Intensive Lifestyle Intervention Increases Plasma Midregional Proatrial Natriuretic Peptide Concentrations in Overweight Children.

Background Overweight adults have low circulating concentrations of ANP (atrial natriuretic peptide) and proANP fragments. We tested the hypothesis that an intensive lifestyle intervention with an intended weight loss would increase plasma concentrations of a proANP fragment in overweight children. Methods and Results We measured MR-proANP (midregional proANP) concentrations in plasma from overweight children who participated in the OOIS (Odense Overweight Intervention Study). OOIS randomized 115 overweight children (11-13 years, 55% girls) to an intensive day-camp intervention arm with increased physical activity and healthy diet or to a less intensive standard intervention arm for 6 weeks. We used linear mixed-effects modeling for repeated measures to estimate the difference in the mean change with 95% CIs in fasting plasma MR-proANP concentrations between the 2 arms, and we used partial least squares regression analysis to identify candidate mediators. Differences in weight, fitness, and metabolic factors were also analyzed. At baseline, fasting plasma MR-proANP concentrations were (median [interquartile range]) 35.0 pmol/L (26.8-42.0) in the day-camp intervention arm and 37.2 pmol/L (31.7-44.7) in standard intervention arm participants, respectively. After 6 weeks intervention, children in the day-camp intervention arm had increased their MR-proANP (5.4 pmol/L [0.8-10.0], P=0.022) and their fitness (2.33 mL O2/min per kg [0.52-4.14], P=0.012) and they had deceased their body mass index (-2.12 kg/m2 [-2.59 to -1.65], P<0.001) as compared with children in standard intervention arm. In the partial least squares analysis, decreases in fasting insulin and in estimated insulin resistance were associated with the observed increase in MR-proANP concentrations. Conclusions An intensive lifestyle intervention increases plasma MR-proANP among overweight children. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01574352.

Association of copeptin, a surrogate marker for arginine vasopressin secretion, with insulin resistance: Influence of adolescence and psychological stress.

In middle-aged and elderly individuals, circulating copeptin concentrations, a surrogate marker for arginine vasopressin (AVP) secretion, associates with insulin resistance (IR). Whether this association is present in adolescents and young adults is unclear. Because psychological stress associates with higher circulating copeptin concentrations and IR, it has been speculated that increased AVP secretion could be a link between psychological stress and IR. We measured plasma copeptin concentrations in 351 14-16-year-old adolescents and 617 20-28-year-old young adults from the Danish site of the European Youth Heart Study, a population-based cardiovascular risk factor study in adolescents and young adults. IR was determined by the homeostatic model assessment method. Among the young adults, we used symptoms of depression, evaluated by means of the Major Depression Inventory (MDI) scale, as a measure of psychological stress. We applied linear regressions to examine associations, expressed as unstandardized regression coefficients (B) with 95% confidence intervals (CIs), between variables of interest, stratified by age group and adjusting for age, sex and Tanner stages. Copeptin and IR were log-transformed. Among the young adults, copeptin associated with IR (B (95%CI) = 0.19 (0.11 to 0.27), P < 0.001). This association was not found among the adolescents (B=-0.01 (-0.12 to 0.09), P = 0.78). MDI score associated with IR (B = 0.010 (0.004 to 0.016), P < 0.001) and copeptin (B=0.010 (0.004 to 0.015); P<0.002) in the young adults. Adjusted for copeptin, the strength of the association between MDI score and IR somewhat diminished (to B=0.008). In conclusion, adolescence and psychological stress appear to influence the association between copeptin and IR.

Associations of Proatrial Natriuretic Peptide with Components of the Metabolic Syndrome in Adolescents and Young Adults from the General Population.

BACKGROUND: In middle-aged and elderly populations, circulating natriuretic peptide concentrations are negatively associated with several components of the metabolic syndrome. Whether these negative associations are also present in healthy adolescents and young adults from the general population are unknown. METHODS: In a cross-sectional setting, we measured plasma concentrations of mid-regional proatrial natriuretic peptide (MR-proANP) in 343 adolescents (age 14-16 years) and 616 young adults (age 20-28 years) from the Danish site of the European Youth Heart Study, which is a population-based study of cardiovascular disease risk factors in children, adolescents and young adults. We used linear regression analysis to examine the associations, expressed as standardized regression coefficients, of various variables of interest with MR-proANP stratified according to age group, adjusting for age and gender. RESULTS: Among the young adults, MR-proANP was negatively associated with body mass index (BMI) (ß = -0.10, P = 0.02), waist circumference (WC) (ß = -0.14, P < 0.001), systolic blood pressure (BP) (ß = -0.08, P = 0.03), diastolic BP (ß = -0.23, P < 0.001), insulin (ß = -0.15, P < 0.001), and triglycerides (ß = -0.14, P < 0.001). Among the adolescents a somehow different pattern was observed since MR-proANP was not significantly associated with BMI (ß = -0.00, P = 0.98), WC (ß = -0.01, P = 0.90) and insulin (ß = -0.02, P = 0.69). Nevertheless, among the adolescents, MR-proANP was negatively associated with triglycerides (ß = -0.13, P = 0.01), diastolic BP (ß = -0.12, P = 0.01) and systolic BP (ß = -0.10, P = 0.10), although the latter association was of borderline significance. CONCLUSIONS: The young adults displayed significant negative associations between MR-proANP and several components of the metabolic syndrome, whereas such associations were not found among the adolescents besides triglycerides and diastolic BP.

Mid-regional pro-atrial natriuretic peptide and blood pressure in adolescents: effect of gender and pubertal stage.

Little is known about blood pressure in relation to circulating natriuretic peptide concentrations and gender in generally healthy adolescents. We studied 15-year-old females and males (n = 335) from the Danish site of the European Youth Heart Study (EYHS). Blood pressure was measured using a standardized protocol, sexual maturity was assessed according to Tanner stage, and as a surrogate for atrial natriuretic peptide, we measured mid-regional pro-atrial natriuretic peptide (MR-proANP) in plasma. Compared with boys, girls had lower systolic blood pressure (SBP) (mean ± SD: 109.6 ± 9.9 mmHg vs 116.9 ± 11.4 mmHg, p < 0.0001) and higher plasma MR-proANP concentrations [median (interquartile range): 42.1 pmol/l (31.9-50.2 pmol/l) vs 36.6 pmol/l (30.6-44.9 pmol/l), p = 0.0046]. When female adolescents were further subdivided according to Tanner stage, there were no differences in blood pressure and plasma MR-proANP concentrations between post-pubertal and pubertal girls (p > 0.17). In contrast, after similar subdivision, post-pubertal boys had higher SBP (mean ± SD: 117.7 ± 11.7 mmHg vs 111.4 ± 7.9 mmHg, p = 0.029) and lower plasma MR-proANP concentrations [median (interquartile range): 36.2 pmol/l (30.6-43.1 pmol/l) vs 46.4 pmol/l (30.3-51.1 pmol/l), p = 0.043] compared with pubertal boys. Given their higher SBP, boys had lower than expected plasma concentrations of MR-proANP compared with girls, and given their higher SBP, post-pubertal boys had lower than expected plasma concentrations of MR-proANP compared with pubertal boys.