The atherogenic role of triglycerides (TG) as an independent cardiovascular risk factor has been discussed for many years, largely because hypertriglyceridaemia (HTG) is a complex metabolic entity of multiple aetiology involving processes of diverse nature. In this chapter, a discussion will be presented on the current recommendations for the management of mild-moderate hypertriglyceridaemia (150-880mg/dL). The aim of the interventions used is to decrease the LDL-cholesterol (c-LDL) and control the HTG. This entails reducing apoprotein B (ApoB) levels, the number of remaining TG-rich lipoproteins (LRP), non-HDL-cholesterol (c-non-HDL), and increasing HDL-cholesterol (c-HDL). The management strategy includes healthy lifestyle recommendations, and subsequent use of lipid-lowering drugs, including statins, fibrates, n-3 fatty acids and PCSK9 inhibitors.

Presence of diabetes (types 1 and 2) increases the risk of atherosclerotic cardiovascular disease. Despite adequate metabolic control and treatment of vascular risk factors until the goals recommended by the clinical practice guidelines are achieved, residual cardiovascular risk may be very high in some patients with diabetes. Stratifying the vascular risk for each patient as precisely as possible is therefore necessary. Consolidated strategies to improve patient prognosis include aggressive reduction of LDL cholesterol, blood pressure control, achievement of the best HbA1c control possible without inducing hypoglycemia, use of hypoglycemic drugs shown to have cardiovascular benefits, and use of platelet aggregation inhibitors in patients with greater initial risk. Emerging strategies for patients with very high or extreme risk would include use of drugs intended to decrease triglyceride-rich lipoproteins and inflammation.

There is no doubt about the relationship between LDL-c and cardiovascular risk, as well as about the benefits of statin treatment. Once the objective of LDL-c has been achieved, the evidences that demonstrate the persistence of a high cardiovascular risk, a concept called residual risk, are notable. The residual risk of lipid origin is based on atherogenic dyslipidemia, characterized by an increase in triglycerides and triglyceride-rich lipoproteins, a decrease in HDL-c and qualitative alterations in LDL particles. The most commonly used measures to identify this dyslipidemia are based on the determination of total cholesterol, triglycerides, HDL, non-HDL cholesterol and remaining cholesterol, as well as apolipoprotein B100 and lipoprotein (a) in certain cases. The treatment of atherogenic dyslipidemia is based on weight loss and physical exercise. Regarding pharmacological treatment, we have no evidence of cardiovascular benefit with drugs aimed at lowering triglycerides and HDL-c, fenofibrate seems to be effective in situations of atherogenic dyslipidemia.

Pandemics of metabolic síndrome, obesity, and type 2 diabetes is a major challenge for the next years and supported the grat burden of cardiovascular diseases. The R3i (Residual Risk Reduction initiative) has previously highlighted atherogenic dyslipidaemia as an important and modifiable contributor to the lipid related residual cardiovascular risk. Atherogenic dyslipidaemia is defined as an imbalance between proatherogenic triglycerides-rich apoB-containing lipoproteins and antiatherogenic AI containing lipoproteins. To improve clinical management of atherogenic dyslipidaemia a despite of lifestyle intervention includes pharmacological approach, and fibrates is the main option for combination with a statin to further reduce non-HDL cholesterol.

The treatment of patients with high cardiovascular risk and mixed hyperlipidemia is difficult due to multiple quantitative and qualitative lipid abnormalities. The priority is to reduce LDL-c levels, for which statins are the drug of choice. Despite the benefits of statins, the residual cardiovascular risk is very high in patients with atherogenic dyslipidemia. To reduce this risk, we also need to control non-HDL cholesterol levels, decreasing triglyceride levels and increasing HDL-c levels. To achieve these objectives and lifestyle changes, the use of combined therapy is often required. Fibrates are drugs that can be used in combination with statins to reduce this residual risk. Fenofibrate is well tolerated in combination with statins. The fixed combination of pravastatin/ fenofibrate has been shown to have complementary benefits in the atherogenic lipid profile in general. The combination is well tolerated and is indicated in patients with high risk and mixed hyperlipidemia who have controlled or are close to their objectives for LDL-c levels, using 40-mg pravastatin in monotherapy. The beneficial eff ect of the combination on LDL-c levels is minimal and is primarily observed in non-HDL cholesterol, triglycerides and HDL-c. The combination of pravastatin 40 and fenofibrate 160 can provide a considerable clinical benefit to patients with high risk and mixed atherogenic dyslipidemia, to patients with LDL-c levels that are controlled or near the objectives for decreasing their residual risk of lipid origin and is especially useful for patients with type 2 diabetes, obesity and combined metabolic syndrome and familial hyperlipidemia.

Atherogenic dyslipidemia (AD) consists of the combination of an increase in very low density lipoproteins (VLDL), which results in increased plasma triglyceride (TG) levels, with a reduction of levels of high-density lipoprotein bound cholesterol (HDL-C), also accompanied by a high proportion of small and dense LDL particles. AD is considered the main cause of the residual risk of experiencing cardiovascular disease (CVD), which is still presented by any patient on treatment with statins despite maintaining low-density lipoprotein bound cholesterol (LDL-C) levels below the values considered to be the objective. Non-HDL cholesterol (non-HDL-c) reflects the number of atherogenic particles present in the plasma. This includes VLDL, intermediate density lipoproteins (IDL) and LDL. Non-HDL-c provides a better estimate of cardiovascular risk than LDL-c, especially in the presence of hypertriglyceridemia or AD. The European guidelines for managing dyslipidemia recommend that non-HDL-c values be less than 100 and 130 mg/dL for individuals with very high and high cardiovascular risk, respectively. However, these guidelines state that there is insufficient evidence to suggest that raising HDL-c levels incontrovertibly results in a reduction in CVD. Therefore, the guidelines do not set recommended HDL-c levels as a therapeutic objective. The guidelines, however, state that individuals with AD on treatment with statins could benefit from an additional reduction in their risk by using fibrates.

The dyslipidaemias are conditions that are still under-diagnosed, under-treated, and poorly controlled. This condition is common to the rest of the risk factors considered fundamental. Within the dyslipidaemias, the data that we have available, generally refer to the hypercholesterolaemias or in particular to the dyslipidaemias not dependent on LDL in patients who are already being treated with statins. However, there is only limited data available on atherogenic dyslipidaemia, characterised by the elevation of triglycerides and/or a decrease in HDL-cholesterol. However, given its profile, to determine the particularities of this atherogenic dyslipidaemia could help to control this anomaly more effectively. The present study, conducted in accordance with the Delphi method, has as its purpose to demonstrate the level of agreement or disagreement of an expert group, made up from different scientific societies, on what atherogenic dyslipidaemia is and represents, as well as what is the most suitable diagnostic and therapeutic approach. It has been concluded that the level of knowledge of the epidemiological aspects, its association with cardiovascular risks, of clinical identification, and specific treatment, has reached a significant level of agreement between the experts consulted. However, some aspects have been detected that, even today, are still subject to controversy: the role of isolated hypertriglyceridaemia as a risk factor, and its consideration as a therapeutic objective both in primary and secondary prevention, the effects linked to HDL-cholesterol, and that are strictly associated with the capacity to produce cholesterol efflux, the appropriateness of the therapeutic objectives to individual particularities, as well as the need to employ - frequently - combined treatment to correctly approach the correction of the lipid profile as a whole.