Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk
BackgroundCoronary 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...
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1080938/full |
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| author | Cathy Degroote Roland von Känel Livia Thomas Livia Thomas Claudia Zuccarella-Hackl Claudia Zuccarella-Hackl Nadine Messerli-Bürgy Hugo Saner Roland Wiest Petra H. Wirtz Petra H. Wirtz Petra H. Wirtz |
| author_facet | Cathy Degroote Roland von Känel Livia Thomas Livia Thomas Claudia Zuccarella-Hackl Claudia Zuccarella-Hackl Nadine Messerli-Bürgy Hugo Saner Roland Wiest Petra H. Wirtz Petra H. Wirtz Petra H. Wirtz |
| author_sort | Cathy Degroote |
| collection | DOAJ |
| description | BackgroundCoronary 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.MethodsEighty-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.ResultsThe groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η2p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η2p=.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,η2p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η2p=.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 (AUCdayCort: p=.021,η2p=.10,f=0.33;AUCCAR: p=.028,η2p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUCdayCort: p=.017,ΔR2= 0.12;AUCCAR: p=.082).ConclusionWe 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. |
| first_indexed | 2024-04-10T04:33:47Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-10T04:33:47Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Endocrinology |
| spelling | doaj.art-549be2fcab2b418caa89a138d64347f12023-03-10T05:16:21ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-03-011410.3389/fendo.2023.10809381080938Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD riskCathy Degroote0Roland von Känel1Livia Thomas2Livia Thomas3Claudia Zuccarella-Hackl4Claudia Zuccarella-Hackl5Nadine Messerli-Bürgy6Hugo Saner7Roland Wiest8Petra H. Wirtz9Petra H. Wirtz10Petra H. Wirtz11Biological Work and Health Psychology, University of Konstanz, Konstanz, GermanyDepartment of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandBiological Work and Health Psychology, University of Konstanz, Konstanz, GermanyDepartment of Psychology, University of Bern, Bern, SwitzerlandDepartment of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, SwitzerlandDepartment of Psychology, University of Bern, Bern, SwitzerlandInstitute of Psychology, University of Lausanne, Lausanne, SwitzerlandInstitute for Social and Preventive Medicine, University of Bern, Bern, SwitzerlandSupport Center of Advanced Neuroimaging, Institute of Diagnostic and Interventional Neuroradiology, University Hospital Bern, University of Bern, Bern, SwitzerlandBiological Work and Health Psychology, University of Konstanz, Konstanz, GermanyDepartment of Psychology, University of Bern, Bern, SwitzerlandCentre for the Advanced Study of Collective Behaviour, University of Konstanz, Konstanz, GermanyBackgroundCoronary 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.MethodsEighty-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.ResultsThe groups differed in repeated daytime cortisol (dayCort) secretion (p=.005,η2p=.03,f=0.18) and cortisol awakening response (CAR) (p=.006,η2p=.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,η2p=.04,f=0.20) with highest levels in HT (p´s≤.050), and in diurnal slope between waking and evening cortisol (p=.033,η2p=.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 (AUCdayCort: p=.021,η2p=.10,f=0.33;AUCCAR: p=.028,η2p=.09,f=0.31) 3.00 ± 0.06(SEM) years later, with risk prediction most pronounced in fibrinogen (AUCdayCort: p=.017,ΔR2= 0.12;AUCCAR: p=.082).ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fendo.2023.1080938/fullHPA-axiscortisolcoronary heart diseasehypertensioncoagulation |
| spellingShingle | Cathy Degroote Roland von Känel Livia Thomas Livia Thomas Claudia Zuccarella-Hackl Claudia Zuccarella-Hackl Nadine Messerli-Bürgy Hugo Saner Roland Wiest Petra H. Wirtz Petra H. Wirtz Petra H. Wirtz Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk Frontiers in Endocrinology HPA-axis cortisol coronary heart disease hypertension coagulation |
| title | Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk |
| title_full | Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk |
| title_fullStr | Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk |
| title_full_unstemmed | Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk |
| title_short | Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk |
| title_sort | lower diurnal hpa axis activity in male hypertensive and coronary heart disease patients predicts future chd risk |
| topic | HPA-axis cortisol coronary heart disease hypertension coagulation |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1080938/full |
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