THEROSCLEROSIS IS THOUGHTto begin in childhood and to develop silently for decades before clinical events such as myocardial infarction or stroke occur. Autopsy studies in children and adolescents have confirmed the presence of preclinical atherosclerotic lesions and shown their associations with antemortem vascular risk factors. [1][2][3] Studies using ultrasound imaging have demonstrated atherosclerotic wall thickening in the arteries of children with risk factors. [4][5][6] Longitudinal studies have shown that risk factor levels measured in childhood are predictive of risk factor levels in adulthood. [7][8][9] Moreover, levels of serum cholesterol measured in young adult men have been associated with cardiovascular disease in midlife. 10,11 Al-
Background-Endothelial vasodilator dysfunction and carotid intima-media thickening (IMT) are 2 indicators of subclinical cardiovascular disease. We examined their correlation and interaction with risk factors in a large, community-based cohort of young adults. Methods and Results-As part of the longitudinal Cardiovascular Risk in Young Finns Study, we measured endothelium-dependent brachial artery flow-mediated dilatation (FMD) and carotid artery IMT by ultrasound in 2109 healthy adults aged 24 to 39 years. FMD was inversely associated with IMT (PՅ0.001) in a multivariate model adjusted for age, sex, brachial vessel size, and several risk variables. The subjects with age-and sex-specific FMD values in the extreme deciles were classified into groups of impaired (nϭ204, FMDϭ1.1Ϯ1.4%, meanϮSD) and enhanced (nϭ204, FMDϭ16.3Ϯ2.9%) FMD response. The number of risk factors was correlated with increased IMT in subjects with an impaired FMD response (PϽ0.05) but not in subjects with an enhanced FMD response (PϾ0.2). Conclusions-Brachial FMD is inversely associated with carotid IMT. The number of risk factors in young adults is correlated with increased IMT in subjects with evidence of endothelial dysfunction, but not in subjects with preserved endothelial function. These observations suggest that endothelial dysfunction is an early event in atherosclerosis and that the status of systemic endothelial function may modify the association between risk factors and atherosclerosis.
We evaluated the correlates of baroreflex sensitivity (BRS) in healthy subjects. The study consisted of 117 healthy, normal-weight, nonsmoking male and female subjects aged 23-77 yr. Baroreflex control of heart rate was measured by using the phenylephrine bolus-injection technique. Frequency- and time-domain analysis of heart rate variability and an exercise test were performed. Plasma norepinephrine, epinephrine, insulin, and arginine vasopressin concentrations and plasma renin activity were measured. In the univariate analysis, BRS correlated with age (r = -0.65, P < 0.001), diastolic blood pressure (r = -0.47, P < 0.001), exercise capacity (r = 0.60, P < 0.001), and the high-frequency component of heart rate variability (r = 0.64, P < 0.001). There was also a significant correlation between BRS and plasma norepinephrine concentration (r = -0.22, P < 0.05) and plasma renin activity (r = 0.32, P < 0.001). According to the multivariate analysis, age and gender were the most important physiological correlates of BRS. They accounted for 52% of interindividual BRS variation. In addition, diastolic blood pressure and high-frequency component of heart rate variability were significant independent correlates of BRS. BRS was significantly higher in men than in women (15.0 +/- 1.2 vs. 10.2 +/- 1.1 ms/mmHg, respectively; P < 0.01). Twenty-four percent of women > 40 yr old and 18% of men > 60 yr old had markedly depressed BRS (< 3 ms/mmHg). We conclude that physiological factors, particularly age and gender, have significant impact on BRS in healthy subjects. In addition, we demonstrate that BRS values that have been proposed to be useful in identifying postinfarction patients at high risk of sudden death are frequently found in healthy subjects.
Background The clinical utility of identifying pediatric metabolic syndrome (MetS) is controversial. This study sought to determine the status of pediatric MetS as a risk factor for adult subclinical atherosclerosis (carotid intima-media thickness, cIMT) and type 2 diabetes mellitus (T2DM), and compare and contrast this prediction with its individual components. Methods and Results Using data from the population-based, prospective, observational Bogalusa Heart and Cardiovascular Risk in Young Finns studies, we examined the utility of four categorical definitions of youth MetS and their components in predicting adult high cIMT, and T2DM among 1781 participants aged 9–18 years at baseline (1984–88) who were then examined 14–27 years later (2001–2007) when aged 24–41 years. Youth with MetS were at 2–3 times the risk of having high cIMT, and T2DM as adults compared with those free of MetS at youth. Risk estimates using high body mass index (BMI) were similar to that of MetS phenotypes in predicting adult outcomes. Comparisons of area under the receiver operating characteristic curve and net reclassification suggested that prediction of adult MetS, high cIMT, and T2DM in adulthood using youth MetS was either equivalent or inferior to classification based on high BMI or overweight and obesity. Conclusions Youth with MetS are at increased risk of meaningful adult outcomes, however, the simplicity of screening for high BMI or overweight and obesity in the pediatric setting offers a simpler, equally accurate alternative to identifying youth at risk of developing adult MetS, high cIMT, or T2DM.
Background-The American Heart Association (AHA) defined a new concept, cardiovascular health, and determined metrics needed to monitor it over time as part of its 2020 Impact Goal definition. Ideal cardiovascular health is defined by the presence of both ideal health behaviors and ideal health factors. The applicability of this concept to a cohort of children and its relationship with cardiometabolic outcomes in adulthood has not been reported. Methods and Results-The
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