Postprandial lipemia and heart disease
The term postprandial lipemia refers to the dynamic changes in lipids and lipoproteins that occur after a high-fat meal.
Triglyceride metabolism
It is known that triglycerides are components of lipoproteins. Their metabolism should be discussed in connection with TRL, especially in the postprandial period, when large changes occur in TRL.
Consumption of a meal leads to absorption and incorporation of long-chain fatty acids and cholesterol into chylomicrons in the intestine, which enter circulation through the lymphatic vessels and thoracic duct. Chylomicrons are then hydrolyzed by lipoprotein lipase, converted to fatty acids, which are stored in adipose tissue and hydrolyzed in muscle, leading to the formation of a spectrum of remnant chylomicrons (CMR). Cholesterol esters of cholesterol are transferred from high-density lipoprotein (HDL) particles to CMR by ester transfer protein (CETP), gradually enriching CMR with cholesterol and changing triglyceride levels. CMR reaches the liver via remnant receptors, mainly low-density lipoprotein (LDL), protein (LDL-LRP) and receptors (LDL-R). In this way, the liver is supplied with fatty acids from the diet and also resynthesized. The liver uses them to synthesize triglycerides, which are aggregated into very low density lipoproteins (VLDL). VLDL triglycerides are hydrolyzed by LPL, generating VLDL remnants known as VLDLR. Triglycerides are transported from the circulation by triglyceride-rich lipoproteins and chylomicrons of VLDL and their remnants. After a meal, newly formed chylomicrons and VLDL are processed, going through various stages. In healthy people, dynamic postprandial changes occur 4-6 hours after a meal, gradually leading to a state in which CM is absent. VLDL, CMR, and VLDLR remain in the blood serum, but at lower levels. In people with hyperlipidemia, these changes take much longer.
Hypertriglyceridemia
If this phenomenon occurs after 12 hours of fasting, it is a consequence of impaired triglyceride processing. Depending on the cause, TRC values differ in the fasting and postprandial situation. When CM and VLDL accumulate as a result of defective TG hydrolysis, medium or high HTG occurs, which increases the risk of pancreatitis. When remnants accumulate due to impaired absorption by the liver, HTG is not as high, but is combined with hypercholesterolemia. It reflects the high cholesterol content in remnants. This type of dyslipidemia is considered more atherogenic.
Postprandial lipemia
The only parameter that changes significantly in the basic lipademic profile is serum TG. The rest – cholesterol, LDC cholesterol, HDL cholesterol, show no difference, or show a negligible difference. This is true in healthy people, but also in those with hyperlipidemia. In addition, dynamic changes in the composition appear in all types of serum lipoproteins, indicating that the importance of postprandial lipemia in the development of vascular diseases is not only associated with changes in TRL but also in other types of lipoproteins, as well as with other mechanisms.
Mechanisms Responsible for the Development of Vascular Diseases as a Result of Postprandial Lipemia
Whether serum triglycerides are an independent risk factor for vascular diseases is a matter of debate. TGS are only an indicator.
Role of Postprandial Lipoproteins
Because chylomicrons and VLDL are large molecules, they cannot pass through the vessel lumen and contribute to the formation of atherosclerotic deposits. Residual chylomicrons, which are small but enriched with cholesterol, play a direct role in the genesis of atherosclerosis. Studies based on the measurement of apolipoprotein B-100 and apolipoprotein B-48 separately as markers of VLDLR and CMR have shown that both VLDLR and CMP play a role in the genesis of atherosclerosis.
In addition to this role, triglycerides contribute to atherosclerotic changes in the composition of LDL and HDL. Transfer of CE in exchange for TG between TRL and LDL and HDL leads to the formation of TG enriched with LDL and HDL particles. They become better substrates for LPL and hepatic lipase HL. This leads to the formation of smaller and denser LDL particles, which are more atherogenic forms of LDL particles.
Actions of Postprandic Lipoproteins Beyond Predisease
Atherosclerosis is increasingly being characterized as an inflammatory process. Evidence from multiple sources indicates that postprandial TG-rich levels of lipoproteins induce a pre-inflammatory state in the vessels by activating toll-like receptors. However, these data are not conclusive. There are indications that some of these products have anti-inflammatory effects. Some studies have shown that TG-rich lipoproteins increase the activity of vascular cell adhesion molecule-1 (VCAM1), intercellular adhesion molecule-1 (ICAM-1), and MCP1 cells, which accumulate monocytes and macrophages in vessels and atherosclerotic plaques. These pathological changes increase the production of inflammatory cytokines such as interleukins, tumor necrosis factors, and metalloproteinases. The association between TRL and inflammatory processes requires confirmation in cohort studies.
Hypertriglyceridemia contributes to coagulation via increased levels of fibrinogen and coagulant factors as well as impairing fibrinolysis via increased levels of plasminogen activator inhibitor1.
Furthermore, there is evidence that postprandial TRL contributes to endothelial dysfunction via impaired vesodilation. This may contribute to increased oxidative stress and reduced nitric oxide production.
Genes associated with postprandial lipemia
Many processes associated with postprandial lipemia are also associated with apolipoprotein A5, C2, C3 IE, lipolytic enzyme genes such as lipase and hepatic lipase, transfer protein genes such as triglyceride protein and CETP, fatty acid linking proteins, as well as receptor proteins such as LDL-LRP, LDL-R and remnant receptor. In addition, these processes are associated with genes such as PPAR-a, PPAR-y, lipase maturation factor 1, GPIHBP1, protein 4 and perilipin.
Risk Factors and Postprandial Lipemia
The response to dietary fat is not a uniform phenomenon. Some risk factors for vascular disease include:
Age
has always been cited as one of the determinants of postprandial lipemia. However, Perez-Cabalero describes that healthy individuals over 65 years of age are not at higher risk of postprandial lipemia than younger individuals.
Gender and Menopause
Differences were found in TG levels and responses to dietary fat. However, there were no differences between the sexes in the formation and storage of adipose tissue. Our research group investigated the effect of CETP on lipemia and found a difference between the sexes.
Obesity, Blood Pressure, Metabolic Syndrome
Increased triglyceride levels have been observed in patients with diabetes etc. According to our study, hypertension is associated with postprandial lipemia via abdominal obesity and increased TG levels during fasting.
Smoking
Abnormal lipemia is observed in smokers, This is due in part to impaired clearance of CMS and CMR. According to Bloomer, smokers experience higher TG levels after fat ingestion than nonsmokers.
Sedentary lifestyle
Studies have shown that fat absorption was faster in runners than in men with a sedentary lifestyle. Consequently, postprandial lipemia in runners showed lower values.
Postprandial lipemia and high risk of coronary artery disease
Their connection has been known since 1950. Zilversmit proved that chylomicron remnants play a role in the genesis of atherosclerosis. The Copenhagen City Heart Study, which included 14,000 Danes over a period of 26 years, proved that the level of triglycerides (with normal meal consumption) was associated with cardiovascular diseases in both sexes. It was also shown that when the level of triglycerides is ≥ 440 mg/dl during the period of fasting, there is a 17-fold higher risk of heart attack in women and 5-fold higher in men. Asia Pacific Cohort Studies – these studies brought results in the form of conclusions about the relationship between the level of triglycerides with normal meal consumption and the prediction of the development of cardiovascular diseases. Similar results were obtained in a meta-analysis of 300,000 people from outside Europe and in a group of women only. Uiterwaal indicates that descendants of people with heart disease have longer-lasting postprandial hyperglycemia.
Peripheral Arterial Disease – PAD
Lupatelli demonstrated that the postprandial lipemic response was higher than in the control group. Geanzer demonstrated that these increased values had an impact on the disruption of the patency function of the brachial artery. Valdivelso observed that fasting and postprandial apoliprotein B48 levels were only slightly elevated in diabetic patients with PAD, and in statistical regression, only smoking and postprandial B48 levels were independently associated with PAD, in addition to diabetes. High TG levels are associated with the risk of stroke.
Conclusions
Currently, the association between postprandial TG levels and vascular diseases is confirmed. TG levels can be used as markers of hyperglyceridemia and atherosclerosis genesis processes.
• Kolovou G.1, Head of Outpatient and Preventive Cardiology
• Vassiliadis Ioannis 1, Cardiologist-Research Associate • OoiTeik Chye2, FRCPC, FRACP, FACE, FAHA
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