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

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

JOURNAL=Frontiers in Endocrinology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2023.1080938

DOI=10.3389/fendo.2023.1080938

ISSN=1664-2392

ABSTRACT=<sec><title>Background</title><p>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.</p></sec><sec><title>Methods</title><p>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.</p></sec><sec><title>Results</title><p>The groups differed in repeated daytime cortisol (dayCort) secretion (<italic>p</italic>=.005,η<sup>2</sup><sub>p</sub>=.03,<italic>f</italic>=0.18) and cortisol awakening response (CAR) (<italic>p</italic>=.006,η<sup>2</sup><sub>p</sub>=.03,<italic>f</italic>=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 (<italic>p</italic>=.015,η<sup>2</sup><sub>p</sub>=.04,<italic>f</italic>=0.20) with highest levels in HT (<italic>p</italic>´s≤.050), and in diurnal slope between waking and evening cortisol (<italic>p</italic>=.033,η<sup>2</sup><sub>p</sub>=.04,<italic>f</italic>=0.20) with steepest slopes in HT (<italic>p</italic>´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<sub>dayCort</sub>: <italic>p</italic>=.021,η<sup>2</sup><sub>p</sub>=.10,<italic>f</italic>=0.33;AUC<sub>CAR</sub>: <italic>p</italic>=.028,η<sup>2</sup><sub>p</sub>=.09,<italic>f</italic>=0.31) 3.00 ± 0.06(<italic>SEM</italic>) years later, with risk prediction most pronounced in fibrinogen (AUC<sub>dayCort</sub>: <italic>p</italic>=.017,Δ<italic>R</italic><sup>2</sup>= 0.12;AUC<sub>CAR</sub>: <italic>p</italic>=.082).</p></sec><sec><title>Conclusion</title><p>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 <italic>via</italic> effects on coagulation.</p></sec>