Relationship of Urinary Cotinine and Secondhand Smoke Exposure With Metabolic Syndrome Among Self-Reported Never-Smokers

Background and Objectives: Misclassification of smoking status in epidemiologic studies may obscure the cardiometabolic risks of nicotine exposure.This study evaluated the independent and joint associations of urinary cotinine positivity and self-reported secondhand smoke (SHS) exposure with metabolic syndrome (MetS) among self-reported never-smokers.Methods: We analyzed 120,919 Korean adults who self-identified as never-smokers and underwent health screening.Cotinine positivity was defined as urinary cotinine 50 ng/mL, and SHS exposure was assessed by questionnaire.Participants were categorized into the cotinine(-)/ SHS(-) (reference), cotinine(-)/SHS(+), cotinine(+)/SHS(-), and cotinine(+)/SHS(+) groups.Logistic regression models were used to estimate adjusted odds ratios (ORs) for MetS.Results: Among self-reported never-smokers, 1.9% were cotinine-positive and 23.2% reported SHS exposure.Both cotinine(+) and SHS exposure were independently associated with MetS (ORs [95% confidence interval], 1.34 [1.08-1.67]and 1.10 [1.02-1.20],respectively).Compared to the cotinine(-)/SHS(-) group, the other 3 groups had higher odds of MetS, with the highest observed in cotinine(+)/SHS(-) individuals (1.46 [1.07-2.01]),presumed to represent undisclosed smokers.A significant interaction between cotinine and SHS exposure was observed (p for interaction=0.019).Cotinine(+) significantly increased MetS odds only among the groups without SHS exposure, and cotinine(+) was particularly associated with elevated triglyceride and low high-density lipoprotein cholesterol levels.Conclusions: Relying solely on self-reported smoking and SHS exposure may lead to an underestimation of the association between nicotine exposure and MetS.Incorporating objective markers, such as urinary cotinine, may help improve exposure classification, although further longitudinal studies are needed to confirm these findings.