Association between serum vitamin D levels and atherogenic lipid subfractions: insights from NMR-based lipid profiling in a large adult population

Abstract

Vitamin D deficiency is increasingly recognized as a potential risk factor for cardiovascular disease (CVDs); however, its specific impact on lipoprotein particle size and subclass distribution remains understudied. This study investigated the independent association between serum 25-hydroxyvitamin D [25(OH)D] levels and detailed lipoprotein subfractions, specifically atherogenic small dense LDL (sdLDL), using high-throughput nuclear magnetic resonance (NMR) spectroscopy. In a large cohort of 11,551 adults, we quantified 25(OH)D levels via chemiluminescent immunoassay and comprehensive lipid profiles, including six LDL subfractions (LDL-1-LDL-6), using the Bruker IVDr NMR system. Multivariable ordinal logistic regression adjusted for age and sex revealed that higher vitamin D levels were significantly associated with a favorable lipid profile, characterized by lower triglycerides (aOR = 0.714, p < 0.001) and higher HDL cholesterol (aOR = 1.389, p < 0.001). While total LDL cholesterol showed only a modest inverse association, a striking differential pattern emerged within LDL subfractions. Vitamin D deficiency was robustly linked to elevated levels of highly atherogenic sdLDL particles, with higher concentrations of LDL-5 and LDL-6 significantly reducing the likelihood of belonging to higher vitamin D categories (aOR = 0.783 and aOR = 0.756, respectively; p < 0.001). These findings indicate that vitamin D deficiency is independently associated with an atherogenic dyslipidemia marked by hypertriglyceridemia, reduced HDL-C, and a specific phenotypic shift toward small dense LDL particles, highlighting the clinical value of NMR-based subfraction analysis in cardiovascular risk assessment.