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The existing literature has demonstrated that variables such as gender, body mass index (BMI), and age play a significant role in the risk assessment of hiatal hernia. This study aims to comprehensively investigate the association between these risk factors and hiatal hernia through a retrospective analysis and Mendelian randomization (MR) analysis.
Methods
In this study, the examination results and basic information of 685 patients who underwent routine esophagogastroduodenoscopy (EGD) at the gastroesophageal Reflux Center of Xuanwu Hospital from 2018 to 2024 were retrospectively collected. logistic regression was used to analyze the potential risk factors. Meanwhile, a two-sample MR analysis was used to further validate and supplement these risk factors.
Results
A retrospective study showed that the incidence of hiatal hernia diagnosed by endoscopy was 28.7%, in the population without GERD, the incidence was 22.8%In the multivariate logistic regression analysis, male sex (P = 0.033), age (P < 0.001), heavy physical labor (P < 0.001), and gastroesophageal reflux disease (GERD) (P < 0.001) were independent risk factors for hiatal hernia, while an increase in BMI, smoking, alcohol consumption, and the number of pregnancies and deliveries in women were not statistically significant. The inverse variance weighting (IVW) results of the MR analysis showed that an increased waist–hip ratio (ORIVW = 2.57, CI 1.32–5.01, P = 0.0057), trunk fat (ORIVW = 3.53, CI 1.76–7.07, P = 0.0004), smoke initiation (ORIVW = 1.47, CI 1.02–2.13, P = 0.0408), and alcohol intake frequency (ORIVW = 2.23, CI 1.18–4.20, P = 0.0134) were associated with hiatal hernia, but the causal relationship between alcohol intake frequency and hiatal hernia was not established.
Conclusion
This study showed that male gender, age, heavy physical labor, and GERD were independent risk factors for hiatal hernia. MR analysis showed that abdominal obesity and smoking may be genetically associated with hiatal hernia. However, there was no statistical significance between increased BMI and hiatal hernia in multivariate analysis and MR analysis.
Hongyi Dong and Xing Du have contributed to the work equally and should be regarded as co-first authors.
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Hiatal hernia is generally defined as the herniation of internal organs into the chest through the diaphragmatic hiatal hole. According to different hernia contents and anatomy, hiatal hernia can be divided into four types, of which type I is sliding hiatal hernia, accounting for more than 95% of hiatal hernia, type II, type III, and type IV are para-esophageal hernia, accounting for about 5% [1]. Sliding hiatal hernia is thought to result from weakening and elongation of the phrenoesophageal ligament and widening of the diaphragmatic hiatus. These changes lead to displacement of the esophagogastric junction (EGJ) into the thoracic cavity, disrupting the anti-reflux barrier and thereby contributing to the pathogenesis of gastroesophageal reflux disease (GERD) [2]. Furthermore, patients with type I hiatal hernias experience prolonged gastric acid clearance, which impairs the drainage of fluid from the distal esophagus. This is exacerbated by "secondary reflux" from the hernia sac during swallowing. The prevalence of hiatal hernia among GERD patients ranges from 48.6% to 68%, increasing to 78.1% in those with reflux esophagitis and 88.2% in those with Barrett’s esophagus [3, 4]. As such, hiatal hernia is a significant risk factor for GERD.
The exact pathogenesis of sliding hiatal hernia remains incompletely understood. However, it is widely accepted that the development of the disease is primarily influenced by three interrelated factors. Current research on the risk factors for hiatal hernia largely focuses on these mechanisms: I. Degenerative changes in the phrenoesophageal ligament, including reduced collagen fibers, have been implicated in the development of sliding hiatal hernias [5, 6]; II. increased intra-abdominal pressure; III. reflux of gastric acid into the esophagus, which stimulates reflex contraction of the esophageal smooth muscle, causing esophageal shortening. This pulling force shifts the esophagogastric junction (EGJ) into the thoracic cavity. Meta-analyses by Menon et al., along with other recent studies, have identified male sex, high body mass index (BMI), and advanced age as significant risk factors for hiatal hernia [7, 8]. Additionally, a small number of studies suggest that pregnancy [9], kyphosis, and the resulting abnormal gastrointestinal motility, along with osteoporosis, may also contribute to the development of hiatal hernia [10].
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To investigate the risk factors associated with the development of hiatal hernia, we identified potential contributors and employed a retrospective study, combined with MR analysis, to explore these factors as comprehensively as possible.
Methods
Study design
First, we conducted a retrospective analysis to explore the relationship between adiposity, smoking, and drinking and hiatal hernia. The data collected in the study were all from the patients' medical records and doctors' physical examination and consultation, and the data were anonymous and easily accessible to the public. This study was approved by the Ethics Committee of our Hospital (Reference No. 2024P209702). In addition, we used large sample summary statistics and conducted multiple two-sample MR analysis to explore the causal relationship between adiposity, smoking, and drinking and hiatal hernia, which must meet the three assumptions of MR: (a) high correlation between the genetic tool and the exposure factor (P < 5 × 10−8 ~ 5 × 10−6); (b) no association between the genetic tool and potential confounding factors; and (c) the impact of the genetic tool on the outcome is only through the exposure factor. At the same time, we tested for the multi-collinearity effect, i.e., determining whether the instrumental variable affects the outcome through exposure factors other than the exposure. In addition, the Mendelian randomization (STROBE-MR) guidelines are being followed in this study to enhance the reporting of observational epidemiologic studies [11]. The flowchart of the MR analysis is shown in Fig. 1.
Fig. 1
Flow chart of two-sample Mendelian randomization analysis
The retrospective study data were collected from 685 patients who voluntarily underwent esophagogastroduodenoscopy (EGD) and met the inclusion criteria at the Department of General Surgery, Xuanwu Hospital of Capital Medical University from 2018 to 2024. The exclusion criteria were as follows: (1) esophageal or proximal gastric neoplasms; (2) previous repair of hiatal hernia; (3) previous laparoscopic surgery before EGD; (4) previous major external abdominal injury; and (5) incomplete clinical data. In the MR analysis, the instrumental variables for BMI, alcohol intake frequency, trunk fat, waist–hip ratio, and smoking were all sourced from the UK Biobank, Integrated Epidemiology Unit (IEU) database, and the Consortium of Alcohol and Nicotine Use (GSCAN) database. The single-nucleotide polymorphisms (SNPs) associated with the exposure factors were required to have a p-value as small as possible (< 5 × 10–8), and if the number of instrumental variables was limited, the p-value could be relaxed to < 10–6.. The chain of balance (LD, R2 ≤ 0.001), H-W equilibrium, and genetic distance less than 10,000 kb were also required. Then, the major allele, allele frequency, beta value, p-value, and standard error (SEs) of each SNP were collected. Previous MR studies have shown that using high-quality instrumental variables can effectively improve the accuracy and validity of the model estimates. To avoid bias due to weak instruments, the F-statistic was calculated, and the instrumental variables without F-statistic < 10 were excluded. The outcome data were collected from the FinnGen Biobank database (n cases = 5741, controls = 190,557).
Observation indication and diagnosis
We primarily collected data on patients' gender (male, female), age, BMI, occupation, as well as their smoking and drinking habits. Additionally, we recorded the incidence of GERD and gathered obstetric histories from some female patients. Regular drinking was defined as consuming alcoholic beverages (regardless of type) ≥ 4 times per week. Heavy physical labor was defined as work in agriculture or heavy industry. The diagnostic criteria for GERD included the following : (1) GERD Q score ≥ 8; (2) diagnosis of reflux esophagitis classified as LA-B or higher based on EGD [12]; and (3) the presence of typical GERD symptoms (such as acid regurgitation and heartburn) requiring continuous use of acid-suppressive medication. The diagnostic criteria for hiatal hernia included the following: measurement of the distance between the squamocolumnar junction and the esophageal hiatus impression being > 2 cm during EGD [13, 14], or the presence of longitudinal gastric mucosal folds extending above the diaphragmatic indentation, and the identification of a gastric pouch herniating cranially across the crural impression.
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Statistical analysis
This study utilized SPSS 26.0 software (IBM Corp., New York, USA) for data analysis. For normally distributed continuous variables, the results are presented as mean ± standard deviation (x ± s), and independent samples t-tests were used for group comparisons. For non-normally distributed continuous variables, data are expressed as median (25th percentile, 75th percentile), with non-parametric rank-sum tests employed for intergroup comparisons. Categorical data are presented as counts (percentages) n (%), and intergroup comparisons were performed using χ2 tests. To identify the independent risk factors for hiatal hernia, binary logistic regression analysis was conducted. We initially performed univariate analysis to screen for potential risk factors, which were then included in a multivariable logistic regression model. P value of < 0.05 was considered statistically significant.
In the MR analysis, we conducted two-sample MR to assess the effect alleles from GWAS related to various exposure factors and hiatal hernia. We employed five default methods from the two-sample MR package, with the inverse variance weighting (IVW) method demonstrating the best statistical performance, thus serving as the primary method to explore the association between relevant exposure factors and hiatal hernia, utilizing random-effects inverse variance methods to calculate causal estimates. The remaining four methods served as supplements: the MR-Egger method detects and adjusts for systematic biases in instrumental variables through the intercept term in the regression model and can also identify the instances that violate standard instrumental variable assumptions, providing robust effect estimates under these conditions. The weighted median method offers reliable estimates of causal effects, even when up to 50% of the data may derive from ineffective instrumental variables. Additionally, we assessed heterogeneity in the analysis using the P value from the Cochran Q test, applied MR-PRESSO to evaluate pleiotropy in the model, and employed a leave-one-SNP-out method to calculate the combined effect of each remaining SNP. The basic information and detailed results of these analyses are presented in Table 1.
Table 1
Basic information on studies and consortia, along with the results of sensitivity analyses and pleiotropy in Mendelian randomization results
Europeans accounted for the majority (83.16% of European-descent individuals, 6.11% of Asians, and 10.73% of Africans), with 66,742 European-descent individuals
BMI,waist hip ratio, tobacco use, physical activity
9
61
8
0.03
0.59
0.13
ukb-b-5779
Results
In our retrospective study, a total of 685 patients were included, comprising 335 males and 350 females. The median age of the overall sample was 56 (45.5, 65.0), and there was a significant association between increasing age and hiatal hernia incidence (P < 0.001). The overall prevalence of hiatal hernia was found to be 28.7%, with a higher prevalence in males compared to females, showing statistical significance (male: 33.7%, female: 23.7%, P = 0.004). After excluding patients with GERD, the incidence was 22.8%. Furthermore, there were differences in the prevalence of hiatal hernia among individuals with different BMI categories as follows: underweight (BMI < 18):5% (1/20); normal weight (BMI 18.5–22.9):25.7% (47/183); overweight for Asian population or normal weight (BMI 23–24.9):25.1% (42/162); obese for Asian population or overweight (BMI 25–29.9):33.5% (92/275); and obese (BMI ≥ 30):32.5% (13/40). Hiatal hernia prevalence demonstrated an association with increased BMI (P = 0.011). Regarding lifestyle habits, drinking habit (P = 0.018), regular drinking (P = 0.022), and engaging in heavy physical labor (P < 0.001) were all significantly associated with the incidence of hiatal hernia. The presence of GERD symptoms also showed an association with the occurrence of hiatal hernia (P < 0.001), as summarized in the Table 2.
Table 2
Results of univariate analysis
Classify
Research group (n = 196)
Control group (n = 489)
χ2/Z
P
Male
113 (57.65%)
222 (45.40%)
8.409
0.004
Female
83 (42.35%)
267 (54.60%)
Overweight (BMI ≥ 25)
104 (53.06%)
209 (42.74%)
6.006
0.17
BMI
25.32 (22.97,27.03)
24.56 (22.31,26.57)
2.584
0.011
Age
59.00 (50.25,76.00)
55.00 (44.00,64.00)
3.689
< 0.001
Ever smoke
51 (26.02%)
102(20.86%)
2.149
0.156
Smoke per day
49 (25.00%)
100(20.45%)
1.702
0.192
Drinking habit
67 (34.18%)
123 (25.15%)
5.692
0.018
Regular drinking
24 (12.24%)
33 (6.75%)
5.541
0.022
Heavy physical labor
23 (11.73%)
21 (4.29%)
12.886
< 0.001
GERD
72 (36.73%)
70 (14.31%)
42.799
< 0.001
Only female (n = 350)
Ever been pregnant
80 (96.39%)
253 (96.25%)
0.003
1.000
Gravidity
1 (1,3)
1 (1,2)
1.542
0.123
Parity
1 (1,2)
1 (1,2)
1.386
0.166
BMI body mass index, GERD gastroesophageal reflux disease
After conducting univariate analysis, the logistic step-by-step regression model was employed to perform statistical analysis with hiatal hernia as the dependent variable and independent variables exhibiting statistically significant differences. The findings revealed that being male (P = 0.033), advancing age (P < 0.001), engaging in heavy physical labor (P < 0.001), and having GERD (P < 0.001) were identified as independent risk factors for GERD. However, no significant correlation was observed between BMI or regular drinking and the occurrence of hiatal hernia, as indicated in the Table 3.
Table 3
Multivariate logistic regression results
Factors
β
SE
χ2 Wald
P
OR
95%CI
Male/female
0.418
0.195
4.571
0.033
1.519
1.035–2.227
Age
0.037
0.008
21.863
< 0.001
1.037
1.021–1.053
BMI
0.039
0.028
1.866
0.172
1.039
0.983–1.099
Regular drinking
0.16
0.327
0.241
0.624
1.174
0.619–2.227
Heavy physical labor
1.296
0.336
14.844
< 0.001
3.655
1.890–7.066
GERD
1.294
0.209
38.19
< 0.001
3.649
2.420–5.502
BMI body mass index, GERD gastroesophageal reflux disease
In our MR analysis, a higher genetically predicted waist-to-hip ratio and trunk fat content were found to be associated with an increased risk of hiatal hernia. The odds ratios (ORs) and associations for trunk fat content (ORIVW = 3.53, CI 1.76–7.07, P = 0.0004) were stronger than those for waist–hip ratio (ORIVW = 2.57, CI 1.32–5.01, P = 0.0057). Additionally, initiation of smoking and alcohol intake frequency were also shown to be associated with an increased risk of hiatal hernia; however, the association with initiation of smoking was weak (ORIVW = 1.47, CI 1.02–2.13, P = 0.0408), while the association with frequency of alcohol consumption was significant (ORIVW = 2.23, CI 1.18–4.20, P = 0.0134). Interestingly, the MR-Egger analysis showed opposite directions for these associations. Furthermore, no genetically predicted BMI was observed to be associated with an increased risk of hiatal hernia (ORIVW = 1 0.45, CI 0 0.93–2.25, P = 0.1016). The results obtained from the MR analysis methods are presented in Fig. 2.
The robustness of the primary results was assessed through sensitivity analyses which included examining each single-nucleotide polymorphism SNP individually and calculating the combined effect by using leave-one-out method. Heterogeneity assessed by Cochran's Q test and pleiotropy evaluated by MR-Egger regression are displayed in Table 1. Notably, based on both IVW and MR-Egger regression analyses, no heterogeneity is detected among the results. In MR-egger analysis, we found horizontal pleiotropy only for alcohol intake frequency (P = 0.03), but not for smoke initiation, BMI, trunk fat, waist–hip ratio. Furthermore, the leave-one-out sensitivity analysis demonstrated that no single SNP significantly influenced the overall causal effects. The detailed outcomes from leave-one-out sensitivity analysis can be found in the Supplementary Material.
Discussion
Our retrospective study showed that the incidence of hiatal hernia was 28.6%, higher than the 21% in European samples diagnosed by gastrointestinal endoscopy and the 17% in other Asian samples [15, 16]. Our baseline characteristics were similar to those studied by Sgouros et al. [15], including age and BMI. After excluding patients with GERD, we obtained a similar incidence of 22.8% (124/544). With increasing age, degenerative changes occur in the phrenoesophageal ligament, including a reduction in collagen fibers, which leads to decreased tensile strength and compromised elastic recoil. These structural alterations diminish the ligament’s ability to maintain the position of the EGJ during physiological movement of the esophagus through the hiatus. As a result, the weakened ligament may contribute to the cranial migration of the lower esophagus and gastric cardia into the thoracic cavity, thereby predisposing individuals to the development of sliding hiatal hernia [17]. Our study shows that age is an independent risk factor for hiatal hernia, a conclusion that is consistent with the results of most studies. In addition, our study found that male gender was also an independent risk factor for hiatal hernia. Previous studies have pointed out that an increased ratio of type I to type III collagen and an overall decrease in type I /III collagen in the phrenoesophageal ligament may be associated with the pathogenesis of hiatal hernia [18, 19]. Asling B et al. found that the COL3A1 gene was associated with hiatal hernia in adult males, and that the COL3A1 gene encodes type III collagen protein [20], which, to some extent, supports our conclusion.
A meta-analysis by Menon et al. involving 3,597 patients indicated that the incidence of hiatal hernia is associated with an increase in BMI (OR 1.93, 95% CI 1.10–3.39, P = 0.002) [7]. However, this study reported a high level of heterogeneity between BMI and the occurrence of hiatal hernia (I2 = 81%). In our retrospective study, we did not find an association between overweight (BMI ≥ 25) and the occurrence of hiatal hernia, and we did not observe similar results when BMI was used as a continuous variable in the multivariate analysis. Previous research has shown that, at the same BMI level, Asians tend to have a higher total fat content compared to Europeans [21]. A study by Lear et al. also demonstrated that, across all BMI levels, the percentage of body fat distribution among Chinese participants is similar to that of European participants. However, when waist circumference exceeds 71.0 cm, Chinese participants exhibit significantly higher visceral adipose tissue (VAT) compared to Europeans (P = 0.017) [22]. These findings suggest that Asians are more prone to abdominal obesity at the same BMI and may even develop abdominal obesity within the normal BMI range. Existing studies indicate that an increase in waist circumference or elevated intra-abdominal pressure due to the use of a belt can lead to proximal displacement of the EGJ (P < 0.05), and this effect is exacerbated by increased acid exposure [23]. This implies that abdominal obesity may concurrently promote the development of both hiatal hernia and GERD. Waist–hip ratio and trunk fat distribution are accurate indicators of abdominal obesity, and our MR analysis shows that both are genetically associated with the occurrence of hiatal hernia (P = 0.0057 and P = 0.0004), and a causal relationship is established. This provides a plausible explanation for the heterogeneity observed in Menon et al. 's study, as the meta-analysis included studies with diverse ethnic backgrounds, and the definition of overweight in Asian populations was still based on a BMI ≥ 25 kg/m2. Consistent with our conclusions, another study by Alsahafi et al., which included 2805 samples, similarly used endoscopy as the method of diagnosis of hiatal hernia [4]. However, the mean BMI of their sample was 29.7 (± 8.6) kg/m2, which was close to obese status. In fact, Ribieras et al. stated in their study that the detection rate of EGD in obese patients was rather unsatisfactory, with a perioperative detection rate of only 38% in patients undergoing Sleeve Gastrectomy (SG) surgery [24]. Therefore, different BMI baselines and diagnostic methods may be important reasons for the different experimental results.
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Similar to the study by Wu et al. [25], our MR Analysis also suggested a genetic correlation between hiatal hernia and smoking (ORIVW = 1.47, CI 1.02–2.13, P = 0.0408). However, the same results were not achieved in our retrospective study. In fact, there is still a great controversy about whether smoking is related to the incidence of hiatal hernia [25‐28]. GERD is essentially the reflux of gastric contents to the esophagus. Long-term reflux will lead to acidic damage to the esophageal mucosa, which will cause contraction and shortening of the longitudinal esophageal muscle, thereby inducing the occurrence of hiatal hernia. Kishikawa et al. found that increased gastric acid secretion is an independent risk factor for hiatal hernia, and although this is not direct evidence, it does promote the occurrence of GERD [29]. Our retrospective study, in which GERD was diagnosed by patient symptom scores and endoscopic findings, showed that its occurrence was also an independent risk factor for hiatal hernia. However, these findings do not provide objective clinical evidence of the development of GERD, and it is difficult to say whether hiatal hernias occur before or after GERD. In addition, our study found that engaging in heavy physical labor is also an independent risk factor for hiatal hernia, which may be related to long-term increased intra-abdominal pressure. It is important to note that our definition of heavy physical labor favors activities that involve substantial muscle force, such as carrying, farming, and plowing, rather than large-scale aerobic exercise.
Our study has a number of limitations. In this retrospective study, we did not collect waist circumference and waist–hip ratio, we restricted smoking and alcohol consumption to frequency rather than quantity, and we included a small sample of women with a detailed history of pregnancy, which may bias the results. Endoscopic criteria were used in the diagnosis of hiatal hernia, which may also lead to missed diagnosis in some patients with extreme BMI. In the MR Analysis, our outcome data were for diaphragmatic hernia rather than hiatal hernia, which is not equivalent although 95% of diaphragmatic hernia are hiatal hernia and share many similarities in pathogenesis and clinical manifestations [30]. Furthermore, the small number of SNPs included in our MR analysis limits the robustness of our findings. We also attempted to conduct MR analyses on additional risk factors, such as heavy physical labor, osteoporosis, and kyphosis; however, we were unable to perform these analyses due to the limited number of instrumental variables available.
Conclusion
This study showed that male gender, age, heavy physical labor, and GERD were independent risk factors for hiatal hernia. MR analysis showed that abdominal obesity and smoking may be genetically associated with hiatal hernia. However, there was no statistical significance between increased BMI and hiatal hernia in multivariate analysis and MR analysis.
Acknowledgements
We thank researcher Chaoli Liu for his assistance and suggestions in reviewing the paper.
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Declarations
Disclosures
Hongyi Dong, Xing Du, Jin Zhao, Diangang Liu, and Haijun Du have no conflict of interest or financial ties to disclose.
Ethical approval
A multi-center clinical study on the efficacy and safety of hiatal hernia repair (Reference No. 2024P209702).
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Ob der Nachweis von positiven Schnitträndern nach radikaler Prostatektomie mittelfristig mit einem erhöhten Risiko für biochemische Rezidive und für Metastasen einhergeht, hängt auch von der Ausdehnung des Randbefalls ab.
Für die Therapie von Patientinnen – betroffen sind fast ausschließlich Frauen – mit Lipödem existiert eine Reihe von Optionen, mit einem eindeutigen Favoriten in puncto Effektivität. Ein großes Problem ist jedoch die korrekte Diagnose.
Wenn sich in der Medizin verhängnisvolle Komplikationen oder Fehler ereignen, gibt es neben den betroffenen Patienten oft ein zweites Opfer: die behandelnden Ärztinnen oder Ärzte. Eine dafür besonders anfällige Disziplin ist die Chirurgie.
Ergebnisse einer Metaanalyse sprechen dafür, dass eine adjuvante präoperative Behandlung mit 5-Alpha-Reduktase-Inhibitoren bei Männern mit benigner Prostatahyperplasie zu einem geringeren Blutverlust während einer transurethralen Prostataresektion (TURP) beitragen kann.
