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Markers of hypercoagulation, von Willebrand factor and anticardiolipin antibodies in postmenopausal women with unstable coronary artery disease: Discriminatory Ability Regarding Unstable Coronary Artery Disease and Coronary Atherosclerosis Using Receiver Operating Characterstics
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Molecular and Clinical Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-2608-2062
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Aims - Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenecity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD).

Methods and results - 158 patients with unstable CAD and 101 controls were examined. 16% of the patients had nonnal vessels and 84% had coronary atherosclerosis at coronary angiography. Mean plasma concentrations of von Willebrand factor-antigen, soluble fibrin (SF), thrombin-antithrombin complex and Ddimer were significantly higher, whereas there was no difference regarding prothrombin fragment 1 +2 between patients and controls. Patients with coronary atherosclerosis had higher mean plasma levels for most variables compared to those with normal coronary vessels, but the only significant difference was for SF. D-dimer was significantly higher in patients with nonnal coronary vessels compared to the control group. Anticardiolipin antibody (ACA) levels were significantly lower in the patient group compared to the control group. Receiver operating characteristics (ROC) showed that none of the variables represented high diagnostic accuracy in distinguishing patients with unstable CAD from healthy controls, or patients with from those without coronary atherosclerosis.

Conclusion - Our results are in favour of a hypercoagulable state in postmenopausal women with unstable CAD and coronary atherosclerosis, even in the absence of myocardial marker elevation, whereas this does not seem to be the case in patients with nonnal vessels. ROC revealed no variable to be particularly clinical useful in separating patients and control or patients with and without coronary atherosclerosis.

Keyword [en]
Coagulation, Unstable Coronary Artery Disease, Women, ROC Curve, Cardiolipin, Coronary Atherosclerosis
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79489OAI: oai:DiVA.org:liu-79489DiVA: diva2:542987
Available from: 2012-08-06 Created: 2012-08-06 Last updated: 2013-09-11Bibliographically approved
In thesis
1. Clinical and Laboratory Investigations in Postmenopusal Women with Unstable Coronary Artery Disease
Open this publication in new window or tab >>Clinical and Laboratory Investigations in Postmenopusal Women with Unstable Coronary Artery Disease
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Coronary artery disease (CAD) is the major cause of death in both sexes in the western world. In men with chest pain the diagnostic methods are more useful than in women. An exercise test is considered less reliable in women, mostly due to a high percentage offalse positive tests. Furthermore, 20-40% of women with typical angina have normal vessels at coronary angiography. The mechanisms behind the chest pain in these patients are unknown, but could be due to disturbances in endothelial, thrombogenetic and/or fibrinolytic function.

In a prospective multicentre trial we examined 200 postmenopausal women with unstable CAD and 101 healthy controls. At coronary angiography 15% had normal vessels, 14% had non-significant atherosclerosis and 71% had at least one significant stenosis.

The diagnostic information from basic clinical parameters, ECG and an early exercise test were evaluated. The prevalence of coronary atherosclerosis was high, 85%, and the early exercise test was just as valuable as in men for identifying patients with significant CAD.

Endothelial markers, cyclic GMP (cGMP) and immunoreactive endothelin (irET), were analysed regarding presence or not of coronary atherosclerosis. Patients with normal vessels had low levels of ir-Ef, indicating different mechanisms for ischemia/angina in these patients compared with patients with atherosclerosis. No differences were found regarding cGMP, unless the patient had long-term nitroglycerin treatment, which increased plasma cGMP. Patients with exerciseinduced ischemia had higher cGMP plasma levels compared to those without. This may reflect a general compensatory mechanism.

New lipid variables, apolipoproteins and lipoprotein particles, were no better than the routine lipid examination in separating women with and without coronary atherosclerosis, and the measurement of apolipoproteins and lipoprotein particles on the basis of diagnostic accuracy alone is not justified. Also, elevated triglycerides was most pronounced in women with unstable CAD and coronary atherosclerosis.

Plasma total homocysteine (tHey) is considered a risk factor for CAD, but the relationship between tHey and well-defined CAD in women is still unclear. Mild hyperhomocysteinemia was not related to the risk of unstable CAD in postmenopausal women. Our study stresses the importance of adjusting tHey for the covariates, i.e. age and serum values of folate, vitamin Bl2 and creatinine.

Fibrinolytic and coagulation variables did neither reveal signs of disturbed fibrinolysis nor were in favour of a hypercoagulable/hyperthrombotic state in patients with unstable CAD and normal vessels.

In summary, the prevalence of coronary atherosclerosis in postmenopausal women with signs and symptoms of unstable CAD is high. An early exercise test together with basic clinical parameters is a valuable diagnostic tool. Although there were differences in biochemical markers between patients with and without coronary atherosclerosis, the overlapping between the groups was high. No clinically useful test to separate these two groups was found. Patients with normal vessels were much alike the control group and it is still unclear whether these patients have CAD without atherosclerosis or another mechanism for their chest pain.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 105 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 615
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27526 (URN)12182 (Local ID)91-7219-572-X (ISBN)12182 (Archive number)12182 (OAI)
Public defence
2000-02-04, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-06Bibliographically approved

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Nielsen, Niels ErikErnerudh, JanSwahn, Eva

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