Novel cardiovascular risk factors in childhood

Individuals with type 1 diabetes (T1D) have a 2 to 3-fold increased risk for cardiovascular disease compared to non-diabetic subjects. Exposure to a broad panel of risk factors in childhood may cause vascular damage with potentially long-term consequences for cardiovascular morbidity. The aims of the studies were to investigate in young patients with T1D whether: frequency of acute infections correlates with atherogenic vascular changes (Study I); diabetes-predisposing genotype HLA-DQ 2/8 is associated with phenotypes of atherosclerosis and systemic microvascular dysfunction (Study II-III); exposure to environmental tobacco smoke (ETS) affects heart rate variability (HRV), and whether this association is influenced by diabetes-risk HLA (Study IV). The aim of study V was to investigate in an animal model susceptible to vascular disease whether repeated challenge with a respiratory pathogen poses cumulative adverse effects on microvascular function. Our findings suggest that in young patients with T1D: diabetes-risk genotype HLA DQ 2/8 is associated with functional disturbances in both large arteries and microcirculation, and with atherogenic lipid phenotype (studies II and III); frequent exposure to ETS is associated with disturbances in HRV, especially in those with diabetes-risk genotype HLA-DQ 2/8 (study IV); high frequency of RTI is associated with early signs of accelerated atherosclerosis in carotid artery, particularly in those regularly exposed to ETS (study I). At least in a hypercholesterolemic milieu, the risk of developing microvascular dysfunction seems to rise with increasing number of infectious episodes (study V). Further studies are needed to provide additional mechanistic insights into the putative gene-environment interactions on the cardiovascular system in young patients with T1D, and to investigate eventual relationship to cardiovascular complications later in life. Also, large-scale prospective studies on young populations presenting diabetes-risk (as well as other autoimmunity-risk) HLA are needed to elucidate whether these putative gene-environment influences on the cardiovascular system may be present already before the onset of the disease predisposed by these HLA

HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes

This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = - 0.3; n = 62) and FMD (p = 0.03, r = - 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.Peer reviewe

Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets

Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB

Early Complications After Percutaneous Closure of Atrial Septal Defect in Infants with Procedural Weight Less than 15 kg

Atrial septal defect (ASD) is the most common congenital cardiac lesion accounting for 10-15% of all cardiac malformations. In the majority of cases, the secundum type of the ASD is closed percutaneously in the catheterization laboratory. Although transcatheter closure of ASD is considered safe and effective in pediatric patients, there are limited data regarding the efficacy and safety of device ASD closure in smaller infants. The aim of this study was to determine risk of complications within 72 h following device closure of ASD in children of body weight <15 kg compared to larger children. Overall 252 children who underwent transcatheter closure of ASD at Children's Heart Centre in Lund, Sweden, between 1998 and 2015 were included. Data regarding demographics, comorbidity and complications occurring during and after device procedure until discharge were retrieved from the hospital's databases. Echocardiographic data were obtained from the digital and videotape recordings. Nearly half of the study cohort (n = 112; 44%) had a procedural weight <15 (median 11.3) kg with a median procedural age of 2.02 years. Among this study group, 22 (9%) children had post-procedural in-hospital complications, of which 16 (7%) were considered as major and six (2%) considered as minor. No deaths occurred. There was no significant difference in of the occurrence of major or minor complications between the two groups (p = 0.32). Larger ASD was more often associated with minor complications, OR 1.37 (95% CI 0.99-1.89), which most often consisted of transient arrhythmias during or after the procedure. Percutaneous ASD device closure can be performed safely in low-weight infants with a risk of post-procedural in-hospital complications comparable to larger/older children. Nevertheless, careful considerations of the indications to device closure is needed, particularly in children with larger ASD, as recommended by the current international guidelines for ASD closure

Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes are associated with diabetes high-risk HLA genotype

Expression of human leukocyte antigen (HLA) class II molecules on islet endothelial cells is a central vascular event in the pathogenesis of Type 1 diabetes. Previous studies demonstrated the ability of other vascular endothelial cells to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for Type 1 diabetes, is associated with early atherosclerosis in youths with this disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) and carotid artery intima-media thickness (CA-IMT), as well as markers of systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], HbA(1C), LDL, HDL, and total cholesterol, were assessed in 86 children and adolescents with Type 1 diabetes (mean age and diabetes duration, 15 and 7 yr, respectively) between 2004 and 2006. HLA genotypes were determined in dried blood spots by an oligoblot hybridization method. As a result, HLA-DQ2/8 was detected in 34 patients (DQ2/8). When this group was compared with the remaining patients (non-DQ2/8, n = 52), there were no differences in age, diabetes duration, HbA(1C), body mass index, inflammatory markers, and IMT (P >= 0.4). In the DQ2/8 group, LDL-to-HDL ratio was elevated compared with that in the non-DQ2/8 group (1.8 vs. 1.3, respectively; P = 0.001), whereas FMD did not significantly differ between the groups (5.3% vs. 6.7%, respectively; P = 0.08). When patients were further categorized in relation to CRP (cut- off value, 1 mg/ l), BA-FMD was significantly lower (3%, P = 1 patients compared with the remaining three subgroups. These associations remained significant after adjustment for age, diabetes duration, and HbA(1C) by analysis of covariance. The brachial artery responses to nitroglycerine were similar in all subgroups. In conclusion, the diabetes-predisposing HLA-DQ2/8 genotype in children and adolescents with Type 1 diabetes interferes with endothelial and lipid-related mechanisms of early atherosclerosis, possibly in part through inflammatory pathways

Preoperative Coronary Anatomy Assessment with Echocardiography and Morbidity After Arterial Switch Operation of Transposition of the Great Arteries

In transposition of the great arteries (TGA), certain coronary patterns have been associated with major adverse events early after the arterial switch operation (ASO). We sought to determine the impact of preoperative echocardiographic (ECHO) diagnosis on the intra­ and postoperative morbidity. All patients with TGA born between June 2001 and June 2017 and who underwent ASO were reviewed. Data on presumed coronary anatomy (CA) preoperatively were obtained from the preoperative ECHO report. Intraoperative CA was categorized according to Yacoub classification. Major postoperative morbidity included at least one of the following: delayed sternal closure (DSC), prolonged (> 72 h) mechanical ventilation, reintubation, peritoneal dialysis (PD), ECMO, reoperation, and readmission within 30 days after surgery. 240 patients with median age of 5 days (range 1–614) and mean weight at surgery was 3.6 kg (1.8–8.4) were included. Preoperative ECHO assessment of CA was available in 228 patients. Intraoperatively, 181 patients (75%) were found to have type A, 25 patients had type B or C or intramural (B–C–IM; 10%), and 34 patients had type D or E (D–E; 14%). Patients with types B, C, and intramural coronary (B–C–IM) had increased risk for delayed sternum closure (9/25 vs. 20/181 in type A and 8/34 in type D–E; p = 0.04), peritoneal dialysis (4/25 vs. 8/181 and 1/34; p = 0.04), and ECMO (2/25 vs. 1/131 and 1/34; p = 0.02). Within the B–C–IM group, preoperative ECHO raised suspicion of type A in 13 patients (i.e., incorrect diagnosis, ID; 52%), whereas non-A CA was suspected in 12 patients (i.e., correct diagnosis, CD; 48%). With the exception of reoperation, which was seen only in the ID subgroup (4/12 vs. 0/10 in the CD subgroup; p = 0.04), the intraoperative (cardiopulmonary bypass time and cross-clamp time) and postoperative morbidity indices were comparable in both ID and CD subgroups (p > 0.1). Although there is a significant risk for early postoperative morbidity in TGA patients with single, interarterial, and intramural CA, there seems to be relatively limited influence of preoperative ECHO assessment of coronary anatomy on this morbidity burden