Association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and gallstones among US adults aged ≤ 50 years: a cross-sectional study from NHANES 2017-2020

Abstract

Background: The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet.

Methods: 3,772 people, all under 50, were included in this study, and their full data came from the National Health and Nutrition Examination Survey (NHANES) database for the years 2017-2020. Information on gallstones was obtained through self-reported questionnaires. Smoothed curve fitting multifactorial logistic regression was utilized to evaluate the connection of NHHR with gallstone formation incidence. Subsequently, subgroup analysis and interaction tests were applied. Finally, to create a prediction model, logistic regression and feature screening by last absolute shrinkage and selection operator (LASSO) were used. The resulting model was displayed using a nomogram.

Results: In multivariate logistic regression that accounted for all factors, there was a 77% increase in the likelihood of gallstones for every unit rise in lnNHHR (OR 1.77 [CI 1.11-2.83]). Following NHHR stratification, the Q4 NHHR level was substantially more linked to the risk of gallstones than the Q1 level (OR 1.86 [CI 1.04-3.32]). This correlation was stronger in women, people under 35, smokers, abstainers from alcohol, non-Hispanic White people, those with excessively high cholesterol, people with COPD, and people without diabetes. After feature screening, a predictive model and visualized nomogram for gallstones were constructed with an AUC of 0.785 (CI 0.745-0.819), which was assessed by DCA to be clinically important.

Conclusion: In the group of people ≤ 50 years of age, elevated NHHR levels were substantially linked to a higher incidence of gallstones. This correlation was stronger in several specific groups such as females, under 35 years of age, smokers, and so on. Predictive models constructed using the NHHR have potential clinical value in assessing gallstone formation.

Keywords: Cross-sectional study; Gallstone; NHANES; NHHR.

Fig. 1

Flowchart of the participants’ selection from NHANES 2017–2020

Fig. 2

Definition of some of the covariates

Fig. 3

Smooth curve fitting for probing NHHR and gallstones

Fig. 4

Subgroup analyses of the association between NHHR and gallstones

Fig. 5

Characteristics used to predict gallstones by LASSO regression screening. (A) Regression coefficient profiles. Each curve indicates the trajectory of each feature coefficient; (B) LASSO regression cross-validation profile. Each red dot indicates the mean square error (MSE) for each value of λ. The vertical coordinate is the coefficient value, the horizontal coordinate (upper) is the number of nonzero coefficients in the model, and the horizontal coordinate (lower) is the logarithmic value of the regularization parameter λ. The dashed line on the left indicates the minimum value of λ (λmin, log(λ)=-5.696). For prediction of gallstones, we used λmin as a variable screen. Eleven characteristics were selected: gender, age, race, education level, smoking, BMI, CHD, COPD, diabetes, ALT, and total cholesterol

Fig. 6

Performance evaluation of a predictive gallstones model. (A) ROC curve. The AUC of the model was 0.785 (CI 0.745–0.819), the specificity and sensitivity of the model were 73.89% and 71.22%, respectively. (B) Decision curve analysis (DCA). Red line for the net benefit of the predictive model, and the black line indicates that the predictive model was not used

Fig. 7

Nomogram used to predict gallstone risk. The horizontal line at the top is the column of scores, and the total score based on the sum of the itemized scores is the risk of developing gallstones. Gender, age, race, BMI, COPD, diabetes, and NHHR are indicators of the individual scores. Within race, 1 indicates “Mexican American,” 2 indicates “Other Hispanic,” 3 indicates “Non-Hispanic White,” 4 indicates “Non-Hispanic Black”, and 5 indicates “Other Race”