The association between life’s essential 8 and gallstones: A cross-sectional study

Abstract

This study investigates the relationship between Life’s Essential 8 (LE8), a measure of cardiovascular health (CVH), and the risk of gallstones in adult Americans. We analyzed data from 5,024 participants aged 20 and older, using information from the 2017–2020 National Health and Nutrition Examination Survey. Gallstone presence was determined via a standard questionnaire. LE8 scores, representing four health behaviors (sleep, tobacco/nicotine exposure, physical activity, and diet) and four health factors (body mass index, non-high-density lipoprotein cholesterol, blood glucose, and blood pressure), were categorized into low, moderate, and high CVH groups. Weighted logistic regression, restricted cubic splines (RCS), and stratified analyses were used to assess the association between LE8 and gallstones. Of the 5,024 participants, 543 (11.22%) had gallstones. In fully adjusted models, participants with high CVH (LE8 ≥ 80) had a 59% lower risk of gallstones compared to those with low CVH (LE8 < 50) (OR: 0.41, 95% CI: 0.23–0.72, P = 0.010). RCS analyses suggested a nonlinear relationship between LE8 and gallstones. Stratified analysis showed a stronger association in participants under 65 (OR: 0.26, 95% CI: 0.15–0.44), females (OR: 0.44, 95% CI: 0.24–0.81), those with higher education (OR: 0.39, 95% CI: 0.19–0.78), non-white individuals (OR: 0.28, 95% CI: 0.13–0.60), and married participants (OR: 0.40, 95% CI: 0.20–0.80).

Higher CVH, as measured by LE8, is associated with a lower risk of gallstones among adult Americans.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-89024-x.

Introduction

Gallstones are a common digestive disorder worldwide and a leading cause of hospital admissions, imposing significant health and economic burdens^1,2. In the United States, over 800,000 cholecystectomies are performed annually, with approximately $62 billion spent each year on prevention and treatment^3–7. While many patients with gallstones remain asymptomatic, 3–8% may experience severe complications, including acute cholecystitis, gallstone ileus, pancreatitis, sepsis, or gallbladder perforation. Furthermore, gallstones significantly increase the risk of gallbladder cancer^8–10. Given these factors, gallstones are considered a major global public health issue.

In 2010, the American Heart Association (AHA) introduced the concept of cardiovascular health (CVH) to shift the focus from disease treatment to promoting and maintaining health throughout life. CVH is defined by seven key health behaviors and factors, including smoking, physical activity, obesity, diet, total cholesterol, blood pressure, and blood glucose, collectively known as “Life’s Simple 7 (LS7)”^11,12. In 2022, the AHA expanded this model to “Life’s Essential 8 (LE8)”, adding sleep as an eighth factor to better assess and manage CVH¹³. LE8 evaluates overall health by measuring healthy diet, physical activity, nicotine avoidance, sleep, healthy weight, and maintaining healthy levels of blood lipids, blood glucose, and blood pressure. This comprehensive measure has been validated as an effective tool for monitoring public health and developing primary prevention strategies to improve cardiovascular outcomes¹⁴.

Although previous studies have shown that gallstone disease is an independent risk factor for cardiovascular disease, there has been no research examining whether CVH affects gallstone development. This study aims to investigate the relationship between CVH, as assessed by LE8, and the risk of gallstones in adults.

Methods

This study utilized data from the National Health and Nutrition Examination Survey (NHANES), a program designed to evaluate the health and nutritional status of adults and children in the United States. Conducted by the National Center for Health Statistics (NCHS), part of the Centers for Disease Control and Prevention (CDC), NHANES follows a strict protocol approved by the NCHS Institutional Review Board, with all participants providing written informed consent.

We obtained survey data from the NHANES website for the period 2017 to 2020, which included demographic information, dietary habits, physical examination results, laboratory data, and questionnaire responses. The survey involved a total of 15,560 participants.

For this study, we excluded 6,328 participants due to missing data on gallstone history. Additionally, we excluded 268 participants with unknown education status, 2 participants with unknown marital status, and 479 participants with missing data on the family poverty income ratio (PIR). After these exclusions, 5,024 participants remained in the analysis, of whom 534 reported a history of gallstones (Fig. 1).

Fig. 1.

The flowchart of screening participants.

Definition of gallstones

Gallstone presence was identified through participants’ responses to the question, “Has a doctor ever told you that you have gallstones?” Participants who answered “Yes” were categorized as having gallstones, while those who answered “No” were categorized as not having gallstones.

Life’s essential 8

CVH was assessed using LE8, which includes four health behaviors (sleep, tobacco/nicotine exposure, physical activity, and diet) and four health factors (body mass index [BMI], non-high-density lipoprotein cholesterol [non-HDL], blood glucose, and blood pressure). The diet component was assessed using the Dietary Approaches to Stop Hypertension (DASH) score (Supplementary Table 1). Data on physical activity, tobacco/nicotine exposure, sleep, and medication use were self-reported, while standardized protocols were followed to measure height, weight, blood glucose, and blood pressure at mobile health centers. BMI was calculated as weight in kilograms divided by height in meters squared. Mean blood pressure was calculated from all available readings, and blood samples were analyzed at central laboratories for fasting glucose, non-HDL cholesterol, and glycated hemoglobin. Supplementary Table 2 provides detailed descriptions and scoring methods for each LE8 component^13–16. LE8 scores range from 0 to 100, with overall scores representing the average of the eight components. According to AHA guidelines, LE8 scores of 80–100, 50–79, and 0–49 correspond to high, moderate, and low CVH, respectively.

Covariates

Covariates included in the analysis were age, gender, race/ethnicity, marital status, education level, and family PIR. Race/ethnicity was categorized as Mexican American, other Hispanic, non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, or other race. Education level was classified as less than high school, high school graduate, or college and above.

Statistical analysis

All statistical analyses accounted for the complex, multi-stage, stratified probability sampling design of NHANES, following NHANES guidelines for including sample weights, clustering, and stratification. Continuous variables were presented as survey-weighted means with 95% confidence intervals (CI), and categorical variables as survey-weighted percentages with 95% CI. Three weighted logistic regression models were constructed to examine the relationship between LE8 and gallstones: Model 1 (unadjusted), Model 2 (adjusted for gender, age, and race/ethnicity), and Model 3 (adjusted for gender, age, race/ethnicity, education level, PIR, and marital status). Restricted cubic spline (RCS) regression was used to investigate nonlinear relationships between LE8, health behaviors, health factors, and gallstones. Stratified analyses were performed by gender, age (< 65 or ≥ 65 years), race/ethnicity, education level, marital status, and PIR (< 1.3, 1.3 to < 3.5, and ≥ 3.5). Interaction p-values were calculated by adding multiplicative interaction terms between LE8 and each covariate.

All statistical analyses were performed using R version 4.3.1 and EmpowerStats version 4.0, with significance set at p < 0.05.

Results

Baseline characteristics of study participants

Table 1 summarizes the baseline characteristics of the participants. The mean age was 48.74 years, with 52.30% female and 65.15% non-Hispanic white. Of the 5,024 participants, 543 (11.22%) had gallstones. In terms of CVH, 10.81% had low CVH (LE8 < 50), 65.74% had moderate CVH (50 ≤ LE8 < 80), and 23.45% had high CVH (LE8 ≥ 80). Participants with gallstones were more likely to be female, older, non-Hispanic white, have a lower PIR, and lower scores on health behaviors, health factors, and overall LE8.

Table 1.

Population demographics and clinical characteristics stratified by gallstones.

Characteristics	Total	No gallstones	Gallstones	P value
Number of patients, N	5024	4481	543
Age(years), Mean(95%CI)	48.74 (47.40 ,50.08)	47.63 (46.24 ,49.02)	57.50 (56.02 ,58.99)	< 0.001
PIR, Mean(95%CI)	3.19 (3.09 ,3.30)	3.22 (3.11 ,3.34)	2.95 (2.80 ,3.10)	0.003
Gender, N(%)				< 0.001
Male	2404 (47.70)	50.28 (48.31 ,52.25)	27.29 (22.02 ,33.27)
Female	2620 (52.30)	49.72 (47.75 ,51.69)	72.71 (66.73 ,77.98)
Race/ethnicity, N(%)				< 0.001
Mexican American	565 (7.80)	7.89 (5.83 ,10.59)	7.08 (5.09 ,9.77)
Other Hispanic	483 (7.25)	7.39 (5.81 ,9.35)	6.13 (4.16 ,8.94)
Non-Hispanic White	1937 (65.15)	64.37 (58.44 ,69.89)	71.29 (65.77 ,76.24)
Non-Hispanic Black	1293 (10.50)	10.97 (8.33 ,14.32)	6.76 (4.79 ,9.47)
Non-Hispanic Asian	502 (5.18)	5.61 (4.21 ,7.44)	1.80 (0.88 ,3.64)
Other Race - Including Multi-Racial	244 (4.13)	3.77 (3.04 ,4.67)	6.93 (3.43 ,13.52)
Education, N(%)				0.035
Less than high school	752 (8.97)	15.28 (12.32 ,18.80)	13.21 (10.56 ,16.41)
High school or equivalent	1158 (26.62)	64.37 (58.44 ,69.89)	71.29 (65.77 ,76.24)
College or above	3114 (64.42)	20.35 (16.61 ,24.69)	15.49 (10.64 ,22.02)
Marital, N(%)				0.006
Married	2983 (63.72)	63.64 (60.89 ,66.31)	64.29 (55.93 ,71.86)
Widowed/Divorced/Separated	1123 (18.21)	17.51 (15.85 ,19.30)	23.72 (18.95 ,29.27)
Never married	918 (18.08)	18.85 (16.82 ,21.06)	11.98 (7.82 ,17.94)
AHA LE8 score, Mean (95%CI)
LE8 score	68.13 (67.16 ,69.09)	68.81 (67.91 ,69.72)	62.70 (60.67 ,64.73)	< 0.001
Health behaviors score	69.30 (67.95 ,70.65)	69.67 (68.34 ,70.99)	66.41 (63.79 ,69.04)	0.012
HEI-2015 diet score	43.60 (41.25 ,45.95)	43.54 (41.09 ,45.99)	44.09 (39.98 ,48.19)	0.797
Sleep health score	84.19 (82.83 ,85.54)	84.24 (82.87 ,85.61)	83.78 (80.21 ,87.34)	0.801
Tobacco/nicotine exposure score	75.31 (73.31 ,77.31)	75.55 (73.39 ,77.72)	73.37 (69.14 ,77.60)	0.373
Physical activity score	74.11 (72.36 ,75.85)	75.34 (73.62 ,77.05)	64.41 (59.21 ,69.62)	< 0.001
Health factors score	66.95 (65.85 ,68.05)	67.96 (66.89 ,69.03)	58.99 (56.66 ,61.33)	< 0.001
Blood pressure score	67.70 (66.25 ,69.15)	68.71 (67.17 ,70.25)	59.68 (56.42 ,62.93)	< 0.001
Blood glucose score	76.16 (75.20 ,77.12)	77.16 (76.13 ,78.20)	68.24 (64.68 ,71.81)	< 0.001
Blood lipid score	68.03 (66.02 ,70.04)	68.35 (66.22 ,70.48)	65.47 (61.78 ,69.16)	0.160
Body mass index score	55.92 (54.13 ,57.71)	57.60 (55.80 ,59.41)	42.59 (38.45 ,46.73)	< 0.001
CVH, N(%)				< 0.001
Low	10.81 (9.68 ,12.06)	9.94 (8.89 ,11.10)	17.68 (13.61 ,22.66)
Moderate	65.74 (63.30 ,68.10)	65.16 (62.76 ,67.48)	70.34 (64.40 ,75.67)
High	23.45 (20.81 ,26.31)	24.90 (22.31 ,27.68)	11.97 (7.84 ,17.86)
Health behaviors score, N(%)				0.019
Low	15.73 (13.83 ,17.84)	15.42 (13.53 ,17.52)	18.23 (13.94 ,23.48)
Moderate	48.52 (46.20 ,50.85)	47.96 (45.46 ,50.47)	52.96 (48.34 ,57.53)
High	35.74 (32.46 ,39.16)	36.62 (33.24 ,40.14)	28.81 (23.06 ,35.33)
Health factors score, N(%)				< 0.001
Low	20.34 (18.66 ,22.13)	18.78 (17.08 ,20.60)	32.68 (28.61 ,37.02)
Moderate	49.43 (46.47 ,52.38)	48.97 (45.92 ,52.03)	53.04 (46.68 ,59.30)
High	30.24 (27.28 ,33.36)	32.25 (29.14 ,35.53)	14.28 (9.70 ,20.55)

For continuous variables: survey-weighted mean (95% CI).

For categorical variables: survey-weighted percentage (95% CI).

CVH, cardiovascular health; LE8, Life’s Essential 8; AHA, American Heart Association; HEI, Healthy Eating Index; CI, confidence interval; PIR, family poverty income ratio.

Association between LE8 and gallstones

As shown in Table 2, three models were used to assess the association between LE8 and gallstones, adjusting for various confounders. In Model 3, after adjusting for age, gender, race/ethnicity, education level, marital status, and PIR, participants with high CVH (LE8 ≥ 80) had a 59% lower risk of gallstones compared to those with low CVH (LE8 < 50) (OR: 0.41, 95% CI: 0.23–0.72, P = 0.010). Similarly, participants with high health factor scores (LE8 ≥ 80) had a significantly lower risk of gallstones (OR: 0.38, 95% CI: 0.27–0.54, P < 0.001). However, the association between health behavior scores and gallstones was weaker, with the high health behavior group showing an OR of 0.79 (95% CI: 0.52–1.21) compared to the low group. RCS analysis further highlighted significant associations between LE8, health factors, and health behaviors with gallstones (Fig. 2). Notably, a nonlinear relationship was observed between LE8 and health factors with gallstones, while a linear relationship was found between health behaviors and gallstones.

Table 2.

The weighted logistic regression analysis model demonstrated the correlation between the use of LE8 assessment for CVH and gallstones.

	Model 1		Model 2		Model 3
	OR (95% CI)	P value	OR (95% CI)	P value	OR (95% CI)	P value
LE8 score
Low(< 50)	Ref		Ref		Ref
Moderate(50–79)	0.61 (0.45, 0.82)	0.004	0.72 (0.53, 0.99)	0.060	0.76 (0.56, 1.04)	0.117
High(≥ 80)	0.27 (0.17, 0.43)	< 0.001	0.37 (0.22, 0.62)	0.002	0.41 (0.23, 0.72)	0.010
P for trend		< 0.001		< 0.001		0.006
Health behaviors score
Low(< 50)	Ref		Ref		Ref
Moderate(50–79)	0.93 (0.71, 1.23)	0.632	1.00 (0.76, 1.32)	0.978	1.10 (0.83, 1.47)	0.522
High(≥ 80)	0.67 (0.45, 0.98)	0.051	0.69 (0.46, 1.02)	0.081	0.79 (0.52, 1.21)	0.306
P for trend		0.028		0.037		0.178
Health factors score
Low(< 50)	Ref		Ref		Ref
Moderate(50–79)	0.62 (0.50, 0.77)	< 0.001	0.75 (0.60, 0.93)	0.021	0.76 (0.62, 0.95)	0.031
High(≥ 80)	0.25 (0.17, 0.38)	< 0.001	0.36 (0.25, 0.51)	< 0.001	0.38 (0.27, 0.54)	< 0.001
P for trend		< 0.001		< 0.001		< 0.001

Model 1: Unadjusted model.

Model 2: Adjusted for age, race/ethnicity and gender.

Model 3: Additionally adjusted for age, gender, race/ethnicity, PIR, education level, and marital status.

CVH, cardiovascular health; LE8, Life’s Essential 8; OR, adjusted odds ratio; CI, confidence interval and Ref, reference.

Fig. 2.

The association between LE8 score, health behavior score, and health factor score with gallstones. Restricted cubic splines demonstrated the nonlinear relationship between adjusted age, gender, race/ethnicity, PIR, education level, and marital status with LE8 score, health behavior score, and health factor score, after adjustment.

Stratification analysis

We conducted stratified analyses by age, gender, race/ethnicity, education level, marital status, and PIR to explore the association between LE8 and gallstones (Supplementary Table 3). The association was stronger in participants under 65 years (OR: 0.26; 95% CI: 0.15–0.44), females (OR: 0.44; 95% CI: 0.24–0.81), those with a college education or higher (OR: 0.39; 95% CI: 0.19–0.78), non-white individuals (OR: 0.28; 95% CI: 0.13–0.60), and married participants (OR: 0.40; 95% CI: 0.20–0.80). No significant interactions were observed between age, gender, race/ethnicity, marital status, or PIR with LE8 scores, though a significant interaction was noted between education level and LE8.

Discussion

This study, based on a nationally representative sample of American adults, aimed to explore the association between LE8 scores and gallstones. The results indicated that higher LE8 scores were linked to a lower risk of gallstones in the U.S. adult population. Stratified analysis further revealed that this association was stronger in individuals under 65 years of age, females, non-white participants, married individuals, and those with higher education levels. Additionally, the study found that the relationship between health factors and gallstones was more consistent than that between health behaviors and gallstones.

While previous research has examined the relationship between gallstones and overall mortality, cardiovascular disease mortality^17,18, and certain cancers^19–21, few studies have investigated how CVH levels affect gallstone risk. Unlike the earlier LS7, LE8 incorporates sleep as a key health factor and uses an optimized algorithm to provide a more comprehensive assessment of CVH. This improvement allows for a more accurate understanding of individual health differences. Our study is the first to investigate the association between CVH, as measured by LE8, and gallstones, offering new insights for evaluating CVH and developing strategies to prevent gallstones.

The analysis showed a significant negative association between LE8 scores and gallstones, with health factor subcomponents also demonstrating a strong link to gallstones. LE8 scores and health behavior scores exhibited a nonlinear relationship with gallstones, while health factor scores showed a negative linear relationship with gallstones. Specifically, when LE8 scores exceeded 65.3, the risk of gallstones decreased significantly. In contrast, the association between health behaviors and gallstones remained stable at lower levels, showing a decline only after a specific threshold was reached. This suggests that stricter management of health behaviors may be necessary to significantly lower gallstones risk. On the other hand, health factor scores showed a consistent negative linear relationship with gallstones, highlighting the importance of monitoring and optimizing modifiable biomarkers to reduce the risk of gallstones in high-risk populations.

The potential mechanisms underlying the association between LE8 scores and gallstones may reflect the role of LE8 in identifying metabolic disorders and unhealthy behaviors that contribute to gallstone formation. Obesity is a major risk factor, with higher gallstone prevalence among obese individuals, consistent with existing literature^22–25. This increased risk likely results from metabolic changes, including the secretion of cholesterol-saturated bile and impaired gallbladder function²⁶. Although obesity directly contributes to gallstone formation, rapid weight loss through surgery or low-calorie diets can also increase risk^27–29, indicating a complex relationship between weight changes and gallstone formation. Hypertension has also been linked to a higher risk of gallstones, with a dose-response relationship suggesting that elevated blood pressure may accelerate gallstone formation^30,31. Similarly, the connection between lipid metabolism and gallstones is supported by evidence that high triglycerides and low high-density lipoprotein cholesterol levels increase gallstone susceptibility^32–35. The relationship between diabetes and gallstones is more complex. While some studies have not found consistent associations^36–39, recent Mendelian randomization studies suggest that type 2 diabetes may have a causal relationship with gallstone risk, independent of BMI²⁵. Possible mechanisms include hepatic insulin resistance and reduced gallbladder function, which may promote cholesterol crystallization in bile^40,41. In terms of health behaviors, dietary patterns play a significant role in gallstone risk. A Western diet rich in refined grains and fats is associated with a higher risk of gallstones^42,43, while the Mediterranean diet appears to offer protective effects⁴⁴. Dietary carbohydrates may play a role in the formation of cholesterol gallstones by altering bile movement and enhancing cholesterol crystallization⁴². Physical activity has also been shown to have a protective role, although this association is less significant than that of health factors^45–47. Smoking is another recognized risk factor⁴⁸, and disruption of circadian rhythms has been linked to altered lipid metabolism and increased gallstone formation⁴⁹. Importantly, our study found that health factors had a greater impact on gallstone risk than health behaviors. This suggests that while promoting healthy behaviors is essential, managing key health factors like obesity, hypertension, and diabetes may be more critical for preventing gallstones.

Stratified analysis revealed that the association between LE8 and gallstones was more pronounced in individuals under 65 years old, females, non-white participants, married individuals, and those with higher education levels. These findings align with previous studies. For example, research has shown that gallstones are more common among Americans under 50 years old⁵⁰, and the prevalence is significantly higher in women, likely due to factors such as hormone replacement therapy, oral contraceptive use, and multiple pregnancies^51,52. Estrogen and progesterone may also play a role, as estrogen increases cholesterol secretion, potentially leading to cholesterol saturation in bile, while progesterone inhibits gallbladder emptying, causing bile stasis⁵³.

Although our understanding of the genetics and pathophysiology of gallstones has expanded in recent years, current treatments still rely heavily on invasive surgery¹. Studies show that regardless of the approach, about two-thirds of patients experience relief from pain following cholecystectomy⁵⁴. Future research should focus on developing new prevention strategies to reduce gallstone formation and recurrence, especially in high-risk populations. LE8, as a comprehensive and user-friendly tool, assesses both health behaviors and factors, addressing the limitations of previous studies that focused solely on individual factors. Our study provides additional evidence that maintaining ideal CVH may be an effective strategy for the prevention and management of gallstones.

This study has several strengths. First, it is based on a nationally representative sample of U.S. adults, making the results broadly applicable to the general population. Second, we used the updated LE8 to assess CVH, examining each component in detail to provide more accurate conclusions. Lastly, we adjusted for potential confounders and conducted stratified analyses, making the results more robust. However, there are some limitations. Although we adjusted for multiple confounders, we did not control for certain variables that may affect gallstone risk, such as alcohol consumption, family history, lipid-lowering medications, female hormone preparations, and antibiotic use. Future studies should consider these factors to minimize residual confounding. Additionally, the reliance on self-reported data may introduce recall bias, particularly in the assessment of health behaviors such as diet, physical activity, nicotine exposure, and sleep duration. Lastly, as an observational cross-sectional study, we cannot establish causality, and reverse causality cannot be ruled out. For instance, individuals with gallstones may reduce physical activity due to pain, which could affect their cardiovascular health scores. Therefore, our findings should be interpreted cautiously and in conjunction with other types of research. Future longitudinal studies will help clarify the directionality of these associations.

Conclusion

In conclusion, our study demonstrates a negative association between CVH, as assessed by LE8, and the risk of developing gallstones. These findings highlight the potential of LE8 as a valuable tool in clinical practice for identifying individuals at higher risk of gallstones and informing targeted prevention strategies.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

NHANES

National health and nutrition examination survey

RCS

Restricted cubic spline

CI

Confidence interval

CHV

Cardiovascular health

LE8

Life’s essential 8

AHA

American heart association

DASH

Dietary approaches to stop hypertension

Non-HDL

Non-high-density lipoprotein cholesterol

NCHS

National center for health statistics

CDC

Centers for disease control and prevention

BMI

Body mass index

PIR

Poverty-income ratio

Author contributions

YZ and XSL were responsible for study design and data acquisition. YZ analyzed and processed the data. YZ, JRH and CTY wrote the manuscript. BF and JFZ edited the manuscript. All authors approved the submitted and final versions.

Funding

No funding.

Data availability

The relevant data used in this study are accessible from the NHANES website. https://www.cdc.gov/nchs/nhanes/index.htm.

Declarations

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

The NHANES received approval from the National Center for Health Statistics Ethics Review Board (https://www.cdc.gov/nchs/nhanes/irba98.htm). Written informed consent was obtained from all participants prior to their involvement. No external ethical approval was necessary, as all research was already approved by the National Center for Health Statistics Ethics Review Board. All methods in this study were performed in accordance with relevant NHANES guidelines and regulations.