Although depressive symptomatology has long been known to negatively impact the clinical outcomes of HF patients, little is known about the relationship between depressive symptoms and NT-proBNP, the most valuable marker of HF. This study provides evidence that there is a significant correlation between depressive symptoms and NT-proBNP as well as health status and clinical outcomes in HF patients.
However, these results are not consistent with those of some other studies. Van den Broek et al. (2011) and Lossnitzer et al. (2020), for example, found no significant association between NT-proBNP and depressive symptoms, despite demonstrating that these symptoms negatively impact clinical outcomes in HF patients similar to this one.8,9 However, inconsistent findings can be partially attributed to the use of different assessment instruments for affective symptoms: Broek et al. (2011) used the 10-item Center for Epidemiologic Studies Depression Scale (CES-D), while Lossnitzer et al. (2020) applied the nine-item depression module of the Patient Health Questionnaire (PHQ‐9), which covers depressive symptoms in the past two weeks. In addition, given that depressive symptoms are able to affect HF outcomes, it would be reasonable to assume that they also have some relationship with the HF marker NT-proBNP. This may explain why some HF patients continue to have high levels of NT-proBNP despite optimal HF management, suggesting that they may be suffering from worsening affective symptoms or unrecognized underlying depression. That would be in line with previous studies showing that patients suffering from depressive disorders often have higher levels of NT-proBNP.15,16 A drawback of these studies, though, is their limited power, as they examined only a single time point. This work is thus unique as it also tracked changes over one year. These findings could therefore improve the detection of clinically relevant depressive symptoms in this group of patients by a biological marker and may help monitor and adjust antidepressant treatment.
It is important to note that correlation does not necessarily imply causation. A correlation simply indicates that there is a relationship between two variables, meaning that they may affect each other. HF leads to chronic cerebral hypoperfusion, systemic inflammation, and endothelial dysfunction, all of which lead to cognitive impairment and mental illness.17 Moreover, HF symptoms limit physical abilities and affect health status, causing feelings of hopelessness and sadness that can culminate in depressive symptomatology.18 Depressive symptoms, in turn, may increase levels of catecholamine and stress hormones and promote inflammatory pathways, all of which have a negative impact on HF progression.19,20 In addition, depressed HF patients treated with antidepressants are at higher risk for medication non-adherence and less likely to receive guideline-based drug therapy.7 It is then a vicious circle in which both conditions feed into each other.
Identifying a significant correlation between both variables can therefore be advantageous in breaking this vicious circle, as it is supposed to work both ways. This implies that improving either cardiac or mental health could enhance the status of the other. It is likely that this would explain the reduction in depression scores observed in this study, which could partly be attributed to the optimization of HF treatment as well as the reassurance provided to patients through regular follow-ups and telephone support.
However, the mechanisms by which affective symptoms and HF influence each other are complex and poorly understood. This also applies to this study, as no clear explanation can be found for the presence of these associations with depressive symptoms, but not with anxiety. The literature on the association between anxiety and HF is insufficient, and the findings are conflicting. In a meta-analysis of 20 studies, only 10 found an association between anxiety and cardiovascular disease.21 Another meta-analysis that found a significant association between anxiety and poor cardiac outcomes also noted that this relationship disappeared when the analysis was adjusted for other medical variables, suggesting that its original findings may have been largely driven by these cofactors.22
Taken together, the current study found a significant association between depressive symptomatology and NT-proBNP, in contrast to anxiety. It also highlights the significant impact of depressive symptoms on clinical outcomes in HF. These findings may help develop a tailored therapeutic approach for both disorders.
Limitations
This was a single-center study, so the results cannot be generalized. In addition, it may be that a one-year observation period is not long enough to capture associations between anxiety, NT-proBNP levels, and clinical outcomes. Similar studies with longer time frames would help confirm these findings.
Another limitation is the use of only one screening questionnaire to assess anxiety and depression. Multiple questionnaires should have been used to confirm these results. Furthermore, the assessment of psychopathology by a self-report questionnaire has to be distinguished from the clinical diagnosis of an affective or anxiety disorder. However, the objective of the study was to simulate daily practice with an easy-to-use but scientifically recommended screening instrument. In future studies, different questionnaires alongside clinical assessments should be compared to find out the one best suited for this group of patients.
Finally, This study was a sub-study from the EPCHF trial. Since the EPCHF trial is still in progress, the current work was unable to assess the effects of early palliative care on this group of patients. However, this study was only aimed to investigate the relationship between depression, NT-proBNP and health status. The impact of early palliative care on clinical outcomes will be published separately once the data are available.