Glycemic Control Status and Long-Term Clinical Outcomes in Diabetic Chronic Total Occlusion Patients: An Observational Study.

BACKGROUND: Whether good glycemic control can result in clinical benefits for diabetic chronic total occlusion (CTO) patients is still a matter of debate. METHODS: We studied 1029 diabetic CTO patients. Based on one-year glycosylated hemoglobin A (HbA1c) levels, we assigned the patients into 2 groups: HbA1c<7% group (n = 448) and HbA1c ≥ 7% group (n = 581). We further subdivided the patients into the successful CTO revascularization (CTO-SR) and nonsuccessful CTO revascularization (CTO-NSR) groups. Kaplan-Meier analysis and Cox regression before and after propensity score matching were used to compare major adverse cardiovascular events (MACE) and other endpoints. RESULTS: There were no significant differences between the groups in terms of most endpoints in the overall patients. After propensity score-matched analysis, patients with HbA1c < 7.0 tended to be superior in terms of MACE, which was mainly attributed to repeat revascularization but the other endpoints. Furthermore, the benefit of the HbA1c < 7 group was more prominent among patients with CTO-NSR in terms of MACE, repeat revascularization, and target vessel revascularization (TVR); and the improvement of the HbAc1 < 7 group was more prominent among patients without chronic heart failure (CHF) (P=0.027). CONCLUSIONS: HbA1c < 7.0 was associated with a reduced incidence of MACE, which was mainly attributed to a reduction in repeat revascularization. Good glycemic control can improve diabetic CTO patients' clinical prognosis, especially in CTO-NSR patients.

LncRNA-LUNAR1 Levels Are Closely Related to Coronary Collaterals in Patients with Chronic Total Coronary Occlusion.

Coronary collaterals can effectively improve myocardial blood supply to the area of CTO (chronic total coronary occlusion) and can, thus, reduce infarct size. LUNAR1(leukemia-induced noncoding activator RNA-1) is a specific LncRNA regulated by Notch signaling that not only can enhance the expression of IGFR-1 but also can promote angiogenesis and cell survival. Here, we investigated the relationship between LncRNA-LUNAR1 levels in peripheral plasma and the formation of coronary collaterals. In total, 172 patients with CTO were enrolled and followed up for 12 months. Coronary collaterals were scored according to the Rentrop scoring system. Preclinical tests of tube formation were used to address the mechanisms behind the association between LncRNA-LUNAR1 and development of collaterals. Clinical data and inflammatory factors, including comorbidity, CD14++CD16- monocytes, and CCL2 (chemokine motif ligand 2), were compared and analyzed. Real-time PCR was used to detect the expression of LncRNA-LUNAR1 in peripheral blood plasma. The Rentrop score was positively correlated with LncRNA-LUNAR1 levels in patients with CTO (R = 0.47, p < 0.001). Tube formation assay proved the direct association between LncRNA-LUNAR1 and development of collaterals (p = 0.011). The univariate Kaplan-Meier analysis revealed that patients with low LncRNA-LUNAR1 expression exhibited worse clinical outcomes than those with high LncRNA-LUNAR1 levels (p = 0.008). Receiver operating characteristic (ROC) curve and correlation analysis further confirmed that LncRNA-LUNAR1 expression was closely related to chronic inflammatory diseases, especially diabetes (area = 0.644, p = 0.001; 95% CI, 0.562-0.726). Furthermore, both CD14++CD16- monocytes (r = - 0.37; p < 0.001) and CCL2 levels (r = - 0.35; p < 0.001) negatively affected the expression of LncRNA-LUNAR1. LncRNA-LUNAR1 expression was positively correlated with coronary collaterals in patients with CTO. Inflammatory factors, including CD14++CD16- monocytes and CCL2, may be risk factors affecting LncRNA-LUNAR1 expression.

Interplay of TNF-α, soluble TNF receptors and oxidative stress in coronary chronic total occlusion of the oldest patients with coronary heart disease.

BACKGROUND: The interplay of tumour necrosis factor-α (TNF-α) and oxidative stress was related to severities of coronary atherosclerosis and congestive heart failure. We tried to identify TNF-α, soluble tumour necrosis factor-α receptor-1 (sTNFR-1), soluble tumour necrosis factor-α receptor-2 (sTNFR-2) and oxidative stress as potential non-invasive diagnostic and therapeutic biomarkers for coronary chronic total occlusion (CCTO) in the oldest patients with coronary heart disease (CHD). METHODS: We determined the expression levels of TNF-α, sTNFR-1, sTNFR-2, oxidative stress biomarkers (malondialdehyde [MDA], aldosterone [ALD], angiotensin II [Ang II], and high sensitivity C-reactive protein [hs-CRP]) in oldest patients with CCTO. RESULTS: The levels of TNF-α, sTNFR-1, sTNFR-2, MDA, ALD, Ang II and hs-CRP were increased in oldest patients with CCTO (P < 0.001). The CCTO of oldest patients with CHD may involve the interplay of TNF-α, sTNFR-1, sTNFR-2 and oxidative stress. CONCLUSIONS: The TNF-α, sTNFR-1, sTNFR-2 and oxidative stress could be considered as potential non-invasive diagnostic and therapeutic biomarkers for CCTO in the oldest patients with CHD.

Prognostic value of neutrophil gelatinase-associated lipocalin and glycosylated hemoglobin for non-ST-segment elevation myocardial infarction patients with single concomitant chronic total occlusion following primary percutaneous coronary intervention: A prospective observational study.

To investigate factors predicting the onset of major adverse cardiovascular and cerebrovascular events (MACCEs) after primary percutaneous coronary intervention (pPCI) for patients with non-ST-segment elevation infarction (NSTEMI) and single concomitant chronic total occlusion (CTO). Neutrophil gelatinase-associated lipocalin (NGAL) and glycosylated hemoglobin (HbA1c) both play essential role in cardiovascular and cerebrovascular homoeostasis. However, current knowledge of its predictive prognostic value is limited.422 patients with NSTEMI and CTO (59.7 ±â€Š12.4 years, 74.2% men) who underwent successful pPCI were enrolled and followed for 2 years. Multivariate cox regression analysis and receiver operating characteristic (ROC) curve analysis were performed to determine the factors predicting MACCEs.140 patients (33.2%) experienced MACCEs in the follow-up period. Multivariate cox regression analysis found when we process the model with NGAL at admission, low left ventricular ejection fraction (LVEF, HR = 0.963, 95% CI 0.940 to 0.987, P = .003) and fasting blood glucose (HR = 1.078, 95% CI 1.002 to 1.159, P = .044), but not NGAL at admission, were independent predictors of 2 years MACCEs. While HbA1C (HR = 1.119, 95% CI 1.014 to 1.234, P = .025), LVEF (HR = 0.963, 95% CI 0.939 to 0.987, P = .003), estimated glomerular filtration rate (HR = 1.020, 95% CI 1.006 to 1.035, P = .006) and NGAL value 7 day (HR = 1.020, 95% CI 1.006 to 1.035, P = .006) showed their predictive value in another model. ROC analysis indicated NGAL 7 day (AUC = 0.680, P = .0054 and AUC = 0.622, P = .0005) and LVEF (AUC = 0.691, P = .0298 and AUC = 0.605, P = .0021) could predict both in-hospital and 2 years MACCEs, while higher NGAL at admission could only predict poorer in-hospital prognosis (AUC = 0.665, P = .0103). Further analysis showed the prognostic value of NGAL was particularly remarkable among those HbA1C<6.5%.Patients with NSTEMI and single concomitant CTO receiving pPCI with higher NGAL on 7 days during hospitalization are more likely to suffer 2 years MACCEs, particularly in those with lower HbA1C.

Acute myocardial infarction and transient elevated anticardiolipin antibody in a young adult with possible familial hypercholesterolemia: a case report : Anticardiolipin antibody and myocardial infarction.

BACKGROUND: Familial hypercholesterolemia (FH) can lead to premature coronary heart disease. Anticardiolipin antibody may be a contributor for thrombosis. Here, we report an adult with possible FH suffered from premature myocardial infarction that may be triggered by transient increased anticardiolipin antibody. CASE PRESENTATION: A 29-year-old male had presented with a history of 2-h chest pain and numbness of left upper arm before 5 days. The electrocardiogram (ECG) had demonstrated inferior wall myocardial infarction (MI). Five days later he was admitted to our hospital and diagnosed as acute MI and possible FH (premature coronary heart disease, low density lipoprotein cholesterol of 5.90 mmol/L) with increased anticardiolipin antibody (up to 120 RU/ml). Other auto-antibodies including ß2-glicoprotein antibodies IgM, IgA, IgG, lupus anticoagulant (LA), antinuclear antibodies, anti-myocardial antibody were normal. Coronary artery angiography (CAG) showed right coronary artery was total occlusion from the middle segment. Then he underwent percutaneous coronary intervention with a stent. Four days later, he was discharged with complete recovery. CAG showed intra-stent restenosis and anticardiolipin antibody level was normal and the patient had no any symptoms at 6-month follow-up. CONCLUSIONS: Transient elevated anticardiolipin antibody may be a trigger or biomarker of cardiac thrombotic events in younger atherosclerotic patients.

VEGF-A plasma levels are associated with microvascular obstruction in patients with ST-segment elevation myocardial infarction.

BACKGROUND: Microvascular obstruction (MVO) is associated with poor outcome after ST-segment elevation myocardial infarction (STEMI). Vascular endothelial growth factor-A (VEGF-A) is a vascular permeability inducer playing a key role in MVO pathogenesis. We aimed to assess whether VEGF-A levels are associated with MVO, when evaluated by magnetic resonance imaging (MRI) in STEMI patients. METHODS: The multicenter prospective PREGICA study included a CMR substudy with all consecutive patients with a first STEMI who had undergone cardiac MRI at baseline and at 6-month follow-up. Patients with initial TIMI flow >1 were excluded. VEGF-A levels were measured in blood samples drawn at inclusion. RESULTS: Between 2010 and 2017, 147 patients (mean age 57 ±â€¯10 years; 84% males) were included. MVO was present in 65 (44%) patients. After multivariate analysis, higher troponin peak (OR 1.005; 95% CI 1.001-1.008; p = 0.007) and VEGF-A levels (OR 1.003; 95% CI 1.001-1.005; p = 0.015) were independently associated with MVO. When considering only patients with successful percutaneous coronary intervention (final TIMI flow 3, n = 130), higher troponin peak (p = 0.004) and VEGF-A levels (p = 0.03) remained independently predictive of MVO. Moreover, MVO was associated with adverse left ventricular (LV) remodeling and VEGF-A levels were significantly and inversely correlated with LV ejection fraction (EF) at 6-month follow-up. CONCLUSION: Our results show that VEGF-A levels were independently associated with MVO during STEMI and correlated with mid-term LVEF alteration. VEGF-A could therefore be considered as a biomarker of MVO in STEMI patients and be used to stratify patient prognosis.

Reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion.

BACKGROUND: The extent of coronary collateral formation is a primary determinant of the severity of myocardial damage and mortality after coronary artery occlusion. Type 2 diabetes mellitus (T2DM) represents an important risk factor for impaired collateral vessel growth. However, the mechanism of reduced coronary collateralization in type 2 diabetic patients remains unclear. METHODS: With the reference to the recent researches, this review article describes the pathogenic effects of T2DM on collateral development and outlines possible clinical and biochemical markers associated with reduced coronary collateralization in type 2 diabetic patients with chronic total occlusion (CTO). RESULTS: Diffuse coronary atherosclerosis in T2DM reduces pressure gradient between collateral donor artery and collateral recipient one, limiting collateral vessel growth and function. An interaction between advanced glycation end-products and their receptor activates several intracellular signaling pathways, enhances oxidative stress and aggravates inflammatory process. Diabetic condition decreases pro-angiogenic factors especially vascular endothelial growth factor and other collateral vessel growth related parameters. Numerous clinical and biochemical factors that could possibly attenuate the development of coronary collaterals have been reported. Increased serum levels of glycated albumin, cystatin C, and adipokine C1q tumor necrosis factor related protein 1 were associated with poor coronary collateralization in type 2 diabetic patients with stable coronary artery disease and CTO. Diastolic blood pressure and stenosis severity of the predominant collateral donor artery also play a role in coronary collateral formation. CONCLUSIONS: T2DM impairs collateral vessel growth through multiple mechanisms involving arteriogenesis and angiogenesis, and coronary collateral formation in patients with T2DM and CTO is influenced by various clinical, biochemical and angiographic factors. This information provides insights into the understanding of coronary pathophysiology and searching for potential new therapeutic targets in T2DM.

Serum CXCL10 and CXCL12 chemokine levels are associated with the severity of coronary artery disease and coronary artery occlusion.

BACKGROUND: Cardiovascular disease constitutes a major cause of death worldwide. Inflammation plays an important role in atherosclerosis formation, coronary artery disease progression, acute coronary thrombosis and occlusion. Chemokines are inflammatory mediators disposing several bio-functions, as leukocyte migration towards inflammatory signals and vascular injuries. The present study was designed to evaluate the potential correlation between serum levels of chemokines CXCL-10 and CXCL-12 and the degree of coronary artery occlusion. METHODS: Eighty eight patient candidates for coronary angiography with coronary artery disease symptoms and potentially high risk of coronary artery occlusion were recruited. Chemokine serum levels were measured with the ELISA method and patients underwent coronary angiography. All patients with coronary artery disease (CAD) were divided into four groups according to the Gensini score. Data were presented as mean±SD. All P values <0.05 were considered significant. RESULTS: Our demographic data showed that of the 88 patients, 46 were male and 42 female. The mean age of patients was 57.95±11.13. Following increased coronary artery occlusion the serum levels of chemokines were significantly increased (CXCL-10 and CXCL-12; P<0.0001 and P<0.0001, respectively). CONCLUSION: In this novel study, a significant correlation between the serum levels of CXCL-10 and CXCL-12 and the severity of coronary artery occlusion was found. This could be attributed to the role of these chemokines in the processes of angiogenesis and angiostasis, a biological phenomenon that can play key role in the development of collateral circulation.

Endocan: a novel biomarker associated with well-developed coronary collateral circulation in patients with stable angina and chronic total occlusion.

Angiogenesis and arteriogenesis have a crucial role in the formation of coronary collateral vessels. It has been shown that endocan and vascular cell adhesion molecule-1 (VCAM-1) are potential angiogenetic factors. We investigated the relationship between serum endocan levels and grade of coronary collaterals, and also the correlation of endocan levels with serum VCAM-1 levels. Patients with stable angina and at least one total coronary occlusion at invasive coronary angiography were included in our study. Collateral degree was graded according to Rentrop and Cohen's classification. Patients who had grade 0 or 1 collateral vessels were included in the poorly-developed collateral group, and those with grade 2 or 3 coronary collateral vessels were included in the well-developed collateral group. Serum endocan and VCAM-1 levels were significantly higher in the well-developed collateral group (436.6 ± 213.3 ng/mL vs. 216.1 ± 78.5 ng/mL, p < .001; 11.02 ± 6.58 ng/mL vs. 6.78 ± 1.14 ng/mL, p < .001, respectively). In a logistic regression analysis, only serum endocan level remained as an independent predictor for good collateral development. In the ROC curve analysis, 282 ng/mL endocan level had an a 82 % sensitivity and 86 % specificity for prediction of the well-developed collateral group. Higher endocan level was related to better coronary collateral development. In the event that these results are confirmed in further studies, endocan may be considered as an anti-ischemic treatment strategy in order to improve collateral development.

Lipoprotein(a) as a predictor of poor collateral circulation in patients with chronic stable coronary heart disease

As a mechanism compensating for obstructive coronary artery disease, coronary collateral circulation (CCC) has attracted cardiologists for a long time to explore its potential impact. In the present study, Chinese patients suffering from ≥95% coronary stenosis, as diagnosed by angiography, have been investigated for the correlation between CCC and lipoprotein(a) [Lp(a)] levels. A cohort of 654 patients was divided into four categories according to Rentrop grades 0, 1, 2, and 3. Lp(a) levels were divided into model 1, discretized with critical values of 33 and 66%, and model 2, discretized with a cutoff value of 30.0 mg/dL. Furthermore, we evaluated the correlation between CCC and serum Lp(a) levels. The four groups had significantly different Lp(a) levels (25.80±24.72, 18.99±17.83, 15.39±15.80, and 8.40±7.75 mg/dL; P<0.001). In model 1, concerning R0, the risk in the third Lp (a) tertile (OR=3.34, 95%CI=2.32-4.83) was greater than that in the first tertile. In model 2, concerning R0, the risk in Lp(a) >30.0 group (OR=6.77, 95%CI=4.44-10.4) was greater than that of Lp(a) <30.0 mg/dL. The worst condition of CCC can be predicted independently by Lp(a) levels. In addition to clinical usage, Lp(a) levels can also be utilized as biological markers.

Impact of crossing technique on the incidence of periprocedural myocardial infarction during chronic total occlusion percutaneous coronary intervention.

OBJECTIVES: We sought to evaluate the impact of crossing strategy on the incidence of periprocedural myocardial infarction (PMI) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI). BACKGROUND: The optimal technique for crossing coronary CTOs remains controversial. METHODS: We retrospectively examined the incidence of PMI among 184 consecutive patients who underwent CTO PCI at our institution between 2012 and 2015. Creatine kinase-myocardial band fraction (CK-MB) and troponin were measured before and after PCI in all patients. PMI was defined as CK-MB increase ≥3× upper limit of normal (ULN). RESULTS: Mean age was 65 ± 8 years, 98% of patients were men, 57% had diabetes mellitus, 36% were current smokers, 38% had prior heart failure, 31% had prior coronary artery bypass graft surgery (CABG), and 55% had prior PCI. The retrograde approach was used in 38% of cases. As compared with antegrade wire escalation and antegrade dissection/re-entry, use of the retrograde approach was associated with higher J-CTO (Multicenter CTO Registry of Japan) scores (P < 0.0001), higher frequency of moderate or severe calcification (P = 0.0061), longer CTO length (P < 0.0001), more frequent proximal cap ambiguity (P < 0.0001), and lower technical (P = 0.0007) and procedural (P = 0.0014) success. The frequency of PMI for the antegrade-only and retrograde cases was 10% and 33%, respectively (P = 0.0001). On multivariate analysis, use of the retrograde approach and moderate/severe calcification were independently associated with higher incidence of PMI. CONCLUSIONS: As compared with antegrade-only crossing techniques, the retrograde approach is used in patients with more complex anatomy but may carry higher risk for PMI. © 2016 Wiley Periodicals, Inc.

The association of plasma vitamin A and E levels with coronary collateral circulation.

OBJECTIVE: To investigate if plasma levels of vitamin A and E have an association with coronary collateral development. METHODS: A total of 189 patients who underwent coronary angiography and had total occlusion in at least one major epicardial coronary artery were enrolled in the study. To classify coronary collateral circulation (CCC), the Rentrop scoring system was used. Patients were classified as having poor CCC (Rentrop grades 0-1) or good CCC (Rentrop grades 2-3), and all patients were also screened for hypertension, hypercholesterolemia, diabetes, and smoking history. RESULTS: There were no differences in plasma vitamin A and E levels between the two groups (vitamin A: 2.37 ± 0.65 vs. 2.35 ± 0.78, p = 0.253; vitamin E: 47.1 ± 12.8 vs. 44.6 ± 15.1, p = 0.082), and plasma vitamin A and E levels were not associated with CCC. Serum high-sensitivity C-reactive protein (hs-CRP) levels were significantly higher in patients with poor CCC (4.68 ± 2.52 vs. 3.89 ± 1.78, p = 0.001). The higher frequency of diabetes and higher serum hs-CRP levels were found to be an independent predictor for poor CCC (odds ratio = 2.44, p = 0.006; odds ratio = 1.24, p = 0.007, respectively). And a higher frequency of total occluded RCA was found to be a positive predictor for good CCC (odds ratio = 2.36, p = 0.06) in a multivariate logistic regression analysis. CONCLUSIONS: We found that serum hs-CRP levels, presence of diabetes, and total occlusion of RCA have an effect on coronary collateral development. We found no correlation between plasma vitamin A and E levels and CCC.

Predictors of contrast-induced nephropathy in chronic total occlusion percutaneous coronary intervention.

AIMS: Contrast-induced nephropathy (CIN) is a leading cause of morbidity and mortality in patients undergoing percutaneous coronary intervention (PCI). Limited data, however, are available on predictors of CIN in PCI for chronic total occlusion (CTO) lesions. The aim of the study was to determine the risk of developing CIN in patients undergoing CTO PCI by studying the effects of clinical variables, interventional techniques, and CTO lesion characteristics on renal function. METHODS AND RESULTS: This retrospective analysis included consecutive patients referred for CTO PCI between January 2002 and December 2009. CIN was defined as an elevated serum creatinine level ≥25% of baseline serum creatinine level at 48-72 hours after procedure. Patient characteristics, Mehran score, lesion characteristics, interventional procedure, and devices used were compared between CIN and non-CIN groups. For the 516 patients eligible for analysis, the incidence of CIN was 5.4% (28/516). Two patients needed transient haemodialysis (0.4%, 2/516). Analysis of risk using Mehran scoring found that the incidence of CIN was 0.5% (1/207) among low-risk patients, 3.4% (7/205) among moderate-risk patients, 15.9% (14/88) among high-risk patients and 37.5% (6/16) among very high-risk patients. The Mehran score high-risk group (11-15) and the very high-risk group (≥16) were definitely predictors of CIN after CTO PCI (OR: 27.022 [95% CI: 2.787-262.028, p=0.004]; OR: 32.512 [95% CI: 2.149-491.978, p=0.012]). Severe tortuosity was the only predictor of CIN after CTO PCI in angiographic and procedural findings (OR: 6.621 [95% CI: 1.090-40.227, p=0.040]). CONCLUSIONS: Being in the Mehran score high-risk group (11-15) or the very high-risk group (≥16) and severe tortuosity were predictors of CIN after CTO PCI.

Impact of percutaneous coronary intervention on biomarker levels in patients in the subacute phase following myocardial infarction: the Occluded Artery Trial (OAT) biomarker ancillary study.

BACKGROUND: The purpose of the Occluded Artery Trial (OAT) Biomarker substudy was to evaluate the impact of infarct related artery (IRA) revascularization on serial levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and dynamics of other biomarkers related to left ventricular remodeling, fibrosis and angiogenesis. METHODS: Patients were eligible for OAT-Biomarker based on the main OAT criteria. Of 70 patients (age 60.8 ± 8.8, 25% women) enrolled in the substudy, 37 were randomized to percutaneous coronary intervention (PCI) and 33 to optimal medical therapy alone. Baseline serum samples were obtained prior to OAT randomization with follow up samples taken at one year. The primary outcome was percent change of NT-proBNP from baseline to 1 year. The secondary outcomes were respective changes of matrix metalloproteinases (MMP) 2 and 9, tissue inhibitor of matrix metalloproteinase 2 (TIMP-2), Vascular Endothelial Growth Factor (VEGF), and Galectin-3. RESULTS: Paired (baseline and one-year) serum samples were obtained in 62 subjects. Baseline median NT-proBNP level was 944.8 (455.3, 1533) ng/L and decreased by 69% during follow-up (p < 0.0001). Baseline MMP-2 and TIMP-2 levels increased significantly from baseline to follow-up (p = 0.034, and p = 0.027 respectively), while MMP-9 level decreased from baseline (p = 0.038). Levels of VEGF and Galectin-3 remained stable at one year (p = NS for both). No impact of IRA revascularization on any biomarker dynamics were noted. CONCLUSIONS: There were significant changes in measured biomarkers related to LV remodeling, stress, and fibrosis following MI between 0 and 12 month. Establishing infarct vessel patency utilizing stenting 24 hours-28 days post MI did not however influence the biomarkers' release.

Aspirin plus clopidogrel for optimal platelet inhibition following off-pump coronary artery bypass surgery: results from the CRYSSA (prevention of Coronary arteRY bypaSS occlusion After off-pump procedures) randomised study.

OBJECTIVE: To determine the individual variability in the response to aspirin and/or clopidogrel and its impact on graft patency after off-pump coronary artery bypass grafting. DESIGN: A single-centre prospective randomised controlled study designed according to the Consolidated Standards of Reporting Trials statement. Randomisation was obtained by a computer-generated algorithm. SETTING: University medical school in Italy. PATIENTS: 300 patients who underwent off-pump coronary artery bypass grafting were randomised to receive aspirin (n=150) or aspirin plus clopidogrel (n=150). INTERVENTION: Aspirin 100 mg or aspirin 100 mg plus clopidogrel 75 mg daily was initiated when postoperative chest tube drainage was ≤ 50 ml/h for 2 h and patients were followed up for 12 months. MAIN OUTCOME MEASURES: Qualitative and quantitative assessment of platelet function, angiographic evaluation of coronary revascularisation by 64-slice CT and clinical outcome. RESULTS: In the aspirin group, 49 patients (32.6%) were aspirin resistant and, in the aspirin-clopidogrel group, 19 patients (12.6%) were aspirin and clopidogrel resistant. The platelet response to aspirin was similar in all aspirin responders despite the study arm (Aspirin Reaction Units 313.2 ± 44.8 vs 323.6 ± 53.6; p=0.07). The platelet response to clopidogrel was enhanced by aspirin in patients responsive to both aspirin and clopidogrel (synergistic effect) compared with responders to clopidogrel only (P2Y12 Reaction Units 139.9 ± 15.5 vs 179.4 ± 18.5; p<0.001). Combined therapy was associated with a reduced vein graft occlusion rate (7.4% vs 13.1%; p=0.04). Antiplatelet resistance was a predictor of graft occlusion (RR 3.6, 95% CI 2.5 to 6.9; p<0.001). Synergistic aspirin and clopidogrel activity was a strong predictor of vein graft patency (RR 5.1, 95% CI 1.4 to 16.3; p<0.01). CONCLUSIONS: Combined clopidogrel and aspirin overcome single drug resistances, are safe for bleeding and improve venous graft patency.

Can early cardiac troponin I measurement help to predict recent coronary occlusion in out-of-hospital cardiac arrest survivors?

OBJECTIVE: Recent guidelines recommend the immediate performance of a coronary angiography when an acute myocardial infarction is suspected as a cause of out-of-hospital cardiac arrest. However, prehospital factors such as postresuscitation electrocardiogram pattern or clinical features are poorly sensitive in this setting. We searched to evaluate if an early measurement of cardiac troponin I can help to detect a recent coronary occlusion in out-of-hospital cardiac arrest. DESIGN: Retrospective analysis of a prospective electronic registry database. SETTING: University cardiac arrest center. PATIENTS: Between January 2003 and December 2008, 422 out-of-hospital cardiac arrest survivors without obvious extra-cardiac cause have been consecutively studied. An immediate coronary angiography has been systematically performed. The primary outcome was the finding of a recent coronary occlusion. INTERVENTION: First, blood cardiac troponin I levels at admission were analyzed to assess the optimum cutoff for identifying a recent coronary occlusion. Second, a logistic regression was performed to determine early predictive factors of a recent coronary occlusion (including cardiac troponin I) and their respective contribution. MEASUREMENTS AND MAIN RESULTS: An ST-segment elevation was present in 127 of 422 patients (30%). During coronary angiography, a recent occlusion has been detected in 193 of 422 patients (46%). The optimum cardiac troponin I threshold was determined at 4.66 ng·mL(-1) (sensitivity 66.7%, specificity 66.4%). In multivariate analyses, in addition of smoking and epinephrine initial dose, cardiac troponin I (odds ratio 3.58 [2.03-6.32], p < .001) and ST-segment elevation (odds ratio 10.19 [5.39-19.26], p < .001) were independent predictive factors of a recent coronary occlusion. CONCLUSIONS: In this large cohort of out-of-hospital cardiac arrest patients, isolated early cardiac troponin I measurement is modestly predictive of a recent coronary occlusion. Furthermore, the contribution of this parameter even in association with other factors does not seem helpful to predict recent occlusion. As a result and given the high benefit of percutaneous coronary intervention for such patients, the dosage of cardiac troponin I at admission could not help in the decision of early coronary angiogram.

Common haplotype of interleukin-6 gene is associated with chronic total occlusions of coronary arteries.

AIM: Genetic polymorphisms in genes coding for cytokines may predispose patients to coronary artery disease and chronic total occlusion (CTO) of coronary arteries. The aim of the study was to evaluate association of common genetic variations of interleukins (IL) with CTOs. METHODS: We reviewed coronary angiograms and evaluated presence of CTOs in 684 consecutive patients with no history of revascularization. The following genetic variations were analyzed: IL-1B +3954 C>T, IL-1B -511 C>T, IL-1RN VNTR and haplotypes of IL-6 encompassing IL-6 -596 G>A, IL-6 -572 G>C, IL-6 -373 AnTn and IL-6 -174 G>C polymorphisms. RESULTS: In 254 patients (37.1%) CTO of at least one artery was found. We observed nine IL-6 haplotypes, of which five were common (>1%) and one (GG9/12G, n=8) was not previously reported in literature. The most prevalent IL-6 haplotype (AG8/12C or Hap*1, 49.5%) correlated with CTOs, that were present in 31.5%, 36.5% and 44.5% of patients with none, one and two Hap*1, respectively (OR [95%CI] 1.252 [0.844-1.856] and 1.746 [1.104-2.762] for heterozygots and homozygots, respectively). In multivariate analysis this association became non-significant (OR [95%CI] 1.202 [0.805-1.796] and 1.529 [0.955-2.450]). In subgroup analysis Hap*1 was, however, associated with CTOs in the left anterior descending artery (p for trend 0.032) and the left circumflex artery (P=0.047), but not in the right coronary artery (p=0.799). In multivariate analysis CTOs of the left coronary arteries were associated only with total cholesterol (OR [95%CI] 1.170 [1.020-1.341]) and Hap*1 (OR [95%CI] 1.469 [0.914-2.361] and 1.970 [1.151-3.372] for heterozyogots and homozygots, respectively). CONCLUSION: Our study suggests that common IL-6 haplotype (AG8/12C or Hap*1) is associated with development of CTOs in left coronary arteries.

Oestradiol supplement minimises coronary occlusion-induced myocardial infarction and ventricular dysfunction in oophorectomised female rats.

BACKGROUND: Endogenous oestrogen deficiency after menopause is associated with high risk of acute cardiac events and the protection of exogenous oestrogen supplements remains uncertain. This study investigates whether oestrogen therapy protects the heart from ischemic injury in oophorectomised rats. METHODS: Sexually mature female Sprague-Dawley rats (6 for each group) with bilateral oophorectomy underwent selective ligation (occlusion) of left coronary artery for 4 weeks. 17ß-oestradiol (E2) supplements (10 µg, i.m., every other day) were started before (preventive-therapeutic supplement) or after coronary occlusion (therapeutic supplement). RESULTS: In oophorectomised rats plasma levels of E2 declined from 1301 ± 80 to 196 ± 48 pmol/L (p<0.01) and cardiac expression of oestrogen receptors (ER) decreased by ∼60%. E2 supplements recovered the ER expression. Selective ligation of left coronary led myocardial infarction in the left ventricle, with an increase in plasma cardiac troponin I (cTn-I), decrease in systolic blood pressure (SBP), and reduction of left ventricular pressures. Preventive-therapeutic but not therapeutic E2 supplement reduced cTn-I levels (from 21.9 ± 2.0 to 6.0 ± 0.3 ng/mL, p<0.01), minimised infarction (from 37.0 ± 1.2% to 18.1 ± 2.3%, p<0.05), increased SBP (from 82 ± 4.2 to 97 ± 4.4mm Hg, p<0.05), and improved left ventricular end pressures in the oophorectomised rats following coronary occlusion. CONCLUSION: Postmenopausal (ooporectomised) oestrogen supplement commenced before establishment of myocardial ischemia minimises myocardial infarction and ventricular dysfunction following the coronary artery occlusion. Cellular and molecular mechanisms underlying the cardiac protection of oestrogen therapy remain unclear, in which activation of cardiac ER expression and increasing in circulating CD90(+) stem cells may be involved.

Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease.

BACKGROUND: Fibroblast growth factor 23 (FGF-23) is a phosphorus-regulating hormone. In chronic kidney disease (CKD), circulating FGF-23 levels are markedly elevated and independently associated with mortality. Left ventricular hypertrophy and coronary artery calcification are potent risk factors for mortality in CKD, and FGFs have been implicated in the pathogenesis of both myocardial hypertrophy and atherosclerosis. We conducted a cross-sectional study to test the hypothesis that elevated FGF-23 concentrations are associated with left ventricular hypertrophy and coronary artery calcification in patients with CKD. METHODS AND RESULTS: In this study, 162 subjects with CKD underwent echocardiograms and computed tomography scans to assess left ventricular mass index and coronary artery calcification; echocardiograms also were obtained in 58 subjects without CKD. In multivariable-adjusted regression analyses in the overall sample, increased log FGF-23 concentrations were independently associated with increased left ventricular mass index (5% increase per 1-SD increase in log FGF-23; P=0.01) and risk of left ventricular hypertrophy (odds ratio per 1-SD increase in log FGF-23, 2.1; 95% confidence interval, 1.03 to 4.2). These associations strengthened in analyses restricted to the CKD subjects (11% increase in left ventricular mass index per 1-SD increase in log FGF-23; P=0.01; odds ratio of left ventricular hypertrophy per 1-SD increase in log FGF-23, 2.3; 95% confidence interval, 1.2 to 4.2). Although the highest tertile of FGF-23 was associated with a 2.4-fold increased risk of coronary artery calcification > or =100 versus <100 U compared with the lowest tertile (95% confidence interval, 1.1 to 5.5), the association was no longer significant after multivariable adjustment. CONCLUSIONS: FGF-23 is independently associated with left ventricular mass index and left ventricular hypertrophy in patients with CKD. Whether increased FGF-23 is a marker or a potential mechanism of myocardial hypertrophy in CKD requires further study.