Katherine K. Anagnostopoulou

Assessment and Clinical Relevance of Non-Fasting and Postprandial Triglycerides: An Expert Panel Statement

An Expert Panel group of scientists and clinicians met to consider several aspects related to non-fasting and postprandial triglycerides (TGs) and their role as risk factors for cardiovascular disease (CVD). In this context, we review recent epidemiological studies relevant to elevated non-fasting TGs as a risk factor for CVD and provide a suggested classification of non-fasting TG concentration. Secondly, we sought to describe methodologies to evaluate postprandial TG using a fat tolerance test (FTT) in the clinic. Thirdly, we discuss the role of non-fasting lipids in the treatment of postprandial hyperlipemia. Finally, we provide a series of clinical recommendations relating to non-fasting TGs based on the consensus of the Expert Panel: 1). Elevated non-fasting TGs are a risk factor for CVD. 2). The desirable non-fasting TG concentration is <2 mmol/l (<180 mg/dl). 3). For standardized postprandial testing, a single FTT meal should be given after an 8 h fast and should consist of 75 g of fat, 25 g of carbohydrates and 10 g of protein. 4). A single TG measurement 4 h after a FTT meal provides a good evaluation of the postprandial TG response. 5). Preferably, subjects with non-fasting TG levels of 1-2 mmol/l (89-180 mg/dl) should be tested with a FTT. 6). TG concentration ≤ 2.5 mmol/l (220 mg/dl) at any time after a FTT meal should be considered as a desirable postprandial TG response. 7). A higher and undesirable postprandial TG response could be treated by aggressive lifestyle modification (including nutritional supplementation) and/or TG lowering drugs like statins, fibrates and nicotinic acid.

The prevalence of metabolic syndrome in various populations.

The insulin resistance/metabolic syndrome is characterized by the variable co-existence of hyperinsulinemia, obesity, dyslipidemia (small dense low-density lipoprotein, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol), and hypertension. The pathogenesis of the syndrome has multiple origins. However, obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. This multifactorial and complex trait of metabolic syndrome leads to increased risk of cardiovascular disease. The scope of this review is to examine the differences in prevalence of the metabolic syndrome in various groups (eg, according to age, sex, ethnicity, social status, or presence of obesity) that could help with the better understanding of the pathogenesis of this syndrome. This review also considers the impact of metabolic syndrome on cardiovascular disease.

Postprandial Lipemia in Men with Metabolic Syndrome, Hypertensives and Healthy Subjects

BackgroundThe metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects.ResultsOFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG ≥ 150 [MetS+TG, (n = 22)] or <150 mg/dl [MetS-TG (n = 11)], and into those with or without hypertension [MetS+HTN (n = 24), MetS-HTN (n = 9), respectively]. TG concentrations were measured before and at 4, 6 and 8 h after OFTT and the postprandial response was quantified using the area under the curve (AUC) for TG.The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 ± 1016 vs. 1620 ± 494 and 1019 ± 280, respectively, p ≤ 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001).ConclusionFasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.

Apolipoprotein E knockout models.

Atherosclerosis is a multifactorial and long-lasting process in humans. Therefore, animal models where more rapid changes occur can be useful for the study of this process. Among such models are the apolipoprotein (apo) E knock out mice. Apo E deficient mice show impaired clearing of plasma lipoproteins and they develop atherosclerosis in a short time. The current review considers lipid metabolism and inflammation as well as nutritional and pharmacological agents affecting atherosclerosis, using the apo E knock out mouse model.

Definitions of Metabolic Syndrome: Where are We Now?

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities including abdominal obesity, glucose intolerance, hypertension and dyslipidaemia and is associated with an increased risk of vascular events. Since the initial description of the MetS, several expert groups produced different definitions. This variability led to confusion and absence of comparability between studies. Although there is agreement that the MetS is a major public health challenge worldwide and consistent evidence stresses the need for intervention, the definition of the syndrome remains a matter of debate. This review considers the different definitions of the MetS. These include those proposed by the World Health Organisation, the European Group for the Study of Insulin Resistance, the National Cholesterol Education Program Adult Treatment Panel III, the American College of Endocrinology and American Association of Clinical Endocrinologists and the latest International Diabetes Federation definition which includes ethnic-specific waist circumference cut-off points. These definitions share several features but also include important differences; all have limitations. Selected (after a Medline search) studies comparing the different definitions are also considered. There is a need for a standardised definition of the MetS. Furthermore, a definition tailored for children and adolescents is essential. Prospective long-term studies are needed to validate the prognostic power of these definitions. As new information becomes available the definition of the MetS might be further modified.

Tangier Disease Four Decades of Research: A Reflection of the Importance of HDL

Reduced circulating levels of high density lipoprotein cholesterol (HDL-C) are a frequent lipoprotein disorder in coronary heart disease patients and can be caused by either genetic and/or environmental factors (sedentary lifestyle, diabetes mellitus, smoking, obesity or a diet enriched in carbohydrates). Extremely low serum HDL-C levels occur in patients with Tangier disease (TD), which is caused by mutations in the adenosine triphosphate (ATP)-binding cassette transporter A1 (ABCA1). Clinical manifestations are related to the storage of cholesteryl esters in reticuloendothelial tissues and to peripheral neuropathy. This review focuses on the genetic and lipid abnormalities of TD, the consequence of these on clinical outcome and the possible treatment options. These abnormalities reflect the importance of HDL in the pathogenesis of vascular disease.

Metabolic syndrome and gender differences in postprandial lipaemia

Background Postprandial hyperlipidaemia may be a predictor of vascular risk. Design We evaluated postprandial lipaemia after an oral fat tolerance test (OFTT) in men (n = 41) and women (n = 21) with metabolic syndrome (MetS). Methods Triglyceride (TG) levels were measured before and 2, 4, 6 and 8 h after the fat load. Results Men showed a greater plasma TG response 8 h after the fat load (284 ± 117 versus 224 ± 126 mg/dl, P = 0.029). Only fasting TG levels significantly predicted the TG area under the curve (AUC) and incremental AUC. Conclusions Men had a more pronounced postprandial hypertriglyceridaemia and seem to have delayed TG clearance.

Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia

BackgroundThis study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia.MethodsWe selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h).ResultsIn the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup.ConclusionIn conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.

The Effect of Statins on Postprandial Lipemia

Several studies showed that postprandial plasma triglyceride (TG) concentrations are higher in patients with coronary heart disease. TG-rich lipoprotein remnants accumulated in the postprandial state are involved in atherogenesis and in events leading to thrombosis. Lipid lowering drugs, such as 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) are of significant benefit in the primary and secondary prevention of atherosclerosis. Statins can decrease total cholesterol and low density lipoprotein cholesterol as well as TG concentrations and improve postprandial lipoprotein metabolism. Since abnormal postprandial lipemia is associated with pathological conditions, its treatment is relevant. This review considers the effect of statins on postprandial lipemia.

Gender differences in the lipid profile of dyslipidemic subjects

OBJECTIVE We evaluated the gender-associated differences in lipid profile of subjects intended to receive lipid-lowering therapy with emphasis on the associations between triglycerides (TG) and other plasma lipid variables. DESIGN Lipid profiles of 1385 patients [aged 55+/-11 years, 549 women (40%)] were evaluated. Eligible subjects fulfilled one or more of the following criteria: total cholesterol (TC)>or=6.2 mmol/l, TG>or=1.7 mmol/l, and high-density lipoprotein cholesterol (HDL-C)<1.0 mmol/l. Patients were divided into subgroups according to TG and HDL-C levels. RESULTS Women aged on average 3.5 years older, had higher TC and HDL-C, lower TG and a correspondingly lower TC/HDL-C ratio than men. High TG and low HDL-C in tandem appeared twice more frequently in men. Inverse correlations between HDL-C and TG levels were found to exist in the entire cohort (r=-0.354, p<0.001) and in all various subgroups. In the subgroup with TG<1.7 mmol/l, women had higher TC and HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. In the subgroup with TG>or=1.7 mmol/l, women had higher TC and HDL-C levels and lower TC/HDL ratio compared with men. In the subgroup with HDL-C>or=1.0 mmol/l women had higher HDL-C, lower TG levels and lower TC/HDL-C ratio compared with men. CONCLUSIONS Elevated TG levels and low HDL-C in tandem are common lipid abnormalities in the clinical setting of primary and secondary preventions. Gender-associated differences in the lipid profile are evident in subjects presenting with dyslipidemia and might be of potential relevance for diagnostics and therapy for the prevention of atherosclerosis.