Constipation Effect On Readmission In Heart Failure Patients

Constipation, a prevalent gastrointestinal disorder in Japan, affects 34.8 per 1000 individuals, rising with age and linked to factors like reduced dietary fiber and physical activity. Chronic constipation, unlike other functional gastrointestinal diseases, exhibits a significantly higher mortality risk, particularly notable in cardiovascular patients. Despite its impact, limited research explores constipation’s prognostic effects on acute heart failure. This study aims to investigate the association between constipation and outcomes in acute heart failure, focusing on all-cause mortality and heart failure re-admissions.

 

THE BACKGROUND OF THE STUDY

Constipation, characterized by symptoms such as straining, hard stools, infrequent bowel movements, and abdominal bloating, is a prevalent gastrointestinal disorder in Japan, affecting 34.8 individuals per 1000 [1]. The prevalence of constipation rises with age, notably impacting approximately 10% of individuals over 80 years [1]. The multifactorial nature of constipation involves reduced intake of food, dietary fiber, and water, decreased physical activity, and the potential effects of some oral medications [1].

Chronic constipation stands out among functional gastrointestinal diseases due to its association with a significantly higher mortality risk, particularly notable in patients with cardiovascular diseases [2]. Intriguingly, constipation’s impact extends beyond its gastrointestinal origins, with constipation status and laxative use independently linked to a higher risk of all-cause death, incident ischemic stroke, and coronary cardiac disease in the general population [3]. Despite the recognized health implications, there is a notable research gap concerning the predictive effects of constipation on patients with acute heart failure. Existing studies have focused on outcomes such as hospital stay length or bleeding events, with none concentrating on all-cause mortality or heart failure re-admission [4, 5].

This study aims to fill this gap by exploring the association between constipation and the outcomes of patients with short-term heart failure, with a primary focus on all-cause mortality and heart failure re-admission. Through a comprehensive examination of these outcomes, the research seeks to provide valuable insights into the broader health implications of constipation, particularly acute heart failure.

Characteristics of patients with heart failure

The baseline characteristics of heart failure (H.F.) patients reveal distinctive differences based on left ventricular ejection fraction (L.V.E.F.) categories. Heart failure with preserved L.V.E.F. (HFpEF) patients, in contrast to those with reduced L.V.E.F. (HFrEF), were more frequently women, senior citizens, and had a higher body mass index. HFpEF patients exhibited a higher prevalence of comorbidities, including a history of atrial fibrillation, diabetes, pulmonary disease, peripheral artery disease, and hypertension. Conversely, few HFpEF patients had a history of coronary revascularization. Systolic blood pressure was higher in HFpEF and heart rate in HFrEF. Treatment patterns also differed, with a majority of HFrEF and heart failure with mid-range L.V.E.F. (HFmrEF) patients receiving renin-angiotensin inhibitors, angiotensin II receptor inhibitors, or angiotensin receptor-neprilysin inhibitor compared to a lower percentage in HFpEF. Thiazides, calcium antagonists, and oral anticoagulants were more commonly prescribed in HFpEF [2].

Furthermore, HFpEF patients exhibited a lower estimated glomerular filtration rate (eGFR), lower hemoglobin levels, and a higher prevalence of anemia than HFrEF patients. High-sensitive C-reactive protein (hs-CRP) levels were also higher in HFpEF. Electrocardiogram (E.C.G.) findings revealed a significantly higher incidence of atrial fibrillation (A.F.) in HFpEF and HFmrEF compared to HFrEF.  Laboratory results and E.C.G. findings aligned with the 2016 European Society of Cardiology (E.S.C.) H.F. guidelines further highlighted these differences among the H.F. categories [2].

 

THE STUDY METHOD

The study included 438 consecutive patients admitted to the hospital for acute heart failure between December 2020 and December 2022. After excluding 36 patients who died in the hospital and 5 with current gastrointestinal tract cancer, the final study cohort comprised 397 patients diagnosed with heart failure based on the Framingham Study criteria. Patient characteristics, such as sex, age, B.M.I. (Body Mass Index), admission status and post-hospitalization medication use were systematically analyzed. Comorbidities like hypertension, diabetes mellitus, and dyslipidemia were extracted from medical records, and the Hospital Frailty Risk (HFR) score was utilized to assess patient frailty. Patients were put into two groups based on constipation status, defined by regular laxative use or an ICD-10 diagnosis of constipation (K590), representing various constipation types.

The study’s clinical outcomes focused on all-cause mortality and re-admission due to heart failure after hospital discharge. Retrospective reviews of medical charts provided data on post-discharge outcomes, considering the patient’s history of regular hospital visits and communication with family and family doctors. The study stuck to the principles outlined in the Declaration of Helsinki, with approval from the Ethics Committee of Sendai City Medical Center (number 2023-0051), and obtained written informed consent from all participating patients.

 

ANALYSIS

The analysis utilized straightforward statistical methods: continuous data were presented as means or medians and compared with the Student’s t-test. In contrast, categorical data were shown as percentages and compared using the chi-squared test. Kaplan–Meier estimates with log-rank tests were employed to evaluate the link between constipation and the risk of death or heart failure re-admission.

Two models were built: an unadjusted one and a fully adjusted model considering 14 variables influencing heart failure re-admission. These variables included sex, age, and B.M.I (Body Mass Index), walking ability, Hospital Frailty Risk (HFR) score, prior heart failure and stroke admissions, atrial fibrillation, N-terminal pro-B-type natriuretic peptide level, hemoglobin level, blood urea nitrogen level, estimated glomerular filtration rate, serum albumin level, and left ventricular ejection fraction. Propensity scores for constipation were calculated, matching 57 pairs of patients for further analysis. Values less than 0.05 were taken to be statistically significant, and J.M.P. (Jump) software, version 17.1.0, developed by S.A.S. Institute in Cary, North Carolina, U.S.A., was used for all analyses, addressing missing data for key variables like N-terminal pro-B-type natriuretic peptide levels and left ventricular ejection fraction.

 

RESULTS

1. Study Population:

   – Retrospective investigation of 397 patients with a mean age of 81 ± 13 years.

   – Gender distribution: 54% men.

   – Constipation prevalence: 32.2% (n=128) based on regular laxatives (n=107) and ICD-10 criteria (n=104).

1. Baseline Characteristics:

 – Patients with constipation were older, less able to walk independently, had higher HFR scores, and a higher history of heart failure admissions and atrial fibrillation morbidity compared to those without constipation.

   – Laboratory findings: Patients with constipation exhibited higher left ventricular ejection fraction but lower hemoglobin and albumin concentrations.

3. Follow-up Period:

   – Mean follow-up period: 236 ± 236 days (median 173 days).

   – All-cause mortality: 8.8% (35 patients).

   – Re-admission due to heart failure: 18.6% (74 patients), with 30 and 44 occurrences in patients with and without constipation, respectively.

4. Kaplan–Meier Analysis:

   The risk of death tended to be higher in patients with constipation (log-rank P= 0.092).

   – Significantly higher risk of re-admission due to heart failure in patients with constipation (log-rank P= 0.014).

5. Cox Proportional Hazards Models:

   – Unadjusted model: Hazard ratio for all-cause death and re-admission due to heart failure in patients with constipation compared to those without.

   – Fully adjusted model: The risk of all-cause death was not associated with constipation, but the risk of re-admission due to heart failure was significantly greater in patients with constipation.

 

6. Significant Independent Variables:

   – Age, previous stroke admission, previous heart failure admission, and N-terminal pro-B-type natriuretic peptide level were significant independent variables for re-admission due to heart failure.

7. Propensity Score Matching:

   – After matching using 14 variables, Kaplan–Meier analysis revealed a substantively higher risk of re-admission due to heart failure in patients with constipation (log-rank test P= 0.0027).

These findings suggest a potential link between constipation and an increased risk of re-admission due to heart failure, even after adjusting for various influencing factors. Further investigation is warranted to demystify the underlying mechanisms contributing to this association.

 

DISCUSSION

Constipation emerges as a common challenge among heart failure patients, a phenomenon exacerbated by aging—a shared risk factor for both constipation and cardiovascular diseases [8]. The treatment of heart diseases, particularly heart failure, may contribute to constipation through factors such as water restriction and diuretic use [9]. This study delves into the potential mechanisms linking constipation and heart failure prognosis.

One proposed mechanism suggests that changes in the intestinal microbiota due to constipation may promote atherosclerosis—a process influenced by the metabolite Trimethylamine-N-oxide (T.M.A.O.). T.M.A.O., primarily metabolized by the intestinal microbiota, enhances platelet activation and is associated with increased risks of death, myocardial infarction, and stroke [10] [11] [13]. However, the relationship between constipation, intestinal microbiota, and atherosclerosis remains to be fully confirmed [10].

Straining during bowel movements, a common symptom of constipation, is implicated in increasing blood pressure and potentially triggering cardiovascular events. Although some studies have demonstrated a higher risk of death and coronary heart disease in patients with constipation, the implications for heart failure were not extensively explored [2] [3] [18].

For the first time, the study establishes a link between constipation and an increased risk of re-admission in patients with heart failure, suggesting that improved constipation management may positively impact heart failure prognosis. Interestingly, the study did not find a higher mortality rate in patients with constipation compared to those without. However, the risk of re-admission for heart failure was significantly higher in patients with constipation, emphasizing the importance of addressing constipation in heart failure management [4].

The study acknowledges limitations, including variations in the intestinal microbiota characteristics of patients with constipation and the relatively small sample size. In conclusion, while common and potentially impactful, constipation in heart failure patients necessitates further investigation to fully understand its mechanisms and establish effective management strategies for improving heart failure outcomes. The study underscores the need for a comprehensive approach to heart failure management, considering cardiac factors and general noncardiac conditions.

 

LIMITATIONS OF THE STUDY

• Retrospective and Observational Design:

   – The study’s retrospective, observational nature poses inherent limitations, limiting the establishment of causal relationships.

2. Single-Center Setting:

   – Conducted at a single center, the study may need more generalizability due to potential variations in patient demographics and clinical practices across different centers.

3. Limited Sample Size:

   – Results were derived from a relatively small number of patients, raising concerns about statistical power and the ability to detect subtle associations.

4. Constipation Definition:

   – The definition of constipation relied on laxative use or ICD-10 criteria rather than employing the ROME IV criteria for functional constipation. This choice may impact the accuracy of identifying patients with constipation.

5. Heart Failure Diagnosis Criteria:

   – The diagnosis of heart failure was based on the Framingham Study criteria, utilizing clinical symptoms, signs, and chest X-ray findings, without incorporating contemporary methods like echocardiographic findings or biomarkers such as B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide.

6. Contemporary Relevance of Criteria:

   – Using criteria from the Framingham Study, which may not align with current contemporary standards, could introduce potential bias and influence the study results.

7. Need for Larger, Multicenter Studies:

   – The study highlights the necessity for additional research with larger sample sizes obtained from multiple centers to validate its conclusions. Such studies could better inform constipation management strategies and ascertain the potential improvement in the prognosis of heart failure patients through constipation management.

 

CONCLUSION

In navigating the constipation-heart failure relationship, this study illuminates constipation as a potential predictor of heart failure re-admission. However, its retrospective, single-center design and reliance on outdated diagnostic criteria warrant caution. The intriguing connection between Trimethylamine-N-oxide (T.M.A.O.) and cardiovascular dynamics adds depth. This study beckons for broader, multicenter investigations to validate findings and modernize diagnostic approaches. Constipation, once a mere symptom, emerges here as a protagonist in the heart failure narrative, urging further exploration for a more nuanced understanding and refined management strategies.

 

REFERENCES

1. 1Ministry of Health, Labour and Welfare. Vital Statistics, (2019). [Online] Available at: https://www.mhlw.go.jp/english/database/db-hss/dl/report_gaikyo_2019. PDF. Accessed October 20, 2023.
2. 2Chang JY, Locke GR III, McNally MA, Halder SL, Schleck CD, Zinsmeister AR, et al. Impact of functional gastrointestinal disorders on survival in the community. Am J Gastroenterol 2010;105:822-832. Doi 10.1038/ajg.2010.403 https://doi.org/10.1053/j.gastro.2016.02.031 
3. 3.3Sumida K, Molnar MZ, Potukuchi PK, Thomas F, Lu JL, Yamagata K, et al. Constipation and risk of death and cardiovascular events. Atherosclerosis 2019;281:114-120. doi:10.1016/j.atherosclerosis.2018.12.021. https://doi.org/10.1053/j.gastro.2016.02.031 
4. 4Staller K, Khalili H, Kuo B. Constipation prophylaxis reduces the length of stay in elderly hospitalized heart failure patients with home laxative use. J Gastroenterol Hepatol 2015;30:1596-1602. doi:10.1111/jgh.13011. https://doi.org/10.1053/j.gastro.2016.02.031 
5. 5 Yamamoto J, Yamamoto M, Hara H, Hiroi Y. Relation between laxative use and risk of major bleeding in patients with atrial fibrillation and heart failure. Heart Vessels 2023;38:938-948. doi:10.1007/s00380-023-02249-6. https://doi.org/10.1053/j.gastro.2016.02.031 
6. 2C. Linde et al. ESC Heart Failure2022;9: 2125–2138DOI: 10.1002/ehf2.13922 https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.14650 
7. 8Shiyama Y, Hoshide S, Mizuno H, Kario K. Constipation-induced pressor effects as triggers for cardiovascular events. J Clin Hypertens (Greenwich) 2019;21:421-425. doi:10.1111/jch.13489. https://doi.org/10.1053/j.gastro.2016.02.031 
8. 9 Elliott WJ, Ram CV. Calcium channel blockers. J Clin Hypertens (Greenwich) 2011;13:687-689. doi:10.1111/j.1751-7176.2011.00513. https://doi.org/10.1053/j.gastro.2016.02.031 
9. 10Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, DuGar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57-63. doi:10.1038/nature09922. https://doi.org/10.1053/j.gastro.2016.02.031 
10. 11Tang W.H.W., Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, et al. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med 2013;368:1575-1584. doi:10.1056/NEJMoa1109400. https://doi.org/10.1053/j.gastro.2016.02.031 
11. 13Zhu W, Gregory JC, Org E, Buffa JA, Gupta N, Wang Z, et al. Gut microbial metabolite T.M.A.O. enhances platelet hyper-reactivity and thrombosis risk.Cell2016;165:111-124.   doi:10.1016/j.cell.2016.02.011. https://doi.org/10.1053/j.gastro.2016.02.031 
12. 18Honkura K, Tomata Y, Sugiyama K, Kaiho Y, Watanabe T, Zhang S, et al.Defecation frequency and cardiovascular disease mortality in Japan: The Ohsaki cohort study.Atherosclerosis2016;246:251-256.  doi:10.1016/j.atherosclerosis.2016.01.007. https://doi.org/10.1053/j.gastro.2016.02.031 

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  • Verbal Communication and Masks
  • Sugammadex Versus Neostigmine in Thyroidectomy
  • SGLT Inhibitors on Weight and Lipid Metabolism in Diabetes
  • Saxagliptin: Obese Patients with Impaired Glucose Tolerance
  • Levothyroxine Therapy and Depression
  • Grave’s Disease and Risk of Systemic Lupus Erythematosus
  • Benign Thyroid Removal and Patient Satisfaction
  • MF- Biology, Management, and a Case Study of Ocular Manifestation
  • Quality Of Life In Adolescent Cancer Survivors
  • Cancer Opioid Risk Score
  • Oncology-Specific Opioid Risk Calculator In Cancer Survivors
  • 3D MRI for Non-invasive Ocular Proton Therapy of Uveal Melanomas
  • Sexual Dysfunction in Prostate Cancer Patients 
  • 3-Day Surprise Question To Predict Survival Rates in Advanced Cancer Patients

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