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. 2023 Jan 18;13(1):e062098. doi: 10.1136/bmjopen-2022-062098

Table 6.

Endo-PAT 2000 in paediatric patients with other miscellaneous paediatric conditions (10 studies)

Title, lead author Year Study design Population: n=sample size, age; mean±SD or median (range), (F/M) Control group: n=sample size, age; mean±SD or median (range), (F/M) Results: RHI reported. if RHI not specified, we reported p/r values Outcomes
Vascular endothelial function in inflammatory bowel disease (IBD). Winderman et al60 2018 Case–control study n=16 with IBD (all in clinical remission), age 16.7±2.6 years,(F/M 8/7) n=16, age 15.1±2.8 years,(F/M 7/8) RHI IBD vs controls 1.66 vs 2.02 (p=0.036). IBD group had a mean RHI within the range associated with VD risk in adults (1.67). IBD group lower RHI compared with controls. IBD patients may need to be monitored for thromboembolic phenomena.
Endothelial health in childhood acute lymphoid leukaemia (ALL) survivors: pilot evaluation with peripheral artery tonometry. Ruble et al52 2015 Case–control study n=16 ALL survivors, age 8–20 years (12.9±0.9),(F/M 8/8). n=16 healthy sibling pairs 13.8 (0.9),(F/M 10/6). Both groups similar in cardiovascular risk measures but survivors had lower RHI (1.54 vs sibling 1.77; p=0.0474). Evidence of poorer vascular health in cancer survivors.
Microvascular endothelial function in Japanese early adolescents. Odanaka et al95 2017 Control study n=157 healthy adolescents divided by gender. Womwen n=82, median age 14, (1) 13.7±0.9 years Males n=75, median age 14 (2) years No difference in RHI according to sex: boys and girls 1.85
±0.6, 1.82
±0.66 and 1.87±0.54. RHI was significantly associated with systolic and diastolic BP, and had no correlation with anthropometric parameters and arterial stiffness markers.
RHI among adolescents were similar to those reported in previous studies on children and early adolescents.
Endothelial dysfunction and the effect of arginine and citrulline supplementation in children and adolescents with mitochondrial diseases. Al Jasmi, et al59 2020 Case–control study Nine participants, age 6–17 years (mean 9.6). 3–15 years (mean 9.4). Baseline endothelial dysfunction was assessed in controls. Lower RHI with mitochondrial diseases. RHI increased with arginine or citrulline supplementation Supplementation with NO precursors may improve ED by enhancing NO production. First study to use Endo-PAT methodology in mitochondrial diseases.
Assessment of traditional and non-traditional risk factors for premature atherosclerosis in children with juvenile dermatomysoitis (JDM) and paediatric controls. Wahezi et al96 2020 Retrospective controlled study n=40 JDM, age 6–22 (mean 12.4±4.1) years,(F/M 28/12) n=20 controls, age 12.7±3.9 years, (F/M 14/8) RHI controls 1.43(1.2, 1.7) and JDM 1.57(1.2,1.9). If controlled for lipoprotein A (atherogenic confounder), JDM patients had 41% RHI increase, thus indicating less ED compared with controls. Rheumatological childhood disorders may be at increased risk of developing ED, but sociodemographic factors may have a greater role in developing cardiovascular disease.
Vascular health of children conceived via in vitro fertilization (IVF). Zhang et al97 2019 Cross-sectional pilot study n=17 IVF children, 10–14 years. Also used carotid ultrasound and pulse wave velocity measurements. Compared
to published norms or to historical Stanford controls
Mean Endo-PAT index in the IVF cohort was 1.66±0.52, 71% had abnormal values (<1.9). Mean RHI was not significantly different between IVF and controls. Children conceived by IVF seem to have evidence of abnormal vascular health.
Endothelial dysfunction in South African youth living with perinatally acquired human immunodeficiency virus (PHIV) on antiretroviral therapy. Mahtab et al98 2020 Case–control study n=431 PHIV, median 14.1 (12.8, 15.5) years,(F/M 213/218) n=93 without HIV, median 13.9 (12.1, 15.3) years,(F/M 53/40) PHIV had higher rates of ED (50% vs 34%; p=0.01); relationship persisted after adjusting for age, sex, BMI, high BP, high cholesterol (RR, 1.43; p=0.02). PHIV, CD4 count, viral load and current ART class were not associated with ED after adjustment. PHIV appear to have increased risk of ED. These findings have important implications as HIV has increased risk of premature CVD and complications.
Soluble CD14 (sCD14) is associated with endothelial dysfunction in South African youth on ART. Dirajlal-Fargo et al62 2020 Case–control study n=283 perinatally acquired HIV (PHIV), 9–14 years. n=69 age-matched without HIV PHIVs had lower RHI despite viral suppression (RHI=1.36 vs 1.52, p<0.01). sCD14 at 24 months correlated with ED (p≤0.04). PHIV with ED, sCD14 was associated with lower RHI (β−0.05, p=0.01). Higher sCD14 is independently associated with ED in PHIVs.
Role of insulin resistance and hyperandrogenemia in early vascular dysfunction in adolescents with PCOS. Bartz et al99 2015 Conference abstract n=14 PCOS adolescents PCOS (on no treatment). n=7 non-PCOS. Both groups had similar age, tanner stage, race, glucose tolerance status. Despite higher peripheral and hepatic insulin resistance with PCOS, RHI is not significantly lower when compared with controls of similar total body and abdominal adiposity. PCOS has evidence of increased vascular inflammation. Hyperandrogenemia and insulin resistance may play an important role in vascular inflammation.
Endothelial function in children and adolescents is mainly influenced by age, sex and physical activity-an analysis of reactive hyperemic peripheral artery tonometry. Mueller et al85 2017 Randomised controlled study, Leipzig School Project followed over 5-year period. n=931 RHI measurements in 445 students, age 10–17 years (baseline 11.66±0.93).
n=247: 60 min physical exercise (PE) daily (intervention group).
n=181: 2 units of 45 min PE weekly (control group). Higher RHI in the intervention group: 0.09 (−0.05, 0.23). Increase RHI from 1.53±0.42 in the youngest to 1.96±0.59 in the oldest students. This increase adjusted by age and sex was estimated as 0.11 (0.08, 0.14)per year. If Endo-PAT is used for research in adolescents, age and sex must to be taken in account when reporting RHI results.

ALL, acute lymphoid leukaemia; ED, endothelial dysfunction; IBD, inflammatory bowel disease; IVF, in vitro fertilisation; NO, nitric oxide; PCOS, polycystic ovarian syndrome; PE, physical exercise; PHIV, perinatally acquired human immunodeficiency virus; RHI, reactive hyperemia index; sCD14, soluble CD 14.