Estudio Metabólico y cardiovascular en una Cohorte de Pacientes Infectados por el VIH-1: Predisposición Genética, Aterosclerosis Subclínica y Eventos Coronarios

Abstract

The incidence of cardiovascular disease (CVD) has increased among HIV-infected patients. Both HIV replication and antiretroviral therapy may contribute independently to increase the risk of CVD. However, the cause of this increased risk is multifactorial. _x000D_ Methods: This thesis focuses on the study of metabolic and cardiovascular disorders in a cohort of HIV-infected patients. Three studies were conducted: A first study was designed with the purpose of ascertaining whether a combined analysis of several genetic variants in some of the genes responsible of lipid abnormalities helped discriminate HIV-infected patients with high triglycerides and low levels of HDL-cholesterol (patients with atherogenic profile), clear marker of cardiovascular risk. It was carried out metabolic and genetic characterization of 321 HIV-infected patients receiving antiretroviral therapy, through the determination of the lipid profile, determination of remnant cholesterol particles and determination of genes involved in the formation, as in removing remaining particles from circulation. Several genes responsible for modulation of lipid parameters in this population were identified. However, the cross-sectional design of the study and the small sample size does not allow definitive conclusions about the association between polymorphisms in genes associated with lipid metabolism and lipid disorders in HIV-infected patients. _x000D_ The second study focused on the early detection of subclinical atherosclerosis. For this, arterial elasticity was evaluated through the determination of the pulse wave velocity (PWV) in HIV-infected patients, compared to non-infected subjects. Risk factors associated with impaired arterial compliance were identified. HIV-infected patients with virologic suppression showed similar arterial elasticity than non-infected subjects. HIV-related conditions were not associated with arterial stiffness. However, high diastolic pressure at the time of the PWV and high triglycerides were risk factors. _x000D_ Finally, we conducted a descriptive, observational, retrospective study (third study) to determine the prevalence of coronary disease in a Mediterranean cohort of HIV-infected patients, also identified the most important modifiable risk factors and the management of these in the clinical practice. We observed a low prevalence of coronary events in this population, the cardiovascular risk factors were poorly controlled, low percentage of patients reached optimal levels in lipid parameters after coronary event and poor control of non-lipid risk factors was performed. The retrospective design of this study did not allow to determinate the actual rate of some risk factors and therefore assess changes over time. However, it gives us a clear picture of actual clinical practice and has given us to know the weaknesses in this context._x000D_ Conclusions: Some genetic variants are predictive of changes in lipid parameters; genetic information could help physicians individualize patient management to reduce cardiovascular risk. We must be more proactive in the diagnosis, management and monitoring of these risk factors in the population infected by HIV and cardiovascular health plans are a priority to implement and control of cardiovascular risk factors in these subjects.

Date of Award	17 Dec 2015
Original language	Undefined/Unknown
Awarding Institution	Germans Trias i Pujol Health Sciences Research Institute (IGTP)
Supervisor	Bonaventura Clotet Sala (Director), Jordi Tor Aguilera (Tutor) & Maria Eugenia Negredo Puigmal (Director)