Michael R. Skilton

Aortic wall thickness in newborns with intrauterine growth restriction

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.

Associations Between Anxiety, Depression, and the Metabolic Syndrome

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.

Treatment of obstructive sleep apnoea leads to improved microvascular endothelial function in the systemic circulation

Background: Obstructive sleep apnoea (OSA) is a common and potentially reversible cause of systemic hypertension. The mechanisms whereby OSA leads to hypertension and the effects of treatment on arterial function, however, are not well established. Microvascular arterial endothelial and smooth muscle function was assessed in subjects with OSA before and after treatment with continuous positive airways pressure (CPAP). Methods: Ten subjects of mean (SE) age 49 (8) years with at least moderately severe OSA had detailed forearm vascular reactivity studies before and after 3 months of CPAP treatment. The systemic circulation was assessed by measuring brachial artery pressure, flow and resistance responses to intra-arterial infusions of acetylcholine (ACh; an endothelium dependent vasodilator), sodium nitroprusside (SNP; an endothelium independent vasodilator), l-NMMA (a nitric oxide (NO) antagonist), and l-arginine (the substrate for NO). Results: Before CPAP, ACh and SNP infusions increased forearm blood flow in a dose dependent manner (p<0.01). After CPAP, endothelium dependent dilation to ACh was significantly increased (434 (23)% of baseline after CPAP v 278 (20)% before CPAP, p<0.001), whereas SNP induced dilation was unchanged. Resting NO production was higher after CPAP, evidenced by a significantly greater reduction in basal flow by l-NMMA (p = 0.05). l-Arginine reversed the effect of l-NMMA in all cases. Conclusion: In patients with OSA, treatment with CPAP improves baseline endothelial NO release and stimulates endothelium dependent vasorelaxation in the systemic circulation. This is a potential mechanism for improving systemic and vascular function in patients with OSA treated with CPAP.

A diagnosis of the metabolic syndrome in youth that resolves by adult life is associated with a normalization of high carotid intima-media thickness and type 2 diabetes mellitus risk: the Bogalusa heart and cardiovascular risk in young Finns studies.

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.

Longitudinal displacement of the carotid wall and cardiovascular risk factors: associations with aging, adiposity, blood pressure and periodontal disease independent of cross-sectional distensibility and intima-media thickness

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.

Nutritional intervention to reduce the n −6/ n −3 fatty acid ratio increases adiponectin concentration and fatty acid oxidation in healthy subjects

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/α-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-α (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) μg/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.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.min, P=0.02) and hyperinsulinaemic conditions (baseline: 3.6 (s.d. 0.1), post-intervention: 3.3 (s.d. 0.1) mg/kg.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.

Total dietary carbohydrate, sugar, starch and fibre intakes in the European Prospective Investigation into Cancer and Nutrition

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.

Beneficial effects of a 5-week low-glycaemic index regimen on weight control and cardiovascular risk factors in overweight non-diabetic subjects.

The glycaemic index (GI) has been developed in order to classify food according to the postprandial glycaemic response. This parameter is of interest, especially for people prone to glucose intolerance; however, the effects of a low-GI (LGI) diet on body weight, carbohydrate and lipid metabolism remain controversial. We studied the effects of either a LGI or high-GI (HGI) diet on weight control and cardiovascular risk factors in overweight, non-diabetic subjects. The study was a randomized 5-week intervention trial. The thirty-eight subjects (BMI 27.3 (sem 0.2) kg/m2) followed an intervention diet in which usual starch was replaced ad libitum with either LGI or HGI starch. Mean body weight decrease was significant in the LGI group ( - 1.1 (sEM 0.3) kg, P = 0.004) and was significantly greater than in the HGI group ( - 0.3 (sEM 0.2) kg, P = 0.04 between groups). Hunger sensation scales showed a trend towards a decrease in hunger sensation before lunch and dinner in the LGI group when compared with the HGI group (P = 0.09). No significant increase in insulin sensitivity was noticed. The LGI diet also decreased total cholesterol by 9.6 % (P < 0.001), LDL-cholesterol by 8.6 % (P = 0.01) and both LDL-:HDL-cholesterol ratio (10.1 %, P = 0.003) and total:HDL-cholesterol ratio (8.5 %, P = 0.001) while no significant changes were observed in the HGI group. Lowering the GI of daily meals with simple dietary recommendations results in increased weight loss and improved lipid profile and is relatively easy to implement with few constraints. These potential benefits of consuming a LGI diet can be useful to develop practical dietetic advice.

Intrauterine Risk Factors for Precocious Atherosclerosis

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.

Noninvasive Measurement of Carotid Extra-Media Thickness: Associations With Cardiovascular Risk Factors and Intima-Media Thickness

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.