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Plasma levels of cyclic GMP and endothelin in postmenopausal women with unstable coronary artery disease
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Cardiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medical and Health Sciences, Endocrinology. Linköping University, Faculty of Health Sciences.
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1999 (English)In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 59, no 5, 325-334 p.Article in journal (Refereed) Published
Abstract [en]

Many women with typical anginal chest pain have normal coronary angiograms, which may be due to altered endothelial function. We evaluated the endothelial markers cyclic GMP (cGMP) and immunoreactive endothelin (ir-ET) regarding presence of coronary atherosclerosis in women with clinical signs of unstable coronary artery disease (CAD). Plasma levels of cGMP and ir-ET were determined in 118 patients and 84 controls. Ischaemia was evaluated at an exercise test. Of the patients 20% had normal vessels, 14% insignificant CAD and 66% significant stenosis at coronary angiography. Mean (95% CI) concentration of cGMP (nmol/l) was higher in patients than in controls (5.05 (4.53; 5.58) vs. 3.79 (3.34; 4.23)). Separating patients according to daily intake of nitroglycerin, only patients with this medication had significantly higher cGMP level (5.73 (4.88; 6.58)), whereas the difference between those without (4.35 (3.76; 4.94)) and controls disappeared. Patients with ischaemia at exercise test had higher cGMP level than those without (6.01 (5.13; 6.88) vs. 4.30 (3.66; 4.94)), even after adjusting for nitroglycerin treatment. ir-ET (pmol/l) was lower in patients with normal vessels than patients with coronary atherosclerosis (0.83 (0.78; 0.88) vs. 0.98 (0.92; 1.04)) and than the control group (0.91 (0.87; 0.94)). The difference between the control group and patients with atherosclerosis was also significant. Patients with unstable CAD and long-term nitroglycerin treatment have increased cGMP level. Patients with exercise-induced ischaemia have higher cGMP level than those without, irrespective of nitroglycerin treatment, which may reflect a general compensatory mechanism. Patients with normal vessels have low level of ir-ET, indicating different mechanisms for ischaemia/angina in these patients compared with patients with atherosclerosis.

Place, publisher, year, edition, pages
1999. Vol. 59, no 5, 325-334 p.
Keyword [en]
Coronary atherosclerosis, cyclic GMP, endothelin, exercise test, nitroglycerin, women
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-26737DOI: 10.1080/00365519950185517Local ID: 11332OAI: oai:DiVA.org:liu-26737DiVA: diva2:247287
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2017-12-13Bibliographically 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 ErikAhlner, JohanSwahn, Eva

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