Biological Work and Health Psychology, University of Konstanz, Konstanz, Germany.
Department of Consultation-Liaison Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
Front Endocrinol (Lausanne). 2023 Mar 10;14:1080938. doi: 10.3389/fendo.2023.1080938. eCollection 2023.
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.
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.
The groups differed in repeated daytime cortisol (dayCort) secretion (=.005,η =.03,=0.18) and cortisol awakening response (CAR) (=.006,η =.03,=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 (=.015,η =.04,=0.20) with highest levels in HT (´s≤.050), and in diurnal slope between waking and evening cortisol (=.033,η =.04,=0.20) with steepest slopes in HT (´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: =.021,η =.10,=0.33;AUC: =.028,η =.09,=0.31) 3.00 ± 0.06() years later, with risk prediction most pronounced in fibrinogen (AUC: =.017,Δ = 0.12;AUC: =.082).
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 effects on coagulation.
冠心病（CHD）及其主要危险因素高血压均与下丘脑-垂体-肾上腺（HPA）轴活性改变有关，但与不良疾病结局的前瞻性关联的生物学机制尚不清楚。我们研究了 CHD 患者、高血压（HT）和健康血压正常男性（NT）的日间 HPA 轴活性，并检测了与生物冠心病风险因素的前瞻性关联。
83 名男性 CHD 患者、54 名 HT 和 54 名 NT 男性连续两天反复测量唾液皮质醇。通过基线和随访之间促血栓形成因子 D-二聚体和纤维蛋白原、促炎标志物白细胞介素（IL）-6、肿瘤坏死因子-α（TNF-α）和急性相蛋白 C 反应蛋白（CRP）的变化，以及总胆固醇（tChol）/高密度脂蛋白胆固醇（HDL）比值的血脂来评估前瞻性冠心病风险。我们将凝血和炎症指标聚合为各自的指标。
组间重复日间皮质醇（dayCort）分泌（=.005，η =.03，=0.18）和皮质醇觉醒反应（CAR）（=.006，η =.03，=0.18）存在差异，与 NT 相比，CHD 患者和 HT 患者的总体 dayCort 和 CAR 均较低。组间在清晨皮质醇（=0.015，η =.04，=0.20）方面存在进一步差异，HT 组水平最高（´s≤0.050），在清晨与傍晚皮质醇之间的日间斜率（=0.033，η =.04，=0.20）方面存在差异，HT 组斜率最陡（´s≤0.039），尽管部分斜率差异不受混杂因素的影响。以曲线下面积（AUC）表示的聚合日间 Cort 和 CAR 降低独立预测未来整体冠心病风险增加（AUC：=.021，η =.10，=0.33；AUC：=.028，η =.09，=0.31），3.00 ± 0.06（）年后，纤维蛋白原的风险预测最明显（AUC：=.017，Δ=0.12；AUC：=.082）。
我们发现 CHD 和 HT 中存在 HPA 轴活性低下的证据，较低的日间 HPA 轴活性预测心血管风险增加，这表现为促动脉粥样硬化血栓形成风险的生物标志物循环水平增加。基础 HPA 轴活性的下调可能导致 CHD 中动脉粥样硬化和血栓形成的发病机制——对凝血的影响。
