Many research groups on atherosclerosis have sought through prospective large-scale epidemiological studies to better understand which residual factors would be associated with cardiovascular risk. Thus, atherogenic dyslipidemia was defined, such as the presence in an individual of decreased HDL-C levels, increased triglyceride levels, and a relatively high proportion of small and dense LDL-C particles. On the other hand, it was found that atherogenic dyslipidemia is present in cases of insulin resistance and metabolic syndrome (low HDL-C and elevated triglycerides are part of the definition of this syndrome) and consequently in patients with type 2 diabetes mellitus. Regarding treatment, there are studies in diabetic patients with risk reduction with fenofibrate, and the guidelines recommend the association of fenofibrate with statins. Diabetes mellitus is also an important cause of hospitalizations and proportional mortality, also assuming that most deaths register only the immediate cause of this death, which is often the result of diabetes complications. Most of these complications are cardiovascular diseases, which may manifest as coronary heart disease, cerebrovascular disease or peripheral arteriopathies. These are the so-called macrovascular complications of type 2 diabetes and are present even before the onset of hyperglycemia, due to the presence of insulin resistance and associated metabolic syndrome. Metabolic syndrome is characterized by the presence in the patient of at least 3 out of 5 parameters (increased abdominal waist, high glycemia, hypertriglyceridemia, low HDL-C and arterial hypertension) and is one of the factors responsible for the macrovascular changes.
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Peroxisome Proliferator Activated Receptor sits part of the family of nuclear receptors, which has about 50 known receptors, including thyroid hormone receptors, which have the function of regulating metabolism and metabolizing and eliminating substances. These receptors, to act, must be activated by ligands, form a heterodmer with the retinoic acid receptor, recruit activating cofactors, release inhibitory cofactors to which they are bound, and then act on the responsive element of target gene. Three species of peroxisome proliferator activated receptor are known: PPARa, PPARγ and PPARβ (also known as PPARd or β/d). The prototypes of PPARa activators are the derivatives of fibricacid, of which the first representative was clofibrate, used as a lipid-lowering factor in the 1960s and 1970s. Although there may be a small variation among the various fibrates regarding the mechanism of action, these drugs are basically PPARa activators. In the action of fibrates, there is a reduction of triglycerides, with a decrease in the synthesis of VLDL, increase of HDL particles and transformation of small and dense LDL into larger, less dense LDL and with lower atherogenic potential. Fibrates are second-choice substances, and statins are the first for the treatment of hypertriglyceridemia. Fibrates are efficient for the treatment of patients with low HDL-C, decrease macro and microvascular disease of diabetic patients. The recommendation is do not associate gemfibrozil with statins. Other fibrates may be associated, and preference should be given to the association of statins that are not metabolized by CYP3A4: rosvastatin, pravastatin and fluvastatin.
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