Morning plasma cortisol as a cardiovascular risk factor: Findings from prospective cohort and Mendelian randomization studies

Andrew Crawford, Stefan Söderberg, Clemens Kirschbaum, Lee Murphy, Mats Eliasson, Shah Ebrahim, George Davey Smith, Tommy Olsson, Naveed A. Sattar, Debbie Lawlor, Nicholas Timpson, Rebecca M Reynolds, Brian R Walker

Research output: Contribution to journalArticle (Academic Journal)

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Abstract

Objective: The identification of new causal risk factors has the potential to improve cardiovascular disease (CVD) risk prediction and the development of new treatments to reduce CVD deaths. In the general population, we sought to determine whether cortisol is a causal risk factor for CVD and coronary heart disease (CHD).

Design and Methods: Three approaches were adopted to investigate the association between cortisol and CVD/CHD. First, we used multivariable regression in two prospective nested case-control studies (total 798 participants, 313 incident CVD/CHD with complete data). Second, a random-effects meta-analysis of these data and previously published prospective associations was performed (total 6680 controls, 696 incident CVD/CHD). Finally, one- and two-sample Mendelian randomization analyses were performed (122,737 CHD cases, 547,261 controls for two-sample analyses).

Results: In the two prospective nested case-control studies, logistic regression adjusting for sex, age, body mass index, smoking and time of sampling, demonstrated a positive association between morning plasma cortisol and incident CVD (OR 1.28 per 1 SD higher cortisol, 95% CI 1.06-1.54). In the meta-analysis of prospective studies the equivalent result was OR 1.18, 95% CI 1.06-1.31. Results from the two-sample Mendelian randomization were consistent with these positive associations: OR 1.06, 95% CI 0.98-1.15.

Conclusions: All three approaches demonstrated a positive association between morning plasma cortisol and incident CVD. Together these findings suggest that elevated morning cortisol is a causal risk factor for CVD. The current data suggest strategies targeted at lowering cortisol action should be evaluated for their effects on CVD.
Original languageEnglish
Pages (from-to)429
Number of pages438
JournalEuropean Journal of Endocrinology
Volume181
Issue number4
DOIs
Publication statusPublished - 1 Oct 2019

Keywords

  • Mendelian Randomization
  • Prospective Case-Control Study
  • Cardiovascular Disease
  • Cortisol

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  • Projects

    IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

    Gaunt, L. F. & Davey Smith, G.

    1/04/1831/03/23

    Project: Research

    MRC UoB UNITE Unit - Programme 1

    Davey Smith, G.

    1/06/1331/03/18

    Project: Research

    Cite this

    Crawford, A., Söderberg, S., Kirschbaum, C., Murphy, L., Eliasson, M., Ebrahim, S., Davey Smith, G., Olsson, T., Sattar, N. A., Lawlor, D., Timpson, N., Reynolds, R. M., & Walker, B. R. (2019). Morning plasma cortisol as a cardiovascular risk factor: Findings from prospective cohort and Mendelian randomization studies. European Journal of Endocrinology, 181(4), 429. https://doi.org/10.1530/EJE-19-0161