller plaques in shrunken segments are associated with stable angina pectoris.
METHODS—Patients selected for percutaneous transluminal coronary angioplasty (PTCA) were divided into two groups, one with stable angina pectoris (stable group, n = 37) and one with unstable angina or postmyocardial infarction angina of the infarct related artery (unstable group, n = 32). In both groups, remodelling at the culprit lesion site was determined by intravascular ultrasound before the intervention. Remodelling was calculated as relative vessel area: [vessel area culprit lesion site ÷ mean vessel area of both proximal and distal reference sites] × 100%. Compensatory enlargement was defined as remodelling of ⩾ 105%, whereas shrinkage was defined as remodelling of ⩽ 95%.
RESULTS—In the unstable group, the vessel area at the culprit lesion site was larger than in the stable group, at mean (SD) 18.1 (5.3) v 14.6 (5.4) mm2 (p = 0.008). Lumen areas were similar. Consequently, plaque area and percentage remodelling were larger in the unstable group than in the stable group: mean (SD) 14.8 (4.8) v 11.6 (4.9) mm2 (p = 0.009) and 112 (31)% v 95 (17)% (p = 0.005), respectively. Significantly more culprit lesion sites were classified as shrunken in the stable group (21/37) than in the unstable group (8/32; p = 0.014). On the other hand, more lesion sites were classified as enlarged in the unstable group (16/23) than in the stable group (8/37; p = 0.022).
CONCLUSIONS—In patients selected for PTCA, the mode of remodelling is related to clinical presentation.

Keywords: atherosclerosis; coronary disease; remodelling; intravascular ultrasound
PMCID: PMC1760264  PMID: 10490561
11.  Fractional Flow Reserve Is Not Associated with Inflammatory Markers in Patients with Stable Coronary Artery Disease 
PLoS ONE  2012;7(10):e46356.
Atherosclerosis is an inflammatory condition and increased blood levels of inflammatory biomarkers have been observed in acute coronary syndromes. In addition, high expression of inflammatory markers is associated with worse prognosis of coronary artery disease. The presence and extent of inducible ischemia in patients with stable angina has previously been shown to have strong prognostic value. We hypothesized that evidence of inducible myocardial ischemia by local lesions, as measured by fractional flow reserve (FFR), is associated with increased levels of blood based inflammatory biomarkers.
Whole blood samples of 89 patients with stable angina pectoris and 16 healthy controls were analyzed. The patients with stable angina pectoris underwent coronary angiography and FFR of all coronary lesions.
We analyzed plasma levels of cytokines IL-6, IL-8 and TNF-α and membrane expression of Toll-like receptor 2 and 4, CD11b, CD62L and CD14 on monocytes and granulocytes as markers of inflammation.
Furthermore, we quantified the severity of hemodynamically significant coronary artery disease by calculating Functional Syntax Score (FSS), an extension of the Syntax Score.
For the majority of biomarkers, we observed lower levels in the healthy control group compared with patients with stable angina who underwent coronary catheterization.
We found no difference for any of the selected biomarkers between patients with a positive FFR (≤0.75) and negative FFR (>0.80). We observed no relationship between the investigated biomarkers and FSS.
The presence of local atherosclerotic lesions that result in inducible myocardial ischemia as measured by FFR in patients with stable coronary artery disease is not associated with increased plasma levels of IL-6, IL-8 and TNF-α or increased expression of TLR2 and TLR4, CD11b, CD62L and CD14 on circulating leukocytes.
PMCID: PMC3473026  PMID: 23091596
12.  Reduced plasma adiponectin levels relative to oxidized low density lipoprotein and nitric oxide in coronary artery disease patients 
Clinics  2011;66(7):1129-1135.
Adiponectin is a circulating hormone that is produced exclusively by adipocytes and has anti-inflammatory and anti-atherogenic properties. The hypothesis that there are differences in adiponectin levels between stable and unstable coronary-artery disease patients remains controversial. Furthermore, the potential relationships between the plasma adiponectin level and the inflammatory and non-inflammatory markers (oxidized low density lipoprotein and nitric oxide) in patients with stable and unstable coronary-artery disease relative to normal subjects have not been assessed.
To assess whether plasma adiponectin levels differ among patients with stable and unstable coronary-artery disease and among control subjects, and to correlate plasma adiponectin level with inflammatory and clinical risk factors (such as oxidized-LDL and nitric oxide) in these patients.
This study included 50 control subjects, 50 stable angina patients and 50 unstable angina patients with angiographically documented coronary-artery disease. Plasma adiponectin and oxidized-LDL levels were determined using an enzyme immunoassay. Plasma nitric oxide, high sensitivity C-reactive protein and lipid profile levels were also measured.
Plasma adiponectin levels were lower in the unstable angina patients (4.9±1.30 µg/mL) than in the stable angina patients (6.34±1.0 µg/mL) or in the controls (9.25±1.8 µg/mL); these levels were also significantly lower in stable angina patients versus controls (p<0.001). Plasma adiponectin levels were negatively correlated with oxidized-LDL, high sensitivity C-reactive protein, lipid profile and other clinical risk factors but positively correlated with nitric oxide.
Plasma adiponectin levels were found to be lower in both stable and unstable angina patients relative to control subjects, and the correlation between plasma adiponectin and cardiovascular markers is weakened in these patients.
PMCID: PMC3148453  PMID: 21876963
Adiponectin; Nitric oxide; Ox-LDL; Stable; Unstable
13.  Clinical implications of tenascin-C and OX40 ligand in patients with acute coronary syndrome 
Biomedical Reports  2013;2(1):132-136.
Acute coronary syndrome (ACS) typically occurs when coronary artery disease results in the obstruction of the coronary arteries. Tenascin-C (TNC) and OX40 ligand (OX40L) were shown to be involved in the pathogenesis of atherosclerosis. In this study, 50 healthy controls and 170 patients, including 50 patients with stable angina (SA), 70 with unstable angina and 50 with acute myocardial infarction, were evaluated to assess serum TNC and plasma OX40L levels. The serum TNC levels were measured by a quantitative automated particle-enhanced immunonephelometric assay. ELISA was used to determine the expression levels of OX40L. All the coronary stenoses with a ≥30% diameter reduction were assessed by angiographic coronary stenosis morphology. The patients with ACS exhibited a significant increase in TNC expression levels (39.39±19.80 ng/ml) compared to the levels in the control and SA groups (28.65±12.32 ng/ml, P<0.01 and 31.22±18.92 ng/ml, P<0.05, respectively). The levels of OX40L were also found to be higher in patients with ACS (38.59±15.76 ng/ml) compared to those in the control and SA groups (19.42±11.19 ng/ml, P<0.001 and 21.52±10.30 ng/ml, P<0.001, respectively). The TNC and OX40L levels were positively correlated with each other (r1=0.68; P<0.001) and with fibrinogen levels (r3=0.76 and r4=0.45, respectively; P<0.001). A positive correlation was also observed between the expression of TNC and OX40L and complex coronary stenosis (r5=0.69 and r6=0.55, respectively; P<0.001). We concluded that TNC and OX40L may act synergistically in coronary plaque formation and may be also be involved in the pathogenesis of coronary lesions. Patients with ACS exhibited increased TNC and OX40L expression levels, which may have created a prothrombotic milieu, aggravating the development of atherosclerosis and the instability of atherosclerotic plaques. Therefore, the expression of TNC and OX40L may be a valuable marker for predicting the severity of ACS.
PMCID: PMC3917010  PMID: 24649084
tenascin-C; OX40 ligand; acute coronary syndrome
14.  Increased serum neopterin: a marker of coronary artery disease activity in women 
Heart  2000;83(3):346-350.
OBJECTIVE—To assess whether neopterin concentrations in women with unstable angina differ from those in women with chronic stable angina.
DESIGN—Prospective cohort study.
SETTING—University hospital in south west London.
PATIENTS—114 consecutive women with angina were studied: 82 had chronic stable angina (typical exertional chest pain, positive exercise ECG testing, and/or abnormal myocardial scintigraphy; symptoms stable for at least three months), and 32 had unstable angina (Braunwald class III). All patients with chronic stable angina (100%) and 18 with unstable angina (56.3%) underwent digital coronary angiography; neopterin concentrations were determined using a commercially available immunoassay.
MAIN OUTCOME MEASURES—Major clinical events during one year follow up were readmission with Braunwald's class IIIb unstable angina, non-fatal myocardial infarction, and cardiac death.
RESULTS—Major events occurred in 12 women with chronic stable angina (14.6%) and nine women with unstable angina (28.1%). Mean (range) neopterin concentrations were significantly higher in women with unstable angina than in those with chronic stable angina (7.6 (5.1-11.5) nmol/l v 5.9 (4.4-7.5) nmol/l; p = 0.003), even after adjustment for variables which were significantly different on univariate analysis. In women with chronic stable angina, baseline neopterin concentrations were higher in those with cardiac events than in those without events (7.1 (5.9-9.1) nmol/l v 5.7 (3.9-7.3 nmol/l); p = 0.010), even after adjustment for variables with significant differences between both groups on univariate analysis.
CONCLUSIONS—On average, women with unstable angina had significantly higher neopterin concentrations than women with chronic stable angina. Women with chronic stable angina with events during follow up had higher neopterin concentrations than those without events. Neopterin concentrations were similar in patients with unstable angina and women with chronic stable angina who developed events. Neopterin concentrations may therefore be a marker of risk in women with coronary artery disease.

Keywords: neopterin; women; coronary artery disease
PMCID: PMC1729345  PMID: 10677418
15.  Decreased Plasma IL-35 Levels Are Related to the Left Ventricular Ejection Fraction in Coronary Artery Diseases 
PLoS ONE  2012;7(12):e52490.
Accumulating evidence shows that the novel anti-inflammatory cytokine IL-35 can efficiently suppress effector T cell activity and alter the progression of inflammatory and autoimmune diseases. The two subunits of IL-35, EBI3 and p35, are strongly expressed in human advanced plaque, suggesting a potential role of IL-35 in atherosclerosis and coronary artery disease (CAD). However, the plasma levels of IL-35 in patients with CAD have yet to be investigated.
Plasma IL-35, IL-10, TGF-β1, IL-12 and IL-27 levels were measured using an ELISA in 43 stable angina pectoris (SAP) patients, 62 unstable angina pectoris (UAP) patients, 56 acute myocardial infarction (AMI) patients and 47 chest pain syndrome patients as a control group.
The results showed that plasma IL-35 levels were significantly decreased in the SAP group (90.74±34.22 pg/ml), the UAP group (72.20±26.63 pg/ml), and the AMI group (50.21±24.69 pg/ml) compared with chest pain syndrome group (115.06±32.27 pg/ml). Similar results were also demonstrated with IL-10 and TGF-β1. Plasma IL-12 and IL-27 levels were significantly increased in the UAP group (349.72±85.22 pg/ml, 101.75±51.42 pg/ml, respectively) and the AMI group (318.05±86.82 pg/ml, 148.88±68.45 pg/ml, respectively) compared with chest pain syndrome group (138.68±34.37 pg/ml, 63.60±22.75 pg/ml, respectively) and the SAP group (153.84±53.86 pg/ml, 70.84±38.77 pg/ml, respectively). Furthermore, lower IL-35 levels were moderately positively correlated with left ventricular ejection fraction (LVEF) in CAD patients (R = 0.416, P<0.01), whereas higher IL-27 levels were weakly negatively correlated with LVEF in CAD patients(R = −0.205, P<0.01).
The results of the present study show that circulating IL-35 is a potentially novel biomarker for coronary artery disease. Regulating the expression of IL-35 also provides a new possible target for the treatment of atherosclerosis and CAD.
PMCID: PMC3528657  PMID: 23285065
16.  Contraindications for Percutaneous Transluminal Coronary Angioplasty in Treatment of Unstable Angina Pectoris 
Texas Heart Institute Journal  1988;15(3):152-154.
In recent years, the indications for percutaneous transluminal coronary angioplasty have expanded to include multivessel disease, unstable angina pectoris, stenosis of coronary bypass grafts, and recent total coronary occlusion. To evaluate our experience in using percutaneous transluminal coronary angioplasty to treat unstable angina, we reviewed the records of the patients who underwent this procedure at our hospital between January 1983 and December 1986.
Of the 689 patients who underwent balloon angioplasty during the study period, 454 had stable angina and 235 had unstable angina; of the latter group, 34 (14.5%) required emergency coronary artery bypass grafting after balloon angioplasty failed. This outcome was associated with 2 risk factors: previous myocardial infarction and triple-vessel disease.
Our data suggest that, in cases of unstable angina pectoris, percutaneous transluminal coronary angioplasty should be reserved for patients with single-vessel disease and no evidence of previous myocardial infarction. They also lend credence to the conclusion that the disease process in unstable angina is different from that in stable angina, and that therapy should be directed towards reducing platelet aggregation and correcting global ischemia, rather than towards balloon angioplasty of “culprit lesions.” (Texas Heart Institute Journal 1988;15:152-154)
PMCID: PMC324817  PMID: 15227244
Angioplasty, transluminal; angina, unstable; aortocoronary bypass; myocardial infarction; ischemia, global; multivessel disease
17.  Coronary angioplasty in unstable angina and stable angina: a comparison of success and complications. 
British Heart Journal  1988;60(5):367-372.
One hundred and five patients with unstable angina and 175 with chronic stable angina were treated by primary percutaneous transluminal coronary angioplasty. Patients with unstable angina had had symptoms for a shorter time and were more likely to have angiographically complex lesions and lesions less than 10 mm in length than patients with chronic stable angina. Other baseline variables were not significantly different in the two groups. The overall primary success rate was similar in both groups (87% v 86%). Nine of the 14 unsuccessful procedures in those with unstable angina and nine of the 24 unsuccessful procedures in those with stable angina were the result of acute occlusion. These results led to a 9% frequency of procedure related myocardial infarction in patients with unstable angina and a 5% rate in those with stable angina (NS). The procedure related infarct rate tended to be higher in patients with unstable angina who had coronary angioplasty soon after an episode of unstable angina (mean 10 days) than in those in whom it was delayed (mean 35 days) (12% v 3%) (NS). In patients with unstable angina who had had a previous myocardial infarction procedure related infarction was significantly more common (18%) than in patients with no previous myocardial infarction (3%). The difference between those with and without previous infarction was also significant in patients with stable angina (10% v 3%).
PMCID: PMC1216592  PMID: 2974297
18.  Lack of association between haemostatic variables and the presence or the extent of coronary atherosclerosis. 
British Heart Journal  1988;59(3):287-291.
Blood samples were taken for haemostatic analysis from 225 patients with angina pectoris who were admitted to hospital for coronary angiography. beta thromboglobulin, platelet factor 3, platelet factor 4, factor VII:C, factor VIII:C, von Willebrand factor antigen, activated partial thromboplastin time, fibrinogen, antithrombin III, protein C:Ag, plasminogen, and antiplasmin were measured before angiography. Patients who had had a myocardial infarction in the two months before the investigation were excluded from the study. Multiple linear regression analysis showed that none of the haemostatic variables contributed independently to the prediction of an angiographic score that indicated the extent of coronary atherosclerosis. History of myocardial infarction, male sex, worsening of angina pectoris, serum triglycerides, and ejection fraction were independently associated with the angiographic score. There were some significant correlations between haemostatic variables and conventional risk factors for coronary heart disease. Thus data obtained from haemostatic analyses of peripheral venous blood do not permit the presence or the extent of atherosclerosis in coronary arteries to be predicted.
PMCID: PMC1216461  PMID: 3258521
19.  Risk stratification in unstable angina and non-Q wave myocardial infarction using soluble cell adhesion molecules 
Heart  2001;85(6):623-627.
OBJECTIVE—To assess prospectively the prognostic value of soluble cellular adhesion molecules (CAMs) in patients with unstable angina and non-Q wave myocardial infarction and to compare their prognostic accuracy with that of C reactive protein (CRP).
DESIGN AND SETTING—Prospective observational study of patients presenting acutely with unstable angina and non-Q wave myocardial infarction to a single south Dublin hospital.
METHODS—Patients with Braunwald IIIA unstable angina and non-Q wave myocardial infarction had serum samples taken at presentation before initiation of antithrombotic treatment and were followed for six months. The primary end point was the occurrence of major adverse cardiovascular events (recurrent unstable angina, non-fatal myocardial infarction, and cardiovascular death) at six months. Concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble endothelial selectin, and soluble platelet selectin were measured using an enzyme linked immunosorbent assay technique. CRP was measured with an immunophelometric assay.
RESULTS—91 patients (73 men and 18 women, mean (SD) age 61 (11) years) were studied; 27 patients (30%) had major adverse cardiac events during the six months of follow up. Concentration of CRP were significantly raised in patients who had an ischaemic event (mean (SEM) 11.5 (6.4) mg/l v 5.4 (2.5) mg/l, p < 0.001). Concentrations of sVCAM-1 were also significantly raised in the ischaemic event group (979 (30) ng/ml v 729 (22) ng/ml, p < 0.001). Both sVCAM-1 and CRP concentrations correlated strongly with the occurrence of an adverse event. The sensitivity of CRP > 3 mg/l and sVCAM-1 > 780 ng/ml for predicting future events was > 90%. There was no difference in concentrations of sICAM-1, soluble endothelin selectin, or soluble platelet selectin between event and non-event groups.
CONCLUSION—Raised concentrations of sVCAM-1 and CRP are predictive of an increased risk of major adverse cardiovascular events six months after presentation with unstable angina and non-Q wave myocardial infarction. These findings suggest that the intensity of the vascular inflammatory process at the time of presentation is a determinant of clinical outcome in unstable coronary artery disease. 

Keywords: cell adhesion molecules; risk stratification; unstable angina
PMCID: PMC1729754  PMID: 11359739
20.  Evaluation of Leptin and Adiponectin Levels in Patients with Stable Angina Pectoris 
ARYA Atherosclerosis  2010;6(2):50-55.
Leptin and adiponectin are two adipose tissue hormones and their association with the incidence of cardiovascular diseases is under evaluation. The aim of this study was to determine the relationship of leptin and adiponectin with coronary artery diseases.
One hundred and seventy patients with angina pectoris and indications of coronary angiography underwent angiography. Serum levels of blood lipids, leptin, and adiponectin were measured. The gathered data was evaluated using SPSS15 software, by multivariate variance analysis.
Analysis of the data demonstrated that 45.1% of the patients had positive angiographic findings. The serum levels of leptin and adiponectin were significantly lower than the minimum levels specified by the kit. However, the two groups, i.e., patients with positive angiographic findings and those with negative findings were not significantly different according to the serum levels of the hormones. Moreover, no significant correlation between the serum levels of the hormones and serum lipids was observed.
Various studies have demonstrated that high serum level of leptin and the incidence of coronary artery diseases are correlated. On the other hand, they have reported that adiponectin has cardioprotective role. Confirmation of these findings requires more detailed studies.
PMCID: PMC3347818  PMID: 22577414
Leptin; Adiponectin; Coronary artery disease
21.  Hyperintense plaque identified by magnetic resonance imaging relates to intracoronary thrombus as detected by optical coherence tomography in patients with angina pectoris 
Many investigators have speculated that hyperintense plaques (HIPs) of the carotid artery on non-contrast T1-weighted imaging (T1WI) in magnetic resonance indicate the presence of mural or intraplaque haemorrhage containing methemoglobin. Coronary plaque imaging with T1WI is challenging, and the clinical significance of coronary HIP on T1WI remains unknown. The aim of this study was to compare HIPs on T1WI with coronary plaque morphology assessed by optical coherence tomography (OCT), which allows us to identify not only plaque rupture, but also fibrous cap thickness and intracoronary thrombus in vivo, in patients with angina pectoris.
Methods and results
Twenty-six lesions from 26 patients with either stable or unstable angina pectoris were examined in this study. All patients underwent T1WI within 24 h before the day on which invasive coronary angiography was performed, and pre-interventional OCT was performed on a native atherosclerotic lesion, considered to be the culprit lesion. Of the 26 lesions studied, 16 (62%) were HIPs and 10 (38%) were non-HIPs. The signal intensity of the coronary plaque to cardiac muscle ratio in HIPs was significantly higher than that in non-HIPs. There were no significant differences in the frequency of lipid-rich plaque, thin-cap fibroatheroma, plaque rupture, and calcification between HIPs and non-HIPs. In contrast, the frequency of thrombus was significantly higher in HIPs than in non-HIPs (P = 0.004).
This study shows that the HIPs on T1WI in angina patients relate to the presence of intracoronary thrombus as detected by OCT imaging.
PMCID: PMC3342851  PMID: 22277117
Coronary artery disease; Atherosclerotic plaque; Magnetic resonance imaging; Thrombosis; Optical coherence tomography
22.  Circulating miR-214 is associated with the severity of coronary artery disease 
To study whether miR-214 is regulated in coronary artery disease (CAD) patients and whether placental growth factor (PLGF) is a possible target for miR-214 in atherosclerosis.
Circulating miR-214 was measured by quantitative PCR using RNA isolated from 40 patients with CAD, including 12 with stable angina pectoris, 16 with unstable angina pectoris and 12 with acute myocardial infarction, and 15 controls without CAD. Plasma level of PLGF was measured by ELISA.
The miR-214 level was significantly lower in CAD patients compared with that in controls (P < 0.01). Compared to controls, patients with unstable angina pectoris (UAP, 38.6±9.1 pg/mL) and acute myocardial infarction (AMI, 46.3±13.4 pg/mL) had significantly higher level of plasma PLGF, but not those with stable angina pectoris (SAP; P = 0.012, UAP vs. Control; P = 0.005, AMI vs. Control). In patients with AMI, the plasma level of miR-214 was positively correlated to that of PLGF.
The results suggest that miR-214 is a beneficial microRNA for CAD patients. Loss of its protection may lead to increased PLGF levels and worsening atherosclerosis. Circulating miR-214 is a promising biomarker for alerting severe CAD.
PMCID: PMC3627710  PMID: 23610572
Atherosclerosis; miR-214; Placental growth factor; Coronary artery disease
23.  Thyrotoxicosis Presenting as Unstable Angina and Ventricular Tachycardia with Normal Coronary Arteries 
A 38-year-old black woman with thyrotoxicosis, whose first symptom was angina pectoris, is described. Chest pain became progressively more frequent, and an unstable angina pattern developed. Angina attacks were associated with transient ischemic electrocardiographic changes and recurrent ventricular tachycardia was documented. Coronary angiography revealed no significant obstructive lesions. The patient became free of pain with antithyroid treatment and angina has not recurred.
It is important to recognize that angina pectoris may be the major presenting symptom of thyrotoxicosis; unstable angina requires careful work-up and management including the performance of coronary angiography.
PMCID: PMC2552568  PMID: 7420455
24.  Effect of Folic Acid Supplementation on Levels of Circulating Monocyte Chemoattractant Protein-1 and the Presence of Intravascular Ultrasound Derived Virtual Histology Thin-Cap Fibroatheromas in Patients with Stable Angina Pectoris 
PLoS ONE  2013;8(7):e70101.
Virtual Histology Intravascular Ultrasound (VH–IVUS) may be used to detect early signs of unstable coronary artery disease. Monocyte Chemoattractant Protein-1 (MCP-1) is linked with coronary atherosclerosis and plaque instability and could potentially be modified by folic acid treatment.
In a randomized, prospective study, 102 patients with stable angina pectoris (SAP) received percutaneous coronary intervention and established medical treatment as well as either homocysteine-lowering folic acid/vitamin B12 (±B6) or placebo (±B6) for 1 year before VH–IVUS was performed. The presence of VH-Thin-Cap Fibroatheroma (VH-TCFA) in non-intervened coronary vessels was registered and serum levels of MCP-1 were measured. The patients were subsequently followed for incident myocardial infarction (MI).
Patients treated with folic acid/vitamin B12 had a geometric mean (SD) MCP-1 level of 79.95 (1.49) versus 86.00 (1.43) pg/mL for patients receiving placebo (p-value 0.34). VH-TCFA lesions were present in 7.8% of patients and did not differ between intervention arms (p-value 0.47). Serum levels of MCP-1 were 1.46 (95% CI 1.12 to 1.92) times higher in patients with VH-TCFA lesions than in those without (p-value 0.005). Afterwards, patients were followed for median 2.1 years and 3.8% experienced a myocardial infarction (MI), which in post-hoc Cox regression analyses was independently predicted by both MCP-1 (P-value 0.006) and VH-TCFA (p-value 0.01).
In patients with SAP receiving established medical treatment, folic acid supplementation is not associated with either presence of VH-TCFA or levels of MCP-1. MCP-1 is however associated with VH-TCFA, a finding corroborated by increased risk for future MI. Identifier: NCT00354081.
PMCID: PMC3723764  PMID: 23936148
25.  The Relationship Between Ankle-Brachial Index and Number of Involved Coronaries in Patients with Stable Angina 
ARYA Atherosclerosis  2010;6(1):6-10.
Atherosclerosis is the commonest cause of vascular disease which can involve peripheral and/or cardiac vessels. This study was conducted to evaluate the possible link between Ankle-Brachial Index (ABI) and coronary vessel involvement in patients with stable angina.
This cross-sectional study was conducted in 2008 on 120 individuals who were hospitalized in Chamran Heart Center and underwent coronary angiography. A questionnaire was completed to obtain demographic information, history of previous heart disease and smoking. Body height and weight, as blood pressure on hand and foot were measured. The patients underwent angiography and the extent of coronary involvement (> 75%) was determined. After12-14-hour of fasting, blood sugar was obtained to measure total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). The Ankle Brachial Pressure Index (ABI) was calculated as the ratio of the blood pressure in the ankles to the blood pressure in the arms. The data were analyzed by SPSS-15 using ANOVA, T-Student test, Spearman's rank correlation coefficient, and discriminant analysis.
Samples were 46 women (38.33%) and 74 men (61.67%) with a mean age of 55.50 ± 10.49. Mean and SD of ABI in men and women was 0.72 ± 0.20 and 0.80 ± 0.19 with no significant difference (P=0.012). The correlation between ABI and extent of coronary involvement was 0.47 (P < 0.0001). The group with lower ABI had the highest levels of coronary involvement (triple vessel, P < 0.05).
ABI had a significant relationship with the degree of coronary involvement and a significant predictive value. Therefore ABI seems to be a reliable indicator of high coronary risk.
PMCID: PMC3347808  PMID: 22577406
Ankle to brachial index; Coronary involvement; Stable angina

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