The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis

Hulthe, Johannes; Bokemark, Lena; Wikstrand, John; Fagerberg, Björn

doi:10.1161/01.atv.20.9.2140

Cited by 215 publications

(87 citation statements)

References 53 publications

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“…Small LDL particles have been suggested to be inherently more atherogenic because of their more facile penetration in the arterial wall (22,23) and a greater susceptibility to oxidative modification (24) than large LDL particles. In patients with metabolic syndrome, small LDL particle size was associated with increased intimamedia area in the carotid and femoral arteries (25). In our study, fenofibratetreated subjects had large reductions in small LDL particles (AUC Ϫ495 nmol/l) and smaller increases in large LDL particles relative to placebo-administered subjects (AUC ϩ185 nmol/l) such that total LDL particles were lowered by 19% (P ϭ 0.0033).…”

Section: Safety Studiessupporting

confidence: 46%

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

et al. 2007

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OBJECTIVE -The aim of this study was to determine the effects of fenofibrate (160 mg/day) on fasting and postprandial lipoproteins, oxidized fatty acids, and inflammatory mediators in subjects with hypertriglyceridemia and the metabolic syndrome.RESEARCH DESIGN AND METHODS -Fifty-nine subjects with fasting hypertriglyceridemia (Ն1.7 and Ͻ6.9 mmol/l) and two or more of the Adult Treatment Panel III criteria for the metabolic syndrome were randomly assigned to fenofibrate (160 mg/day) or placebo in a double-blind, controlled clinical trial.RESULTS -Fenofibrate treatment lowered fasting triglycerides (Ϫ46.1%, P Ͻ 0.0001) and postprandial (area under the curve) triglycerides (Ϫ45.4%, P Ͻ 0.0001) due to significant reductions in postprandial levels of large (Ϫ40.8%, P Ͻ 0.0001) and medium (Ϫ49.5%, P Ͻ 0.0001) VLDL particles. The number of fasting total LDL particles was reduced in fenofibratetreated subjects (Ϫ19.0%, P ϭ 0.0033) primarily due to reductions in small LDL particles (Ϫ40.3%, P Ͻ 0.0001); these treatment differences persisted postprandially. Fasting and postprandial oxidized fatty acids were reduced in fenofibrate-treated subjects compared with placebo-administered subjects (Ϫ15.3%, P ϭ 0.0013, and 31.0%, P Ͻ 0.0001, respectively), and fenofibrate therapy lowered fasting and postprandial soluble vascular cell adhesion molecule-1 (VCAM-1) (Ϫ10.9%, P ϭ 0.0005, and Ϫ12.0%, P ϭ 0.0001, respectively) as well as fasting and postprandial soluble intercellular adhesion molecule-1 (ICAM-1) (Ϫ14.8%, P Ͻ 0.0001, and Ϫ15.3%, P Ͻ 0.0001, respectively). Reductions in VCAM-1 and ICAM-1 were correlated with reductions in fasting and postprandial large VLDL particles (P Ͻ 0.0001) as well as postprandial oxidized fatty acids (P Ͻ 0.0005).CONCLUSIONS -Triglyceride-lowering therapy with fenofibrate reduced fasting and postprandial free fatty acid oxidation and inflammatory responses, and these antiatherosclerotic effects were most highly correlated with reductions in large VLDL particles. Diabetes Care 30:1945-1951, 2007T he metabolic syndrome represents an agglomeration of interrelated risk factors that include abnormally high fasting triglyceride levels (1,2). In a recent analysis, hypertriglyceridemia (Ն1.7 mmol/l) represented the component of the metabolic syndrome most strongly associated with a history of myocardial infarction and stroke (3). Furthermore, elevated fasting triglyceride levels (Ն1.4 mmol/l) and an enlarged waist circumference (Ͼ89 cm) were the two characteristics of the metabolic syndrome that were associated with the greatest increased risk for all-cause mortality and cardiovascular deaths among postmenopausal women (4).Hypertriglyceridemia signifies the presence of increased plasma triglycerideremnant lipoproteins, and the concentrations of remnant-like lipoproteins are further enhanced postprandially among hypertriglyceridemic subjects (5). Remnant-like proteins have been shown to increase intracellular oxidant concentrations and lipid peroxide levels in culture media and to activate nuclear factor-B ...

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Section: Safety Studiessupporting

confidence: 46%

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

et al. 2007

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“…Mori et al (53,56) showed that DHA and not EPA supplementation increased LDL particle size, suggesting that the lipid-regulating effects of DHA are at least as important as those of EPA. Reduced LDL particle size is an important cardiovascular risk factor (57) and correlates with sub-clinical atherosclerosis as measured by intima-media thickening (58) .…”

Section: Effects On Plasma Lipids and Lipoproteinsmentioning

confidence: 99%

Dietary n-3 PUFA and CVD: a review of the evidence

Mori

2013

Proc. Nutr. Soc.

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Many clinical and epidemiological studies have shown that the polyunsaturated n-3 fatty acids EPA and DHA from fish and fish oils, provide cardiovascular protection, particularly in the setting of secondary prevention. n-3 Fatty acids beneficially influence a number of cardiometabolic risk factors including blood pressure, cardiac function, vascular reactivity and lipids, as well as having anti-platelet, anti-inflammatory and anti-oxidative actions. They do not appear to adversely interact with other medications such as statins and other lipid-lowering drugs or antihypertensive medications. n-3 Fatty acids have gained widespread usage by general practitioners and clinicians in a number of clinical settings such as pregnancy and infant development, secondary prevention in CHD patients, treatment of dyslipidaemias and haemodialysis patients. Small doses are achievable with consumption of two to three oily fish meals per week or via purified encapsulated preparations now readily available. n-3 Fatty acids, particularly when consumed as fish, should be considered an important component of a healthy diet. The present paper reviews the effects of n-3 fatty acids on cardiometabolic risk factors, concentrating particularly on the evidence from randomised controlled studies in human subjects.

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“…The primary objective of the Atherosclerosis and Insulin Resistance (AIR) study was to examine the association between insulin sensitivity and ultrasound-assessed atherosclerosis in 58-year-old men of Swedish ancestry [13]. Exclusion criteria were prevalent cardiovascular disease or treatment with cardiovascular drugs (in order to avoid the confounding effect of treatment on study variables), cancer and other severe disease.…”

Section: Study Populationmentioning

confidence: 99%

“…This syndrome is steadily increasing in modern society and is associated with an increased risk of cardiovascular death [11,12]. A specific feature of the metabolic syndrome and insulin resistance is the increased occurrence of small LDL particles [13].…”

Section: Introductionmentioning

confidence: 99%

Low birth weight in combination with catch‐up growth predicts the occurrence of the metabolic syndrome in men at late middle age: the Atherosclerosis and Insulin Resistance study

Fagerberg

Bondjers

Nilsson

2004

Journal of Internal Medicine

126

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Abstract. Fagerberg B, Bondjers L, Nilsson P (Institute of Internal Medicine and Sahlgrenska University Hospital, Göteborg; and Malmö University Hospital, Lund University, Lund; Sweden). Low birth weight in combination with catch-up growth predicts the occurrence of the metabolic syndrome in men at late middle age: the Atherosclerosis and Insulin Resistance study. Objectives. To study the combined effects of a low birth weight and a pronounced weight increase up to early adulthood on the presence of cardiovascular risk factors constituting the metabolic syndrome in late middle age. Design and setting. A structured sample of 396 men, 58 years old from the general population. Birth weight and weight at 18 years were obtained from medical records and registers. Main outcome measures. Body mass index (BMI), waist : hip ratio (WHR), blood pressure, serum concentrations of insulin, triglycerides, HDL cholesterol and LDL particle size at age 58 years. Results. The ratio between weight at age 18 years and birth weight correlated with a number of characteristics at age 58 years: BMI (r ¼ 0.24, P < 0.001), WHR (r ¼ 0.24, P < 0.001), diastolic blood pressure (r ¼ 0.13, P < 0.05), insulin (r ¼ 0.14, P < 0.01), triglycerides (r ¼ 0.10, P < 0.05), HDL cholesterol (r ¼ )0.13, P < 0.01) and LDL particle size (r ¼ )0.17, P < 0.05). The metabolic syndrome, according to current definitions, were more common at the age of 58 years in the third tertile of the weight at 18/birth ratio, than in the other tertiles (P ¼ 0.008). Conclusions. The interaction between a low birth weight and an accelerated catch-up growth to early adulthood is associated with the occurrence of the metabolic syndrome in the late middle age. These findings are in accord with the concept that the effects of genes are conditioned by fetal growth, and that the effects of a small body size at birth are conditioned by growth during childhood and by environmental factors in childhood and adult life.

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The Metabolic Syndrome, LDL Particle Size, and Atherosclerosis

Cited by 215 publications

References 53 publications

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

Dietary n-3 PUFA and CVD: a review of the evidence

Low birth weight in combination with catch‐up growth predicts the occurrence of the metabolic syndrome in men at late middle age: the Atherosclerosis and Insulin Resistance study

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