Abstract
Dyslipidemia and hyperuricemia are recognized as significant risk factors for cardiovascular and metabolic diseases. However, the relationship between the novel lipid metabolism marker, non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR), and serum uric acid levels or hyperuricemia remains unclear. This study aimed to analyze these associations using data from a nationally representative population, with an emphasis on sex-specific differences and nonlinear relationships. Data from the National Health and Nutrition Examination Survey conducted from 2005 to 2018 were examined, involving 9439 adults, following the application of exclusion criteria. Weighted linear and logistic regression models categorized by sex were used to investigate the relationships between NHHR, uric acid concentrations, and hyperuricemia. Nonlinear relationships were assessed using restricted cubic splines, and threshold effects were explored using 2-part regression models. Subgroup analyses were conducted to evaluate potential modifiers of the relationship between NHHR and hyperuricemia. NHHR was significantly associated with serum uric acid levels and hyperuricemia in the general population with notable sex-specific differences. In females, NHHR was found to have a very significant positive correlation with hyperuricemia (OR 1.44, 95% confidence interval [CI]: 1.31-1.58, P < .001); however, this correlation was not as strong in males (OR = 1.07, 95% CI: 0.95-1.20, P = .20). Repeated analyses with nonlinear models showed that NHHR had a threshold relationship with hyperuricemia concentration which reached its highest level of 3.91 for the general population, with male and female inflection points at 4.637 and 4.452, respectively. Subgroup analyses demonstrated significant interactions with body mass index (BMI), smoking status, and stroke, further highlighting the heterogeneity of the NHHR-hyperuricemia relationship. NHHR is independently associated with serum uric acid levels and hyperuricemia, with significant sex-specific and nonlinear patterns. These findings suggest that the NHHR may serve as a valuable biomarker for assessing hyperuricemia risk, particularly in females. Further research is warranted to explore the underlying mechanisms and the clinical implications of these associations.