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Association between ambulatory saliva cortisol levels and plasma levels of matrix metalloproteinase-9 in a normal population
Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Health and Society. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
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(English)Manuscript (Other academic)
Abstract [en]

Background: Psychosocial strain has been demonstrated to be a risk factor for coronary artery disease (CAD) and also to be associated with a dysfunctional HPA-axis. Based on a proposal on cortisol resistance in maladaptive monocytes as a potential mechanism linking psychosocial strain with CAD, this study aimed at testing the association between levels of salivary cortisol and matrix metalloproteinase-9 (MMP-9) in a normal population.

Methods: 359 participants (50 % women) aged 45-69 were enrolled to this study, randomly drawn from a normal population in Sweden. Saliva samples were collected thrice per day (at awakening, 30 minutes after awakening, and just before going to bed) during three consecutive days. Cortisol levels at awakening and 30 minutes after awakening were used to estimate the diurnal peak. Cortisol was analyzed using a radioimmunoassay method. MMP-9 was measured in plasma using an ELISA-method.

Results: After adjustment for age and sex, significant trends regarding MMP-9 were found both for cortisol peak quintiles (beta +1.9 ng/mL per quintile, p=0.029) and cortisol evening values (beta +2.1 ng/ml per quintile, p=0.017). These findings were consistent in regressions either excluding participants with known diagnoses of myocardial infarction, angina pectoris, rheumatoid arthritis, diabetes, cancer with ongoing treatment, chronic obstructive lung disease, osteoporosis and hypothyroidism, or adjusting for these diseases, also after adjustment for cardiovascular risk factors.

Conclusions: The associations found between cortisol levels and MMP-9 in a normal population hint at a potential pathway linking prolonged psychosocial strain with cardiovascular events.

Keyword [en]
Cardiovascular, cortisol, HPA‐axis, metalloproteinases, inflammation
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-14928OAI: oai:DiVA.org:liu-14928DiVA: diva2:25617
Available from: 2008-09-30 Created: 2008-09-30 Last updated: 2010-01-14
In thesis
1. Plasma levels of matrix metalloproteinase‐9 in a normal population: a psychoneuroendocrinological approach
Open this publication in new window or tab >>Plasma levels of matrix metalloproteinase‐9 in a normal population: a psychoneuroendocrinological approach
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Several large‐scale epidemiological studies have demonstrated the prognostic significance of psychosocial factors and stress for coronary artery disease (CAD). Observations of sudden changes in CAD incidence have led to the proposal of mechanisms regarding atherosclerotic plaque vulnerability. The collagen‐degrading enzyme matrix metalloproteinase-9 (MMP-9) is increased in rupture‐prone plaques with high inflammatory activity, and circulating levels of MMP-9 are raised in patients with acute coronary syndrome. However, the distribution of MMP‐9 levels and its relations to psychosocial factors and the stress hormone cortisol have not been previously explored in a normal population.The aim of this dissertation was to examine in a normal population the association of circulating levels of MMP-9 with traditional cardiovascular risk factors including levels of C-reactive protein (CRP), with psychosocial factors, and with saliva levels of cortisol. In addition, the reliability of a new method of ambulatory saliva sampling for assessment of cortisol levels was evaluated. A sub‐sample of the Life conditions, Stress, and Health (LSH)-study, a population based study exploring psychoneuroendocrinological pathways mediating the differences in CAD incidence over socioeconomic status, was used. Plasma levels of MMP-9 were examined in a sample randomly drawn from the LSH‐study (n=400), aged 45 to 69 years at enrollment.The main findings were: 1) there was a positive association between plasma MMP-9 levels and total risk load of cardiovascular risk factors. The findings were persistent after adjusting for CRP and could not be attributed to a single risk factor. 2) After adjusting for traditional cardiovascular risk factors and CRP, MMP-9 levels were positively associated with psychosocial risk factors and negatively associated with psychosocial resources. 3) Pooling saliva samples prior to laboratory analysis were as reliable as arithmetic means for assessment of diurnal cortisol variation in a field research setting. 4) There was a positive association between circulating levels of MMP‐9 and saliva levels of cortisol, both diurnal peak level and evening level of cortisol. The observed associations between MMP‐9 and traditional cardiovascular risk factors, psychosocial factors, and saliva cortisol levels suggest a psychoneuroendocrinological pathway linking stress to plaque vulnerability and provide increased understanding of the association between psychosocial factors and CAD.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2008. 131 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1072
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-14929 (URN)9789173938310 (ISBN)
Public defence
2008-10-03, Berzeliussalen, ingång 63, Campus US, Linköpings universitet, Linköping, 13:00 (English)
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Available from: 2008-09-30 Created: 2008-09-30 Last updated: 2017-12-18Bibliographically approved

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Garvin, Peter Carstensen, JohnJonasson, LenaNilsson, LennartKristenson, Margareta

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