{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:21:21Z","timestamp":1791415281232,"version":"4.3.3"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T00:00:00Z","timestamp":1678406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats: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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats: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-\u03b1), 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The groups differed in repeated daytime cortisol (dayCort) secretion (<jats:italic>p<\/jats:italic>=.005,\u03b7<jats:sup>2<\/jats:sup><jats:sub>p<\/jats:sub>=.03,<jats:italic>f<\/jats:italic>=0.18) and cortisol awakening response (CAR) (<jats:italic>p<\/jats:italic>=.006,\u03b7<jats:sup>2<\/jats:sup><jats:sub>p<\/jats:sub>=.03,<jats:italic>f<\/jats: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 (<jats:italic>p<\/jats:italic>=.015,\u03b7<jats:sup>2<\/jats:sup><jats:sub>p<\/jats:sub>=.04,<jats:italic>f<\/jats:italic>=0.20) with highest levels in HT (<jats:italic>p<\/jats:italic>\u00b4s\u2264.050), and in diurnal slope between waking and evening cortisol (<jats:italic>p<\/jats:italic>=.033,\u03b7<jats:sup>2<\/jats:sup><jats:sub>p<\/jats:sub>=.04,<jats:italic>f<\/jats:italic>=0.20) with steepest slopes in HT (<jats:italic>p<\/jats:italic>\u00b4s\u2264.039), 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<jats:sub>dayCort<\/jats:sub>: <jats:italic>p<\/jats:italic>=.021,\u03b7<jats:sup>2<\/jats:sup><jats:sub>p<\/jats:sub>=.10,<jats:italic>f<\/jats:italic>=0.33;AUC<jats:sub>CAR<\/jats:sub>: <jats:italic>p<\/jats:italic>=.028,\u03b7<jats:sup>2<\/jats:sup><jats:sub>p<\/jats:sub>=.09,<jats:italic>f<\/jats:italic>=0.31) 3.00 \u00b1 0.06(<jats:italic>SEM<\/jats:italic>) years later, with risk prediction most pronounced in fibrinogen (AUC<jats:sub>dayCort<\/jats:sub>: <jats:italic>p<\/jats:italic>=.017,\u0394<jats:italic>R<\/jats:italic><jats:sup>2<\/jats:sup>= 0.12;AUC<jats:sub>CAR<\/jats:sub>: <jats:italic>p<\/jats:italic>=.082).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats: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 <jats:italic>via<\/jats:italic> effects on coagulation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1080938","type":"journal-article","created":{"date-parts":[[2023,3,10]],"date-time":"2023-03-10T05:16:30Z","timestamp":1678425390000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Lower diurnal HPA-axis activity in male hypertensive and coronary heart disease patients predicts future CHD risk"],"prefix":"10.3389","volume":"14","author":[{"given":"Cathy","family":"Degroote","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"von K\u00e4nel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Zuccarella-Hackl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"Messerli-B\u00fcrgy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Saner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roland","family":"Wiest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra H.","family":"Wirtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000950","article-title":"Heart disease and stroke statistics-2021 update: A report from the American heart association","volume":"143","author":"Virani","year":"2021","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.11.006","article-title":"2017 ACC\/AHA\/AAPA\/ABC\/ACPM\/AGS\/APhA\/ASH\/ASPC\/NMA\/PCNA guideline guideline for the prevention, detection, evaluation, and management of high blood pressure in adults","volume":"71","author":"Whelton","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/S0140-6736(07)61299-9","article-title":"Essential hypertension","volume":"370","author":"Messerli","year":"2007","journal-title":"Lancet"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.101.3.329","article-title":"Essential hypertension. 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