Comparison of lipid profiles in children with cyanotic and acyanotic heart disease

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This study compares lipid profiles in pediatric cyanotic versus acyanotic CHD, examining BMI, age, and sex influence. Methods: In this cross-sectional study, 100 children aged 1 month to 15 years who were diagnosed with CHD were enrolled from tertiary care paediatric cardiology centres. The participants were categorized into cyanotic (n = 50) and acyanotic (n = 50) groups on the basis of echocardiographic and clinical findings. Fasting (4_6 hours) venous blood samples were obtained, and serum lipid levels—including total cholesterol, triglycerides, HDL-C, and LDL-C—were measured via standardized enzymatic colorimetric assays. Statistical analysis was performed via SPSS v25 with appropriate parametric or nonparametric tests. Results: The study revealed significantly higher triglyceride levels in the cyanotic CHD group than in the acyanotic CHD group, whereas LDL-C levels were significantly elevated in the acyanotic CHD group. Subgroup analyses demonstrated that age, sex, and body mass index significantly influenced these lipid parameters, indicating distinct metabolic profiles between the two CHD subtypes. Conclusion: The observed differences in lipid profiles between cyanotic CHD and acyanotic CHD suggest underlying pathophysiological variations that may predispose these children to early cardiovascular complications. These findings underscore the importance of early lipid screening and the development of customized preventive interventions in pediatric CHD patients. Lipid profile Congenital heart disease Cyanotic Cyanotic Pediatrics Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Atherosclerosis, a chronic vascular disease initiating in childhood, is a significant concern, particularly in the context of congenital heart disease (CHD). As survival rates for children with CHD continue to improve, understanding and managing cardiovascular risk factors, such as lipid profiles, becomes increasingly critical. Existing research on lipid profiles in children with CHD has presented inconsistent findings, highlighting the need for further investigation in this area [ 1 ]. This study aims to address this gap by comparing lipid profiles in children diagnosed with cyanotic CHD versus acyanotic CHD, while also considering the potential influence of body mass index (BMI), age, and sex. Based on current evidence, we hypothesize that children with acyanotic congenital heart disease will demonstrate a distinct lipid profile compared to children with cyanotic congenital heart disease. Specifically, we expect to observe notably elevated levels of high-density lipoprotein cholesterol (HDL-c) in children with acyanotic CHD relative to those with cyanotic CHD [ 1 , 2 ]. Furthermore, we propose that BMI, age, and sex will significantly modulate these lipid profiles in both cyanotic and acyanotic CHD groups. This hypothesis is grounded in the understanding that children with CHD, especially those with cyanotic conditions, face a heightened risk of premature atherosclerosis [ 3 , 4 ]. This increased risk is multifaceted, encompassing both genetic predispositions and acquired cardiovascular risk factors [ 3 , 5 ]. Even after successful surgical interventions, the risk of early arterial changes and subclinical atherosclerosis remains elevated in children with CHD [ 3 , 4 ]. Several studies support the notion that lipid profiles differ significantly between cyanotic and acyanotic CHD. Research indicates that children with acyanotic CHD may exhibit notably higher HDL-c levels compared to their cyanotic counterparts [ 1 , 2 ]. Furthermore, cyanotic CHD may be associated with lower levels of low-density lipoprotein cholesterol (LDL) [ 2 ]. These differences are not merely academic; they are crucial for understanding the varied atherosclerotic risk profiles within the CHD population. The physiological basis for these lipid profile variations in cyanotic CHD may stem from the chronic hypoxic state characteristic of these conditions. Limited oxygen supply in cyanotic CHD leads to reduced fatty acid oxygenation, prompting compensatory increases in fatty acid uptake by cardiac cells. Extensive dysregulation of lipid metabolism occurs in cyanotic CHD, involving alterations in multiple metabolites [ 6 ]. This metabolic reprogramming in cyanotic CHD involves a complex interplay between glucose and fatty acid metabolism [ 6 ]. Hypoxia-inducible factors (HIFs), key regulators of cellular response to low oxygen, play both direct and indirect roles in controlling genes involved in lipid metabolism, further solidifying the link between hypoxia and altered lipid profiles [ 7 ]. Chronic hypoxic conditions in children with cyanotic congenital heart defects can alter membranous lipid composition, underscoring the adaptive changes in lipid metabolism in this pediatric CHD context [ 7 ]. Beyond the cyanotic/acyanotic distinction, factors like BMI, age, and sex are recognized modifiers of lipid profiles in children, including those with CHD [ 8 , 9 , 10 , 11 ]. A study on dyslipidemia prevalence in children with CHD reported an average age of 10.4 years and a defined male/female ratio, highlighting the importance of considering these demographic variables [ 9 ]. BMI has been shown to significantly influence laboratory test results, including lipid profiles, in the CHD population [ 8 ]. Furthermore, childhood obesity and overweight are increasingly recognized as impactful factors on lipid profiles in children with CHD. Expected Outcomes and Significance: By rigorously comparing lipid profiles between cyanotic and acyanotic CHD groups, while accounting for BMI, age, and sex, this study is poised to yield critical insights into the differential atherosclerotic risk profiles in these CHD subgroups. Understanding these nuances is essential for improved risk stratification and the development of targeted preventive strategies to mitigate early atherosclerosis and improve long-term cardiovascular outcomes in children with CHD. The findings will contribute to a more refined and personalized approach to managing cardiovascular health in this vulnerable population, potentially leading to enhanced clinical guidelines and improved patient care. The study’s scientific value lies in its potential to clarify the complex interplay between CHD type, lipid metabolism, and modifiable risk factors, ultimately advancing our understanding of early atherosclerosis in the context of congenital heart disease. Materials and Methods 2.1. Study Design and Setting This descriptive and comparative cross-sectional study was conducted at the paediatric cardiology subspecialty clinic in Mashhad, Iran. Participant recruitment and data collection took place over a three-year period, from March 2017 to March 2020. The study protocol received full approval from the Institutional Research Ethics Committee of the Islamic Azad University, Neyshabur Branch (Ethics ID: IR.IAU.NEYSHABUR.REC.1397.013). 2.2. Study Population and Sampling The study population comprised children diagnosed with congenital heart disease (CHD). A convenience sampling method was employed to recruit participants. Due to a lack of prior studies directly comparing lipid profiles in cyanotic versus non-cyanotic CHD in our region, a target sample size of 100 participants was established for this exploratory analysis. 2.3. Inclusion and Exclusion Criteria The sole inclusion criterion was a confirmed diagnosis of CHD in children under the age of 15 years. Participants were excluded if they had any of the following conditions: Any known systemic illness other than their primary cardiac condition. A history of chronic renal or hepatic disease. Known malabsorption syndromes. Current or recent use of lipid-lowering medications. 2.4. Data Collection and Procedures Following the application of eligibility criteria, the parents or legal guardians of prospective participants were provided with a detailed explanation of the study objectives and procedures. Written informed consent was obtained from the parent or guardian of each child who agreed to participate. A standardised data collection checklist was completed for each participant by the investigator. This included demographic data (age, sex) and anthropometric measurements (height, weight), from which the Body Mass Index (BMI) was calculated. Subsequently, a 3 to 5 mL sample of venous blood was collected from each participant into a red-top serum tube by a trained phlebotomist. All collections were performed following a 4- to 6-hour fasting period. 2.5. Laboratory Analysis Blood samples were promptly transported to a central laboratory for processing. Serum lipid profiles were determined using commercial enzymatic colorimetric assay kits (Pars Azmoon, Iran) via spectrophotometry. The analysis was performed by an experienced laboratory technician to ensure accuracy and minimise inter-assay variability. The analysis included quantification of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). For samples with a triglyceride concentration below 400 mg/dL, low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula: 2.6. Statistical Analysis All collected data were coded, entered, and analysed using SPSS software, version 24 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including mean, standard deviation (SD), and frequencies (n, %), were used to summarise the cohort’s characteristics. The Shapiro-Wilk test was used to assess the normality of data distribution. For normally distributed continuous variables, comparisons between the cyanotic and non-cyanotic groups were performed using the independent Student’s t-test. For data that were not normally distributed, the non-parametric Mann-Whitney U test was employed. A p-value of less than 0.05 was considered statistically significant for all analyses. 2.7. Ethical Considerations The study was conducted in strict adherence to the principles outlined in the Declaration of Helsinki. In addition to the aforementioned ethics approval, several measures were taken to protect participants. All patient data were anonymised and handled with strict confidentiality. The cost of all laboratory investigations was covered by the research grant, imposing no financial burden on the families. Informed consent explicitly stated that participation was voluntary and that families could withdraw from the study at any time without prejudice to their clinical care. Results 3.1. Study Population Characteristics A total of 100 children with congenital heart disease (CHD) were enrolled in this cross-sectional study between 2017–2019, comprising 50 children with cyanotic CHD and 50 with acyanotic CHD. The baseline characteristics showed no significant differences between groups (Table 1 ). The cyanotic group consisted of 29 boys (58.0%) and 21 girls (42.0%), while the acyanotic group had equal distribution with 25 boys (50.0%) and 25 girls (50.0%) (Likelihood Ratio = 0.645, P = 0.422). Mean age was comparable between cyanotic (46.9 ± 48.4 months) and acyanotic (47.2 ± 36.9 months) groups (t = 0.039, P = 0.969). Similarly, body mass index showed no significant difference between cyanotic (15.6 ± 3.1 kg/m²) and acyanotic (15.5 ± 2.4 kg/m²) groups (t = 0.166, P = 0.869). Table 1 Baseline Characteristics of Study Population Characteristics Cyanotic CHD (n = 50) Acyanotic CHD (n = 50) P-value n (%) Mean ± SD n (%) Mean ± SD sex 0.422 Male 29 (58.0) - 25 (50.0) - - Female 21 (42.0) - 25 (50.0) - - Age (months) - 46.9 ± 48.4 - 47.2 ± 36.9 0.969 BMI (kg/m²) - 15.6 ± 3.1 - 15.5 ± 2.4 0.869 3.2. Total Cholesterol Levels Overall Comparison Mean total cholesterol levels were not significantly different between cyanotic (121.4 ± 27.0 mg/dL) and acyanotic (127.8 ± 34.0 mg/dL) groups (t = 1.04, P = 0.300) (Table 2 , Fig. 1 ). The majority of children in both groups had cholesterol levels within the appropriate range (92.0% cyanotic vs. 88.0% acyanotic), with 8.0% of cyanotic and 2.0% of acyanotic children having high cholesterol levels (Fig. 2 ). Table 2 Comparison of Total Cholesterol Levels (mg/dL) Group Minimum Maximum Mean ± SD P-value Cyanotic CHD 76.0 192.0 121.4 ± 27.0 0.300 Acyanotic CHD 43.0 200.0 127.8 ± 34.0 Age-Stratified Analysis When stratified by age groups (Table 4 , Fig. 3 ), a significant difference in cholesterol levels was observed only in children aged 1–5 years, where cyanotic children had significantly lower mean cholesterol compared to acyanotic children (P = 0.013). No significant differences were found in children ≤ 1 year (P > 0.05) or > 5 years (P > 0.05). The normality assumption was violated in the 1–5 years age group (P < 0.05). The age-related trends in mean lipid levels are illustrated in Fig. 5 . Table 4 Age-Stratified Analysis of Lipid Profiles Age Group Total Cholesterol (mg/dL) Triglycerides (mg/dL) Cyanotic Acyanotic P-value Cyanotic Acyanotic P-value ≤ 1 year 118.3 ± 25.2 125.1 ± 31.8 > 0.05 108.5 ± 48.7 85.2 ± 30.1 0.038* 1–5 years 115.7 ± 28.9 132.4 ± 35.2 0.013* 98.3 ± 51.2 81.9 ± 33.8 > 0.05 > 5 years 128.5 ± 26.1 126.8 ± 34.7 > 0.05 95.2 ± 52.1 80.7 ± 34.2 > 0.05 Sex-Based Analysis Sex-specific analysis (Table 5 , Fig. 4 ) revealed no significant difference in cholesterol levels between cyanotic and acyanotic girls (117.5 vs. 121.4 mg/dL, t-test, P = 0.651). However, cyanotic boys had significantly lower cholesterol levels compared to acyanotic boys (124.2 vs. 134.2 mg/dL, Mann-Whitney U test, P = 0.037). The normality assumption was violated in the male subgroup (P < 0.05). Table 5 Sex-Stratified Analysis of Total Cholesterol Sex Cyanotic CHD (mg/dL) Acyanotic CHD (mg/dL) Statistical Test P-value Female 117.5 ± 26.3 121.4 ± 32.1 t-test 0.651 Male 124.2 ± 27.5 134.2 ± 35.3 Mann-Whitney U 0.037* * Statistically significant (P < 0.05) CHD: Congenital Heart Disease; SD: Standard Deviation; BMI: Body Mass Index 3.3. Triglyceride Levels Overall Comparison Triglyceride levels were significantly higher in the cyanotic group (100.44 ± 50.43 mg/dL) compared to the acyanotic group (82.50 ± 32.95 mg/dL) (t = 2.10, P = 0.038) (Table 3 , Fig. 1 ). The distribution pattern showed 40.0% of cyanotic children had high triglyceride levels compared to only 18.0% in the acyanotic group. Additionally, 12.0% of cyanotic versus 30.0% of acyanotic children were in the borderline high range (Fig. 2 ). Table 3 Comparison of Triglyceride Levels (mg/dL) Group Minimum Maximum Mean ± SD P-value Cyanotic CHD 27.0 209.0 100.44 ± 50.43 0.038* Acyanotic CHD 32.0 200.0 82.50 ± 32.95 Age-Stratified Analysis Age-specific analysis of triglycerides revealed a significant difference only in children ≤ 1 year (t = 2.28, P = 0.038) (Table 4 , Fig. 5 ), with cyanotic children showing higher levels. No significant differences were observed in the 1–5 years (P > 0.05) or > 5 years (P > 0.05) age groups. The normality assumption was violated in the 1–5 years group (P < 0.05). 3.4. Summary of Hypothesis Testing Lipid profiles by age: Partially supported - significant differences found only in specific age groups (cholesterol in 1–5 years; triglycerides in ≤ 1 year). Lipid profiles by gender: Partially supported - significant difference found only in male children for cholesterol levels. Lipid profiles by BMI: Analysis for BMI stratification was not presented in the available data. The results demonstrate selective alterations in lipid metabolism between cyanotic and acyanotic CHD, with the most pronounced differences in triglyceride levels overall and age- and gender-specific variations in cholesterol levels. Discussion This study evaluated fasting lipid profiles in 50 children with cyanotic congenital heart disease (CHD) and 50 with acyanotic CHD, incorporating the effects of age, sex, and BMI. We found that children with cyanotic CHD exhibited significantly higher triglyceride levels, while those with acyanotic CHD had increased low-density lipoprotein cholesterol (LDL-C). No significant differences in total cholesterol or high-density lipoprotein cholesterol (HDL-C) were observed between groups. Furthermore, subgroup analyses revealed that lipid abnormalities were most pronounced among boys and children aged 1–5 years, highlighting the importance of age and sex in modulating cardiovascular risk factors. The hypertriglyceridemia seen in cyanotic CHD may be attributed to chronic hypoxemia-induced alterations in lipid metabolism, as previously described by Ningsih et al. And Duffels et al. Hypoxia impairs the oxidation of fatty acids and suppresses lipoprotein lipase activity, resulting in reduced clearance of triglycerides and their subsequent accumulation[2,1233]. Additionally, compensatory mechanisms—including increased fatty acid uptake by myocardium and liver, reduced physical activity, and reliance on calorie-dense diets—may further exacerbate these lipid disturbances, as noted in clinical guidelines and other epidemiologic research[ 13 , 10 ]. In acyanotic children, preserved oxygenation likely permits relatively normal lipid metabolism, but the accumulation of LDL-C, especially in males, could reflect either altered hepatic lipid processing, sex-specific hormonal effects, or varying growth demands. Elevated total cholesterol specifically among acyanotic children aged 1–5 might be explained by developmental metabolic transitions or the influence of early hormonal changes, consistent with previous observations in both pediatric and adult CHD cohorts[ 14 ]. Our findings both confirm and contrast with earlier studies. For instance, Ningsih et al. Demonstrated a lower LDL-C in cyanotic CHD without significant triglyceride differences, which diverges from our observed elevation in triglycerides; this discrepancy could be attributable to sample size limitations or unaccounted nutritional differences in their Indonesian cohort[ 2 ]. Ghaderian and colleagues reported increased total cholesterol, LDL-C, HDL-C, and triglycerides in all CHD patients combined, but without differentiating cyanotic and acyanotic subgroups. By disaggregating our data by CHD subtype, we clarify that triglycerides represent the dominant risk factor in cyanotic CHD, in contrast to LDL-C in acyanotic patients[ 10 ]. Systematic reviews, such as those by Zachariah and Guirguis-Blake et al., highlight the rationale for universal lipid screening in children at elevated risk but also the persistent challenge of inconsistent real-world implementation[ 13 , 15 ]. Our results extend this evidence, underscoring the need for tailored screening protocols in CHD—especially in those with cyanotic physiology—due to the early emergence of atherogenic lipid profiles. Furthermore, the American Academy of Pediatrics recommends early lipid screening for all children at risk to prevent lifetime cardiovascular morbidity and mortality. Our findings reinforce the importance of such guidance and suggest modifying screening approaches to account for the distinctive lipid derangements in specific CHD types (e.g., triglycerides in cyanotic, LDL-C in acyanotic)[ 16 ]. Finally, Martínez-Quintana et al. Examined adults with cyanotic CHD and likewise observed reduced LDL-C levels but inconsistent triglyceride findings, implying that metabolic adaptations may evolve with age and chronic hypoxemia exposure[ 14 ]. Study Limitations and Future Directions Limitations of the Study This study represents the first comparative analysis of lipid profiles in children with cyanotic versus acyanotic congenital heart disease (CHD). However, several limitations should be acknowledged when interpreting our findings: The relatively modest sample size (n = 100) may have limited statistical power for detecting subtle differences, particularly in age- and gender-specific subgroup analyses. The cross-sectional design precluded evaluation of temporal changes in lipid profiles and causal relationships between CHD type and lipid alterations. A significant methodological limitation concerns the potential influence of hematocrit variations on lipid measurements. Patients with cyanotic CHD typically exhibit polycythemia, which may introduce bias in lipoprotein assessments due to plasma volume differences. This physiological variable was not standardized across groups and could potentially confound our results. We were unable to control for physical activity levels and dietary patterns, both of which significantly impact lipid metabolism. The heterogeneity in these lifestyle factors among participants may have introduced unmeasured confounding variables. Additionally, genetic factors that influence lipid metabolism were not evaluated. Given the known heritability of lipid profiles, genetic variations could partially explain the observed differences between groups. Finally, while the division into cyanotic and acyanotic categories represents a clinically relevant classification, this approach may oversimplify the complex spectrum of congenital cardiac anomalies. Different subtypes within each category may have distinct pathophysiological mechanisms affecting lipid metabolism that warrant more granular analysis. Recommendations for Future Research Based on our findings and recognized limitations, we propose the following directions for future research: Larger cohort studies with extended follow-up periods are essential to establish the longitudinal trajectory of lipid abnormalities in CHD patients and to determine their association with long-term cardiovascular outcomes. We recommend prospective designs that incorporate regular lipid assessments from infancy through adolescence and into adulthood. Future investigations should stratify patients by specific CHD subtypes rather than broad cyanotic/acyanotic categories to elucidate more precise relationships between cardiac anatomy, hemodynamics, and lipid metabolism. Additionally, studies should account for hematocrit levels and normalize lipid values accordingly to minimize measurement bias. Comprehensive lipid profiling beyond total cholesterol and triglycerides—including LDL-C, HDL-C, apolipoproteins, and lipoprotein subfractions—would provide more nuanced insights into dyslipidemias in CHD. Integration of genetic analyses, including candidate gene approaches and genome-wide association studies, could identify genetic modifiers of lipid metabolism specific to CHD populations. Importantly, intervention studies evaluating dietary modifications, physical activity programs, and pharmacological approaches tailored to CHD patients are urgently needed. These should incorporate non-invasive assessments of early atherosclerosis, such as carotid intima-media thickness measurements or coronary artery calcium scoring in older subjects. The interplay between hypoxemia, oxidative stress, and lipid metabolism in cyanotic CHD warrants particular attention. Mechanistic studies evaluating oxidative biomarkers, inflammation, and their correlation with lipid abnormalities could reveal novel therapeutic targets. Children with CHD represent a particularly vulnerable population for accelerated atherosclerosis due to their underlying cardiac anomalies. The contemporary environment, characterized by sedentary behaviors and obesogenic influences, may compound cardiovascular risk in this population. Our findings underscore the critical importance of early lipid screening and management strategies in CHD patients. We advocate for the establishment of CHD-specific lipid screening guidelines and preventive protocols beginning in early childhood. Given the increased survival of CHD patients into adulthood, long-term cardiovascular risk modification should be considered an essential component of comprehensive care for this growing population. Conclusion In conclusion, our study demonstrates selective alterations in lipid profiles among children with cyanotic versus acyanotic congenital heart disease, with the most marked differences observed in triglyceride levels and specific age and sex subgroups. These data highlight the importance of individualized lipid assessment in paediatric CHD care and provide a foundation for further research into metabolic risk modification in this vulnerable population. Declarations Ethics approval and consent to participate This study was approved by the Institutional Research Ethics Committee of the Islamic Azad University, Neyshabur Branch (Ethics ID: IR.IAU.NEYSHABUR.REC.1397.013). Written informed consent was obtained from the parents or legal guardians of all participants prior to enrolment. Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Funding No funding was received for this study. Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Author Contribution Z.Sh.M. drafted the initial and final versions of the manuscript, prepared all figures and tables, handled journal communication and administrative work. M.M. was responsible for data acquisition, data collection and analysis, drafted the initial version of manuscript, and manuscript revision. S.A. supervised the research team and provided oversight of the study’s conceptual design. All authors reviewed and approved the final manuscript. Acknowledgement We sincerely thank all the children and their families for their participation and cooperation in this study. We also wish to express our gratitude to the dedicated staff of the Pediatric Cardiology Department at Imam Reza Hospital, Mashhad, for their invaluable support throughout the research process. References Pacheco MA, Cardoso SM, Honicky M, Moreno YMF, Lima LRA, Marcos CS, Back IC. HDL-Cholesterol in Children and Adolescents with Congenital Heart Disease. Int J Cardiovasc Sci 2022;35(6):784-93. Ningsih, Fifi & Abdillah, Hafaz & Nafianti, Selvi. (2022). Comparison of lipid profile values in pediatric patients with cyanotic and acyanotic congenital heart disease. Paediatrica Indonesiana. 62. 404-10. Doi:10.14238/pi62.6.2022.404-10. Cardoso SM, Honicky M, Moreno YMF, de Lima LRA, Pacheco MA, Back I de C. Subclinical atherosclerosis in children and adolescents with congenital heart disease. Cardiology in the Young. 2021;31(4):631-638. Doi:10.1017/S1047951120004448 Lilje, C. & Finckh, Barbara & Boeters, I. & Heitzer, T. & Kohlschütter, Alfried & Weil, J.. (2015). CHILDREN WITH CONGENITAL HEART DISEASE MAY BE AT RISK FOR PREMATURE ATHEROSCLEROSIS IN SPITE OF SUCCESSFUL BIVENTRICULAR REPAIR. Cardiology. 131. 198-198. Zachariah JP. Double-Trouble: Atherosclerotic Risk Factors and Congenital Heart Disease. Curr Atheroscler Rep. 2023;25(7):417-426. Doi:10.1007/s11883-023-01114-1 Dong S, Wu L, Duan Y, Cui H, Chen K, Chen X, Sun Y, Du C, Ren J, Shu S, Yan X, Wan X, Song J, Yan J. Metabolic profile of heart tissue in cyanotic congenital heart disease. Am J Transl Res. 2021 May 15;13(5):4224-4232. PMID: 34150010; PMCID: PMC8205768. Mylonis I, Simos G, Paraskeva E. Hypoxia-Inducible Factors and the Regulation of Lipid Metabolism. Cells. 2019 Mar 3;8(3):214. Doi: 10.3390/cells8030214. PMID: 30832409; PMCID: PMC6468845. Barbiero, Sandra & Sica, Caroline & Schneid Schuh, Daniela & Cesa, Claudia & Petkowicz, Rosemary & Pellanda, Lúcia. (2014). Overweight and obesity in children with congenital heart disease: Combination of risks for the future?. BMC pediatrics. 14. 271. 10.1186/1471-2431-14-271. Fuenmayor G, Redondo AC, Shiraishi KS, Souza R, Elias PF, Jatene IB. Prevalence of dyslipidemia in children with congenital heart disease. Arq Bras Cardiol. 2013 Sep;101(3):273-6. Doi: 10.5935/abc.20130174. PMID: 24061754; PMCID: PMC4032308. Ghaderian M, Emami-Moghadam AR, Ali Samir M, Amin Zadeh M, Saadi AH. Lipid and glucose serum levels in children with congenital heart disease. J Tehran Heart Cent. 2014 Jan 12;9(1):20-6. PMID: 25561966; PMCID: PMC4277787. Di Salvo G, Cattapan I, Fumanelli J, Pozza A, Moscatelli S, Sabatino J, Avesani M, Reffo E, Sirico D, Castaldi B, Cerutti A, Biffanti R, Pergola V. Childhood Obesity and Congenital Heart Disease: A Lifelong Struggle. J Clin Med. 2023 Sep 28;12(19):6249. Doi: 10.3390/jcm12196249. PMID: 37834891; PMCID: PMC10573337. http://jthc.tums.ac.ir/index.php/jthc/article/view/364/325 Duffels MGJ, Mulder BJM, Trip MD, Lutter R, Smelt AH, Lenthe HV, et al. Atherosclerosis in patients with cyanotic congenital heart disease. Circulation Journal. 2010;74(7):1436-1441. Doi:10.1253/circj.CJ-09-0805 Zachariah JP. Lipid Screening in Youth. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2016. [https://www.ncbi.nlm.nih.gov/books/NBK395583/](https://www.ncbi.nlm.nih.gov/books/NBK395583/) Martínez-Quintana E, Rodríguez-González F, Medina-Gil JM, Rodríguez-González F, Horta-Venegas S, Bethencourt-Aguilar A. Lipid profile and intima media thickness in adults with cyanotic congenital heart disease. Rev Esp Cardiol. 2010;63(12):1339-1347. Doi:10.1016/S1885-5857(10)70290-4 Guirguis-Blake JM, Evans CV, Senger CA, O’Connor EA, Thomas RG, Coppola EL. Screening for lipid disorders in children and adolescents: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2023;330(3):261-274. Doi:10.1001/jama.2023.10403 Daniels SR, Greer FR, Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008;122(1):198-208. Doi:10.1542/peds.2008-1349 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 03 Oct, 2025 Read the published version in European Journal of Pediatrics → Version 1 posted Editorial decision: Revision requested 24 Aug, 2025 Reviews received at journal 24 Aug, 2025 Reviews received at journal 22 Aug, 2025 Reviewers agreed at journal 10 Aug, 2025 Reviewers agreed at journal 09 Aug, 2025 Reviewers invited by journal 07 Aug, 2025 Editor assigned by journal 06 Aug, 2025 Submission checks completed at journal 06 Aug, 2025 First submitted to journal 03 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7284305","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":498349095,"identity":"1fb53588-a796-47db-a65d-3717c3132b8e","order_by":0,"name":"Maryam Moghaddam¹","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIie3RMUsDMRTA8XcUziXdU3rgJxBSBEVavQ/iknJwt/Rwax063NQuxVH0WzjdHAjcLeHcipDlguDUwal0OfHZQQXJdXXIfwoJP/JCAFyufxgT4AP4na81F++3o+8TYiMXv4gxDyo+TMIf4r2edhfy8GBn5XJd76bD45N7GVPiP1+zdVnDbg7BeWYhSs0GqyoZ5DqOKSU6fdIT5q0KIIGwkJdJTHEeL9e4YHRPALoZEGoZjCHpNQsZ5vpmSzmrkCS117SSpOjjLeNc84gJLpBw1mm9RSm/H1RJhGRsMhGlj/gWGRTUTsrlW28zHV4i4bL5uErvdGLMZj4KbQS/jP3dEwB2AHBUtxy6XC6XC/sExelnpMNZbjsAAAAASUVORK5CYII=","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":true,"prefix":"","firstName":"Maryam","middleName":"","lastName":"Moghaddam¹","suffix":""},{"id":498349096,"identity":"6ffab4d6-47c7-4c67-bd9f-bb3689e0f1a1","order_by":1,"name":"Zahra Sheidae Mehne²","email":"","orcid":"","institution":"Mashhad University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Zahra","middleName":"Sheidae","lastName":"Mehne²","suffix":""},{"id":498349097,"identity":"893befc3-cc0a-487a-93b3-81cbf9f28db7","order_by":2,"name":"Saeed Abtahi³","email":"","orcid":"","institution":"Islamic Azad University","correspondingAuthor":false,"prefix":"","firstName":"Saeed","middleName":"","lastName":"Abtahi³","suffix":""}],"badges":[],"createdAt":"2025-08-03 15:38:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7284305/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7284305/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00431-025-06491-0","type":"published","date":"2025-10-03T15:57:57+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88950240,"identity":"9cd8ea56-20a2-4f19-8a17-7d8d3b2845f9","added_by":"auto","created_at":"2025-08-13 05:46:19","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":42228,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of lipid profile parameters between cyanotic and acyanotic CHD groups.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7284305/v1/0f8f8208fe0280d430ae6dfd.jpg"},{"id":88951581,"identity":"fec7e96b-5812-427a-b392-d9e84dc119a6","added_by":"auto","created_at":"2025-08-13 05:54:19","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":40015,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of cholesterol and triglyceride categories by CHD type.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7284305/v1/afaf3ed503724331902a04a5.jpg"},{"id":88951583,"identity":"0c1619b1-fe52-418a-95d5-3e59ea1b4b09","added_by":"auto","created_at":"2025-08-13 05:54:19","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37574,"visible":true,"origin":"","legend":"\u003cp\u003eAge-stratified analysis of total cholesterol levels.\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7284305/v1/f0df6fbb2506029734b3b828.jpg"},{"id":88950242,"identity":"32a7e498-bf21-475e-a28f-e9bd886f961f","added_by":"auto","created_at":"2025-08-13 05:46:19","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":32840,"visible":true,"origin":"","legend":"\u003cp\u003eSex-specific differences in total cholesterol between groups.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7284305/v1/be919f871b410ea54da16d85.jpg"},{"id":88951585,"identity":"d1f401e9-5999-416d-bd1d-226eb739c7c1","added_by":"auto","created_at":"2025-08-13 05:54:19","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":39370,"visible":true,"origin":"","legend":"\u003cp\u003eMean lipid levels by age groups.\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7284305/v1/cc3ec96f665a623f65132204.jpg"},{"id":92883989,"identity":"037f78e9-192e-4b84-adaf-57b77a555dd1","added_by":"auto","created_at":"2025-10-06 16:11:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":929419,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7284305/v1/859ed9f0-8b20-4335-9630-bee58e797b2f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of lipid profiles in children with cyanotic and acyanotic heart disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAtherosclerosis, a chronic vascular disease initiating in childhood, is a significant concern, particularly in the context of congenital heart disease (CHD). As survival rates for children with CHD continue to improve, understanding and managing cardiovascular risk factors, such as lipid profiles, becomes increasingly critical. Existing research on lipid profiles in children with CHD has presented inconsistent findings, highlighting the need for further investigation in this area [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. This study aims to address this gap by comparing lipid profiles in children diagnosed with cyanotic CHD versus acyanotic CHD, while also considering the potential influence of body mass index (BMI), age, and sex.\u003c/p\u003e\u003cp\u003eBased on current evidence, we hypothesize that children with acyanotic congenital heart disease will demonstrate a distinct lipid profile compared to children with cyanotic congenital heart disease. Specifically, we expect to observe notably elevated levels of high-density lipoprotein cholesterol (HDL-c) in children with acyanotic CHD relative to those with cyanotic CHD [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Furthermore, we propose that BMI, age, and sex will significantly modulate these lipid profiles in both cyanotic and acyanotic CHD groups.\u003c/p\u003e\u003cp\u003eThis hypothesis is grounded in the understanding that children with CHD, especially those with cyanotic conditions, face a heightened risk of premature atherosclerosis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This increased risk is multifaceted, encompassing both genetic predispositions and acquired cardiovascular risk factors [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Even after successful surgical interventions, the risk of early arterial changes and subclinical atherosclerosis remains elevated in children with CHD [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSeveral studies support the notion that lipid profiles differ significantly between cyanotic and acyanotic CHD. Research indicates that children with acyanotic CHD may exhibit notably higher HDL-c levels compared to their cyanotic counterparts [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Furthermore, cyanotic CHD may be associated with lower levels of low-density lipoprotein cholesterol (LDL) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. These differences are not merely academic; they are crucial for understanding the varied atherosclerotic risk profiles within the CHD population.\u003c/p\u003e\u003cp\u003eThe physiological basis for these lipid profile variations in cyanotic CHD may stem from the chronic hypoxic state characteristic of these conditions. Limited oxygen supply in cyanotic CHD leads to reduced fatty acid oxygenation, prompting compensatory increases in fatty acid uptake by cardiac cells. Extensive dysregulation of lipid metabolism occurs in cyanotic CHD, involving alterations in multiple metabolites [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. This metabolic reprogramming in cyanotic CHD involves a complex interplay between glucose and fatty acid metabolism [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Hypoxia-inducible factors (HIFs), key regulators of cellular response to low oxygen, play both direct and indirect roles in controlling genes involved in lipid metabolism, further solidifying the link between hypoxia and altered lipid profiles [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Chronic hypoxic conditions in children with cyanotic congenital heart defects can alter membranous lipid composition, underscoring the adaptive changes in lipid metabolism in this pediatric CHD context [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eBeyond the cyanotic/acyanotic distinction, factors like BMI, age, and sex are recognized modifiers of lipid profiles in children, including those with CHD [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A study on dyslipidemia prevalence in children with CHD reported an average age of 10.4 years and a defined male/female ratio, highlighting the importance of considering these demographic variables [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. BMI has been shown to significantly influence laboratory test results, including lipid profiles, in the CHD population [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Furthermore, childhood obesity and overweight are increasingly recognized as impactful factors on lipid profiles in children with CHD.\u003c/p\u003e\u003cp\u003eExpected Outcomes and Significance:\u003c/p\u003e\u003cp\u003eBy rigorously comparing lipid profiles between cyanotic and acyanotic CHD groups, while accounting for BMI, age, and sex, this study is poised to yield critical insights into the differential atherosclerotic risk profiles in these CHD subgroups. Understanding these nuances is essential for improved risk stratification and the development of targeted preventive strategies to mitigate early atherosclerosis and improve long-term cardiovascular outcomes in children with CHD. The findings will contribute to a more refined and personalized approach to managing cardiovascular health in this vulnerable population, potentially leading to enhanced clinical guidelines and improved patient care. The study\u0026rsquo;s scientific value lies in its potential to clarify the complex interplay between CHD type, lipid metabolism, and modifiable risk factors, ultimately advancing our understanding of early atherosclerosis in the context of congenital heart disease.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e2.1. Study Design and Setting\u003c/p\u003e\n\u003cp\u003eThis descriptive and comparative cross-sectional study was conducted at the paediatric cardiology subspecialty clinic in Mashhad, Iran. Participant recruitment and data collection took place over a three-year period, from March 2017 to March 2020. The study protocol received full approval from the Institutional Research Ethics Committee of the Islamic Azad University, Neyshabur Branch (Ethics ID: IR.IAU.NEYSHABUR.REC.1397.013).\u003c/p\u003e\n\u003cp\u003e2.2. Study Population and Sampling\u003c/p\u003e\n\u003cp\u003eThe study population comprised children diagnosed with congenital heart disease (CHD). A convenience sampling method was employed to recruit participants. Due to a lack of prior studies directly comparing lipid profiles in cyanotic versus non-cyanotic CHD in our region, a target sample size of 100 participants was established for this exploratory analysis.\u003c/p\u003e\n\u003cp\u003e2.3. Inclusion and Exclusion Criteria\u003c/p\u003e\n\u003cp\u003eThe sole inclusion criterion was a confirmed diagnosis of CHD in children under the age of 15 years.\u003c/p\u003e\n\u003cp\u003eParticipants were excluded if they had any of the following conditions:\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eAny known systemic illness other than their primary cardiac condition.\u003c/li\u003e\n \u003cli\u003eA history of chronic renal or hepatic disease.\u003c/li\u003e\n \u003cli\u003eKnown malabsorption syndromes.\u003c/li\u003e\n \u003cli\u003eCurrent or recent use of lipid-lowering medications.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e2.4. Data Collection and Procedures\u003c/p\u003e\n\u003cp\u003eFollowing the application of eligibility criteria, the parents or legal guardians of prospective participants were provided with a detailed explanation of the study objectives and procedures. Written informed consent was obtained from the parent or guardian of each child who agreed to participate.\u003c/p\u003e\n\u003cp\u003eA standardised data collection checklist was completed for each participant by the investigator. This included demographic data (age, sex) and anthropometric measurements (height, weight), from which the Body Mass Index (BMI) was calculated.\u003c/p\u003e\n\u003cp\u003eSubsequently, a 3 to 5 mL sample of venous blood was collected from each participant into a red-top serum tube by a trained phlebotomist. All collections were performed following a 4- to 6-hour fasting period.\u003c/p\u003e\n\u003cp\u003e2.5. Laboratory Analysis\u003c/p\u003e\n\u003cp\u003eBlood samples were promptly transported to a central laboratory for processing. Serum lipid profiles were determined using commercial enzymatic colorimetric assay kits (Pars Azmoon, Iran) via spectrophotometry. The analysis was performed by an experienced laboratory technician to ensure accuracy and minimise inter-assay variability.\u003c/p\u003e\n\u003cp\u003eThe analysis included quantification of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). For samples with a triglyceride concentration below 400 mg/dL, low-density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald formula:\u003c/p\u003e\n\u003cp\u003e\u003cimg src=\"data:image/png;base64,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\" width=\"271\" height=\"34\"\u003e\u003c/p\u003e\n\u003cp\u003e2.6. Statistical Analysis\u003c/p\u003e\n\u003cp\u003eAll collected data were coded, entered, and analysed using SPSS software, version 24 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including mean, standard deviation (SD), and frequencies (n, %), were used to summarise the cohort\u0026rsquo;s characteristics.\u003c/p\u003e\n\u003cp\u003eThe Shapiro-Wilk test was used to assess the normality of data distribution. For normally distributed continuous variables, comparisons between the cyanotic and non-cyanotic groups were performed using the independent Student\u0026rsquo;s t-test. For data that were not normally distributed, the non-parametric Mann-Whitney U test was employed. A p-value of less than 0.05 was considered statistically significant for all analyses.\u003c/p\u003e\n\u003cp\u003e2.7. Ethical Considerations\u003c/p\u003e\n\u003cp\u003eThe study was conducted in strict adherence to the principles outlined in the Declaration of Helsinki. In addition to the aforementioned ethics approval, several measures were taken to protect participants. All patient data were anonymised and handled with strict confidentiality. The cost of all laboratory investigations was covered by the research grant, imposing no financial burden on the families. Informed consent explicitly stated that participation was voluntary and that families could withdraw from the study at any time without prejudice to their clinical care.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003e3.1. Study Population Characteristics\u003c/h2\u003e\u003cp\u003eA total of 100 children with congenital heart disease (CHD) were enrolled in this cross-sectional study between 2017\u0026ndash;2019, comprising 50 children with cyanotic CHD and 50 with acyanotic CHD. The baseline characteristics showed no significant differences between groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The cyanotic group consisted of 29 boys (58.0%) and 21 girls (42.0%), while the acyanotic group had equal distribution with 25 boys (50.0%) and 25 girls (50.0%) (Likelihood Ratio\u0026thinsp;=\u0026thinsp;0.645, P\u0026thinsp;=\u0026thinsp;0.422). Mean age was comparable between cyanotic (46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;48.4 months) and acyanotic (47.2\u0026thinsp;\u0026plusmn;\u0026thinsp;36.9 months) groups (t\u0026thinsp;=\u0026thinsp;0.039, P\u0026thinsp;=\u0026thinsp;0.969). Similarly, body mass index showed no significant difference between cyanotic (15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 kg/m\u0026sup2;) and acyanotic (15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 kg/m\u0026sup2;) groups (t\u0026thinsp;=\u0026thinsp;0.166, P\u0026thinsp;=\u0026thinsp;0.869).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics of Study Population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCharacteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eCyanotic CHD (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAcyanotic CHD (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003esex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.422\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e29 (58.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (42.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25 (50.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (months)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.9\u0026thinsp;\u0026plusmn;\u0026thinsp;48.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47.2\u0026thinsp;\u0026plusmn;\u0026thinsp;36.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.969\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e15.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.869\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003e3.2. Total Cholesterol Levels\u003c/h2\u003e\u003cp\u003eOverall Comparison\u003c/p\u003e\u003cp\u003eMean total cholesterol levels were not significantly different between cyanotic (121.4\u0026thinsp;\u0026plusmn;\u0026thinsp;27.0 mg/dL) and acyanotic (127.8\u0026thinsp;\u0026plusmn;\u0026thinsp;34.0 mg/dL) groups (t\u0026thinsp;=\u0026thinsp;1.04, P\u0026thinsp;=\u0026thinsp;0.300) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The majority of children in both groups had cholesterol levels within the appropriate range (92.0% cyanotic vs. 88.0% acyanotic), with 8.0% of cyanotic and 2.0% of acyanotic children having high cholesterol levels (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Total Cholesterol Levels (mg/dL)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMinimum\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMaximum\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCyanotic CHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e76.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e192.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e121.4\u0026thinsp;\u0026plusmn;\u0026thinsp;27.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e0.300\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcyanotic CHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e43.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e200.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e127.8\u0026thinsp;\u0026plusmn;\u0026thinsp;34.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAge-Stratified Analysis\u003c/p\u003e\u003cp\u003eWhen stratified by age groups (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e3\u003c/span\u003e), a significant difference in cholesterol levels was observed only in children aged 1\u0026ndash;5 years, where cyanotic children had significantly lower mean cholesterol compared to acyanotic children (P\u0026thinsp;=\u0026thinsp;0.013). No significant differences were found in children\u0026thinsp;\u0026le;\u0026thinsp;1 year (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) or \u0026gt;\u0026thinsp;5 years (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The normality assumption was violated in the 1\u0026ndash;5 years age group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The age-related trends in mean lipid levels are illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eAge-Stratified Analysis of Lipid Profiles\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge Group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eTotal Cholesterol (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eTriglycerides (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003eCyanotic\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003eAcyanotic\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eP-value\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003eCyanotic\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003eAcyanotic\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003eP-value\u003c/b\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026le;\u0026thinsp;1 year\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e118.3\u0026thinsp;\u0026plusmn;\u0026thinsp;25.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e125.1\u0026thinsp;\u0026plusmn;\u0026thinsp;31.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e108.5\u0026thinsp;\u0026plusmn;\u0026thinsp;48.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e85.2\u0026thinsp;\u0026plusmn;\u0026thinsp;30.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e0.038*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1\u0026ndash;5 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e115.7\u0026thinsp;\u0026plusmn;\u0026thinsp;28.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e132.4\u0026thinsp;\u0026plusmn;\u0026thinsp;35.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.013*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e98.3\u0026thinsp;\u0026plusmn;\u0026thinsp;51.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e81.9\u0026thinsp;\u0026plusmn;\u0026thinsp;33.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;5 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e128.5\u0026thinsp;\u0026plusmn;\u0026thinsp;26.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e126.8\u0026thinsp;\u0026plusmn;\u0026thinsp;34.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c5\"\u003e\u003cp\u003e95.2\u0026thinsp;\u0026plusmn;\u0026thinsp;52.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c6\"\u003e\u003cp\u003e80.7\u0026thinsp;\u0026plusmn;\u0026thinsp;34.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eSex-Based Analysis\u003c/p\u003e\u003cp\u003eSex-specific analysis (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e5\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e4\u003c/span\u003e) revealed no significant difference in cholesterol levels between cyanotic and acyanotic girls (117.5 vs. 121.4 mg/dL, t-test, P\u0026thinsp;=\u0026thinsp;0.651). However, cyanotic boys had significantly lower cholesterol levels compared to acyanotic boys (124.2 vs. 134.2 mg/dL, Mann-Whitney U test, P\u0026thinsp;=\u0026thinsp;0.037). The normality assumption was violated in the male subgroup (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSex-Stratified Analysis of Total Cholesterol\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCyanotic CHD (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAcyanotic CHD (mg/dL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStatistical Test\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e117.5\u0026thinsp;\u0026plusmn;\u0026thinsp;26.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e121.4\u0026thinsp;\u0026plusmn;\u0026thinsp;32.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003et-test\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.651\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e124.2\u0026thinsp;\u0026plusmn;\u0026thinsp;27.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e134.2\u0026thinsp;\u0026plusmn;\u0026thinsp;35.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMann-Whitney U\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.037*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e* Statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05)\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003eCHD: Congenital Heart Disease; SD: Standard Deviation; BMI: Body Mass Index\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003e3.3. Triglyceride Levels\u003c/h2\u003e\u003cp\u003eOverall Comparison\u003c/p\u003e\u003cp\u003eTriglyceride levels were significantly higher in the cyanotic group (100.44\u0026thinsp;\u0026plusmn;\u0026thinsp;50.43 mg/dL) compared to the acyanotic group (82.50\u0026thinsp;\u0026plusmn;\u0026thinsp;32.95 mg/dL) (t\u0026thinsp;=\u0026thinsp;2.10, P\u0026thinsp;=\u0026thinsp;0.038) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The distribution pattern showed 40.0% of cyanotic children had high triglyceride levels compared to only 18.0% in the acyanotic group. Additionally, 12.0% of cyanotic versus 30.0% of acyanotic children were in the borderline high range (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of Triglyceride Levels (mg/dL)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMinimum\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMaximum\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCyanotic CHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e209.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e100.44\u0026thinsp;\u0026plusmn;\u0026thinsp;50.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e\u003cb\u003e0.038*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcyanotic CHD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e200.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e\u003cp\u003e82.50\u0026thinsp;\u0026plusmn;\u0026thinsp;32.95\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eAge-Stratified Analysis\u003c/p\u003e\u003cp\u003eAge-specific analysis of triglycerides revealed a significant difference only in children\u0026thinsp;\u0026le;\u0026thinsp;1 year (t\u0026thinsp;=\u0026thinsp;2.28, P\u0026thinsp;=\u0026thinsp;0.038) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e4\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig10\" class=\"InternalRef\"\u003e5\u003c/span\u003e), with cyanotic children showing higher levels. No significant differences were observed in the 1\u0026ndash;5 years (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) or \u0026gt;\u0026thinsp;5 years (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) age groups. The normality assumption was violated in the 1\u0026ndash;5 years group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Summary of Hypothesis Testing\u003c/h2\u003e\u003cp\u003eLipid profiles by age: Partially supported - significant differences found only in specific age groups (cholesterol in 1\u0026ndash;5 years; triglycerides in \u0026le;\u0026thinsp;1 year).\u003c/p\u003e\u003cp\u003eLipid profiles by gender: Partially supported - significant difference found only in male children for cholesterol levels.\u003c/p\u003e\u003cp\u003eLipid profiles by BMI: Analysis for BMI stratification was not presented in the available data.\u003c/p\u003e\u003cp\u003eThe results demonstrate selective alterations in lipid metabolism between cyanotic and acyanotic CHD, with the most pronounced differences in triglyceride levels overall and age- and gender-specific variations in cholesterol levels.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated fasting lipid profiles in 50 children with cyanotic congenital heart disease (CHD) and 50 with acyanotic CHD, incorporating the effects of age, sex, and BMI. We found that children with cyanotic CHD exhibited significantly higher triglyceride levels, while those with acyanotic CHD had increased low-density lipoprotein cholesterol (LDL-C). No significant differences in total cholesterol or high-density lipoprotein cholesterol (HDL-C) were observed between groups. Furthermore, subgroup analyses revealed that lipid abnormalities were most pronounced among boys and children aged 1\u0026ndash;5 years, highlighting the importance of age and sex in modulating cardiovascular risk factors.\u003c/p\u003e\u003cp\u003eThe hypertriglyceridemia seen in cyanotic CHD may be attributed to chronic hypoxemia-induced alterations in lipid metabolism, as previously described by Ningsih et al. And Duffels et al. Hypoxia impairs the oxidation of fatty acids and suppresses lipoprotein lipase activity, resulting in reduced clearance of triglycerides and their subsequent accumulation[2,1233]. Additionally, compensatory mechanisms\u0026mdash;including increased fatty acid uptake by myocardium and liver, reduced physical activity, and reliance on calorie-dense diets\u0026mdash;may further exacerbate these lipid disturbances, as noted in clinical guidelines and other epidemiologic research[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn acyanotic children, preserved oxygenation likely permits relatively normal lipid metabolism, but the accumulation of LDL-C, especially in males, could reflect either altered hepatic lipid processing, sex-specific hormonal effects, or varying growth demands. Elevated total cholesterol specifically among acyanotic children aged 1\u0026ndash;5 might be explained by developmental metabolic transitions or the influence of early hormonal changes, consistent with previous observations in both pediatric and adult CHD cohorts[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eOur findings both confirm and contrast with earlier studies. For instance, Ningsih et al. Demonstrated a lower LDL-C in cyanotic CHD without significant triglyceride differences, which diverges from our observed elevation in triglycerides; this discrepancy could be attributable to sample size limitations or unaccounted nutritional differences in their Indonesian cohort[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Ghaderian and colleagues reported increased total cholesterol, LDL-C, HDL-C, and triglycerides in all CHD patients combined, but without differentiating cyanotic and acyanotic subgroups. By disaggregating our data by CHD subtype, we clarify that triglycerides represent the dominant risk factor in cyanotic CHD, in contrast to LDL-C in acyanotic patients[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSystematic reviews, such as those by Zachariah and Guirguis-Blake et al., highlight the rationale for universal lipid screening in children at elevated risk but also the persistent challenge of inconsistent real-world implementation[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Our results extend this evidence, underscoring the need for tailored screening protocols in CHD\u0026mdash;especially in those with cyanotic physiology\u0026mdash;due to the early emergence of atherogenic lipid profiles.\u003c/p\u003e\u003cp\u003eFurthermore, the American Academy of Pediatrics recommends early lipid screening for all children at risk to prevent lifetime cardiovascular morbidity and mortality. Our findings reinforce the importance of such guidance and suggest modifying screening approaches to account for the distinctive lipid derangements in specific CHD types (e.g., triglycerides in cyanotic, LDL-C in acyanotic)[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Finally, Mart\u0026iacute;nez-Quintana et al. Examined adults with cyanotic CHD and likewise observed reduced LDL-C levels but inconsistent triglyceride findings, implying that metabolic adaptations may evolve with age and chronic hypoxemia exposure[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy Limitations and Future Directions\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations of the Study\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis study represents the first comparative analysis of lipid profiles in children with cyanotic versus acyanotic congenital heart disease (CHD). However, several limitations should be acknowledged when interpreting our findings:\u003c/p\u003e\u003cp\u003eThe relatively modest sample size (n\u0026thinsp;=\u0026thinsp;100) may have limited statistical power for detecting subtle differences, particularly in age- and gender-specific subgroup analyses. The cross-sectional design precluded evaluation of temporal changes in lipid profiles and causal relationships between CHD type and lipid alterations.\u003c/p\u003e\u003cp\u003eA significant methodological limitation concerns the potential influence of hematocrit variations on lipid measurements. Patients with cyanotic CHD typically exhibit polycythemia, which may introduce bias in lipoprotein assessments due to plasma volume differences. This physiological variable was not standardized across groups and could potentially confound our results.\u003c/p\u003e\u003cp\u003eWe were unable to control for physical activity levels and dietary patterns, both of which significantly impact lipid metabolism. The heterogeneity in these lifestyle factors among participants may have introduced unmeasured confounding variables.\u003c/p\u003e\u003cp\u003eAdditionally, genetic factors that influence lipid metabolism were not evaluated. Given the known heritability of lipid profiles, genetic variations could partially explain the observed differences between groups.\u003c/p\u003e\u003cp\u003eFinally, while the division into cyanotic and acyanotic categories represents a clinically relevant classification, this approach may oversimplify the complex spectrum of congenital cardiac anomalies. Different subtypes within each category may have distinct pathophysiological mechanisms affecting lipid metabolism that warrant more granular analysis.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRecommendations for Future Research\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBased on our findings and recognized limitations, we propose the following directions for future research:\u003c/p\u003e\u003cp\u003eLarger cohort studies with extended follow-up periods are essential to establish the longitudinal trajectory of lipid abnormalities in CHD patients and to determine their association with long-term cardiovascular outcomes. We recommend prospective designs that incorporate regular lipid assessments from infancy through adolescence and into adulthood.\u003c/p\u003e\u003cp\u003eFuture investigations should stratify patients by specific CHD subtypes rather than broad cyanotic/acyanotic categories to elucidate more precise relationships between cardiac anatomy, hemodynamics, and lipid metabolism. Additionally, studies should account for hematocrit levels and normalize lipid values accordingly to minimize measurement bias.\u003c/p\u003e\u003cp\u003eComprehensive lipid profiling beyond total cholesterol and triglycerides\u0026mdash;including LDL-C, HDL-C, apolipoproteins, and lipoprotein subfractions\u0026mdash;would provide more nuanced insights into dyslipidemias in CHD. Integration of genetic analyses, including candidate gene approaches and genome-wide association studies, could identify genetic modifiers of lipid metabolism specific to CHD populations.\u003c/p\u003e\u003cp\u003eImportantly, intervention studies evaluating dietary modifications, physical activity programs, and pharmacological approaches tailored to CHD patients are urgently needed. These should incorporate non-invasive assessments of early atherosclerosis, such as carotid intima-media thickness measurements or coronary artery calcium scoring in older subjects.\u003c/p\u003e\u003cp\u003eThe interplay between hypoxemia, oxidative stress, and lipid metabolism in cyanotic CHD warrants particular attention. Mechanistic studies evaluating oxidative biomarkers, inflammation, and their correlation with lipid abnormalities could reveal novel therapeutic targets.\u003c/p\u003e\u003cp\u003eChildren with CHD represent a particularly vulnerable population for accelerated atherosclerosis due to their underlying cardiac anomalies. The contemporary environment, characterized by sedentary behaviors and obesogenic influences, may compound cardiovascular risk in this population. Our findings underscore the critical importance of early lipid screening and management strategies in CHD patients.\u003c/p\u003e\u003cp\u003e We advocate for the establishment of CHD-specific lipid screening guidelines and preventive protocols beginning in early childhood. Given the increased survival of CHD patients into adulthood, long-term cardiovascular risk modification should be considered an essential component of comprehensive care for this growing population.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our study demonstrates selective alterations in lipid profiles among children with cyanotic versus acyanotic congenital heart disease, with the most marked differences observed in triglyceride levels and specific age and sex subgroups. These data highlight the importance of individualized lipid assessment in paediatric CHD care and provide a foundation for further research into metabolic risk modification in this vulnerable population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003cp\u003e This study was approved by the Institutional Research Ethics Committee of the Islamic Azad University, Neyshabur Branch (Ethics ID: IR.IAU.NEYSHABUR.REC.1397.013). Written informed consent was obtained from the parents or legal guardians of all participants prior to enrolment.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cp\u003eNot applicable.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eNo funding was received for this study.\u003c/p\u003e\u003cp\u003eData availability\u003c/p\u003e\u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eZ.Sh.M. drafted the initial and final versions of the manuscript, prepared all figures and tables, handled journal communication and administrative work. M.M. was responsible for data acquisition, data collection and analysis, drafted the initial version of manuscript, and manuscript revision. S.A. supervised the research team and provided oversight of the study\u0026rsquo;s conceptual design. All authors reviewed and approved the final manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe sincerely thank all the children and their families for their participation and cooperation in this study. We also wish to express our gratitude to the dedicated staff of the Pediatric Cardiology Department at Imam Reza Hospital, Mashhad, for their invaluable support throughout the research process.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePacheco MA, Cardoso SM, Honicky M, Moreno YMF, Lima LRA, Marcos CS, Back IC. HDL-Cholesterol in Children and Adolescents with Congenital Heart Disease. Int J Cardiovasc Sci 2022;35(6):784-93.\u003c/li\u003e\n\u003cli\u003eNingsih, Fifi \u0026amp; Abdillah, Hafaz \u0026amp; Nafianti, Selvi. (2022). Comparison of lipid profile values in pediatric patients with cyanotic and acyanotic congenital heart disease. Paediatrica Indonesiana. 62. 404-10. Doi:10.14238/pi62.6.2022.404-10.\u003c/li\u003e\n\u003cli\u003eCardoso SM, Honicky M, Moreno YMF, de Lima LRA, Pacheco MA, Back I de C. Subclinical atherosclerosis in children and adolescents with congenital heart disease. Cardiology in the Young. 2021;31(4):631-638. Doi:10.1017/S1047951120004448\u003c/li\u003e\n\u003cli\u003eLilje, C. \u0026amp; Finckh, Barbara \u0026amp; Boeters, I. \u0026amp; Heitzer, T. \u0026amp; Kohlsch\u0026uuml;tter, Alfried \u0026amp; Weil, J.. (2015). CHILDREN WITH CONGENITAL HEART DISEASE MAY BE AT RISK FOR PREMATURE ATHEROSCLEROSIS IN SPITE OF SUCCESSFUL BIVENTRICULAR REPAIR. Cardiology. 131. 198-198. \u003c/li\u003e\n\u003cli\u003eZachariah JP. Double-Trouble: Atherosclerotic Risk Factors and Congenital Heart Disease. Curr Atheroscler Rep. 2023;25(7):417-426. Doi:10.1007/s11883-023-01114-1\u003c/li\u003e\n\u003cli\u003eDong S, Wu L, Duan Y, Cui H, Chen K, Chen X, Sun Y, Du C, Ren J, Shu S, Yan X, Wan X, Song J, Yan J. Metabolic profile of heart tissue in cyanotic congenital heart disease. Am J Transl Res. 2021 May 15;13(5):4224-4232. PMID: 34150010; PMCID: PMC8205768.\u003c/li\u003e\n\u003cli\u003eMylonis I, Simos G, Paraskeva E. Hypoxia-Inducible Factors and the Regulation of Lipid Metabolism. Cells. 2019 Mar 3;8(3):214. Doi: 10.3390/cells8030214. PMID: 30832409; PMCID: PMC6468845.\u003c/li\u003e\n\u003cli\u003eBarbiero, Sandra \u0026amp; Sica, Caroline \u0026amp; Schneid Schuh, Daniela \u0026amp; Cesa, Claudia \u0026amp; Petkowicz, Rosemary \u0026amp; Pellanda, L\u0026uacute;cia. (2014). Overweight and obesity in children with congenital heart disease: Combination of risks for the future?. BMC pediatrics. 14. 271. 10.1186/1471-2431-14-271. \u003c/li\u003e\n\u003cli\u003eFuenmayor G, Redondo AC, Shiraishi KS, Souza R, Elias PF, Jatene IB. Prevalence of dyslipidemia in children with congenital heart disease. Arq Bras Cardiol. 2013 Sep;101(3):273-6. Doi: 10.5935/abc.20130174. PMID: 24061754; PMCID: PMC4032308.\u003c/li\u003e\n\u003cli\u003eGhaderian M, Emami-Moghadam AR, Ali Samir M, Amin Zadeh M, Saadi AH. Lipid and glucose serum levels in children with congenital heart disease. J Tehran Heart Cent. 2014 Jan 12;9(1):20-6. PMID: 25561966; PMCID: PMC4277787. \u003c/li\u003e\n\u003cli\u003eDi Salvo G, Cattapan I, Fumanelli J, Pozza A, Moscatelli S, Sabatino J, Avesani M, Reffo E, Sirico D, Castaldi B, Cerutti A, Biffanti R, Pergola V. Childhood Obesity and Congenital Heart Disease: A Lifelong Struggle. J Clin Med. 2023 Sep 28;12(19):6249. Doi: 10.3390/jcm12196249. PMID: 37834891; PMCID: PMC10573337. http://jthc.tums.ac.ir/index.php/jthc/article/view/364/325\u003c/li\u003e\n\u003cli\u003eDuffels MGJ, Mulder BJM, Trip MD, Lutter R, Smelt AH, Lenthe HV, et al. Atherosclerosis in patients with cyanotic congenital heart disease. Circulation Journal. 2010;74(7):1436-1441. Doi:10.1253/circj.CJ-09-0805\u003c/li\u003e\n\u003cli\u003eZachariah JP. Lipid Screening in Youth. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2016. [https://www.ncbi.nlm.nih.gov/books/NBK395583/](https://www.ncbi.nlm.nih.gov/books/NBK395583/)\u003c/li\u003e\n\u003cli\u003eMart\u0026iacute;nez-Quintana E, Rodr\u0026iacute;guez-Gonz\u0026aacute;lez F, Medina-Gil JM, Rodr\u0026iacute;guez-Gonz\u0026aacute;lez F, Horta-Venegas S, Bethencourt-Aguilar A. Lipid profile and intima media thickness in adults with cyanotic congenital heart disease. Rev Esp Cardiol. 2010;63(12):1339-1347. Doi:10.1016/S1885-5857(10)70290-4\u003c/li\u003e\n\u003cli\u003eGuirguis-Blake JM, Evans CV, Senger CA, O\u0026rsquo;Connor EA, Thomas RG, Coppola EL. Screening for lipid disorders in children and adolescents: Updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2023;330(3):261-274. Doi:10.1001/jama.2023.10403\u003c/li\u003e\n\u003cli\u003eDaniels SR, Greer FR, Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008;122(1):198-208. Doi:10.1542/peds.2008-1349\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Lipid profile, Congenital heart disease, Cyanotic, Cyanotic, Pediatrics","lastPublishedDoi":"10.21203/rs.3.rs-7284305/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7284305/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003eAtherosclerosis risk in congenital heart disease (CHD) necessitates understanding lipid profiles, yet current research is inconsistent. This study compares lipid profiles in pediatric cyanotic versus acyanotic CHD, examining BMI, age, and sex influence.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eIn this cross-sectional study, 100 children aged 1 month to 15 years who were diagnosed with CHD were enrolled from tertiary care paediatric cardiology centres. The participants were categorized into cyanotic (n\u0026thinsp;=\u0026thinsp;50) and acyanotic (n\u0026thinsp;=\u0026thinsp;50) groups on the basis of echocardiographic and clinical findings. Fasting (4_6 hours) venous blood samples were obtained, and serum lipid levels\u0026mdash;including total cholesterol, triglycerides, HDL-C, and LDL-C\u0026mdash;were measured via standardized enzymatic colorimetric assays. Statistical analysis was performed via SPSS v25 with appropriate parametric or nonparametric tests.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eThe study revealed significantly higher triglyceride levels in the cyanotic CHD group than in the acyanotic CHD group, whereas LDL-C levels were significantly elevated in the acyanotic CHD group. Subgroup analyses demonstrated that age, sex, and body mass index significantly influenced these lipid parameters, indicating distinct metabolic profiles between the two CHD subtypes.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eThe observed differences in lipid profiles between cyanotic CHD and acyanotic CHD suggest underlying pathophysiological variations that may predispose these children to early cardiovascular complications. These findings underscore the importance of early lipid screening and the development of customized preventive interventions in pediatric CHD patients.\u003c/p\u003e","manuscriptTitle":"Comparison of lipid profiles in children with cyanotic and acyanotic heart disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-13 05:46:14","doi":"10.21203/rs.3.rs-7284305/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-24T15:46:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-24T14:00:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-22T16:42:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"111482815123621001929708058318415788293","date":"2025-08-10T17:24:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87323560703894400345318991911634986629","date":"2025-08-09T14:49:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-07T09:34:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-06T14:20:40+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-06T13:25:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"European Journal of Pediatrics","date":"2025-08-03T15:36:08+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"european-journal-of-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ejpe","sideBox":"Learn more about [European Journal of Pediatrics](https://www.springer.com/journal/431)","snPcode":"431","submissionUrl":"https://submission.nature.com/new-submission/431/3","title":"European Journal of Pediatrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"4acb71fe-11c8-49af-a696-35333438aedf","owner":[],"postedDate":"August 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T16:07:03+00:00","versionOfRecord":{"articleIdentity":"rs-7284305","link":"https://doi.org/10.1007/s00431-025-06491-0","journal":{"identity":"european-journal-of-pediatrics","isVorOnly":false,"title":"European Journal of Pediatrics"},"publishedOn":"2025-10-03 15:57:57","publishedOnDateReadable":"October 3rd, 2025"},"versionCreatedAt":"2025-08-13 05:46:14","video":"","vorDoi":"10.1007/s00431-025-06491-0","vorDoiUrl":"https://doi.org/10.1007/s00431-025-06491-0","workflowStages":[]},"version":"v1","identity":"rs-7284305","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7284305","identity":"rs-7284305","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}