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Age-related changes in hypothalamic–pituitary–adrenal axis activity in patients with manifest arterial disease

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Abstract

Reports on age-related changes of hypothalamic–pituitary–adrenal (HPA) axis activity are equivocal. In addition, subtle changes in HPA axis activity are associated with cardiovascular risk factors. This study evaluates the effect of age in a large sample of patients with arterial disease on several parts of the circadian rhythm of the HPA axis. Within the Second Manifestations of Arterial Disease-Magnetic Resonance (SMART-MR) study, a prospective cohort study among patients with manifest arterial disease, cross-sectional analyses were performed in 419 patients (age 63 ± 9 years). Circadian cortisol rhythm was assessed with six saliva samples, collected at awakening and 30, 45, and 60 min thereafter and at 10 and 11 pm. Furthermore, a low dose of dexamethasone (0.5 mg) was administered at 11 pm, and saliva was sampled the next morning to test the cortisol suppression. Linear regression analyses adjusted for sex, awakening time, workday, smoking, blood pressure, BMI, diabetes mellitus, and dyslipidemia showed that older age was associated with a blunted cortisol awakening response. Per year increase, the rise (β = −0.15 nmol/l; 95%CI −0.25 to −0.05) and diurnal pattern (β = −0.14 nmol/l; 95%CI −0.25 to −0.02) decreased. Furthermore, older age was associated with higher evening levels (β log transformed = 0.01; 95%CI 0.01–0.02) and higher mean cortisol after dexamethasone (β log transformed = 0.01; 95%CI 0.002–0.02). In patients with arterial disease, HPA axis activity showed reduced variability with older age, independent of cardiovascular risk factors.

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Acknowledgments

We gratefully acknowledge the members of the SMART Study Group of University Medical Center Utrecht: A. Algra, MD, PhD, Julius Center for Health Sciences and Primary Care and Rudolf Magnus Institute for Neurosciences, Department of Neurology; P.A. Doevendans, MD, PhD, Department of Cardiology; Y.van der Graaf, MD, PhD, D.E. Grobbee, MD, PhD, and G.E.H.M. Rutten, MD, PhD, Julius Center for Health Sciences and Primary Care; L.J. Kappelle, MD, PhD, Department of Neurology; W.P.Th.M. Mali, MD, PhD, Department of Radiology; F.L. Moll, MD, PhD, Department of Vascular Surgery; and F.L.J. Visseren, MD, PhD, Department of Vascular Medicine.

Declaration of interest

The authors report no conflicts of interest.

Funding

Supported by a program grant from the Netherlands Organization for Scientific Research-Medical Sciences (NWO-MW: project no. 904-65-095); a VIDI grant from the Netherlands Organization for Scientific Research (NWO: project no. 917-66-311); and the Internationale Stichting Alzheimer Onderzoek. The funding sources had no involvement in the writing of this article or in the decision to submit it for publication.

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Authors and Affiliations

  1. University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Stratenum 6.131, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Arnoud J. G. Knoops, Yolanda van der Graaf & Mirjam I. Geerlings

  2. Department of Radiology, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands

    Willem P. Th. M. Mali

Authors
  1. Arnoud J. G. Knoops
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  2. Yolanda van der Graaf
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  3. Willem P. Th. M. Mali
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  4. Mirjam I. Geerlings
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Corresponding author

Correspondence to Mirjam I. Geerlings.

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This study is conducted for the SMART study group.

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Knoops, A.J.G., van der Graaf, Y., Mali, W.P.T.M. et al. Age-related changes in hypothalamic–pituitary–adrenal axis activity in patients with manifest arterial disease. Endocr 37, 231–238 (2010). https://doi.org/10.1007/s12020-009-9291-y

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  • DOI: https://doi.org/10.1007/s12020-009-9291-y

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