Cardiovascular disease in human immunodeficiency virus infected patients: A true or perceived risk?

Abstract

After the successful introduction of highly active antiretroviral agents the survival of patients infected with the human immunodeficiency virus (HIV) in developed countries has increased substantially. This has allowed the surfacing of several chronic diseases among which cardiovascular disease (CVD) is prominent. The pathogenesis of CVD in HIV is complex and involves a combination of traditional and HIV related factors. An accurate assessment of risk of CVD in these patients is still elusive and as a consequence the most appropriate preventive and therapeutic interventions remain controversial.

Keywords: Antiretroviral therapy; Atherosclerosis; Cardiovascular death; Cardiovascular risk; Dyslipidemia; Human immunodeficiency virus infection; Hypertension; Smoking.

Figure 1

Putative mechanisms by which the human immunodeficiency virus virion increases the risk of atherosclerosis. The virus induces expression of adhesion molecules for leukocytes, reduce the secretion of nitric oxide with reduced vasodilation and induce endothelial cells apoptosis. ICAM: Intercellular adhesion molecule; VCAM: Vascular cell adhesion molecule; eNOS: Endothelial nitric oxide synthase; NO: Nitric oxide; HIV: Human immunodeficiency virus.

Figure 2

The human immunodeficiency virus promotes a state of low-grade chronic inflammation that increases the risk of atherosclerosis through the activation of lymphocytes, monocytes and macrophages. HIV: Human immunodeficiency virus; HLA: Human leukocyte antigen.

Figure 3

All algorithms currently used to estimate risk of cardiovascular disease in the general population underestimate the actual risk of human immunodeficiency virus positive patients. Although unproven, it is likely that a combination of traditional risk factors, risk linked with some anti-retroviral agents and data on subclinical atherosclerosis collected via imaging, may improve risk prediction in the future. ASCVD: Atherosclerotic cardiovascular disease; HAART: Highly active antiretroviral therapies; HIV: Human immunodeficiency virus.

Figure 4

The pathophysiology of human immunodeficiency virus associated atherosclerosis is very complex; a high prevalence of traditional risk factors, direct effects of the human immunodeficiency virus virion and side effects of some the antiretroviral agents, along with yet unknown genetic and epigenetic factors predispose these patients to a high incidence of cardiovascular disease. The impact of anti-retroviral therapy is particularly difficult to estimate since suppression of viral replication may have an anti-atherosclerotic activity (curved arrow with negative sign) while side effect of some antiretroviral drugs may promote atherosclerosis (curved arrow with positive sign). HAART: Highly active antiretroviral therapies; LDL: Low-density lipoprotein; VLDL: Very low-density lipoprotein; HIV: Human immunodeficiency virus.