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Objective: Dislipidaemia in type 2 diabetes mellitus contributes to arterial endothelial dysfunction and an increased risk of cardiovascular disease. Fenofibrate, a lipid-regulating peroxisome proliferator-activated receptor-α (PPARα) agonist, has been shown to reduce vascular complications in adults with type 2 diabetes. However, the mechanisms for such benefit are not well understood. We examined the effects of fenofibrate on brachial artery endothelial function in adults with type 2 diabetes., Methods: In a prospectively designed substudy of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, we assessed arterial flow-mediated dilatation (FMD; endothelium-dependent dilatation) and dilator responses to glyceryl trinitrate (GTN, an endothelium-independent dilator) in a subset of 193 representative adults. Traditional risk factors were assessed at baseline, 4 months and 2 years after randomised treatment allocation to fenofibrate (200 mg daily) or placebo. The prespecified primary study endpoint was the difference in FMD between treatment groups at 4 months., Results: Fenofibrate was associated with a significant improvement at 4 months compared with placebo (+1.05% (absolute); P=0.03); GTN-dilator responses were unchanged (P=0.77). After 2 years, FMD was similar in both groups (P=0.46). In multivariable models, none of the fenofibrate-related changes in lipoproteins and lipids were significantly associated with improved FMD on fenofibrate at 4 months., Conclusion: Treatment with fenofibrate significantly improved arterial endothelial function after 4 months. However, the effect was no longer apparent after 2 years. The long-term beneficial vascular effects of fenofibrate in type 2 diabetes are likely to be mediated via mechanisms other than improvement in endothelium-dependent dilatation of conduit arteries, and may differ for the microcirculation., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: n-3 Fatty acid supplementation in adults results in cardiovascular benefits. However, the cardiovascular effects of n-3 supplementation in early childhood are unknown., Objective: The objective was to evaluate blood pressure (BP) and arterial structure and function in 8-y-old children who had participated in a randomized controlled trial of dietary n-3 and n-6 modification over the first 5 y of life., Design: The children (n = 616; 49% girls) were randomly assigned antenatally to active (n = 312; increase in n-3 intake and decrease in n-6 intake) or control (n = 304) diet interventions implemented from the time of weaning or introduction of solids until 5 y of age. At age 8.0 +/- 0.1 y, BP, carotid intima-media thickness, carotid artery distensibility, augmentation index, and brachial pulse wave velocity were measured in 405 of these children. Venous blood was collected for measurement of plasma fatty acids, lipoproteins, high-sensitivity C-reactive protein, and asymmetric dimethylarginine. Plasma fatty acid concentrations were also assessed during the intervention., Results: Plasma concentrations of n-3 fatty acids were higher and of n-6 were lower in the active than in the control diet group at 18 mo and 3 and 5 y (P < 0.0001). Concentrations of n-3 and n-6 fatty acids were similar at 8 y. At 8 y of age, no significant differences were found in BP, carotid intima-media thickness, carotid artery distensibility, augmentation index, asymmetric dimethylarginine, high-sensitivity C-reactive protein, or lipoproteins between diet groups., Conclusion: A dietary supplement intervention to increase n-3 and decrease n-6 intakes from infancy until 5 y does not result in significant improvements in arterial structure and function at age 8 y. This trial was registered at the Australian Clinical Trials Registry as ACTRN012605000042640.

Asian Indians appear particularly susceptible to coronary heart disease compared with other ethnic groups. We compared the effects of vascular risk factors on carotid intima-media thickness (IMT) in a population of South Asians from Andhra Pradesh, India with a population of Caucasians from Perth, Australia. Cardiovascular risk factors and ultrasound-assessed carotid IMT were measured in randomly selected adults from two villages in rural India (n=303) and compared to those for randomly sampled adults from Australia (n=1111). Regression models with interaction terms were used to compare the strengths of associations between risk factors and carotid IMT, in these two populations. There were stronger associations of cholesterol (p for interaction=0.009) and diabetes (p=0.04) with carotid IMT in the Indian compared to the Australian population. Also, while increasing HDL-cholesterol was associated with decreasing carotid IMT in the Australian population the reverse was true for the Indian population (p<0.001). The associations with IMT of blood pressure, triglycerides, age, HDL to total cholesterol ratio, glucose, BMI, waist, waist to hip ratio and smoking were not different between the populations. Greater adverse effects of total cholesterol and diabetes on atherosclerosis and no protective effect of HDL-cholesterol amongst Asian Indians provide a novel possible explanation for observed excess rates of cardiovascular disease amongst these populations.

Much epidemiological evidence has linked low birthweight with late cardiovascular risk. We measured aortic wall thickness (a marker of early atherosclerosis) by ultrasonography in 25 newborn babies with intrauterine growth restriction and 25 with normal birthweight. Maximum aortic thicknesses were significantly higher in the babies with intrauterine growth restriction (810 microm [SD 113]) than in those without (743 microm [76], p=0.02), more so after adjustment for birthweight (300 microm/kg [45] vs 199 microm/kg [29], p<0.0001). Newborn babies with growth restriction have significant aortic thickening, suggesting that prenatal events might predispose to later cardiovascular risk.