Levels of Activated FXII in Survivors of Myocardial Infarction – Association with Circulating Risk Factors and Extent of Coronary Artery Disease

1998 ◽  
Vol 79 (01) ◽  
pp. 14-18 ◽  
Author(s):  
Hans Kohler ◽  
Angela Carter ◽  
Max Stickland ◽  
Peter Grant

SummaryLittle data is available regarding the activated form of factor XIIa (FXIIa) in survivors of myocardial infarction. 292 Caucasian patients characterised for extent of coronary atheroma by angiography and for a past history of myocardial infarction and 77 healthy controls were included in the study. To investigate the relationship between coronary artery disease, activated factor XII and other circulating factors, we studied levels of FXIIa, cholesterol, triglycerides, fasting insulin, fibrinogen, FVII:C, t-PA antigen and PAI-1 antigen. Factor XIIa levels were higher in all patients [2.5 (2.3-2.6) ng/ml] and in patients with a history of MI [2.6 (2.4-2.9) ng/ml] than in controls [1.9 (1.7-2.1) ng/ml], p <0.0001. In patients, FXIIa levels positively correlated with FVII:C, BMI, cholesterol, insulin, PAI-1 antigen, t-PA antigen and triglycerides. In controls FXIIa levels only correlated with PAI-1 antigen and triglycerides. FXIIa levels were strongly associated with extent of coronary stenosis: 2.8 (2.6-3.1) ng/ml and 2.6 (2.3-2.9 ng/ml) in those with 2 and 3 vessels stenosed compared to 2.1 (1.9-2.3) ng/ml in those with 0 vessel stenosed (p = 0.0004). Activated FXII relates to both extent of coronary atheroma and to a past history of myocardial infarction and clusters with features of insulin resistance.

2001 ◽  
Vol 12 (7) ◽  
pp. 1516-1523 ◽  
Author(s):  
AUSTIN G. STACK ◽  
WENDY E. BLOEMBERGEN

Abstract. Despite the high prevalence of coronary artery disease (CAD) among patients with end-stage renal disease (ESRD), few studies have identified clinical correlates using national data. The purpose of this study was to determine the prevalence and clinical associations of CAD in a national random sample of new ESRD in the United States in 1996/1997 (n = 4025). Data on demographic characteristics and comorbidities were obtained from the Dialysis Morbidity and Mortality Study, Wave 2. The principal outcome was CAD, defined as the presence of a previous history of CAD, myocardial infarction, or angina, coronary artery bypass surgery, coronary angioplasty, or abnormal coronary angiographic findings. Multivariate logistic regression analysis was used to assess the relationship of conventional factors and proposed uremic factors to the presence of CAD. CAD was present in 38% of patients. Of the total cohort, 17% had a history of myocardial infarction and 23% had angina. Several conventional risk factors, including advancing age, male gender, diabetes mellitus, and smoking, were significantly associated with CAD. Of the proposed uremic factors, lower serum albumin levels but higher residual renal function and higher hematocrit values were significantly associated with the presence of CAD. Vascular comorbid conditions, structural cardiac abnormalities, white race, and geographic location were also strongly correlated with the presence of CAD. This national study suggests that several conventional CAD risk factors may also be risk factors for CAD among the ESRD population. This study identifies nonconventional factors such as serum albumin levels, vascular comorbid conditions, and structural cardiac abnormalities as important disease correlates. Future logitudinal studies are required to explore the relative importance of the relationships observed here.


2007 ◽  
Vol 97 (03) ◽  
pp. 458-463 ◽  
Author(s):  
Zsuzsanna Bereczky ◽  
Éva Katona ◽  
Róza Ádány ◽  
László Muszbek ◽  
Zoltán Vokó

SummarySeveral studies suggested that Val34Leu variant of factor XIII (FXIII) might have a protective effect against coronary artery disease (CAD), but studies not supporting these findings have also been published. The authors performed a meta-analysis of 16 studies on 5,346 cases and 7,053 controls that investigated the association between Val34Leu polymorphism and CAD defined as history of myocardial infarction or significant stenosis on a coronary artery assessed by coronary angiography. Because of the heterogeneity of the study-specific results, the pooled effect estimates were calculated by a random-effects empirical Bayes model. The combined odds ratios for CAD were 0.82 (95% confidence interval [95% Cl] 0.73, 0.94) for the heterozygotes of the FXIIIVal34Leu variant, 0.89 (95% CI 0.69, 1.13) for the homozygotes, and 0.81 (95% CI 0.70, 0.92) for the heterozygotes and homozygotes combined. The results were essentially the same when only myocardial infarction was considered as outcome. The beneficial effect of the polymorphism might be smaller than the effect estimates obtained in this metaanalysis, because the analysis raised the possibility of publication bias. Data published in the literature suggest that gene-gene and gene-environmental interactions might significantly influence the protective effect of FXIII-AVal34Leu polymorphism.


1979 ◽  
Vol 8 (3) ◽  
pp. 419-428 ◽  
Author(s):  
Alfred J. Anderson ◽  
Richard F. Loeffler ◽  
Joseph J. Barboriak ◽  
Alfred A. Rimm

2007 ◽  
Vol 20 (4) ◽  
pp. 791-799 ◽  
Author(s):  
G. Sardella ◽  
L. De Luca ◽  
V. Francavilla ◽  
D. Accapezzato ◽  
A. Di Roma ◽  
...  

T lymphocytes play an important role in the induction and progression of acute coronary syndromes (ACS). To gain insight into how different T cell subsets can influence ACS, we analyzed the frequencies of circulating CD4+T cells producing either pro-inflammatory interferon(IFN)-γ or anti-inflammatory interleukin (IL)-10 in subjects presenting with ST-elevation myocardial infarction (STEMI). The effect of coronary bare metal (BS) and paclitaxel-eluting stent (PES) on the balance between CD4+IFN-γ+ and CD4+IL-10+ lymphocytes was also investigated. Peripheral blood mononuclear cells (PBMC) were isolated from 38 consecutive patients with STEMI before and 48 hrs or 6 days after implantation of either BS or PES. Twenty patients with no history of coronary artery disease were included as basal controls. PBMC were stimulated in vitro with anti-CD3/anti-CD28 monoclonal antibodies, and CD4+IFN-γ+ or CD4+IL-10+ T cells were detected by flow cytometry intracellular staining. The frequency of peripheral CD4+IL-10+ T cells was significantly higher in STEMI patients as compared with controls. Conversely, the frequency of CD4+IFN-γ+ T lymphocytes did not differ between STEMI and subjects without history of coronary artery disease. Six days after the revascularization procedure, the percentage of CD4+IL-10+ T cells was significantly decreased in BS but not in the PES group, whereas the relative percentage of CD4+IFN-γ+ T lymphocytes were diminished in both groups as compared with baseline levels. Our data indicate that STEMI is associated with a peripheral expansion of CD4+IL-10+T lymphocytes, and that primary coronary revascularization with implantation of either BS or PES is followed by a reduction in circulating CD4+IFN-γ+ T lymphocytes. PES implantation, however, appears to inhibit the relative decrease of the IL-10 producing lymphocyte as observed in BS implanted patients, shifting the balance between pro-inflammatory and anti-inflammatory T cell populations in favor of the latter.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14607-e14607
Author(s):  
Aryan Firouzbakht ◽  
Daniel John Renouf ◽  
Leo Chen ◽  
Winson Y. Cheung

e14607 Background: Both 5-FU and raltitrexed are thymidylate synthase inhibitors, but the latter has a toxicity profile that is distinct from 5-FU. Therefore, it is commonly used as an alternative to 5-FU in the treatment of colorectal cancer patients who have a history of cardiac problems or prior 5-FU cardiotoxicity. To date, the population-based risk of cardiac effects from raltitrexed is uncertain. Our aim was to characterize the patterns of treatment and outcomes of patients receiving raltitrexed-based chemotherapy. Methods: We conducted a retrospective study of all patients diagnosed with colorectal cancer from 1988 to 2012, evaluated at 1 of 5 regional cancer centers in British Columbia, Canada and treated with raltitrexed at any point during their disease. At the institutions in our province, raltitrexed use is limited to those in whom 5-FU is contraindicated. Using chi-squared tests and logistic regression analyses, we evaluated the associations between use of raltitrexed and various cardiovascular events, such as angina, myocardial infarction, hypertension and arrhythmias, as well as other toxicity outcomes, including nausea, vomiting and diarrhea. Results: A total of 186 patients were included: median age was 63 years (IQR 55-70), 97 (52%) were men, and 21 (11%) experienced at least one cardiovascular outcome. Only 4 (2%) patients had a documented cardiac history prior to receipt of any systemic therapy. Among the 21 cases of cardiovascular events, 10 reported angina, 1 suffered a myocardial infarction, 6 had hypertension, and 6 experienced arrhythmias. A significant number of patients also presented with other general toxicities: 25 (13%) reported fever, 11 (6%) suffered mucositis, 75 (40%) had nausea, and 51 (27%) experienced diarrhea. On regression analyses, patients with a previous history of coronary artery disease had a higher risk of cardiovascular events than those without (50 vs 11%, p=0.01). Exposure to 5-FU before raltitrexed did not increase cardiovascular outcomes (p=0.81). Conclusions: Raltitrexed is associated with a low risk of cardiovascular events, but its use should be monitored closely in those with prior coronary artery disease.


Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Sheikh Bilal B Khalid ◽  
Javaria Mahmood

Introduction: Cisplatin-based chemotherapeutic regimen (CBCR) is known for increasing risk of venous thromboembolic (TE) disease. We report a unique case of STEMI associated with CBCR which we believe was caused by coronary artery thrombosis. Case description: A 31-yo man with a past history of germ cell tumor presented with chest pain radiating to back and left arm. It started this morning and intensity did not worsen with exertion. He denied any dyspnea, diaphoresis or palpitations. He was non-smoker and non-obese. He denied any family history of premature coronary artery disease. He had undergone unilateral orchiectomy a year ago, and was currently receiving chemotherapy with bleomycin, etoposide and cisplatin; the last dose of his 3 rd cycle was given the day before. EKG showed ST elevation in leads I, aVL, V4 and V5. Troponin I was high to 6.9 ng/ml (ULN 0.045 ng/ml). He received intravenous infusion of thrombolytic. An angiogram done the next day showed moderate mid-LAD disease with residual clot. A CT scan and an echocardiogram later showed left ventricular thrombus (LVT). He was kept on therapeutic enoxaparin along with aspirin. Follow up echocardiogram showed resolution of the thrombus. His chemotherapy was stopped, and he has been kept on active surveillance since then. Discussion: Most cases of CBCR-associated myocardial infarction that have been reported have been seen in the older population with other risk factors for coronary artery disease. Cases where angiographic data was available, coronary artery vasospasm appeared to be the culprit rather than a true plaque rupture. While the presence of LVT raises possibility of thromboembolism to coronaries causing MI, the angiographic findings support accelerated plaque formation to be the cause of infarction. In earlier reports, elevated pre-treatment level of von Willebrand factor has been postulated to have some role in the disease pathogenesis. Other possible mechanisms for pathogenesis include endothelial cell damage, platelet activation, and imbalance between thromboxane-prostacyclin levels. This case emphasizes the need to keep cardiac etiologies of chest pain in the differential when evaluating patients on CBCR as timely intervention is life saving and prevent morbidity.


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