Relationship between insulin-like growth factor-I and blood pressure in children: an observational study

Abstract

Background: Insulin-like growth factor-I (IGF-I) is a relevant hormone in growth regulation. However, dysregulation of IGF-I is also implicated in pathologic states, such as cardiovascular diseases (CVD). CVDs are the main cause of death globally. Subclinical CVD has its roots in childhood. It has been demonstrated that high blood pressure (BP) in childhood correlates with higher BP in adulthood and the onset of hypertension and metabolic syndrome. Elevated BP is therefore a major modifiable risk factor for CVD. Justification: Interventions related to CVD prevention and health promotion are needed, especially in paediatric population. There are conflicting data on published studies defining the association between IGF-I levels and the cardiovascular system. Furthermore, there is a lack of studies reviewing this association in the general paediatric population. Additional knowledge is needed to understand the pathophysiologic mechanisms of IGF-I involved in CVD, which may allow us to perform an early CV risk assessment as well as to apply prevention interventions in those patients at higher risk. Objectives: The aim of this study is to analyse the association of IGF-I serum concentrations with blood pressure in a population of apparently healthy children. Both cross-sectional associations (studies at baseline and at follow-up) as well as predictive associations (longitudinal analysis) will be sought. Other associations, as well as possible interactions, between IGF-I and CV risk factors (waist, insulin, insulin resistance, triacylglycerol, high-density lipoprotein cholesterol and carotid intima-media thickness) will be also studied. Methods: This is an observational prospective, population-based study of a cohort of apparently healthy children in Girona. A target population of 528 children (mean age 8.8 years) were studied; a total of 158 of such children were re-studied after a 4-year period of follow-up (mean age 12.8 years). Data have been extracted from a database compiled between 2011 and 2017. Data analyses have been performed for all the studied subjects and in subgroups thereof defined by tertiles of serum levels of phosphate and calcium (PxCa product), as higher concentrations of these mineral have been associated with increased risk for CVD. Results: Basal study (cross-sectional associations at baseline): IGF-I was associated with all the studied variables (age, weight, height, BMI, waist, SBP, DBP, PP, log10 HOMA-IR, log10 triacylglycerol, HDL-cholesterol, carotid IMT), all p<0.0001. Analyses by PxCa tertiles, showed that the strongest associations between IGF-I and blood pressure parameters (SBP, DBP, PP) were present in children with higher PxCa product. Follow-up study (cross-sectional associations at follow-up): IGF-I maintained the correlation with all the variables studied in the follow-up study: age, weight, height, SBP, PP, log10 HOMA-IR (p<0.0001), BMI (p=0.035), waist (p=0.008), DBP (p=0.001), log10triacylglycerol (p=0.076), HDL-cholesterol (p=0.047) and carotid IMT (p=0.021). Analyses by PxCa tertiles showed that the strongest associations between IGF-I and blood pressure parameters (SBP, DBP, PP) were present in children with higher PxCa product. Prediction study (longitudinal associations of baseline IGF-I with dependent variables at follow-up): IGF-I is correlated with all the variables studied: age, weight, height, BMI, waist, SBP, PP and log10 HOMA-IR (p<0.0001), DBP (p=0.049), log10triacylglycerol (p=0.010), HDLcholesterol (p=0.020) and carotid IMT (p=0.020). Analyses by PxCa tertiles showed that the strongest associations between baseline IGF-I and blood pressure parameters at follow-up (SBP, DBP, PP) were present in children with higher PxCa product. In multivariate regression analyses, the strongest cross-sectional and longitudinal associations of IGF-I levels were with SBP and in children with higher PxCa product. Conclusions: Increasing serum IGF-I levels were found to associate with increasing blood pressure, especially with increasing systolic blood pressure and in children with higher phosphate calcium product.