Atherosclerosis In Adolescents Research Articles

The impact of vildagliptin as an add-on therapy on matrix metalloproteinase-14 levels, liver stiffness and subclinical atherosclerosis in adolescents with type 1 diabetes and non-alcoholic steatohepatitis: A randomized controlled trial.

Many patients with type 1 diabetes mellitus (T1DM) met the histological criteria for non-alcoholic steatohepatitis (NASH), which leads to cardiovascular disease morbidity and mortality. Matrix metalloproteinase-14 (MMP-14) is involved in cardiovascular disease and atherosclerosis. To assess the impact of oral dipeptidyl peptidase-4 inhibitor, vildagliptin, as adjunctive therapy on NASH in adolescents with T1DM and its effect on glycaemic control, MMP-14 levels and carotid intima media thickness (CIMT). Sixty adolescents with T1DM and NASH were randomly assigned to receive oral vildagliptin (50 mg once daily) for 6 months or not. Glycated haemoglobin, lipid profile, hepatic steatosis index, triglyceride glucose (TyG) index and MMP-14 levels were assessed. Transient elastography with controlled attenuation parameter (CAP) was performed together with measuring CIMT. By transient elastography, 12 (20%) patients with T1DM with NASH had elevated liver stiffness ≥7 kPa (F2 stage or higher). Baseline MMP-14 was positively correlated to insulin dose (p = 0.016), triglycerides and TyG index, CIMT, liver stiffness and CAP levels among the studied patients (p < 0.001 for all). After 6 months, patients with T1DM on vildagliptin therapy had significantly lower glycated haemoglobin, lipid profile, hepatic steatosis index and TyG index, as well as MMP-14 (p < 0.001). CIMT, liver stiffness and CAP were significantly decreased post-therapy compared with baseline levels and compared with the control group (p < 0.001). Vildagliptin was safe and well-tolerated. Administration of vildagliptin for adolescents with T1DM and NASH improved glycaemic control, dyslipidaemia and MMP-14 levels and decreased liver stiffness and CIMT; hence, reducing subclinical atherosclerosis and disease progression.

Impact of Lipids and Vascular Damage on Early Atherosclerosis in Adolescents with Parental Premature Coronary Artery Disease.

To assess the relationship of cardiovascular risk factors (CRFs) with carotid intima media thickness (IMT) in adolescents with a parental history of premature coronary artery disease (PCAD). This cross-sectional study included 50 healthy adolescents, aged 14-18years, both sexes, with a parental history of PCAD, that were compared to 50 controls without this history. Questionnaires regarding information of CRFs were applied. Blood chemistry analyses, included lipid profile, lipoprotein (a), low density lipoprotein (LDL) susceptibility to oxidation, and inflammatory cytokine levels. The IMT was evaluated by ultrasound. The mean age of all participants was 15.9years. Anthropometric measurements, blood pressure, and lipid profile were similar in both groups. However, the parental history of PCAD group exhibited lower high density lipoprotein cholesterol concentrations, shorter LDL particle oxidation time, and higher lipoprotein (a) levels compared to the control group. IMT was significantly higher in adolescents with a parental history of PCAD compared to controls, (0.53±0.04mm vs 0.47±0.02mm, p=0.001). Among adolescents with a parental history of PCAD, those with ≥3 CRFs had significantly higher IMT values (0.56mm) than those with <3 CRFs (0.52mm) and controls (0.48mm). Multivariable analyses identified that systolic blood pressure and parental history of PCAD explained 26.8% and 16.1% of the variation in IMT. Furthermore, body mass index, LDL-C, ApoB-100, triglycerides and lipoprotein (a) interact with blood pressure levels to explain the IMT values. Adolescents with a parental history of PCAD had higher IMT values than the control group, primary explained by systolic blood pressure and the parental inheritance. Adolescents with parental history of PCAD and ≥3 CRFs exhibited the highest IMT values. Notably, lipids and systolic blood pressure jointly contribute to explain IMT in these adolescents.

Contemporary Polygenic Scores of Low-Density Lipoprotein Cholesterol and Coronary Artery Disease Predict Coronary Atherosclerosis in Adolescents and Young Adults.

Contemporary Polygenic Scores of Low-Density Lipoprotein Cholesterol and Coronary Artery Disease Predict Coronary Atherosclerosis in Adolescents and Young Adults.

Abstract P236: Association Of Vitamin B Deficiency-induced Hyperhomocysteinemia With Subclinical Atherosclerosis In Adolescents: Implications For Early Cardiovascular Disease Detection

In recent decades, the increased incidence of cardiovascular disease (CVD) mortality among young adults has raised concerns. Although clinical manifestations of CVD typically occur later in life, the underlying pathological processes emerge early on. Numerous studies have demonstrated that elevated homocysteine levels serve as an independent risk factor for endothelial dysfunction and arterial stiffness, which are key contributors to CVD. Notably, vitamin B deficiency, particularly deficiencies in Vitamins B9 and B12, emerges as a significant factor in childhood hyperhomocysteinemia, initiating the development of subclinical atherosclerosis in early life. In this narrative review, we summarize the association between vitamin B deficiency-induced hyperhomocysteinemia and subclinical atherosclerosis in adolescents. We conducted a comprehensive review of relevant literature from prominent bibliographic databases, including PubMed/MEDLINE, PMC Central, Google Scholar, and Cochrane database. Four cross-sectional studies were included and reviewed as part of our analysis. The reviewed studies, focusing on homocysteine levels as an exposure variable and markers of atherosclerosis as outcome measures, demonstrate a strong correlation between homocysteine levels and markers of atherosclerosis, including increased carotid intima-media thickness (CIMT) and endothelial dysfunction. Particularly, adolescents with vitamin B12 deficiency exhibit a significant positive correlation between homocysteine levels and CIMT. These findings underscore the potential of hyperhomocysteinemia as an early marker for detecting subclinical atherosclerosis in adolescents with vitamin B deficiency. Despite limited research in this area, recognizing the importance of early detection and management of subclinical atherosclerosis in adolescents can help mitigate the risk of severe cardiovascular and cerebrovascular events in young adulthood.

Early Detection of Subclinical Atherosclerosis: Hyperhomocysteinemia as a Promising Marker in Adolescents With Vitamin B Deficiency.

In recent decades, the increased incidence of cardiovascular disease (CVD) mortality among young adults has raised concerns. Although clinical manifestations of CVD typically occur later in life, the underlying pathological processes emerge early on. Thisreview article summarizesthe association between vitamin B deficiency-induced hyperhomocysteinemia and subclinical atherosclerosis in adolescents. Numerous studies have demonstrated that elevated homocysteine levels are an independent risk factor for endothelial dysfunction (ED) and arterial stiffness, which are key contributors to CVD. Notably, vitamin B deficiency, particularly in vitaminB9 and vitamin B12, emerges as a significant factor in childhood hyperhomocysteinemia, initiating the development of subclinical atherosclerosis in early life. A comprehensivereview of relevant literature from prominent bibliographic databases, including PubMed/MEDLINE, PubMed Central, Google Scholar, and Cochrane, was performed. Four cross-sectional studiesfocusing on homocysteine levels as an exposure variable and markers of atherosclerosis as outcome measureswere included and reviewed as part of our analysis. The reviewed studies demonstrate apositive correlation between homocysteine levels and markers of atherosclerosis, including increased carotid intima-media thickness (CIMT) and ED.Mainly, adolescents with vitamin B12 deficiency exhibit a significant positive correlation between homocysteine levels and CIMT. These findings underscore the potential of hyperhomocysteinemia as an early marker for detecting subclinical atherosclerosis in adolescents with vitamin B deficiency.Despite limited research in this area, recognizing the importance of early detection and management of subclinical atherosclerosis in adolescents can help mitigate the risk of severe cardiovascular events such as myocardial infarction and stroke in young adulthood.

Risk factors for pre-clinical atherosclerosis in adolescents with type 1 diabetes

AimsTo assess whether, besides “traditional” risk factors, overall oxidative stress, oxidized lipoproteins, and glycemic variability are associated with early macro-vascular damage in type 1 diabetes (T1D). MethodsIn 267 children/adolescents with T1D (130 girls, age 9.1–23.0 years) we evaluated: derivatives of reactive oxygen metabolites [d-ROMs], serum total antioxidant capacity [TAC] and oxidized LDL-cholesterol [oxLDL]; markers of early vascular damage (Lipoprotein-associated phospholipase A2 [Lp-PLA2], z-score of carotid intima-media thickness [z-cIMT] and carotid–femoral pulse wave velocity [z-PWV]); CGM metrics of four weeks preceding the visit, central systolic/diastolic blood pressures (cSBP/cDBP), and HbA1c, z-score of BP (z-SBP/z-DBP) and circulating lipids longitudinally collected since T1D onset.. Three general linear models were built with z-cIMT, z-PWV adjusted for current cDBP, and Lp-PLA2 as independent variables. ResultsThe z-cIMT was associated with male gender (B = 0.491, η2 = 0.029, p = 0.005), cSBP (B = 0.023, η2 = 0.026, p = 0.008) and oxLDL (B = 0.022, η2 = 0.022, p = 0.014). The z-PWV was associated with diabetes duration (B = 0.054, η2 = 0.024, p = 0.016), daily insulin dose (B = 0.52, η2 = 0.018, p = 0.045), longitudinal z-SBP (B = 0.18, η2 = 0.018, p = 0.045) and dROMs (B = 0.003, η2 = 0.037, p = 0.004). Lp-PLA2 was associated with age (B = 0.221, η2 = 0.079, p = 3*10−6), oxLDL (B = 0.081, η2 = 0.050, p = 2*10−4), longitudinal LDL-cholesterol (B = 0.031, η2 = 0.043, p = 0.001) and male gender (B = -1.62, η2 = 0.10, p = 1.3*107). ConclusionsOxidative stress, male gender, insulin dose, diabetes duration and longitudinal lipids and blood pressure, contributed to the variance of early vascular damage in young patients with T1D.

Subclinical atherosclerosis in adolescents and young adults and the risk of cardiovascular disease: The Strong Heart Family Study (SHFS)

Background and aimsRates of cardiovascular disease (CVD) among American Indians (AI) have been increasing. Although we have observed an association between atherosclerosis and CVD in older adults, the potential association among young AI is unclear. Therefore, we aim to describe the prevalence of atherosclerosis among young AI and determine its association with CVD and all-cause mortality. Methods and resultsWe evaluated AI participants from the Strong Heart Family Study (SHFS), who were <40 years old and CVD free at the baseline examination, 2001–2003 (n = 1376). We used carotid ultrasound to detect baseline atherosclerotic plaque. We identified CVD events and all-cause mortality through 2019, with a median follow-up of 17.8 years. We used shared frailty Cox Proportional Hazards models to assess the association between atherosclerosis and time to CVD event or all-cause mortality, while controlling for covariates.Among 1376 participants, 71 (5.2%) had atherosclerosis at baseline. During follow-up, 120 (8.7%) had CVD events and 104 (7.6%) died from any cause. CVD incidence was higher in participants who had baseline atherosclerosis (13.51/1000 person-years) than in those who did not (4.95/1000 person-years, p = 0.0003). CVD risk and all-cause mortality were higher in participants with atherosclerosis, while controlling for covariates (CVD HR = 1.85, 95%CI = 1.02–3.37, p = 0.0420; all-cause mortality HR = 2.04, 95%CI = 1.07–3.89, p = 0.0291). ConclusionsAmong young AI, atherosclerosis was independently associated with incident CVD and all-cause mortality later in life. Thus, atherosclerosis begins early in life and interventions in adolescents and young adults to slow the progression of disease could prevent or delay CVD events later in life.

Urban Air Pollution and Subclinical Atherosclerosis in Adolescents and Young Adults

PurposeThe contribution of air pollution to subclinical atherosclerosis in a young population remains limited. This study aimed to assess whether long-term exposure to urban air pollutants increases carotid intima-media thickness (CIMT) in adolescents and young adults. MethodsThis study included 789 subjects between the ages of 12 and 30 years who lived in the Taipei metropolis from a cohort of young Taiwanese individuals. Residential addresses were geocoded, and annual average concentrations of particulate matter (PM) of different diameters, e.g., PM10, PM2.5–10, PM2.5, and nitrogen oxides (NOX), were assessed using land use regression models. The generalized least squares strategy with error term to consider the cluster effect of living addresses between individuals was used to examine the associations between urban air pollution and CIMTs. ResultsAfter adjusting for potential confounders, we found that interquartile range increases in PM2.5 (8.2 μg/m3) and NOX (17.5 μg/m3) were associated with 0.46% (95% CI: 0.02–0.90) and 1.00% (95% CI: 0.10–1.91) higher CIMTs, respectively. Stratified analyses showed that the relationships between CIMT and PM2.5 and NOX were more evident in subjects who were 18 years or older, female, nonsmoking, nonhypertensive, and nonhyperglycemic than in their respective counterparts. DiscussionLong-term exposure to PM2.5 and NOX is associated with subclinical atherosclerosis in a young population. Age, sex, and health status may influence the vulnerability of air pollution-associated subclinical atherosclerosis.

Effect of metformin as an add-on therapy on neuregulin-4 levels and vascular-related complications in adolescents with type 1 diabetes: A randomized controlled trial

BackgroundInflammation is closely associated with atherosclerosis and plays a crucial role in the development of cardiovascular disease. Metformin sensitizes body cells to insulin, which may cause a reduction of atherogenic lipid fractions. Low neuregulin-4 (Nrg-4) levels, an adipokine, are linked to obesity, insulin resistance, impaired glucose tolerance and type 2 diabetes. ObjectivesWe assessed the effect of oral supplementation with metformin on glycemic control, neuregulin-4 levels and carotid intima media thickness (CIMT) as a marker for subclinical atherosclerosis in adolescents with type 1 diabetes mellitus (T1DM) and microvascular complications. MethodsThis randomized placebo-controlled trial included 80 type 1 diabetic patients with microvascular complications who were randomly divided to receive either 24 weeks of metformin 500 mg/day or matching placebo. Fasting blood glucose (FBG), HbA1c, C-reactive protein (CRP), urinary albumin creatinine ratio (UACR), lipid profile, Nrg-4 and CIMT were assessed at baseline and study end. ResultsBoth groups were well-matched as regards baseline clinical and laboratory data (p greater than 0.05). After 24-weeks, metformin therapy for the intervention group resulted in a significant decrease of HbA1c, CRP, UACR, total cholesterol and CIMT while Nrg-4 levels were increased compared with baseline levels (p < 0.001) and with placebo group(p < 0.001). Baseline Nrg-4 levels were negatively correlated to FBG, HbA1c, total cholesterol, CRP and CIMT. Metformin was well-tolerated. ConclusionsOral metformin supplementation once daily for 24 weeks as an adjuvant therapy to intensive insulin in pediatric T1DM was safe and effective in improving glycemic control, dyslipidemia and Nrg-4 levels; hence, it decreased inflammation, microvascular complications and subclinical atherosclerosis.

Urban Fine Particulate Matter and Elements Associated with Subclinical Atherosclerosis in Adolescents and Young Adults.

The relationships between the elemental constituents of PM2.5 and atherosclerosis remain limited, especially in young populations. This study included 755 subjects aged 12-30 years in the Taipei metropolis. A land use regression model was used to estimate residential annual mean concentrations of PM2.5 and eight elemental constituents. We evaluated the percent differences in carotid intima-media thickness (CIMT) with PM2.5 and elemental constituent exposures by linear regressions. Interquartile range increments for PM2.5 (4.5 μg/m3), sulfur (108.6 ng/m3), manganese (2.0 ng/m3), iron (34.5 ng/m3), copper (3.6 ng/m3), and zinc (20.7 ng/m3) were found to associate with 0.92% (95% confidence interval (CI): 0.17-1.66), 0.51% (0.02-1.00), 0.36% (0.05-0.67), 0.98% (0.15-1.82), 0.74% (0.01-1.48), and 1.20% (0.33-2.08) higher CIMTs, respectively. Factor analysis identified four air pollution source-related factors, and the factors interpreted as traffic and industry sources were associated with higher CIMTs. Stratified analyses showed the estimates were more evident in subjects who were ≥18 years old, females, or who had lower household income. Our study results provide new insight into the impacts of source-specific air pollution, and future research on source-specific air pollution effects in young populations, especially in vulnerable subpopulations, is warranted.

Вопросы своевременной диагностики дефицита лизосомной кислой липазы у детей и молодых взрослых с нарушениями липидного профиля. Мнение экспертов

Lysosomal acid lipase deficiency (LAL-D) is a monogenic progressive life-threatening condition characterized by abnormal lipid profiles in most patients of all ages. Timely diagnosis and early pathogenetically-oriented treatment (available in Russia) are crucial for children and young adults since abnormal serum levels of lipids are associated with the onset and severity of atherosclerosis in adolescence, young and middle age. The prognosis of LAL-D without pathogenetically oriented treatment is poor. Data on cholesteryl ester storage disease (a variant of LAL-D in children and adults), early atherosclerosis, coronary heart disease, aortic calcification, etc., are available. However, early diagnosis of LAL-D is difficult due to long-term latent course and nonspecific clinical signs. In December 2020, a panel of leading Russian experts in the diagnosis and treatment of orphan diseases and lipidologists was held in Moscow. This panel developed an algorithm to optimize the early diagnosis of dyslipidemias in children and young adults and identify patients with LAL-D in a total population of patients with lipid profile abnormalities. KEYWORDS: lysosomal acid lipase deficiency, lipid profile, atherosclerosis, lipid center. FOR CITATION: Ezhov M.V., Zakharova E.Yu., Avramenko A.A. et al. Timely diagnosis of lysosomal acid lipase deficiency in children and young adults with lipid profile abnormalities. Expert opinion. Russian Journal of Woman and Child Health. 2021;4(3):268–276 (in Russ.). DOI: 10.32364/2618-8430-2021-4-3-268-276.

Preclinical atherosclerosis in adolescents with psychotic or bipolar disorders investigated with carotid high-frequency ultrasound.

ObjectiveEarly‐onset psychosis (EOP) and bipolar disorder (EOBP) (at <18 years of age), are associated with an increased future risk of cardiovascular disease (CVD) and premature death. Yet it is unknown whether the arteries show visible signs of atherosclerosis in EOP and EOBP. This study investigated whether having EOP or EOBP was associated with detectable signs of preclinical atherosclerosis.MethodBy using 22 MHz high‐frequency ultrasound, different layers of the arterial wall of the left common carotid artery (LCCA) were assessed in 77 individuals with EOP (n = 25), EOBP (n = 22), and in age‐matched healthy controls (n = 30). Conventional CVD confounders were included in the analyses.ResultsAdolescents with EOP and EOBP, compared to controls, had a significantly thicker LCCA intima thickness (0.132 vs. 0.095 mm, p < .001) and intima/media ratio (0.24 vs. 0.17 p < .001). There was a nonsignificant intima difference between EOP and EOBP. Conventional CVD risk factors did not explain the association between EOP/EOBP and intima thickness. In the group of EOP/EOBP, there was a significant correlation between the dose of current antipsychotic medication and intima thickness; however, the correlation was attenuated to a nonsignificant level when adjusted for global function.ConclusionsAdolescents with EOP or EOBP had an increased LCCA intima thickness, interpreted as a sign of preclinical atherosclerosis. Global function of the disorders was the strongest determinant of intima thickness. The findings, if replicated, might have implications for long‐term treatment of EOP and EOBP in order to reduce a future risk of CVD.

Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process.&#x0D; AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]).&#x0D; METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019).&#x0D; RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p &lt; 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p &lt; 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p &lt; 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p &lt; 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%).&#x0D; CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

Relationship between vitamin D deficiency and premature atherosclerosis in an adolescents with type 1 DM through inflammatory IFN-γ

Vitamin D deficiency has been related to increased risk of myocardial infarction, stroke. Type 1 DM patients have a higher risk of atherosclerosis, which is the leading cause of death in most patients, and IFN-γ is a pro inflammatory cytokine, and type 1 DM is a chronic inflammation. In our study, we try to detect the premature atherosclerosis in adolescents with type 1 DM who have vitamin D deficiency through inflammatory IFN-γ. The study is a case control with 31 diabetic children aged 6 to 18 years as a case group, and control group 35 healthy children aged 10-18 years. We analysis the vitamin D, IFN- and ,HbA1c, and using Doppler US for cIMT of common carotid artery(CCA), and flow mediated dilation index(FMD%) of the brachial artery. And analysis the data through SPSS version16.0. Type 1 DM group have higher levels of IFN-γ (p-0.005) and cIMT (p-0.01.) and both were significant, while the correlation effect of vitamin D deficiency and IFN-γ on both cIMT and FMD% were (p-0.294) and (p-0.270) (p-0.794)and (p-0.894) respectively and both insignificant, and correlation effect of HbA1c on cIMT was significant with (p-0.002), and correlation effect of HbA1c on FMD% was insignificant with (p-0.222). We concluded that there is significantly higher of IFN-γ in type 1 DM, also a significant correlation effect of HbA1c on cIMT, and no relationship between vitamin D deficiency and premature atherosclerosis in an adolescents with type 1 DM through inflammatory IFN-γ.

【論文摘要】The Association of Long-term PM2.5 Absorbance Exposure with Carotid-intima-media Thickness in Young Taiwanese

Background/Synopsis: The contribution of long-term air pollution exposures to subclinical atherosclerosis in young age has not been fully studied. Objectives/Purpose: This study is to evaluate to assess the associations of carotid intima-media thickness (CIMT) values in adolescents or young adults with one-year exposures to different sizes of particulate matter (PM) and traffic-related exhausts. Methods/Results: We recruited 789 school age subjects who resided in Taipei City and participated in the YOung TAiwanese (YOTA) Cohort between 1992 and 2000. Of all study subjects, 303 subjects were elevated blood pressures (EBP) and 486 subjects had normal BP (NBP) in the childhood. The CIMT values at different segments were measured at the age of 12-30 in the follow-up health examination from 2006 to 2008. Land-use regression models were used to estimate participants' one-year exposures to particulate matter (PM) of different sizes and traffic-related exhausts, including PM2.5 absorbance, nitrogen oxides, and nitrogen dioxides. Generalized linear regression was applied to assess the associations of CIMT values in adolescents or young adults with one-year exposures to six air pollutants. Our findings indicate one-year exposure to PM2.5 absorbance is associated with increased mean and maximum CIMT at different carotid segments. Specifically, exposure to PM2.5 absorbance among subjects who exhibited elevated childhood blood pressure is associated with an increases in mean CMIT at common carotid artery by 3.94% (95%CI: 0.24, 7.64), carotid bulb by 7.77% (95%CI: 2.95, 12.95), and internal carotid artery by 4.75% (95%CI: 0.67, 8.84). Similar increases in the maximum CIMT values were evident at the aforementioned sites. Moreover, older age, gender and health status (overweight, elevated blood pressure, hyperglycemia and hypercholesterolemia), coupled with high level exposure to PM2.5 absorbance (≥2.18 10-5 m-1; 75th percentile), are particularly at risk for developing increased CIMT. Conclusion: Long-term exposure to PM2.5 absorbance is positively associated with subclinical atherosclerosis in adolescents or young adults. The atherosclerosis developed since early childhood depending on individual cardiovascular risk factors including overweight, hypertension, hyperglycemia, or hypercholesterolemia, and can be modified by PM2.5 absorbance concentration.

Assessment of biomarkers of inflammation and premature atherosclerosis in adolescents with type-1 diabetes mellitus.

Background Type-1 diabetes mellitus (T1DM) causes endothelial dysfunction and early atherosclerosis, which can result in premature coronary artery disease. The aim of this study was to determine the impact of glycemic control, vascular oxidative stress and inflammation on vascular health in adolescents with T1DM. Methods This was a cross-sectional study in adolescents with age- and sex-matched T1DM who were ≥12 years and were at least 2 years post-diagnosis. Recruitment was balanced to include individuals with hemoglobin A1c (HbA1c) ≤8.5% (n=27) or with HbA1c ≥9.5% (n=25). Biomarkers of inflammation were measured in the blood including C-reactive protein (CRP), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), E-selectin, fibrinogen and tumor necrosis factor-α (TNF-α). Carotid intima media thickness (cIMT) and peripheral arterial tonometry (PAT) were assessed. Results Plasma E-selectin level was significantly different between the two groups with higher levels in the group with HbA1c ≥9.5% (65.0±27.7 ng/mL vs. 48.8±21.5 ng/mL, p=0.02). Though cIMT and PAT were not significantly different between the groups, Pearson correlation showed a significant direct relationship between rising HbA1c and mean right cIMT (p=0.02; r=0.37), PAT (p=0.03, r=0.31) and fibrinogen (p=0.03, r=0.03). Conclusions Elevated E-selectin level is an early marker of oxidative stress in T1DM patients with an elevated HbA1c level. Suboptimal glycemic control as evidenced by a rising HbA1c causes early atherosclerosis.

Increased asymmetric dimethylarginine in vitamin B12 deficient adolescents

Vitamin B12 deficiency induces hyper-hyperhomocysteinemia by inhibiting intracellular methionine re-methylation. Hyper-hyperhomocysteinemia increases the risk of atherosclerosis. Asymmetric dimethylarginine is an endogenous inhibitor of nitric oxide synthase and its level elevates in cardiovascular diseases. In this study, we aimed to examine the relationship between asymmetric dimethylarginine and arterial stiffness and atherosclerosis in adolescents with vitamin B12 deficiency. A total of 88 adolescents with age ranging between 11 and 17 years of age were enrolled for this study. Among them, 50 patients had vitamin B12 deficiency 200 pg/ml. In all cases, the levels of asymmetric dimethylarginine were measured with high performance liquid chromatography method. The carotid artery intima media thickness and left ventricular mass index were measured using echocardiography. All these measurements of the study groups were compared. Both plasma levels of asymmetric dimethylarginine and carotid artery intima media thickness were significantly higher in the vitamin B12 deficiency group than in the control group. Correlation analysis showed significant negative correlation of vitamin B12 with homocysteine, asymmetric dimethylarginine, and carotid artery intima media thickness (p&lt;0.05). Our results suggest that endothelial dysfunction starts in the early stage of adolescent vitamin B12 deficiency, and vitamin B12-deficient adolescents have increased circulating asymmetric dimethylarginine, showing that endothelial dysfunction and increased carotid artery intima media thickness be related to atherosclerosis.

Positive Association between Urinary Concentration of Lead, Cadmium and Subclinical Atherosclerosis in Adolescents and Young Adults

Backgrounds: Urinary cadmium and lead have been associated with hypertension and cardiovascular diseases (CVD) in large population studies. However, there are still limited information linking exposure to heavy metal with subclinical atherosclerosis, particularly in young population.Methods: From a nationwide mass urine screening for renal health, conducted in 1992-2000 among school children 6 to 18 years of age in Taiwan, we recruited 789 subjects to participate in the cardiovascular health examination in 2006-2008. In the present study we evaluated the association between urinary levels of cadmium, lead, chromium, manganese, iron, nickel, copper, and zinc with carotid intima-media thickness (CIMT) in a cross-sectional analysis of 739 adolescents and young adults.Results: CIMT at all segments of carotid arteries significantly increased with the urinary lead and cadmium in a dose-response relationship after adjustment for major CVD risk factors. Multivariate logistic regression analysis showed that higher quartiles of urinary concentrations of lead and cadmium were associated with a higher risk of thicker CIMT (greater than 75th percentile). Compared to subjects with the lowest quartile (Q1) of urinary lead, the adjusted odds ratios (aORs) (95% confidence interval (CI)) for thicker CIMT among subjects with higher urinary lead were 2.56(1.35-4.85) for Q2, 3.76(2.00-7.08) for Q3, and 17.64(9.32-33.39) for subjects at Q4. Comparing those with lowest urinary cadmium, the corresponding aORs (95% CI) were 1.48(0.77-2.85) for Q2, 4.68(2.57-8.52) for Q3, and 13.58(7.34-25.13) for subjects at Q4.Conclusion: Higher urinary concentration of lead and cadmium was strongly associated with subclinical atherosclerosis in adolescents and young adults.

Evaluation of Lipid Profile in Adolescents

Abstract Background: Atherosclerosis is a chronic, multifactorial and insidious disease that can begin in childhood and adolescence, and whose major consequences appear during adulthood. Serum levels of lipoproteins, such as LDL-c, total cholesterol (TC), HDL-c, and non-HDL-c can be used as a screening method for disease diagnosis. In Brazil, few studies have correlated the serum levels of those lipoproteins with age. Objective: To evaluate the serum concentrations of TC, LDL-c, HDL-c, VLDL-c, non-HDL-c and triglycerides (TG) of adolescents aged 10 to 19 years in the municipality of Araucaria, Parana state. Methods: Cross-sectional retrospective study, collecting the following data from 600 adolescents: age, sex and serum levels of TC, LDL-c, HDL-c and TG from June to December 2016. Data were analyzed using the SPSS software 2.0, with Mann-Whitney U test and Spearman coefficient of correlation to identify statistical significance (p < 0.05). Results: The female sex showed higher serum levels of TC, TG and LDL-c than the male sex. The HDL-c levels were identical in both sexes, with 48% of desirable values and 52% of low values. This study identified a strong correlation between the lipids and association with the age group of 10 to 14 years. Conclusion: Non-HDL-c showed stronger correlation with the other lipids (TG, LDL-c and TC) as compared to LDL-c, suggesting that non-HDL-c can be used as an effective complementary diagnostic method to assess the risks for atherosclerosis in adolescents.

Abstract P112: Genes in Genome-wide Association Study-identified Loci and Risk of Atherosclerosis in Adolescents and Young Adults

Background: Genome-wide association studies (GWASs) have identified multiple genomic loci associated with atherosclerotic diseases. However, specific genes underlying the observed associations are largely unknown. Objectives: We aimed to examine the associations between genes that harbor variants in high LD with index variants in GWAS-identified loci and pathologically determined atherosclerosis in major arteries from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Methods and Results: Data for 1,938 single nucleotide polymorphisms (SNPs) from 28 genes were retrieved from whole exome sequence data. Atherosclerosis was confirmed by postmortem examination of major arteries from 1,005 young persons (aged 15-34 years) who died from non-cardiovascular causes. Logistic regression was used to evaluate associations between common SNPs and atherosclerosis controlling for age and sex. Gene-based analysis was conducted using Sequence Kernel Association Test (SKAT) method to test the combined effect of rare and common variants on atherosclerosis controlling for age and gender. All analyses were performed separately in blacks and whites. Statistical significance was determined by false positive discovery rate (FDR) method. In gene-based analyses, BUD13 ( P =1.11х10 -2 ) and COL4A1 ( P =3.58х10 -2 ) were associated with atherosclerosis among young blacks; none of the 28 genes was associated with atherosclerosis in whites. In single marker analysis of common SNPs, LRP1 missense variant rs7397167 ( P =8.50х10 -3 ), COL4A1 variant rs16975492 ( P =4.60х10 -3 ), STK32B variant rs168985 ( P =4.00х10 -3 ), and SMARCA4 variant rs8104480 ( P =1.20х10 -3 ) were associated with atherosclerosis in blacks; MIA3 variant rs17465637 ( P =8.00х10 -3 ), DUS4L missense variant rs6957510 ( P =6.4х10 -3 ), BOLL variant rs771018 ( P =6.2х10 -3 ), BUD3 missense variant rs11820589 ( P =2.1х10 -3 ), and COL4A1 variant rs1133219 ( P =1.8х10 -3 ) were associated with atherosclerosis in whites. Conclusion: Genes in GWAS-identified loci may play a role in the development of atherosclerosis at a young age.