Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors: JACC State-of-the-Art Review.

Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed.

Maternal cigarette smoking is associated with reduced high-density lipoprotein cholesterol in healthy 8-year-old children.

AIMS: Smoking in pregnancy is common. Its effects on lipoprotein levels and arterial structure in childhood are not well characterized. We aimed to determine the effects of maternal smoking in pregnancy on lipoprotein levels and arterial wall thickness in healthy pre-pubertal children. METHODS AND RESULTS: A community-based longitudinal study with prospective ascertainment of exposure to smoking in pregnancy and environmental tobacco smoke (ETS) since birth and then lipoprotein and arterial measurements at age 8 years. In 616 newborn infants (gestation >36 weeks and birth weight >2.5 kg) data were collected prospectively by questionnaire on smoking in pregnancy and ETS exposure in childhood. At age 8-years, 405 of the children had measurements of lipoproteins, blood pressure (BP) and carotid intima-media thickness. Children born to mothers who smoked in pregnancy had lower HDL cholesterol [1.32 vs. 1.50 mmol/L, 95% confidence interval (CI) for difference -0.28 to -0.08, P = 0.0005], higher triglycerides (1.36 vs. 1.20 mmol/L, 95% CI for ratio 1.01-1.30, P = 0.04) and higher systolic BP (102.1 vs. 99.9 mmHg, 95% CI for difference 0.6-3.8, P = 0.006). After adjustment for maternal passive smoking, post-natal ETS exposure, gender, breast feeding duration, physical inactivity, and adiposity, smoking in pregnancy remained significantly associated with lower HDL cholesterol (difference = -0.22 mmol/L, 95% CI -0.36 to -0.08, P = 0.003) but not with higher systolic BP. Neither smoking in pregnancy nor post-natal ETS exposure was associated with alterations of carotid artery wall thickness. CONCLUSION: Smoking in pregnancy is independently associated with significantly lower HDL cholesterol in healthy 8-year-old children.

Snoring is not associated with adverse effects on blood pressure, arterial structure or function in 8-year-old children: the Childhood Asthma Prevention Study (CAPS).

AIMS: To study the association between childhood snoring and cardiovascular risk factors. METHODS: Cross-sectional analyses of a population-based birth cohort, who had been participants in a randomised controlled trial of interventions to prevent asthma and who were assessed at age 8 years. The presence and frequency of snoring were assessed by parent-completed questionnaire. We measured a wide range of cardiovascular function markers including non-fasting serum lipoproteins, blood pressure, high-sensitivity C-reactive protein, carotid artery intima media thickness (by ultrasound), brachial pulse wave velocity and augmentation index (by applanation tonometry). RESULTS: Of 409 children whose snoring status was assessed at age 8 years, 321 had lipid and 386 had arterial structure and function measurements. Snoring was not independently associated with blood pressure, carotid artery intima media thickness or measures of arterial stiffness (all P > 0.05). Increasing snoring frequency was independently associated with lower high-density lipoprotein cholesterol (-0.032 g/dL per step, 95% confidence interval -0.060 to -0.003), although the difference in high-density lipoprotein between snorers and non-snorers was not significant (P = 0.052). An association of snoring frequency with brachial pulse wave velocity differed according to body mass index (P = 0.03) and was the reverse of that expected. CONCLUSIONS: Parentally reported snoring was not independently associated with adverse measurements of metabolic markers, vascular structure or function in 8-year-old children. Parental reports of snoring may be below the treatment threshold without additional diagnosis via sleep studies.

Extensive pulmonary artery embolisation caused by cardiac hydatid cyst rupture.

This case study is a rare example of cardiac hydatidosis in a high-income country, where a middle-aged man presented with a ruptured right ventricular cyst causing anaphylaxis, pulmonary emboli and dissemination of Echinococcus throughout the lung. He survived the cyst rupture and underwent cardiac surgery but had incomplete resection and experienced progressive cardiopulmonary hydatidosis despite antihelminthic therapy. As a result, he experienced an array of cardiopulmonary sequelae over his lifespan. This case report highlights rare clinical manifestations of hydatid disease and potential complications of its treatment.

Renal Denervation for the Management of Refractory Ventricular Arrhythmias: A Systematic Review.

OBJECTIVES: The authors performed a systematic review and meta-analysis to determine the efficacy of renal denervation (RDN) in patients with refractory ventricular arrhythmias (VA) or electrical storm (ES). BACKGROUND: Although catheter ablation is efficacious for the treatment of structural heart disease ventricular tachycardia (VT), there are proportion of patients who have refractory VT despite multiple procedures. In this setting, novel adjunctive therapies such as renal denervation have been performed. METHODS: A systematic review of published data was performed. Studies that evaluated patients undergoing RDN for VA or ES were included. Outcome measures of VA, sudden cardiac death, ES, or device therapy were required. Case reports, editorials, and conference presentations were excluded. Random effects meta-analysis was conducted to explore change or final mean values in the study outcomes. RESULTS: A total of 328 articles were identified by the literature search. Seven studies met the eligibility criteria and were included in the systematic review, with a total of 121 pooled patients. The weighted mean age was 63.8 ± 13.1 years, ejection fraction 30.5 ± 10.3%, 76% were men, 99% were on a beta blocker, 79% were on amiodarone, 46% had previously undergone catheter ablation, and 8.3% had previously undergone cardiac sympathetic denervation. Meta-analysis demonstrated a significant effect of RDN in reducing implantable cardiac defibrillator therapies, with a standardized mean difference (SMD) of -3.11 (p < 0.001). RDN also reduced the number of VA episodes (SMD -2.13; p < 0.001), antitachycardia pacing episodes (SMD -2.82; p = 0.002), and shocks (SMD -2.82; p = 0.002). CONCLUSIONS: RDN is an effective treatment for refractory VAs and ES, although randomized data are lacking.

Protocol for the Stimulating ß3-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial: a double-blinded, randomised, placebo-controlled study evaluating the effects of mirabegron on functional performance in patients with peripheral arterial disease.

INTRODUCTION: There is currently only one approved medication effective at improving walking distance in people with intermittent claudication. Preclinical data suggest that the ß3-adrenergic receptor agonist (mirabegron) could be repurposed to treat intermittent claudication associated with peripheral artery disease. The aim of the Stimulating ß3-Adrenergic Receptors for Peripheral Artery Disease (STAR-PAD) trial is to test whether mirabegron improves walking distance in people with intermittent claudication. METHODS AND ANALYSIS: The STAR-PAD trial is a Phase II, multicentre, double-blind, randomised, placebo-controlled trial of mirabegron versus placebo on walking distance in patients with PAD. A total of 120 patients aged ≥40 years with stable PAD and intermittent claudication will be randomly assigned (1:1 ratio) to receive either mirabegron (50 mg orally once a day) or matched placebo, for 12 weeks. The primary endpoint is change in peak walking distance as assessed by a graded treadmill test. Secondary endpoints will include: (i) initial claudication distance; (ii) average daily step count and total step count and (iii) functional status and quality of life assessment. Mechanistic substudies will examine potential effects of mirabegron on vascular function, including brachial artery flow-mediate dilatation; MRI assessment of lower limb blood flow, tissue perfusion and arterial stiffness and numbers and angiogenesis potential of endothelial progenitor cells. Given that mirabegron is safe and clinically available for alternative purposes, a positive study is positioned to immediately impact patient care. ETHICS AND DISSEMINATION: The STAR-PAD trial is approved by the Northern Sydney Local Health District Human Research Ethics Committee (HREC/18/HAWKE/50). The study results will be published in peer-reviewed medical or scientific journals and presented at scientific meetings, regardless of the study outcomes. TRIAL REGISTRATION NUMBER: ACTRN12619000423112; Results.

HDL-cholesterol, blood pressure, and asymmetric dimethylarginine are significantly associated with arterial wall thickness in children.

OBJECTIVE: Atherosclerosis is found at autopsy in the arteries of adolescents and young adults. Arterial wall thickening may be assessed in vivo by ultrasound measurement of the carotid intima media thickness (CIMT), a marker of subclinical atherosclerosis. As the determinants of arterial wall thickness in childhood are unknown, we assessed the influence of cardiovascular risk factors on CIMT in 8-year-old children. METHODS AND RESULTS: A community-based sample of 405 children (age 8.0+/-0.1 years, 49% girls) had anthropometry, family history, blood pressure (BP), and CIMT measured. A blood sample was collected for HDL and non-HDL cholesterol, apolipoproteins A1 and B, high-sensitivity C-reactive protein, bilirubin, and asymmetric dimethylarginine (ADMA, an endogenous nitric oxide inhibitor). CIMT was significantly associated with systolic BP (r=0.17, P<0.001), diastolic BP (r=0.10, P=0.04), HDL (r=-0.13, P=0.02), and ADMA (r=0.18, P=0.001). CIMT was significantly higher in children with premature parental CHD (0.63+/-0.07 versus 0.59+/-0.06 mm, P=0.03). On multivariate analysis, HDL (beta coefficient=-0.02, P=0.04), ADMA (beta coefficient=0.05, P<0.001), and systolic BP (beta coefficient=0.001, P=0.003) were significantly and independently associated with CIMT. CONCLUSIONS: Lower HDL-cholesterol, higher levels of ADMA, and systolic BP are significantly associated with greater arterial wall thickness in early childhood.

Fenofibrate effects on carotid artery intima-media thickness in adults with type 2 diabetes mellitus: A FIELD substudy.

AIM: Dyslipidemia in type 2 diabetes contributes to 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. The mechanisms for such benefit, however, are not yet well understood. We examined the effects of fenofibrate on carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis, 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 carotid IMT in a subset of 422 representative adults. Traditional risk factors and IMT were assessed at 2 and 4 years after randomisation to fenofibrate (200 mg daily) or placebo. The prespecified primary study endpoint was the difference in IMT between treatment groups at 4 years. Post-hoc analyses were performed according to dyslipidemia and metabolic syndrome status. RESULTS: There was no difference in carotid IMT comparing those assigned to fenofibrate or placebo at 2 or 4 years, despite statistically significant improvement in lipid and lipoprotein parameters at 2 and 4 years, including TC, LDL-C and TG, and HDL-C at 4 months and 2 years. Similarly, there was no difference in carotid IMT on fenofibrate compared with placebo in those with dyslipidemia or metabolic syndrome. CONCLUSIONS: Fenofibrate was not associated with improved carotid IMT in adults with type 2 diabetes when compared with placebo, despite a statistically significant improvement in TC, LDL-C and TG at 2 and 4 years, and HDL-C at 4 months and 2 years.

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.

Telomere length in early childhood: Early life risk factors and association with carotid intima-media thickness in later childhood.

BACKGROUND: Reduced telomere length is a measure of biological aging that is predictive of cardiac events in adults, and has been mechanistically implicated in the onset and progression of atherosclerosis. We sought to describe the early life factors associated with leukocyte telomere length in early childhood, and to determine whether telomere length measured during early childhood is associated with arterial wall thickening later in childhood. DESIGN: A longitudinal birth cohort recruited antenatally in Sydney from 1997 to 1999. METHODS: Leukocyte telomere length was measured in 331 children at age 3.6 years (SD 1.0); of whom 268 children without diabetes had carotid intima-media thickness assessed by ultrasound at age 8 years. RESULTS: Male sex, younger paternal age and higher maternal body mass index were associated with shorter telomere length in early childhood, which in turn was associated with greater carotid intima-media thickness at age 8 years (standardised ß = -0.159, P = 0.01). There was a graded association across quartiles of telomere length (Ptrend = 0.001) with the highest odds of elevated intima-media thickness (>75th percentile) being in children with the shortest telomeres (odds ratio 4.00 (95% confidence interval 1.58 to 10.14) relative to those with the longest telomeres, P = 0.003). This association remained after adjustment for early life risk factors (Ptrend = 0.001). CONCLUSIONS: Reduced telomere length in early childhood is independently associated with arterial wall thickness in later childhood, suggesting that reduced telomere length during early childhood may be a marker of vascular disease risk.

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.

Effects of raloxifene on endothelium-dependent dilation, lipoproteins, and markers of vascular function in postmenopausal women with coronary artery disease.

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.

Fenofibrate effects on arterial endothelial function in adults with type 2 diabetes mellitus: A FIELD substudy.

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.

Cigarette smoking and albuminuria are associated with impaired arterial smooth muscle function in patients with type 2 diabetes mellitus: a FIELD substudy.

AIM: Impaired arterial function has been implicated in diabetes-related atherosclerosis, but its determinants in high-risk adults have not been well characterised. We investigated factors associated with impaired arterial function in adults with type 2 diabetes. METHODS: Flow-mediated dilatation (a marker of endothelial function) and dilator response to glyceryl trinitrate (to assess smooth muscle function) of the brachial artery were assessed at baseline in 193 patients with type 2 diabetes from the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Traditional risk factors were assessed and a multivariable model was constructed to identify factors independently associated with impaired arterial function. RESULTS: Median age was 64 years (interquartile range, 58-69; 61% male) and duration of diabetes was 4 years (interquartile range, 2-9). Flow-mediated dilatation (3.06 ± 0.25%, mean ± SEM) was severely impaired but not significantly associated with other risk factors. Dilator responses to glyceryl trinitrate (10.56 ± 0.52%) were significantly and independently impaired in past and present cigarette smokers (P = 0.005) and in subjects with increased urinary albumin/creatinine ratio (P = 0.01). CONCLUSIONS: In adults with type 2 diabetes and known or suspected atherosclerosis, arterial smooth muscle-dependent dilatation was shown to be significantly impaired in cigarette smokers and those with elevated urinary albumin levels.

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.

Weight gain in infancy and vascular risk factors in later childhood.

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.

High plasma thiocyanate levels modulate protein damage induced by myeloperoxidase and perturb measurement of 3-chlorotyrosine.

Smokers have an elevated risk of atherosclerosis but the origin of this elevated risk is incompletely defined, though increasing evidence supports a role for the oxidant-generating enzyme myeloperoxidase (MPO). In previous studies we have demonstrated that smokers have elevated levels of thiocyanate ions (SCN(-)), relative to nonsmokers, and increased thiol oxidation, as SCN(-) is a favored substrate for MPO, and the resulting hypothiocyanous acid (HOSCN) targets thiol groups rapidly and selectively. In this study we show that increased HOSCN formation by MPO diminishes damage to nonthiol targets on both model proteins and human plasma proteins. Thus high SCN(-) levels protect against HOCl- and MPO-mediated damage to methionine, tryptophan, lysine, histidine, and tyrosine residues on proteins. Furthermore, levels of the HOCl-mediated marker compound 3-chlorotyrosine and the cross-linked product dityrosine are decreased. Plasma protein 3-chlorotyrosine levels induced by HOCl exposure in nonsmokers are elevated over the levels detected in smokers when exposed to identical oxidative insult (P<0.05), and a strong inverse correlation exists between plasma SCN(-) levels and 3-chlorotyrosine concentrations (r=0.6182; P<0.0001). These correlations were also significant for smokers (r=0.2724; P<0.05) and nonsmokers (r=0.4141; P<0.01) when analyzed as individual groups. These data indicate that plasma SCN(-) levels are a key determinant of the extent and type of protein oxidation induced by MPO on isolated and plasma proteins and that smoking status and resulting high SCN(-) levels can markedly modulate the levels of the widely used biomarker compound 3-chlorotyrosine.

Impaired fetal growth and arterial wall thickening: a randomized trial of ω-3 supplementation.

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.