Several RVFs have been proposed to support the classical criteria for the detection of subclinical atherosclerosis. In our profile we have selected those considered most useful by the scientific community. These so-called emerging markers of vascular risk include lipid parameters: Lipoprotein (a), Apolipoprotein A-1, Apolipoprotein B, inflammatory biomarkers such as ultra-sensitive C-reactive protein and fibrinogen; and nutritional markers associated with premature atherothrombosis such as plasma homocysteine, in addition to the classical HDL and LDL cholesterol with direct measurement.
Ultra-sensitive C-reactive protein (us-PCR)
Acute phase protein synthesised by the liver and is a non-specific marker of inflammation. Prospective research has shown a direct association between high CRP levels and the risk of vascular disease (myocardial infarction, stroke and peripheral vascular disease).
A glycoprotein synthesised by the liver that is actively involved in blood coagulation. There are four mechanisms by which increased F can promote arterial disease: atherogenesis, platelet aggregation, fibrin thrombus formation and increased plasma viscosity.
A sulphur amino acid that is generated in almost all human tissues as a result of the intermediate metabolism of methionine, an essential amino acid, which is obtained from the diet or endogenously. Homocysteine metabolism depends on methionine concentrations, the enzymes involved in each of the metabolic processes, and cofactors such as vitamin B6, B12 and folate; any deficiency in enzyme activity, mainly in methylene-tetrahydrofolate reductase associated with the C677T mutation of the MTHFR gene, or in cofactors could cause hyperhomocysteinemia, which is associated with an increased risk of cardiovascular disease.
Lipoprotein (a) [Lp(a)].
A protein whose homology with plasminogen causes interference with fibrinolysis, increasing thrombotic risk. Lp(a) is a risk factor for coronary artery disease (CAD), especially in white, hypercholesterolaemic men. It acts as a predictive marker of angiographic severity in young, male-onset CAD. In the elderly, elevated Lp(a) is an independent risk factor for stroke or transient ischaemic attack and death from vascular disease.
Main protein found in high-density lipoproteins (HDL), although it is also present in chylomicrons. Apo A-1 is described as a non-atherogenic protein, with an inverse correlation between Apo A-1 levels and cardiovascular risk. The main role of apolipoprotein A-1 is the activation of lecithin cholesterol acyltransferase (LCAT) and the removal of free cholesterol from extra-hepatic tissues.
Protein found in low-density lipoproteins (LDL), but also in all forms of potentially atherogenic particles (LDL, VLDL and IDL). Apo B is the main cholesterol transport protein in the blood. Apo B concentration indicates the total number of dangerous particles and is therefore very useful for the overall assessment of vascular risk, being a good predictor of fatal myocardial infarction and acute myocardial infarction.
Apolipoprotein E (Apo E)
Protein synthesised mainly in the liver, but also in the brain, spleen, adrenal glands, ovaries, kidneys, muscle cells and macrophages. Apo E has many functions including the transport of triglycerides into liver tissue (as part of VLDL), and the distribution of cholesterol between cells (as part of HDL). Apo E is associated with atherosclerotic lesion formation by inhibiting platelet aggregation. Decreased Apo E levels are associated with the E4 polymorphism of the APOE gene and with high levels of total cholesterol and triglycerides, promoting premature atherosclerosis.
Direct HDL cholesterol
There is an inverse relationship between serum HDL-Cholesterol (HDL-C) levels and the prevalence of cardiovascular disease. The direct measurement of HDL-C provides better accuracy and reproducibility compared to other methods used.
Direct LDL cholesterol
It has been shown that most of the cholesterol deposited in atheroma plaques comes from LDL. For this reason LDL-cholesterol (C-LDL) is considered the most important single predictive marker for atherosclerosis and the target marker in lipid-lowering therapies for the prevention or reduction of atherosclerosis. The direct method of determination offers great advantages over the commonly used calculation using the Friedewald formula.
Triglycerides are esters of glycerol and fatty acids that come from the diet or are mainly synthesised in the liver. Hypertriglyceridaemia is considered an independent risk factor. It is often associated with other vascular risk factors.
Vascular risk indices
The ApoB/ApoA-1 ratio is superior to the total cholesterol/HDL cholesterol ratio, or the LDL/HDL cholesterol ratio as an overall risk index and as a risk index for cardiovascular events for patients on statin therapy.