Atherosclerosis In Children Research Articles

Risk factors for atherosclerosis in children and adolescents with family history of premature coronary artery disease

Risk factors for atherosclerosis in children and adolescents with family history of premature coronary artery disease

Monogenic hypercholesterolemia: new insights in pathogenesis and treatment.

Monogenic hypercholesterolemia: new insights in pathogenesis and treatment.

Ten years follow up of the precursors of early atherosclerosis in children

Ten years follow up of the precursors of early atherosclerosis in children

Risk factors of atherosclerosis in children

The aim of this work is to assess trace metal pollution status (Cd, Cu, Ni, Pb, Zn) in the waters of Saronikos Gulf, Greece, in line with the WFD and MSFD European Directives, based on data collected over a decade (2000–2010). Dissolved metal background levels are estimated for the first time for Greek marine waters and the upper limits are: Cd: 0.574 nmol L−1; Cu: 8.26 nmol L−1; Ni: 7.94 nmol L−1; Pb: 2.60 nmol L−1; Zn: 115 nmol L−1. The variability of dissolved and particulate metals reflected the presence of several point sources and revealed the importance of natural mechanisms acting as non-point sources. The status of Saronikos Gulf is classified as ‘High’ for most metals studied. An exception to this is the enclosed Elefsis Bay where Cu, Ni and Zn concentrations are found above background. Our work will assist the implementation of WFD and MSFD directives in Greece.

Natural history and risk factors of atherosclerosis in children and youth: the PDAY study.

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study was organized to document the natural history of athersclerosis and to determine the relation of cardiovascular risk factors to atherosclerosis in young subjects. Pathology laboratories in 15 centers collected coronary arteries, aortas, and other tissues from over 3,000 subjects age 15 to 34 who died of external causes between 1987 and 1994. The extent, prevalence, and topography of arterial lesions were evaluated and risk factors were analyzed in a central laboratory. Postmortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus and body mass index (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. The PDAY study confirmed the origin of atherosclerosis in childhood, showed that progression toward clinically significant lesions may occur in young adulthood and demonstrated that the progression of atherosclerosis is strongly influenced by coronary heart disease (CHD) risk factors. Recent PDAY studies have shown that a significant number of advanced coronary artery lesions have microscopic qualities associated with susceptibility to rupture and that CHD risk factors are associated with the development of these characteristic microscopic qualities. The PDAY archive continues to provide an important resource for new investigators throughout the world that contribute to the understanding of atherosclerosis, the underlying cause of most cardiovascular disease and the leading cause of debilitating illness and death in this country. The PDAY findings emphasize the need to modify risk factors in young people to retard the development of atherosclerotic lesions, particularly clinically significant lesions. Thus, true primary prevention of atherosclerosis must being in childhood or early adolescence.

Ultrasonic evaluation of early atherosclerosis in children and adolescents with type 1 diabetes mellitus.

To assess early atherosclerosis using B-mode imaging of the carotid artery in children and adolescents with type 1 diabetes mellitus (T1DM) and to evaluate the relationship between various risk factors and intimal plus medial thickness (IMT) in this population. Fifty-two children and adolescents (aged 3-18 years) with uncomplicated T1DM and 43 age- and gender-matched healthy controls were examined. B-mode imaging was used to determine the intimal plus medial thickness (IMT) of the carotid artery in all subjects. Patients with T1DM and control subjects were divided into two groups according to age and gender. Furthermore, duration of DM was considered for comparison. Patients and control subjects showed no association between IMT and sex, systolic blood pressure (sBP), diastolic blood pressure (dBP), serum lipid levels or left ventricular ejection fraction (LVEF). However, statistical analysis indicated a good correlation between age and carotid arterial wall thickness in both diabetic and control groups. These findings were consistent with those in the literature. No correlation was found between IMT and the duration of DM. This study indicates that there is no association between T1DM and IMT in children and adolescents with T1DM.

Lipoprotein profile in long term theophylline administration in children with asthma

Atherosclerosis in childhood has a slowly progressive course and its clinical features usually become prominent in middle ages. Hypercholesterolemia is one of the major risk factors for the development of atherosclerosis. A clear correlation exists between hypercholesterolemia in childhood and atherosclerotic lesions extending into adulthood.In this study, we evaluated the effect of slow release theophylline (SRT) treatment on plasma lipid profile and assessed the risk for atherosclerotic coronary heart disease in children with bronchial asthma. Group 1 consisted of 15 children with a mean age of 10.8 3.19 years who received SRT for bronchial asthma for a mean period of 9.13 2.17 months. Group 2 was composed of 15 children with a mean age of 11.40 3.78 years and followed up for bronchial asthma, who received no SRT treatment. Group 3 comprised 15 children with a mean age of 9.00 3.76 years and no history of asthma or wheezing. In all patients lipid profiles were assessed by measuring levels of plasma triglyceride, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) apolipoprotein A (Apo-A) and apolipoprotein B (Apo-B). In group 1, the mean total cholesterol level was 175.53 24.36 mg/dl, LDL-C level was 91.00 24.07 mg/dl and Apo-B level was 87.27 12.74 mg/dl after SRT treatment. In group 1, group 2 (control group with asthma) and group 3 (the non-asthmatic control group), the mean plasma lipid level after SRT treatment was significantly higher than that before SRT treatment. In conclusion, long-term SRT treatment in children with bronchial asthma may alter lipid profile and may increase the risk for developing atherosclerotic coronary heart disease.

NATURAL HISTORY AND RISK FACTORS OF ATHEROSCLEROSIS IN CHILDREN AND YOUTH: THE PDAY STUDY

The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study was organized to document the natural history of atherosclerosis and to determine the relation of cardiovascular risk factors to atherosclerosis in young subjects. Pathology laboratories in 15 centers collected coronary arteries, aortas, and other tissues from over 3,000 subjects age 15 to 34 who died of external causes between 1987 and 1994. The extent, prevalence, and topography of arterial lesions were evaluated and risk factors were analyzed in a central laboratory. Post-mortem risk factors included serum lipoproteins, serum thiocyanate (smoking), glycohemoglobin (diabetes), thickness of panniculus adiposus and body mass index (obesity), changes in small renal arteries (hypertension), and apoprotein isoforms. The PDAY study confirmed the origin of atherosclerosis in childhood, showed that progression toward clinically significant lesions may occur in young adulthood and demonstrated that the progression of atherosclerosis is strongly influenced by coronary heart disease (CHD) risk factors. Recent PDAY studies have shown that a significant number of advanced coronary artery lesions have microscopic qualities associated with susceptibility to rupture and that CHD risk factors are associated with the development of these characteristic microscopic qualities. The PDAY archive continues to provide an important resource for new investigators throughout the world that contribute to the understanding of atherosclerosis, the underlying cause of most cardiovascular disease and the leading cause of debilitating illness and death in this country. The PDAY findings emphasize the need to modify risk factors in young people to retard the development of atherosclerotic lesions, particularly clinically significant lesions. Thus, true primary prevention of atherosclerosis must being in childhood or early adolescence.

Cardiovascular disease risk factors and atherosclerosis in children and adolescents.

As more is learned about the natural history of the development of atherosclerosis, it is clear that the process that results in morbidity and mortality in adults has its origins in childhood and adolescence. It is also clear that the traditional risk factors, such as hypertension and dyslipidemia, are important in the early stages of the process. It appears that the prevalence and severity of obesity are increasing in children and adolescents in the United States. This trend is associated with increasing blood pressure and the occurrence of type 2 diabetes mellitus in young individuals. These trends may result in increased cardiovascular morbidity and mortality as these overweight pediatric patients become obese adults. Intervention and prevention strategies should be directed at the pediatric population as a whole, as well as at higher-risk individuals. For the latter, it will be necessary to identify those at highest risk. Both nonpharmacologic and pharmacologic approaches may be necessary for treatment of pediatric patients with hyperlipidemia and hypertension. Studies are needed that evaluate the longer-term impact of intervention on cardiovascular risk factors in young patients.

Noninvasive assessment of the early progression of atherosclerosis in adolescents with Kawasaki disease and coronary artery lesions.

The severity of carotid arteriosclerosis, defined as increased intima-media thickness (IMT) visible with B-mode ultrasound, is correlated with risk factors for coronary heart disease. Little is known, however, about the relation of IMT, the stiffness of the common carotid artery, and the progression of atherosclerosis in children with Kawasaki disease (KD) and coronary artery lesions (CAL). We investigated the associations among total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglyceride, TC/HDL-C, ApoE genotype, glycohemoglobin, IMT, and arterial stiffness by high resolution ultrasound in 20 adolescents with KD and CAL (age: 16.6 +/- 4.1 years, males: 60%) and 20 sex- and age-matched healthy controls (Cont). No significant differences were observed in the values of body mass index and blood pressure between the 2 groups. Also no significant differences were observed in the levels of TC, LDL-C, HDL-C, triglyceride, TC/HDL-C within normal values, or the allele frequency of Apo E4 between the 2 groups. However, the values of IMT, stiffness, and glycohemoglobin in patients with KD were significantly higher than those in Cont (0.53 +/- 0.07 vs 0.46 +/- 0.05 mm, P <.05; 4.11 +/- 0.86 vs 2.94 +/- 0.91, P <.001; 5.0 +/- 0.4 vs 4.6 +/- 0.2%, P <.05). A significant relationship was observed between sex and the mean IMT (r = 0.46) in Cont; however, no significant correlation was found between mean IMT and other variables in either group. Although the arterial stiffness was strongly related to body mass index (r = 0.58) and systolic blood pressure (r = 0.55) in Cont, no significant relationship was observed between the stiffness and any variable tested in patients with KD. The less distensible carotid wall in patients with KD compared with that in Cont without major alteration of the lipid profile is likely to be secondary to the changes in arterial walls after a diffuse vasculitis involving noncoronary arteries. These results indicate that the coronary arteries may be predisposed to accelerated atherosclerosis in patients with KD and CAL.

Does maternal or paternal heredity affect carotid atherosclerosis in children with familial hypercholesterolaemia?

Maternal hypercholesterolaemia has recently been shown to increase the number of fatty streaks in the foetal aorta, as well as subsequent progression of fatty streaks to more advanced lesions. We compared carotid intima‐media thickness by B‐mode ultrasonography in children who inherited familial hypercholesterolaemia from their mothers or fathers, hypothesizing that children whose mothers were hypercholesterolaemic during pregnancy had increased atherogenesis compared with children whose mothers did not have familial hypercholesterolaemia.We found that carotid intima‐media thickness and prevalence of plaque did not differ between children with familial hypercholesterolaemia who inherited FH maternally or paternally.

Origin of atherosclerosis in childhood and adolescence

Atherosclerosis begins in childhood as deposits of cholesterol and its esters, referred to as fatty streaks, in the intima of large muscular arteries. In some persons and at certain arterial sites, more lipid accumulates and is covered by a fibromuscular cap to form a fibrous plaque. Further changes in fibrous plaques render them vulnerable to rupture, an event that precipitates occlusive thrombosis and clinically manifest disease (sudden cardiac death, myocardial infarction, stroke, or peripheral arterial disease). In adults, elevated non-HDL-cholesterol concentrations, low HDL-cholesterol concentrations, hypertension, smoking, diabetes, and obesity are associated with advanced atherosclerotic lesions and increased risk of clinically manifest atherosclerotic disease. Control of these risk factors is the major strategy for preventing atherosclerotic disease. To determine whether these risk factors also are associated with early atherosclerosis in young persons, we examined arteries and tissue from approximately 3000 autopsied persons aged 15-34 y who died of accidental injury, homicide, or suicide. The extent of both fatty streaks and raised lesions (fibrous plaques and other advanced lesions) in the right coronary artery and in the abdominal aorta was associated positively with non-HDL-cholesterol concentration, hypertension, impaired glucose tolerance, and obesity and associated negatively with HDL-cholesterol concentration. Atherosclerosis of the abdominal aorta also was associated positively with smoking. These observations indicate that long-range prevention of atherosclerosis and its sequelae by control of the risk factors for adult coronary artery disease should begin in adolescence and young adulthood.

Atherosclerosis in children and youth. A morphometric multinational investigation of WHO/ISFC (1986–96) using atherometric system

Atherosclerosis in children and youth. A morphometric multinational investigation of WHO/ISFC (1986–96) using atherometric system

若年者における動脈硬化のリスクファクター

若年者における動脈硬化のリスクファクター

Prevention of atherosclerosis in childhood

The occurrence in the aorta of fatty streaks, or early atherosclerotic lesions, in infants all over the world, irrespective of ethnicity or prevalence of coronary heart disease (CHD) in the population, is well recognised.1 Although these aortic fatty streaks in childhood are evanescent, the progression of subclinical coronary atherosclerosis in childhood to CHD in adulthood is becoming increasingly clear.1 Moreover, fatty streaks and raised collagen-capped fibrous plaques in the coronary arteries also begin in childhood, especially in industrialised countries, where the risk of CHD is high.

Influence of maternal hypercholesterolaemia during pregnancy on progression of early atherosclerotic lesions in childhood: Fate of Early Lesions in Children (FELIC) study

Children generally have low cholesterol and no clinical manifestations of atherosclerosis, but fatty-streak formation begins in fetuses and is greatly increased by maternal hypercholesterolaemia during pregnancy. In the FELIC study we assessed the evolution of such lesions during childhood. Computer-assisted imaging was used to measure the area of the largest individual lesion and the cumulative lesion area per section in serial cross-sections through the entire aortic arch and abdominal aorta of 156 normocholesterolaemic children aged 1-13 years, who died of trauma and other causes. Children were classified by whether their mother had been normocholesterolaemic (n=97) or hypercholesterolaemic (n=59) during pregnancy. Atherosclerosis was correlated with 13 established or potential risk factors. Findings The largest fatty streaks in the aortic arch of children younger than 3 years of hypercholesterolaemic mothers were 64% smaller than those previously found in corresponding fetuses (p<0.0001), which suggests that fetal fatty streaks may regress after birth. In the two groups, lesion size in the aortic arch and abdominal aorta increased linearly with age (r=0.87-0.98). However, lesions progressed strikingly faster in children of hypercholesterolaemic mothers than in those of normocholesterolaemic mothers (p<0.0001). Conventional risk factors for atherosclerosis in children or mothers correlated with lesion size, but did not account for the faster progression of atherogenesis in normocholesterolaemic children of hypercholesterolaemic mothers. Our results suggest that maternal hypercholesterolaemia during pregnancy induces changes in the fetal aorta that determine the long-term susceptibility of children to fatty-streak formation and subsequent atherosclerosis. If so, cholesterol-lowering interventions in hypercholesterolaemic mothers during pregnancy may decrease atherogenesis in children.

Evaluation of some risk factors of atherosclerosis in children of high risk families

Evaluation of some risk factors of atherosclerosis in children of high risk families

Prediction of atherosclerosis in children and the possibility of early prevention of coronary heart disease

Cardiovascular diseases caused by atherosclerosis (coronary artery disease, cerebrovascular pathology, etc.) are responsible for 40-50% of all deaths in adults. Of particular concern to clinicians is the emerging unfavorable tendency to "rejuvenate" these diseases. Currently, the fact that atherosclerosis (AS) begins to form in childhood and adolescence is indisputable.

Imaging of subclinical atherosclerosis in children and young adults

Atherosclerosis begins in childhood and has a long preclinical phase before ischaemic symptoms appear. This provides an opportunity for subclinical detection of the disease and identification of high-risk subjects. Recent advances in imaging technology have identified many early functional and structural vascular changes, some of which may reflect subclinical atherosclerosis, and therefore provide areas of potential interest for diagnostic tests of preclinical atherosclerosis. These early events include changes in arterial vasodilatory function, alterations in arterial elasticity, thickening of arterial walls and calcification of atherosclerotic lesions. Clinical testing for presymptomatic atherosclerosis should involve methods that are safe, noninvasive, reliable and reproducible, and which correlate with the extent of the atherosclerotic process. Although no such tests are currently widely used in clinical practice, potential methods for detecting the processes outlined above include ultrasound, positron emission tomography, magnetic resonance imaging and ultrafast computed tomography. With further developments, noninvasive imaging techniques for the study of arterial function and structure may soon provide clinically useful ways of detecting early atherosclerosis in high-risk asymptomatic subjects at a stage where preventive strategies are most likely to have important health benefits.

Genetics in childhood atherosclerosis

It is generally accepted that atherosclerosis is the extreme manifestation of what begins as a protective, fibroproliferative response to injury. Atherosclerosis can become pathological as a result of chronic, excessive exposure to particular causative agents. Several pathophysiological systems, including the inflammatory response, the immune response, cellular growth and proliferation, lipoprotein metabolism and coagulation, each of which operates as the result of the contributions of numerous gene products, can contribute to atherosclerosis either individually or in concert. In theory, identifying the genetic component(s) of atherosclerosis has become possible with molecular technologies and analytical methods. Reductionist experimental models have produced a list of several hundred candidate genes for the study of the genetic component of atherosclerosis. Within some families and isolated communities, the effect of a single gene upon atherosclerosis susceptibility may be profound, such as in the case of mutations within the gene encoding the low density lipoprotein receptor. However, at the level of the general population, particular candidate genes have small effects on atherosclerosis, or on one of its intermediate phenotypes. Furthermore, there are other factors, such as pleiotropy, epistasis, variations in genetic background, differences in individual environmental landscape, non-linear interactions among gene products and interactions between genes and the environment, which can confound the study of the genetic component of atherosclerosis.