Metabolic syndrome definitions and cardiovascular risk concordance in the Negrito population: Insights from lipid-derived risk indices, inflammation and endothelial biomarkers.

Metabolic syndrome (MetS) definitions may perform differently in indigenous populations with distinct genetic and lifestyle exposures. The Negrito community remains under-represented in cardiometabolic research despite emerging risk. Building on earlier observations of atypical biomarker patterns in this population, potentially linked to CDH13-related vascular mechanisms, this study aimed to determine MetS prevalence using the International Diabetes Federation (IDF) and Harmonized Joint Interim Statement (JIS) definitions, evaluate agreement between these definitions and their concordance with cardiovascular risk scores (CRS), and examine relationships between inflammatory and vascular biomarkers in the context of MetS. A cross-sectional study was conducted among Negrito adults. MetS was categorized using the IDF and JIS definitions. CRS included the Framingham risk score (FRS), Castelli risk index (CRI)-I, CRI-II and the atherogenic index of plasma (AIP). High-sensitivity C-reactive protein, lipoprotein(a), soluble intercellular adhesion molecule-1 (sICAM-1), and T-cadherin were quantified. Agreement statistics, correlations, logistic and linear regression models were applied. Among 153 adults, MetS prevalence was 11.8% (IDF) and 16.3% (JIS) with near-perfect agreement (κ = 0.81), although McNemar testing indicated slight asymmetry between definitions. Concordance between MetS and CRS was generally weak, with AIP showing the highest agreement (IDF κ = 0.17; JIS κ = 0.30), followed by CRI-II (IDF κ = 0.05; JIS κ = 0.20). CRI-I showed slight agreement with both definitions (IDF κ = 0.07; JIS κ = 0.15), while FRS showed no meaningful alignment (IDF κ = -0.07; JIS κ = -0.01). sICAM-1 showed weak but consistent positive correlations with all CRS (r = 0.20-0.26, P = .017-.002). T-cadherin did not correlate with CRS but was inversely associated with sICAM-1 (r = -0.28, P = .001). In multivariable logistic models, CRI-I (OR = 3.20), CRI-II (OR = 2.32) and AIP (OR = 2.15) remained independently associated with MetS. In linear models, sICAM-1 showed consistent associations with each CRS (FRS R2 = 0.03; CRI-I R2 = 0.06; CRI-II R2 = 0.06; AIP R2 = 0.03). IDF and JIS definitions classified MetS similarly but showed limited concordance with CRS. AIP and CRI demonstrated stronger cross-sectional associations with MetS than FRS. Biomarker analyses indicated that sICAM-1 correlated with CRS. The inverse relationship between T-cadherin and sICAM-1 raises the possibility of compensatory vascular-protective mechanisms. Collectively, these findings suggest a distinct lipid-inflammatory cardiometabolic phenotype in the Negrito population, where endothelial activation markers may capture early vascular stress beyond traditional risk scores.