Such multigenic effects depend predominantly on environmental influences, which suggests that most premature cardiovascular deaths can be prevented if action is taken to avoid, or modify, external factors that may influence a genetic predisposition to become clinically relevant.

The SNPs assessed in this panel are found on the genes; LPL, APOC3, CETP, APOE and PON1. If a number of gene variants in this panel convey moderate to high risk impacts, it may be prudent to assess an individual’s cholesterol profile (liposcan) – paying special attention to cholesterol sub-fractions. Personalised interventions can then be implemented based on that individual’s specific genetic profile.

Cardiovascular disease (CVD) encompasses a group of diseases of the heart & blood vessels, including coronary heart disease, stroke, heart failure, heart arrhythmias, and heart valve problems. Major risk factors that lead to the development of CVD are hypertension, dyslipidemia, atherosclerosis, diabetes, and obesity, with a major underlying cause being that of chronic, low grade inflammation. This review will focus mainly on the areas of dyslipidemia and atherosclerosis.

Pathway Description

Dyslipidemia is characterised by an abnormal amount, or an altered ratio, of lipids (triglycerides, cholesterol and/or fat phospholipids) in the blood, and contributes toward the development of atherosclerosis.

Endogenously, lipids are synthesized in the liver, and exogenously, sources come from dietary fat. They have a diverse range of biological functions in cell membranes as phospholipids, and as a major source of stored energy in adipose tissue as triacylglycerols (TAGs). Cholesterol is also crucial for the production of bile acid, vitamin D as well as several hormones, including the stress hormone, cortisol, and the sex hormones testosterone, progesterone, and oestrogen. Cholesterol is transported in the blood in the form of apolipoproteins.

Different forms of apolipoprotein cholesterol exist. Chylomicrons are the least dense and largest of the lipoprotein family. Chylomicrons undergo a maturation process and, with successive hydrolysis of triglycerides, the size of chylomicrons decreases, forming so-called chylomicron remnants, which are rapidly removed from the circulation by the liver. The next dense class of lipoproteins is the very low-density lipoprotein (VLDL) particle, which is rich in triglycerides, and can be hydrolysed by lipoprotein lipases. During this lipolytic removal of triglycerides, the particle size of VLDL decreases while the particle density increases. With time, the particles are converted from triglyceride-rich VLDL to cholesteryl ester-rich low-density lipoprotein (LDL) particles, which are much smaller than VLDL. LDL particles are the primary transporters of cholesterol to peripheral tissues and, in contrast to the other lipoprotein species, LDL particles possess just one single copy of an apolipoprotein called apolipoprotein B-100 (Apo-B100). Apo-B100 is a large, non-exchangeable, amphipathic single-chain glycoprotein which plays a central role in particle stabilization as well as in cellular recognition and receptor mediated endocytosis of LDL. High density lipoproteins (HDL) are the smallest and densest lipoprotein that are rich in protein and hold different amounts of exchangeable apolipoproteins, of which apolipoprotein A-I (Apo-AI) is the most abundant. HDL plays a significant role in reverse cholesterol transport for the efflux of cholesterol from the tissue to HDL. HDL returns excess cholesterol to the liver, where it is converted to bile acids and eliminated from the liver. HDL thus protects from atherosclerosis development.

When there is a trigger for oxidative stress insult, such as with smoking, hypertension, hyperglycaemia, and hyperlipidaemia status, reactive oxygen species (ROS) production is increased, overpowering the endogenous antioxidant response. This oxidative stress insult increases oxidation of LDL particles and impairs endothelial function. In the initial phase of LDL modification, the lipid components interact with ROS, and produce many types of lipid oxidation products. The lipid oxidation products, such as lysophospholipid products, attach to the Apo B protein. After interaction with scavenger receptors, the macrophages are activated and uptake of ox-LDL is initiated, which also induces several pro-inflammatory conditions.

Interventions

Individuals who eat a diet high in refined carbohydrates also have an increased risk of dyslipidaemia, specifically hypertriglyceridaemia. It is suggested to replace refined carbohydrates with low glycaemic (GI) alternatives and also to consider increasing MUFA intake. Those with hypertriglyceridaemia are recommended to take in 2g to 4g of n-3 fatty acids (FA), mixed EPA/DHA, per day.

Research also emphasises a diet high in both soluble and insoluble fibre can help to manage total cholesterol. Plant sterols have also been shown to improve dyslipidaemia, and a diet high in phytonutrients with a high dietary intake of vegetables and fruit is protective against atherosclerosis development.

Also, following a Mediterranean style dietary pattern has been shown to decrease risk for atherosclerosis and cardiovascular disease. Weight management and losing up to 10% of total body weight, if overweight, is associated with improved metabolic outcomes. Stress management and cessation of smoking is imperative.

Personalised lifestyle and nutrition interventions for balancing lipid metabolism and decreasing risk for atherosclerosis will be given according to genotype. It is, however, important to take the full genetic panel into account to ensure an holistic, personalised plan is given. One must also consider other key biochemical areas that influence atherosclerosis risk, including the inflammatory pathways and antioxidant status.