sdLDL-C, alkaline phosphatase, and their composite ratio are associated with early vascular aging in type 2 diabetes mellitus: a retrospective cross-sectional study
Year: 2026
Type: article
Study design: Observational Study
Abstract: Early vascular aging (EVA) is highly prevalent among individuals with type 2 diabetes mellitus (T2DM), yet the metabolic and calcific determinants underlying this accelerated vascular decline remain insufficiently understood. Small dense LDL cholesterol (sdLDL-C) reflects lipid-driven vascular injury, whereas alkaline phosphatase (ALP) is a key mediator of medial calcification. However, their combined role—and potential age-dependent interactions—in EVA has not been systematically investigated. This retrospective cross-sectional study included 480 consecutive T2DM patients. Vascular aging was assessed using brachial–ankle pulse wave velocity (baPWV), with EVA defined as baPWV > mean + 2 SD of an age-stratified healthy reference population. sdLDL-C, ALP, and the sdLDL-C/ALP ratio were evaluated as primary exposures through multivariable linear and logistic regression, forward stepwise modeling, age-stratified analyses, interaction testing, and ROC curve assessment. sdLDL-C, ALP, and particularly the sdLDL-C/ALP ratio were significantly associated with EVA. The sdLDL-C/ALP ratio demonstrated the strongest independent association (per 0.001 increase: OR = 1.32, 95% CI 1.15–1.51), with a clear dose–response trend across tertiles ( P for trend < 0.001). Age-stratified analyses revealed a pronounced age-dependent gradient: the ratio showed a 2.32-fold increased risk of EVA in adults ≤ 55 years, attenuated associations in the 56–65 group, and no significant association beyond 65 years. The interaction term (ratio × age) was significant ( P = 0.009), confirming age as a major effect modifier. In ROC analysis, the sdLDL-C/ALP ratio outperformed sdLDL-C and ALP alone (AUC = 0.742), whereas the combined model achieved the highest discrimination (AUC = 0.811). sdLDL-C, ALP, and especially their composite ratio are robustly associated with EVA in T2DM patients. The sdLDL-C/ALP ratio captures integrated metabolic and calcific vascular stress and exhibits clear age-dependent effect attenuation. These findings highlight the sdLDL-C/ALP ratio as a potentially valuable biomarker for EVA screening and early vascular risk stratification, particularly in younger and middle-aged diabetic populations.
Authors: Yunxia Ji, Chunling Mu, Yingjuan Han
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,190
OpenAlex ID: W7153448283