Early effects of cigarette smoke on adolescent endothelial functions: a novel endocan/cotinine ratio approach

This study aimed to investigate the early effects of cigarette smoke exposure on endothelial function in healthy adolescents by analyzing blood endocan levels and urinary cotinine concentrations. A novel endocan/cotinine ratio was proposed to enhance the assessment of endothelial response to tobacco exposure.

In this cross-sectional case-control study, 88 adolescents aged 13-18 years were recruited from Istanbul University between January and August 2021. Participants were divided into two groups: exposed (n=44) and non-exposed (n=44) to cigarette smoke. Blood endocan and urine cotinine levels were measured using ELISA. Statistical analysis included the Mann-Whitney U test and Spearman's correlation.

Among the exposed participants, 11.4 % (n=5) were active smokers and 88.6 % (n=39) were passive smokers. Systolic blood pressure was significantly higher in the exposed group (p=0.03). Although endocan levels did not differ significantly between groups (p=0.74), median values were higher in the exposed group (1847.5 pg/mL, range: 14.79-3,121.63) compared to controls (1806.2 pg/mL, range: 116.83-4,618.90). Urinary cotinine levels were markedly elevated in the exposed group (p<0.001).Significant positive correlations were found between exposure duration (pack-years) and both endocan levels (r=0.318, p=0.01) and cotinine levels (r=0.524, p<0.001). A significant negative correlation was identified between cotinine and endocan levels specifically in the exposed group (r=-0.435, p=0.003), with regression analysis showing that each 1 ng/mL increase in urinary cotinine was associated with a 3.23 pg/mL reduction in serum endocan (R²=0.189, p=0.003), suggesting that cotinine levels accounted for 18.9 % of the variability in endocan concentrations. No such correlation was observed in the control group (r=-0.015, p=0.925).The endocan/cotinine ratio showed a decreasing trend in the exposed group (median: 25.69, mean: 28.76 ± 21.45) compared to non-exposed participants (median: 34.24, mean: 47.31 ± 53.89), though this difference did not reach statistical significance (U=1,149.0, p=0.132). A negative correlation was found between BMI and endocan levels (r=-0.337, p=0.001), while a weak positive correlation was observed between age and cotinine concentration (r=0.222, p=0.038).

Cigarette smoke exposure in adolescents leads to elevated cotinine levels and increased blood pressure (p=0.03), indicating early vascular changes. The observed negative correlation between cotinine and endocan levels (r=-0.435, p=0.003) may reflect a compensatory endothelial response. The endocan/cotinine ratio could serve as a novel, early biomarker for endothelial dysfunction in youth exposed to cigarette smoke.