In:
Frontiers in Endocrinology, Frontiers Media SA, Vol. 14 ( 2023-3-10)
Kurzfassung:
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,η 2 p =.03, f =0.18) and cortisol awakening response (CAR) ( p =.006,η 2 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,η 2 p =.04, f =0.20) with highest levels in HT ( p ´s≤.050), and in diurnal slope between waking and evening cortisol ( p =.033,η 2 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,η 2 p =.10, f =0.33;AUC CAR : p =.028,η 2 p =.09, f =0.31) 3.00 ± 0.06( SEM ) years later, with risk prediction most pronounced in fibrinogen (AUC dayCort : p =.017,Δ R 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.
Materialart:
Online-Ressource
ISSN:
1664-2392
DOI:
10.3389/fendo.2023.1080938
DOI:
10.3389/fendo.2023.1080938.s001
Sprache:
Unbekannt
Verlag:
Frontiers Media SA
Publikationsdatum:
2023
ZDB Id:
2592084-4
