Severe depressive symptoms are associated with elevated endothelin-1 in younger patients with acute coronary syndrome

Abstract

Objective To explore the relationship of depressive symptom severity to circulating Endothelin (ET) – 1 in younger patients with acute coronary syndrome (ACS). Younger patients report greater depressive symptom severity, which predicts poorer post-ACS prognosis. The pathways linking depression to post-ACS prognosis require further elucidation. ET-1 is a potent endogenous vasoconstrictor which has been previously linked to adverse post-ACS outcomes. Methods The sample (n=153) included males ≤50 years of age and females ≤55 years of age who participated in a larger study. Blood samples for ET-1 assessment were collected within 2–3 hours of ACS admission. Depressive symptoms were assessed with the Beck Depression Inventory (BDI) II within 2–5 days of admission. ET-1 was treated as a transformed continuous variable (ET-1T). BDI-II scores were classified into four categories using conventional thresholds demarcating mild, moderate, and severe levels of depressive symptoms. The relationship of classified BDI-II score to ET-1T was examined in simple and multivariable linear regression models. Results Classified BDI-II score was related to ET-1T in both unadjusted (χ2 = 9.469, p = 0.024) and multivariable (χ2 = 8.430, p = 0.038) models, with ET-1T being significantly higher in patients with severe depressive symptoms than in those with mild and moderate depressive symptoms. Conclusions In this sample of younger post-ACS patients, severe depressive symptoms were associated with elevated ET-1. We acknowledge that the observed association could be eliminated by the inclusion of some unmeasured variable(s). Longitudinal research should examine whether ET-1 mediates the relationship of depressive symptoms to long-term post-ACS outcomes.

Two-year prognosis after acute coronary syndrome in younger patients: Association with feeling depressed in the prior year, and BDI-II score and Endothelin-1

“…In our previous cross-sectional study of the current sample, depression symptom severity, as determined by the BDI-II score, was associated with circulating ET-1 levels at the time of hospitalization for an ACS event [13]. Hypothesizing that pathological vascular processes may comprise one of the mechanisms by which depression contributes to adverse post-ACS outcomes, in this prospective study we examined the effects of depression and ET-1 on subsequent events.…”

“…The role of ET-1 following ACS events can be detrimental, and in several studies, circulating ET-1 measured soon after ACS was found to strongly predict adverse post- event prognosis [9–11]. Burg et al demonstrated an association between depression and circulating ET-1 in older patients with chronic stable coronary artery disease (CAD) [12], and in a cohort of younger ACS patients (males ≤50 years of age and females ≤55 years of age), we have previously shown that depression symptom severity was associated with circulating ET-1 at the time of hospitalization [13]. In the current analyses we report on the 2-year follow-up of this cohort and the contribution of depression and ET-1 at the time of index ACS to subsequent major adverse events.…”

Retracted: Downregulated microRNA‐224 aggravates vulnerable atherosclerotic plaques and vascular remodeling in acute coronary syndrome through activation of the TGF‐β/Smad pathway

“…Based on the findings of our study, the serum ET-1 content significantly increased, while the NO content decreased notably in rats treated with miR-224 inhibitor in comparison to MI rats without other treatment, which were reversed in rats treated with the inhibitor of the TGF-β/Smad pathway (SB431542). ET-1, a candidate endogenous vasoconstrictor, is found to be associated with adverse outcomes and poor prognosis of ACS (Yammine, Frazier, Padhye, Burg, & Meininger, 2014). NO regulates the coronary blood flow through the process of vasodilatation, preventing the development of coronary circulatory failure and atherosclerosis (Toda, Tanabe, & Nakanishi, 2011).…”

Elevated Plasma C-Terminal Endothelin-1 Precursor Fragment Concentrations Are Associated with Less Anxiety in Patients with Cardiovascular Risk Factors. Results from the Observational DIAST-CHF Study

“…Previous studies have demonstrated that, in patients with coronary artery disease, the severity of depressive symptoms predicts elevated ET-1 [ 2 , 3 ], therefore, the purpose of the present re-analysis of DIAST-CHF data was to elucidate whether the circulating precursor CT-proET-1 is linked to anxiety, independent of depression. In particular, we aimed to clarify a putative anxiolytic effect due to ET-1, or its precursor molecules or proteolytic fragments, in humans and to decipher its mechanistic pathways.…”

“…Whether the 21-amino acid neuropeptide ET-1 is also linked to anxiety states has not been investigated so far. However, two studies have reported a positive association between circulating ET-1 levels and depressive symptom severity in patients with coronary artery disease [ 2 , 3 ], indicating that this vasoactive peptide modulates brain functions [ 4 ]. In addition, it was shown that ET-1 decreases the high-affinity uptake of the excitatory amino acid glutamate in primary cultured astrocytes from rat cerebral cortex, suggesting a direct effect on membrane depolarisation [ 5 ].…”