Abstract
PURPOSE: Cholesterol metabolism is a risk factor for cardiovascular disease, and recent studies have shown that cholesterol metabolism poses a residual risk of cardiovascular disease even when conventional lipid risk factors are in the optimal range. The association between remnant cholesterol (RC) and cardiovascular disease has been demonstrated; however, its association with hypertension, type 2 diabetes mellitus (T2DM), and the concomitance of the two diseases requires further study. This study aimed to evaluate the association of RC with hypertension, T2DM, and both in a large sample of the U.S. population, and to further explore the potential mechanisms involved. METHODS: This cross-sectional study used data from the 2005-2018 cycles of the National Health and Nutrition Examination Survey (N = 17,749). Univariable and multivariable logistic regression analyses were performed to explore the relationships of RC with hypertension, T2DM, and both comorbidities. A restricted cubic spline regression model was used to reveal the dose effect. Mediation analyses were performed to explore the potential mediating roles of inflammation-related indicators in these associations. RESULTS: Of the 17,749 participants included (mean [SD] age: 41.57 [0.23] years; women: 8983 (50.6%), men: 8766 (49.4%)), the prevalence of hypertension, T2DM, and their co-occurrence was 32.6%, 16.1%, and 11.0%, respectively. Higher RC concentrations were associated with an increased risk of hypertension, T2DM, and their co-occurrence (adjusted odds ratios for per unit increase in RC were 1.068, 2.259, and 2.362, and 95% confidence intervals were 1.063-1.073, 1.797-2.838, and 1.834-3.041, respectively), with a linear dose-response relationship. Even when conventional lipids were present at normal levels, positive associations were observed. Inflammation-related indicators (leukocytes, lymphocytes, monocytes, and neutrophils) partially mediated these associations. Among these, leukocytes had the greatest mediating effect (10.8%, 14.5%, and 14.0%, respectively). CONCLUSION: The results of this study provide evidence that RC is associated with the risk of hypertension, T2DM, and their co-occurrence, possibly mediated by an inflammatory response.