Chronic Pain And Its Association With Depressive Symptoms And Renal Function in Hypertensive Patients Ⅱ

4. Discussion 

Arterial hypertension represents a highly prevalent entity that rarely appears in isolation and is frequently accompanied by several comorbidities, such as diabetes mellitus, obesity, coronary artery disease, and heart failure [22]. As a result, a multidisciplinary approach is usually warranted for the most appropriate multifactorial management of hypertensive patients [23]. However, certain aspects of hypertension management remain incompletely understood, including the relationship of hypertension with chronic pain. According to earlier studies with a sound pathophysiologic basis, chronic pain may be considered a risk factor for the incidence of hypertension [24], while a recent cross-sectional study has documented an association between chronic pain and hypertension [25].

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Chronic pain was a very frequent characteristic of our hypertensive patient population, with a prevalence rate of 44%. In the logistic regression analysis, the female sex was independently associated with chronic pain while other established cardiovascular risk factors were not associated with chronic pain. Previous studies have shown that patients with chronic pain are more likely to be older and female [26], in accordance with our findings. Moreover, chronic pain in hypertensive individuals with impaired renal function (eGFRCKD-EPI < 60 mL/min/1.73 m2 ) was also highly prevalent at a rate of approximately 49%. Although its frequency was similar compared to those with preserved renal function (eGFRCKD-EPI ≥ 60 mL/min/1.73 m2 ), our results confirm previous data showing that chronic pain is a very common symptom in people with CKD [9,27–29]. The epidemiology of chronic pain has not been adequately assessed in non-dialysis dependent CKD, as our patient population, with a recent meta-analysis reporting a higher prevalence according to one study [29]. One possible explanation for this discrepancy with our study may be the low prevalence of chronic pain risk factors in our CKD patients [1]. The high prevalence of pain in this subgroup of patients implies a significant potential for pain management in routine clinical practice. Indeed, there is a growing international trend toward increasing efforts to integrate the principles of palliative care, pain, and symptom management into the care of patients with chronic kidney disease [30].

Besides the well-established comorbidities in hypertension, depression is commonly encountered in hypertensive patients, as reported in a recent systematic review and meta-analysis [31]. Depression has also been associated with inadequate BP control [32], while improvement of depressive symptoms might result in BP lowering [33]. Chronic pain is an additional consideration in the interplay of hypertension with depression since the role of chronic pain and depression in BP-lowering treatment efficacy and adherence has been recognized [34]. In our study, hypertensive participants with depressive symptoms in the upper quartile (over 75th percentile) experienced chronic pain at a significantly higher rate compared to those who did not have depressive symptoms, a finding that was also present in the subgroup of patients with impaired renal function. The coexistence of chronic pain and depression is a challenging combination for managing patients in primary health care. It has been reported that 35% of patients with chronic pain have depression as a comorbidity [35]. Most importantly, depression remained as an independent predictor of pain in our hypertensive cohort after the logistic regression analysis, highlighting its potential importance as a risk factor. 

Our study has inherent limitations. To begin with, the associations observed cannot imply causality due to the cross-sectional design of our study. It should also be noted that none of the patients had end-stage renal disease, which may be related to a higher prevalence of chronic pain and depressive disorders [36,37], mandating further research in that field as these factors may hinder the quality of life of affected patients [37,38]. Moreover, the small number of individuals recruited might be insufficient to constitute potent associations. Furthermore, causes of chronic pain due to other conditions could not be assessed, and it is uncertain if they would have accounted for residual confounding. Last but not least, the presence of pain was based on a simple self-reported questionnaire and not according to other more detailed measures. 

5. Conclusions 

We found that hypertensive individuals report chronic pain at high rates. A significantly higher prevalence of chronic pain was detected in patients with depression scores at the highest percentile than those who do not have depression. Based on the potential causal association between chronic pain and arterial hypertension as well as the association of pain with depressive symptoms in our hypertensive cohort, the prompt recognition and management of pain and depression appears reasonable in order to achieve BP goals and reduce the excess morbidity and mortality associated with poor BP control. Future studies are needed to validate our findings and prospectively assess the importance of interventions toward pain and depression in hypertensive patients. 

Supplementary Materials: The following supporting information can be downloaded at: https: //www.mdpi.com/article/10.3390/ijerph19031899/s1, Table S1: Baseline hematologic, biochemical, inflammatory, and lipid markers of the study population.; Table S2: Laboratory characteristics of the study population stratified by the presence of self-reported chronic pain; Table S3: Clinical, psychometric, and laboratory characteristics of patients with impaired renal function (eGFR < 60 mL/min/1.73 m2 ) stratified by self-reported chronic pain. 

Author Contributions: Conceptualization, R.G.K. and K.C.S.; methodology, R.G.K., K.C.S., and P.S.; statistical analysis, R.G.K., P.T. and P.S.; resources, R.G.K. and K.C.S.; data curation, R.G.K.; writing- original draft preparation, P.T., K.T. and A.V.; writing-review and editing, R.G.K., P.T., P.S., K.T., A.V. and K.C.S.; supervision, R.G.K. and K.C.S.; project administration, R.G.K. All authors have read and agreed to the published version of the manuscript. 

Funding: This research received no external funding.

Institutional Review Board Statement: The study was conducted by the "Declaration of Helsinki" and approved by the Institutional Review Board of the University Hospital of Ioannina (35443/18 December 2013).

Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. 

Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon request. 

Conflicts of Interest: The authors declare no conflict of interest

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