Association between constipation and risk of coronary heart disease: a systematic review and meta-analysis of cohort studies

Abstract

Objective:

This systematic review and meta-analysis aimed to evaluate the association between constipation and risk of coronary heart disease (CHD).

Methods:

We systematically searched PubMed, Web of Science, and Cochrane Library until 28 February 2025. Published cohort studies reporting quantitative association measures for CHD in constipated vs. non-constipated individuals were included. The heterogeneity was assessed via the chi-square test based on Cochrane Q statistics. I² > 50% or Q-test p < 0.05 indicated substantial heterogeneity, warranting random-effects modeling; otherwise, fixed-effects models were implemented. Subgroup evaluations were conducted for study design type, region, category of CHD, follow-up duration, and gender.

Results:

Nine studies involving 283,070 constipation cases and 3,343,120 controls were analyzed. Constipation was associated with a 10% increased CHD risk [hazard ratio (HR] = ).10, 95% confidence interval (CI): 1.05–1.15]. Statistical heterogeneity (I² = 42.5%, p = 0.03) was observed in the present study. Subgroup analyses revealed a stronger association with myocardial infarction (HR = 1.14, 95% CI: 1.05–1.23). Notably, constipation showed no CHD risk elevation in women (HR = 1.04, 95% CI: 0.98–1.11), with reduced residual heterogeneity (I² = 30.2%, p = 0.177).

Conclusion:

Our meta-analysis identified a significant positive association between constipation and CHD risk, particularly myocardial infarction. These findings suggest that constipation may either accelerate the pathological processes underlying CHD or that both conditions share common etiological pathways, warranting further mechanistic and interventional studies.

Introduction

Cardiovascular diseases (CVDs), particularly coronary heart disease (CHD), persist as the foremost contributor to global mortality. CHD continues to pose a critical public health challenge, with its burden escalating worldwide. Epidemiological surveillance reveals a sustained upward trajectory in CHD-related mortality since 1990, culminating in 9.14 million deaths and 197 million prevalent cases in 2019 (1). The Global Burden of Disease Study quantifies disease burden attributable to 88 modifiable risk factors. The results showed that key cardiovascular risk drivers include high blood pressure, dietary risks, high LDL cholesterol, air pollution, tobacco, high body mass index, high fasting plasma glucose, and kidney dysfunction among others (2). Emerging epidemiological evidence suggests that constipation may represent a novel modifiable risk factor for cardiovascular disease (3–6).

Constipation, with a global prevalence exceeding 10%, emerges as both a common clinical manifestation of gastrointestinal dysmotility and a significant public health priority worldwide (7). This condition manifests through suboptimal defecation experience, resulting from either reduced bowel movement frequency, straining during evacuation, incomplete rectal emptying, or the co-occurrence of colonic hypomotility and pelvic floor dyssynergia (8). A growing body of evidence has recently emerged examining the potential association between constipation and the risk of CHD. Although Ma et al. reported that increased frequency of bowel movements was positively associated with higher CHD risk, other studies have indicated a significant relationship between constipation and the development of CHD (3, 4, 9). Despite the increasing number of epidemiological studies on this topic, the nature and direction of the association between constipation and CHD risk remain inconsistent and subject to ongoing debate. This systematic review and meta-analysis were therefore conducted to quantitatively synthesize existing evidence regarding their association and evaluate the association between constipation and risk of CHD.

Methods

Search strategy

This systematic review and meta-analysis were executed in full compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting standards. The study protocol was prospectively registered with the International Prospective Register of Systematic Reviews (registration ID: CRD42024615729). A comprehensive literature search spanning PubMed, Web of Science, and the Cochrane Library was conducted through 28 February 2025 using the following Boolean search syntax: (“cardiovascular disease” OR “cardiovascular diseases” OR “CVD” OR “cardiovascular events” OR “heart disease” OR “heart diseases” OR “coronary artery disease” OR “coronary heart disease” OR “ischemic heart disease” OR “CHD” OR “myocardial infarction” OR “angina pectoris”) AND (“constipation” OR “bowel movement frequency”).

Inclusion criteria

Studies were eligible for inclusion if they met the following criteria: (1) peer-reviewed original research articles published in full text; (2) conducted in human populations; (3) studies defining constipation exposure through validated diagnostic criteria; (4) comparative design with constipated and non-constipated cohorts, reporting quantitative association measures [hazard ratio (HR), relative risk (RR), or odds ratio (OR)] with 95% confidence intervals (CIs), or providing sufficient data for their calculation.

Exclusion criteria

The following study types were systematically excluded during screening: (1) animal studies; (2) non-longitudinal study designs (cross-sectional analyses, case reports), gray literature (conference abstracts), and non-peer-reviewed materials (reviews, editorials); (3) non-English publications; (4) studies lacking extractable outcome metrics (risk ratios with 95% CIs or raw data for their computation).

Data abstraction and quality assessment

Dual-independent data extraction was performed by two investigators using a predefined extraction template, with discrepancies adjudicated through iterative discussion. In cases where multiple studies might have utilized the same registry or database, only one study per distinct cohort was retained to avoid double-counting. Extracted parameters encompassed: first author's name, publication year, country, study design, participants, definition of constipation, sample sizes in comparison groups, follow-up duration, and adjusted confounders. Methodological rigor was evaluated via the Newcastle-Ottawa Scale (NOS), employing its tripartite assessment framework: (1) cohort selection (0–4 points), (2) intergroup comparability (0–2 points), and (3) exposure ascertainment (0–3 points). Studies were stratified by total NOS scores (maximum 9 points), with higher scores denoting superior methodological quality.

Statistical analysis

For each study, we pooled effect estimates as the HR and their 95% confidence intervals (95% CIs). Logarithmic transformation was applied to HR values to calculate standard errors. Heterogeneity among studies was quantified via Cochran's Q statistic (chi-square test) and I² index (percentage of total variation attributable to heterogeneity). A priori thresholds for heterogeneity interpretation were established: I² > 50% or Q-test p < 0.05 indicated substantial heterogeneity, warranting random-effects modeling; otherwise, fixed-effects models were implemented. Galbraith radial plots identified outlier studies contributing to residual heterogeneity. To explore possible explanations for homogeneity and test the robustness of the association between constipation and risk of CHD, we preplanned subgroup analyses by study design type, region, category of CHD, follow-up duration, and gender. Meanwhile, we conducted sensitivity analyses based on leave-one-out iterative recalculation of pooled estimates. Funnel plot asymmetry was evaluated through Begg's rank correlation and Egger's weighted regression tests. A trim-and-fill non-parametric analysis of publication bias were used to address potential publication bias. All analyses were conducted in Stata 18.0 (Stata Corp, College Station, TX, USA) with two-tailed p < 0.05 defining statistical significance.

Results

Study characteristics

The systematic review initially retrieved 2,773 records from electronic databases. After title/abstract screening and eligibility assessment (Figure 1), nine studies comprising 283,070 constipation-affected participants and 3,343,120 non-constipated controls were ultimately included. During screening, we excluded three studies that provided only OR on constipation and CHD risk, which we thought would affect our inference of causality (10–12). Heterogeneous diagnostic criteria for constipation across studies were systematically documented. Table 1 details the cohort characteristics of included investigations. The meta-analysis incorporated eight cohort studies and one nested case-control study, the latter included due to its unique exposure–outcome ascertainment framework (3–6, 9, 13–16). Geographically, the studies comprised four US-based investigations, four from Asian nations, and one European cohort. Sex distribution analysis revealed seven studies with mixed-sex cohorts and two exclusively female populations. Methodological rigor was evaluated using the NOS, with all nine studies meeting the predefined quality threshold (NOS score ≥ 6). Comprehensive risk-of-bias assessments are shown in Table 2. In addition, Supplementary Table S1 describes a concise summary of the bias risk evaluations for all included studies.

Figure 1

Constipation and risk of CHD

Figure 2 presents the multivariable-adjusted hazard ratios (HRs) for CHD risk associated with constipation across included studies. Pooled analysis demonstrated a statistically significant 10% increased CHD risk among constipated participants vs. controls (HR=1.10, 95% CI: 1.05–1.15). Three studies reporting solely ORs were excluded from primary analysis due to the inherent limitations of ORs in causal inference. However, a meta-analysis incorporating these OR-based and HR-based studies (total N = 12) demonstrated strengthened pooled effect estimates for the constipation–CHD risk association (OR=1.12 vs. 1.10 in primary analysis), suggesting potential underestimation in our original model (Supplementary Figure S1). Moderate heterogeneity was detected (I² = 42.5%, p = 0.03), with Galbraith plot analysis identifying potential outlier studies contributing to between-study variation (Figure 7A). To evaluate potential study design effects, we performed subgroup analyses stratified by study type. Cohort studies demonstrated a robust association between constipation and elevated CHD risk (HR=1.09, 95% CI: 1.04–1.14), as illustrated in Figure 3A. Geographic subgroup analyses revealed significantly elevated CHD risk associated with constipation across all regions: Americas (HR=1.09, 95% CI: 1.02–1.16), Asia (HR=1.07, 95% CI: 1.02–1.12), and Europe (HR=1.24, 95% CI: 1.14–1.34), as shown in Figure 3B.

Figure 2

Figure 3

Coronary artery obstruction represents only one component in the multifactorial pathogenesis of ischemic heart disease, yet most prior studies have not rigorously differentiated ischemic heart disease from CHD terminologically (17). Accordingly, we adopted an operational classification strategy that aligned subgroup definitions with the specific nomenclature used by the original investigators. Subgroup analysis by CHD category demonstrated a significant association between constipation and myocardial infarction risk (HR=1.14, 95% CI: 1.05–1.23). No significant associations were observed for angina pectoris, ischemic heart disease, or coronary heart disease (Figure 4A). Given the substantial reduction in heterogeneity (I² < 25%) within the ischemic heart disease subgroup, we performed additional fixed-effect meta-analysis. This analysis confirmed a significant constipation–ischemic heart disease association (HR=1.07, 95% CI: 1.02–1.12), as detailed in Supplementary Figure S2. Stratified by follow-up duration, constipated individuals with <10 years of follow-up demonstrated significantly elevated CHD risk (HR=1.11, 95% CI: 1.05–1.16), whereas no statistically significant association emerged in cohorts with ≥10 years of surveillance (HR=1.08, 95% CI: 0.97–1.19) (Figure 4B). Given the sex-specific design of included studies, we conducted sex-stratified analyses evaluating constipation–CHD associations. The female-specific analysis revealed a non-significant association (HR=1.04, 95% CI: 0.98–1.11) with reduced residual heterogeneity (I² = 30.2%, p = 0.177), as detailed in Figure 5A. Of the nine cohort studies included in the analysis, only one provided sex-stratified risk estimates specific to male patients, which precluded a meaningful subgroup analysis for this population. Recognizing that heterogeneous definitions of constipation could introduce substantial variability into the pooled estimates, we performed a subgroup analysis stratified by the specific diagnostic criteria used to define constipation across the included studies (Figure 5B). Our results showed that patients diagnosed with constipation according to self-reported constipation (via validated questionnaires or patient interviews), Rome III criteria, and ICD criteria have a significantly increased risk of CHD (HR=1.08, 95% CI: 1.01–1.16; HR=1.42, 95% CI: 1.14–1.69; HR=1.16, 95% CI: 1.04–1.29). In the subgroup diagnosed with constipation according to frequency criteria, although heterogeneity was significantly reduced, constipation was not observed to increase CHD risk (HR=1.04, 95% CI: 0.98–1.11).

Figure 4

Figure 5

Sensitivity analysis and publication bias

Sensitivity analysis using leave-one-out iteration demonstrated robustness of the constipation–CHD association, with all recalculated pooled estimates remaining statistically significant (HR range=1.04–1.17) (Figure 6). This consistency confirms the stability of our meta-analytic findings. To address potential publication bias, we implemented a three-tiered assessment protocol: (1) visual inspection of funnel plot asymmetry, (2) Begg's rank correlation test, and (3) Egger's weighted regression test. Although there was no statistical evidence of publication bias using Egger's test (p = 0.340) (Figure 7B) and Begg's test (p = 0.343) (Figure 7C), initial funnel plot asymmetry prompted non-parametric trim-and-fill analysis. This method estimates the number of theoretically missing studies required to achieve funnel plot symmetry, incorporating five imputed studies in our analysis (Figure 7D). The adjusted model maintained statistical significance, showing an 8% elevated CHD risk in constipated individuals (HR=1.08, 95% CI: 1.03–1.14).

Figure 6

Figure 7

Discussion

Our meta-analysis incorporating nine cohort studies demonstrated a consistent risk elevation for CHD among constipation patients (HR=1.10, 95% CI: 1.05–1.15). Geographically stratified analyses revealed comparable effect magnitudes across regions: Americas, Asia, and Europe. Disease-stratified analysis revealed differential associations: myocardial infarction exhibited heightened susceptibility (HR=1.14, 95% CI: 1.05–1.23), whereas angina pectoris showed no statistically significant relationship. Notably, sex-specific effects emerged, with null association observed in female subgroups (HR=1.04, 95% CI: 0.98–1.11).

CHD constitutes the predominant etiology of cardiovascular mortality across both genders, accounting for >50% of total cardiovascular disease burden (18). CHD arises from progressive atherosclerotic transformation of the coronary vasculature, pathologically characterized by endothelial barrier compromise, chronic inflammatory infiltrates, and focal accumulation of lipid-rich macrophage foam cells. Structural instability in high-risk plaques precipitates fibrous cap fissure, initiating platelet-rich thrombus formation and subsequent acute coronary syndrome manifestations (19). The pathophysiology of CHD has undergone a remarkable evolution over the past decade. Formerly characterized as a passive cholesterol accumulation disorder, contemporary models delineate atherogenesis as a complex interaction of risk factors including cells of the artery wall and the blood and molecular messages that they exchange (20). Modern clinical evidence establishes CHD as a preventable disease, where pre-emptive screening coupled with risk-tailored interventions demonstrates significant prognostic benefits, across both established patients and asymptomatic high-risk populations (21). At present, the traditional risk factors of CHD, such as hypertension, diabetes, hyperlipidemia, behavior (tobacco use, physical inactivity), and diet (excessive sodium intake, sugar-sweetened beverage consumption), have been widely concerned (22). Our meta-analysis demonstrated a 10% elevated risk of CHD events among individuals with constipation compared to non-constipated controls, providing epidemiological evidence supporting constipation as a modifiable risk determinant in cardiovascular prevention frameworks. To our knowledge, our study is the first systematic review and meta-analysis to examine the association between constipation and CHD risk.

Constipation represents a prevalent gastrointestinal disorder encountered in clinical settings across Western nations, with epidemiological studies estimating a global prevalence in the range of 12%–19% (23). Constipation is more frequent in North America and Europe compared to Asia, probably attributed to variations in cultural practices, dietary patterns, and environmental exposures (24). Based on colonic transit, it can be categorized into three subtypes: normal colonic transit, rectal evacuation disorders, and slow colonic constipation (25). The multifactorial pathophysiology of constipation complicates precise alignment of causative factors with these subtypes.

The exact mechanism behind the increased risk of CHD observed in patients with constipation in our study is still unclear, and we speculate that it may be mediated through multiple pathways. First, the gut–heart axis, which serves as a pivotal bidirectional communication axis between the gut and the heart, may play an important role in the connection between constipation and CHD (26). Intestinal changes, such as dysbiosis and altered permeability of the epithelial barrier, have been observed in patients with constipation (27). Emerging evidence delineates compromised intestinal barrier integrity, dysregulated microbial communities, and microbiota-derived bioactive metabolites as pivotal mediators contribute to the occurrence and development of CHD via the gut–heart axis pathway (26). The gut microbiota promotes the development of atherosclerosis by producing intermediate metabolites, including trimethylamine-N-oxide (TMAO), endotoxin and phenylacetyl glutamine, and reducing butyrate (28). The most compelling evidence that links gut microbiota and CAD is related to microbial metabolism of dietary factors such as carnitine and choline. The source of TMAO is trimethylamine, which is produced by the gut microbiota from nutrients containing L-carnitine or phosphatidylcholine, and subsequently oxidized to TMAO by hepatic flavin-containing monooxygenases (29–31). Current evidence underscores that TMAO precursors drive foam cell formation and atherosclerotic plaque progression, while TMAO itself induces dysregulation of cholesterol homeostasis, elicits proinflammatory responses, oxidative stress, and endothelial activation—collectively synergizing to advance CHD pathogenesis (26, 30). Second, constipation contributes to sustained hypertension through psychogenic stress, enhanced colonic water absorption, and gut dysbiosis-induced neuroinflammatory signaling (11, 32). During defecation, constipation can often cause straining, during which patients may breathe in a strained manner similar to the Valsalva maneuver (33). This may induce transient blood pressure elevation, potentially precipitating acute coronary syndrome events. Third, constipated patients have upregulated biosynthesis and release of serotonin, a vasoconstrictor that promotes thrombus formation and is related to the development of atherosclerotic plaques and elevated risks of CHD (34–36).

Notably, our meta-analysis revealed no significant association between constipation and CHD risk in female participants, a finding warranting further mechanistic exploration. We hypothesized that pathophysiological mechanisms intrinsic to the predominant constipation phenotype in women underpin this observation. As previously noted, constipation exhibits three distinct phenotypes, with women being more likely to be affected by functional defecatory disorders than men (37). Among women, dyssynergic defecation is the most prevalent subtype and isolated slow transit constipation is uncommon (38). We postulate that accelerated colonic transit in dyssynergic defecation may reduce microbial fermentation time, thereby mitigating gut dysbiosis, compared to slow transit constipation. This diminished dysbiosis could attenuate the constipation–CHD association in women by reducing pathogenic microbial metabolite production (e.g., TMAO) and associated endothelial dysfunction. Subgroup analysis by classification of diseases revealed no significant constipation–CHD risk associations in angina pectoris or CHD subgroups, potentially attributed to sex distribution imbalances (female predominance) within these populations. We also did not observe an increased CHD risk for constipation in the subgroup diagnosed with constipation according to frequency criteria. Unlike definitions based on self-report, Rome III, or ICD codes, which often incorporate symptoms of straining, incomplete evacuation, or hard stools, a frequency-based definition likely identifies a more heterogeneous population. This group may include individuals with transient, diet-related, or behavioral bowel patterns who do not share the underlying autonomic dysregulation, chronic inflammation, or gut microbiome alterations associated with long-term, pathophysiologically significant constipation. Consequently, while frequency-based criteria may reduce heterogeneity by providing an objective measure, they might also dilute the effect by including many individuals without the persistent gut dysfunction that potentially drives CHD risk. In addition, a subgroup with ≥10 years of follow-up showed no significant association between constipation and CHD risk. This null finding may reflect residual confounding from sex-specific factors, laxative exposure duration, and age-related comorbidities.

This meta-analysis has several limitations that require cautious interpretation. First, statistical heterogeneity was observed (I² = 42.5%, p = 0.03), potentially attributable to be factors such as region, disease classification, follow-up time, gender, diet, and medication use. Subgroup analyses based on gender and region showed reduced heterogeneity, confirming these factors as potential confounders. Second, the limited number of studies in subgroup analyses by disease classification means that further research is needed to validate the association between constipation and different CHD subtypes. Third, due to an insufficient number of studies, a formal dose–response analysis between bowel movement frequency categories and CHD risk could not be performed. Fourth, sex-specific subgroup studies are limited, and we did not analyze constipation and CHD risks in men, highlighting the need for future prospective studies with pre-specified sex-stratified analyses.

Conclusion

Our meta-analysis demonstrated a significant positive association between constipation and CHD risk (OR=1.10, 95% CI: 1.05–1.15). Further subgroup analysis found that patients with constipation had a 14% higher risk of myocardial infarction compared to non-constipated individuals. These findings suggest that constipation may either accelerate the pathological processes underlying CHD or that both conditions share common etiological pathways. Future studies are warranted to investigate the risk of CHD in patients with constipation and to explore the factors driving this association, in order to confirm and expand upon these results.

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