Background: Previous studies have shown that dyslipidemia is closely associated with the formation and progression of cholelithiasis. However, most of these studies were cross-sectional, limiting the ability to establish causal relationships. In contrast, the ratio of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol (NHHR) is an emerging composite indicator in lipidology, and its association with the incidence of cholelithiasis has yet to be fully explored in cohort studies. Methods: In this study, we enrolled participants from a tertiary hospital in northeastern China who underwent at least two health examinations between 2014 and 2024 and met the inclusion criteria. We investigated the relationship between NHHR and the risk of developing cholelithiasis. Our analysis incorporated Kaplan-Meier estimation of cumulative incidence, multivariable Cox proportional hazards regression, restricted cubic spline (RCS) analysis, and threshold effect analysis to examine the dose-response relationship. Additionally, subgroup and sensitivity analyses were conducted to assess the robustness of our findings. Results: Among the 65 362 participants, 1976 cases of cholelithiasis were confirmed during follow-up. In the multivariable Cox regression model (Model 3), participants in the highest NHHR quartile (Q4) exhibited a 34% increased risk of developing cholelithiasis compared with those in the lowest quartile (Q1) (HR = 1.34, 95% CI: 1.12–1.61, P < 0.001). Both RCS and threshold effect analyses revealed a U-shaped relationship between NHHR and cholelithiasis risk, with the lowest risk observed at an NHHR value of approximately 1.84. Conclusions: Our findings suggest that elevated NHHR is significantly associated with an increased risk of incident cholelithiasis, demonstrating a U-shaped relationship with a nadir at approximately 1.84. These results underscore the potential of NHHR as a valuable clinical marker for assessing cholelithiasis risk, guiding individualized intervention strategies, and alleviating both economic burdens and the risk of severe complications.
Ming et al. (Tue,) studied this question.