The association of hemorrhoids with the incidence of heart failure: a nationwide cohort study

Introduction

Hemorrhoids are normal vascular structures located around the lower rectum and anal canal, playing a key role in maintaining anal control (1). However, hemorrhoids are usually referred to as pathologic alterations and downward movement of hemorrhoidal tissue, a condition known as hemorrhoidal disease (1). Hemorrhoids are one of the most common diseases, affecting almost 40% of the adult population (2). They can lead to significant discomfort, functional impairments, and a reduction in quality of life (3). Hemorrhoids not only present a considerable medical challenge but also have substantial socio-economic implications, placing a significant burden on healthcare systems (4).

Heart failure (HF) is a condition where the heart struggles to pump blood effectively, causing problems with blood flow or filling of the heart’s chambers (5). HF is a common cardiovascular disease worldwide and presents a major health challenge due to its increasing occurrence (6). Despite progress in treatment and prevention, HF remains a leading cause of illness and death (7). Identifying risk factors for HF is essential for effective management and potential risk reduction. Key risk factors for HF include coronary artery disease, hypertension, diabetes, aortic plaque, smoking, and poor oral hygiene. These highlight the importance of managing lifestyle and health conditions to reduce HF risk. However, our understanding of HF is still growing, and further research is needed to identify other modifiable risk factors (8,9).

Hemorrhoids can be considered a clinical manifestation of loss of vascular integrity (10). Recent reports suggest that hemorrhoids, along with other chronic venous diseases, may be linked to the risk of cardiovascular disease (11). Moreover, hemorrhoids and HF may share several risk factors such as obesity or hypertension (12). Therefore, a potential association between hemorrhoids and HF may exist. However, studies evaluating the relationship between hemorrhoid presence and HF incidence remain limited. This study hypothesizes that hemorrhoid presence is related to an increased risk of HF. The objective of this research is to evaluate the association between hemorrhoid presence and treatment with HF incidence through a nationwide longitudinal study of the general population. We present this article in accordance with the STROBE reporting checklist (available at https://atm.amegroups.com/article/view/10.21037/atm-24-218/rc).

Methods

Data source

The Korean National Health Insurance System (NHIS) provides an extensive database encompassing demographic information, socio-economic status, medical diagnoses, and treatment modalities. It also includes a national health examination database and a medical care facilities database (13-15). The NHIS policy recommends that members have standardized health check-ups every two years (16). Our study used data from the NHIS-National Health Screening Cohort (NHIS-HEALS). The NHIS-HEALS cohort includes data from a cluster random sample of 10% of all health examination participants between 2002 and 2019. The NHIS-HEALS cohort included individuals over 40 who took part in the NHIS health screening programs. We collected data from this group, such as demographic details, height, weight, household income, smoking and drinking habits, physical activity, medical history, and health conditions. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Institutional Review Board of Ewha Womans University Seoul Hospital (No. EUMC 2024-03-006). The requirement for informed consent was waived due to the retrospective nature of the study and the minimal risk to patient.

Study population

This study utilized the NHIS-HEALS cohort database, enrolling 381,031 individuals who participated in a national health screening program between 2003 and 2007. Follow-up data were collected until December 31, 2019. To exclude participants with a prior history of HF, a washout period was established from January 1, 2002, to the baseline period (2003–2007). During this period, individuals diagnosed with HF under the International Classification of Diseases, Tenth Revision (ICD-10) code I50 were excluded (n=6,225). Furthermore, participants with incomplete or missing data (n=20,867) and those with a follow-up period of less than 30 days (n=249) considering reverse association were also excluded. Finally, 353,690 participants were included in this study (Figure 1).

Figure 1 Flow chart of inclusion and exclusion criteria. PSM, propensity score matching.

Definition of hemorrhoids

The presence of hemorrhoids was defined as at least two separate claims with an ICD-10 code of I84 based on a previous study (17). Regarding the procedure or surgical treatment of hemorrhoids, procedure codes for thrombosed hemorrhoid surgery (Q3012), hemorrhoidectomy (Q3013), surgery for strangulated circumferential hemorrhoids (Q3014), hemorrhoids included thrombectomy and excision of the skin tag (Q3015), coagulation, cauterization, sclerotherapy, and rubber band ligation (Q3016), circular stapled hemorrhoidectomy (Q3017) were investigated (17).

Outcome and covariates

The primary outcome of this study was HF, as defined by the ICD-10 diagnostic code I50, with at least twice the number of claims. To identify potential covariates affecting the onset of HF, demographic and clinical variables were collected, including sex, age, body mass index, socio-economic status based on income level, smoking status, alcohol consumption frequency, a detailed profile of comorbid conditions, and the Charlson comorbidity index at the index date. Detailed definitions of comorbidities are provided in the Appendix 1. Follow-up was carried out until December 31, 2019, death, or the first incidence of HF (18-21).

Statistical analysis

Baseline characteristics were compared between participants with and without hemorrhoids using an independent t-test for continuous variables and a chi-squared test (or Fisher’s exact test) for categorical variables. To balance baseline characteristics and minimize potential confounding between the two groups, 1:5 propensity score matching (PSM) was applied (22,23). The effectiveness of PSM was evaluated using the standardized mean difference (SMD), with PSM deemed adequate when the absolute SMD value was less than 0.1 (24,25).

To evaluate the incidence of HF, Kaplan-Meier survival curves were utilized, and differences between participants with and without hemorrhoids were assessed using log-rank tests. Cox proportional hazards models were employed to estimate hazard ratios (HR) and 95% confidence intervals (CI). To reduce the impact of reverse causality, a landmark analysis was conducted, considering HF occurrence one year after the index date. Additionally, subgroup analyses were performed to explore the association between hemorrhoid presence and HF based on demographic factors and covariates, with interaction P values visualized using forest plots.

Considering the association between the severity and treatment effect of hemorrhoids with HF, a sensitivity analysis was performed to assess the association of the surgical procedure or treatment for hemorrhoids with the incidence of HF before and after PSM, using Cox regression analysis. Moreover, we performed further analysis after excluding I84.2 (internal hemorrhoids without complication), I84.6 (residual hemorrhoidal skin tags), and I84.9 (unspecified hemorrhoids without complication). All statistical analyses were performed using SAS 9.4 version (SAS Inc., Cary, NC, USA) and R software (version 4.2.1; R Foundation for Statistical Computing, Vienna, Austria). Statistical significance for all tests was set at a P value <0.05.

Results

Baseline characteristics according to the presence of hemorrhoids are shown in Table 1. The mean age of overall participants was 54.3±9.7 years and 53.8% were female. Participants with hemorrhoids were younger and predominantly male. Participants with hemorrhoids had fewer histories of smoking, heavy alcohol consumption, hypertension, and diabetes mellitus. In contrast, participants with hemorrhoids had higher incidences of covariates, including dyslipidemia, chronic obstructive pulmonary disease, stroke, cancer, renal disease, and liver disease (Table 1). After PSM, participants with and without hemorrhoids were well-balanced (Table 1).

During a median follow-up of 13.33 years (interquartile range: 10.4–16.26) years, the cumulative incidence of HF was 15.5%, comparable to the previous prospective Framingham cohort (26). The Kaplan-Meier survival curves for the occurrence of HF according to the presence of hemorrhoids are shown in Figure 2. Participants had an increased incidence of HF according to the presence of hemorrhoids, regardless of PSM (P<0.001). In the multivariate analysis, participants with hemorrhoids consistently showed a higher incidence of HF compared to those without hemorrhoids before PSM (HR, 1.073; 95% CI: 1.028–1.121, P<0.001) and after PSM (HR, 1.073; 95% CI: 1.018–1.131; P<0.001; Table 2, Table S1). This positive association remained consistent in the landmark analysis, irrespective of PSM (Table S2). In the subgroup analysis, the relationship between the presence of hemorrhoids and the incidence of HF was consistently observed after PSM (Figure 3).

Figure 2 Kaplan-Meier survival curves for the occurrence of HF according to the presence of hemorrhoids. HF, heart failure.

Figure 3 Forest plots of subgroup analysis according to demographic data and comorbidities for the association of hemorrhoidal disease with incidence risk of all-cause dementia before propensity score matching (A) and after propensity score matching (B). CI, confidence interval; HR, hazard ratio.

The clinical characteristics before and after PSM according to surgical procedures or treatments of hemorrhoids are described in Table 3. Detailed information on the frequency of surgical procedures and treatments for hemorrhoids are shown in Table S3. Regarding the relationship between surgical interventions or treatment for hemorrhoids and the incidence of HF, participants who received surgical treatment or other hemorrhoid treatments had a lower incidence of HF, both before PSM (HR, 0.919; 95% CI: 0.845–1.001, P=0.06) and after PSM (HR, 0.941; 95% CI: 0.880–1.001; P=0.059; Table 4, Table S4).

In additional sensitivity analysis after excluding population with claims for I84.2 (internal hemorrhoids without complication), I84.6 (residual hemorrhoidal skin tags), and I84.9 (unspecified hemorrhoids without complication), the presence of hemorrhoids consistently showed a higher incidence of HF compared to those without hemorrhoids before PSM (HR, 1.051; 95% CI: 1.010–1.094, P<0.001) and after PSM (HR, 1.055; 95% CI: 1.012–1.100; P<0.001; Tables S5,S6). However, regarding the relationship between surgical procedures or treatment for hemorrhoids and the incidence of HF, participants who underwent surgical procedures or treatment for hemorrhoids showed a showed a non-significant decreased trend for the incidence risk of HF before PSM (HR, 0.920; 95% CI: 0.845–1.000, P=0.053) and after PSM (HR, 0.921; 95% CI: 0.841–1.001, P=0.06; Tables S7,S8).

Discussion

The key finding of our study was that the presence of hemorrhoids was associated with a higher incidence of HF, even after PSM, in a nationwide longitudinal study of the general population. Moreover, even though statistically non-significant, surgical procedures and treatments for hemorrhoids may be associated with a lower incidence of HF.

Previous studies have shown that hemorrhoids are associated with obesity, hypertension, diabetes mellitus, liver cirrhosis, peripheral artery occlusive disease, and coronary artery disease, which are conditions commonly associated with HF (12,27). Moreover, the incidence of hemorrhoids is higher in patients initially diagnosed with HF (28). However, one previous study did not show any association between hemorrhoids and HF (29). As such, the evidence regarding the association between HF and hemorrhoids is currently controversial. Our study confirmed that the presence of hemorrhoids is related to an increased incidence of HF in the general population. This finding is significant because it provides additional information on existing evidence on the association between hemorrhoids and various other diseases.

However, the pathophysiology of hemorrhoids is not fully understood. Although personal hygiene, dietary habits, lifestyle, physical activity, and immune and genetic factors can all contribute to the development of hemorrhoids, the prevailing theory is the downward movement of the anal cushion (10,30). This cushion, composed of mucous membranes, elastic fibers, smooth muscle, blood vessels, and other submucosal components, can protrude into the anal canal and contribute to hemorrhoids as a result of hypertrophy or degeneration of its supporting tissue. Furthermore, many studies have suggested the presence of inflammatory cells and newly generated microvessels in the hemorrhoidal tissue (31,32). Moreover, various enzymes and mediators that play a role in the degradation of supportive tissue have been identified (33).

Several pathological mechanisms have been proposed to explain the association between hemorrhoids and HF. First, hemorrhoids and HF share several risk factors. The risk factors for hemorrhoids, such as obesity, pregnancy, depression, and lack of physical activity, are well known to be associated with HF (34-39). Obesity leads to increased release of inflammatory cytokines and acute phase proteins, which continuously activate the innate immune system and contribute to the development of metabolic diseases including HF (40). Additionally, pregnancy increases the risk of hemorrhoids due to venous congestion caused by an enlarged uterus and changes in gastrointestinal motility influenced by pregnancy-related hormones (41). Second, elevated intra-abdominal pressure is common in patients with HF (42,43). Elevated intra-abdominal pressure, whether associated with obesity, pregnancy, or in HF, may also be linked to the development of hemorrhoids. Chronic elevation of intra-abdominal pressure, along with the lack of valves in the rectal veins, can impede venous drainage from the sinusoids during defecation, leading to abnormal dilation of the arteriolar-venular anastomoses in the hemorrhoidal plexus (44,45). Third, the relaxation and deterioration of supportive connective tissue exacerbate permanent prolapse of the anal cushions. Collagen abnormalities are frequently observed in aging individuals, contributing to the deterioration of connective tissue. Recently, increased activity of matrix metalloproteinase (MMP)-2 and MMP-9, which degrade elastic fibers and promote tissue remodeling, has been observed in patients with hemorrhoids. Furthermore, these MMPs have recently been associated with left ventricular dysfunction in patients with HF (46,47). Finally, changes in the gut microbiome within the anorectal region may contribute to hemorrhoids and other anorectal disorders. Gut bacteria play a role in regulating the inflammatory process and may be associated with functional gastrointestinal disorders that develop constipation (48). Several studies have also investigated the gut microbiome in patients with constipation, a known risk factor for hemorrhoids (49). Furthermore, recently, alterations in the gut microbiome have been associated with HF (50,51).

Our study found that the group receiving surgical treatment or other interventions for relatively severe hemorrhoids showed a trend for reduced incidence of HF compared with the group that did not receive such treatments. In other words, our research suggests that actively treating hemorrhoids, if present, might help reduce the incidence of HF. This could be due to improvements in inflammatory responses or dysbiosis, as explained above. However, since we did not investigate the exact mechanisms, further analysis is necessary. Additionally, because our study only showed statistically nonsignificant associations, it is possible that more important factors, such as obesity and metabolic syndrome, may be more strongly associated with the incidence risk of HF than surgical treatment or interventions for hemorrhoids.

Our study had several limitations. First, the potential ethnic bias in our results may limit the ability to apply our conclusions to other demographic groups. Therefore, further study in diverse racial and ethnic populations is essential. Second, although we performed a sub-analysis of the hemorrhoid population that had undergone surgical procedures or treatment, it was difficult to confirm imaging findings and accurately classify hemorrhoids because our dataset contained claims data. Third, given that hemorrhoids were identified using administrative claims data, it is unclear whether the study distinguishes between symptomatic and asymptomatic cases or between transient and chronic conditions. This lack of granularity may introduce misclassification bias, potentially diluting or exaggerating the association with HF. Fourth, potential and important confounders such as physical inactivity, dietary habits, and genetic factors were not included our dataset. Finally, while our study was a nationwide cohort study, its retrospective nature poses difficulties in establishing clear cause-and-effect relationships.

Conclusions

Our study revealed a significantly increased incidence of HF in patients with hemorrhoids. Therefore, it should be noted that when hemorrhoids are present, the risk of developing HF in the future may be increased. Further studies with high evidence, such as randomized controlled trials, are needed to investigate whether active treatment of hemorrhoids can reduce the incidence of HF in the future.

Acknowledgments

This study used National Health Insurance Service-Senior Cohort data (NHIS-2024-10-2-145), made by National Health Insurance Service.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://atm.amegroups.com/article/view/10.21037/atm-24-218/rc

Data Sharing Statement: Available at https://atm.amegroups.com/article/view/10.21037/atm-24-218/dss

Peer Review File: Available at https://atm.amegroups.com/article/view/10.21037/atm-24-218/prf

Funding: This work was supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (No. RS-2022-II220621 to T.J.S., Development of artificial intelligence technology that provides dialog-based multi-modal explainability), and was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2023-00262087 to T.J.S.). The funding source had no role in the design, conduct, or reporting of this study.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-24-218/coif). T.J.S. reports that this work was supported by Institute of Information & Communications Technology Planning & Evaluation (IITP) grant funded by the Korea government (MSIT) (No. RS-2022-II220621 to T.J.S., Development of Artificial Intelligence Technology that provides dialog-based multi-modal explainability); and was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: RS-2023-00262087 to T.J.S.). The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments, and was approved by the Institutional Review Board of Ewha Womans University Seoul Hospital (No. EUMC 2024-03-006). The requirement for informed consent was waived due to the retrospective nature of the study and the minimal risk to patient.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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