Blunted circadian cortisol in children is associated with poor cardiovascular health and may reflect circadian misalignment

Dai, Weiying; Wagh, Swanand A.; Chettiar, Steffi; Zhou, Grace D.; Roy, Runia; Qiao, Xingye; Visich, Paul S.; Hoffman, Eric P.

doi:10.1016/j.psyneuen.2021.105252

Cited by 6 publications

(3 citation statements)

References 44 publications

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“…We found a longitudinal association between lower diurnal HPA-axis activity and higher overall CHD risk increase comprising increases in all three aggregated biological risk factor indices, and in particular with fibrinogen increases. Despite evidence for cross-sectional associations between basal HPA-axis activity and inflammation (37) or hyperlipidemia (39,61), we could not detect prospective associations between daytime cortisol or CAR levels and changes in inflammation markers and blood lipid profiles. These results are in line with a study in 9-to-10 year-old children where baseline cortisol did not predict blood lipid levels 1 year later (61).…”

Section: Discussioncontrasting

confidence: 76%

“…Despite evidence for cross-sectional associations between basal HPA-axis activity and inflammation (37) or hyperlipidemia (39,61), we could not detect prospective associations between daytime cortisol or CAR levels and changes in inflammation markers and blood lipid profiles. These results are in line with a study in 9-to-10 year-old children where baseline cortisol did not predict blood lipid levels 1 year later (61).…”

Section: Discussioncontrasting

confidence: 76%

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

Degroote

Känel²,

Thomas³

et al. 2023

Front. Endocrinol.

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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.

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Section: Discussioncontrasting

confidence: 76%

Section: Discussioncontrasting

confidence: 76%

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

Degroote

Känel²,

Thomas³

et al. 2023

Front. Endocrinol.

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“… 19 One reason for increased levels of pregnenolone metabolites following an acute myocardial infarction might be activation of the hypothalamic–pituitary–adrenal axis caused by the stressful event. 20 However, in this case, the pregnenolone metabolites were evaluated years before the event, and it has been published that low levels of downstream metabolites, such as testosterone 21 and cortisol, 22 , 23 are associated with future CVD or a high CVD risk. A recent experimental study showed that testosterone increased endothelial nitric oxide synthesis and activity of superoxide dismutase and reduced catalase activity, with potential vascular protective effects, 24 suggesting potential pathophysiological events at the molecular level by low levels of this androgen.…”

Section: Discussionmentioning

confidence: 99%

Large‐Scale Metabolomics and the Incidence of Cardiovascular Disease

Lind

Fall

Ärnlöv

et al. 2023

JAHA

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Background The study aimed to show the relationship between a large number of circulating metabolites and subsequent cardiovascular disease (CVD) and subclinical markers of CVD in the general population. Methods and Results In 2278 individuals free from CVD in the EpiHealth study (aged 45–75 years, mean age 61 years, 50% women), 790 annotated nonxenobiotic metabolites were measured by mass spectroscopy (Metabolon). The same metabolites were measured in the PIVUS (Prospective Investigation of Vasculature in Uppsala Seniors) study (n=603, all aged 80 years, 50% women), in which cardiac and carotid artery pathologies were evaluated by ultrasound. During a median follow‐up of 8.6 years, 107 individuals experienced a CVD (fatal or nonfatal myocardial infarction, stroke, or heart failure) in EpiHealth. Using a false discovery rate of 0.05 for age‐ and sex‐adjusted analyses and P <0.05 for adjustment for traditional CVD risk factors, 37 metabolites were significantly related to incident CVD. These metabolites belonged to multiple biochemical classes, such as amino acids, lipids, and nucleotides. Top findings were dimethylglycine and N‐acetylmethionine. A lasso selection of 5 metabolites improved discrimination when added on top of traditional CVD risk factors (+4.0%, P =0.0054). Thirty‐five of the 37 metabolites were related to subclinical markers of CVD evaluated in the PIVUS study. The metabolite 1‐carboxyethyltyrosine was associated with left atrial diameter as well as inversely related to both ejection fraction and the echogenicity of the carotid artery. Conclusions Several metabolites were discovered to be associated with future CVD, as well as with subclinical markers of CVD. A selection of metabolites improved discrimination when added on top of CVD risk factors.

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A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state

Roy,

Dang,

Huffman

et al. 2024

Psychoneuroendocrinology

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Blunted circadian cortisol in children is associated with poor cardiovascular health and may reflect circadian misalignment

Cited by 6 publications

References 44 publications

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

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

Large‐Scale Metabolomics and the Incidence of Cardiovascular Disease

A population-based study of children suggests blunted morning cortisol rhythms are associated with alterations of the systemic inflammatory state

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