A retrospective observational study: are gallstone patients aging, or are the elderly more susceptible to gallstones?

Abstract

Background

Gallstone disease is a common clinical condition worldwide, with a global incidence ranging from less than 10% to over 40% and affecting approximately 3–11% of the population in China. This high and increasing prevalence places a significant burden on healthcare resources due to the costs associated with diagnosis, treatment, and long-term follow-up. More importantly, gallstones can lead to severe complications, such as acute cholecystitis, cholangitis, and pancreatitis, establishing the disease as a major public health concern. Although traditionally associated with a higher incidence in middle-aged women, the number of elderly patients with gallstones is rising as Chinese society ages. However, large-scale epidemiological studies covering the entire adult age spectrum and explicitly exploring the relationship between age and gallstone incidence remain scarce. Furthermore, while numerous studies have investigated risk factors for gallstone formation, few have examined the dynamic changes in individual-level data before and after stone formation—an approach that could offer more valuable insights for personalized prevention. Therefore, this study aims to address these gaps through a retrospective analysis of 10 years of health examination data, to explore the incidence trend and preventable risk factors for gallstones, and ultimately to provide a basis for improving clinical management and prevention strategies.

Methods

Through the retrospective analysis from January 2012 to December 2021 in Xuanwu Hospital, Capital Medical University physical examination center for health examination related data, select those who have no gallstones on baseline data and receive two or more ultrasound examinations. A total of 37,440 subjects were included in the study, Age (44.48 ± 16.06) (range 16–103 years). Gallstones were confirmed by repeated ultrasound examinations. Then, according to the data before and after the formation of gallstones, the subjects were divided into study group and control group. Rank-sum test and χ2 test were used to analyze the data statistically and explored the risk factors for gallstone formation by Logistic regression analysis. Results: 1401 subjects were confirmed the gallstones, 699 men, 702 women, age (59.57 ± 16.12) years (range: 22–103 years old), and the incidence of gallstones was 3.73%. The incidence of gallstones in the elderly aged 65 years and above was significantly higher than that in the young and middle-aged group below 65 [11.88% (553 / 4653): 2.59% (848 / 32788)], and the difference was statistically significant (χ2 = 3183.17, P < 0.001), the incidence of gallstones in men and women increased with age. The incidence was lower in women than in men before age 30. After age 30, it is more common in female than in male. Multivariate logistic-analysis found statistically significant differences in age, waist circumference, aspartate aminotransferase, fasting blood glucose, triglycerides, and high-density lipoprotein.

Conclusion

The incidence of gallstones in the elderly aged 65 years and above is significantly higher than that in the young and middle-aged people. The incidence of gallstones increases with age, the older the age, the higher the incidence of gallstones, as was seen in both men and women. Age, waist circumference, aspartate aminotransferase and fasting blood glucose are risk factors for gallstone formation, triglycerides and high-density lipoprotein are protective factors for gallstone formation.

Background

Gallstone disease is a common clinical disease, the incidence varies around the world, from less than 10% to more than 40% [1].The incidence rate in China is about 3–11% [2], and it is increasing every year. The diagnosis and treatment and follow-up of a large number of patients with gallstones have increased significant medical burden. Some of patients suffer from complications like acute cholecystitis, secondary acute cholangitis, pancreatitis, gallstone ileus, gall-bladder empyema or perforation, causing gallstone diseases to be a major public health problem. As China enters the aging society, more and more elderly gallstone patients are also encountered in the clinical work, and the increasing incidence of gallstone disease in the elderly deserves further exploration. Previous studies have suggested that gallstones are high incidence in 40-year-old women [3].Many recent studies have not found the curve of the middle-age peak of gallstones, but have found that the incidence of gallstones increases with age in a certain age group [2, 4].However, there have been few large-scale epidemiological studies covering the whole age group to explore the relationship between gallstones and the age of onset. The formation of gallstones is generally considered to be the result of the combination of multiple factors, and many literatures explored the risk factors of gallstone formation. There is no literature studying the data changes of gallstone patients before and after stone formation, which may be more valuable for gallstone prevention in individual population. Therefore, we retrospectively analyzed the 10 years of physical examination data from the physical Examination Center of Xuanwu Hospital of Capital Medical University, in order to explore the incidence regularity and preventable etiology of gallstones, to provide a basis for the diagnosis and treatment and prevention of gallstone.

Methods

Subject investigated

A total of 124,315 individuals (61,375 males and 62,940 females) who underwent medical examinations between January 2012 and December 2021 were initially screened for this retrospective study. The participants ranged in age from 14 to 103 years.

Inclusion criteria were as follows: (1) at least two hepatobiliary ultrasound examinations with an interval greater than 3 months but within 2 years; and (2) no prior diagnosis of gallstones.

Exclusion criteria included: (1)Incomplete research data ; (2) only a single ultrasound examination was excluded to minimize the risk of false-positive diagnoses and to exclude the possibility that patients were in the lithogenic phase of gallstone formation (n = 86,875); and (3) presence of gallstones (included asymptomatic cases) or a history of cholecystectomy at baseline (n = 1,145).

After applying these criteria, a total of 37,440 subjects (17,781 males and 19,659 females), aged 16 to 103 years, were included in the final analysis. The participant selection process is illustrated in Fig. 1. This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki (2000 version) of the World Medical Association. No clinical interventions were involved, and no personally identifiable information was collected; therefore, informed consent was waived. The study protocol was reviewed and ethically approved by the Ethics Committee of Xuanwu Hospital (approval ID: LYS[2021]070).

Fig. 1.

STROBE flow chart of the study cohort

Study design

Based on the ultrasound examination results, a total of 1,401 subjects developed gallstones during the follow-up period and were assigned to the study group. For each of these cases, data from individuals who had no evidence of gallstones at their initial and follow-up physical examinations were matched and assigned to the control group. The study group consisted of 699 males and 702 females, with a mean age of 59.60 ± 16.13 years (range: 20–103 years). The control group also included 699 males and 702 females, with a mean age of 54.06 ± 15.93 years (range: 20–100 years). This retrospective study aimed to investigate the association between age and the development of gallstones in an asymptomatic population undergoing routine health check-ups.

Data collection

Exploratory variables included sex, age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBiL), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and the presence of gallbladder polyps. BMI was calculated as weight in kilograms divided by the square of height in meters (kg/m²). Blood samples were collected in the morning following an 8–12-hour overnight fast. Blood pressure was measured from the upper arm while the participant was seated quietly. Height was measured without shoes, and weight was measured with light clothing. Gallbladder polyps were defined as localized lesions protruding from the gallbladder wall into the lumen, which remained unchanged with changes in body position.

Statistical analysis

Statistical analyses were performed using SPSS software, version 29.0 (IBM Corp., Armonk, NY, USA). Quantitative variables that did not follow a normal distribution were expressed as medians with interquartile ranges (IQRs), while qualitative variables were presented as frequencies and percentages. The Mann–Whitney U test was used to compare continuous variables between groups (Age, BMI, WC, Blood pressure, AST/ALT, FBG, Total cholesterol, Triglyceride and Low-density lipoprotein), and the chi-square (χ²) test was used to compare categorical variables (Age and sex group). Variables that showed statistically significant differences in univariate analyses were subsequently included in a multivariate logistic regression model to identify independent risk factors. A two-sided P value of < 0.05 was considered statistically significant.

Results

Demographic characteristics of the study population

A total of 37,440 individuals who underwent at least two hepatobiliary ultrasonography examinations and had no gallstones at baseline were included in the study. The observation period spanned from January 2012 to December 2021. During this time, 1,401 participants developed gallstones, yielding a cumulative incidence of 3.73%, corresponding to an annual incidence rate of approximately 0.38%. The shortest time to gallstone formation, as detected by follow-up ultrasound, was 5 months. The incidence of gallstones among elderly individuals aged 65 years and older was significantly higher than that among those younger than 65 years [11.88% (553/4,653) vs. 2.59% (848/32,788); χ² = 3183.17, P < 0.001], as shown in Fig. 2a. Subjects were also categorized by age in 10-year intervals. A clear age-related trend in gallstone incidence was observed, with rates increasing progressively with advancing age, as illustrated in Fig. 2b and detailed in Table 1.

Fig. 2.

A Comparison of gallstone incidence before and after the age of 65 years. B Age-related trend in gallstone incidence

Table 1.

The incidence of gallstones by age group and sex (%)

Age group (years)	Male case	Female case	χ2	p value
<20	0 (0/22)	0 (0/30)	/	/
20–29	0.53 (16/3035)	0.32 (15/4679)	1.963	0.161
30–39	1.35 (56/4160)	1.67 (83/4960)	1.614	0.204
40–49	3.00 (104/3469)	3.72 (140/3759)	2.911	0.088
50–59	4.15 (125/3009)	4.98 (162/3253)	2.438	0.118
60–69	8.19 (167/2038)	8.48 (151/1781)	0.10	0.751
70–79	8.92 (114/1278)	9.05 (80/884)	0.011	0.917
80–89	13.23 (95/718)	20.82 (61/293)	9.181	0.002
≥ 90	42.31 (22/52)	50.00 (10/20)	0.346	0.556
Total	3.93 (699/17781)	3.58 (702/19632)	3.17	0.075

The relationship between the incidence of gallstones and sex

The overall incidence of gallstones was 3.93% (699/17,781) in men and 3.57% (702/19,659) in women, with no statistically significant difference between the sexes according to result of chi-square test (P = 0.66). Age-stratified analysis was conducted by grouping participants into 10-year age intervals, with < 20 years and ≥ 90 years each defined as separate groups. In both men and women, the incidence of gallstones increased progressively with advancing age. Notably, among individuals aged 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, and ≥ 90 years, the incidence of gallstones was consistently higher in women than in men, as shown in Table 1; Fig. 3.

Fig. 3.

The incidence of gallstones by age group and sex

Risk factor analysis of the study group and the control group

Significant differences were observed between the study group and the control group in the following variables: age (Z = − 18.216, P < 0.001), waist circumference (Z = − 11.307, P < 0.001), systolic blood pressure (Z = − 6.745, P < 0.001), fasting blood glucose (Z = − 13.858, P < 0.001), aspartate aminotransferase (Z = − 7.030, P < 0.001), alanine aminotransferase (Z = − 2.299, P = 0.022), triglycerides (Z = − 3.115, P = 0.002), and high-density lipoprotein (Z = − 11.486, P < 0.001). No statistically significant differences were found between the groups in terms of sex, BMI, diastolic blood pressure, total bilirubin, total cholesterol, low-density lipoprotein, or gallbladder polyps (P > 0.05).

Variables included in the multivariate logistic regression analysis were age, waist circumference, systolic blood pressure, aspartate aminotransferase, alanine aminotransferase, fasting blood glucose, triglycerides, and high-density lipoprotein. Compared with the control group, the study group showed statistically significant associations with age, waist circumference, aspartate aminotransferase, fasting blood glucose, triglycerides, and high-density lipoprotein (P < 0.05). No significant associations were found for systolic blood pressure or alanine aminotransferase (P > 0.05), as shown in Table 3.

Table 3.

Multivariate logistic-analysis (n = 1,401)

Characteristics	B	standard error	Wald	OR and 95% Cl	P value
Age (one group per 10 years)	0.452	0.019	543.576	1.572(1.513, 1.633)	<0.001
WC (85 cm ratio: 85 cm)	0.520	0.064	66.052	1.682(1.484, 1.906)	<0.001
SBP (≥ 140 mmHg:<140 mmHg)	0.015	0.067	0.048	1.015(0.890, 1.158)	0.826
AST (> 40 U/L: ≤40 U/L)	0.408	0.166	6.035	1.503(1.086, 2.082)	0.014
ALT (> 40 U/L: ≤40 U/L)	0.038	0.121	0.101	1.039(0.821, 1.316)	0.750
FBG (> 6.1 mmol/L: ≤6.1 mmol/L)	0.442	0.070	40.286	1.556(1.358, 1.784)	<0.001
TG (≥ 1.7mmol/L: <1.7 mmol/L)	-0.248	0.066	14.091	0.780(0.685, 0.888)	<0.001
HDL (≥ 1.55 mmol/L :<1.55 mmol/L)	-0.581	0.067	76.320	0.559(0.491, 0.637)	<0.001

Discussion

The formation of gallstones is widely recognized as a multifactorial process, and numerous studies have explored their incidence and associated risk factors. Unlike many previous reports, this study, based on large-scale epidemiological data, demonstrated that the incidence of gallstones increases steadily with age in both men and women. The previously reported peak incidence at 40 years of age is no longer applicable; rather, gallstone disease now exhibits a distinct trend of aging. Evidence suggests that a significant proportion of symptomatic gallstone cases may be preventable through healthy lifestyle interventions, including a balanced diet, abstinence from smoking, moderate alcohol consumption, regular coffee intake, routine physical activity, and weight management [5]. However, among individuals living in the same geographic area and sharing similar dietary patterns, only a subset develops gallstones. This raises the question: What distinguishes gallstone patients from others? It is therefore essential to compare clinical data before and after gallstone formation in order to identify key risk factors and develop effective prevention strategies.

The relationship between age and gallstone

Several studies have reported a strong association between age and gallstone formation. A study from Taipei identified age as a significant risk factor [6], and Colvin et al. corroborated this finding [7]. Shabanzadeh et al. reported a linear increase in gallstone incidence among individuals aged 30–60 years [1]. Similarly, Zhang et al. analyzed data from 318,403 individuals in southwestern China and found a linear increase in gallstone prevalence with age up to 90 years, followed by a declining trend thereafter [2]. However, a report from JAMA noted that gallstone prevalence could reach as high as 80% in individuals over 90 years of age residing in long-term care facilities [8], indicating variability across different populations and settings. Previous studies by Xu Li and Pujun Gao also identified older age as a significant risk factor for gallstone disease, with a concurrent increase in both gallstones and fatty liver prevalence with advancing age [9]. In our prior analysis based on data from the physical examination center, we similarly found that gallstone incidence increased with age across both sexes. Notably, in contrast to Zhang et al., our study did not observe a decline in incidence in individuals over 90 years of age [10]. In the present study, age was confirmed as a significant risk factor for gallstone formation in both univariate and multivariate analyses (see Tables 2 and 3). The incidence of gallstones showed a clear upward trend with increasing age, further supporting the notion that gallstone disease is progressively aging-related. Festi et al. have also emphasized that increasing age and BMI are definitive risk factors for gallstone disease [11]. These findings collectively underscore the critical role of age in the development of gallstones.

Table 2.

Univariate risk analysis (n = 1,401)

		study group	control group	Z/χ²	p value
Sex (%)	Male	699(49.89)	702(50.11)	0.000	1.000
	Female	702(50.11)	699(49.89)
Age (year)		60(47,71)	54(42,64)	-18.216	<0.001
BMI (kg/m2)		25.22(23.06,27.78)	25.28(23.07,27.73)	-0.757	0.449
WC (cm)		87(80,94)	84(77,91)	-11.307	<0.001
SBP (mmHg)		131(119,144)	127(116,140)	-6.745	<0.001
DBP (mmHg)		78(70,85)	77(69,85.75)	-1.228	0.219
FBG (mmol / L)		5.46(5.03,6.22)	5.25(4.87,5.76)	-13.858	<0.001
AST (U/L)		22(19,26)	20(17,25)	-7.030	<0.001
ALT (U/L)		19(14,27)	18(13,26)	-2.299	0.022
Total bilirubin		13.05(10.25,17.59)	12.12(9.68,15.74)	-1.819	0.069
Total cholesterol (mmol/L)		4.80(4.14,5.44)	4.83(4.29,5.46)	-0.920	0.357
Triglyceride (mmol/L)		1.26(0.90,1.83)	1.33(0.93,1.88)	-3.115	0.002
Low-density lipoprotein (mmol/L)		2.85(2.30,3.42)	2.90(2.35,3.47)	-1.133	0.257
High-density lipoprotein (mmol/L)		1.34(1.12,1.62)	1.48(1.26,1.73)	-11.486	<0.001
cholecystic polypus (%)	polyps	221(51.8)	206(48.2)	0.622	0.43
	no polyps	1180(49.7)	1195(50.3)

The incidence of gallstones increases with age, and advancing age is recognized as a major risk factor for gallstone formation. This association may be attributed to age-related changes in the gallbladder and biliary tract, including both morphological and functional degeneration. Animal studies have demonstrated that aging is linked to increased cholesterol gallstone formation due to multiple physiological changes: enhanced bile secretion, increased intestinal absorption of cholesterol, reduced hepatic synthesis and secretion of bile salts, and diminished gallbladder motility [12]. With increasing age, a reduced rate of the cholesterol 7α-hydroxylase reaction and increased activity of HMG-CoA reductase have been observed, leading to decreased bile acid synthesis, increased biliary cholesterol production, and elevated cholesterol saturation, all of which favor cholesterol crystallization and stone formation [13]. In addition, liver function tends to decline with age, accompanied by reduced detoxification capacity, slower hepatic regeneration, and decreased drug clearance. For instance, ceftriaxone can bind to calcium ions in bile and form reversible precipitates, which may crystallize and lead to gallstone formation in elderly patients [14]. Another plausible explanation for the higher prevalence of gallstones among older individuals is the increased incidence of metabolic syndrome with age, which has been identified as a contributing risk factor for gallstone disease [15]. Gallstone disease is a chronic condition, and thus, its prevalence naturally rises over time. Furthermore, with advancing age, individuals are more likely to accumulate multiple risk factors simultaneously, thereby increasing the likelihood of gallstone formation [16]. Collectively, these physiological, metabolic, and pharmacological factors contribute to the elevated risk and higher incidence of gallstones observed in the elderly population.

Other risk factors for gallstones

Sex: Sex-related differences in gallstone prevalence have been reported to vary across geographic regions and ethnic groups. Numerous studies have suggested that women have a higher risk of developing gallstones compared to men. In Western populations, estrogen is considered a key contributing factor, as it has been shown to reduce gallbladder contractility and increase bile cholesterol concentration, thereby promoting cholesterol stone formation [17]. Cholesterol stones are the predominant type in Western countries. Jones et al. reported that women of reproductive age using estrogen-containing oral contraceptives have a two-fold increased risk of developing gallstones [18]. A study from South Africa also highlighted the influence of reproductive hormones on bile lithogenicity in both sexes, though the exact sex-related differences in gallstone incidence remain only partially understood [19]. In contrast, several studies conducted in Asian populations have not found a consistent sex-related difference in gallstone prevalence [20]. For example, Chen et al. reported no significant sex difference in gallstone prevalence in Taiwan [21]. while Li-Ying Chen et al. found a higher incidence in men than in women [22]. Wang et al., in a large-scale study involving over 2 million individuals from the Meinian Health Center in China, also observed a higher incidence of gallstones in men compared to women [4]. Additionally, a study on elderly patients with non-alcoholic fatty liver disease (NAFLD) revealed a greater prevalence of gallstones among male patients, further suggesting that sex may not be a dominant risk factor in certain populations [23]. Furthermore, literature indicates that sex-based differences in gallstone incidence tend to diminish with advancing age [24].

In our multivariate analysis, gender was not an independent risk factor for gallstones. However, as shown in our figures, a higher proportion of elderly patients with gallstones were female. This observation may be attributed to several factors. First, postmenopausal physiological changes in women, including alterations in hepatic metabolism, gastrointestinal motility, hormonal levels (notably estrogen decline), and lipid metabolism, may collectively contribute to an increased risk of gallstone formation in aging females. These mechanisms have been implicated in previous studies linking menopause and age-related hormonal shifts to gallstone pathogenesis [25]. Second, the higher proportion of elderly women in our cohort may reflect gender differences in life expectancy, as women tend to live longer than men globally. Consequently, in the older age groups, females naturally constitute a larger share of the population, which may partly explain the observed age-gender pattern in gallstone incidence.

Metastatic enzymes: Previous research has indicated that elevated serum ALT levels may serve as a predictor for gallstone disease due to transient biliary obstruction, which can lead to increased bile duct pressure and secondary hepatocellular injury [26]. However, in our study, AST rather than ALT was identified as a significant risk factor for gallstone formation. This discrepancy may be attributed to differences in study populations and sample characteristics.

Blood pressure: Zhang et al. analyzed large-scale population data and demonstrated a significant association between hypertension and the risk of gallstone disease, with a dose-response relationship—the higher the blood pressure, the greater the risk [2]. Similarly, Kazuya Higashizono et al. reported that hypertension may contribute to an increased risk of cholelithiasis [27]. In our study, systolic blood pressure (SBP) was significantly associated with gallstone formation in univariate analysis but lost statistical significance in multivariate logistic regression, suggesting potential confounding factors.

Waist circumference and body mass index: Waist circumference is a marker of central obesity and may be more predictive of gallstone risk than BMI alone. Stokes reported that weight gain is an established risk factor, with increased BMI being causally linked to symptomatic gallstone disease [28]. Liu et al. suggested that a model combining waist circumference and BMI provides better predictive accuracy for new-onset gallstones [29]. Parra-Landazury et al. further emphasized that central obesity, through mechanisms involving insulin resistance and increased hepatic cholesterol secretion, plays a central role in gallstone pathogenesis [30]. A study focusing on cholecystectomy also found waist circumference to be more strongly associated with gallstone risk than BMI, particularly in women [31]. In our study, BMI was not significantly associated with gallstone formation, while waist circumference emerged as a more robust predictor, indicating that central obesity is a key risk factor.

Blood glucose: Several studies have shown that elevated fasting blood glucose is associated with gallstone disease. THT et al. reported a close relationship between fasting glucose and gallstone formation [32]. and Yuan et al. identified type 2 diabetes as an independent causal factor [33]. Wang et al. observed that elevated fasting glucose and HbA1c levels were associated with an increased risk of gallstones in patients with type 2 diabetes [34]. Possible mechanisms include impaired gallbladder motility, inhibition of bile secretion, altered nucleation of cholesterol crystals, and increased mucin secretion in bile under hyperglycemic conditions [35]. Consistent with these findings, our study identified elevated fasting blood glucose as a significant risk factor for gallstone formation.

Blood lipids: Wang J et al. reported that elevated triglycerides, total cholesterol (TC), low-density lipoprotein (LDL), and apolipoprotein levels were associated with an increased risk of gallstone formation, while high-density lipoprotein (HDL) was identified as a protective factor [4]. Similarly, Hung MC et al. found a strong association between lower HDL-C levels, elevated triglycerides, and the risk of gallstone disease. Hyperlipidemia contributes to cholesterol supersaturation in bile, thereby promoting gallstone formation [23]. The mechanisms underlying this association may involve enhanced activity of HMG-CoA reductase, cholesterol supersaturation, and decreased gallbladder sensitivity to cholecystokinin, resulting in impaired contractility [36]. However, Zhang M, through multivariate logistic regression, found no significant association between TC, triglycerides, and gallstone risk in patients from Tianjin Medical University Cancer Institute and Hospital. A meta-analysis subgroup analysis showed that triglyceride levels were positively associated with gallstone risk in women but not in men [37]. Kim et al. also noted that hypertriglyceridemia was a risk factor for asymptomatic cholelithiasis only in women. The lack of association in men may relate to higher alcohol consumption and a greater prevalence of alcohol-induced hypertriglyceridemia in Korean men [36]. Moreover, Yuan et al. suggested that genetically predicted lipid profiles were not causally related to gallstone disease, although their sample was primarily European (> 90%), and whether these findings are applicable to Asian populations requires further investigation [38]. A study from Shanghai, using univariate analysis, even found that elevated triglyceride levels were associated with a reduced risk of gallstone disease [39]. In our study, total cholesterol and LDL were not significantly associated with gallstone formation. Interestingly, both triglycerides and HDL levels showed a negative correlation with gallstone formation. The inverse association with triglycerides contradicts several previous findings. One possible explanation is that dietary fat intake may promote gallbladder contraction and reduce stone formation, although this hypothesis requires further investigation and validation with additional data.

Gallbladder polyps: Shabanzadeh DM et al., in a cohort study and meta-analysis, identified gallbladder polyps as an independent predictor of gallstone formation [1]. Gareth Morris-Stiff et al. similarly reported that gallbladder polyps are a risk factor for asymptomatic gallstones [40]. However, our study did not find a statistically significant association between gallbladder polyps and gallstone formation.

Although the study population was randomly selected from individuals across various industries and age groups who attended a hospital-based health screening center, several limitations exist. First, only 9.72% of the study participants were aged ≥ 65 years, yet they accounted for 31.97% of gallstone cases, potentially limiting the representativeness of the sample. Second, reproductive factors such as the number of pregnancies and estrogen use were not collected for female participants. Third, some participants may have been taking long-term medications such as hypoglycemic agents, lipid-lowering drugs, or antihypertensives, which could have influenced biochemical markers. Fourth, the before-and-after analysis of gallstone formation in individuals was not conducted using a randomized or parallel-controlled design, which may affect the strength of the conclusions.

For elderly patients aged ≥ 80 years with gallstones, the optimal timing of surgery remains controversial. While early laparoscopic cholecystectomy (defined as surgery within 7 days of symptom onset) has been shown to reduce hospital stay and prevent emergency complications, multiple studies have highlighted increased surgical difficulty, higher conversion rates, and greater perioperative risks in octogenarians. A single-center study from Colombia found that age over 90 years (RR 4.6 CI95% 1.07–20.13), presence of cholecystitis (RR 8.2 CI95% 1.29–51.81), and time from admission to cholecystectomy (RR 1.2 CI95% 1.10–1.40) were the variables that presented statistically significant differences as risk factors for mortality [41]. This result suggested that nonagenarian patients have a higher rate of complications, conversion rate, subtotal cholecystectomy rate, and mortality.

In contrast, for frail elderly patients, delayed elective laparoscopic cholecystectomy after preoperative optimization of nutrition and comorbidities has been associated with significantly lower 30-day and 2-year mortality rates. A study of patients aged ≥ 80 years identified ASA class III–IV as an independent predictor of reduced 2-year survival (HR = 2.71, 95% CI: 1.20–6.14). In these patients, the safety of elective surgery outweighed the short-term benefits of Early LC, suggesting that early surgery may compromise long-term outcomes [40]. For nonagenarian patients (≥ 90 years old), perioperative risk increases markedly. Studies show that laparoscopic cholecystectomy in this age group carries a mortality rate of up to 6.8%, with substantially elevated rates of complications and conversion (RR = 4.6, 95% CI: 1.07–20.13). Moreover, “time from admission to surgery” is a significant predictor of mortality (RR = 1.2 per day, 95% CI: 1.10–1.40) [42]. As a result, it is recommending comprehensive multidisciplinary preoperative assessments in this population, with optimization of cardiopulmonary function and correction of malnutrition. When possible, delayed elective surgery or percutaneous transhepatic gallbladder drainage should be prioritized to balance safety with adequate disease control. Elective LC after stabilization of chronic inflammation has been shown to reduce mortality and complications compared to acute surgery, while preserving therapeutic efficacy .

There are several limitations to our study. First, the sample size of nonagenarians was relatively small, which may have introduced bias in estimating the incidence in this age group. Second, certain known risk factors for gallstones—such as parity and estrogen use—were not included in the analysis, potentially leading to residual confounding, particularly among female participants. However, given the influence of the national family planning policy, the impact of these factors on the overall results is likely to be limited.

Our findings suggest that the incidence of gallstones increases with age, showing a clear aging trend, with no significant sex difference. Greater attention should be given to gallstone prevention and management in the elderly. Age, central obesity (waist circumference), liver dysfunction, elevated blood glucose, and altered lipid profiles were associated with increased risk. Since intrinsic factors such as age, sex, and genetics cannot be modified, preventive strategies should focus on modifiable lifestyle factors including regular physical activity, a healthy diet, glycemic and lipid control, and weight management to reduce the risk of gallstone formation. We also found that, among patients who developed gallstones during follow-up, a higher proportion exhibited sonographic findings such as biliary sludge, gallbladder polyps, gallbladder atrophy, and morphological deformities (e.g., gourd-shaped or tubular gallbladder) prior to stone formation. These features may represent imaging manifestations of the lithogenic process and warrant further in-depth investigation.

Conclusions

The incidence of gallstones in the elderly aged 65 years and above is significantly higher than that in the young and middle-aged people. The incidence of gallstones increases with age, the older the age, the higher the incidence of gallstones, as was seen in both men and women. Age, waist circumference, aspartate aminotransferase and fasting blood glucose are risk factors for gallstone formation, triglycerides and high-density lipoprotein are protective factors for gallstone formation.

Abbreviations

BMI

Body mass index

WC

Waist circumference

SBP

Systolic blood pressure

DBP

Diastolic blood pressure

FBG

Fasting blood glucose

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

TBiL

Total bilirubin

TC

Total cholesterol

TG

Triglycerides

LDL-C

Low-density lipoprotein cholesterol

HDL-C

High-density lipoprotein cholesterol

IQRs

Interquartile ranges

NAFLD

Non-alcoholic fatty liver disease

Authors’ contributions

Dr. Liguo Gu and Dr. Jie Cai wrote the main manuscript text and prepared all tables and figures .Dr. Fangzhou Wang made a significant contribution during the revision stage, including manuscript editing and visualization, Dr. Yue Huang, Dr. Zhen Zhou and Dr. Xiang Gao finished modification and data analysis.Corresponding author Yamin Zheng was responsible for the conceptualization and design of the study; project coordination and administration; and supervision, review, editing, and final approval of the manuscript.All authors reviewed the manuscript.

Funding

Not applicable.

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

Declarations

Ethics approval and consent to participate

This study was reviewed and approved by the Ethics Committee of Xuanwu Hospital (approval ID: LYS[2021]070).All procedures performed in this study involving human participants were in accordance with the ethical standards of this institutional research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.