Carotid extramedial thickness is associated with local arterial stiffness in children.

OBJECTIVES: Experimental evidence suggests that structural changes to the arterial adventitia may be a key vascular determinant of early arterial stiffening, although this has not been directly studied. Accordingly, we hypothesized that in young children, in whom this relationship would not be altered by atheroma, carotid extramedial thickness (EMT), a measure that incorporates the thickness of the arterial adventitia, perivascular tissues and the internal jugular venous wall, would be associated with localized arterial stiffness of the same arterial region. METHODS: We studied 248 healthy prepubescent children (aged 8 years). Carotid diameter and carotid EMT were measured by high-resolution ultrasound. Carotid blood pressure was derived from brachial blood pressure and carotid tonometry. Three measures of localized arterial stiffness (ß stiffness index, distensibility coefficient and incremental modulus of elasticity) were calculated for the common carotid artery. Results were adjusted for heart rate and DBP, two important hemodynamic determinants of arterial stiffness. RESULTS: Carotid EMT was associated with all three measures of arterial stiffness (ß stiffness index: standardized ß = 0.121, P = 0.03; distensibility coefficient: standardized ß = -0.121, P = 0.05; incremental modulus of elasticity: standardized ß = 0.140, P = 0.02). These associations remained significant after adjustment for potential confounders such as sex, height, waist circumference, BMI and body surface area. CONCLUSION: Carotid EMT is associated with the stiffness of the same arterial segment in children, suggesting that the arterial adventitia may be involved in early changes in arterial stiffness during childhood.

Weight gain in infancy is associated with carotid extra-medial thickness in later childhood.

OBJECTIVE: Early life is an important period for determining future risk of cardiovascular disease. Carotid extra-medial thickness is a novel noninvasive measure that estimates arterial adventitial thickness, information concerning vascular health not captured by assessment of arterial intima-media thickness alone. We sought to determine whether fetal growth and early postnatal growth are associated with carotid extra-medial thickness in 8 year old children. METHODS: Carotid extra-medial thickness was assessed by high-resolution ultrasound in 379 non-diabetic children aged 8-years, with complete data for birth weight, gestational age, early postnatal weight gain and carotid extra-medial thickness. RESULTS: Weight gain during infancy, from birth to 18 months of age, was significantly and positively associated with carotid EMT (11 µm per kg length-adjusted weight gain [95% CI 3, 18], P=0.007). This association was significantly stronger in boys than girls (Pheterogeneity=0.005). By contrast, there was no significant association between birth weight and carotid EMT (6 µm/kg birth weight [95% CI -12, 24], P=0.51). CONCLUSION: Excessive weight gain during infancy is associated with increased carotid extra-medial thickness, indicating that the alterations to the vasculature associated with excessive early postnatal growth likely include arterial adventitial thickening.

An old friend in a new light: the role of osteocalcin in energy metabolism.

Accumulating evidence suggests interactions between bone and energy metabolism, which may affect the risk of cardiovascular disease. Recent animal studies indicate that osteocalcin (OC) plays a key role in the coordinated regulation of glucose and insulin metabolism while insulin receptors on osteoblasts may regulate bone turnover and circulating OC levels. Association studies, weight loss interventions, and observational data lend some support to the existence and relevance of these mechanisms in humans. However, corroborating evidence from pharmacologic interventions in either bone or glucose metabolism is limited by the number, design, and complex pharmacological effects of the drugs used. Furthermore, such clinical trials are complicated by the alteration of metabolic feedback mechanisms in the insulin resistant state. Purpose-designed studies are needed to further establish the existence and significance of the role of OC and its subfractions in human insulin metabolism. In this review we summarize existing animal evidence regarding the role of OC and its subfractions in bone and energy metabolism and assess current clinical trial evidence relating to the significance and consequences of this relationship in humans.

Carotid extra-medial thickness in childhood: early life effects on the arterial adventitia.

OBJECTIVE: Structural modification of the arterial adventitia may be an early event in atherosclerosis. Carotid extra-medial thickness is a new measure of arterial adventitial thickness. We examined the association of cardiovascular risk factors with extra-medial thickness, in childhood. METHODS: Carotid extra-medial thickness was assessed by high-resolution ultrasound in 389 non-diabetic children aged 8-years. A non-fasting blood sample was collected from 314 participants. Associations of gender, age, lipoproteins, blood pressure, BMI z-score, waist:height ratio and parental history of early vascular disease, with extra-medial thickness were examined. RESULTS: Carotid extra-medial thickness was lower in girls (r=-.163, P=.001) and directly associated with systolic (r=.128, P=.009), diastolic blood pressure (r=.130, P=.009), and height (r=.170, P=.0006). These associations remained after adjustment for carotid intima-media thickness. In multivariable analysis including carotid intima-media thickness, only gender and height were significantly associated with carotid extra-medial thickness. In gender-stratified analysis, the strongest associations with extra-medial thickness were BMI z-score (r=.181, P=.01), height (r=.210, P=.003) and diastolic blood pressure (r=.167, P=.02) for boys; and systolic blood pressure (r=.153, P=.03) and parental history of premature cardiovascular disease (r=.139, P=.05) for girls. The association of BMI z-score with extra-medial thickness differed by gender (P-interaction=.04). CONCLUSIONS: Carotid extra-medial thickness is independently associated with gender and height in childhood. Extra-medial thickness may provide important information concerning early arterial health, particularly related to the arterial adventitia.

Reducing maternal mortality: a review of progress and evidence-based strategies to achieve millennium development goal 5.

Maternal mortality represents a major global health challenge. Millennium Development Goal 5 (MDG 5) set a range of targets pertaining to maternal mortality and universal access to reproductive health care. While the realization of these targets seems unlikely, cost-effective population-level approaches in combination with evidence-based interventions targeting the acute management of the major causes of maternal mortality present the potential for considerable progress as the 2015 deadline approaches.