Management of aortic disease in children with FBN1-related Marfan syndrome.

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000-1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients. Prompt diagnosis, appropriate follow-up, and timely treatment can prevent aortic events. Currently there are no specific recommendations for treatment of children with MFS, and management is greatly based on adult guidelines. Furthermore, due to the scarcity of studies including children, there is a lack of uniform treatment across different centres. This consensus document aims at bridging these gaps of knowledge. This work is a joint collaboration between the paediatric subgroup of the European Network of Vascular Diseases (VASCERN, Heritable Thoracic Aortic Disease Working Group) and the Association for European Paediatric and Congenital Cardiology (AEPC). A group of experts from 12 different centres and 8 different countries participated in this effort. This document reviews four main subjects, namely, (i) imaging of the aorta at diagnosis and follow-up, (ii) recommendations on medical treatment, (iii) recommendations on surgical treatment, and (iv) recommendations on sport participation.

Pulmonary Atresia with Intact Ventricular Septum, a National Comparison Between Interventional and Surgical Approach, in Combination with a Systemic Literature Review.

This study aimed to compare long-term morbidity in patients with pulmonary atresia with intact ventricular septum (PA-IVS) treated with catheter-based intervention (group A) versus those undergoing heart surgery (group B) as initial intervention. Additionally, we conducted a systematic literature review on PA-IVS treatment. All neonates born in Sweden with PA-IVS between 2007 and 2019 were screened for inclusion. The inclusion criterion was decompression of the right ventricle for initial intervention. Medical records were reviewed, as well as the initial preoperative angiogram, and the diagnostic echocardiogram. Comparisons between groups were performed with Mann-Whitney U-test and Fisher´s exact test. A systematic literature review of original studies regarding treatment of PA-IVS (2002 and onward) was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, to assess the outcomes of patients with PA-IVS. 34 (11 females) patients were included, 18 in group A and 16 in group B. There was no mortality in either group. Follow-up time ranged from 2 to 15 years (median 9). All attempted perforations in group A were successful, and 16 out of 18 patients reached biventricular circulation. In the surgical group 15 out of 16 patients reached biventricular circulation. The literature review presented heterogeneity in standards for treatment. This retrospective population-based multicenter study demonstrates that both catheter-based intervention and heart surgery are safe procedures. Our results are comparable to, or exceed, those in the systematic literature review. The systematic literature review displays a great heterogeneity in study design, with no definitive golden standard treatment.

Long-Term Survival After Single-Ventricle Palliation: A Swedish Nationwide Cohort Study.

BACKGROUND: Long-term survival after single-ventricle palliation and the effect of dominant ventricle morphology in large, unselected series of patients are scarcely reported. METHODS AND RESULTS: This nationwide cohort study included all children undergoing operation with single-ventricle palliation during their first year of life in Sweden between January 1994 and December 2019. Data were obtained from institutional records and assessment of underlying cardiac anomaly and dominant ventricular morphology was based on complete review of medical records, surgical reports, and echocardiographic examinations. Data on vital status and date of death were retrieved from the Swedish Cause of Death Register, allowing for complete data on survival. Among 766 included patients, 333 patients (43.5%) were classified as having left or biventricular dominance, and 432 patients (56.4%) as having right ventricular (RV) dominance (of whom 231 patients had hypoplastic left heart syndrome). Follow-up was 98.7% complete (10 patients emigrated). Mean follow-up was 11.3 years (maximum, 26.7 years). Long-term survival was significantly higher in patients with left ventricular compared with RV dominance (10-year survival: 91.0% [95% CI, 87.3%-93.6%] versus 71.1% [95% CI, 66.4%-75.2%]). RV dominance had a significant impact on outcomes after first-stage palliation but was also associated with impaired survival after completed total cavopulmonary connection. In total, 34 (4.4%) patients underwent heart transplantation. Of these 34 patients, 25 (73.5%) had predominant RV morphology. CONCLUSIONS: This study provides clinically relevant knowledge about the long-term prognosis in patients with different underlying cardiac anomalies undergoing single-ventricle palliation. RV dominance had a significant impact on outcomes after initial surgical treatment but was also associated with impaired survival after completed Fontan circulation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03356574.

Bone mineral density in pediatric heart transplanted patients: A retrospective single-center study at Skåne University Hospital in Lund 1988-2016.

BACKGROUND: Impaired bone mineral density (BMD) and osteoporosis are commonly found in patients who have undergone heart transplantation (HT), which increases the risk for bone fractures which is associated with increased morbidity and mortality in adults. However, the long-term evolution of BMD after HT in pediatric patients has not been thoroughly investigated. METHOD: Bone mineral density up to 10 years after HT was investigated in 30 patients who underwent HT at an age <20 years at Skåne University Hospital in Lund 1988-2016. RESULTS: The total observed time was 235 person-years. Before HT, 86% had low BMD for chronologic age in the lumbar spine. In lumbar spine, BMD was significantly lower than normal for chronological age before HT (p = .034), but recovered at the 4th year (p = .009). In whole body, BMD was normal at the 4th annual check-up (p = .030) and remained so throughout the follow-up period. The median T score in the lumbar spine and femoral neck 10 years after HT did not differ between the two groups based on age at HT (<20 years vs 20 years or older; p = .779 in the lumbar spine and p = .388 in the femoral neck). CONCLUSIONS: Patients who undergo HT at an age of <20 years have low BMD for chronological age already before HT, but BMD may recover completely within the first 4 years after HT. The results indicate no difference in BMD at 10 years after HT between pediatric and adult patients.

Echocardiographic Predictors of Recoarctation After Surgical Repair: A Swedish National Study.

BACKGROUND: After surgical repair of aortic coarctation (CoA) there is a risk for restenosis (reCoA), particularly in the first year of life. This study aimed to identify reCoA risk factors by analyzing postoperative predischarge echocardiograms. METHODS: This was a retrospective analysis of echocardiograms of children born operated on for CoA in Sweden in 2011 to 2017. RESULTS: A total of 253 children were included. Median age at surgery was 10 days; median follow-up was 4.6 years. Risk for restenosis occurred in 34 patients (13%; 74% by 6 months and 91% by 12 months). We generated 2 reCoA risk models applying aortic dimensions and the respective Z-scores combined with surgical and demographic factors. We defined reCoA risk categories as low (≤10%), moderate (11% to 29%), moderate to high (30% to 49%), or high (≥50%). Patients with either isthmus of 3.3 mm or less (1- and 5-year event-free survival of 38% and 32%, respectively) or isthmus Z-score of -2.8 or less with a weight at surgery of less than 4.4 kg (1- and 5-year event free survival of 21% and 16%, respectively) were at highest risk for reCoA. Conversely, patients at low risk had isthmus greater than 3.7 mm and distal aortic arch greater than 3.5mm (1- and 5-year event free survival of 97% and 97%, respectively), and isthmus and proximal aortic arch Z-score greater than -2.8 or operative weight greater than 4.4 kg with an isthmus Z-score of -2.8 or less (1- and 5-year event-free survival of 97% and 97%, respectively). CONCLUSIONS: Risk for reCoA can be predicted based on postoperative predischarge echocardiographic variables combined with surgical and demographic factors. We suggest tailoring follow-up intervals individually according to the predicted reCoA risk.

Surgical Age and Morbidity After Arterial Switch for Transposition of the Great Arteries.

BACKGROUND: Transposition of the great arteries (TGA) is a complex congenital heart disease that requires early diagnosis as well as advanced surgical repair and postoperative support. This study sought to investigate the impact of surgical timing on early postoperative morbidity. METHODS: This study reviewed all patients with TGA repaired at a single institution (Skåne University Hospital, Lund, Sweden) by arterial switch operation (ASO) between June 2001 and June 2017. Major postoperative morbidity (MPM) and death within 30 days after ASOs were documented. Patients with double-outlet right ventricle, chromosomal abnormalities, and noncardiac diseases were excluded. MPM was defined as the presence of at least 1 of the following: delayed sternum closure, reoperation, prolonged mechanical ventilation, noninvasive ventilation after extubation, peritoneal dialysis, extracorporeal membrane oxygenation, and readmission. RESULTS: A total of 241 patients were included, with medians for birth weight, gestational week, and age at surgery of 3.5 kg, 39 weeks, and 5 days, respectively. MPM was encountered in 32.3% of patients. Prematurity (P = .001) and need for aortic arch repair at the time of ASO (P = .04) were associated with a significant increase in MPM. Non-A coronary anatomy, associated ventricular septal defect requiring surgical closure, and fetal diagnosis of TGA had no significant impact on MPM (P = .35, .08, and .21, respectively). There was no significant difference in MPM among the surgical groups (P = .49). CONCLUSIONS: Early complications after ASO do occur and are mostly associated with prematurity and the need for aortic arch repair. Timing of surgical repair does not seem to influence the rate of these complications.

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.

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

AIMS: This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). METHODS: 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. RESULTS: 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. CONCLUSIONS: The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.

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.

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 (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). 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.

Endothelial cell death and intimal foam cell accumulation in the coronary artery of infected hypercholesterolemic minipigs.

Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) and serial sections were processed for the detection of EC apoptosis, histology, and transmission electron microscopy (TEM) studies. There was a significantly higher number of TUNEL-positive ECs in infected compared to noninfected groups [0.2942 % (interquartile ranges (IR), 0.2941; n = 26) versus 0 % (IR, 0; n = 12), p < 0.01]. Caspase-3 staining was negative. Cholesterol diet together with infections induced widening of the subendothelial space and appearance of increased numbers of foam cells. TEM revealed degenerative changes in cytoplasmic organelles and signs of EC necrosis. In conclusion, infection leads to an increase in coronary EC death and seems to exacerbate cholesterol-induced intimal thickening and foam cell accumulation.

Infection-induced coronary dysfunction and systemic inflammation in piglets are dampened in hypercholesterolemic milieu.

The synergism of infection with conventional cardiovascular risk factors in atherosclerosis is much debated. We hypothesized that coronary arterial injury correlates with infection recurrence and pathogen burden and is further aggravated by hypercholesterolemia. Forty-two Göttingen minipigs were assigned to repeated intratracheal inoculation of PBS, Chlamydia pneumoniae (Cpn), or both Cpn and influenza virus at 8, 11, and 14 wk of age. Animals were fed either standard or 2% cholesterol diet (chol-diet). At 19 wk of age coronary vasomotor responses to acetylcholine (ACh) and adenosine were assessed in vivo and blood and tissue samples were collected. Nonparametric tests were used to compare the groups. In cholesterol-fed animals, total cholesterol/HDL was significantly increased in infected animals compared with noninfected animals [3.13 (2.17-3.38) vs. 2.03 (1.53-2.41), respectively; P = 0.01]. C-reactive protein (CRP) rose in infected animals [10.60 (4.96-18.00) vs. 2.47 (1.44-3.01) µg/ml in noninfected; P < 0.01] without significant difference between the mono- and coinfected groups. Among coinfected animals, both CRP and haptoglobin were lower in those fed chol-diet than in those fed standard diet (P < 0.05). The vasoconstricting response to ACh was most prominent in coinfected animals {769.3 (594-1,129) cm; P = 0.03 vs. noninfected [342 (309-455) cm] and P = 0.07 vs. monoinfected [415 (252.5-971.8) cm]}. Among monoinfected animals, similar to CRP, a trend for less vasoconstriction was observed in those fed chol-diet (P = 0.08). Coinfection of piglets appears to be associated with more pronounced coronary muscarinic vasomotor dysfunction. In monoinfected animals, use of chol-diet seems to dampen both coronary dysfunction and systemic inflammation induced by infection.

Poor vitamin C status is associated with increased carotid intima-media thickness, decreased microvascular function, and delayed myocardial repolarization in young patients with type 1 diabetes.

BACKGROUND: Vascular endothelial dysfunction, accelerated thickening of arterial intima, and changes in ventricular repolarization contribute to increased cardiovascular morbidity in type 1 diabetes (T1D). Although vitamin C has important antioxidant functions and increased oxidative stress is a central mechanism of cardiovascular dysfunction in T1D, the relation between vitamin C and the cardiovascular system in young diabetic patients has not been investigated. OBJECTIVE: In a cohort of young patients with T1D, we investigated the relation of plasma concentrations of vitamin C with indexes of vascular function and structure and duration of the QT interval corrected for heart rate (QT(c)). DESIGN: Carotid artery intima-media thickness, cutaneous microvascular function, and duration of the QT(c) interval were measured in 59 patients (mean age: 17 y; range: 10-22 y) with T1D (diabetes duration: 3-20 y). Plasma vitamin C was analyzed by HPLC with coulometric detection. RESULTS: Carotid artery intima-media thickness and duration of the QT(c) interval were higher in patients in the lowest tertile of vitamin C than in those in the highest tertile (P < 0.05 for both). The cutaneous microvascular response to acetylcholine was lower (P = 0.003) in the lowest tertile group than in the highest tertile group, but the response to sodium nitroprusside was not significantly different between these 2 groups. All differences remained significant after adjustment for age, sex, diabetes duration, body mass index, and glycated hemoglobin. CONCLUSIONS: In this relatively small-scale cross-sectional study of young patients with T1D, lower plasma concentrations of vitamin C seem to be associated with adverse changes in the microcirculation, peripheral arteries, and ventricular repolarization. Large-scale prospective studies are needed to confirm these results and to clarify the underlying mechanisms.

Cutaneous microvascular dysfunction is associated with human leukocyte antigen-DQ in youths with type 1 diabetes.

Functional disturbances in microcirculation in juvenile type 1 diabetes (T1D) are believed to underlie, in part, the later occurrence of cardiovascular complications. Some epidemiologic studies suggested greater risk of microvascular complications in those with T1D-risk genotypes of human leukocyte antigen (HLA). We investigated whether HLA-DQ2/8, which is linked to highest T1D morbidity, influences microvascular function in young diabetic patients. Cutaneous microvascular endothelium-dependent and independent reactivity and HLA genotypes were assessed in young patients (age: 9-21 y) with T1D (duration: 2-20 y). HLA-DQ2/8 was identified in 29 of 75 patients. The DQ2/8 and non-DQ2/8 groups were similar in age, body mass index, diabetes duration, glycosylated hemoglobin, and C-reactive protein (CRP). Compared with the non-DQ2/8 group, the DQ2/8 group showed decreased endothelium-dependent responses (p = 0.03 after adjustment for age, diabetes duration, glycosylated hemoglobin, and CRP) and elevated soluble intercellular adhesion molecule-1 (p = 0.05). In these but not in non-DQ2/8 patients, CRP correlated with both systolic (r = 0.76; p < 0.001) and diastolic (r = 0.50; p = 0.01) blood pressure. HLA-DQ2/8 is associated with endothelial microvascular dysfunction in young patients with T1D, and future studies are needed to provide mechanistic insights. The findings could explain in part the previously reported epidemiologic link between T1D-risk HLA and microvascular complications.

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 > or = 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 < 0.01), whereas LDL-to-HDL ratio increased further (2.2, P < 0.001) in the subgroup of DQ2/8 and CRP > or = 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.