Abstract
BackgroundHeart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer.MethodsRetrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival.ResultsA total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607–1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802–2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599–1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706–2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications.ConclusionsHeart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV.
Highlights
In 2018 there were over 1.8 million newly diagnosed colorectal cancer patients worldwide and over 14,000 in the Netherlands alone
Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer
Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low heart rate variability (HRV)
Summary
In 2018 there were over 1.8 million newly diagnosed colorectal cancer patients worldwide and over 14,000 in the Netherlands alone. It has been suggested that efferent vagal activity is inversely related with fundamental mechanisms of tumorigenesis as inflammation, oxidative stress and excessive sympathetic activity [7]. These mechanisms are believed to be controlled by the vagus nerve via a bi-directional brain-to-immune pathways through the release of neurotransmitters via the cholinergic anti-inflammatory pathway [10,11]. Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer
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