1. In this prospective cohort study, fecal hemoglobin concentration (f-Hb) was associated with all-cause mortality in Danish citizens aged 50-74.

2. Higher fecal-hemoglobin concentration (f-Hb) was associated with mortality from all causes excluding colorectal cancer (CRC), as well as mortality from cardiovascular, respiratory, or other cancer-related causes.

Evidence Rating Level: 2 (Good)

Study Rundown:  Colorectal cancer (CRC) screening using fecal testing significantly impacts CRC mortality, sufficiently to affect all-cause mortality. The quantitative fecal immunochemical test (FIT) is the most frequently used test. In the Danish CRC screening program, participants with a positive FIT are referred to colonoscopy, but many of these do not reveal neoplastic findings that explain the bleeding. Previous research has found a relationship between fecal hemoglobin concentration (f-Hb) and chronic conditions, but these studies were limited by poor methods. This study aimed to investigate the association between f-Hb and mortality in a FIT-tested cohort of participants in the Danish CRC screening program. Between 2014 and 2017, Danish citizens in the eligible age group (50 – 74) were invited to participate by submitting a fecal sample, and the FIT participation rate was 62.6% during the invitation period. Individual-level follow-up was conducted for all participants using multiple different databases including the Danish Colorectal Screening Database and the Danish National Patient Register. The primary outcomes measured were all-cause mortality and disease-specific mortality, including all-cause mortality excluding CRC as an outcome. 1,228,365 participants were included in the study population and were divided into five groups based on the f-Hb. With respect to the primary outcome, a multivariate analysis revealed that all-cause mortality was significantly higher in those with a higher f-Hb; all-cause mortality adjusted hazard ratio (aHR) in those with a f-Hb of 7.1 – 11.9 μg Hb/g feces was 1.38 (95% CI: 1.32, 1.44) versus 2.20 (95% CI 2.10, 2.30) for those with f-Hb ≥60 μg Hb/g feces. A similar trend was present for all-cause mortality excluding CRC as a cause, as well as respiratory disease, cardiovascular disease, and mortality as a result of other cancers. In addition, there was an increase in the risk of CRC death with increasing f-Hb as well. Multivariate analysis showed that participants with a f-Hb 60 μg Hb/g feces had an aHR of 16.22, which was significantly higher than the other f-Hb groups. Overall, the findings from this study suggest a correlation between f-Hb and the presence of non-communicable chronic diseases, which is consistent with previous research. Limitations of this study include the limited-follow up length and the risk of misclassification in the causes of death from the Danish database. This study contributes to the growing body of evidence supporting the association of f-Hb and other diseases, and future research should further investigate the potential of f-Hb as a biomarker for conditions other than CRC.

Click to read the study in BMC Medicine

Relevant Reading: Faecal Haemoglobin Estimated by Faecal Immunochemical Tests – An Indicator of Systemic Inflammation with Real Clinical Potential

In-Depth [prospective cohort study]: This prospective cohort study investigated the association of f-Hb with all-cause mortality, as well as all-cause mortality excluding CRC and disease-specific mortality. Danish citizens between 50 to 74 were invited to participate from 2014 to 2017 by submitting a fecal sample. Overall, 1,228,365 participants were included in the study population and stratified into five different groups based on f-Hb. Male sex, increased age, lower education level and income, baseline GI bleeding, and higher frequency of comorbidity were associated with increasing f-Hb. During the study period, 21,857 (1.78%) participants died, 630 from CRC, and 21,227 of causes other than CRC. The overall tendency was an increase in the proportion of deaths with increasing f-Hb. The median follow-up time in the entire population was 2.68 years. With respect to outcomes, all-cause mortality aHR increased from 1.38 (95% CI: 1.32, 1.44) in those with a f-Hb of 7.11-11.9 μg Hb/g feces to 2.20 (95% CI: 2.10, 2.30) for those with f-Hb ≥60 μg Hb/g feces. This trend remained for all-cause mortality excluding CRC deaths, with an aHR of 1.37 (95% CI: 1.31, 1.43) in those with f-Hb 7.1 – 11.9 μg Hb/g feces and an aHR of 1.98 (95% CI: 1.89, 2.08) in those with f-Hb ≥60 μg Hb/g feces. Similar trends were seen in the mortality risk because of respiratory disease and cardiovascular disease. The mortality risk due to diabetes showed a similar trend, but with wide and overlapping confidence intervals. The risk of dying from other cancers excluding CRC also increased with increasing f-Hb. In terms of colorectal cancer mortality risk, multivariate analysis revealed an aHR of 1.95 (95% CI: 1.43, 2.66) in participants with 7.1 – 11.9 μg Hb/g feces and an aHR of 22.58 (95% CI: 18.88, 27.00) in participants with a ≥60 μg Hb/g feces, which was statistically significant (P<.001). Overall, the findings from this study suggest that f-Hb is associated with all-cause mortality, specifically of other causes excluding colorectal cancer in Danish citizens aged 50-74 years.

Image: PD

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