Studies - Articles


Postprandial Lipaemia and Cardiovascular Disease
Postprandial lipaemia refers to the dynamic changes in serum lipids and lipoproteins (mainly triglycerides) that occur after a fat load or a meal.

Recent data indicate that postprandial or non-fasting Triglyceride (TG) levels which are determined without any fasting period are better predictors of cardiovascular disease suggesting that this efficiency of postprandial handling of these factors will help the pathogenesis of these diseases.

Metabolism of Triglycerides As it is known, the triglycerides are components of the circulated lipoproteins. Their metabolism should be discussed in conjunction the metabolism of TRL, especially during the postprandial period when major changes in TRL occur.

The consumption of a meal results in absorption and incorporation of long chain fatty acids and cholesterol into TG-rich intestinal chylomicrons (CM), which enter circulation via lymphatics and the thoracic duct. Then Chylomicrons are hydrolyzed by lipoprotein lipase (LPL) in fatty acids, which are stored in the adipose tissue or hydrolyzed in muscles resulting in a spectrum of Chylomicron remnants (CMR). Cholesterol esters are transferred from high density lipoproteins (HDL) particles to CMR by cholesterol ester transfer protein (CETP), enriching CMR progressively with cholesterol while being partially depleted of TGs. CMR are taken up by the liver via remnant receptors, mainly low density lipoprotein (LDL) receptor-related protein (LDL-LRP) and LDL receptors (LDL-R). In this way the liver delivers the dietary fatty acids as well as the fatty acids which are synthesized de novo and uses them for the synthesis of TGs which are assembled into very low density lipoproteins (VLDL). VLDL TGs are also hydrolyzed by LPL, generating VLDL remnants (VLDLR). TGs are thus carried in the circulation by the rich in triglycerides lipoproteins, chylomicrons and VLDL and their remnants. Postprandially, the recently formed CM and VLDL are transformed into different stages of their final remnants. Specially, in healthy subjects, the dynamic postprandial changes occur over 4-6 hours leading gradually to a steady state in which CM are no longer present and VLDL, CMR and VLDLR remain in serum but at lower levels than in the postprandial state. In hyperlipidaemic subjects, postprandial changes are exaggerated and last longer.

Hypertriglyceridemia, after a 12 hour fasting, is the consequence of abnormal postprandial TGs handling. Depending on the culprit defect, the values of TRL vary both in fasting or postprandial situation. When CM and VLDL accumulate, as a result of defective TG hydrolysis, moderate to severe HTG appears with high risk for pancreatitis. When remnants accumulate as a result of impaired hepatic uptake of remnants, HTG is less severe but it tends to be related to hypercholesterolaemia, reflecting the presence of a significant amount of cholesterol in remnants. This type of dyslipidemia is considered more atherogenic.

Postprandial Lipaemia
The only parameter in the basic clinical lipidaemic profile that changes significantly after a meal is serum TG. The rest, total cholesterol, LDL cholesterol and HDL cholesterol, show little or no change. This is generally true in healthy and hyperlipidaemic subjects. Moreover, dynamic compositional changes occur postprandially in all classes of serum lipoproteins implying that the relevance of postprandial lipaemia to vascular disease is not just related to changes in TRL but also to the other lipoproteins. In addition to this, the pro-atherogenic postprandial state extends except beyond lipoproteins to other mechanisms to.

Mechanisms Responsible For Promotion of Vascular Disease by Postprandial Lipaemia
While there is a lot of discussion on whether serum TGs is an independent risk factor for vascular disease, it is necessary to think of TGs as only a marker.

The role of Postprandial Lipoproteins
As the chylomicrons and the VLDL are large molecules and cannot pass through the endothelium of the vessel and participate directly in the formation of the atheroma, their remnants, which are smaller and cholesterol-enriched, have a direct role in atherogenesis. Studies based on the ability to measure apolipoprotein B-100 and apolipoprotein B-48 separately as markers of VLDLR and CMR, indicated that both VLDLR and CMR play an important role in atherogenesis.

In addition to this, despite the fact that postprandial TRL play a direct role in atherogenesis, they also promote the pro-atherogenic changes of the composition of LDL and HDL particles. The CETP-mediated transfer of CE in exchange for TG between TRL and LDL and HDL result in TG-enriched LDL and HDL particles. They become better substrates for LPL and hepatic lipase (HL), resulting in smaller and denser LDL particles which are the more atherogenic forms of LDL particles as well as in smaller HDL particles which are more rapidly catabolised giving lower HDL cholesterol levels in plasma.

Actions of Postprandial Lipoproteins beyond the pre – atherogenic processes
Increasingly, atherosclerosis is characterized as inflammatory process. Evidence from many fronts show that postprandial rich in TGs lipoproteins promote the pre – inflammatory vascular state as this is induced by TRL lipolytic products through activation of Toll receptor. These data, however, are not entirely comprehensive. There are still indications that some of these products have anti – inflammatory action. In some studies it is shown that the rich in TGs lipoproteins increase the expression of the vascular cell adhesion molecule -1 (VCAM-1), the intercellular adhesion molecule -1 (ICAM-1) and the monocyte chemoattracted protein -1 (MCP-1), which recruit and accumulate the monocyte and the macrophages in the arterial intimal atherosclerotic plaques of the vessels. These lesions increase the production of inflammatory cytokines, such as interleukin 6 (IL6) of the tumor necrosis factor –α (TNF –α), and metalloproteinases. This relationship between TRL and pro-inflammatory processes needs confirmation in large cohorts.

Hypertriglyceridemia promotes coagulation through elevated levels of fibrinogen and coagulation factors VII and XII and impairment of fibrinolysis through increased levels of plasminogen activator inhibitor-1.

Moreover, there is also evidence that postprandial TRL promote endothelial dysfunction taking the form of impaired flow-mediated vasodilatation. Underlying this defect might be an increase in oxidative stress and a reduction in nitric oxide (NO) production. There is also some evidence that postprandial remnants may accelerate endothelial progenitor cell senescence leading to impaired vascular repair.

Genes relate to Postprandial Lipaemia
Many processes involved in postprandial lipaemia are affected by the genes' expression as: apolipoprotein A5, C2, C3 and E, genes of lipolytic enzymes like lipoprotein lipase and hepatic lipase, genes of transfer proteins like microsomal transfer triglyceride protein and CETP, fatty acid bind proteins and receptor proteins as LDL-LRP, LDL-R and scavenger receptor. Recently, genes like PPAR-α, PPAR-γ, lipase maturation factor 1, GPIHBP1, angiopoietin like protein 4 and perilipin.

Postprandial Lipaemia and risk factors
The postprandial response to the dietary fat is not a uniform phenomenon. Some of the risk factors for cardiovascular diseases that affect the postprandial response in the nutritional fat are:

Age has been proposed for many years as a determinant of postprandial lipaemia. However, Perez – Caballero et al described that healthy people older than 65 years do not present higher postprandial lipaemia in relation to younger subjects.

Sex and Menopause
Significant gender differences were found in postprandial TG response to fat loading. However, no differences were found between the two sexes when matched for visceral adipose tissue accumulation. Our research group has studied the effect of the CETP polymorphism on sex and postprandial lipaemia and found differences between the two sexes.

Obesity, Blood Pressure, Metabolic Syndrome, Diabetes
An enhanced TG rise postprandially has been reported in patients with obesity, hypertension, metabolic syndrome and diabetes mellitus. According to our findings, hypertension associates with postprandial lipaemia, a situation that charges the prognosis of hypertensive patients. The metabolic syndrome is associated to postprandial lipaemia through abdominal obesity and increased fasting TGs' levels.

Cigarette smokers are known to experience abnormal postprandial lipaemia. This is mediated partially by a defective clearance of CMs and CMR . Bloomer et al reported that smokers experience an exaggerated TGs and oxidative stress response to high fat feeding, compared with non smokers.

Sedentary Living
Few decades ago have been showed that the clearance of an intravenously injected fat emulsion is faster in runners than in sedentary men and was indicated that postprandial lipaemia is lower in athletes than in sedentary men. Opposite, Gabriel at al reported that the 30 min of brisk walking attenuates postprandial TG levels and markers of oxidative stress after the consumption of a high-fat meal.

Postprandial Lipaemia and High Risk for Cardiovascular Diseases Coronary Disease
Since 1950, the relationship between postprandial Lipaemia and coronary disease is known. Zilversmit showed that the chylomicron remnants play an important role in atherogenesis. A prospective study with 26-31 years follow-up of 13,000 untreated individuals from the Danish general population, the Copenhagen City Heart Study, showed that non-fasting TGs >5 mmol/l (445 mg/dl) versus 1 mmol/l (89 mg/dl) in age adjusted analyses marked a 17 and 5 fold increased risk of myocardial infarction and a 4 and 2 fold increased risk of early death. Similar results were revealed by a meta – analysis on 300.000 people and in non- European populations of patients and exclusively in women populations. Uiterwaal et al reports that the descendants from parents with coronary disease have prolonged postprandial hypertriglyceridemia.

Peripheral Arterial Disease PAD
Lupattelli et al reported that postprandial lipaemia response was higher in patients with PAD than in control subjects. Gaenzer et al demonstrated that pronounced postprandial lipaemia was associated with transient impairment of endothelial function of the brachial artery. Valdivielso et al reported that the levels of apolipoprotein B48, both fasting and postprandial, were only significantly raised in the diabetic mellitus patients who had PAD and in binary logistic regressionanalyses, only smoking and postprandial apolipoprotein B48 levels, in addition to diabetes, were independently associated with PAD. Also, enhanced postprandial lipaemia has been associated with carotid artery atherosclerosis disease, too. Finally, it has been observed that the increased fasting TGs prices are related to the high risk for ischemic stroke.

Nowadays, the relation between the postprandial TGs levels and the vascular diseases is confirmed. The processes which are involved in this pathogenesis are also known. Hence, the TGs levels can be used as a marker both for hypertriglyceridemia and atherogenic processes that were analyzed above.
• Kolovou G.1, Head of Outpatient and Preventive Cardiology
• Vassiliadis Ioannis 1, Cardiologist-Research Associate

1.Cardiology Sector, Onassis Cardiac Surgery Center Athens 2.Chronic Disease Program, Ottawa Hospital Research Institute; and Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.