Gender and age differences in peripheral vascular endothelial function in healthy children and adolescents

  • Ms Alexandra Brinkåker, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden
  • Prof Peter Friberg, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden
  • Dr Walter Osika, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden
  • Dr Frida Dangardt, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden
  • Mr Krister Berggren, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden
  • Dr Eva Gronowitz, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden
  • Dr Yun Chen, Department of Melucular and Clinical Medicine, Sahlgrenska Academy/Hospital at the University of Gothenburg, Sweden

Objective: Atherosclerosis begins and progresses during childhood and adolescence. Endothelial dysfunction is one of the earliest abnormalities that can be detected in the development of atherosclerosis. Reactive hyperemia peripheral arterial tonometry (RH-PAT) is a novel technique for measuring endothelial function. Given that there is a large variability in the time course of the flow-mediated dilatation in children, we wanted to investigate the temporal nature of the reactive hyperaemic response in children and adolescents, and since men are more often suffer from cardiovascular diseases, we also studied the differences between girls and boys.

Methods: A total of 207 (109 males) healthy children (mean age 10 years; range 7-12 years) and 156 (69 males) healthy adolescences (mean age 17 years; range 15-19 years) from schools in Gothenburg participated in this study. Endothelial function was assessed using RH-PAT method with Endo-PAT® device (Itamar Medical Ltd, Israel). One forearm was occluded for 5 minutes and pulse wave amplitude in fingertips was recorded for 5 minutes before (baseline) and after 5-minute arterial flow occlusion in both occluded arm and contra-lateral arm. Reactive hyperemic response was calculated as a ratio of pulse wave amplitude after occlusion to pulse wave amplitude at baseline. Peak value of the reactive hyperemic response, time to peak and area under curve (AUC) of the entire 5-min post occlusion period were obtained using GraphPad 5. Age and sex differences were tested with ANOVA (SPSS15.0).

Results: In younger children, the AUC was 5.97 ± 1.1704 for girls and 5.11 ± 1.2620 for boys which was a statistically significance different between sexes (p=0.037). Also in adolescents, the AUC was greater in girls than in boys (6.87 ± 3.2259 vs. 5.60 ± 1.9055, p=0.02). Furthermore, there was an age difference for girls (p=0.024) but not for boys. The peak value of the reactive hyperemic response in younger children was 1.63 ± 0.4900 for girls and 1.39 ± 0.3833 for boys (n.s.).
In adolescents, however, the peak value of the reactive hyperemic response was greater in girls than in boys (2.08 ± 1.0773 vs. 1.67 ± 0.6904, p=0.02). There was an age difference for girls (p<0.0001) but not for boys. Time to peak, pulse wave response, in younger children was 3.44 ± 1.1240 min for girls and 3.39 ± 1.1119 min for boys (n.s.), while adolescents it was 2.15 ± 0.7949 min for girls and 2.84 ± 1.0525 min for boys (p=0.0002). Both sexes demonstrated age difference (p<0.0001 for girls, p=0.004 for boys).

Conclusions: Female adolescents have higher peak reactive hyperemic response and shorter time to reach peak value than the age-matched males, suggesting that female adolescents have better endothelial function than males. The reactive hyperemic response increases with age, but this is only seen in the females. Our data highlights the importance of analyzing entire response curve when assessing endothelial function in children and adolescents, and to underscore the importance of set differences, perhaps constituting one factor for the future development of vascular abnormalities.