Insignificant Coronary Stenosis Research Articles

Investigation of miR-26a-5p and miR-19a-3p expression levels in angiographically confirmed coronary artery disease

Background MicroRNAs have been found to have an essential role in cardiovascular diseases. In previous experiments, the changed expressions of miR-26a-5p and miR-19a-3p were confirmed in patients with severe coronary atherosclerosis by miRNA microarrays. However, the role of two miRNAs in coronary artery diseases (CAD) still needs to be investigated further. Our current study aimed to analyse two miRNAs in angiographically confirmed CAD and non-CAD with insignificant coronary stenosis. This study aimed to identify the potential diagnostic value of circulating miRNA with CAD. Methods The CAD patients (n = 50) and non-CAD controls (n = 43) were studied. miRNAs (miR-26a-5p and miR-19a-3p) were quantified by TaqMan miRNA assays using real-time PCR. We subsequently assessed the diagnostic value of the miRNAs and correlations of miRNA with clinical parameters. Target prediction tools were utilised to identify miRNA target genes. Results The expression of miR-26a-5p was significantly increased in CAD compared to non-CAD controls (p < 0.05). Tertile groups were formed according to the expression levels of miRNAs, and high expression tertile (T3) was compared with low expression tertile (T1). It was found that CAD presence was more prevalent in T3 of miR-26a-5p, and the frequency of diabetes was higher in T3 of miR-19a-3p. There were significant correlations between miRNAs and diabetes risk factors such as HbA1c, glucose levels, and BMI (p < 0.05). Conclusions Our findings show that miR-26a-5p expression is altered in CAD presence while miR-19a-3p expression is different in diabetes. Both miRNAs are closely related to risk factors of CAD, therefore, could be therapeutic targets for CAD treatment.

Prognostic Impact of Indeterminate Diastolic Function in Patients With Functionally Insignificant Coronary Stenosis

Cardiac diastolic dysfunction is an independent predictor of mortality, regardless of left ventricular (LV) systolic function. However, the current guidelines that define cardiac diastolic dysfunction may underrate the clinical implications of those with indeterminate diastolic function. We sought to evaluate the prognostic implications of indeterminate diastolic function on echocardiography and its association with coronary microvascular dysfunction (CMD). A total of 330 patients without LV systolic dysfunction and significant epicardial coronary stenosis (fractional flow reserve > 0.80) were analyzed from a prospective registry. Cardiac diastolic dysfunction was defined according to 2 algorithms depending on the presence of myocardial disease. First, the presence of myocardial disease and evidence of elevated LV filling pressure indicated diastolic dysfunction. Second, diastolic function in those without myocardial disease was defined using echocardiographic parameters (E/e', e' velocity, tricuspid regurgitation velocity, and left atrial volume index). Patients who did not meet half of the available criteria were classified as having indeterminate diastolic function. Coronary microvascular dysfunction was defined as coronary flow reserve < 2.0 and index of microcirculatory resistance ≥ 25 U. The primary outcome was cardiovascular death or admission for heart failure at 5years. Coronary flow reserve was lower in patients with indeterminate diastolic function compared with those with no diastolic dysfunction (3.5±1.6 vs 3.2±1.6, P=.002). The prevalence of CMD was also higher in patients with indeterminate diastolic function than in those with no diastolic dysfunction (10.6% vs 4.9%, P<.034). Patients with indeterminate diastolic function showed significantly higher risk of cardiovascular death or admission for heart failure than those without indeterminate diastolic function but not greater than those with definite diastolic dysfunction (cumulative incidence: 12.6%, 27.2%, and 32.7%, respectively, log-rank P<.001). Presence of CMD and elevated LV filling pressure (E/e'>14) were independent predictors for cardiovascular death or admission for heart failure in patients with indeterminate diastolic function. Patients with indeterminate diastolic function on echocardiogram showed higher risk of cardiovascular death or admission for heart failure than those with no diastolic dysfunction. Presence of CMD and elevated LV filling pressure were independent predictors for cardiovascular death or admission for heart failure among patients with indeterminate diastolic function.

Peripheral Blood Mononuclear Cells Expression Levels of miR-196a and miR-100 in Coronary Artery Disease Patients

ABSTRACT As a chronic inflammatory disease, coronary artery disease (CAD) is a common cause of death worldwide. Dysregulation of microRNA expression levels in peripheral blood mononuclear cells (PBMCs) may contribute to CAD and serve as a potential diagnostic biomarker. Here, we evaluated PBMC expression of two CAD-related inflammatory miRNAs, miR-196a and miR-100, in PBMCs of CAD patients with significant stenosis (CAD, n: 72), patients with insignificant coronary stenosis (ICAD, n: 30), and controls (n: 74) and checked whether they can segregate study groups. MiRNA expression was evaluated using the standard stem-loop RT-qPCR method. MiR-196a expression was downregulated in ICAD compared to CADs and healthy groups. MiR100 expression levels were not different between groups. The receiver operating characteristic (ROC) curve analysis acquainted that miR-196a expression levels in PBMC could segregate CAD individuals or any of its clinical manifestations (i.e. unstable angina, stable angina, acute myocardial infarction) from ICADs. In conclusion, this study reported a distinct miR-196a expression pattern in PBMCs of all patient groups and recommended a biomarker potential for miR-196a in discriminating ICADs from CADs or healthy controls.

Hsa-miR-584-5p as a novel candidate biomarker in Turkish men with severe coronary artery disease.

Coronary artery disease (CAD) is still the preliminary cause of mortality and morbidity in the developed world. Identification of novel predictive and therapeutic biomarkers is crucial for accurate diagnosis, prognosis and treatment of the CAD. The aim of this study was to detect novel candidate miRNA biomarker that may be used in the management of CAD. We performed miRNA profiling in whole blood samples of angiographically confirmed Turkish men with CAD and non-CAD controls with insignificant coronary stenosis. Validation of microarray results was performed by qRT-PCR in a larger cohort of 62 samples. We subsequently assessed the diagnostic value of the miRNA and correlations of miRNA with clinical parameters. miRNA-target identification and network analyses were conducted by Ingenuity Pathway Analysis (IPA) software. Hsa-miR-584-5p was one of the top significantly dysregulated miRNA observed in miRNA microarray. Men-specific down-regulation (p = 0.040) of hsa-miR-584-5p was confirmed by qRT-PCR. ROC curve analysis highlighted the potential diagnostic value of hsa-miR-584-5p with a power area under the curve (AUC) of 0.714 and 0.643 in men and in total sample, respectively. The expression levels of hsa-miR-584-5p showed inverse correlation with stenosis and Gensini scores. IPA revealed CDH13 as the only CAD related predicted target for the miRNA with biological evidence of its involvement in CAD. This study suggests that hsa-miR-584-5p, known to be tumor suppressor miRNA, as a candidate biomarker for CAD and highlighted its putative role in the CAD pathogenesis. The validation of results in larger samples incorporating functional studies warrant further research.

Dysregulated expression of STAT1, miR-150, and miR-223 in peripheral blood mononuclear cells of coronary artery disease patients with significant or insignificant stenosis.

Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood-mononuclear cells (PBMCs), as a critical component of immune system, actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine-tuning CAD-related inflammatory processes. This study evaluated PBMC expressions of STAT1, and its regulators (miR-150 and miR-223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( < 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real-time polymerase chain reaction (RT-qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR-150, miR-223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR-150 and miR-223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1, miR-150, and miR-223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.

Association of Major Adverse Cardiac Events up to 5Years in Patients With Chest Pain Without Significant Coronary Artery Disease in the Korean Population.

BackgroundSignificant coronary artery disease has a well‐known association with long‐term adverse cardiovascular events. In this study, we aimed to evaluate its association with long‐term major adverse clinical events (MACE) up to 5 years in patients who presented with chest pain without significant coronary artery disease.Methods and ResultsA total of 5890 subjects with chest pain without significant coronary artery disease were prospectively enrolled in this study. The mean follow‐up duration was 3.4 years. Multivariable Cox proportional hazards regression analysis was performed for assessing the independent risk factors for MACE or sustained angina pectoris. MACE was defined as the composite of total death, myocardial infarction, coronary revascularization, stroke, and hospitalization because of heart failure. Ninety‐one (2.2%) patients developed MACE, and 309 (8.1%) patients developed sustained angina pectoris, both within 5 years. In multivariable Cox proportional hazards regression analysis, the risk of MACE was significantly associated with age (per 5 years; hazard ratio [HR], 1.44; 95% CI, 1.30–1.60) and insignificant coronary stenosis (30%–70%; HR, 2.03; 95% CI; 1.28–3.21). The risk of sustained angina pectoris was significantly associated with age (per 5 years; HR, 1.05; 95% CI, 1.01–1.11), dyslipidemia (HR, 1.34; 95% CI, 1.06–1.70), insignificant coronary stenosis (HR, 2.54; 95% CI, 1.94–3.31), coronary artery spasm (HR, 1.42; 95% CI, 1.11–1.80), and myocardial bridge (HR, 1.37; 95% CI, 1.04–1.81).ConclusionsIn patients without significant CAD, aging and insignificant coronary stenosis have a strong association with future long‐term MACE. Also, aging, dyslipidemia, insignificant coronary stenosis, coronary artery spasm, and myocardial bridge are strongly associated with future angina pectoris.

Expression pattern of miR-21, miR-25 and PTEN in peripheral blood mononuclear cells of patients with significant or insignificant coronary stenosis

Coronary artery disease (CAD) is primarily caused by atherosclerosis, which is a series of chronic inflammatory processes leading to the initiation and progression of vascular endothelial cell injury enhancing plaque formation. As critical components of the immune system, peripheral blood mononuclear cells (PBMCs) actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in altered PBMC expression pattern. This study explored PBMC expression levels of miR-21, miR-25 and PTEN in patients with angiographically proven significant coronary stenosis (the CAD group), patients with insignificant coronary stenosis (the ICAD group) and healthy subjects, and assessed potentials of PBMC expressions in discriminating groups of study subjects. In-silico analysis was also performed to obtain insights into CAD-related pathways and biological processes that may be influenced by altered miRNA expressions. A reduced level of PBMC miR-21 was observed in the ICAD group compared to the CAD group (P: 0.004) or healthy controls (P: 0.0001). PBMC miR-21 level was negatively correlated with the PTEN expression (Spearman r: −0.43, P: 3.9e−09). The PTEN expression was increased in the CAD or ICAD group compared to the control group (CAD vs. controls P: 0.0003, ICAD vs. controls P: 0.03). A stepwise increase in PBMC miR-25 levels was observed from healthy controls to ICADs and CAD patients (Kruskal-Wallis P: 7.68e−12). PBMC gene expressions had reasonable power to discriminate between pairs of study groups. PBMC miR-21 levels were able to discriminate ICADs from both CADs and controls and miR-25 levels had potentials to differentiate among all pairs of study groups (i.e. CADs-ICADs, CADs-controls, CADs-all other subjects, ICADs-controls). PBMC PTEN expression was able to discriminate patients with CAD or ICAD from control subjects. Overrepresentation enrichment analysis of experimentally validated targets of miR-21 and miR-25 highlighted key biological processes and pathways, such as “angiogenesis” and “leukocyte cell-cell adhesion”, that may be influenced by dysregulation of PBMC miR-21 and miR-25. In conclusion, these findings suggest that patients with insignificant coronary stenosis may have a distinct PBMC miRNA expression profile than those with significant stenosis or healthy controls.

Development of a multivariate model to predict significant coronary artery disease in Thai patients with left ventricular systolic dysfunction and determine the applicability of coronary angiography: a single-center, retrospective, case–control study

Abstract Background Coronary angiography (CAG) or stress imaging has been performed in almost all Thai patients with left ventricular (LV) systolic dysfunction. If CAG results reveal insignificant coronary stenosis, such patients are diagnosed with nonischemic cardiomyopathy (NICM); however, CAG is considered to provide no benefit and may even harm these patients because it is invasive. Objectives To identify predictors associated with significant coronary artery disease (CAD) (stenosis) in Thai patients with LV systolic dysfunction without angina and without LV regional wall motion abnormality and create a prediction score. Method Retrospective data from patients at a single tertiary-care center with LV systolic dysfunction (LV ejection fraction &lt;50%) diagnosed between August 2000 and October 2014 were separated into a group with ischemic cardiomyopathy (ICM) and a group with NICM according to CAG. Predictors associated with CAD found in normal populations were determined. Multivariate analysis was used to identify predictors associated with significant coronary stenosis in patients with LV systolic dysfunction to develop a model to create a prediction score. Results We included data registered from 240 Thai patients with LV systolic dysfunction. Predictors associated with ICM were age (&gt;60 years), sex (male), and a history of diabetes mellitus (DM). Predictors associated with NICM were body mass index (BMI) &gt;25 kg/m2 and the presence of left bundle branch block (LBBB) on electrocardiography. A simplified equation to predict significant CAD in patients with LV systolic dysfunction is: 3(male sex) + 3(age &gt;60 y) – 5(BMI &gt;25 kg/m2) - 5(LBBB) + 5(DM) - 5. The sensitivity and specificity of this score are 60.5% and 85.1%, respectively. Conclusion Our prediction score has modest sensitivity, but high specificity for predicting significant CAD and can be used to determine who should not undergo CAG.

Patients with non-obstructive coronary artery disease admitted with acute myocardial infarction carry a better outcome compared to those with obstructive coronary artery disease.

BackgroundThe characterization of patients who have acute myocardial infarction (AMI) and insignificant coronary stenosis is unclear.AimThe present study aimed to investigate the clinical profile, in-hospital and 3-month outcome of AMI patients with insignificant coronary stenosis in comparison with those with significant disease.MethodsThis prospective observational study included 200 consecutive patients admitted with AMI. Group I (100 patients) included patients with insignificant CAD (all lesions <50% stenosis). Group II (100 patients) included patients with one or more lesions >70% stenosis. Patients with previous CABG were excluded. Patients with significant CAD had successful total revascularization.ResultsPatients with insignificant CAD were significantly younger (61 vs. 67 years, p < 0.001), more likely to be females (41% vs. 23%, p = 0.006), less likely to smoke (p = 0.006), less likely to have diabetes mellitus (p < 0.001), and less likely to have history of CAD (p = 0.042) or prior PCI (p = 0.037). They were also less likely to have typical anginal pain at presentation (61% vs 91%, p < 0.001), less likely to have heart failure at presentation (9% vs 30%, p < 0.001), less likely to have ischemic ST-segment changes on presentation (10% vs 46%, p < 0.001), lower peak troponin (p < 0.001) and CK-MB levels (p < 0.001), with lower LDL-C (p = 0.006), and higher HDL-C level (p = 0.020). They were less likely to be treated with b-blockers (p = 0.002), ACEI/ARBS (p = 0.007), and higher rates of calcium channel blocker therapy (p < 0.001). They had lower prevalence of major adverse clinical events at follow-up (readmission for ACS (p = 0.009), need for revascularization (p = 0.035), recurrent chest pain (p = 0.009), and cardiogenic shock (p = 0.029).ConclusionPatients with AMI and insignificant CAD have different clinical profile and outcome compared to those with significant disease.

Three-year follow-up of patients with acetylcholine-induced coronary artery spasm combined with insignificant coronary stenosis

BackgroundCoronary artery spasm (CAS) and significant coronary stenosis are known to be major causes of myocardial ischemia. However, their association and the impact of insignificant coronary stenosis (ICS) on long-term clinical outcomes of CAS patients are largely unknown. MethodsA total of 2797 patients without significant coronary artery disease (CAD) who underwent the acetylcholine (ACH) provocation test between November 2004 and October 2010 were enrolled. Significant CAS was defined as having ≥70% of temporary narrowing by ACH test and ICS as having <70% of fixed stenosis on angiography. Patients were divided into two groups: ICS group (n=764) and non-ICS group (n=845). To adjust potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. Primary endpoint was the composite of total death, myocardial infraction (MI), de novo percutaneous coronary intervention (PCI), and cerebrovascular accidents (CVA). Secondary endpoint was the incidence of recurrent angina requiring repeat coronary angiography (CAG) at 3years. ResultsAfter PSM analysis, two well-balanced groups (548 pairs, total=1096) were generated. The baseline clinical characteristics were similar between the two groups. During the ACH test, compared with the non-ICS group, the ICS group had smaller spastic narrowing diameter (0.69±0.35 vs. 0.73±0.37, P=0.039) and incidence of ST-segment depression (4.0% vs. 0.9%, P=0.001). The incidence of primary and secondary endpoints was similar between the two groups up to 3years. ConclusionsAlthough, the ICS group was expected to have more adverse long-term clinical outcomes, it was not associated with the increased incidence of major adverse clinical outcomes compared with the non-ICS group up to 3years. Longer term follow-up studies are needed.

Epidemiological and clinical characteristics of patients with unstable angina and critical coronary stenosis detected by angiography

Certain clinical predictors like age, cardiac biomarker positivity, ST segment depression and congestive heart failure (CCF) can help effectively in predictinghigh risk group patients with critical coronary artery disease. Khat chewing is a significant risk factor for ACS in Yemenite patients, but correlation of heavy Khat chewing with critical artery stenosis in unstable angina (UA) patients is notstudied. The aim of this study is to define the epidemiological and clinicalcharacteristics in UA patients included in this prospective clinical study. Based onthe angiographic findings, patients with UA were classified into 2 groups: Group (I): patients with coronary stenosis (≥70%), significant enough to require PCI or CABG, (n=213) and Group II (control) patients who had insignificant coronary stenosis (≤50%), (n=42). Our results showed that group I patients were more likely to be males, elderly, with a prior history of CAD and MI, heavy khat chewers and in heart failure. Mean of age was 66.54 years, and 78.87 % were males. Age ≥ 65 years was found in 29.11%. Predictors of high risk CAD (critical stenosis) were found to be significantly in group I, compared to group II patients. We concluded that age ≥ 65 years, male gender, aspirin use and heavy Khat chewing during the last week, CCF with EF

Lipid profile, inflammatory response and endothelial dysfunction markers in patients with coronary artery stenosis

Objectives: To assess the parameters of lipid profile, inflammatory and endothelial dysfunction in patients with significant coronary stenosis compared to patients with insignificant coronary stenosis.

Acute Myocardial Injury and Complete Atrioventricular Block Induced by Transient Coronary Artery Spasm

A 65-year-old man with no previous history of heart disease presented with cardiogenic shock. Acute right ventricular failure following extensive inferior wall myocardial infarction and complete atrioventricular block were noted and emergent angiography revealed insignificant coronary arterial stenosis. In view of the finding and absence of myocardial vasculitis, coronary artery spasm was implicated as the cause of myocardial infarction and complete atrioventricular block. After the reversal of the shock and successful angioplasty, the patient continued to take lercanidipine and had been angina-free during follow-up of 5 months. (Hong Kong j.emerg.med. 2013;20:396-399)

Acute Myocardial Injury and Complete Atrioventricular Block Induced by Transient Coronary Artery Spasm

A 65-year-old man with no previous history of heart disease presented with cardiogenic shock. Acute right ventricular failure following extensive inferior wall myocardial infarction and complete atrioventricular block were noted and emergent angiography revealed insignificant coronary arterial stenosis. In view of the finding and absence of myocardial vasculitis, coronary artery spasm was implicated as the cause of myocardial infarction and complete atrioventricular block. After the reversal of the shock and successful angioplasty, the patient continued to take lercanidipine and had been angina-free during follow-up of 5 months. (Hong Kong j.emerg.med. 2013;20:396-399)

SIGNIFICANT CORONARY ARTERY STENOSIS IN PATIENTS WITH LOW CORONARY ARTERY CALCIUM SCORE

Background: Coronary artery disease is a major cause of morbidity and mortality. Non-invasive techniques for diagnosis are becoming increasingly popular and multidetector coronary computed tomography has emerged as a promising modality. Quantifying the amount of coronary artery calcium with unenhanced CT calcium score has been shown to be a reliable noninvasive technique for screening risk of future cardiac events. In previous trials low coronary artery calcium score has been shown to rule out coronary artery disease with high predictive value.&#x0D; Objective: To evaluate the level of agreement between severity of stenosis on CT angiography and calcium burden as measured by dedicated CT protocols for calcium scoring, comparing their results.&#x0D; Material and Method: The study was conducted at Radiology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre and Heart and Body Scan Centre, Lahore. Duration of study was 6 months. The study design was a cross sectional survey.&#x0D; Results: Mean age of patients was 38.65+5.72. Male to female ratio was 2.5:1 (72 males: 27 females).Agreement of low calcium score and insignificant coronary stenosis was found in 78 patients while 22 showed no agreement. Kappa test was applied, p value was recorded. 0.0005. 50% (11 out of 22) of the patients with calcium score of 0 had significant coronary stenosis.&#x0D; Conclusion: The results of study reveal that absence of calcium or low calcium does not exclude significant coronary stenosis. Depending on presentation, it is recommended to get calcium score and coronary CT angiography done in the same setting.

Diverse Effects of Oxygen Inhalation on the Regional Myocardial Functions Related to the Degree of Coronary Artery Stenosis

In patients with stable coronary artery disease, the effect of oxygen (O2) inhalation to regional myocardial functions and its relation to the degree of the coronary artery stenosis is still unclear. This article investigates the effect of O2 therapy on regional myocardial functions in patients with coronary atherosclerosis according to the severity of stenosis. Myocardial segments were evaluated via tissue velocities, strain, strain rate, and tissue tracking. While O2 inhalation improves late diastolic myocardial velocity and tissue tracking in normally perfused myocardial regions, a negative effect was observed on systolic and diastolic parameters of myocardial segments, which are perfused by insignificantly stenotic coronary arteries. Although nasal O2 treatment has unfavorable effects on regional myocardial functions in patients with coronary artery disease, this effect remains subclinic with short-term inhalation. However, it is reasonable to pursue the effects of longer-term O2 inhalation on myocardial function especially in patients with insignificant coronary stenosis.

Clinical significance of myocardial perfusion abnormalities in patients with varying degree of coronary artery stenosis

(1) To identify myocardial perfusion abnormalities in a cohort of patients having coronary artery disease (CAD) risk factors, with either suspected or clinical evidence of ischaemic heart disease (IHD), and with varying degree of coronary artery stenosis. (2) To evaluate the clinical significance of the extent and severity of perfusion abnormalities assessed by myocardial perfusion scintigraphy (MPS) in relation to the anatomical location of coronary stenosis demonstrated by five-vessel selective coronary angiography (SCA). One hundred and thirty-eight patients (106 male, 32 female) with suspected or clinical evidence of IHD underwent diagnostic evaluation at the Central Hospital of Nicosia, between November 2002 and August 2003. The diagnostic work-up included clinical examination, exercise tolerance test, SCA and myocardial perfusion scintigraphy (MPS) using either Tl chloride or Tc-tetrofosmin. Based on the results of SCA, patients were divided into five groups on the basis of stenosis as cross-sectional area of coronary artery lumen and its haemodynamic significance, ranging from group 1=less than 50% coronary stenosis to group 5=100% stenosis (occlusion). Nine of 11 (40.9%) patients with angiographically normal coronary arteries (group 1) had moderate inducible reversible ischaemia on MPS and 9/47 (19.1%) patients with insignificant coronary stenosis (less than 75% stenosis=group 2) had fixed perfusion defects, compatible with previous myocardial infarction. The extent of perfusion abnormalities in post-stress MPS patients from group 2 was not found to be statistically significant (P>0.05) when compared to patients belonging to groups 3, 4 and 5. However, the extent of perfusion abnormalities between patients from group 2, when compared to groups 3, 4 and 5 demonstrated significant statistical difference (P<0.05) on post-rest MPS studies. Furthermore, there was no significant statistical correlation between anatomical location of coronary stenosis and severity of perfusion abnormalities in the corresponding myocardial segments. Patients with CAD risk factors, and coronary arteries with insignificant stenosis on angiography, may demonstrate inducible reversible myocardial ischaemia. This is suggestive of coronary endothelial dysfunction. Patients with insignificant coronary artery stenosis and no previous history of adverse coronary events may demonstrate features of previous myocardial infarction on MPS. The severity of perfusion defects demonstrated by MPS may be independent of the anatomical location of coronary artery stenosis.

Association between Toll-like receptors and the extent and severity of coronary artery disease in patients with stable angina

Toll-like receptors mediate the innate immune response triggered by pathogen-associated molecular patterns, and atherosclerosis can be considered a state of chronic inflammation whereby immune system cells accumulate within the intima of the arterial wall. The goal of this study was to determine the relation of Toll-like receptors to the extent and severity of coronary artery disease. Angiographic vessel score and Gensini score were used to evaluate the extent and severity of coronary atherosclerosis. Sixty-two consecutive patients with stable angina were grouped as follows: those with insignificant (<50%) coronary stenosis (group 1), and those with 1 (group 2), 2 (group 3), or 3-vessel disease (group 4). The expression of Toll-like receptor 1, 2, and 4 on circulating CD14+ monocytes was analyzed by flow-cytometry in all patients. Toll-like receptor 2 had a positive correlation with the vessel score and Gensini score (r=0.46, P<0.001; r=0.32, P<0.02, respectively). Toll-like receptor 4 also positively correlated with the vessel score and Gensini score (r=0.47, P<0.001; r=0.29, P<0.05, respectively). No significant correlation existed between the expression of Toll-like receptor 1 and the vessel score or Gensini score. Further, there was no significant correlation between high-sensitivity C-reactive protein and the vessel score or Gensini score. These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease.

The Association of QT Dispersion and QT Dispersion Ratio with Extent and Severity of Coronary Artery Disease

Although prolongation of the QT intervals in acute ischemic conditions, such as acute myocardial infarction, intracoronary balloon inflation, and exercise induced ischemia, has been shown, association of rest QT intervals with extent and severity of stable coronary artery disease (CAD) has not been assessed so far. The effects of extent and severity of stable CAD on rest QT interval were analyzed in this study. Rest 12-lead electrocardiograms (ECG) were recorded in 162 clinically stable subjects undergoing coronary angiography before the angiography for measurement of corrected QT dispersion (cQTd) and the QT dispersion ratio (QTdR) defined as QT dispersion divided by cycle length and expressed as a percentage. Angiographic "vessel score,""diffuse score," and "Gensini score" were used to evaluate the extent and severity of coronary atherosclerosis. Subjects were grouped as follows: those with normal angiogram (Group 1), those with insignificant (<50%) coronary stenosis (Group 2), and those with 1- (Group 3), 2- (Group 4), or 3-vessel disease (Group 5). cQTd and QTdR were higher in Group 3 compared with Group 1 (P < 0.001 and P = 0.001, respectively), in Group 4 compared with Group 1 (P < 0.001 for both) and Group 2 (P = 0.001 and P = 0.003, respectively), and in Group 5 compared with Group 1 (P < 0.001 for both) and Group 2 (P < 0.001 and P = 0.003, respectively). cQTd and QTdR were positively correlated with the vessel score (r = 0.422, P < 0.001; r = 0.358, P < 0.001, respectively), diffuse score (r = 0.401, P < 0.001; r = 0.357, P < 0.001, respectively) and Gensini score (r = 0.378, P < 0.001; r = 0.373, P < 0.001, respectively). In multiple linear regression analyses, cQTd was found to be independently associated only with diffuse score (beta= 0.325, P = 0.038). Also, QTdR was independently associated with diffuse score (beta= 0.416, P = 0.006) and Gensini score (beta= 0.374, P = 0.011). Rest cQTd and QTdR are increased, and related to the extent and severity of coronary atherosclerosis in patients with stable CAD.

Coronary vasospasm as a possible cause of elevated cardiac troponin I in patients with acute coronary syndrome and insignificant coronary artery disease

Background Abnormal levels of serum cardiac troponin I (cTnI) are occasionally found in patients presenting with acute coronary syndromes but having insignificant coronary artery disease. Before one concludes that an abnormal cTnI level is a false-positive result, the possibility of coronary vasospasm should be considered. This study investigated whether coronary vasospasm could be a reason for elevated cTnI in this patient population. Methods and Results This investigation enrolled 93 patients who presented to the emergency department with suspected coronary ischemia and had insignificant coronary artery disease. cTnI was elevated in 23 patients (25%) and was normal in 70 patients (75%). Coronary vasospasm, documented by an ergonovine provocation test, was found in 38 patients (41%). Patients with elevated cTnI levels, compared with those with normal cTnI, were older (63 ± 13 y vs 56 ± 14 y, P =.032), had a higher incidence of males (78% vs 52%, P =.049) and positive ergonovine provocation tests (74% vs 30%, P <.0001), and tended to have a lower incidence of hypercholesterolemia (26% vs 48%, P =.088) and normal electrocardiograms (48% vs 70%, P =.078). Multivariate analysis showed that the variables independently associated with an elevated cTnI level included coronary vasospasm (odds ratio 2.41, 95% CI 1.48-3.18, P <.0001) and hypercholesterolemia (odds ratio 0.64, 95% CI 0.47-0.99, P =.049). Coronary vasospasm (positive ergonovine provocation test) could explain 74% of elevated cTnI levels in patients with insignificant coronary stenosis. Conclusions In patients with acute coronary syndrome with elevated cTnI and insignificant coronary artery disease, the possibility of coronary vasospasm as a cause of elevated cTnI should be considered. (Am Heart J 2002;144:275-81.)