Search

Objective: We hypothesized that early weight gain would be associated with incident obesity, higher blood pressure, systemic inflammation, and arterial wall thickening in later childhood., Methods: A longitudinal birth cohort was recruited antenatally from 2 maternity hospitals in Sydney, Australia, between September 1997 and December 1999. Three hundred ninety-five nondiabetic children who were followed to age 8 years had complete data for early weight gain and arterial wall thickness., Results: Independent predictors of excess early weight gain (age 0-18 months; adjusted for height gain) included male gender (0.411 kg [SE: 0.103], P < .001), fewer weeks' gestation (-0.121 kg [SE: 0.044] per week, P = .006), birth length (0.156 kg [SE: 0.024] per cm, P < .001), and failure to breastfeed to 6 months of age (0.498 kg [SE: 0.108], P < .001). Early height-adjusted weight gain was significantly associated with later childhood overweight (odds ratio [OR]: 1.67 [95% confidence interval (CI): 1.26 to 2.20] per kg) and obesity (OR: 2.07 [95% CI: 1.53 to 2.79] per kg), excess central adiposity (OR: 1.54 [95% CI: 1.20 to 1.98] per kg), higher systolic blood pressure (1.24 mm Hg [SE: 0.33] per kg, P < .001), higher C-reactive protein (0.17 mg/dL [SE: 0.06] per 100% increase in weight gain, P = .006), and greater carotid intima-media thickness (0.012 mm [SE: 0.004] per kg, P = .002)., Conclusions: Early postnatal weight gain from birth to age 18 months is significantly associated with later childhood overweight and obesity, excess central adiposity, and greater arterial wall thickness.

Reduced fetal growth is associated with increased systolic blood pressure. Recently, we found an inverse association between serum ω-3 fatty acids and systolic blood pressure in young adults born with impaired fetal growth. We investigated the associations of dietary intake in childhood of the long-chain ω-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid with blood pressure parameters in children born with reduced birth weight. We analyzed data from 3457 children aged 8 to 15 years participating in the continuous National Health and Nutrition Examination Survey 2003-2004, 2005-2006, and 2007-2008. Dietary intake was assessed by two 24-hour dietary recalls, birth weight by questionnaire, and blood pressure was measured. Systolic blood pressure was 1.1 mm Hg higher in those with reduced (<10th centile) compared with normal birth weight (≥ 10th centile), consistent with previous findings, although not statistically significant (P=0.40); however, pulse pressure was significantly higher in these children (3.4 mm Hg). In the 354 participants with reduced birth weight, when compared with children with the lowest tertile of intake, those who had the highest tertile of dietary eicosapentaenoic acid and docosahexaenoic acid intake had significantly lower systolic blood pressure (-4.9 mm Hg [95% confidence interval, -9.7 to -0.1]) and pulse pressure (-7.7 mm Hg [95% confidence interval, -15.0 to -0.4]). High-dietary intakes of eicosapentaenoic acid and docosahexaenoic acid are associated with lower systolic blood pressure and pulse pressure in children born with reduced birth weight. These data are consistent with the hypothesis that long-chain ω-3 fatty acids reduce blood pressure in those with impaired fetal growth.

Study Objectives: Preeclampsia affects 5% to 7% of pregnancies, is strongly associated with low birth weight and fetal death, and is accompanied by sleep disordered breathing. We hypothesized that sleep disordered breathing may link preeclampsia with reduced fetal movements (a marker of fetal health), and that treatment of sleep disordered breathing might improve fetal activity during sleep., Design, Setting, and Participants: First, a method of fetal movement recording was validated against ultrasound in 20 normal third trimester pregnancies. Second, fetal movement was measured overnight with concurrent polysomnography in 20 patients with preeclampsia and 20 control subjects during third trimester. Third, simultaneous polysomnography and fetal monitoring was done in 10 additional patients with preeclampsia during a control night and during a night of nasal CPAP., Intervention: Overnight continuous positive airway pressure., Measurements and Results: Women with preeclampsia had inspiratory flow limitation and an increased number of oxygen desaturations during sleep (P = 0.008), particularly during REM sleep. Preeclampsia was associated with reduced total fetal movements overnight (319 [SD 32]) versus controls (689 [SD 160], P < 0.0001) and a change in fetal movement patterns. The number of fetal hiccups was also substantially reduced in preeclampsia subjects (P < 0.0001). Continuous positive airway pressure treatment increased the number of fetal movements and hiccups (P < 0.0001 and P = 0.0002, respectively)., Conclusions: The effectiveness of continuous positive airway pressure in improving fetal movements suggests a pathogenetic role for sleep disordered breathing in the reduced fetal activity and possibly in the poorer fetal outcomes associated with preeclampsia.

Carotid intima-media-thickness (cIMT) and carotid distensibility (distensibility), structural and functional properties of carotid arteries respectively, are early markers, as well as strong predictors of cardiovascular disease (CVD). The characteristic of these two parameters in individuals with BMI>40.0 kg/m(2) (Class III obesity), however, are largely unknown. The present study was designed to document cIMT and distensibility in this population and to relate these to other factors with established association with CVD in obesity. The study included 96 subjects (65 with BMI>40.0 kg/m(2) and 31, age- and gender-matched, with BMI of 18.5 to 30.0 kg/m(2)). cIMT and distensibility were measured by non-invasive high resolution ultrasonography, circulatory CD133(+)/KDR(+) angiogenic cells and endothelial microparticles (EMP) by flow cytometry, and plasma levels of adipokines, growth factors and cytokines by Luminex immunoassay kits. The study results demonstrated increased cIMT (0.62±0.11 mm vs. 0.54±0.08 mm, P = 0.0002) and reduced distensibility (22.52±10.79 10(-3)kpa(-1)vs. 29.91±12.37 10(-3)kpa(-1), P<0.05) in individuals with BMI>40.0 kg/m(2). Both cIMT and distensibility were significantly associated with traditional CVD risk factors, adiposity/adipokines and inflammatory markers but had no association with circulating angiogenic cells. We also demonstrated, for the first time, elevated plasma EMP levels in individuals with BMI>40.0 kg/m(2). In conclusion, cIMT is increased and distensibility reduced in Class III obesity with the changes predominantly related to conventional CVD risk factors present in this condition, demonstrating that both cIMT and distensibility remain as CVD markers in Class III obesity.

Background: Impaired fetal growth is independently associated with an increased risk of cardiovascular events in adulthood. Prevention strategies that can be implemented during adulthood have not been identified., Objective: The objective was to determine whether habitual omega-3 (n-3) fatty acid intake is associated with the rate of increase of carotid intima-media thickness during adulthood in individuals with impaired fetal growth., Design: This was a population-based, prospective cohort study of 1573 adults in Finland. Carotid intima-media thickness was assessed in 2001 (at ages 24-39 y) and in 2007. Participants were categorized as having had impaired fetal growth (term birth with birth weight <10th percentile for sex or preterm birth with birth weight <25th percentile for gestational age and sex; n = 193) or normal fetal growth (all other participants; n = 1380). Omega-3 fatty acid intake was assessed by using a food-frequency questionnaire and on the basis of serum fatty acid concentrations., Results: In multivariable models, the 6-y progression of carotid intima-media thickness was inversely associated with dietary omega-3 fatty acids in those with impaired fetal growth (P = 0.04). Similarly, serum omega-3 fatty acid concentrations were inversely associated with the 6-y progression of carotid intima-media thickness in those with impaired fetal growth (P = 0.04) but were not noted in those with normal fetal growth (P = 0.94 and P = 0.26, respectively)., Conclusion: Dietary intake of omega-3 fatty acids is associated with a slower rate of increase in carotid intima-media thickness in those with impaired fetal growth.

Objectives: The aim of this study was to examine the effect of resolution from metabolic syndrome (MetS) between youth and adulthood on carotid artery intima-media thickness (IMT) and type 2 diabetes mellitus (T2DM)., Background: Published findings demonstrate that youth with MetS are at increased risk of cardio-metabolic outcomes in adulthood. It is not known whether this risk is attenuated in those who resolve their MetS status., Methods: Participants (n = 1,757) from 2 prospective cohort studies were examined as youth (when 9 to 18 years of age) and re-examined 14 to 27 years later. The presence of any 3 components (low high-density lipoprotein cholesterol, high triglycerides, high glucose, high blood pressure, or high body mass index) previously shown to predict adult outcomes defined youth MetS; the harmonized MetS criteria defined adulthood MetS. Participants were classified according to their MetS status at baseline and follow-up and examined for risk of high IMT and T2DM., Results: Those with MetS in youth and adulthood were at 3.4 times the risk (95% confidence interval: 2.4 to 4.9) of high IMT and 12.2 times the risk (95% confidence interval: 6.3 to 23.9) of T2DM in adulthood compared with those that did not have MetS at either time-point, whereas those that had resolved their youth MetS status by adulthood showed similar risk to those that did not have MetS at either time-point (p > 0.20 for all comparisons)., Conclusions: Although youth with MetS are at increased risk of adult high IMT and T2DM, these data indicate that the resolution of youth MetS by adulthood can go some way to normalize this risk to levels seen in those who have never had MetS., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The recently discovered longitudinal displacement of the common carotid arterial wall (i.e., the motion along the same plane as the blood flow), may be associated with incident cardiovascular events and represents a novel and relevant clinical information. At present, there have only been a few studies that have been conducted to investigate this longitudinal movement. We propose here a method to assess noninvasively the wall bi-dimensional (two-dimensional [2-D], cross-sectional and longitudinal) motion and present an original approach that combines a robust speckle tracking scheme to guidance by minimal path contours segmentation. Our method is well suited to large clinical population studies as it does not necessitate strong imaging prerequisites. The aim of this study is to describe the association between the longitudinal displacement of the carotid arterial wall and cardiovascular risk factors, among which periodontal disease. Some 126 Indigenous Australians with periodontal disease, an emerging risk factor, and 27 healthy age- and sex-matched non-indigenous control subjects had high-resolution ultrasound scans of the common carotid artery. Carotid intima-media thickness and arterial wall 2-D motion were then assessed using our method in ultrasound B-mode sequences. Carotid longitudinal displacement was markedly lower in the periodontal disease group than the control group (geometric mean (IQR): 0.15 mm (0.13) vs. 0.42 mm (0.30), respectively; p < 0.0001), independent of cardiovascular risk factors, cross-sectional distensibility and carotid intima-media thickness (p < 0.0001). A multivariable model indicated that the strongest correlates of carotid longitudinal displacement in adults with periodontal disease were age (β-coefficient = -.235, p = .03), waist (β-coefficient = -.357, p = 0.001), and pulse pressure (β-coefficient = .175, p = 0.07), independent of other cardiovascular risk factors, cross-sectional distensibility and pulse wave velocity. Carotid longitudinal displacement, estimated with our approach, is impaired in the periodontal disease group, independent of established cardiovascular risk factors and other noninvasive measures of arterial stiffness, and may represent an important marker of cardiovascular risk., (Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Increasing dietary n-3 PUFA decreases the risk of CHD. Since n-6 PUFA compete with n-3 PUFA for common metabolic enzymes, the n-6:n-3 ratio intake rather than the n-3 PUFA intake levels per se may be critical. We aimed to examine whether altering the n-6:n-3 ratio affects cardiovascular risk factors in hypercholesterolaemic patients on lipid management with statins. Adhering to a randomised, crossover study design, patients on statins (n 11) were placed on one of two dietary interventions (Diet high-ratio (HR) - n-6:n-3 = 30:1 or Diet low-ratio (LR) - n-6:n-3 = 1·7:1) for 4 weeks followed after an 8-week washout period by the alternate diet. Foods enriched with n-3 or n-6 PUFA were delivered to each patient, who were given clear guidance on consumption expectations for the study. Measures of lipid profile, blood pressure and vascular function were determined. Diet LR significantly reduced body weight, LDL-cholesterol, high-sensitivity C-reactive protein, blood pressure and the apoA-1:apoB ratio. While Diet HR trended towards a similar cardioprotective profile, most of the parameters examined did not reach statistical significance. A direct comparison between diets demonstrated no significant superiority of Diet LR over Diet HR. These results suggest that a dietary intervention focused on n-6 and n-3 fatty acids may improve cardiovascular risk factors in patients over and above standard lipid management, but there is no significant advantage of a low n-6:n-3 ratio diet when compared to a high-ratio diet.

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.)

Objectives: Impaired fetal growth is an independent cardiovascular risk factor and is associated with arterial wall thickening in children. No preventive strategy has been identified. We sought to determine whether dietary ω-3 fatty acid supplementation during early childhood prevents the association between impaired fetal growth and carotid arterial wall thickening., Methods: The Childhood Asthma Prevention Study was a randomized, controlled single-blind trial in 616 children born at term, recruited antenatally from maternity hospitals in Sydney. Participants were randomized to either a 500-mg-daily fish oil supplement and canola-based margarines and cooking oil (ω-3 group), or a 500-mg-daily sunflower oil supplement and ω-6 fatty acid-rich margarines and cooking oil (control group), from the start of bottle-feeding or 6 months of age until 5 years of age. Carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, was the primary endpoint of a cardiovascular substudy (CardioCAPS) at age 8 years. We examined the association of fetal growth with carotid IMT in children with birth weight <90th percentile (ω-3 group [n = 187], control group [n = 176])., Results: In the control group, fetal growth was inversely associated with carotid IMT, but this was prevented in the ω-3 group (difference between groups of 0.041 mm [95% confidence interval 0.006, 0.075] per kg birth weight, adjusted for gestational age and gender, P(heterogeneity) = .02)., Conclusions: The inverse association of fetal growth with arterial wall thickness in childhood can be prevented by dietary ω-3 fatty acid supplementation over the first 5 years of life.

Objective: Impaired fetal growth is associated with cardiovascular disease in adulthood. The mechanisms of this association remain poorly described. We aimed to determine the associations of impaired fetal growth and preterm birth with cardiovascular risk factors and arterial health in a large cohort of young adults., Methods and Results: Carotid intima-media thickness, brachial flow-mediated dilatation and cardiovascular risk factors were compared between young adults (24-45 years) born at term with impaired fetal growth (birth weight <10th percentile; n=207), born preterm (<37 weeks' gestation; n=253), and a control group born at term with normal fetal growth (birth weight 50-90th percentile; n=835), in the Cardiovascular Risk in Young Finns study. Compared with controls, those with impaired fetal growth had elevated triglycerides (P=0.006), C-reactive protein (P=0.004), low-density lipoprotein cholesterol, systolic blood pressure (both P=0.06), and intima-media thickness and impaired flow-mediated dilatation (both P=0.02), the latter partially mediated by systolic blood pressure, C-reactive protein, and triglycerides. Those born preterm had higher intima-media thickness (P=0.005) and lower flow-mediated dilatation (P=0.03) compared with controls, although this was restricted to those with concurrent fetal growth restriction., Conclusions: Impaired fetal growth is associated with impaired endothelial function and elevated preclinical atherosclerosis in young adults, partly mediated by inflammation, blood pressure, and triglycerides. This association is most marked for those also born preterm.

Background: Indigenous Australians experience an overwhelming burden of chronic disease, including cardiovascular diseases. Periodontal disease (inflammation of the tissues surrounding teeth) is also widespread, and may contribute to the risk of cardiovascular diseases via pathogenic inflammatory pathways. This study will assess measures of vascular health and inflammation in Indigenous Australian adults with periodontal disease, and determine if intensive periodontal therapy improves these measures over a 12 month follow-up. The aims of the study are: (i) to determine whether there is a dose response relationship between extent and severity of periodontal disease and measures of vascular health and inflammation among Indigenous Australian adults with moderate to severe periodontal disease; and (ii) to determine the effects of periodontal treatment on changes in measures of vascular health and inflammation in a cohort of Indigenous Australians., Methods/design: This study will be a randomised, controlled trial, with predominantly blinded assessment of outcome measures and blinded statistical analysis. All participants will receive the periodontal intervention benefits (with the intervention delayed 12 months in participants who are randomised to the control arm). Participants will be Indigenous adults aged ≥25 years from urban centres within the Top End of the Northern Territory, Australia. Participants assessed to have moderate or severe periodontal disease will be randomised to the study's intervention or control arm. The intervention involves intensive removal of subgingival and supragingival calculus and plaque biofilm by scaling and root-planing. Study visits at baseline, 3 and 12 months, will incorporate questionnaires, non-fasting blood and urine samples, body measurements, blood pressure, periodontal assessment and non-invasive measures of vascular health (pulse wave velocity and carotid intima-media thickness). Primary outcome measures are pulse wave velocity and carotid intima-media thickness., Discussion: The study will assess the periodontal-cardiovascular disease relationship among Indigenous Australian adults with periodontal disease, and the effectiveness of an intervention aimed at improving periodontal and cardiovascular health. Efforts to understand and improve Indigenous oral health and cardiovascular risk may serve as an important means of reducing the gap between Indigenous and non-Indigenous health in Australia., Trial Registration: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12610000817044.

Aim: Parity is associated with an increased risk of coronary heart disease and type 2 diabetes, possibly mediated by long-term modification of metabolic health. Studying associations between the number of children with health and disease in men in addition to women allows for differentiation between the social and lifestyle influences of child-rearing, and the biological influences of childbearing. We sought to determine whether the number of children is associated with the incidence of raised fasting glucose (fasting plasma glucose≥6.1 mmol/L) and changes in glucose, insulin, insulin resistance and β-cell function over 9-years., Methods: Analysis of 1798 women and 1737 men from the DESIR study., Results: The number of children was associated with change in fasting glucose for women (P(trend)=0.02) and men (P(trend)=0.03), and increased incidence of raised fasting glucose by 30% (95% CI: 15, 47%) per child for men, but not women (3% [95% CI: -8, 15%]). There was a J-shaped association between number of children and change in insulin (P=0.01) and insulin resistance (P=0.005) for women, and a reduction in β-cell function in parous women (P=0.07). Men with children had increases in insulin (P=0.02), insulin resistance (P=0.02), and β-cell function (P=0.07)., Conclusions: The number of children a person has is associated with changes in metabolic health indices long after childbirth for both men and women. The distinct gender differences in deterioration of metabolic health indices emphasize that childbearing and child-rearing are likely to have differential influences on metabolic health., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Objective: To determine which metabolic and cardiovascular risk factors are associated with the change in ankle brachial pressure index and incident peripheral arterial disease over 9 years, and whether these associations differ between healthy weight and overweight & obese individuals., Methods: Metabolic factors, change in ankle brachial pressure index and incidence of peripheral arterial disease (ankle brachial pressure index <0.90) over 9-years were determined in 2139 healthy weight and 1453 overweight & obese participants from the D.E.S.I.R. study., Results: Fasting glucose, insulin, HDL-cholesterol, systolic blood pressure and pulse pressure were all directly associated with the incidence of peripheral arterial disease, however BMI and the metabolic syndrome were not. There was some evidence that the associations of fasting insulin (P(heterogeneity)=0.06), insulin resistance (P(heterogeneity)=0.08) and β-cell function (P(heterogeneity)=0.004) with change in ankle brachial pressure index, differed between healthy weight and overweight & obese subjects. Principal components analysis identified a classical metabolic syndrome cluster, and an alternative clustering of metabolic factors that was characterised by high pulse pressure, high HDL-cholesterol and low triglycerides. This alternative cluster of cardiovascular and metabolic risk factors was associated with reductions in ankle brachial pressure index and an increased incidence of peripheral arterial disease (both P<0.0001)., Conclusions: Overweight & obesity do not increase the risk of developing peripheral arterial disease. We identified an alternative cluster of metabolic factors that is strongly associated with reductions in ankle brachial pressure index and an increased incidence of peripheral arterial disease., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: Carotid intima-media thickness is a well established non-invasive surrogate marker of cardiovascular disease, however there is evidence that structural modification of the arterial adventitia also accompanies cardiovascular risk factors and might be involved causally in atherosclerosis. We sought to determine the relative contributions of the intima-media and adventitia to variation in ultrasound and magnetic resonance derived measures of carotid wall thickness., Methods: Carotid ultrasound and magnetic resonance imaging were undertaken in 20 participants. Carotid intima-media thickness, carotid extra-media thickness (which incorporates the arterial adventitia) and total wall thickness (a combined near-wall intima-media thickness and carotid extra-media thickness) using high-resolution ultrasound, and wall thickness using magnetic resonance imaging, were obtained., Results: All ultrasound-derived measures of the arterial wall thickness were highly correlated with wall thickness by magnetic resonance imaging (all P<0.001); as expected the total wall thickness by ultrasound measure was most tightly correlated (correlation coefficient=0.814, P<0.0001). In multivariable models, there was evidence that both carotid intima-media thickness and carotid extra-media thickness contributed independently to the variance in wall thickness by magnetic resonance imaging, especially for the most severe focal thickening. Measures of carotid wall thickness that incorporated all three layers of the arterial wall were more closely correlated with the number of cardiovascular risk factors than carotid intima-media thickness alone., Conclusions: These results indicate that the arterial adventitia is an important contributor to the wall thickness measure derived by magnetic resonance imaging, and that carotid extra-media thickness likely provides additional information concerning arterial structure than that obtained from carotid intima-media thickness alone., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To describe dietary carbohydrate intakes and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study., Methods: Between 1995 and 2000, 36 034 subjects, aged between 35-74 years, were administered a standardized, 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes (g/day) of total carbohydrate, sugars, starch and fibre were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age, total energy intake, height and weight, and were weighted by season and day of recall., Results: Adjusted mean total carbohydrate intakes were highest in Italy and in the UK health-conscious cohort, and were lowest in Spain, Greece and France. Total fibre intakes were highest in the UK health-conscious cohort and lowest in Sweden and the UK general population. Bread contributed the highest proportion of carbohydrates (mainly starches) in every centre. Fruit consumption contributed a greater proportion of total carbohydrates (mainly sugars) among women than among men, and in southern centres compared with northern centres. Bread, fruits and vegetables represented the largest sources of fibre, but food sources varied considerably between centres. In stratified analyses, carbohydrate intakes tended to be higher among subjects who were physically active, never-smokers or non-drinkers of alcohol., Conclusions: Dietary carbohydrate intakes and in particular their food sources varied considerably between these 10 European countries. Intakes also varied according to gender and lifestyle factors. These data will form the basis for future aetiological analyses of the role of dietary carbohydrates in influencing health and disease.

Objectives: We sought to develop a noninvasive technique to quantify the thickness of a segment of the carotid artery wall that incorporates the adventitia and to identify whether differences in this measure are associated with cardiovascular risk factors., Background: There is increasing evidence that the arterial adventitia undergoes extensive structural alteration, including thickening, in response to arterial injury. However, there is currently no widely accepted noninvasive technique for studying the thickness of the arterial adventitia in humans., Methods: The carotid artery and jugular vein were imaged simultaneously in longitudinal section with the use of high-resolution ultrasound. The distance from the jugular intima-lumen interface to the carotid media-adventitia margin was denominated as the carotid extra-media thickness (EMT). This measure includes the arterial adventitia but not the arterial intima or media. We measured the carotid EMT and intima-media thickness (IMT) in 175 subjects, including 54 with diabetes, 43 with dyslipidemia, 26 with other cardiovascular risk factors, and 52 healthy control subjects., Results: When compared with control subjects, the EMT was increased in both the diabetes (p < 0.0001) and dyslipidemia (p = 0.04) groups. Multivariate linear regression analyses revealed that diabetes, high-density lipoprotein cholesterol (inverse association), and systolic blood pressure (J-shaped association) were the factors most strongly associated with EMT. These associations appear to be independent of carotid IMT., Conclusions: Carotid EMT can be assessed by ultrasonography. It is physically distinct from IMT and provides additional information concerning the vascular changes associated with cardiovascular risk factors. As such, the measurement of EMT, in addition to IMT, may provide a more complete indication of the structural modification of the vasculature associated with cardiovascular risk factors than that obtained by the measurement of carotid IMT alone.

Background/objectives: Consumption of n-3 polyunsaturated fatty acids (PUFA) has a favourable impact on inflammation and cardiovascular disease. However, the Western diet is characterized by a low n-3 PUFA intake and an imbalance in the n-6/n-3 PUFA ratio. Study the effect 10-week of diet modification to decrease the n-6/n-3 PUFA ratio on cardiovascular risk factors and resting energy expenditure., Subjects and Methods: Ten-week dietary intervention in 17 healthy subjects. Dietary intake, euglycemic hyperinsulinemic clamp, indirect calorimetry, lipid profile, hormones, inflammatory markers and erythrocyte membrane fatty acid composition were recorded before and at the end of the intervention. Comparisons are between baseline and post-treatment levels., Results: Dietary records of the linoleic acid/alpha-linolenic acid ratio (baseline: 32.2 (s.d. 3.7) vs post-intervention: 2.2 (s.d. 0.1), P<0.0001) and erythrocyte membrane fatty acid composition reflected good compliance. Dietary intervention was associated with significant reductions in TNF-alpha (baseline: 2.2 (s.d. 0.3), post-intervention: 1.5 (s.d. 0.3) pg/ml, P=0.01) and low-density lipoprotein-cholesterol (baseline: 2.5 (s.d. 0.2), post-intervention: 2.3 (s.d. 0.1) mmol/l, P=0.03) and increased adiponectin (baseline: 6.5 (s.d. 0.7), post-intervention: 7.6 (s.d. 0.6) microg/ml, P=0.02). Fasting lipid oxidation was increased (baseline: 0.7 (s.d. 0.1), post-intervention: 0.9 (s.d. 0.1) mg/kg x min, P=0.01), whereas glucose oxidation decreased in both fasting (baseline: 1.6 (s.d. 0.1), post-intervention: 1.3 (s.d. 0.1) mg/kg x min, P=0.02) and hyperinsulinaemic conditions (baseline: 3.6 (s.d. 0.1), post-intervention: 3.3 (s.d. 0.1) mg/kg x min, P=0.04). Insulin sensitivity was not affected by the intervention., Conclusion: A decreased n-6/n-3 PUFA ratio can be achieved with simple dietary counselling, resulting in multiple, potentially favourable effects on the metabolic and inflammatory profiles.

Aims: The mechanisms by which obesity confers increased cardiovascular risk and the effects of moderate weight loss on cardiovascular health are incompletely understood. We sought to characterize the preclinical changes in cardiac and vascular health that accompany obesity and the influence of lifestyle modification on these parameters., Methods: Preclinical markers of vasculopathy in resistance vessels and conduit arteries and left ventricular structure and function were assessed in 39 obese subjects (BMI > 30 kg/m(2)) and 11 healthy weight controls. The influence of serum on cellular adhesion molecule (CAM) expression on human endothelial cells was studied ex vivo in a subgroup of 13 obese and nine healthy weight subjects. These analyses were repeated in all 17 of the obese subjects who complied with 4-9 months of lifestyle modification treatment (six with weight loss >5% and 11 with weight loss <5%)., Results: Compared with healthy weight controls, obese subjects had decreased peak hyperaemic forearm blood flow (p = 0.015), increased carotid intima-media thickness (p = 0.009), increased left ventricular wall thickness and volume and evidence of systolic and diastolic dysfunction as assessed using tissue Doppler imaging (S', p = 0.09; E'/A', p = 0.02), and serum from obese subjects increased the intercellular CAM-1 expression on human endothelial cells (p = 0.009). However, arterial endothelial function assessed by flow-mediated dilatation was not altered (p = 0.99). Lifestyle modification treatment resulted in potentially beneficial changes in fibrinogen (p = 0.003), HDL cholesterol (p = 0.05) and soluble vascular CAM-1 (p = 0.06). In subjects with weight loss greater than 5% of body weight, there was also a decrease in low-level inflammation (high-sensitivity C-reactive protein, p = 0.05), lipid peroxidation (thiobarbituric acid-reactive substances, p = 0.05) and triglycerides (p = 0.07)., Conclusions: Obesity is associated with widespread alterations in cardiac and vascular structure and function. Moderate short-term weight loss by lifestyle modification results in some beneficial changes in serum profile; however, these are not accompanied by significant alterations to either cardiac or vascular structure and function.

Evidence from noninvasive ultrasound studies of the neonatal aorta and fetal and early childhood postmortem studies indicates that impaired fetal growth, in utero exposure to maternal hypercholesterolemia, and diabetic macrosomia may all be important risk factors for vascular changes consistent with the earliest physical signs of atherosclerosis. Although the exact mechanisms that underlie these associations remain unclear, animal models have suggested that the use of antioxidant, lipid-lowering, and other innovative therapies may counteract the impact of these intrauterine risk factors for cardiovascular disease. This review summarizes the current evidence for intrauterine factors that have a direct impact on atherosclerosis and provides potential treatment and prevention strategies.

Background: There is limited evidence as to whether the metabolic syndrome (MetS) is associated with depression or anxiety and, if so, whether this association is gender-specific. This study investigated in each gender whether the MetS is associated with anxiety or depression and whether these relationships are independent of age, obesity, smoking status, socioeconomic factors, and lifestyle., Methods: Metabolic syndrome (American Heart Association/National Heart, Lung, and Blood Institute criteria), depression, and anxiety (Hospital Anxiety and Depression Scale) were assessed in 1598 subjects at risk of cardiovascular disease., Results: In both men and women, the MetS was associated with an increased prevalence of depression but not anxiety. The number of components of the MetS increased with increasing levels of depression but not anxiety. This association between the MetS and depressive symptoms was independent of age, smoking status, socioeconomic factors, and lifestyle. The relationship was observed across body mass index categories and was independent of anxiety., Conclusions: The MetS is associated with depression and depressive symptoms but not anxiety irrespective of gender and overweight/obesity status in subjects at risk of cardiovascular disease. These findings suggest a potential importance of screening for depression in patients with the MetS.

Objective: Prader-Willi syndrome (PWS) is a genetic obesity syndrome characterized by hyperphagia, behavioural disturbance and intellectual disability. PWS appears to be associated with a high incidence of sudden death, suspected to be cardiopulmonary in origin. We therefore sought to provide an assessment of cardiac and vascular structure and function in patients with PWS., Patients: Nine patients with genetically confirmed PWS, mean age 28 years, body mass index (BMI) 42 kg/m2, were compared with nine age- and gender-matched lean controls., Measurements: Lipid parameters, high-sensitivity C-reactive protein (hs-CRP) and fasting glucose and insulin were measured. To assess cardiac structure and function, a resting electrocardiogram (ECG), exercise stress test, 24-h continuous ECG monitoring, and echocardiogram were obtained. Patients and control subjects also underwent comprehensive noninvasive vascular assessment, including venous-occlusion forearm plethysmography, brachial artery flow-mediated dilatation (FMD), radial artery tonometry and carotid intima-media thickness (IMT) measurements., Results: All patients with PWS had significantly elevated hs-CRP (> 3.0 mg/l) (mean 11.5 mg/l, median 11.47, interquartile range: 4.48-15.8 mg/l), compared with controls (P < 0.001). Five of nine patients with PWS had subnormal exercise capacity (< 4 mets on exercise stress testing). Twenty-four-hour ECG monitoring revealed prolonged sinus pauses in one patient, up to 4.8 s, requiring pacemaker insertion. Microvascular function as assessed by peak hyperaemic flow response was decreased in PWS (6.1 +/- 1.0 times baseline flow vs. controls 13.5 +/- 1.6 times baseline flow, P = 0.01). Other measures were similar between PWS and controls., Conclusions: This group of PWS patients had significantly raised levels of the inflammatory marker hs-CRP and evidence of microcirculatory dysfunction, both of which are associated with coronary artery disease and early sudden death. The sinus node dysfunction may in itself be a risk factor for sudden cardiac death.

The metabolic syndrome is associated with increased risk of cardiovascular disease. However, the association between metabolic syndrome and atherosclerosis in hypercholesterolemic patients remains unknown. We examined the association between carotid atherosclerosis and metabolic syndrome definitions using the NCEP-ATPIII, International Diabetes Federation (IDF) and American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) definitions in 1782 subjects at risk of cardiovascular disease including 926 with hypercholesterolemia (LDL cholesterol > or =160 mg/dL; mean=203 mg/dL). Irrespective of definition, carotid intima-media thickness was significantly higher in both men and women diagnosed with the MetS compared to those without MetS. This relationship persists in males with hypercholesterolemia, independently of LDL cholesterol level. Regression analyses, both unadjusted and adjusted for traditional risk factors, indicate that in males the AHA/NHLBI definition, and in females the IDF definition are the strongest predictors of carotid atherosclerosis. These results highlight important gender differences that exist in the current clinical definitions of the metabolic syndrome, with regards to predicting early atherosclerotic lesions. In addition, this study shows that in males with hypercholesterolemia, MetS is independently associated with increased atherosclerosis, supporting screening for MetS among people at risk of CVD.

Purpose: To study the repeatability of common carotid mean wall thickness (MWT) measured with high resolution MRI, in comparison with intima media thickness (IMT) assessed by ultrasound and to investigate the relative capabilities of these two modalities., Materials and Methods: Ten healthy volunteers and 10 subjects with carotid artery atherosclerosis were imaged with both high resolution MRI and US. Measurement of both MWT and IMT was performed by three blinded observers. Intra- and inter-observer repeatability was calculated and a Bland-Altman plot used to compare IMT and MWT. Circumferential variation in arterial wall thickness was also evaluated., Results: Intra- and inter-observer repeatability were comparable between IMT and MWT. The Bland-Altman plot showed a difference between IMT and MWT in controls with a trend towards equivalence in atherosclerotic patients. Analysis of circumferential variation in wall thickness by MRI identified greater focal thickening in patients compared with controls (p<0.001), which was not evident with ultrasound (p=0.98)., Conclusion: MRI and ultrasound have similar repeatability for the assessment of carotid wall thickness. There are differences between MWT and IMT, potentially due to the inclusion of the adventitia by MRI which, in addition to better detection of focal thickening, may provide a more complete estimation of early stage atherosclerosis.

Epidemiological studies suggest a link between fetal/early infant nutrition and adult coronary artery disease. In the present study, we examined the effects of altering nutrition during gestation, lactation and juvenile life on aortic structure and function in rats. Wistar rat dams were fed either a control or low-protein diet throughout pregnancy, or a low-protein diet for the final 7 days of gestation only. At 21 days post-partum, male pups were weaned on to a control, low-protein or high-fat diet. At 12 weeks, the offspring rats were killed. In 46 rats, aortic sections were mounted and stained to assess media thickness and elastin content. In a further 38 rats, aortic rings were suspended in an organ bath and vascular reactivity was tested with dose-response curves to the endothelium-dependent dilator acetylcholine and the endothelium-independent dilator sodium nitroprusside. Rats exposed to maternal protein restriction while in utero had a significantly decreased aortic wall thickness compared with control rats (P=0.005). Total elastin content of the aorta was also decreased by both maternal low-protein (P=0.02) and early postnatal low-protein (P=0.01) diets. Neither maternal nor postnatal low-protein or high-fat diets, however, resulted in any significant changes in arterial dilator function. In conclusion, fetal undernutrition in rats, induced via a maternal low-protein diet, causes a decrease in aortic wall thickness and elastin content without altering aortic dilator function. These changes in vascular structure may amplify aging-related changes to the vasculature and contribute to the pathophysiology of the putative link between impaired fetal growth and adult cardiovascular disease.

Rates of overweight and obesity in both adults and children have risen sharply during the past 20 years. The reasons for this escalation in obesity are not fully determined, however, sedentary lifestyle and dietary changes in combination with genetic predisposition are probably involved. Clinical cardiovascular disease, including myocardial infarction and stroke, are usually only manifest in the fifth decade of life or beyond. However, the earliest physical signs of atherosclerosis, the underlying disease process that leads to these events, may be present from early childhood. There are now a variety of noninvasive tests used to assess both the structural and functional properties of the vasculature and in vivo changes suggestive of 'early atherosclerosis' have now been characterised. These have allowed not only an increased understanding of the atherosclerotic changes to the vasculature that accompany overweight and obesity in children, but have also allowed serial study of the effects of diet and exercise interventions on early atherosclerosis changes, in childhood obesity.

Obesity and its related metabolic diseases, including type 2 diabetes, are associated with alterations in the circulating levels of various peptides. These include the adipocytokines (peptides released by adipocytes which circulate, such as leptin, adiponectin and resistin), and other peptides whose levels are altered in association with obesity (such as ghrelin, neuropeptide Y, interleukin-1 beta and tumour necrosis factor-alpha). While the primary action of these peptides is linked with the regulation and maintenance of energy balance and metabolism, many of them have also been shown to possess vasoactive, inflammatory and other properties that influence vascular biology, vascular physiology and atherogenesis. As such, they may form an important mechanistic link between obesity and cardiovascular disease. In this review, we will outline the vasoactive properties of adipocytokines and other obesity-related peptides. In particular, as pharmacotherapies suggested to achieve weight loss will alter the pathways associated with these peptides, such treatments might have either beneficial or deleterious effects on the incidence and progression of cardiovascular disease.

1. In the present study, we sought to determine whether physiological or pathophysiological concentrations of obesity related peptides influence the key early atherogenic events of monocyte adhesion to endothelial cells and adhesion molecule expression using primary human cells. 2. Human umbilical vein endothelial cells were grown to confluence and human monocytes were obtained by elutriation. Adhesion was assessed by automated cell counting and cell adhesion molecule expression (E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1)) was assayed by ELISA. 3. Experimental conditions included untreated control, ghrelin (100, 150, 450 and 1350 pmol/L), resistin (15, 40 and 100 ng/mL) and combined leptin and insulin (combinations of 30 and 120 pmol/L insulin and 5, 50 and 500 ng/mL leptin). 4. Both resistin and ghrelin produced modest but significant increases in VCAM-1 expression (110 +/- 4 and 117 +/- 13% compared with controls, respectively; both P

A fatty meal induces vasodilatation (of both resting and stimulated forearm flow) in healthy young adults, an effect most likely mediated by the vasodilator actions of insulin. We therefore hypothesized that an impaired meal-related vascular response might be an in vivo marker of vascular insulin resistance, related to the presence of diabetes and/or higher age. Postprandial vascular responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects (age 58 +/- 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older control subjects (age 57 +/- 9 yr), and 15 healthy young control subjects (age 33 +/- 7 yr). Studies were carried out before and 3 and 6 h after a standardized high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured by strain gauge plethysmography and large-artery function by ultrasound. Resting blood flow and hyperemic area under curve (AUC) flow were not significantly different in diabetic subjects (resting 117 +/- 42% and AUC 134 +/- 46% of premeal values) compared with age-matched controls (resting 131 +/- 39% and AUC 134 +/- 47%); however, the response in diabetic subjects was blunted compared with young controls (resting 171 +/- 67% and AUC 173 +/- 99% of premeal values; P = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found that increasing age (but not BMI or diabetes) was significantly associated with impaired postprandial vascular responses (resting: r = -0.4, P = 0.002; AUC: r = -0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator responses in older nondiabetic and diabetic adults, related to aging rather than insulin resistance.

Objectives: We sought to assess the effects of raloxifene, a selective estrogen receptor modulator, on arterial physiology and biology in postmenopausal women with coronary artery disease (CAD)., Background: Raloxifene improves endothelial function and markers of vascular health in vitro in experimental animals and in healthy postmenopausal women. In women whose arteries are affected by advanced atherosclerosis, however, the vascular effects of estrogen receptor modulation are unknown., Methods: We conducted a prospective, randomized, double-blinded, placebo-controlled, crossover trial of raloxifene, 60 mg/day for 8 weeks, in 33 consecutively eligible and consenting postmenopausal women age 50 to 75 years with known CAD. Parameters measured at the beginning and end of each treatment period included brachial artery flow-mediated dilation (FMD), the primary end point, as well as nitroglycerin-induced dilation, peripheral artery tonometry, serum lipoprotein levels, and markers of vascular function, including urinary prostaglandin, serum endothelin-1, and fibrinogen levels., Results: Baseline FMD was impaired in these women, as expected (2.84 +/- 0.60%), but there was no significant difference between the effect of raloxifene (0.26 +/- 0.66% increase) and placebo (0.01 +/- 0.63% decrease) on this marker of endothelial function (p = 0.82). No significant raloxifene-related effects were observed on derived aortic pressure, pulse pressure, augmentation index, total cholesterol or low- and high-density lipoprotein subfractions, markers of thrombosis, or vasoconstrictor or vasodilator substances., Conclusions: In postmenopausal women with treated CAD, selective estrogen receptor modulation with raloxifene does not improve a comprehensive set of parameters examining vascular function and serum lipoprotein levels.

Objective: The vascular effects of fluctuations in testosterone levels within the physiological range in otherwise healthy men are not known. We therefore aimed to study arterial function in hypogonadal men receiving long-term physiological androgen replacement therapy, at trough and peak testosterone levels., Patients and Design: We recruited nine hypogonadal men (aged 35 +/- 4 years) receiving androgen replacement therapy, each treated with 800 mg testosterone (T) depot preparations every 6 months., Measurements: Serum lipid and hormone levels and arterial reactivity were measured, prior to (trough T) and 2-4 weeks following testosterone administration (peak T). Each subject therefore served as their own control. Vessel diameter was measured by ultrasound at rest, during reactive hyperaemia [leading to flow-mediated dilatation (FMD), an endothelium-dependent response] and after sublingual nitroglycerin (GTN, an endothelium-independent dilator)., Results: Serum T (13 +/- 2 nmvs. 27 +/- 3 nm for trough and peak serum T, respectively, P < 0.001; normal adult male range 11-35 nm), and free T (195 +/- 23 pmvs. 510 +/- 93 pm, P < 0.005) significantly increased following subcutaneous depot T administration, as did serum oestradiol (100 +/- 10 pmvs. 175 +/- 9 pm, P = 0.001; normal adult male range < 250 pm). There was a significant decrease in FMD (3.6 +/- 1.1%vs. 3.0 +/- 0.8%, P < 0.01), but GTN responses were similar (9.5 +/- 0.8%vs. 10.4 +/- 1.0%, P > 0.2). Lipid, blood pressure and vessel diameter measurements were also similar before and after testosterone administration., Conclusion: Physiological replacement of testosterone is associated with decreased endothelium-dependent dilatation, in hypogonadal men.