IJCS | Volume 31, Nº5, September / October 2018

540 Roever et al. HIV and cardiovascular disease Int J Cardiovasc Sci. 2018;31(5)538-543 Review Article Pericardial disease Pericardial disease is the most common heart disease among HIV-infected individuals. One of the major risk factors for its development is opportunistic infection, mainly tuberculosis. 36 Pericardial disease can be caused by opportunistic diseases, being used as a marker of progression of HIV infection, because it associates with a shorter survival. 37 Markers of cardiovascular diseases in HIV-infected individuals Somemarkers that aredirectly related to cardiovascular mortality in HIV-infected people can be measured and, therefore, used in clinical practice. Regarding inflammation, interleukin (IL)-6 and C-reactive protein stand out. 38 In HIV-infected people, those markers are increased by 50% to 152% as compared to those of non-infected individuals. 39,40 In addition, they are associated with all-cause mortality, including that due to cardiovascular diseases. 41,42 Of the thrombolytic factors, fibrinogen and D dimer stand out. Those markers are increased by 8% to 94% in HIV-infected people as compared to those in the non- infected population. In addition, they correlate directly with viral load (amount of HIV RNA copies) and all mortality causes. 40,43,44 The endothelial function is measured by use of the vascular cell adhesionmolecule (VCAM) and intercellular adhesion molecule (ICAM). Those molecules relate directly to the viral load and consequent cardiovascular death, because they affect more than 40% of the arterial lumen of HIV-infected patients. 43,45,46 Finally, it is worth noting that the HDL-c concentrations, which are reduced by 13% to 21% in HIV-infected people as compared to non-infected people, are inversely related to the viral load and directly related to cardiovascular mortality. 39,47 Dyslipidemia In HIV-infected people, undergoing or not ART, the change in the lipid profile can promote the atherosclerotic process and increase the risk for cardiovascular diseases. 11 Thus, in clinical practice, it is important to understand how the factors inherent in infection and in treatment can trigger changes in the lipid profile. The HIV infection per se causes changes in the lipid profile. The HIV viremia increases the serum concentrations of triglycerides and LDL-c. 48 Studies on the mechanisms of howHIV causes dyslipidemia are scarce. However, factors, such as an exacerbated inflammatory profile, reduced lipid clearance and increased hepatic vLDL-c synthesis, can be an explanation. 49,50 Another triggering factor of dyslipidemia in HIV- infected people is the use of ART. The drug increases the concentrations of triglycerides, LDL-c and total cholesterol. Although initially associated with the use of protease inhibitors, some studies have shown that nucleoside analog and non-nucleoside analog reverse transcriptase inhibitors can trigger that condition. 51-53 The mechanisms of how the ART causes dyslipidemia have not been totally clarified, but the binding site seems to have high affinity with the catalytic site of the HIV protease, thus, binding and inhibiting the homologous protein involved in the lipid metabolism, inducing an increase in the blood concentrations of that substance. 54 Metabolic syndrome Metabolic syndrome (MS) is characterized by the presence of hyperglycemia or diabetes mellitus, altered blood pressure or systemic arterial hypertension, abdominal obesity and dyslipidemia. 55,56 Metabolic syndrome has been reported to relate to morbidity and mortality worldwide, mainly because of complications involving the cardiovascular system. 57,58 Epidemiological studies have shown that the incidence of MS in HIV- infected people ranges from 18% to 50%. 59-61 Some factors are known to be fundamental for the diagnosis of MS in HIV-infected people. Conditions related to the infection, ART, adipose tissue distribution and dyslipidemia seem to stand out. 62-64 Oneof themajor side effects ofART is the lipodystrophy syndrome, characterized by lipoatrophy (reduced adipose tissue) of the upper and lower limbs and face, with lipohypertrophy (increased adipose tissue) in the central and cervical regions. As a consequence, the waist circumference increases, but forHIV-infected patients this criterion seems not to be fundamental for the diagnosis of MS. 65 Finally, the adipose tissue accumulation in the central region of the body can lead to other disorders, such as insulin resistance and cardiovascular diseases. Glucose metabolism disorder Diabetes mellitus is a systemic disease caused by an insulin and/or glucosemetabolismdisorder. Although the