Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk

Cathy Degroote; Roland von Känel; Livia Thomas; Claudia Zuccarella-Hackl; Nadine Messerli-Bürgy; Hugo Saner; Roland Wiest; Petra H Wirtz

doi:10.3389/fendo.2023.1080938

Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk

Front Endocrinol (Lausanne). 2023 Mar 10:14:1080938. doi: 10.3389/fendo.2023.1080938. eCollection 2023.

Authors

Cathy Degroote¹, Roland von Känel², Livia Thomas^{1

3}, Claudia Zuccarella-Hackl^{2

3}, Nadine Messerli-Bürgy⁴, Hugo Saner⁵, Roland Wiest⁶, Petra H Wirtz^{1

3

7}

Affiliations

¹ Biological Work and Health Psychology, University of Konstanz, Konstanz, Germany.
² Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
³ Department of Psychology, University of Bern, Bern, Switzerland.
⁴ Institute of Psychology, University of Lausanne, Lausanne, Switzerland.
⁵ Institute for Social and Preventive Medicine, University of Bern, Bern, Switzerland.
⁶ Support Center of Advanced Neuroimaging, Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, University of Bern, Bern, Switzerland.
⁷ Centre for the Advanced Study of Collective Behaviour, University of Konstanz, Konstanz, Germany.

Abstract

Background: Coronary heart disease (CHD) and its major risk factor hypertension have both been associated with altered activity of the hypothalamus-pituitary-adrenal (HPA)-axis but the biological mechanisms underlying prospective associations with adverse disease outcomes are unclear. We investigated diurnal HPA-axis activity in CHD-patients, hypertensive (HT) and healthy normotensive men (NT) and tested for prospective associations with biological CHD risk factors.

Methods: Eighty-three male CHD-patients, 54 HT and 54 NT men repeatedly measured salivary cortisol over two consecutive days. Prospective CHD risk was assessed by changes between baseline and follow-up in the prothrombotic factors D-dimer and fibrinogen, the pro-inflammatory measures interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and acute phase protein C-reactive protein (CRP), as well as blood lipids in terms of total cholesterol (tChol)/high-density-lipoprotein cholesterol (HDL)-ratio. We aggregated coagulation and inflammatory measures to respective indices.

Results: The groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η² _p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η² _p=.03,f=0.18), with similarly lower overall dayCort and CAR in CHD-patients and HT, as compared to NT. The groups differed further in cortisol at awakening (p=.015,η² _p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η² _p=.04,f=0.20) with steepest slopes in HT (p´s≤.039), although in part not independent of confounders. Lower aggregated dayCort and CAR in terms of area-under-the-curve (AUC) independently predicted increases in future overall CHD risk (AUC_dayCort: p=.021,η² _p=.10,f=0.33;AUC_CAR: p=.028,η² _p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUC_dayCort: p=.017,ΔR ²= 0.12;AUC_CAR: p=.082).

Conclusion: We found evidence for an HPA-axis hypoactivity in CHD and HT with lower diurnal HPA-axis activity predicting increases in cardiovascular risk as evidenced by increases in circulating levels of biomarkers of atherothrombotic risk. Down-regulation of basal HPA-axis activity may contribute to the pathogenesis of atherosclerosis and thrombosis in CHD via effects on coagulation.

Keywords: HPA-axis; coagulation; coronary heart disease; cortisol; hypertension.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Coronary Disease* / etiology
Coronary Disease* / metabolism
Humans
Hydrocortisone / metabolism
Hypertension*
Hypothalamo-Hypophyseal System / metabolism
Male
Saliva / metabolism

Substances

Hydrocortisone

Grants and funding

This work was supported by research grants from the Swiss National Science Foundation [320030_122406 and PP00P1_128565/1 to PW], from the German Research Foundation [INST 38/550-1 and EXC 2117—422037984 to PHW], the German Scholars Organization [GSO/CZS 2 to PHW], and the University Hospital Bern [F3-1999, to RvK]. The funding sources had no impact on study design, data collection and analysis, writing of the manuscript, or the decision to submit the manuscript for publication.